15,535 results on '"Michael, M."'
Search Results
2. An NCBP3-Domain Protein Mediates Meiotic Silencing by Unpaired DNA
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Erin C. Boone, Hua Xiao, Michael M. Vierling, Logan M. Decker, Victor T. Sy, Rana F. Kennedy, Marilyn A. Bonham, Shannon F. Schmitz, Annie M. John, Thomas M. Hammond, and Patrick K. T. Shiu
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cap-binding proteins (cbps) ,meiosis ,meiotic silencing by unpaired dna (msud) ,neurospora crassa ,rna interference (rnai) ,Genetics ,QH426-470 - Abstract
In the filamentous fungus Neurospora crassa, genes unpaired during meiosis are silenced by a process known as meiotic silencing by unpaired DNA (MSUD). MSUD utilizes common RNA interference (RNAi) proteins, such as Dicer and Argonaute, to target homologous mRNAs for silencing. Previously, we demonstrated that nuclear cap-binding proteins NCBP1 and NCBP2 are involved in MSUD. We report here that SAD-8, a protein similar to human NCBP3, also mediates silencing. Although SAD-8 is not essential for either vegetative or sexual development, it is required for MSUD. SAD-8 localizes predominantly in the nucleus and interacts with both NCBP1 and NCBP2. Similar to NCBP1 and NCBP2, SAD-8 interacts with a component (Argonaute) of the perinuclear meiotic silencing complex (MSC), further implicating the involvement of cap-binding proteins in silencing.
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- 2020
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3. Corrigendum to: Involvement of RNA granule proteins in meiotic silencing by unpaired DNA
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Hua Xiao, Michael M Vierling, Rana F Kennedy, Erin C Boone, Logan M Decker, Victor T Sy, Jackson B Haynes, Michelle A Williams, and Patrick K T Shiu
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Genetics ,QH426-470 - Published
- 2021
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4. Epistasis for head morphology in Drosophila melanogaster
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Ergi D Özsoy, Murat Yılmaz, Bahar Patlar, Güzin Emecen, Esra Durmaz, Michael M Magwire, Shanshan Zhou, Wen Huang, Robert R H Anholt, and Trudy F C Mackay
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Genetics ,QH426-470 - Abstract
AbstractEpistasis—gene–gene interaction—is common for mutations with large phenotypic effects in humans and model organisms. Epistasis impacts quantitative genetic models of speciation, response to natural and artificial selection, genetic mapping, and personalized medicine. However, the existence and magnitude of epistasis between alleles with small quantitative phenotypic effects are controversial and difficult to assess. Here, we use the Drosophila melanogasterjing and inv
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- 2021
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5. Introduction
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Miller, Michael M., primary and Peppin, John F., additional
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- 2020
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6. The genetic basis of differential autodiploidization in evolving yeast populations
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Sudipta Tung, Christopher W Bakerlee, Angela M Phillips, Alex N Nguyen Ba, and Michael M Desai
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Genetics ,QH426-470 - Abstract
AbstractSpontaneous whole-genome duplication, or autodiploidization, is a common route to adaptation in experimental evolution of haploid budding yeast populations. The rate at which autodiploids fix in these populations appears to vary across strain backgrounds, but the genetic basis of these differences remains poorly characterized. Here, we show that the frequency of autodiploidization differs dramatically between two closely related laboratory strains of Saccharomyces cerevisiaeSSD1S. cerevisiaeSSD1
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- 2021
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7. Involvement of RNA granule proteins in meiotic silencing by unpaired DNA
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Hua Xiao, Michael M Vierling, Rana F Kennedy, Erin C Boone, Logan M Decker, Victor T Sy, Jackson B Haynes, Michelle A Williams, and Patrick K T Shiu
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Genetics ,QH426-470 - Abstract
AbstractIn Neurospora crassaNeurosporaCaenorhabditis elegans
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- 2021
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8. Neurological Disorders
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Wodrich, David L., additional, Jarrar, Randa G., additional, and Etzl, Michael M., additional
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- 2019
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9. The Politics of Language Education in Africa
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Kaschula, Russell H. and Kretzer, Michael M.
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- 2019
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10. Effort and Success as Predictors of Passion
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Lex, Maike, primary, Gielnik, Michael M., additional, and Frese, Michael, additional
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- 2019
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11. The Nuclear Cap-Binding Complex Mediates Meiotic Silencing by Unpaired DNA
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Logan M. Decker, Hua Xiao, Erin C. Boone, Michael M. Vierling, Benjamin S. Shanker, Shanika L. Kingston, Shannon F. Boone, Jackson B. Haynes, and Patrick K.T. Shiu
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cap-binding proteins (CBPs) ,meiosis ,meiotic silencing by unpaired DNA (MSUD) ,Neurospora crassa ,RNA interference (RNAi) ,Genetics ,QH426-470 - Abstract
In the filamentous fungus Neurospora crassa, cross walls between individual cells are normally incomplete, making the entire fungal network vulnerable to attack by viruses and selfish DNAs. Accordingly, several genome surveillance mechanisms are maintained to help the fungus combat these repetitive elements. One of these defense mechanisms is called meiotic silencing by unpaired DNA (MSUD), which identifies and silences unpaired genes during meiosis. Utilizing common RNA interference (RNAi) proteins, such as Dicer and Argonaute, MSUD targets mRNAs homologous to the unpaired sequence to achieve silencing. In this study, we have identified an additional silencing component, namely the cap-binding complex (CBC). Made up of cap-binding proteins CBP20 and CBP80, CBC associates with the 5′ cap of mRNA transcripts in eukaryotes. The loss of CBC leads to a deficiency in MSUD activity, suggesting its role in mediating silencing. As confirmed in this study, CBC is predominantly nuclear, although it is known to travel in and out of the nucleus to facilitate RNA transport. As seen in animals but not in plants, CBP20’s robust nuclear import depends on CBP80 in Neurospora. CBC interacts with a component (Argonaute) of the perinuclear meiotic silencing complex (MSC), directly linking the two cellular factors.
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- 2017
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12. Occupational risk factors for heart disease
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Katritsis, Demosthenes G., additional, Anderson, Mark, additional, and Webb-Peploe, Michael M., additional
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- 2018
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13. Regulations concerning individual risk and public safety
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Katritsis, Demosthenes G., additional, Anderson, Mark, additional, and Webb-Peploe, Michael M., additional
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- 2018
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14. The Language of Pain and Addiction (DRAFT)
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Miller, Michael M., primary
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- 2018
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15. Aging, Brain Plasticity, and Integrative Preventive Medicine
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Merzenich, Michael M., primary
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- 2017
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16. Functional Maturation of Induced Pluripotent Stem Cell Hepatocytes in Extracellular Matrix—A Comparative Analysis of Bioartificial Liver Microenvironments
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Bo Wang, Adam E. Jakus, Pedro M. Baptista, Shay Soker, Alejandro Soto-Gutierrez, Michael M. Abecassis, Ramille N. Shah, and Jason A. Wertheim
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Liver ,Stem cell‐microenvironment interactions ,Stem/progenitor cell ,Tissue regeneration ,Induced pluripotent stem cells ,Medicine (General) ,R5-920 ,Cytology ,QH573-671 - Abstract
Induced pluripotent stem cells (iPSCs) are new diagnostic and potentially therapeutic tools to model disease and assess the toxicity of pharmaceutical medications. A common limitation of cell lineages derived from iPSCs is a blunted phenotype compared with fully developed, endogenous cells. We examined the influence of novel three‐dimensional bioartificial microenvironments on function and maturation of hepatocyte‐like cells differentiated from iPSCs and grown within an acellular, liver‐derived extracellular matrix (ECM) scaffold. In parallel, we also compared a bioplotted poly‐l‐lactic acid (PLLA) scaffold that allows for cell growth in three dimensions and formation of cell‐cell contacts but is infused with type I collagen (PLLA‐collagen scaffold) alone as a “deconstructed” control scaffold with narrowed biological diversity. iPSC‐derived hepatocytes cultured within both scaffolds remained viable, became polarized, and formed bile canaliculi‐like structures; however, cells grown within ECM scaffolds had significantly higher P450 (CYP2C9, CYP3A4, CYP1A2) mRNA levels and metabolic enzyme activity compared with iPSC hepatocytes grown in either bioplotted PLLA collagen or Matrigel sandwich control culture. Additionally, the rate of albumin synthesis approached the level of primary cryopreserved hepatocytes with lower transcription of fetal‐specific genes, α‐fetoprotein and CYP3A7, compared with either PLLA‐collagen scaffolds or sandwich culture. These studies show that two acellular, three‐dimensional culture systems increase the function of iPSC‐derived hepatocytes. However, scaffolds derived from ECM alone induced further hepatocyte maturation compared with bioplotted PLLA‐collagen scaffolds. This effect is likely mediated by the complex composition of ECM scaffolds in contrast to bioplotted scaffolds, suggesting their utility for in vitro hepatocyte assays or drug discovery. Significance Through the use of novel technology to develop three‐dimensional (3D) scaffolds, the present study demonstrated that hepatocyte‐like cells derived via induced pluripotent stem cell (iPSC) technology mature on 3D extracellular matrix scaffolds as a result of 3D matrix structure and scaffold biology. The result is an improved hepatic phenotype with increased synthetic and catalytic potency, an improvement on the blunted phenotype of iPSC‐derived hepatocytes, a critical limitation of iPSC technology. These findings provide insight into the influence of 3D microenvironments on the viability, proliferation, and function of iPSC hepatocytes to yield a more mature population of cells for cell toxicity studies and disease modeling.
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- 2016
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17. Designs, applications, and limitations of genetically encoded fluorescent sensors to explore plant biology
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Wolf B. Frommer, Masayoshi Nakamura, Michael M. Wudick, Guido Grossmann, Mayuri Sadoine, Thomas J. Kleist, Cheng-Hsun Ho, and Yuuma Ishikawa
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Ions ,AcademicSubjects/SCI01270 ,AcademicSubjects/SCI01280 ,Physiology ,Chemistry ,AcademicSubjects/SCI02288 ,AcademicSubjects/SCI02287 ,AcademicSubjects/SCI02286 ,Biological Transport ,Plant Science ,Computational biology ,Biosensing Techniques ,Focus Issue on Sensors and Controllers ,Plants ,Plant biology ,Fluorescence ,Update ,Molecular Imaging ,Luminescent Proteins ,Biochemistry and Metabolism ,Genetics ,Biology ,Fluorescent Dyes ,Signal Transduction - Abstract
The understanding of signaling and metabolic processes in multicellular organisms requires knowledge of the spatial dynamics of small molecules and the activities of enzymes, transporters, and other proteins in vivo, as well as biophysical parameters inside cells and across tissues. The cellular distribution of receptors, ligands, and activation state must be integrated with information about the cellular distribution of metabolites in relation to metabolic fluxes and signaling dynamics in order to achieve the promise of in vivo biochemistry. Genetically encoded sensors are engineered fluorescent proteins that have been developed for a wide range of small molecules, such as ions and metabolites, or to report biophysical processes, such as transmembrane voltage or tension. First steps have been taken to monitor the activity of transporters in vivo. Advancements in imaging technologies and specimen handling and stimulation have enabled researchers in plant sciences to implement sensor technologies in intact plants. Here, we provide a brief history of the development of genetically encoded sensors and an overview of the types of sensors available for quantifying and visualizing ion and metabolite distribution and dynamics. We further discuss the pros and cons of specific sensor designs, imaging systems, and sample manipulations, provide advice on the choice of technology, and give an outlook into future developments., Different types of genetically encoded sensors in plants can be used to quantify and visualize ion and metabolite distributions and dynamics.
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- 2021
18. A randomized clinical trial of plasticity-based cognitive training in mild traumatic brain injury
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Chad Grills, Katherine W Sullivan, Harvey S. Levin, Catherine Stasio, Henry W. Mahncke, Morris D. Bell, Annika Rose, Joseph DeGutis, Michael M. Merzenich, Sarah-Jane Kim, Mary R. Newsome, and Louis M. French
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Adult ,Male ,medicine.medical_specialty ,Activities of daily living ,050105 experimental psychology ,law.invention ,cognitive training ,03 medical and health sciences ,0302 clinical medicine ,Cognition ,Double-Blind Method ,Randomized controlled trial ,law ,Concussion ,medicine ,Humans ,0501 psychology and cognitive sciences ,Medical history ,Cognitive rehabilitation therapy ,Brain Concussion ,Neuronal Plasticity ,business.industry ,AcademicSubjects/SCI01870 ,traumatic brain injury ,05 social sciences ,Neuropsychology ,medicine.disease ,Clinical Trial ,Cognitive training ,Brain Injuries ,randomized controlled trial ,Physical therapy ,concussion ,Female ,AcademicSubjects/MED00310 ,Neurology (clinical) ,business ,Cognition Disorders ,brain plasticity ,Software ,030217 neurology & neurosurgery - Abstract
See Whyte and Turkstra (doi:10.1093/brain/awab210) for a scientific commentary on this article. In a randomized controlled trial, Mahncke et al. show that a self-administered computerized cognitive training program drove significant and enduring improvements in cognitive function in people with a history of mild traumatic brain injury and cognitive impairment, compared to an active control (computer games)., Clinical practice guidelines support cognitive rehabilitation for people with a history of mild traumatic brain injury (mTBI) and cognitive impairment, but no class I randomized clinical trials have evaluated the efficacy of self-administered computerized cognitive training. The goal of this study was to evaluate the efficacy of a self-administered computerized plasticity-based cognitive training programmes in primarily military/veteran participants with a history of mTBI and cognitive impairment. A multisite randomized double-blind clinical trial of a behavioural intervention with an active control was conducted from September 2013 to February 2017 including assessments at baseline, post-training, and after a 3-month follow-up period. Participants self-administered cognitive training (experimental and active control) programmes at home, remotely supervised by a healthcare coach, with an intended training schedule of 5 days per week, 1 h per day, for 13 weeks. Participants (149 contacted, 83 intent-to-treat) were confirmed to have a history of mTBI (mean of 7.2 years post-injury) through medical history/clinician interview and persistent cognitive impairment through neuropsychological testing and/or quantitative participant reported measure. The experimental intervention was a brain plasticity-based computerized cognitive training programme targeting speed/accuracy of information processing, and the active control was composed of computer games. The primary cognitive function measure was a composite of nine standardized neuropsychological assessments, and the primary directly observed functional measure a timed instrumental activities of daily living assessment. Secondary outcome measures included participant-reported assessments of cognitive and mental health. The treatment group showed an improvement in the composite cognitive measure significantly larger than that of the active control group at both the post-training [+6.9 points, confidence interval (CI) +1.0 to +12.7, P = 0.025, d = 0.555] and the follow-up visit (+7.4 points, CI +0.6 to +14.3, P = 0.039, d = 0.591). Both large and small cognitive function improvements were seen twice as frequently in the treatment group than in the active control group. No significant between-group effects were seen on other measures, including the directly-observed functional and symptom measures. Statistically equivalent improvements in both groups were seen in depressive and cognitive symptoms.
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- 2021
19. Cellular export of sugars and amino acids: role in feeding other cells and organisms
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Michael M. Wudick, Wolf B. Frommer, Eliza P I Loo, Tin Yau Pang, Ji-Yun Kim, and Martin J. Lercher
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Sucrose ,Membranes, Transport and Bioenergetics ,AcademicSubjects/SCI01280 ,Physiology ,Plant Science ,Plasmodesma ,Phloem ,Update ,chemistry.chemical_compound ,Genetics ,Raffinose ,Sieve tube element ,Amino Acids ,chemistry.chemical_classification ,AcademicSubjects/SCI01270 ,Permease ,AcademicSubjects/SCI02288 ,AcademicSubjects/SCI02287 ,AcademicSubjects/SCI02286 ,Plasmodesmata ,food and beverages ,Membrane Transport Proteins ,Nectar secretion ,Biological Transport ,Amino acid ,Focus Issue on Transport and Signaling ,chemistry ,Biochemistry ,Efflux ,Sugars - Abstract
Sucrose, hexoses, and raffinose play key roles in the plant metabolism. Sucrose and raffinose, produced by photosynthesis, are translocated from leaves to flowers, developing seeds and roots. Translocation occurs in the sieve elements or sieve tubes of angiosperms. But how is sucrose loaded into and unloaded from the sieve elements? There seem to be two principal routes: one through plasmodesmata and one via the apoplasm. The best-studied transporters are the H+/SUCROSE TRANSPORTERs (SUTs) in the sieve element-companion cell complex. Sucrose is delivered to SUTs by SWEET sugar uniporters that release these key metabolites into the apoplasmic space. The H+/amino acid permeases and the UmamiT amino acid transporters are hypothesized to play analogous roles as the SUT-SWEET pair to transport amino acids. SWEETs and UmamiTs also act in many other important processes—for example, seed filling, nectar secretion, and pollen nutrition. We present information on cell type-specific enrichment of SWEET and UmamiT family members and propose several members to play redundant roles in the efflux of sucrose and amino acids across different cell types in the leaf. Pathogens hijack SWEETs and thus represent a major susceptibility of the plant. Here, we provide an update on the status of research on intercellular and long-distance translocation of key metabolites such as sucrose and amino acids, communication of the plants with the root microbiota via root exudates, discuss the existence of transporters for other important metabolites and provide potential perspectives that may direct future research activities., An update on intercellular and long-distance translocation of sugars and amino acids, including plant-root microbiota communication, other metabolite transporters is provided, and perspectives are discussed.
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- 2021
20. Spontaneously Produced Facial Expressions in Infants and Children
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Camras, Linda A., primary, Castro, Vanessa L., additional, Halberstadt, Amy G., additional, and Shuster, Michael M., additional
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- 2017
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21. Interdisciplinarity and the Institutional Context of Knowledge in the American Research University
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Crow, Michael M., primary and Dabars, William B., additional
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- 2017
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22. Physical functioning and work ability
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Ward, Michael M., primary
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- 2016
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23. A phase ii study of continuous low dose panobinostat in paediatric patients with malignant rhabdoid tumours and atypical teratoid rhabdoid tumours.
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Wood P., Desai J., Waldeck K., Cain J., Gottardo N., Strong R., Kinross K., Carr M., Jones J., Wong L., Ziegler D., Hansford J., Michael M., Ashley D., Wood P., Desai J., Waldeck K., Cain J., Gottardo N., Strong R., Kinross K., Carr M., Jones J., Wong L., Ziegler D., Hansford J., Michael M., and Ashley D.
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BACKGROUND: Panobinostat treatment has been shown to terminally differentiate malignant rhabdoid tumours (MRT) and atypical teratoid rhabdoid tumours (ATRT) in pre-clinical models. We report results of the open label, phase II study of oral panobinostat in patients with newly diagnosed or relapsed MRT/ATRT. AIMS: To assess the anti-tumour activity of low dose, continuous oral panobinostat as well as its associated toxicities. To assess the biological activity of low dose panobinostat by measuring histone H4 acetylation status in peripheral mononuclear cells (PMNC), and differentiation markers. METHOD(S): Following primary institutional standard of care induction and consolidation chemotherapy and/or radiation treatment, patients were enrolled and commenced on panobinostat as a continuous daily oral dose starting at 10mg/m2/day, with a three-week wash out period between therapies. Real-time acetylation status, measuring acetylated H4 on PMNC, was performed to determine the pharmacodynamics of panobinostat at different dosing levels. Patients were monitored for toxicity; dose reductions were in decrements of 2mg/ m2/day. RESULT(S): A total of 13 patients with newly diagnosed ATRT/MRT and one patient with relapsed MRT have been enrolled. The average age at enrollment was 3.6 years (range 0.8-6.8 years). The mean treatment duration was 206 days (13-344 days). Currently, six patients (42.9%) remain on study with a mean study duration of 531 days (range 13-895 days). 6/14 patients (42.9%) were removed due to disease progression at a mean study duration of 245 days (44-560 days). 2/14 patients (14.3%) withdrew due to toxicity. 12/14 patients (85.7%) required dose reductions. The main toxicities were thrombocytopaenia and leukopaenia (Grade III-IV). Real-time pharmacodynamic assessment of panobinostat, at a dose as low as 6mg/m2/day resulted in significant acetylation of histone H4 in PMNC. CONCLUSION(S): Treatment with low dose panobinostat is well tolerated in infants and
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- 2022
24. Sustaining Transmission in Different Host Species: The Emblematic Case of Sarcoptes scabiei
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Browne, Elizabeth, Driessen, Michael M., Cross, Paul C., Escobar, Luis E., Foley, Janet, Lopez-Olvera, Jorge R., Niedringhaus, Kevin D., Rossi, Luca, Carver, Scott, Browne, Elizabeth, Driessen, Michael M., Cross, Paul C., Escobar, Luis E., Foley, Janet, Lopez-Olvera, Jorge R., Niedringhaus, Kevin D., Rossi, Luca, and Carver, Scott
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Some pathogens sustain transmission in multiple different host species, but how this epidemiologically important feat is achieved remains enigmatic. Sarcoptes scabiei is among the most host generalist and successful of mammalian parasites. We synthesize pathogen and host traits that mediate sustained transmission and present cases illustrating three transmission mechanisms (direct, indirect, and combined). The pathogen traits that explain the success of S. scabiei include immune response modulation, on-host movement capacity, off-host seeking behaviors, and environmental persistence. Sociality and host density appear to be key for hosts in which direct transmission dominates, whereas in solitary hosts, the use of shared environments is important for indirect transmission. In social den-using species, combined direct and indirect transmission appears likely. Empirical research rarely considers the mechanisms enabling S. scabiei to become endemic in host species-more often focusing on outbreaks. Our review may illuminate parasites' adaptation strategies to sustain transmission through varied mechanisms across host species.
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- 2022
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25. Establishing Antimicrobial Susceptibility Testing Methods and Clinical Breakpoints for Inhaled Antibiotic Therapy
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MMB Medische Staf, Infection & Immunity, Ekkelenkamp, Miquel B., Díez-Aguilar, María, Tunney, Michael M., Elborn, J. Stuart, Fluit, Ad C., Cantón, Rafael, MMB Medische Staf, Infection & Immunity, Ekkelenkamp, Miquel B., Díez-Aguilar, María, Tunney, Michael M., Elborn, J. Stuart, Fluit, Ad C., and Cantón, Rafael
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- 2022
26. Using artificial intelligence to determine the influence of dental aesthetics on facial attractiveness in comparison to other facial modifications
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Obwegeser, Dorothea; https://orcid.org/0000-0001-6728-7470, Timofte, Radu, Mayer, Christoph, Eliades, Theodore; https://orcid.org/0000-0003-2313-4979, Bornstein, Michael M; https://orcid.org/0000-0002-7773-8957, Schätzle, Marc A, Patcas, Raphael; https://orcid.org/0000-0003-3906-9083, Obwegeser, Dorothea; https://orcid.org/0000-0001-6728-7470, Timofte, Radu, Mayer, Christoph, Eliades, Theodore; https://orcid.org/0000-0003-2313-4979, Bornstein, Michael M; https://orcid.org/0000-0002-7773-8957, Schätzle, Marc A, and Patcas, Raphael; https://orcid.org/0000-0003-3906-9083
- Abstract
BACKGROUND Facial aesthetics is a major motivating factor for undergoing orthodontic treatment. OBJECTIVES To ascertain-by means of artificial intelligence (AI)-the influence of dental alignment on facial attractiveness and perceived age, compared to other modifications such as wearing glasses, earrings, or lipstick. MATERIAL AND METHODS Forty volunteering females (mean age: 24.5) with near perfectly aligned upper front teeth [Aesthetic Component scale of the Index of Orthodontic Treatment Need (AC-IOTN) = 1 and Peer Assessment Rating Index (PAR Index) = 0 or 1] were photographed with a standardized pose while smiling, in the following settings (number of photographs = 960): without modifications, wearing eyeglasses, earrings, or lipstick. These pictures were taken with natural aligned dentition and with an individually manufactured crooked teeth mock-up (AC-IOTN = 8) to create the illusion of misaligned teeth. Images were assessed for attractiveness and perceived age, using AI, consisting of a face detector and deep convolutional neural networks trained on dedicated datasets for attractiveness and age prediction. Each image received an attractiveness score from 0 to 100 and one value for an age prediction. The scores were descriptively reviewed for each setting, and the facial modifications were tested statistically whether they affected the attractiveness score. The relationship between predicted age and attractiveness scores was examined with linear regression models. RESULTS All modifications showed a significant effect (for all: P < 0.001) on facial attractiveness. In faces with misaligned teeth, wearing eyeglasses (-17.8%) and earrings (-3.2%) had an adverse effect on facial aesthetics. Tooth alignment (+6.9%) and wearing lipstick (+7.9%) increased attractiveness. There was no relevant effect of any assessed modifications or tooth alignment on perceived age (all: <1.5 years). Mean attractiveness score declined with predicted age, except when wearing glas
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- 2022
27. Prediction of recovery from multiple organ dysfunction syndrome in pediatric sepsis patients
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Fan, Bowen, Klatt, Juliane, Moor, Michael M, Daniels, Latasha A, Swiss Pediatric Sepsis Study, Sanchez-Pinto, Lazaro N, Agyeman, Philipp K A, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Borgwardt, Karsten M, Fan, Bowen, Klatt, Juliane, Moor, Michael M, Daniels, Latasha A, Swiss Pediatric Sepsis Study, Sanchez-Pinto, Lazaro N, Agyeman, Philipp K A, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, and Borgwardt, Karsten M
- Abstract
MOTIVATION: Sepsis is a leading cause of death and disability in children globally, accounting for ∼3 million childhood deaths per year. In pediatric sepsis patients, the multiple organ dysfunction syndrome (MODS) is considered a significant risk factor for adverse clinical outcomes characterized by high mortality and morbidity in the pediatric intensive care unit. The recent rapidly growing availability of electronic health records (EHRs) has allowed researchers to vastly develop data-driven approaches like machine learning in healthcare and achieved great successes. However, effective machine learning models which could make the accurate early prediction of the recovery in pediatric sepsis patients from MODS to a mild state and thus assist the clinicians in the decision-making process is still lacking. RESULTS: This study develops a machine learning-based approach to predict the recovery from MODS to zero or single organ dysfunction by 1 week in advance in the Swiss Pediatric Sepsis Study cohort of children with blood-culture confirmed bacteremia. Our model achieves internal validation performance on the SPSS cohort with an area under the receiver operating characteristic (AUROC) of 79.1% and area under the precision-recall curve (AUPRC) of 73.6%, and it was also externally validated on another pediatric sepsis patients cohort collected in the USA, yielding an AUROC of 76.4% and AUPRC of 72.4%. These results indicate that our model has the potential to be included into the EHRs system and contribute to patient assessment and triage in pediatric sepsis patient care. AVAILABILITY AND IMPLEMENTATION: Code available at https://github.com/BorgwardtLab/MODS-recovery. The data underlying this article is not publicly available for the privacy of individuals that participated in the study. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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- 2022
28. Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control
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Nieves Valcarce, Ana Mariño, Leonid Margolis, Ezequiel Ruiz-Mateos, Wendy Fitzgerald, Andrés Tabernilla, Hortensia Álvarez, Michael L. Freeman, Hisashi Fujioka, Eva Poveda, Manuel Crespo, Félix Gutiérrez, Michael M. Lederman, Marta Grandal, Jose I Bernardino, Ángel Salgado-Barreira, Alexandre Pérez, Juan González-García, and Pharmaceutical and Pharmacological Sciences
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0301 basic medicine ,Mitochondrial DNA ,Viremia ,HIV Infections ,Mitochondrion ,Biology ,DNA, Mitochondrial ,elite controllers ,Tetraspanin 29 ,Flow cytometry ,Pathogenesis ,03 medical and health sciences ,Extracellular Vesicles ,Cell-Derived Microparticles ,medicine ,Immunology and Allergy ,Humans ,Platelet ,Platelet activation ,medicine.diagnostic_test ,HIV ,medicine.disease ,030112 virology ,Microvesicles ,mitochondria ,030104 developmental biology ,Infectious Diseases ,Immunology ,microvesicles - Abstract
Background The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. Methods Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. Results Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. Conclusions A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.
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- 2022
29. Using artificial intelligence to determine the influence of dental aesthetics on facial attractiveness in comparison to other facial modifications
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Dorothea Obwegeser, Radu Timofte, Christoph Mayer, Theodore Eliades, Michael M Bornstein, Marc A Schätzle, Raphael Patcas, and University of Zurich
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Adult ,Index of Orthodontic Treatment Need ,Infant ,610 Medicine & health ,Orthodontics ,2700 General Medicine ,Esthetics, Dental ,10067 Clinic for Orthodontics and Pediatric Dentistry ,Smiling ,Young Adult ,Artificial Intelligence ,Face ,Humans ,Female ,Malocclusion - Abstract
Background Facial aesthetics is a major motivating factor for undergoing orthodontic treatment. Objectives To ascertain—by means of artificial intelligence (AI)—the influence of dental alignment on facial attractiveness and perceived age, compared to other modifications such as wearing glasses, earrings, or lipstick. Material and methods Forty volunteering females (mean age: 24.5) with near perfectly aligned upper front teeth [Aesthetic Component scale of the Index of Orthodontic Treatment Need (AC-IOTN) = 1 and Peer Assessment Rating Index (PAR Index) = 0 or 1] were photographed with a standardized pose while smiling, in the following settings (number of photographs = 960): without modifications, wearing eyeglasses, earrings, or lipstick. These pictures were taken with natural aligned dentition and with an individually manufactured crooked teeth mock-up (AC-IOTN = 8) to create the illusion of misaligned teeth. Images were assessed for attractiveness and perceived age, using AI, consisting of a face detector and deep convolutional neural networks trained on dedicated datasets for attractiveness and age prediction. Each image received an attractiveness score from 0 to 100 and one value for an age prediction. The scores were descriptively reviewed for each setting, and the facial modifications were tested statistically whether they affected the attractiveness score. The relationship between predicted age and attractiveness scores was examined with linear regression models. Results All modifications showed a significant effect (for all: P < 0.001) on facial attractiveness. In faces with misaligned teeth, wearing eyeglasses (−17.8%) and earrings (−3.2%) had an adverse effect on facial aesthetics. Tooth alignment (+6.9%) and wearing lipstick (+7.9%) increased attractiveness. There was no relevant effect of any assessed modifications or tooth alignment on perceived age (all: Conclusions Alignment of teeth improves facial attractiveness to a similar extent than wearing lipstick, but has no discernable effect on perceived age. Wearing glasses reduces attractiveness considerably, but this effect vanishes with age.
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- 2022
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30. Vascular arterial haemodynamics
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Šutalo, Ilija D., primary, Lawrence-Brown, Michael M. D., additional, Liffman, Kurt, additional, and Semmens, James B., additional
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- 2016
- Full Text
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31. The Financing of Biotech
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Owen, Geoffrey, primary and Hopkins, Michael M., additional
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- 2016
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32. The US Takes the Lead
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Owen, Geoffrey, primary and Hopkins, Michael M., additional
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- 2016
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33. Learning from the US
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Owen, Geoffrey, primary and Hopkins, Michael M., additional
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- 2016
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34. Investors Retreat
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Owen, Geoffrey, primary and Hopkins, Michael M., additional
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- 2016
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35. The Role of Government
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Owen, Geoffrey, primary and Hopkins, Michael M., additional
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- 2016
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36. The Persistence of Industrial Leadership
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Owen, Geoffrey, primary and Hopkins, Michael M., additional
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- 2016
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37. A Second Chance for UK Biotech
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Owen, Geoffrey, primary and Hopkins, Michael M., additional
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- 2016
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38. The British Response
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Owen, Geoffrey, primary and Hopkins, Michael M., additional
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- 2016
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39. A New Way of Making Medicines
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Owen, Geoffrey, primary and Hopkins, Michael M., additional
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- 2016
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- View/download PDF
40. Sentencing Policies and Practices in Wisconsin
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O'Hear, Michael M., primary
- Published
- 2016
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41. Membrane remodeling: theoretical principles, structures of protein scaffolds and forces involved
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Kozlov, Michael M., primary, Weissenhorn, Winfried, additional, and Bassereau, Patricia, additional
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- 2016
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42. TMOD-06. CREATION OF PATIENT-DERIVED LOWER GRADE GLIOMA ORGANOID MODELS FOR PERSONALIZED TREATMENT RESPONSE ASSESSMENT
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Kimmo J. Hatanpaa, Timothy Richardson, Michael M Levitt, Milan R. Savani, Joseph Buehler, Samuel K. McBrayer, Alex C. Sternisha, Cylaina E. Bird, and Kalil G. Abdullah
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Oncology ,Cancer Research ,Lower grade ,medicine.medical_specialty ,Temozolomide ,business.industry ,Personalized treatment ,Astrocytoma ,26th Annual Meeting & Education Day of the Society for Neuro-Oncology ,medicine.disease ,Response assessment ,Internal medicine ,Glioma ,Organoid ,medicine ,Neurology (clinical) ,business ,medicine.drug ,Glioblastoma - Abstract
Creating in vitro models of lower grade glioma represents a major challenge in neuro-oncology research. There are few such models that are tractable and widely used, which has hindered understanding of the biology of these tumors. Recently, substantial progress has been made in generating patient-derived in vitro organoid models of high grade glioma, but modeling lower grade disease remains difficult. Based on our experience creating neurosphere cultures of lower grade astrocytomas from genetically engineered mice, we hypothesized that modifying patient-derived organoid generation protocols to incorporate physiological oxygen levels would allow establishment and propagation of lower grade glioma organoids. In this study, we show that this approach supports efficient organoid model generation from primary glioma specimens across all histological subtypes and tumor grades (WHO Grade I-IV, n = 20). These organoid models retain key characteristics of their respective parental tumors, including IDH mutations and other genetic alterations, metabolite profiles, intratumoral heterogeneity, cellular composition, and cytoarchitectural features. Importantly, lower grade glioma organoids can be cultured for months and reanimated after biobanking. Our high success rate ( >90%) in establishing organoid models from primary lower grade glioma tissue samples further highlighted opportunities for treatment response assessments. To perform longitudinal measurements of therapy-induced changes in glioma organoid viability, we designed a novel, non-invasive imaging assay (termed rapid apex imaging) to determine real-time treatment response in low and high grade gliomas. We evaluated longitudinal responses of glioblastoma and IDH1 R132H-positive Grade II astrocytoma organoids to temozolomide and olaparib with and without radiation treatment. We quantified topological changes in organoid structure by building a bioinformatics tool to translate imaging data into a cellularity metric as a biomarker of organoid response. Our work unveils an effective new method to create in vitro, personalized models of lower grade glioma that supports elucidation of treatment sensitivity profiles.
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- 2021
43. Corrigendum to: Involvement of RNA granule proteins in meiotic silencing by unpaired DNA
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Victor T Sy, Rana F Kennedy, Hua Xiao, Michelle A. Williams, Patrick K. T. Shiu, Michael M Vierling, Logan M Decker, Erin C. Boone, and Jackson B Haynes
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AcademicSubjects/SCI01140 ,Neurospora crassa ,AcademicSubjects/SCI00010 ,Biology ,QH426-470 ,AcademicSubjects/SCI01180 ,Cell biology ,Meiosis ,chemistry.chemical_compound ,RNA granule ,chemistry ,Genetics ,AcademicSubjects/SCI00960 ,RNA ,Gene silencing ,RNA Interference ,Gene Silencing ,Corrigendum ,DNA, Fungal ,Molecular Biology ,Genetics (clinical) ,DNA - Abstract
In Neurospora crassa, expression from an unpaired gene is suppressed by a mechanism known as meiotic silencing by unpaired DNA (MSUD). MSUD utilizes common RNA interference (RNAi) factors to silence target mRNAs. Here, we report that Neurospora CAR-1 and CGH-1, homologs of two Caenorhabditis elegans RNA granule components, are involved in MSUD. These fungal proteins are found in the perinuclear region and P-bodies, much like their worm counterparts. They interact with components of the meiotic silencing complex (MSC), including the SMS-2 Argonaute. This is the first time MSUD has been linked to RNA granule proteins.
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- 2021
44. Contribution of interneuron subtype-specific GABAergic signalling to emergent sensory processing in mouse somatosensory whisker barrel cortex
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Liad J. Baruchin, Simon J. B. Butt, Filippo Ghezzi, and Michael M. Kohl
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Mammals ,Sensory Adaptation ,Neocortex ,Interneuron ,Sensory processing ,Cognitive Neuroscience ,Whisking in animals ,medicine.medical_treatment ,Sensory system ,Somatosensory Cortex ,Barrel cortex ,Biology ,Mice ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Interneurons ,Vibrissae ,medicine ,Animals ,GABAergic ,Perception ,Neuroscience ,Vasoactive Intestinal Peptide - Abstract
Mammalian neocortex is important for conscious processing of sensory information with balanced glutamatergic and GABAergic signaling fundamental to this function. Yet little is known about how this interaction arises despite increasing insight into early GABAergic interneuron (IN) circuits. To study this, we assessed the contribution of specific INs to the development of sensory processing in the mouse whisker barrel cortex, specifically the role of INs in early speed coding and sensory adaptation. In wild-type animals, both speed processing and adaptation were present as early as the layer 4 critical period of plasticity and showed refinement over the period leading to active whisking onset. To test the contribution of IN subtypes, we conditionally silenced action-potential-dependent GABA release in either somatostatin (SST) or vasoactive intestinal peptide (VIP) INs. These genetic manipulations influenced both spontaneous and sensory-evoked cortical activity in an age- and layer-dependent manner. Silencing SST + INs reduced early spontaneous activity and abolished facilitation in sensory adaptation observed in control pups. In contrast, VIP + IN silencing had an effect towards the onset of active whisking. Silencing either IN subtype had no effect on speed coding. Our results show that these IN subtypes contribute to early sensory processing over the first few postnatal weeks.
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- 2021
45. Epistasis for head morphology in Drosophila melanogaster
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Robert R. H. Anholt, Shanshan Zhou, Bahar Patlar, Murat Yılmaz, Wen Huang, Esra Durmaz, Michael M. Magwire, Trudy F. C. Mackay, Ergi Deniz Özsoy, and Güzin Emecen
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AcademicSubjects/SCI01140 ,AcademicSubjects/SCI00010 ,ved/biology.organism_classification_rank.species ,Biology ,QH426-470 ,AcademicSubjects/SCI01180 ,genetic interaction network ,Gene mapping ,Genetic algorithm ,Genetic model ,Genetics ,Animals ,Allele ,Model organism ,Molecular Biology ,Alleles ,modifier loci ,Genetics (clinical) ,Investigation ,ved/biology ,Chromosome Mapping ,Epistasis, Genetic ,Drosophila Genetic Reference Panel ,biology.organism_classification ,Phenotype ,Drosophila melanogaster ,genome-wide association analyses ,AcademicSubjects/SCI00960 ,Epistasis ,Genome-Wide Association Study - Abstract
Epistasis—gene–gene interaction—is common for mutations with large phenotypic effects in humans and model organisms. Epistasis impacts quantitative genetic models of speciation, response to natural and artificial selection, genetic mapping, and personalized medicine. However, the existence and magnitude of epistasis between alleles with small quantitative phenotypic effects are controversial and difficult to assess. Here, we use the Drosophila melanogaster Genetic Reference Panel of sequenced inbred lines to evaluate the magnitude of naturally occurring epistasis modifying the effects of mutations in jing and inv, two transcription factors that have subtle quantitative effects on head morphology as homozygotes. We find significant epistasis for both mutations and performed single marker genome-wide association analyses to map candidate modifier variants and loci affecting head morphology. A subset of these loci was significantly enriched for a known genetic interaction network, and mutations of the candidate epistatic modifier loci also affect head morphology.
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- 2021
46. The Regulation of Circulating Hepatokines by Fructose Ingestion in Humans
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Peter Plomgaard and Michael M Richter
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0301 basic medicine ,medicine.medical_specialty ,endocrine system ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Context (language use) ,Glucagon ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin resistance ,FGF21 ,ANGPTL4 ,Internal medicine ,insulin resistance ,medicine ,follistatin ,Ingestion ,Research Articles ,biology ,Chemistry ,Insulin ,Fructose ,medicine.disease ,030104 developmental biology ,Somatostatin ,Endocrinology ,GDF15 ,glucagon ,biology.protein ,hormones, hormone substitutes, and hormone antagonists ,AcademicSubjects/MED00250 ,Follistatin - Abstract
Context Fibroblast growth factor 21 (FGF21), follistatin, angiopoietin-like 4 (ANGPTL4), and growth differential factor 15 (GDF15) are regulated by energy metabolism. Recent findings in humans demonstrate that fructose ingestion increases circulating FGF21, with increased response in conditions of insulin resistance. Objective This study examines the acute effect of fructose and somatostatin on circulating FGF21, follistatin, ANGPTL4, and GDF15 in humans. Methods Plasma FGF21, follistatin, ANGPTL4, and GDF15 concentrations were measured in response to oral ingestion of 75 g of fructose in 10 young healthy males with and without a 15-minute infusion of somatostatin to block insulin secretion. A control infusion of somatostatin was also performed in the same subjects. Results Following fructose ingestion, plasma FGF21 peaked at 3.7-fold higher than basal concentration (P < 0.05), and it increased 4.9-fold compared with basal concentration (P < 0.05) when somatostatin was infused. Plasma follistatin increased 1.8-fold after fructose ingestion (P < 0.05), but this increase was blunted by concomitant somatostatin infusion. For plasma ANGPTL4 and GDF15, no increases were obtained following fructose ingestion. Infusion of somatostatin alone slightly increased plasma FGF21 and follistatin. Conclusion Here we show that in humans (1) the fructose-induced increase in plasma FGF21 was enhanced when somatostatin was infused, suggesting an inhibitory role of insulin on the fructose-induced FGF21 increase; (2) fructose ingestion also increased plasma follistatin, but somatostatin infusion blunted the increase; and (3) fructose ingestion had no stimulating effect on ANGPTL4 and GDF15 levels, demonstrating differences in the hepatokine response to fructose ingestion.
- Published
- 2021
47. Anxiety Disorders
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Reese, Michael M., primary
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- 2015
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48. Shaping the Fiscal Policy Framework
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Bergman, U. Michael, primary, Hutchison, Michael M., additional, and Jensen, Svend E. Hougaard, additional
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- 2015
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49. The Extraterritorial Application of Access to Justice Rights
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Karayanni, Michael M, primary
- Published
- 2014
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50. The Acute Multicultural Entrapment of the Palestinian-Arab Religious Minorities in Israel and the Feeble Measures Required to Relieve It
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Karayanni, Michael M., primary
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- 2014
- Full Text
- View/download PDF
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