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1. Entropic uncertainty relations for Markovian and non-Markovian processes under a structured bosonic reservoir

Author

Dong Wang, Ai-Jun Huang, Ross D. Hoehn, Fei Ming, Wen-Yang Sun, Jia-Dong Shi, Liu Ye, and Sabre Kais

Subjects
Medicine, Science
Abstract

Abstract The uncertainty relation is a fundamental limit in quantum mechanics and is of great importance to quantum information processing as it relates to quantum precision measurement. Due to interactions with the surrounding environment, a quantum system will unavoidably suffer from decoherence. Here, we investigate the dynamic behaviors of the entropic uncertainty relation of an atom-cavity interacting system under a bosonic reservoir during the crossover between Markovian and non-Markovian regimes. Specifically, we explore the dynamic behavior of the entropic uncertainty relation for a pair of incompatible observables under the reservoir-induced atomic decay effect both with and without quantum memory. We find that the uncertainty dramatically depends on both the atom-cavity and the cavity-reservoir interactions, as well as the correlation time, τ, of the structured reservoir. Furthermore, we verify that the uncertainty is anti-correlated with the purity of the state of the observed qubit-system. We also propose a remarkably simple and efficient way to reduce the uncertainty by utilizing quantum weak measurement reversal. Therefore our work offers a new insight into the uncertainty dynamics for multi-component measurements within an open system, and is thus important for quantum precision measurements.

Published
2017
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2. Status of the Vibrational Theory of Olfaction

Author

Ross D. Hoehn, David E. Nichols, Hartmut Neven, and Sabre Kais

Subjects
olfaction, biophyiscs, vibration detection, review literature as topic, GPCRs, Physics, QC1-999
Abstract

The vibrational theory of olfaction is an attempt to describe a possible mechanism for olfaction which is explanatory and provides researchers with a set of principles which permit predictions allowing for structure-odor relations. Similar theories have occurred several times throughout olfactory science; this theory has again recently come to prominence by Luca Turin, who suggested that inelastic electron tunneling is the method by which vibrations are detected by the olfactory receptors within the hose. This work is intended to convey to the reader an up-to-date account of the vibrational theory of olfaction, both the historical iterations as well as the present iteration. This text is designed to give a chronological account of both theoretical and experimental studies on the topic, while providing context, comments, and background where they were found to be needed.

Published
2018
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3. Generalized Remote Preparation of Arbitrary m-qubit Entangled States via Genuine Entanglements

Author

Dong Wang, Ross D. Hoehn, Liu Ye, and Sabre Kais

Subjects
quantum communication, remote state preparation, entangled state, collective unitary operation, success probability, Science, Astrophysics, QB460-466, Physics, QC1-999
Abstract

Herein, we present a feasible, general protocol for quantum communication within a network via generalized remote preparation of an arbitrary m-qubit entangled state designed with genuine tripartite Greenberger–Horne–Zeilinger-type entangled resources. During the implementations, we construct novel collective unitary operations; these operations are tasked with performing the necessary phase transfers during remote state preparations. We have distilled our implementation methods into a five-step procedure, which can be used to faithfully recover the desired state during transfer. Compared to previous existing schemes, our methodology features a greatly increased success probability. After the consumption of auxiliary qubits and the performance of collective unitary operations, the probability of successful state transfer is increased four-fold and eight-fold for arbitrary two- and three-qubit entanglements when compared to other methods within the literature, respectively. We conclude this paper with a discussion of the presented scheme for state preparation, including: success probabilities, reducibility and generalizability.

Published
2015
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7. Treatment response classes in major depressive disorder identified by model-based clustering and validated by clinical prediction models

Author

Darina Czamara, D. Hoehn, Bertram Müller-Myhsok, Rudolf Uher, Philipp G. Sämann, Benno Pütz, Riya Paul, Marcus Ising, Cathryn M. Lewis, Till F. M. Andlauer, and Susanne Lucae

Subjects
0301 basic medicine, Adult, Male, Disease cluster, Predictive markers, Article, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Clinical Decision Rules, medicine, Cluster Analysis, Humans, Cluster analysis, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Depressive Disorder, Major, business.industry, Depression, Remission Induction, Middle Aged, Models, Theoretical, medicine.disease, Antidepressive Agents, Random forest, ddc, Psychiatry and Mental health, 030104 developmental biology, Treatment Outcome, Pharmacogenetics, Cohort, Major depressive disorder, Observational study, Female, business, 030217 neurology & neurosurgery, Algorithms, Clinical psychology, Psychopathology
Abstract

The identification of generalizable treatment response classes (TRC[s]) in major depressive disorder (MDD) would facilitate comparisons across studies and the development of treatment prediction algorithms. Here, we investigated whether such stable TRCs can be identified and predicted by clinical baseline items. We analyzed data from an observational MDD cohort (Munich Antidepressant Response Signature [MARS] study, N = 1017), treated individually by psychopharmacological and psychotherapeutic means, and a multicenter, partially randomized clinical/pharmacogenomic study (Genome-based Therapeutic Drugs for Depression [GENDEP], N = 809). Symptoms were evaluated up to week 16 (or discharge) in MARS and week 12 in GENDEP. Clustering was performed on 809 MARS patients (discovery sample) using a mixed model with the integrated completed likelihood criterion for the assessment of cluster stability, and validated through a distinct MARS validation sample and GENDEP. A random forest algorithm was used to identify prediction patterns based on 50 clinical baseline items. From the clustering of the MARS discovery sample, seven TRCs emerged ranging from fast and complete response (average 4.9 weeks until discharge, 94% remitted patients) to slow and incomplete response (10% remitted patients at week 16). These proved stable representations of treatment response dynamics in both the MARS and the GENDEP validation sample. TRCs were strongly associated with established response markers, particularly the rate of remitted patients at discharge. TRCs were predictable from clinical items, particularly personality items, life events, episode duration, and specific psychopathological features. Prediction accuracy improved significantly when cluster-derived slopes were modelled instead of individual slopes. In conclusion, model-based clustering identified distinct and clinically meaningful treatment response classes in MDD that proved robust with regard to capturing response profiles of differently designed studies. Response classes were predictable from clinical baseline characteristics. Conceptually, model-based clustering is translatable to any outcome measure and could advance the large-scale integration of studies on treatment efficacy or the neurobiology of treatment response.

Published
2019
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8. New Insights into Physical Science Vol. 10

Author

B. D'Angelo, Felice Sorrentino, Bob W. N. J. Ursem, Md. Samiul Haque, Thomas F. Valone, V. Sequino, M. Bawaj, V. E. Shapiro, J. P. Zendri, Uzi Notev, Maria Vilenchik, L. Naticchioni, B. Garaventa, Lev Z. Vilenchik, G. Somashekhara Somashekhara, Floyd. L. Williams, Jurgen Michael Honig, C. Nguyen, Boris Sedunov, M. De Laurentis, Ross D. Hoehn, Daniel Sepunaru, Alexander Alexandrovich Antonov, S. Di Pace, G S Shivaprasanna, and I. Khan

Subjects
Engineering, business.industry, Physical science, Engineering ethics, business
Published
2020
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9. Vertical Ozone Concentration Profiles in the Arabian Gulf Region during Summer and Winter: Sensitivity of WRF-Chem to Planetary Boundary Layer Schemes

Author

Dunia Bachour, Ivan Gladich, Mohammed Ayoub, Christos Fountoukis, Luis Ackermann, Daniel Perez-Astudillo, and Ross D. Hoehn

Subjects
Ozone, 010504 meteorology & atmospheric sciences, Planetary boundary layer, Ozone concentration, Weather research forecasting, 010501 environmental sciences, Atmospheric sciences, 01 natural sciences, Pollution, Troposphere, chemistry.chemical_compound, chemistry, Weather Research and Forecasting Model, Environmental Chemistry, Emission inventory, Air quality index, 0105 earth and related environmental sciences
Abstract

Air quality in the Middle East is changing due to extensive land conversion, intense industrialization and rapid urbanization. In this study, we analyze data from an ozonesonde station operated in Doha, Qatar, by the Qatar Environment and Energy Research Institute (QEERI). Ozonesondes were launched weekly at 13:00 LT (10:00 UTC) during a summer month (August 2015) representative of extremely hot and humid atmospheric conditions and during a winter period (January–February 2016) representative of cool conditions in the area. Unlike similar studies in the region, this work focuses on the lower troposphere and combines high frequency vertical measurement data with the use of the Weather Research Forecasting model coupled with Chemistry (WRF-Chem). A sensitivity study was conducted to identify the most representative planetary boundary layer (PBL) parameterization. Although all three parameterizations that were examined produced similar results, the Yonsei University (YSU) PBL scheme was found to be statistically superior. Comparisons of model predictions against observations show high correlation coefficients and encouragingly low biases in all meteorological variables. During wintertime, ozone is well predicted overall (fractional bias = –0.1). Results from the summertime comparison are more challenging and point towards possible biases in the anthropogenic emission inventory of the Middle East, especially for rapidly-changing urban environments.

Published
2018
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10. Efficient Remote Preparation of Four-Qubit Cluster-Type Entangled States with Multi-Party Over Partially Entangled Channels

Author

Dong Wang, Sabre Kais, Ross D. Hoehn, and Liu Ye

Subjects
Theoretical computer science, Physics and Astronomy (miscellaneous), General Mathematics, Data_CODINGANDINFORMATIONTHEORY, Topology, 01 natural sciences, 010305 fluids & plasmas, Transmission (telecommunications), Qubit, 0103 physical sciences, Communication source, State (computer science), 010306 general physics, Quantum, Cluster type, Computer Science::Information Theory, Mathematics
Abstract

We present a strategy for realizing multiparty-controlled remote state preparation (MCRSP) for a family of four-qubit cluster-type states by taking a pair of partial entanglements as the quantum channels. In this scenario, the encoded information is transmitted from the sender to a spatially separated receiver with control of the transmission by multiple parties. Predicated on the collaboration of all participants, the desired state can be faithfully restored at the receiver’s location with high success probability by application of additional appropriate local operations and necessary classical communication. Moreover, this proposal for MCRSP can be faithfully achieved with unit total success probability when the quantum channels are distilled to maximally entangled ones.

Published
2016
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11. Elucidation of near-resonance vibronic coherence lifetimes by nonadiabatic electronic-vibrational state character mixing

Author

Gregory S. Engel, Sabre Kais, Shu-Hao Yeh, Marco A. Allodi, and Ross D. Hoehn

Subjects
Physics, Multidisciplinary, 010304 chemical physics, Phonon, Exciton, Dephasing, Non-equilibrium thermodynamics, Equations of motion, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Chemical physics, 0103 physical sciences, Vibrational energy relaxation, Electronic energy, Coherence (physics)
Abstract

Recent work suggests that the long-lived coherences observed in both natural and artificial light-harvesting systems (such as the Fenna–Matthews–Olson complex) could be attributed to the mixing of the pigments’ electronic and vibrational degrees of freedom. To investigate the underlying mechanism of these long coherence lifetimes, a sophisticated description of interactions between the molecular aggregates and the nonequilibrium fluctuations in the surrounding environment is necessary. This is done by implementing the hierarchical equations of motion approach on model homodimers, a method used in the intermediate coupling regime for many molecular aggregates wherein the nonequilibrium environment phonons play nontrivial roles in exciton dynamics. Here we report a character change in the vibronic states—reflective of property mixing between the electronic and vibrational states—induced by an interplay between system coupling parameters within the exciton-vibrational near-resonance regime. This mixing dictates vital aspects of coherence lifetime; by tracking the degree of mixing, we are able to elucidate the relationship between coherence lifetime and both the electronic energy fluctuation and the vibrational relaxation dephasing pathways.

Published
2018

12. Role of Water on the Rotational Dynamics of the Organic Methylammonium Cation: A First Principles Analysis

Author

Joseph S. Francisco, Ross D. Hoehn, Ali Kachmar, and Sabre Kais

Subjects
0301 basic medicine, Wannier function, Multidisciplinary, Materials science, Hydrogen bond, Intermolecular force, lcsh:R, Solvation, lcsh:Medicine, Article, 03 medical and health sciences, Molecular dynamics, 030104 developmental biology, 0302 clinical medicine, Physical chemistry, Molecule, lcsh:Q, lcsh:Science, 030217 neurology & neurosurgery, Stationary state, Perovskite (structure)
Abstract

Understanding the degradation mechanisms of lead-halide perovskites (CH3NH3PbI3) under exposure to liquid/aerosol water is an essential problem within the photovoltaic community. Herein we investigate both the static and the dynamic properties of the methylammonuim cation (MA) as it coordinates with invading water molecules (MA.(H2O)n, n = 1, 2, 3, 4) using both stationary state quantum mechanics and first principle molecular dynamics simulations. Various solvation structures of MA were characterized by their stabilization energies, dipoles, and Maximally-Localized Wannier Function (MLWF) centers. Calculation – and analysis – of vibrational shifts in the IR spectral region were performed for hydrated complexes; the locations of $${\bf{N}}{{\bf{H}}}_{{\bf{3}}}^{{\boldsymbol{+}}}$$ N H 3 + stretching vibrations allude to significant hydrogen bonding between MA and the water molecules. Through Fourier analysis of the rotational dynamics on several MA · (H2O)n complexes, we conclude that the water molecules dampen the rotational motion of the MA as the intermolecular bonds formed between the water molecules and the MA act to hinder the rotation of the cation; these findings give explanatory support to earlier computational observations of humidity effects on perovskites (i.e., CH3NH3PbI3) materials. This work is a step toward understanding the water-MA cation interaction in bulk perovskites, thus providing greater understanding of in situ instability/degradation of perovskite bulk materials.

Published
2018

13. Canonical Schottky barrier heights of the transition metal dichalcogenide monolayers in contact with a metal

Author

Dominik Szczęśniak, Sabre Kais, and Ross D. Hoehn

Subjects
Materials science, Condensed matter physics, Condensed Matter - Mesoscale and Nanoscale Physics, business.industry, Band gap, Schottky barrier, FOS: Physical sciences, 02 engineering and technology, 021001 nanoscience & nanotechnology, 01 natural sciences, Transition metal dichalcogenide monolayers, Electronegativity, Semiconductor, Transition metal, Mesoscale and Nanoscale Physics (cond-mat.mes-hall), 0103 physical sciences, Monolayer, 010306 general physics, 0210 nano-technology, Electronic band structure, business
Abstract

The transition metal dichalcogenide ($MX_{2}$, where $M$=Mo, W and $X$=S, Se, Te) monolayers are of high interest for semiconducting applications at the nanoscale level; this interest is due to both their direct band gaps and high charge mobilities. In this regard, an in-depth understating of the related Schottky barrier heights, associated with the incorporation of $MX_{2}$ sheets into novel low-dimensional metal-semiconductor junctions, is of crucial importance. Herein, we generate and provide analysis of the Schottky barrier heights behavior to account for the metal-induced gap states concept as its explanation. In particular, the present investigations concentrate on the estimation of the charge neutrality levels directly by employing the primary theoretical model, $i.e.$ the cell-averaged Green's function formalism combined the complex band structure technique. The results presented herein place charge neutrality levels in the vicinity of the mid-gap; this is in agreement with previous reports and analogous to the behavior of three-dimensional semiconductors. The calculated canonical Schottky barrier heights are also found to be in agreement with other computational and experimental values in cases where the difference between electronegativities of the semiconductor and metal contact is small. Moreover, the influence of the spin-orbit effects is herein considered and supports that Schottky barrier heights have metal-induced gap state-derived character, regardless whether spin-orbit coupling interactions are considered. The results presented within this report constitute a direct and vital verification of the importance of metal-induced gap states in explaining the behavior of observed Schottky barrier heights at $MX_{2}$-metal junctions., 7 pages, 2 figures

Published
2018

14. Entropic uncertainty relations for Markovian and non-Markovian processes under a structured bosonic reservoir

Author

Wen-Yang Sun, Sabre Kais, Ai-Jun Huang, Ross D. Hoehn, Jia-Dong Shi, Liu Ye, Dong Wang, and Fei Ming

Subjects
Physics, Quantum Physics, Multidisciplinary, Quantum limit, Quantum dynamics, Science, FOS: Physical sciences, 16. Peace & justice, 01 natural sciences, Article, 010305 fluids & plasmas, Open quantum system, Quantum process, 0103 physical sciences, Quantum system, Medicine, Weak measurement, Statistical physics, Entropic uncertainty, 010306 general physics, Quantum dissipation, Quantum Physics (quant-ph)
Abstract

The uncertainty relation is a fundamental limit in quantum mechanics and is of great importance to quantum information processing as it relates to quantum precision measurement. Due to interactions with the surrounding environment, a quantum system will unavoidably suffer from decoherence. Here, we investigate the dynamic behaviors of the entropic uncertainty relation of an atom-cavity interacting system under a bosonic reservoir during the crossover between Markovian and non-Markovian regimes. Specifically, we explore the dynamic behavior of the entropic uncertainty relation for a pair of incompatible observables under the reservoir-induced atomic decay effect both with and without quantum memory. We find that the uncertainty dramatically depends on both the atom-cavity and the cavity-reservoir interactions, as well as the correlation time, $\tau$, of the structured reservoir. Furthermore, we verify that the uncertainty is anti-correlated with the purity of the state of the observed qubit-system. We also propose a remarkably simple and efficient way to reduce the uncertainty by utilizing quantum weak measurement reversal. Therefore our work offers a new insight into the uncertainty dynamics for multi-component measurements within an open system, and is thus important for quantum precision measurements., Comment: 17 pages, 9 figures, to appear in Scientific Reports

Published
2017

15. Influence of the intensity gradient upon HHG from free electrons scattered by an intense laser beam

Author

Na Ren, Ross D. Hoehn, Wen-Jun Zhu, Jiaxiang Wang, Ankang Li, Sabre Kais, Pingxiao Wang, and Xiao-Ya Li

Subjects
Free electron model, Quantum optics, Physics, Beam diameter, Physics and Astronomy (miscellaneous), Atomic Physics (physics.atom-ph), General Engineering, FOS: Physical sciences, General Physics and Astronomy, Electron, Laser, Spectral line, Physics - Atomic Physics, Pulse (physics), Intensity (physics), law.invention, law, Physics::Atomic Physics, Atomic physics, Optics (physics.optics), Physics - Optics
Abstract

When an electron is scattered by a tightly-focused laser beam in vacuum, the intensity gradient is a critical factor to influence the electron dynamics, for example, the electron energy exchange with the laser fields as have been explored before [P.X.Wang et al.,J. Appl. Phys. 91, 856 (2002]. In this paper, we have further investigated its influence upon the electron high-harmonic generation (HHG) by treating the spacial gradient of the laser intensity as a ponderomotive potential. Based upon perturbative QED calculations, it has been found that the main effect of the intensity gradient is the broadening of the originally line HHG spectra. A one-to-one relationship can be built between the beam width and the corresponding line width. Hence this finding may provides us a promising way to measure the beam width of intense lasers in experiments. In addition, for a laser pulse, we have also studied the different influences from transverse and longitudinal intensity gradients upon HHG.

Published
2014
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16. Genetic architecture of subcortical brain structures in 38,851 individuals

Author

Mar Matarin, Douglas N. Greve, Nic J.A. van der Wee, Evan Fletcher, Christiane Wolf, Arvin Saremi, Joshua W. Cheung, Randy L. Gollub, David Ames, Honghuang Lin, Nicholas G. Martin, Manon Bernard, Daniel R. Weinberger, Henry Völzke, Manuel Mattheisen, George Davey Smith, Dan J. Stein, Dorret I. Boomsma, John D. Eicher, Henrik Walter, Massimo Pandolfo, Andreas Meyer-Lindenberg, D. Hoehn, Louis N. Vinke, Wiro J. Niessen, G. Bruce Pike, Simon E. Fisher, Jerome I. Rotter, Neeltje E.M. van Haren, Neda Jahanshad, Stephen M. Lawrie, Mark E. Bastin, Sanjay M. Sisodiya, Marcella Rietschel, Jean Shin, Dirk J. Heslenfeld, Ingrid Agartz, Lars Nyberg, Nina Romanczuk-Seiferth, Clifford R. Jack, Markus Scholz, Baljeet Singh, Rachel M. Brouwer, Marco P. Boks, M. Mallar Chakravarty, Magda Tsolaki, André G. Uitterlinden, Amelia A. Assareh, Nastassja Koen, Beng-Choon Ho, Muralidharan Sargurupremraj, Perminder S. Sachdev, James T. Becker, Narelle K. Hansell, Katrin Hegenscheid, Zdenka Pausova, Irina Filippi, Hans van Bokhoven, Miguel E. Rentería, Robert C. Green, M. Kamran Ikram, Vidar M. Steen, Marc M. Bohlken, Iryna O. Fedko, Jayandra J. Himali, Hieab H.H. Adams, Erik G. Jönsson, Esther Walton, Gunter Schumann, Dennis van der Meer, Jordan W. Smoller, Ganesh Chauhan, Simon Lovestone, Kwangsik Nho, Gianpiero L. Cavalleri, Andrew Simmons, Shuo Li, Hannah J. Jones, Lavinia Athanasiu, Shahrzad Kharabian Masouleh, Micael Andersson, Andreas Heinz, Lucija Abramovic, Alexa S. Beiser, Vilmundur Gudnason, Oliver Gruber, Tianye Jia, Daan van Rooij, Philip L. De Jager, Allison Stevens, Thomas W. Mühleisen, Deborah Janowitz, Anita L. DeStefano, Gennady V. Roshchupkin, Maria C. Valdés Hernández, Nynke A. Groenewold, Vince D. Calhoun, Cornelia M. van Duijn, Roberto Toro, Wiepke Cahn, Florian Holsboer, Asta Håberg, Aaron Goldman, Lisa R. Yanek, Jingyun Yang, Matthias L. Schroeter, Patrizia Mecocci, Sven J. van der Lee, Gareth E. Davies, Elena Shumskaya, Jia Yu Koh, Thomas H. Wassink, Wei Wen, A. Veronica Witte, Anders M. Dale, Diana Tordesillas-Gutiérrez, Iwona Kłoszewska, Benedicto Crespo-Facorro, Sylvane Desrivières, Catharina A. Hartman, Saskia P. Hagenaars, Jennifer S. Richards, Martine Hoogman, Philipp G. Sämann, Andre F. Marquand, Stephanie Le Hellard, Christophe Tzourio, Sven Cichon, Tomáš Paus, Ole A. Andreassen, Pieter J. Hoekstra, Gabriel Cuellar-Partida, Joanna M. Wardlaw, Thomas H. Mosley, Bernd Kraemer, Barbara Franke, Joshua C. Bis, Katharina Wittfeld, Christopher D. Whelan, Christine Macare, Unn K. Haukvik, Lars T. Westlye, Loes M. Olde Loohuis, Sudha Seshadri, Michelle Luciano, Shannon L. Risacher, Diane M. Becker, Tamara B. Harris, Georg Homuth, Sungeun Kim, Lenore J. Launer, Debra A. Fleischman, Tulio Guadalupe, Joshua L. Roffman, Marie-José van Tol, Stéphanie Debette, Benno Pütz, Dick J. Veltman, Ching-Yu Cheng, Norman Delanty, Chantal Depondt, Jaap Oosterlaan, Nicola J. Armstrong, Myriam Fornage, Eric Westman, Anouk den Braber, Nanda Rommelse, Qiong Yang, Yasaman Saba, Tatiana Foroud, Susanne Erk, Saima Hilal, Paul M. Thompson, Eco J. C. de Geus, Paul A. Nyquist, Wolfgang Hoffmann, Alexander Teumer, Avram J. Holmes, Qiang Chen, Najaf Amin, Albert V. Smith, Tom V. Lee, Sarah E. Medland, Nazanin Mirza-Schreiber, Alejandro Arias-Vasquez, Grant W. Montgomery, Han G. Brunner, Meike W. Vernooij, Bernard Mazoyer, Guillén Fernández, Henry Brodaty, Claudia L. Satizabal, Thomas Wolfers, Herve Lemaitre, Li Shen, Greig I. de Zubicaray, Pauline Maillard, Hans J. Grabe, Ingrid Melle, Simone Reppermund, Charles DeCarli, Anbupalam Thalamuthu, Helena Schmidt, Peter R. Schofield, Marjolein M.J. van Donkelaar, Thomas Espeseth, Christopher Chen, Matthias Nauck, Norbert Hosten, Clyde Francks, Oliver Grimm, Tonya White, Andrew J. Saykin, Andrew M. McIntosh, Oscar L. Lopez, Philippe Amouyel, William T. Longstreth, Janita Bralten, Nhat Trung Doan, John B.J. Kwok, Charles C. White, Ralph Burkhardt, Jessika E. Sussmann, Michael W. Weiner, Markus M. Nöthen, Katie L. McMahon, Derrek P. Hibar, Dalia Kasperaviciute, Maria J. Knol, Hilleke E. Hulshoff Pol, Markus Loeffler, Bruno Vellas, Matthew J. Huentelman, Owen Carmichael, Jason L. Stein, Ryota Kanai, Lianne Schmaal, Hilkka Soininen, Bruce M. Psaty, Jan K. Buitelaar, Jean-Luc Martinot, Ian J. Deary, Venkata S. Mattay, Theo G.M. van Erp, Arno Villringer, Andrew D. Johnson, Srdjan Djurovic, Benjamin S. Aribisala, Lachlan T. Strike, Phil Lee, David C. Liewald, Tien Yin Wong, Tomas Axelsson, Jessica A. Turner, Marieke Klein, Kristel R. van Eijk, Saud Alhusaini, Konstantinos Arfanakis, M. Arfan Ikram, Stefan Ehrlich, Sebastian Mohnke, Marcel P. Zwiers, Karen A. Mather, Jonathan C Ipser, Joshua M. Shulman, Brenda W.J.H. Penninx, Reinhold Schmidt, Arthur W. Toga, Christopher R.K. Ching, René S. Kahn, Bertram Müller-Myhsok, Yuri Milaneschi, Margaret J. Wright, Martina Papmeyer, Fabrice Crivello, David A. Bennett, Randy L. Buckner, Edith Hofer, Roel A. Ophoff, Steven G. Potkin, Albert Hofman, Dennis van 't Ent, Sudheer Giddaluru, Roberto Roiz-Santiañez, Andrew J. Schork, Jouke-Jan Hottenga, Yanhui Hu, Kazima B. Bulayeva, Xueqiu Jian, Clinical Genetics, Epidemiology, Radiology & Nuclear Medicine, Medical Informatics, Neurology, Child and Adolescent Psychiatry / Psychology, Psychiatry, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), APH - Mental Health, Pediatric surgery, Epidemiology and Data Science, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, APH - Digital Health, General Paediatrics, ARD - Amsterdam Reproduction and Development, Psychiatrie & Neuropsychologie, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), RS: MHeNs - R2 - Mental Health, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Stochastics, Biological Psychology, APH - Methodology, Clinical Neuropsychology, IBBA, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, and Cognitive Psychology

Subjects
Netherlands Twin Register (NTR), LD SCORE REGRESSION, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Caudate nucleus, Genome-wide association study, Bio-Organic Chemistry, Language in Interaction, neuroscience, Cohort Studies, BASAL GANGLIA, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, metabolism [Drosophila melanogaster], Basal ganglia, Adult, Aged, Animals, Brain, Drosophila melanogaster, Humans, Magnetic Resonance Imaging, Middle Aged, Neurodevelopmental Disorders, Organ Size, Genetic Variation, Genome-Wide Association Study, genetics [Drosophila melanogaster], 0303 health sciences, genetics [Neurodevelopmental Disorders], Putamen, 220 Statistical Imaging Neuroscience, 3. Good health, ALZHEIMERS-DISEASE, DROSOPHILA, Globus pallidus, VINTAGE, epidemiology, Synaptic signaling, Neuroinformatics, EXPRESSION, Nucleus accumbens, Biology, 150 000 MR Techniques in Brain Function, Article, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, ddc:570, PLASMA-PROTEIN, pathology [Neurodevelopmental Disorders], Genetics, GENOME-WIDE ASSOCIATION, HEALTHY, METAANALYSIS, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], RISK LOCI, Genetic architecture, ALKALINE-PHOSPHATASE, nervous system, metabolism [Brain], genome-wide association studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, growth & development [Drosophila melanogaster], anatomy & histology [Brain], Neuroscience, 030217 neurology & neurosurgery
Abstract

Aims/hypothesis MODY can be wrongly diagnosed as type 1 diabetes in children. We aimed to find the prevalence of MODY in a nationwide population-based registry of childhood diabetes. Methods Using next-generation sequencing, we screened the HNF1A, HNF4A, HNF1B, GCK and INS genes in all 469 children (12.1%) negative for both GAD and IA-2 autoantibodies and 469 antibody-positive matched controls selected from the Norwegian Childhood Diabetes Registry (3882 children). Variants were classified using clinical diagnostic criteria for pathogenicity ranging from class 1 (neutral) to class 5 (pathogenic). Results We identified 58 rare exonic and splice variants in cases and controls. Among antibody-negative patients, 6.5% had genetic variants of classes 3–5 (vs 2.4% in controls; p = 0.002). For the stricter classification (classes 4 and 5), the corresponding number was 4.1% (vs 0.2% in controls; p = 1.6 × 10−5). HNF1A showed the strongest enrichment of class 3–5 variants, with 3.9% among antibody-negative patients (vs 0.4% in controls; p = 0.0002). Antibody-negative carriers of variants in class 3 had a similar phenotype to those carrying variants in classes 4 and 5. Conclusions/interpretation This is the first study screening for MODY in all antibody-negative children in a nationwide population-based registry. Our results suggest that the prevalence of MODY in antibody-negative childhood diabetes may reach 6.5%. One-third of these MODY cases had not been recognised by clinicians. Since a precise diagnosis is important for treatment and genetic counselling, molecular screening of all antibody-negative children should be considered in routine diagnostics.

Published
2019
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17. Response to Dr Fried & Dr Kievit, and Dr Malhi et al

Author

A. Block, Bartosz Zurowski, Wiro J. Niessen, Katie L. McMahon, D. Schoepf, Roberto Goya-Maldonado, Brenda W.J.H. Penninx, Jess E. Sussmann, Sean N. Hatton, Jim Lagopoulos, ENIGMA-Major Depressive Disorder, Miguel E. Rentería, Michael Czisch, T.G.M. van Erp, Lachlan T. Strike, Meike W. Vernooij, M. A. Ikram, D. Hoehn, D.J. Veltman, Philipp G. Saemann, N.J. van der Wee, G.I. de Zubicaray, Derrek P. Hibar, Oliver Gruber, Beata R. Godlewska, Claus Normann, Neda Jahanshad, S. E. Medland, Elizabeth Loehrer, Lianne Schmaal, Ilya M. Veer, Paul M. Thompson, K. Wittfeld, Bernd Kraemer, Katrin Hegenscheid, Ian B. Hickie, Elisabeth Schramm, L. S. van Velzen, Andrew M. McIntosh, H. J. Grabe, Nathan A. Gillespie, Henrik Walter, Geoffrey B. Hall, Felix Fischer, Carsten Konrad, Heather C. Whalley, Baptiste Couvy-Duchesne, M-J van Tol, Thomas Frodl, and Margaret J. Wright

Subjects
medicine.medical_specialty, business.industry, medicine.disease, 030227 psychiatry, 03 medical and health sciences, Cellular and Molecular Neuroscience, Psychiatry and Mental health, 0302 clinical medicine, medicine, Major depressive disorder, Anxiety, ddc:610, medicine.symptom, Psychiatry, business, Molecular Biology, 030217 neurology & neurosurgery, Early onset
Published
2016
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18. Using Quantum Games To Teach Quantum Mechanics, Part 2

Author

Sabre Kais, Ross D. Hoehn, and Nick Mack

Subjects
Computer Science::Computer Science and Game Theory, Basis (linear algebra), Computer science, Computation, Hilbert space, Observable, General Chemistry, Quantum entanglement, Education, symbols.namesake, Superposition principle, symbols, Calculus, Wave function, Quantum
Abstract

Introductory courses in computational and quantum chemistry introduce topics such as Hilbert spaces, basis set expansions, and observable matrices. These topics are fundamental in the practice of quantum computations in chemistry as most computational methods rely on basis sets to approximate the true wave function. The mechanics of these topics can easily and intuitively be shown through the use of the game quantum tic-tac-toe (QTTT). Herein we propose a series of activities, using the mechanics of both classical tic-tac-toe (CTTT) and QTTT, intended to assist in the student’s understanding of these quantum chemistry topics by exploiting their intuitive comprehension of the game. Quantum tic-tac-toe QTTT is a quantum analogue of CTTT and can be used to demonstrate the use of superposition in movement, qualitative (and later quantitative) displays of entanglement, and state collapse due to observation. QTTT can be used for the benefit of the student’s comprehension in several other topics with the aid of ...

Published
2014
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19. Using Quantum Games To Teach Quantum Mechanics, Part 1

Author

Ross D. Hoehn, Nick Mack, and Sabre Kais

Subjects
Normalization (statistics), Physics, Superposition principle, Quantum games, Probability amplitude, Quantum mechanics, General Chemistry, Quantum entanglement, Quantum, Education
Abstract

The learning of quantum mechanics is contingent upon an understanding of the physical significance of the mathematics that one must perform. Concepts such as normalization, superposition, interference, probability amplitude, and entanglement can prove challenging for the beginning student. Several class activities that use a nonclassical version of tic-tac-toe are described to introduce several topics in an undergraduate quantum mechanics course. Quantum tic-tac-toe (QTTT) is a quantum analogue of classical tic-tac-toe (CTTT) and can be used to demonstrate the use of superposition in movement, qualitative (and later quantitative) displays of entanglement, and state collapse due to observation. QTTT can be used to aid student understanding in several other topics with the aid of proper discussion.

Published
2014
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20. Jet-Cooled Spectroscopy of the α-Methylbenzyl Radical: Probing the State-Dependent Effects of Methyl Rocking Against a Radical Site

Author

Lyudmila V. Slipchenko, Neil J. Reilly, Deepali N. Mehta-Hurt, Michael C. McCarthy, Ben Nebgen, Timothy S. Zwier, Ross D. Hoehn, Nathanael M. Kidwell, and Damian L. Kokkin

Subjects
Jet (fluid), Rotor (electric), Photochemistry, Fluorescence, Molecular electronic transition, law.invention, chemistry.chemical_compound, chemistry, law, Ionization, Physical and Theoretical Chemistry, Spectroscopy, Excitation, Methyl group
Abstract

The state-dependent spectroscopy of α-methylbenzyl radical (α-MeBz) has been studied under jet-cooled conditions. Two-color resonant two-photon ionization (2C-R2PI), laser-induced fluorescence, and dispersed fluorescence spectra were obtained for the D0-D1 electronic transition of this prototypical resonance-stabilized radical in which the methyl group is immediately adjacent to the primary radical site. Extensive Franck-Condon activity in hindered rotor levels was observed in the excitation spectrum, reflecting a reorientation of the methyl group upon electronic excitation. Dispersed fluorescence spectra from the set of internal rotor levels are combined with the excitation spectrum to obtain a global fit of the barrier heights and angular change of the methyl group in both D0 and D1 states. The best-fit methyl rotor potential in the ground electronic state (D0) is a flat-topped 3-fold potential (V3" = 151 cm(-1), V6" = 34 cm(-1)) while the D1 state has a lower barrier (V3' = 72 cm(-1), V6' = 15 cm(-1)) with Δφ = ± π/3, π, consistent with a reorientation of the methyl group upon electronic excitation. The ground state results are compared with calculations carried out at the DFT B3LYP level of theory using the 6-311+G(d,p) basis set, and a variety of excited state calculations are carried out to compare against experiment. The preferred geometry of the methyl rotor in the ground state is anti, which switches to syn in the D1 state and in the cation. The calculations uncover a subtle combination of effects that contribute to the shift in orientation and change in barrier in the excited state relative to ground state. Steric interaction favors the anti conformation, while hyperconjugation is greater in the syn orientation. The presence of a second excited state close by D1 is postulated to influence the methyl rotor properties. A resonant ion-dip infrared (RIDIR) spectrum in the alkyl and aromatic CH stretch regions was also recorded, probing in a complementary way the state-dependent conformation of α-MeBz. Using a scheme in which infrared depletion occurs between excitation and ionization steps of the 2C-R2PI process, analogous infrared spectra in D1 were also obtained, probing the response of the CH stretch fundamentals to electronic excitation. A reduced-dimension Wilson G-matrix model was implemented to simulate and interpret the observed infrared results. Finally, photoionization efficiency scans were carried out to determine the adiabatic ionization threshold of α-MeBz (IP = 6.835 ± 0.002 eV) and provide thresholds for ionization out of specific internal rotor levels, which report on the methyl rotor barrier in the cation state.

Published
2013
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21. Novel genetic loci associated with hippocampal volume

Author

Benjamin S. Aribisala, Marjolein M.J. van Donkelaar, Randy L. Gollub, Rachel M. Brouwer, Norman Delanty, Tomas Axelsson, Oscar L. Lopez, Thomas Espeseth, Alejandro Arias-Vasquez, Kristel R. van Eijk, Tien Yin Wong, Jeroen van der Grond, Georg Homuth, James T. Becker, Sebastian Guelfi, Anton J. M. de Craen, Bruno Vellas, Christopher R.K. Ching, Charles C. DeCarli, Janita Bralten, Lars T. Westlye, Ryota Hashimoto, Sampath Arepalli, Bertram Müller-Myhsok, Loes M. Olde Loohuis, Sudha Seshadri, Simon E. Fisher, K Hegenscheid, Konstantinos Arfanakis, Zdenka Pausova, Robert C. Green, Simone Reppermund, Katie L. McMahon, Ashley Beecham, Daan van Rooij, Marcel P. Zwiers, Karen A. Mather, Randy L. Buckner, Edith Hofer, Marcella Rietschel, Fabrice Crivello, Ronald H. Zielke, G. Bruce Pike, Thomas W. Mühleisen, Myriam Fornage, Kazutaka Ohi, Gareth E. Davies, Chantal Depondt, Gabriel Cuellar-Partida, Iryna O. Fedko, Peter R. Schofield, Steven G. Potkin, Albert Hofman, Paul M. Thompson, Wiro J. Niessen, Deborah Janowitz, Nicholas G. Martin, Li Shen, Mina Ryten, Meike W. Vernooij, Michael E. Weale, Tonya White, Dennis van 't Ent, Sudheer Giddaluru, Nanda Rommelse, Wei Wen, Sven J. van der Lee, Eco J. C. de Geus, Aaron Goldman, Joanne E. Curran, Qiang Chen, Jean Shin, Wayne C. Drevets, Thomas H. Mosley, Matthias Nauck, Massimo Pandolfo, Anders M. Dale, Paul A. Nyquist, Girma Woldehawariat, Francis J. McMahon, Najaf Amin, Emma J. Rose, Norbert Hosten, David J. Stott, Sigurdur Sigursson, Andrew J. Saykin, M. Kamran Ikram, Pieter J. Hoekstra, Neda Jahanshad, Grant W. Montgomery, Michael Weiner, Aad van der Lugt, Esther Walton, Gunter Schumann, Clyde Francks, Narelle K. Hansell, Xinmin Liu, Herve Lemaitre, Cornelia M. van Duijn, Ralph L. Sacco, Clinton B. Wright, Arvin Saremi, Clifford R. Jack, Andre G. Uitterlinden, G. Donohoe, Tomáš Paus, Michael Griswold, Peter T. Fox, Alan B. Zonderman, Lukas Pirpamer, Christiane Wolf, Aiden Corvin, Shannon L. Risacher, Ian Ford, Philippe Amouyel, Henrik Walter, Beng-Choon Ho, William T. Longstreth, M. Arfan Ikram, Hieab H.H. Adams, Colin Smith, Sungeun Kim, Simon Lovestone, Stefan Ehrlich, Benno Pütz, Markus M. Nöthen, Susana Muñoz Maniega, Ian J. Deary, Elena Shumskaya, Susan H. Blanton, Jerome I. Rotter, Neeltje E.M. van Haren, Mar Matarin, I. Kloszewska, Ganesh Chauhan, Anita L. DeStefano, Barbara Franke, Lars Nyberg, Tatiana Foroud, Tianye Jia, Manon Bernard, Unn K. Haukvik, Rebecca F. Gottesman, Srdjan Djurovic, Ching-Yu Cheng, Lachlan T. Strike, Alex P. Zijdenbos, Jouke-Jan Hottenga, Vince D. Calhoun, Yuri Milaneschi, David C. Glahn, Phil Lee, Amelia A. Assareh, Adaikalavan Ramasamy, Emma Sprooten, Debra A. Fleischman, David R. McKay, J. Raphael Gibbs, Bruce M. Psaty, Kazima B. Bulayeva, Bryan J. Traynor, Vilmundur Gudnason, Jessika E. Sussmann, Alexander Teumer, Guillén Fernández, Katharina Wittfeld, Christophe Tzourio, Dennis van der Meer, Wolfgang Hoffmann, Sebastian Mohnke, David C. Liewald, Jordan W. Smoller, Theo G.M. van Erp, Marcel Van Der Brug, Dara M. Cannon, Lenore J. Launer, D. Ames, Juan C. Troncoso, Brenda W.J.H. Penninx, Dhananjay Vaidya, Thomas D. Dyer, Marie-José van Tol, Han G. Brunner, Andrew Singleton, Lavinia Athanasiu, Adam M. Brickman, Eric Westman, P. Mecocci, Sandra Barral, Dick J. Veltman, Catharina A. Hartman, Benedicto Crespo-Facorro, Alexa S. Beiser, Vincent Chouraki, Nhat Trung Doan, Marieke Klein, Jaap Oosterlaan, Natalie A. Royle, John B.J. Kwok, Saud Alhusaini, Ingrid Melle, Roberto Toro, Ravi Duggirala, Allissa Dillman, Reinhold Schmidt, Lisa R. Yanek, Anbupalam Thalamuthu, Helena Schmidt, Derrek P. Hibar, Albert V. Smith, Jean-Luc Martinot, Thomas H. Wassink, Jennifer S. Richards, Oliver Martinez, Joshua L. Roffman, Sylvane Desrivières, Hilkka Soininen, Rene L. Olvera, Ole A. Andreassen, Diana Tordesillas-Gutiérrez, Claudia L. Satizabal, Owen Carmichael, Lianne Schmaal, Bernd Kraemer, Martine Hoogman, Daniah Trabzuni, Oliver Grimm, Andrew M. McIntosh, René S. Kahn, Nazanin Karbalai, Margaret J. Wright, Harald H.H. Göring, Martina Papmeyer, Roberto Roiz-Santiañez, Luigi Ferrucci, David A. Bennett, Kwangsik Nho, Gianpiero L. Cavalleri, Andreas Meyer-Lindenberg, Masashi Ikeda, Avram J. Holmes, Greig I. de Zubicaray, Andreas Heinz, Tatjana Rundek, Maria del C. Valdés Hernández, Dalia Kasperaviciute, Dan L. Longo, Matthew J. Huentelman, Wiepke Cahn, Beverly G. Windham, Michael A. Nalls, Philipp G. Sämann, Stella Trompet, Vidar M. Steen, Marc M. Bohlken, Christopher D. Whelan, Hilleke E. Hulshoff Pol, Susanne Erk, Dorret I. Boomsma, Dirk J. Heslenfeld, Masaki Fukunaga, D. Hoehn, Stephen M. Lawrie, Mark E. Bastin, Marco P. Boks, M. Mallar Chakravarty, M. R. Cookson, C. McDonald, Magda Tsolaki, Badri N. Vardarajan, Jason L. Stein, Jan K. Buitelaar, Erik G. Jönsson, Oliver Gruber, Robert Johnson, Jingyun Yang, Joshua C. Bis, J. Wouter Jukema, Tulio Guadalupe, Nina Romanczuk-Seiferth, Kjetil Nordbø Jørgensen, Henry Brodaty, Diane M. Becker, Anouk den Braber, Allison C. Nugent, Thomas Wolfers, John Hardy, Joanna M. Wardlaw, Michelle Luciano, Christine Macare, Dena G. Hernandez, D. Morris, John Blangero, Andrew J. Schork, Daniel R. Weinberger, Johanna Hass, Andrew Simmons, Micael Andersson, Lucija Abramovic, David S. Knopman, Mark Jenkinson, Roel A. Ophoff, Sanjay M. Sisodiya, Boris A. Gutman, Asta Håberg, Stephanie Le Hellard, Stéphanie Debette, Nicola J. Armstrong, Sarah E. Medland, Hans J. Grabe, Henry Völzke, Thomas E. Nichols, Manuel Mattheisen, Sven Cichon, Venkata S. Mattay, Ingrid Agartz, Stefan Ropele, Lorna M. Lopez, Hans van Bokhoven, Philip L. De Jager, Miguel E. Rentería, Laura Almasy, Arthur W. Toga, Michael Czisch, Florian Holsboer, Ryota Kanai, Nic J.A. van der Wee, Peter Kochunov, Perminder S. Sachdev, Andre F. Marquand, Christian Enzinger, Anderson M. Winkler, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Metacohorts Consortium, Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, sans affiliation, QIMR Berghofer Medical Research Institute, University of Washington [Seattle], Department of Psychiatry, Donders Centre for Neuroscience, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University Medical Center [Utrecht], Department of Neurology and Neurosurgery [Montreal], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Sahlgrenska University Hospital [Gothenburg], Department of Biomedical Engineering, Illinois Institute of Technology (IIT), Rush University Medical Center [Chicago], University of Edinburgh, Lagos State University (LASU), Assistance Publique - Hôpitaux de Marseille (APHM), University of Oslo (UiO), Department of medical sciences, Uppsala University-Molecular Medicine-Science for Life Laboratory, John P. Hussman Institute for Human Genomics, University of Miami Leonard M. Miller School of Medicine (UMMSM), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), Douglas Mental Health University Institute, McGill University = Université McGill [Montréal, Canada], Université Lille Nord de France (COMUE), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe d'imagerie neurofonctionnelle (GIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Haukeland University Hospital, University of Bergen (UiB), Ames Laboratory [Ames, USA], Iowa State University (ISU)-U.S. Department of Energy [Washington] (DOE), Johns Hopkins University School of Medicine [Baltimore], Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, International Max Planck Research School for Language Sciences (IMPRS ), Laboratory of Neuro Imaging [Los Angeles] (LONI), Department of Mathematics [UCLA], Georgia Institute of Technology [Atlanta], Medizinische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Germany, Greifswald University Hospital, Beijing Normal University (BNU), Aalborg University [Denmark] (AAU), UCL Institute of Neurology and Epilepsy Society, Department of Medicine, Imperial College London, Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Medstar Research Institute, Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Genomics, Life and Brain Center, University of Bonn, Institute of Human Genetics, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], VU University Medical Center [Amsterdam], Indiana University School of Medicine, Indiana University System, Indiana Alzheimer Disease Center, Indiana University System-Indiana University System, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Department of Neurology, Statistical Genetics Group, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], Department of Neurology [Austria], Medical University Graz, Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, INSERM, Neuroepidemiology U708, Bordeaux, France, Department of Neurosciences [San Diego], University of California [San Diego] (UC San Diego), Department of Cognitive Sciences [San Diego], Wuhan University [China], Plymouth University, Dpt of Psychiatry [New Haven], Yale University School of Medicine, Queensland Institute of Medical Research, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Department of Genetics, King Faisal Specialist Hospital and Research Centre, Depts of Radiology, Leiden University Medical Center (LUMC), University of Twente [Netherlands], Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), RCMG Ghent, Universiteit Gent = Ghent University [Belgium] (UGENT), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), National Institutes of Health [Bethesda] (NIH), Biospective [Montréal], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Université de Lille, Department of Clinical Genetics, Department of Experimental Physics, National University of Ireland Maynooth (Maynooth University), Texas Biomedical Research Institute [San Antonio, TX], The University of Texas Health Science Center at Houston (UTHealth), 849 Department of Human Genetics, Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Dementia Collaborative Research Centre, Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Department of Psychiatry [Boston], Massachusetts General Hospital [Boston], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], The Mind Research Network, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Division of Molecular and Cellular Therapeutics, Northwestern Polytechnical University [Xi'an] (NPU), Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Division of Medical Genetics, University of Basel (Unibas), Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Trinity College Dublin-St. James's Hospital, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], York Structural Biology Laboratory, Department of Chemistry, University of York [York, UK], Harvard Medical School [Boston] (HMS), Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], School of Psychology, University of Queensland, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratory of Neurogenetics, Department of Genomics, Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), École des hautes études en sciences sociales (EHESS), Department of Radiology, Mayo Clinic, Robertson Centre for Biostatistics, University of Glasgow, Human Genetics Center, Department of Medical and Molecular Genetics, Rensselaer Polytechnic Institute (RPI), Department of Physics, Okayama University, Okayama University, University of New Haven [Connecticut], Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Public Health Genomics Unit, Department of Mathematics, University of Colorado, University of Colorado [Boulder], Faculty of Medicine, University of Iceland [Reykjavik], Icelandic Heart Association, Kopavogur, Iceland., University of Science, VNU-HCM, University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Department of Medical Genetics, HMNC Brain Health, University of Oxford [Oxford], University of Florida [Gainesville] (UF), Göteborgs Universitet (GU), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Brain Centre Rudolf Magnus [Utrecht], School of Psychology, University of Sussex, Brighton BN1 9QH, UK, University of Sussex, Institute of Cognitive Neuroscience, University College of London [London] (UCL), Medical University of Łódź (MUL), Mayo Clinic [Rochester], University of Maryland School of Medicine, University of Maryland System-University of Maryland System-University of Maryland [Baltimore County] (UMBC), University of Maryland System, School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Université de Cergy Pontoise (UCP), Université Paris-Seine, Lymphocyte Cell Biology Unit, Laboratory of Genetics, Psychiatry Institute, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Department of Health and Human Services, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia (UNIPG), Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Medical Faculty [Mannheim], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, University of Mississippi Medical Center (UMMC), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Department of Statistics [Coventry], University of Warwick [Coventry], Delft University of Technology (TU Delft), Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), Osaka University [Osaka], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Cedars-Sinai Medical Center, Politecnico di Milano [Milan] (POLIMI), University of Applied Sciences [Munich], Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, National Institute of Aging, 3rd Department of Neurology, Aristotle University of Thessaloniki-General Hospital of Thessaloniki George Papanikolaou, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Genentech, Inc. [San Francisco], Psychiatry and Leiden Institute for Brain and Cognition, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Community Medicine, Berlin School of Mind and Brain [Berlin], Humboldt-Universität zu Berlin, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Centre for Population Health Sciences, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet [Stockholm], University of Pretoria [South Africa], University of Missouri [Columbia] (Mizzou), University of Missouri System, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], University of Southern California (USC), University of California (UC)-University of California (UC), Sans affiliation, Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], University of Toronto, Radboud University [Nijmegen], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universität Bonn = University of Bonn, Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), Yale School of Medicine [New Haven, Connecticut] (YSM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), King Faisal Specialist Hospital and Research Centre (KFSH & RC), Universiteit Leiden-Universiteit Leiden, University of Twente, University of California [Irvine] (UC Irvine), Universiteit Gent = Ghent University (UGENT), Centre épigénétique et destin cellulaire (EDC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], University of Oxford, University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Università degli Studi di Perugia = University of Perugia (UNIPG), University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Leipzig-Universität Leipzig, University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, University of Eastern Finland, Universiteit Leiden, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt University Of Berlin, Radboud University [Nijmegen]-Radboud University [Nijmegen], School of Medicine / Clinical Medicine, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Other departments, Adult Psychiatry, ARD - Amsterdam Reproduction and Development, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], McGill University-McGill University, Sahlgrenska University Hospital, McGill University, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), University of Bergen (UIB), Iowa State University (ISU)-U.S. Department of Energy (DOE), Beijing Normal University, Karakter Child and Adolescent Psychiatry University Center Nijmegen, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Gènes, Synapses et Cognition, Ghent University [Belgium] (UGENT), National University of Ireland Maynooth (NUIM), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Okayama University [Okayama], University of Florida [Gainesville], Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Aristotle University of Thessaloniki-G. Papanikolaou Hospital, Humboldt Universität zu Berlin, University of Missouri [Columbia], Epidemiology, Radiology & Nuclear Medicine, Medical Informatics, Internal Medicine, Neurology, Biological Psychology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, Cognitive Psychology, IBBA, APH - Personalized Medicine, Amsterdam Neuroscience - Brain Imaging, MUMC+: DA Klinische Genetica (5), Klinische Genetica, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Anatomy and neurosciences, APH - Digital Health, Hal, GIN, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Universidad de Cantabria, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées

Subjects
Male, Netherlands Twin Register (NTR), Genome-wide association study, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, Spatial memory, 0302 clinical medicine, 610 Medicine & health, Child, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Episodic memory, Aged, 80 and over, Subiculum, 220 Statistical Imaging Neuroscience, COMMON VARIANTS, ALZHEIMERS-DISEASE, ddc:500, Alzheimer's disease, genetics [Methionine Sulfoxide Reductases], Science, Locus (genetics), genetics [Protein-Serine-Threonine Kinases], Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Alzheimer Disease, ASTN2 protein, human, Humans, GENOME-WIDE ASSOCIATION, METAANALYSIS, Aged, Glycoproteins, Dentate gyrus, MEMORY, medicine.disease, R1, 030104 developmental biology, nervous system, Genetic Loci, MSRB3 protein, human, 030217 neurology & neurosurgery, 0301 basic medicine, General Physics and Astronomy, genetics [Alzheimer Disease], Hippocampal formation, Hippocampus, Genome-wide association studies, Taugasjúkdómar, Cohort Studies, DPP4 protein, human, TEMPORAL-LOBE EPILEPSY, BRAIN-REGIONS, genetics [Dipeptidyl Peptidase 4], genetics [Nerve Tissue Proteins], Genetics, Multidisciplinary, Neurodegenerative diseases, BIPOLAR DISORDER, Organ Size, Middle Aged, SUBFIELDS, Protein-Serine-Threonine Kinases, growth & development [Hippocampus], Female, genetics [Glycoproteins], Microtubule-Associated Proteins, Medical Genetics, Neuroinformatics, Adult, genetics [Microtubule-Associated Proteins], Adolescent, SUSCEPTIBILITY LOCI, Dipeptidyl Peptidase 4, genetics [Protein Serine-Threonine Kinases], Nerve Tissue Proteins, Bioinformatik och systembiologi, Protein Serine-Threonine Kinases, Biology, physiopathology [Alzheimer Disease], 150 000 MR Techniques in Brain Function, Young Adult, MAST4 protein, human, medicine, Journal Article, Erfðafræði, Genetic Predisposition to Disease, ddc:610, Medicinsk genetik, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Bioinformatics and Systems Biology, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Rannsóknir, General Chemistry, Methionine Sulfoxide Reductases, 150 Psychology, Genome-Wide Association Study
Abstract

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness., published version, peerReviewed

Published
2017
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22. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group

Author

B.W.J.H. Penninx, Henry Völzke, Wiro J. Niessen, Nicholas G. Martin, Bernhard T. Baune, D. Schoepf, Michael Czisch, Neda Jahanshad, Jeremy Hall, Walter Heindel, Knut Schnell, Carsten Konrad, Nikolay A. Bokhan, Miguel E. Rentería, Lyubomir I. Aftanas, Christopher G. Davey, Martin Walter, Sean N. Hatton, M. A. Ikram, Joshua W. Cheung, Baptiste Couvy-Duchesne, M Selonke, Dick J. Veltman, Meng Li, Paul M. Thompson, M-J van Tol, Katharina Wittfeld, Thomas Frodl, L. S. van Velzen, Ben J. Harrison, Matthew D. Sacchet, Bartosz Zurowski, D. Hoehn, Ilya M. Veer, Nils Opel, Beata R. Godlewska, Meike W. Vernooij, Eva-Maria Frey, Henning Tiemeier, Oliver Gruber, Bernd Krämer, Angela Carballedo, Derrek P. Hibar, G.I. de Zubicaray, Ian H. Gotlib, Lianne Schmaal, Dominik Grotegerd, Thomas Nickson, Andrew M. McIntosh, Roberto Goya-Maldonado, Jim Lagopoulos, Philipp G. Sämann, Deborah Janowitz, J.E. Sussmann, Heather C. Whalley, Geoffrey B. Hall, Ivan Brack, Elisabeth Schramm, T.G.M. van Erp, Henrik Walter, Volker Arolt, Daniel Bos, Robin Bülow, Katie L. McMahon, Claus Normann, Sarah E. Medland, Lachlan T. Strike, Glenda MacQueen, Hans-Jörgen Grabe, Nathan A. Gillespie, Benson Mwangi, Bo Cao, Udo Dannlowski, Harald Kugel, Jair C. Soares, Natalie T. Mills, N.J. van der Wee, Margaret J. Wright, Ian B. Hickie, Martina Papmeyer, A. Hofman, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Anatomy and neurosciences, APH - Digital Health, Epidemiology, Radiology & Nuclear Medicine, Neurology, Medical Informatics, and Child and Adolescent Psychiatry / Psychology

Subjects
Male, pathology [Frontal Lobe], Audiology, methods [Magnetic Resonance Imaging], 0302 clinical medicine, взрослые, pathology [Brain], pathology [Gray Matter], diagnostic imaging [Cerebral Cortex], Gray Matter, LIFE-SPAN, Cerebral Cortex, First episode, pathology [Depressive Disorder, Major], Brain, Magnetic Resonance Imaging, Temporal Lobe, Frontal Lobe, 3. Good health, Psychiatry and Mental health, medicine.anatomical_structure, Frontal lobe, VOXEL-BASED MORPHOMETRY, pathology [Gyrus Cinguli], Major depressive disorder, Female, Original Article, DRUG-NAIVE, methods [Neuroimaging], Psychology, psychology [Neuroimaging], Adult, medicine.medical_specialty, MOOD DISORDERS, магнитно-резонансная томография головного мозга, Adolescent, Prefrontal Cortex, Neuroimaging, 610 Medicine & health, SURFACE-AREA, diagnostic imaging [Depressive Disorder, Major], Gyrus Cinguli, behavioral disciplines and activities, 03 medical and health sciences, Cellular and Molecular Neuroscience, THICKNESS, mental disorders, medicine, Humans, ddc:610, Molecular Biology, Anterior cingulate cortex, GRAY-MATTER VOLUME, METAANALYSIS, корковые аномалии, Depressive Disorder, Major, pathology [Temporal Lobe], Voxel-based morphometry, HEALTHY-CHILDREN, medicine.disease, R1, pathology [Prefrontal Cortex], 030227 psychiatry, депрессивные расстройства, Superior frontal gyrus, ANTERIOR CINGULATE CORTEX, Posterior cingulate, pathology [Cerebral Cortex], Orbitofrontal cortex, Neuroscience, подростки, 030217 neurology & neurosurgery
Abstract

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Published
2017
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23. Experimental evaluation of the generalized vibrational theory of G protein-coupled receptor activation

Author

John D. McCorvy, David E. Nichols, Ross D. Hoehn, Sabre Kais, and Hartmut Neven

Subjects
0301 basic medicine, Agonist, Stereochemistry, medicine.drug_class, Central nervous system, Heterocyclic Compounds, 4 or More Rings, Vibration, 03 medical and health sciences, 0302 clinical medicine, Calcium flux, Alternative theory, medicine, Humans, Receptor, Serotonin, 5-HT2A, Receptor, 5-HT receptor, G protein-coupled receptor, Multidisciplinary, Chemistry, Amphetamines, Enzyme Activation, Smell, 030104 developmental biology, medicine.anatomical_structure, Physical Sciences, Receptor activation, Serotonin 5-HT2 Receptor Agonists, 030217 neurology & neurosurgery, Signal Transduction
Abstract

Recently, an alternative theory concerning the method by which olfactory proteins are activated has garnered attention. This theory proposes that the activation of olfactory G protein-coupled receptors occurs by an inelastic electron tunneling mechanism that is mediated through the presence of an agonist with an appropriate vibrational state to accept the inelastic portion of the tunneling electron’s energy. In a recent series of papers, some suggestive theoretical evidence has been offered that this theory may be applied to nonolfactory G protein-coupled receptors (GPCRs), including those associated with the central nervous system (CNS). [Chee HK, June OS (2013) Genomics Inform 11(4):282–288; Chee HK, et al. (2015) FEBS Lett 589(4):548–552; Oh SJ (2012) Genomics Inform 10(2):128–132]. Herein, we test the viability of this idea, both by receptor affinity and receptor activation measured by calcium flux. This test was performed using a pair of well-characterized agonists for members of the 5-HT2 class of serotonin receptors, 2,5-dimethoxy-4-iodoamphetamine (DOI) and N,N-dimethyllysergamide (DAM-57), and their respective deuterated isotopologues. No evidence was found that selective deuteration affected either the binding affinity or the activation by the selected ligands for the examined members of the 5-HT2 receptor class.

Published
2017
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24. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author

G. Bruce Pike, Marcel P. Zwiers, Andreas Meyer-Lindenberg, Jeroen van der Grond, Randy L. Gollub, Karen A. Mather, Andrew J. Schork, Vidar M. Steen, Marc M. Bohlken, Nhat Trung Doan, Derek W. Morris, John B.J. Kwok, Emma J. Rose, Johanna Hass, Andrew Simmons, Tian Ge, Reinhold Schmidt, Micael Andersson, Ian J. Deary, Christopher Chen, Derrek P. Hibar, Simon E. Fisher, Lucija Abramovic, Marcella Rietschel, Edith Hofer, Simon Lovestone, Clyde Francks, Christopher R.K. Ching, Srdjan Djurovic, Lachlan T. Strike, Lorna M. Lopez, Rene L. Olvera, Owen Carmichael, M. Arfan Ikram, Andre F. Marquand, Christine Macare, W.T. Longstreth, Philippe Amouyel, Aaron L. Goldman, Wolfgang Hoffmann, Philip L. De Jager, David C. Liewald, Harald H H Göring, Aad van der Lugt, David Ames, Neeltje E.M. van Haren, Lars Nyberg, Nina Romanczuk-Seiferth, Lukas Pirpamer, Stefan Ehrlich, Alexa S. Beiser, Lianne Schmaal, Hilkka Soininen, Mark Jenkinson, Kazima B. Bulayeva, Anderson M. Winkler, Mike A. Nalls, Diana Tordesillas-Gutiérrez, Martine Hoogman, Lars T. Westlye, Loes M. Olde Loohuis, Andrew Singleton, Gabriel Cuellar-Partida, Randy L. Buckner, Dorret I. Boomsma, Dena G. Hernandez, Steven G. Potkin, Sudha Seshadri, Bertram Müller-Myhsok, D. Hoehn, Gareth E. Davies, Chantal Depondt, Henrik Walter, Michael E. Weale, Deborah Janowitz, Susanne Erk, Iryna O. Fedko, Daniel R. Weinberger, Nic J A van der Wee, Jean-Luc Martinot, Jessica A. Turner, Marieke Klein, Sandra Barral, Sebastian Mohnke, Albert Hofman, Ingrid Melle, Saud Alhusaini, Vincent Chouraki, Stephen M. Lawrie, Mark E. Bastin, Juan C. Troncoso, Jean Shin, Wiro J. Niessen, Diane M. Becker, Laura Almasy, Anders M. Dale, Benjamin S. Aribisala, Dennis van 't Ent, Marco P. Boks, M. Mallar Chakravarty, Paul M. Thompson, David Reese McKay, Michael Griswold, John Blangero, Narelle K. Hansell, Eco J. C. de Geus, Paul A. Nyquist, Susana Muñoz Maniega, Sampath Arepalli, Tatjana Rundek, Dan L. Longo, Anton J. M. de Craen, Rebekah McWhirter, Nazanin Mirza-Schreiber, Henning Tiemeier, Girma Woldehawariat, Sven Cichon, Irene Pappa, Amelia A. Assareh, Sudheer Giddaluru, Pieter J. Hoekstra, Hieab H.H. Adams, Hilleke E. Hulshoff Pol, Grant W. Montgomery, Roel A. Ophoff, Markus M. Nöthen, Sara Pudas, Sigurdur Sigurdsson, Arthur W. Toga, Tien Yin Wong, Massimo Pandolfo, Corina U. Greven, Esther Walton, Tianye Jia, David J. Stott, Gunter Schumann, Marie-José van Tol, Dalia Kasperaviciute, Thomas Wolfers, Henry Völzke, Ian Ford, Shannon L. Risacher, Jessika E. Sussmann, Nicholas G. Martin, Wei Wen, Daniah Trabzuni, Iwona Kłoszewska, Kwangsik Nho, Gianpiero L. Cavalleri, Adam M. Brickman, Sungeun Kim, Andreas Heinz, Ralph L. Sacco, Neda Jahanshad, Velandai Srikanth, Elena Shumskaya, Susan H. Blanton, Katharina Wittfeld, Badri N. Vardarajan, Joshua C. Bis, Joanne E. Curran, Helena Schmidt, Peter T. Fox, Clifford R. Jack, Jason L. Stein, Laura M. E. Blanken, Thomas Espeseth, Dick J. Veltman, Sebastian Guelfi, Margaret J. Wright, Norman Delanty, Michael Czisch, Martina Papmeyer, Oscar L. Lopez, Marjolein M. J. Van Donkelaar, Bruce M. Psaty, Jan K. Buitelaar, Sven J. van der Lee, David A. Bennett, Beng-Choon Ho, Oliver Martinez, Wiepke Cahn, Li Shen, J. Wouter Jukema, Janita Bralten, Peter Kochunov, Greig I. Zubicaray, Marcel P. van der Brug, Ching-Yu Cheng, Philipp G. Sämann, Stella Trompet, Roberto Roiz-Santiañez, David C. Glahn, Allissa Dillman, Venkata S. Mattay, Dara M. Cannon, Michael W. Weiner, Christopher D. Whelan, Alexander Teumer, Sylvane Desrivières, Ole A. Andreassen, Thomas E. Nichols, Manuel Mattheisen, Matthias Nauck, René S. Kahn, Albert V. Smith, Colin Smith, Vilmundur Gudnason, Denis A. Evans, Anouk den Braber, Katie L. McMahon, Han G. Brunner, Florian Holsboer, Yuri Milaneschi, Andrew J. Saykin, Jiemin Liao, Vince D. Calhoun, Neelum T. Aggarwal, Dennis van der Meer, Hans J. Grabe, Anita L. DeStefano, Claudia L. Satizabal, Alan B. Zonderman, Alex P. Zijdenbos, Tulio Guadalupe, Ingrid Agartz, Jordan W. Smoller, Allison C. Nugent, Alejandro Arias-Vasquez, Masashi Ikeda, Avram J. Holmes, Brenda W.J.H. Penninx, John Hardy, Herve Lemaitre, Charles DeCarli, Patrizia Mecocci, Catharina A. Hartman, Tomas Axelsson, Oliver Grimm, Irina Filippi, Wayne C. Drevets, Hans van Bokhoven, Miguel E. Rentería, Aiden Corvin, Ryota Kanai, Kristel R. van Eijk, Andrew M. McIntosh, Jouke-Jan Hottenga, Roberto Toro, Lavinia Athanasiu, Joanna M. Wardlaw, Thomas H. Mosley, Mina Ryten, Meike W. Vernooij, Michelle Luciano, Joshua L. Roffman, Rebecca F. Gottesman, Dhananjay Vaidya, Ryota Hashimoto, Mar Matarin, Adaikalavan Ramasamy, Jerome I. Rotter, Ryan L. Muetzel, Konstantinos Arfanakis, Theo G.M. van Erp, Ganesh Chauhan, Xinmin Liu, Tomáš Paus, Emma Sprooten, Christiane Wolf, David S. Knopman, Manon Bernard, Zdenka Pausova, Bryan J. Traynor, Maria C. Valdés Hernández, Robert C. Green, Russell Thomson, Ravi Duggirala, Lisa R. Yanek, Luigi Ferrucci, Bing Xu, Thomas D. Dyer, Thomas H. Wassink, Eric Westman, Jennifer S. Richards, Phil H. Lee, Benno Pütz, Mark R. Cookson, Benedicto Crespo-Facorro, Natalie A. Royle, Bernd Kraemer, Katrin Hegenscheid, Francis J. McMahon, Tatiana Foroud, M. Kamran Ikram, Myriam Fornage, Nanda Rommelse, Saima Hilal, Perminder S. Sachdev, Qiang Chen, Najaf Amin, Lenore J. Launer, Norbert Hosten, Guillén Fernández, Simone Reppermund, Ashley Beecham, Dirk J. Heslenfeld, Masaki Fukunaga, Cornelia M. van Duijn, Clinton B. Wright, Erik G. Jönsson, Sanjay M. Sisodiya, Oliver Gruber, Christophe Tzourio, André G. Uitterlinden, Robert Johnson, Jaap Oosterlaan, Bernard Mazoyer, H. Ronald Zielke, Stephanie Le Hellard, Jingyun Yang, Georg Homuth, Stéphanie Debette, Nicola J. Armstrong, Sarah E. Medland, Henry Brodaty, Beverly G Windham, Gary Donohoe, Rachel M. Brouwer, James T. Becker, Kumar B. Rajan, Daan van Rooij, Thomas W. Mühleisen, Kazutaka Ohi, Peter R. Schofield, Tonya White, Barbara Franke, Unn K. Haukvik, Debra A. Fleischman, J. Raphael Gibbs, Colm McDonald, Anbupalam Thalamuthu, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Keck School of Medicine [Los Angeles], University of Southern California (USC), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Johns Hopkins University (JHU), QIMR Berghofer Medical Research Institute, Leiden University Medical Center (LUMC), Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of Miami Leonard M. Miller School of Medicine (UMMSM), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, Department of Neurology and Neurosurgery [Montreal], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Royal College of Surgeons in Ireland (RCSI), Umeå University, Illinois Institute of Technology (IIT), Rush University Medical Center [Chicago], University of Edinburgh, Lagos State University (LASU), University of New South Wales [Sydney] (UNSW), Murdoch University, University of Oslo (UiO), Uppsala University, Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Toronto, University of Washington [Seattle], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Columbia University Medical Center (CUMC), Columbia University [New York], Pennington Biomedical Research Center, Louisiana State University (LSU), McGill University = Université McGill [Montréal, Canada], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lieber Institute for Brain Development [Baltimore] (LIBD), University of California [Los Angeles] (UCLA), University of California, Vrije Universiteit Amsterdam [Amsterdam] (VU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Massachusetts General Hospital [Boston], Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Maison de Solenn [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Bergen (UiB), Haukeland University Hospital, Johns Hopkins University School of Medicine [Baltimore], Universität Heidelberg [Heidelberg], University of Mississippi Medical Center (UMMC), International Max Planck Research School for Language Sciences (IMPRS ), Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Language and Genetics Department [Nijmegen], National University of Singapore (NUS), Medical University Graz, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Yale University [New Haven], University College of London [London] (UCL), Imperial College London, Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Medstar Research Institute, Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Institute of Human Genetics, University of Bonn, Department of Genomics, Life and Brain Center, Groupe d'imagerie neurofonctionnelle (GIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Dpt of Psychiatry [New Haven], Yale University School of Medicine, Department of Psychiatry, VU University Medical Center [Amsterdam], Department of Psychology [Minneapolis], University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Indiana University System, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Statistical Genetics Group, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), INSERM, Neuroepidemiology U708, Bordeaux, France, Department of Cognitive Sciences [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Department of Neurosciences [San Diego], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Queensland Institute of Medical Research, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics, King Faisal Specialist Hospital and Research Centre, Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Depts of Radiology, University of Twente [Netherlands], Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Deutsche Bundesbank, National Institutes of Health [Bethesda] (NIH), General Internal Medicine, Johns Hopkins School of Medicine, Biospective [Montréal], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Department of Clinical Genetics, Department of Medical Parasitology and Mycology, School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Tehran University of Medical Siences, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, TX], 849 Department of Human Genetics, Dementia Collaborative Research Centre, Centre for Healthy Brain Ageing, Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Université de Lausanne (UNIL), Department of Psychiatry [Boston], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Division of Molecular and Cellular Therapeutics, Metacohorts Consortium, Division of Medical Genetics, University of Basel (Unibas), Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Trinity College Dublin-St. James's Hospital, Department of Materials Science & Metallurgy, University of Cambridge [UK] (CAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], VU University Amsterdam, Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), School of Psychology, University of Queensland, Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Molecular and Cellular Therapeutics, Department of Neurology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratory of Neurogenetics, Department of Genomics, Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Department of Radiology, Mayo Clinic, Department of Medical and Molecular Genetics, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, Department of Physics, Okayama University, Okayama University, National Institute of Aging, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Public Health Genomics Unit, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Department of Mathematics, University of Colorado, University of Colorado [Boulder], Icelandic Heart Association, Kopavogur, Iceland., Faculty of Medicine, University of Iceland [Reykjavik], Department of Molecular Neurosciences, Institute of Neurology, UCL, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University [Osaka], Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Tohoku University [Sendai], Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Centre for Allergy Research, Karolinska Institutet [Stockholm], Interuniversity Cardiology Institute Netherlands, Institute of Cognitive Neuroscience, School of Psychology, University of Sussex, Brighton BN1 9QH, UK, University of Sussex, Medical University of Łódź (MUL), Mayo Clinic [Rochester], University of Maryland School of Medicine, University of Maryland System-University of Maryland System-University of Maryland [Baltimore County] (UMBC), University of Maryland System, Department of Civil and Structural Engineering, The Hong Kong Polytechnic University [Hong Kong] (POLYU)-The Hong Kong Polytechnic University [Hong Kong] (POLYU), Université de Cergy Pontoise (UCP), Université Paris-Seine, Lymphocyte Cell Biology Unit, Laboratory of Genetics, Laboratoire de Statistique Théorique et Appliquée (LSTA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Psychiatry Institute, Department of Health and Human Services, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia (UNIPG), Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Medical Faculty [Mannheim], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, Université de Toulon - UFR Lettres et Sciences Humaines (UTLN UFR LSH), Université de Toulon (UTLN), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Warwick Manufacturing Group [Coventry] (WMG), University of Warwick [Coventry], Department of Statistics [Warwick], Delft University of Technology (TU Delft), Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre (MNI), Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, Group Health Research Institute, Group Health Cooperative, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Cedars-Sinai Medical Center, Centre for Healthy Brain Ageing [Sydney], The University of Sydney, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Department of Medical Biochemistry and Microbiology, Department of Clinical and Experimental Epilepsy, Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Monash University [Melbourne], Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia, University of Tasmania [Hobart, Australia] (UTAS), Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Department of Epidemiology, Laboratory of Neuro Imaging [Los Angeles] (LONI), University of York [York, UK], Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Genentech, Inc. [San Francisco], Departments of Radiology and of Epidemiology [Rotterdam], Psychiatry and Leiden Institute for Brain and Cognition, Department of Neurology [Rotterdam], Institute for Community Medicine, Berlin School of Mind and Brain [Berlin], Humboldt-Universität zu Berlin, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Centre for Population Health Sciences, Department of Physics [Hong Kong University of Science and Technology], Hong Kong University of Science and Technology (HKUST), Department of Neurobiology, Care Sciences and Society, Research Laboratory for Archaeology & the History of Art, Singapore Eye Research Institute, Singapore National Eye Centre, School of Life Sciences, Arizona State University [Tempe] (ASU), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], University of Missouri [Columbia] (Mizzou), University of Missouri System, Göttingen Zentrum Geowissenschaften, Georg-August-University [Göttingen], Human Genetics Center, Psychiatry, EMGO - Mental health, Amsterdam Neuroscience - Complex Trait Genetics, Anatomy and neurosciences, Klinische Genetica, MUMC+: DA Klinische Genetica (5), RS: FHML non-thematic output, RS: GROW - School for Oncology and Reproduction, RS: GROW - R4 - Reproductive and Perinatal Medicine, Genetica & Celbiologie, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Universidad de Cantabria, Universiteit Leiden, Radboud University [Nijmegen], University of California (UC), Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Bonn = University of Bonn, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Yale School of Medicine [New Haven, Connecticut] (YSM), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), University of California (UC)-University of California (UC), Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), King Faisal Specialist Hospital and Research Centre (KFSH & RC), Universiteit Leiden-Universiteit Leiden, University of Twente, University of California [Irvine] (UC Irvine), Radboud University [Nijmegen]-Radboud University [Nijmegen], Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Università degli Studi di Perugia = University of Perugia (UNIPG), University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Leipzig-Universität Leipzig, University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, Harvard University-Massachusetts Institute of Technology (MIT), University of Eastern Finland, Humboldt University Of Berlin, Georg-August-University = Georg-August-Universität Göttingen, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Epidemiology, Child and Adolescent Psychiatry / Psychology, Ophthalmology, Radiology & Nuclear Medicine, Internal Medicine, Neurosciences, Obstetrics & Gynecology, Neurology, EMGO+ - Mental Health, Biological Psychology, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), McGill University-McGill University, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), McGill University, Technische Universität Dresden (TUD), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], University of Bergen (UIB), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Minnesota [Twin Cities], Karakter Child and Adolescent Psychiatry University Center Nijmegen, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Okayama University [Okayama], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], University of Tasmania (UTAS), Humboldt Universität zu Berlin, Department of Physics [Kowloon], University of Missouri [Columbia], Georg-August-Universität Göttingen, and the Alzheimer's Disease Neuroimaging Initiative, EPIGEN, IMAGEN, SYS

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Genome-wide association study, Disease, methods [Genome-Wide Association Study], Genome-wide association studies, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Cognition, PARKINSONS-DISEASE, pathology [Brain], genetics [Parkinson Disease], 610 Medicine & health, General Neuroscience, growth & development [Brain], physiology [Cognition], 220 Statistical Imaging Neuroscience, COMMON VARIANTS, Brain, Parkinson Disease, Phenotype, 17Q21.31 MICRODELETION, IGF-I, genetics [Oncogene Protein v-akt], Oncogene Protein v-akt, ALZHEIMERS-DISEASE, HEAD CIRCUMFERENCE, Brain size, genetics [Polymorphism, Single Nucleotide], Medical genetics, GROWTH, Neuroinformatics, medicine.medical_specialty, Neuroscience(all), European Continental Ancestry Group, genetics [Genetic Loci], Biology, Genetic correlation, Polymorphism, Single Nucleotide, 150 000 MR Techniques in Brain Function, Article, White People, 03 medical and health sciences, Image processing, SDG 3 - Good Health and Well-being, ddc:570, medicine, Journal Article, Humans, Genetic Predisposition to Disease, Gene, METAANALYSIS, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Neurology & Neurosurgery, Neuroscience (all), Height, [SCCO.NEUR]Cognitive science/Neuroscience, CONSORTIUM, Development of the nervous system, 1702 Cognitive Science, 030104 developmental biology, Genetic Loci, Human genome, BRAIN SIZE, 1109 Neurosciences, genetics [Phosphatidylinositol 3-Kinases], Neuroscience, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Contains fulltext : 165723pub.pdf (Publisher’s version ) (Closed access) Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rhogenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

Published
2016
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25. Impact of atmospheric dust emission schemes on dust production and concentration over the Arabian Peninsula

Author

Ivan Gladich, Ross D. Hoehn, Christos Fountoukis, Mohammed Ayoub, Luis Ackermann, and Adam Skillern

Subjects
geography.geographical_feature_category, 010504 meteorology & atmospheric sciences, High resolution, Atmospheric dust, 010501 environmental sciences, Particulates, Spatial distribution, Atmospheric sciences, 01 natural sciences, Geography, Peninsula, Weather Research and Forecasting Model, Climatology, Range (statistics), Computers in Earth Sciences, Statistics, Probability and Uncertainty, General Agricultural and Biological Sciences, 0105 earth and related environmental sciences, General Environmental Science, Dust emission
Abstract

This study examines the impact of two of the most advanced dust emission schemes on the predictions of the weather research and forecasting model with chemistry (WRF-Chem) over the Middle East during a summer time period. Results show significant differences between the two simulations in the spatial distribution of dust emissions as well as in their size-resolved mass discretization. The AFWA scheme simulation predicts 30 % higher dust emission fluxes than the S11 module over the Arabian Peninsula (6.7 μg m−2 s−1 compared to 4.5 μg m−2 s−1, respectively). In the S11 simulation 70 % of the emitted dust is in the 10–20 μm size range while the AFWA simulation assigns 50 % of dust emitted particles in the 6–12 μm size section. Both simulations reproduce the majority of the ambient PM10 data (more than 70 %) within a factor of two. However, the S11 simulation predicts, on average, 50 % lower PM10 concentrations compared to AFWA over the high resolution (2 × 2 km2) domain of Qatar. Previous applications of WRF-Chem may have substantially overestimated the simulated dust in this region.

Published
2016
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26. Hydrogen bonding and orientation effects on the accommodation of methylamine at the air-water interface

Author

Ross D. Hoehn, Ivan Gladich, Joseph S. Francisco, Xiao Cheng Zeng, Chongjing Zhu, Sabre Kais, Jie Zhong, and Marcelo A. Carignano

Subjects
010304 chemical physics, Methylamine, Hydrogen bond, Radical, Condensation, Inorganic chemistry, General Physics and Astronomy, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Aerosol, chemistry.chemical_compound, chemistry, 0103 physical sciences, Cloud condensation nuclei, Amine gas treating, Physical and Theoretical Chemistry, Methyl group
Abstract

Methylamine is an abundant amine compound detected in the atmosphere which can affect the nature of atmospheric aerosol surfaces, changing their chemical and optical properties. Molecular dynamics simulation results show that methylamine accommodation on water is close to unity with the hydrophilic head group solvated in the interfacial environment and the methyl group pointing into the air phase. A detailed analysis of the hydrogen bond network indicates stronger hydrogen bonds between water and the primary amine group at the interface, suggesting that atmospheric trace gases will likely react with the methyl group instead of the solvated amine site. These findings suggest new chemical pathways for methylamine acting on atmospheric aerosols in which the methyl group is the site of orientation specific chemistry involving its conversion into a carbonyl site providing hydrophilic groups for uptake of additional water. This conversion may explain the tendency of aged organic aerosols to form cloud condensation nuclei. At the same time, formation of NH2 radical and formaldehyde is suggested to be a new source for NH2 radicals at aerosol surfaces, other than by reaction of absorbed NH3. The results have general implications for the chemistry of other amphiphilic organics, amines in particular, at the surface of atmospherically relevant aerosols.

Published
2016

27. A Novel Method for Multiplex Genotyping in a Single Reactor Using GTPlex-PyroSeq

Author

Benjamin D. Hoehn, Sungwhan An, Myungsok Oh, Young-Bok Ko, Youngho Moon, and TaeJeong Oh

Subjects
Genetics, Sequence analysis, Concordance, Genotype, Multiplex polymerase chain reaction, Gene chip analysis, Molecular Medicine, Pyrosequencing, Primer (molecular biology), Biology, Genotyping, Pathology and Forensic Medicine
Abstract

Herein, we describe a novel multiplex genotyping method, GTPlex-PyroSeq. This method consists of two phases: multiplex PCR followed by a single reaction of pyrosequencing. This study demonstrates how GTPlex-PyroSeq can be adapted for the determination of multiple human papillomavirus (HPV) genotypes. A biotinylated consensus primer, GP6+, and 15 high-risk HPV type-specific primers are used for multiplex PCR. Each type-specific primer has a 5′-tag unique ID sequence connected to a pyrosequencing primer binding region. The unique ID sequence is composed of three parts: i) a single nucleotide ID representing a specific genotype; ii) a sign post; and iii) an end mark. This design allows multiple genotype determination under an ID sequence-dependent nucleotide dispensation order during pyrosequencing. Following initial studies using HPV plasmids and cell lines, we evaluated the clinical utility and effectiveness by comparing our assay with direct sequencing and HPV DNA chip analysis of 80 samples from high-risk, HPV-positive patients. We found in single-type infections, 100% concordance with direct sequencing (70 of 80 perfect matches) and 97.5% concordance with HPV DNA chip data (50 of 80 perfect matches). Additionally, our system was superior to direct sequencing in detection of multiple infections (12 of 80), with a limit of detection of 100 copies. The scalability of this multiplex system, with its open-platform design and ability to use various sample types, makes the GTPlex applicable for use in multiple settings.

Published
2012
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28. Entropy of Irreversible Processes Across a Boundary

Author

Jurgen Michael Honig and Ross D. Hoehn

Subjects
Thermodynamic state, Chemistry, Entropy production, General Chemical Engineering, Line integral, Thermodynamics
Abstract

A novel method for determining the entropy associated with irreversible processes has been provided, differing from the conventional theory of irreversible thermodynamics. It permits the direct relation of heat and work transfers in ir- reversible processes to those in reversible changes, in terms of measurable properties. The same technique is applied to the construction of thermodynamic state functions that are no longer limited to reversible phenomena. The results are then used to construct line integrals for the contribution of irreversible processes to the entropy associated with the flow of heat, work, and matter across a junction. Specific examples are provided to illustrate the procedure; they relate to changes of temperature and volume and to cycling of systems interacting with a reservoir via a thin barrier.

Published
2011
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29. The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression

Author

Gerome Breen, Daria Salyakina, Marianne B. Müller, Florian Holsboer, Martin A. Kohli, Henning Tiemeier, Thomas Bettecken, Mathias V. Schmidt, Marcus Ising, Kerry J. Ressler, Marcella Rietschel, Karin Hek, Bertram Müller-Myhsok, Elisabeth B. Binder, Angela Heck, Stephan Ripke, Andreas Menke, Cornelia M. van Duijn, Johannes Schramm, Markus M. Nöthen, Albert J. Becker, Michael Alexander, Johannes M. Hennings, Stefan Schreiber, Cathryn M. Lewis, Wolfgang Maier, Michael Specht, Darina Czamara, Bekh Bradley, Philipp G. Saemann, Susanne Lucae, Christiane Wolf, Ian W. Craig, Sven Cichon, Manfred Uhr, Michael Czisch, Ayse Demirkan, Albert Hofman, D. Hoehn, Epidemiology, Psychiatry, and Child and Adolescent Psychiatry / Psychology

Subjects
Male, Magnetic Resonance Spectroscopy, Hippocampus, Bioinformatics, Linkage Disequilibrium, Mice, 0302 clinical medicine, Gene Frequency, Risk Factors, Germany, Chronic stress, Depression (differential diagnoses), Genetics, 0303 health sciences, General Neuroscience, Middle Aged, Magnetic Resonance Imaging, Pathophysiology, 3. Good health, Female, Adult, Genotype, Neuroscience(all), Nerve Tissue Proteins, Biology, Tritium, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Meta-Analysis as Topic, Downregulation and upregulation, Animals, Humans, Genetic Predisposition to Disease, RNA, Messenger, Gene, 030304 developmental biology, Analysis of Variance, Aspartic Acid, Depressive Disorder, Major, Chromosomes, Human, Pair 12, Mechanism (biology), United Kingdom, Human genetics, Disease Models, Animal, Amino Acid Transport Systems, Neutral, Gene Expression Regulation, Stress, Psychological, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Major depression (MD) is one of the most prevalent psychiatric disorders and a leading cause of loss in work productivity. A combination of genetic and environmental risk factors likely contributes to MD. We present data from a genome-wide association study revealing a neuron-specific neutral amino acid transporter (SLC6A15) as a novel susceptibility gene for MD. Risk allele carrier status in humans and chronic stress in mice were associated with a downregulation of the expression of this gene in the hippocampus, a brain region implicated in the pathophysiology of MD. The same polymorphisms also showed associations with alterations in hippocampal volume and neuronal integrity. Thus, decreased SLC6A15 expression, due to genetic or environmental factors might alter neuronal circuits related to the susceptibility for MD. Our convergent data from human genetics, expression studies, brain imaging and animal models suggest a novel pathophysiological mechanism for MD that may be accessible to drug targeting.

Published
2011
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30. Analysis of Irreversible Processes across Narrow Junctions

Author

Ross D. Hoehn and Jurgen Michael Honig

Subjects
Physics, Rectification, media_common.quotation_subject, Cyclic process, General Physics and Astronomy, Second law of thermodynamics, Statistical physics, General expression, Entropy (arrow of time), Quasistatic process, media_common
Abstract

The rectification of the second law of thermodynamics is used to directly relate irreversible heat and work transfers to reversible processes. This permits the construction of thermodynamic functions of state that include entropy contributions due to irreversible processes. A general expression is set up to determine the entropy changes in terms of experimentally accessible parameters when a system is interacting with its surroundings via quasistatic irreversible operations. The procedure is used to determine the entropy changes across a narrow junction in terms of pressure and temperature differences between the system and its surroundings, including cyclic processes.

Published
2011
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31. Effects of Hawking Radiation on the Entropic Uncertainty in a Schwarzschild Space-Time

Author

Wei-Nan Shi, Liu Ye, Sabre Kais, Wen-Yang Sun, Dong Wang, Fei Ming, and Ross D. Hoehn

Subjects
Physics, Quantum Physics, Uncertainty principle, Event horizon, FOS: Physical sciences, General Physics and Astronomy, 01 natural sciences, 010305 fluids & plasmas, 0103 physical sciences, Schwarzschild metric, Measurement uncertainty, Statistical physics, Quantum information, Entropic uncertainty, Quantum Physics (quant-ph), 010306 general physics, Schwarzschild radius, Hawking radiation
Abstract

Heisenberg uncertainty principle describes a basic restriction on observer's ability of precisely predicting the measurement for a pair of non-commuting observables, and virtually is at the core of quantum mechanics. We herein aim to study entropic uncertainty relation under the background of the Schwarzschild black hole and its control. Explicitly, we develop dynamical features of the measuring uncertainty via entropy in a practical model where a stationary particle interacts with its surrounding environment while another particle --- serving as a quantum memory reservoir --- undergoes freefall in the vicinity of the event horizon of the Schwarzschild space-time. It shows higher Hawking temperatures would give rise to an inflation of the entropic uncertainty on the measured particle. This is suggestive the measurement uncertainty is strongly correlated with degree of mixing present in the evolving particles. Additionally, based on information flow theory, we provide a physical interpretation for the observed dynamical behaviors related with the entropic uncertainty in such a realistic scenario. Finally, an efficient strategy is proposed to reduce the uncertainty by non-tracing-preserved operations. Therefore, our explorations may improve the understanding of the dynamic entropic uncertainty in a curved space-time, and illustrate predictions of quantum measurements in relativistic quantum information sciences., 22 pages, 11 figures, to appear in Annalen der Physik

Published
2018
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33. Quantum Dot-Based Biosensor for Detection of Human Cardiac Troponin I Using a Liquid-Core Waveguide

Author

D. Hoehn, R.C. Stringer, and Sheila A. Grant

Subjects
Analyte, Conformational change, biology, Chemistry, Analytical chemistry, macromolecular substances, Fluorescence, Troponin, Cardiac Troponin complex, Förster resonance energy transfer, Troponin I, Biophysics, biology.protein, Electrical and Electronic Engineering, Instrumentation, Biosensor
Abstract

Human cardiac Troponin I is one of three subunits of the cardiac Troponin complex that are released into the bloodstream upon injury to cardiac muscle, particularly myocardial infarction, where it is absent under normal conditions. Rapid, sensitive detection of blood borne Troponin I is extremely important for early detection of myocardial infarction. An optical biosensor has been proposed as a versatile, adaptable, and effective method for detection of Troponin I. The biosensor architecture utilizes fluorescence resonance energy transfer (FRET), a distance-dependent chemical signal transduction method that occurs between two fluorescent molecules, termed the donor and acceptor. In order to launch FRET, a donor-labeled protein A molecule is bound to an acceptor-labeled capture antibody. When exposed to the Troponin I antigen, the antibody-antigen binding event initiates a conformational change within the structure of the antibody. As this morphological change in the antibody takes place, the distance between the donor and acceptor changes, resulting in a measurable shift in energy transfer. In this study, quantum dots were utilized as the FRET donors to further increase the efficiency of the biosensor system and organic dyes were utilized as the acceptors. This sensing mechanism was then interfaced in a liquid-core waveguide (LCW) platform that was able to capture the resulting fluorescence to achieve highly sensitive and accurate measurements. The biosensor demonstrated an ample sensitivity to the analyte, achieving a lower limit of detection of approximately 32 nM in phosphate buffered saline and 55 nM in human plasma. A high degree of specificity was also observed when the response to cardiac Troponin I is compared with that of a nonspecific protein. Response time of the biosensor was determined to be less than 1 min; an expeditious time compared with other Troponin diagnostic assays.

Published
2008
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34. Neuroreceptor Activation by Vibration-Assisted Tunneling

Author

David E. Nichols, Hartmut Neven, Ross D. Hoehn, and Sabre Kais

Subjects
Agonist, medicine.drug_class, In silico, FOS: Physical sciences, Electrons, Article, Cell Line, chemistry.chemical_compound, Physics - Chemical Physics, medicine, Humans, Physics - Biological Physics, Receptor, 5-HT receptor, G protein-coupled receptor, Chemical Physics (physics.chem-ph), Quantum Physics, Multidisciplinary, Chemistry, Inelastic electron tunneling spectroscopy, Biomolecules (q-bio.BM), Serotonin Receptor Agonists, Lysergic acid, Lysergic Acid Diethylamide, Quantitative Biology - Biomolecules, Models, Chemical, Biological Physics (physics.bio-ph), Doxorubicin, FOS: Biological sciences, Drug Design, Receptors, Serotonin, Biophysics, Quantum Theory, Signal transduction, Quantum Physics (quant-ph), Signal Transduction
Abstract

G protein-coupled receptors (GPCRs) constitute a large family of receptor proteins that sense molecular signals on the exterior of a cell and activate signal transduction pathways within the cell. Modeling how an agonist activates such a receptor is fundamental for an understanding of a wide variety of physiological processes and it is of tremendous value for pharmacology and drug design. Inelastic electron tunneling spectroscopy (IETS) has been proposed as a model for the mechanism by which olfactory GPCRs are activated by a bound agonist. We apply this hypothesis to GPCRs within the mammalian nervous system using quantum chemical modeling. We found that non-endogenous agonists of the serotonin receptor share a particular IET spectral aspect both amongst each other and with the serotonin molecule: a peak whose intensity scales with the known agonist potencies. We propose an experiential validation of this model by utilizing lysergic acid dimethylamide (DAM-57), an ergot derivative, and its deuterated isotopologues; we also provide theoretical predictions for comparison to experiment. If validated our theory may provide new avenues for guided drug design and elevate methods of in silico potency/activity prediction., Comment: Accepted to Scientific Reports; Main text 15 pgs with 4 figs; Sup Materials 10 pgs 7 figs

Published
2015
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35. Für die Freiheit und Zukunft der Medien

Author

Tobias D. Höhn and Tobias D. Höhn

Abstract

Seit 2001 wird der »Preis für die Freiheit und Zukunft der Medien « an Journalisten, Verleger, Publizisten und Institutionen vergeben, die sich mit Risikobereitschaft, Engagement und demokratischer Überzeugung für die Pressefreiheit einsetzen. Diese Zwischenbilanz stellt die bisherigen Preisträger in Porträts vor und versammelt Interviews zur Zukunft des Journalismus, u. a. mit US-Enthüllungsreporter Seymour Hersh, Kriegsfotograf James Nachtwey, stern-Autor Hans-Martin Tillack sowie dem Schriftsteller Erich Loest.

Published
2013

36. Glutathione Peroxidase Overexpression Inhibits Cytochrome c Release and Proapoptotic Mediators to Protect Neurons From Experimental Stroke

Author

Gary K. Steinberg, Midori A. Yenari, Benjamin D. Hoehn, and Robert M. Sapolsky

Subjects
Male, Time Factors, Cell Survival, Genetic Vectors, Ischemia, Apoptosis, Cytochrome c Group, Caspase 3, Pharmacology, Neuroprotection, Drug Administration Schedule, Rats, Sprague-Dawley, Bcl-2-associated X protein, Proto-Oncogene Proteins, medicine, Animals, Simplexvirus, bcl-2-Associated X Protein, Neurons, Advanced and Specialized Nursing, chemistry.chemical_classification, Glutathione Peroxidase, biology, business.industry, Cytochrome c, Glutathione peroxidase, Genetic Therapy, medicine.disease, Corpus Striatum, Rats, Stroke, Disease Models, Animal, Neuroprotective Agents, Proto-Oncogene Proteins c-bcl-2, chemistry, Cytoprotection, Caspases, Immunology, biology.protein, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Peroxidase
Abstract

Background and Purpose— Ischemic injury and reperfusion increases superoxide (O 2 − ) production and reduces the ability of neurons to scavenge free radicals, leading to the release of cytochrome c and apoptosis. Here we test whether overexpression with the use of gene therapy of the antioxidant glutathione peroxidase (Gpx), delivered before or after experimental stroke, is protective against ischemic injury. Methods— Sixty-two rats underwent middle cerebral artery occlusion for 1 hour. Defective herpes simplex viral vectors expressing Gpx/lacZ or lacZ alone (control) were delivered into each striatum 12 hours before or 2 or 5 hours after ischemia onset. Results— Striatal neuron survival at 2 days was improved by 36% when Gpx was delivered 12 hours before ischemia onset, 26% with a 2-hour delay, and 25% when delayed 5 hours. After ischemia, Gpx overexpression significantly reduced cytosolic translocation of cytochrome c and increased the proportion of Bcl-2–positive cells compared with cells transfected with control vector. Bax and activated caspase-3, while present in control-transfected neurons after ischemia, were rarely noted in Gpx-transfected cells. Conclusions— Expression from these herpes simplex viral vectors begins 4 to 6 hours after injection, which suggests a 9- to 11-hour temporal therapeutic window for Gpx. This is the first study to show that overexpression of Gpx with the use of gene therapy protects against experimental stroke, even with postischemic transfection, and the neuroprotective mechanism involves attenuation of apoptosis-related events.

Published
2003
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37. Overexpression of HSP72 after Induction of Experimental Stroke Protects Neurons from Ischemic Damage

Author

Benjamin D. Hoehn, Thomas M. Ringer, Midori A. Yenari, Rona G. Giffard, Robert M. Sapolsky, Gary K. Steinberg, and Lijun Xu

Subjects
Male, Pathology, medicine.medical_specialty, Genetic enhancement, Ischemia, HSP72 Heat-Shock Proteins, Striatum, Pharmacology, Neuroprotection, Brain Ischemia, 030218 nuclear medicine & medical imaging, Rats, Sprague-Dawley, Brain ischemia, Mice, 03 medical and health sciences, 0302 clinical medicine, Heat shock protein, In Situ Nick-End Labeling, medicine, Animals, Vector (molecular biology), Stroke, Cells, Cultured, Heat-Shock Proteins, Neurons, business.industry, Infarction, Middle Cerebral Artery, Genetic Therapy, medicine.disease, Rats, Gene Expression Regulation, Lac Operon, Neurology, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

The 72-kD inducible heat shock protein (HSP72) can attenuate cerebral ischemic injury when overexpressed before ischemia onset. Whether HSP72 overexpression is protective when applied after ischemia onset is not known, but would have important clinical implications. Fifty-seven rats underwent middle cerebral artery occlusion for 1 hour. Defective herpes simplex viral (HSV) vectors expressing hsp72 with lacZ as a reporter were delivered 0.5, 2, and 5 hours after ischemia onset into each striatum. Control animals received an identical vector containing only lacZ. Striatal neuron survival at 2 days was improved by 23% and 15% when HSP72 vectors were delayed 0.5 and 2 hours after ischemic onset, respectively ( P < 0.05). However, when delayed by 5 hours, HSP72 overexpression was no longer protective. This is the first demonstration that HSP72 gene transfer even after ischemia onset is neuroprotective. Because expression from these HSV vectors begins 4 to 6 hours after injection, this suggests that the temporal therapeutic window for HSP72 is at least 6 hours after ischemia onset. Future strategies aimed at enhancing HSP72 expression after clinical stroke may be worth pursuing. The authors suggest that in the future HSP72 may be an effective treatment for stroke.

Published
2001
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38. P.2.b.017 Structural brain alterations in major depression: findings from the ENIGMA Major Depressive Disorder Working Group

Author

Nicholas G. Martin, Thomas Frodl, M. A. Ikram, Henrik Walter, J.E. Sussmann, A. Block, Ian B. Hickie, Meike W. Vernooij, I.M. Veer, T.G.M. van Erp, Bartosz Zurowski, Philip J. Cowen, Elisabeth Schramm, M.J.D. van Tol, A. Hofman, Angela Carballedo, Geoffrey B. Hall, Michael Czisch, Knut Schnell, Sean N. Hatton, Katie L. McMahon, Dick J. Veltman, Baptiste Couvy-Duchesne, Jim Lagopoulos, L. S. van Velzen, Wiro J. Niessen, Natalie T. Mills, Glenda MacQueen, Felix Fischer, Lianne Schmaal, Matthias Rose, Margaret J. Wright, Martina Papmeyer, Philipp G. Sämann, Eva-Maria Frey, S. E. Medland, Bernhard K. Krämer, Paul M. Thompson, D. P. Hibar, N.J. van der Wee, Henning Tiemeier, Elizabeth Loehrer, Neda Jahanshad, Roberto Goya-Maldonado, Thomas Nickson, Hans-Jörgen Grabe, Heather C. Whalley, Oliver Gruber, G. I. de Zubicaray, K Hegenscheid, Lachlan T. Strike, Carsten Konrad, Katharina Wittfeld, Nathan A. Gillespie, Andrew M. McIntosh, Henry Völzke, D. Schoepf, B.W.J.H. Penninx, D. Hoehn, Miguel E. Rentería, Beata R. Godlewska, and Claus Normann

Subjects
Pharmacology, medicine.medical_specialty, business.industry, medicine.disease, Clinical neurology, Psychiatry and Mental health, Neurology, Endogenous depression, medicine, Major depressive disorder, Pharmacology (medical), Neurology (clinical), business, Psychiatry, Biological Psychiatry, Depression (differential diagnoses), Clinical psychology
Published
2015
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39. Painless hypoglossal palsy as an isolated symptom of spontaneous carotid dissection

Author

F. Weber, D. Hoehn, E. Schumann-Spaeth, and J.M. Hennings

Subjects
Local pain, medicine.medical_specialty, Pain, Cranial nerve palsy, Carotid Artery, Internal, Dissection, Hypoglossal Nerve Diseases, Tongue Diseases, Peripheral nerve, medicine, Humans, Paralysis, Aged, Internal carotid artery dissection, Palsy, medicine.diagnostic_test, business.industry, Rehabilitation, Cranial nerves, Anticoagulants, Magnetic resonance imaging, Cranial Nerve Diseases, Surgery, Phenprocoumon, Female, Neurology (clinical), Carotid dissection, Cardiology and Cardiovascular Medicine, business
Abstract

Spontaneous internal carotid artery dissection (sICAD) occurs annually in 2.5 to 3 per 100,000 presenting with signs of ischemic events in the majority of cases. In contrast, lower cranial nerve palsy due to peripheral nerve affection is seldom the presenting clinical sign. In symptomatic cases (>90%), sICAD is most commonly accompanied by local pain. We report a case of a 49-year old woman with a left sICAD presenting with isolated ipsilateral hypoglossal palsy as the sole clinical sign. Compared to other cases, local pain was absent and other cranial nerves were not affected. Further, sICAD could not be detected in repeated Doppler-/Duplex-sonography, but magnetic resonance imaging and MR-angiography only.

Published
2013

40. Analytic ab initio-based molecular interaction potential for the BrO⋅H2O complex

Author

Sachin D. Yeole, Sabre Kais, Joseph S. Francisco, and Ross D. Hoehn

Subjects
010304 chemical physics, Chemistry, Ab initio, General Physics and Astronomy, Electronic structure, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Molecular dynamics, Unpaired electron, Ab initio quantum chemistry methods, Chemical physics, Excited state, 0103 physical sciences, Potential energy surface, Physics::Chemical Physics, Physical and Theoretical Chemistry, Atomic physics, Ground state
Abstract

Radical halogen oxide species play important roles within atmospheric processes, specifically those responsible for the removal of O3. To facilitate future investigations on this family of compounds, RCCSD(T)/aug-cc-pVQZ-level electronic structure calculations were employed to generate individual-molecule optimized geometries, as well as to determine the global minimum energy structure for the BrO⋅H2O complex. This information facilitated the generation of several one-dimensional potential energy surface (PES) scans for the BrO⋅H2O complex. Scans were performed for both the ground state and the first excited state; this inclusion is due to a low-lying first electronic excited-state energy. These rigid-geometry PES scans were used both to generate a novel analytic interaction potential by modifying the existing Thole-type model used for water and to the fitted potential function. This interaction potential features anisotropic atomic polarizabilities facilitating appropriate modeling of the physics regarding the unpaired electron residing within the p-orbitals of the oxygen atom of the bromine oxide radical. The intention of this work is to facilitate future molecular dynamics simulations involving the interaction between the BrO radical and water clusters as a first step in devising possible novel chemistries taking place at the water interface of clouds within the atmosphere.

Published
2016
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41. Genome-wide identification and validation of a novel methylation biomarker, SDC2, for blood-based detection of colorectal cancer

Author

TaeJeong Oh, Nam Kyu Kim, Benjamin D. Hoehn, Hyun Cheol Chung, Chan Hee Park, Tae Soo Kim, Nayoung Kim, Myung Soon Kim, Sungwhan An, and Youngho Moon

Subjects
Adult, Male, Colorectal cancer, Biology, Bioinformatics, Pathology and Forensic Medicine, chemistry.chemical_compound, DNA Microarray Analysis, medicine, Biomarkers, Tumor, Humans, neoplasms, Gene, Early Detection of Cancer, Neoplasm Staging, Aged, 80 and over, Microarray analysis techniques, Genome, Human, Cancer, Methylation, DNA Methylation, Middle Aged, medicine.disease, digestive system diseases, Gene Expression Regulation, Neoplastic, chemistry, Cancer research, Molecular Medicine, Biomarker (medicine), Female, Syndecan-2, Colorectal Neoplasms, DNA
Abstract

Aberrant DNA methylation has shown promise as a biomarker for the early detection of cancer. To discover novel genes frequently methylated at an early stage in colorectal cancer (CRC), DNA microarray analysis coupled with enriched methylated DNA was performed in primary tumors and compared with adjacent nontumor tissues of 12 patients with CRC at stages I to IV. Stepwise filtering for candidate selection in microarray data analysis yielded a set of genes that are highly methylated across all CRC tumors and that can be used as a composite biomarker for CRC detection. Verification assay identified the SDC2 gene as a potential methylation biomarker for early CRC detection. In clinical validation in tissues from 139 CRC patients, a much higher level of aberrant SDC2 methylation was measured in most primary tumors (97.8%), compared with corresponding nontumor tissue of CRC patients, irrespective of clinical stage. Clinical validation of SDC2 methylation in serum DNA from CRC patients (n = 131) at stages I to IV and from healthy individuals (n = 125) by quantitative methylation-specific PCR demonstrated a high sensitivity of 87.0% (95% CI, 80.0% to 92.3%) in detecting cancers, with a specificity of 95.2% (95% CI, 89.8% to 98.2%). Importantly, sensitivity at stage I was 92.3%, indicating the potential of SDC2 methylation as a blood-based DNA test for early detection of CRC.

Published
2012

42. An agent-based model approach to multi-phase life-cycle for contact inhibited, anchorage dependent cells

Author

Sabre Kais, Ashley. M. Schreder, Mohammed Fayez Al Rez, and Ross D. Hoehn

Subjects
Agent-based model, Physics, education.field_of_study, Cell type, Tissue Scaffolds, Multi phase, Guided Tissue Regeneration, Population, Cell Cycle, Motility, Endothelial Cells, Health Informatics, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Computer Science Applications, Cell Movement, Confluence, Humans, Computer Simulation, Logistic function, Cellular model, education, Biological system, Simulation, Algorithms
Abstract

Cellular agent-based models are a technique that can be easily adapted to describe nuances of a particular cell type. Within we have concentrated on the cellular particularities of the human Endothelial Cell, explicitly the effects both of anchorage dependency and of heightened scaffold binding on the total confluence time of a system. By expansion of a discrete, homogeneous, asynchronous cellular model to account for several states per cell (phases within a cell’s life); we accommodate and track dependencies of confluence time and population dynamics on these factors. Increasing the total motility time, analogous to weakening the binding between lattice and cell, affects the system in unique ways from increasing the average cellular velocity; each degree of freedom allows for control over the time length the system achieves logistic growth and confluence. These additional factors may allow for greater control over behaviors of the system. Examinations of system’s dependence on both seed state velocity and binding are also enclosed.

Published
2012

43. Genome-wide identification of OTP gene as a novel methylation marker of breast cancer

Author

Myung Soon Kim, Kwang Sun Seo, Jeung-Hoon Lee, Eilsung Chang, Sungwhan An, Benjamin D. Hoehn, Youngho Moon, TaeJeong Oh, and Jinsun Lee

Subjects
Oncology, Adult, Cancer Research, medicine.medical_specialty, LIM-Homeodomain Proteins, Breast Neoplasms, Nerve Tissue Proteins, Biology, medicine.disease_cause, Breast cancer, Internal medicine, Cell Line, Tumor, medicine, Biomarkers, Tumor, Humans, WT1 Proteins, Aged, Homeodomain Proteins, Gene Expression Profiling, Cancer, General Medicine, Methylation, DNA Methylation, Middle Aged, medicine.disease, Primary tumor, Gene expression profiling, CpG site, DNA methylation, Cancer research, Female, Carcinogenesis, Genome-Wide Association Study, Transcription Factors
Abstract

Aberrant DNA methylation occurs early and frequently in tumorigenesis. Identification of DNA methylation biomarkers is a field that provides potential for improving the clinical process of breast cancer diagnosis. We utilized a genome-wide technique, methylated DNA isolation assay (MeDIA), in combination with high-resolution CpG microarray analysis to identify hypermethylated genes in breast cancer. Among differentially methylated genes between tumor and adjacent normal tissues, 3 candidate genes (LHX2, WT1 and OTP) were finally selected through a step-wise filtering process and examined for methylation status in normal tissues, primary tumor, and paired adjacent normal-appearing tissues from 39 breast cancer patients. Based on the calculated cut-off values, all genes showed significantly higher frequencies of aberrant hypermethylation in primary tumors (43.6% for LHX2, 89.7% for WT1 and 100% for OTP, p

Published
2011

44. Identification of GABRA1 and LAMA2 as new DNA methylation markers in colorectal cancer

Author

Sun-Woo Lee, Hyun-Cheol Chung, Sun-Young Rha, Youngho Moon, Changjin Kim, Benjamin D. Hoehn, Dongjun Jeong, Mi-Ae Yoo, Nam Kyu Kim, Sungwhan An, Chan Hee Park, Seung-Hoon Lee, and TaeJeong Oh

Subjects
Epigenomics, Male, Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, Down-Regulation, Biology, medicine.disease_cause, chemistry.chemical_compound, Cell Line, Tumor, Internal medicine, Biomarkers, Tumor, medicine, Humans, Epigenetics, Oligonucleotide Array Sequence Analysis, Cancer, Methylation, DNA Methylation, Middle Aged, HCT116 Cells, Receptors, GABA-A, medicine.disease, Demethylating agent, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, chemistry, DNA methylation, Cancer research, CpG Islands, Female, Laminin, Caco-2 Cells, Colorectal Neoplasms, Carcinogenesis
Abstract

Aberrant methylation of CpG islands in the promoter region of genes is a common epigenetic phenomenon found in early cancers. Therefore conducting genome-scale methylation studies will enhance our understanding of the epigenetic etiology behind carcinogenesis by providing reliable biomarkers for early detection of cancer. To discover novel hypermethylated genes in colorectal cancer by genome-wide search, we first defined a subset of genes epigenetically reactivated in colon cancer cells after treatment with a demethylating agent. Next, we identified another subset of genes with relatively down-regulated expression patterns in colorectal primary tumors when compared with normal appearing-adjacent regions. Among 29 genes obtained by cross-comparison of the two gene-sets, we subsequently selected, through stepwise subtraction processes, two novel genes, GABRA1 and LAMA2, as methylation targets in colorectal cancer. For clinical validation pyrosequencing was used to assess methylation in 134 matched tissue samples from CRC patients. Aberrant methylation at target CpG sites in GABRA1 and LAMA2 was observed with high frequency in tumor tissues (92.5% and 80.6%, respectively), while less frequently in matched tumor-adjacent normal tissues (33.6% for GABRA1 and 13.4% for LAMA2). Methylation levels in primary tumors were not significantly correlated with clinico-pathological features including age, sex, survival and TNM stage. Additionally, we found that ectopic overexpression of GABRA1 in colon cancer cell lines resulted in strong inhibition of cell growth. These results suggest that two novel hypermethylated genes in colorectal cancer, GABRA1 and LAMA2, may have roles in colorectal tumorigenesis and could be potential biomarkers for the screening and the detection of colorectal cancer in clinical practice.

Published
2011
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45. Resting state network alterations in major Depression

Author

Roberto Goya-Maldonado, Florian Holsboer, Manuel Schröter, Michael Czisch, Philipp G. Sämann, Victor I. Spoormaker, and D. Hoehn

Subjects
Psychiatry and Mental health, medicine.medical_specialty, Resting state fMRI, business.industry, Internal medicine, medicine, Cardiology, Pharmacology (medical), General Medicine, business, Depression (differential diagnoses)
Published
2011
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46. Combined fMRI/EEG to map non-genomic effects of exogeneous cortisol

Author

Roberto Goya-Maldonado, Philipp G. Sämann, Katia C. Andrade, Florian Holsboer, Victor I. Spoormaker, Michael Czisch, D. Hoehn, and S. A. Kiem

Subjects
Psychiatry and Mental health, medicine.diagnostic_test, business.industry, Medicine, Pharmacology (medical), General Medicine, Electroencephalography, business, EEG-fMRI, Neuroscience
Published
2011
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47. Atlas parcellation and voxel based whole brain functional connectivity analysis applied to major depression: group results and biomarker potential

Author

Manuel Schröter, Michael Czisch, R. Goya, V. Holsboer, Philipp G. Sämann, D. Hoehn, and Victor I. Spoormaker

Subjects
Psychiatry and Mental health, medicine.anatomical_structure, Atlas (anatomy), business.industry, Voxel, Functional connectivity, medicine, Pharmacology (medical), General Medicine, business, computer.software_genre, Neuroscience, computer
Published
2011
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48. Dimensional Scaling Treatment with Relativistic Corrections for Stable Multiply Charged Atomic Ions in High-Frequency Super-Intense Laser Fields

Author

Ross D. Hoehn, Sabre Kais, and Jiaxiang Wang

Subjects
Physics, Electron density, Quantum Physics, Field (physics), Atomic Physics (physics.atom-ph), FOS: Physical sciences, General Physics and Astronomy, Electron, Laser, Ion, law.invention, Physics - Atomic Physics, Atomic orbital, law, Physical and Theoretical Chemistry, Atomic physics, Quantum Physics (quant-ph), Relativistic quantum chemistry, Scaling
Abstract

We present a theoretical framework which describes multiply-charged atomic ions, their stability within super-intense laser fields,also lay corrections to the systems due to relativistic effects. Dimensional scaling calculations with relativistic corrections for systems: H, H$^{-}$, H$^{2-}$, He, He$^{-}$, He$^{2-}$, He$^{3-}$ within super-intense laser fields were completed. Also completed were three-dimensional self consistent field calculations to verify the dimensionally scaled quantities. With the aforementioned methods the system's ability to stably bind 'additional' electrons through the development of multiple isolated regions of high potential energy leading to nodes of high electron density is shown. These nodes are spaced far enough from each other to minimized the electronic repulsion of the electrons, while still providing adequate enough attraction so as to bind the excess elections into orbitals. We have found that even with relativistic considerations these species are stably bound within the field. It was also found that performing the dimensional scaling calculations for systems within the confines of laser fields to be a much simpler and more cost-effective method than the supporting D=3 SCF method. The dimensional scaling method is general and can be extended to include relativistic corrections to describe the stability of simple molecular systems in super-intense laser fields.

Published
2011

50. Neurogenesis in rats after focal cerebral ischemia is enhanced by indomethacin

Author

Gary K. Steinberg, Theo D. Palmer, and Benjamin D. Hoehn

Subjects
Male, medicine.medical_specialty, Doublecortin Protein, Indomethacin, Ischemia, Inflammation, Cell Count, Lymphocyte Activation, Monocytes, Brain ischemia, Rats, Sprague-Dawley, Internal medicine, medicine, Animals, Immunologic Factors, Cell Lineage, Advanced and Specialized Nursing, Cerebral Cortex, Neurons, Microglia, biology, Glial fibrillary acidic protein, business.industry, Neurogenesis, Anti-Inflammatory Agents, Non-Steroidal, Nestin, medicine.disease, Corpus Striatum, Doublecortin, Rats, Endocrinology, medicine.anatomical_structure, nervous system, Ischemic Attack, Transient, biology.protein, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, Biomarkers, Cell Division
Abstract

Background and Purpose—Newborn cells may participate in repair following ischemic brain injury, but their survival and function may be influenced by inflammation.Methods—We investigated the effects of indomethacin, a nonsteroidal antiinflammatory drug, on the fate of newborn cells following transient focal ischemia.Results—Bromodeoxyuridine (BrdU)-labeled cells, including migrating neuroblasts, were observed in the neighboring striatum and overlying cortex 1 day poststroke. The density of BrdU+ cells labeled with doublecortin, nestin, glial fibrillary acidic protein, or NG2 was increased at 14 and 28 days. Indomethacin increased BrdU+ cells of all lineages and reduced microglial/monocyte activation.Conclusion—Indomethacin enhanced the accumulation of newborn cells following stroke.

Published
2005

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