Search

Background: Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease., Methods: Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns., Findings: Forty patients (32M:8F, age: 22-98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury., Interpretation: The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established., Funding: UK Research and Innovation/Medical Research Council through the UK Coronavirus Immunology Consortium, Barbour Foundation, General Sir John Monash Foundation, Newcastle University, JGW Patterson Foundation, Wellcome Trust., Competing Interests: Declaration of interests L Milross was supported by a General Sir John Monash Scholarship awarded by the General Sir John Monash Foundation and a Vice-Chancellor's Global Scholarship from Newcastle University in support of a Master of Research in Immunobiology at Newcastle University. A Thomson was supported by funding from the JGW Patterson Foundation. C. J. A. Duncan was supported by a Wellcome Clinical Research Career Development Fellowship (211153/Z/18/Z)., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: Widespread disruption of healthcare services and excess mortality not directly attributed to COVID-19 occurred between March and May 2020. We undertook the first UK multicentre study of coroners' autopsies before and during this period using postmortem reports., Methods: We reviewed reports of non-forensic coroners' autopsies performed during the first COVID-19 lockdown (23 March to 8 May 2020), and the same period in 2018. Deaths were categorised as natural non-COVID-19, COVID-19-related, non-natural (suicide, drug and alcohol-related, traumatic, other). We provided opinion regarding whether delayed access to medical care or changes in behaviour due to lockdown were a potential factor in deaths., Results: Seven centres covering nine coronial jurisdictions submitted a total of 1100 coroners' autopsies (498 in 2018, 602 in 2020). In only 54 autopsies was death attributed to COVID-19 (9%). We identified a significant increase in cases where delays in accessing medical care potentially contributed to death (10 in 2018, 44 in 2020). Lockdown was a contributing factor in a proportion of suicides (24%) and drug and alcohol-related deaths (12%)., Conclusions: Postmortem reports have considerable utility in evaluating excess mortality due to healthcare and wider societal disruption during a pandemic. They provide information at an individual case level that is not available from assessment of death certification data. Detailed evaluation of coroners' autopsy reports, supported by appropriate regulatory oversight, is recommended to mitigate disruption and indirect causes of mortality in future pandemics. Maintaining access to healthcare, including substance misuse and mental health services, is an important consideration., Competing Interests: Competing interests: ISDR, NC, SKS, AG, PJ, MO received payment from HM Coroner for undertaking non-forensic Coronial Post Mortem work during the period of the study. GR holds a patent on the ‘Cadatheter’, a catheter designed specifically for postmortem computed tomography angiography (PI/GB2012/050359). MM has received Research Grant funding from Novartis and Novo Nordisk, and a Fellowship Grant from the British Heart Foundation Oxford Centre for Research Excellence., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Post mortem examination of lung and heart tissue has been vital to developing an understanding of COVID-19 pathophysiology; however studies to date have almost uniformly used tissue obtained from hospital-based deaths where individuals have been exposed to major medical and pharmacological interventions., Methods: In this study we investigated patterns of lung and heart injury from 46 community-based, pre-hospital COVID-19-attributable deaths who underwent autopsy., Results: The cohort comprised 22 females and 24 males, median age 64 years (range 19-91) at time of death with illness duration range 0-23 days. Comorbidities associated with poor outcomes in COVID-19 included obesity (body mass index >30 kg·m -2 ) in 19 out of 46 cases (41.3%). Diffuse alveolar damage in its early exudative phase was the most common pattern of lung injury; however significant heterogeneity was identified with bronchopneumonia, pulmonary oedema consistent with acute cardiac failure, pulmonary thromboembolism and microthrombosis also identified and often in overlapping patterns. Review of clinical records and next of kin accounts suggested a combination of unexpectedly low symptom burden, rapidly progressive disease and psychosocial factors may have contributed to a failure of hospital presentation prior to death., Conclusions: Identifying such advanced acute lung injury in community-based deaths is extremely unusual and raises the question why some with severe COVID-19 pneumonitis were not hospitalised. Multiple factors including low symptom burden, rapidly progressive disease trajectories and psychosocial factors provide possible explanations., Competing Interests: Conflicts of interest: The authors declare no conflict of interest., (Copyright ©The authors 2022.)

We experimentally realize a spin-momentum lattice with a homogeneously trapped Fermi gas. The lattice is created via cyclically rotated atom-laser couplings between three bare atomic spin states, and are such that they form a triangular lattice in a synthetic spin-momentum space. We demonstrate the lattice and explore its dynamics with spin- and momentum-resolved absorption imaging. This platform will provide new opportunities for synthetic spin systems and the engineering of topological bands. In particular, the use of three spin states in two spatial dimensions would allow the simulation of synthetic magnetic fields of high spatial uniformity, which would lead to ultranarrow Chern bands that support robust fractional quantum Hall states.

The lungs are the main site that is affected in severe COVID-19, and post-mortem lung tissue provides crucial insights into the pathophysiology of severe disease. From basic histology to state-of-the-art multiparameter digital pathology technologies, post-mortem lung tissue provides snapshots of tissue architecture, and resident and inflammatory cell phenotypes and composition at the time of death. Contrary to early assumptions that COVID-19 in the lungs is a uniform disease, post-mortem findings have established a high degree of disease heterogeneity. Classic diffuse alveolar damage represents just one phenotype, with disease divisible by early and late progression as well as by pathophysiological process. A distinct lung tissue state occurs with secondary infection; extrapulmonary causes of death might also originate from a pathological process in the lungs linked to microthrombosis. This heterogeneity of COVID-19 lung disease must be recognised in the management of patients and in the development of novel treatment strategies., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Ninety-six people died following a crowd crush at the Hillsborough Football Stadium, Sheffield, UK in 1989. The cause of death in nearly all cases was compression asphyxia. The clinical and pathological features of deaths encountered in crowds are discussed with a particular focus on the Hillsborough disaster., Competing Interests: Competing interests: All authors received payment for their contributions as expert witnesses for the 2014–2016 Hillsborough Inquests., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Excitonic insulators host a condensate of electron-hole pairs at equilibrium, giving rise to collective many-body effects. Although several materials have emerged as excitonic insulator candidates, evidence of long-range coherence is lacking and the origin of the ordered phase in these systems remains controversial. Here, using ultrafast pump-probe microscopy, we investigate the possible excitonic insulator Ta 2 NiSe 5 Below 328 K, we observe the anomalous micrometer-scale propagation of coherent modes at velocities of ~10 5 m/s, which we attribute to the hybridization between phonon modes and the phase mode of the condensate. We develop a theoretical framework to support this explanation and propose that electronic interactions provide a substantial contribution to the ordered phase in Ta 2 NiSe 5 These results allow us to understand how the condensate's collective modes transport energy and interact with other degrees of freedom. Our study provides a unique paradigm for the investigation and manipulation of these properties in strongly correlated materials., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

We study the decay mechanism of the gapped lowest-lying axial excitation of a quasipure atomic Bose-Einstein condensate confined in a cylindrical box trap. Owing to the absence of accessible lower-energy modes, or direct coupling to an external bath, this excitation is protected against one-body (linear) decay, and the damping mechanism is exclusively nonlinear. We develop a universal theoretical model that explains this fundamentally nonlinear damping as a process whereby two quanta of the gapped lowest excitation mode couple to a higher-energy mode, which subsequently decays into a continuum. We find quantitative agreement between our experiments and the predictions of this model. Finally, by strongly driving the system below its (lowest) resonant frequency, we observe third-harmonic generation, a hallmark of nonlinear behavior.

We show that a simple experimental setting of a locally pumped and lossy array of two-level quantum systems can stabilize states with strong long-range coherence. Indeed, by explicit analytic construction, we show there is an extensive set of steady-state density operators, from minimally to maximally entangled, despite this being an interacting open many-body problem. Such nonequilibrium steady states arise from a hidden symmetry that stabilizes Bell pairs over arbitrarily long distances, with unique experimental signatures. We demonstrate a protocol by which one can selectively prepare these states using dissipation. Our findings are accessible in present-day experiments.

Objective: The inhalation of air-borne toxicants is associated with adverse health outcomes which can be somewhat mitigated by enhancing endogenous anti-oxidant capacity. Carnosine is a naturally occurring dipeptide (β-alanine-L-histidine), present in high abundance in skeletal and cardiac muscle. This multi-functional dipeptide has anti-oxidant properties, can buffer intracellular pH, chelate metals, and sequester aldehydes such as acrolein. Due to these chemical properties, carnosine may be protective against inhaled pollutants which can contain metals and aldehydes and can stimulate the generation of electrophiles in exposed tissues. Thus, assessment of carnosine levels, or levels of its acrolein conjugates (carnosine-propanal and carnosine-propanol) may inform on level of exposure and risk assessment., Methods: We used established mass spectroscopy methods to measure levels of urinary carnosine ( n  = 605) and its conjugates with acrolein ( n  = 561) in a subset of participants in the Louisville Healthy Heart Study (mean age = 51 ± 10; 52% male). We then determined associations between these measures and air pollution exposure and smoking behavior using statistical modeling approaches., Results: We found that higher levels of non-conjugated carnosine, carnosine-propanal, and carnosine-propanol were significantly associated with males ( p  < 0.02) and those of Caucasian ethnicity ( p  < 0.02). Levels of carnosine-propanol were significantly higher in never-smokers ( p  = 0.001) but lower in current smokers ( p  = 0.037). This conjugate also demonstrated a negative association with mean-daily particulate air pollution (PM 2.5 ) levels ( p  = 0.01)., Conclusions: These findings suggest that urinary levels of carnosine-propanol may inform as to risk from inhaled pollutants.

Over the past two decades, researchers have discovered a special form of alternative splicing that produces a circular form of RNA. Although these circular RNAs (circRNAs) have garnered considerable attention in the scientific community for their biogenesis and functions, the focus of current studies has been on the tissue-specific circRNAs that exist only in one tissue but not in other tissues or on the disease-specific circRNAs that exist in certain disease conditions, such as cancer, but not under normal conditions. This approach was conducted in the relative absence of methods that analyze a group of common circRNAs that exist in both conditions, but are more abundant in one condition relative to another (differentially expressed). Studies of differentially expressed circRNAs (DECs) between two conditions would serve as a significant first step in filling this void. Here, we introduce a novel computational tool, seekCRIT (seek for differentially expressed CircRNAs In Transcriptome), that identifies the DECs between two conditions from high-throughput sequencing data. Using rat retina RNA-seq data from ischemic and normal conditions, we show that over 74% of identifiable circRNAs are expressed in both conditions and over 40 circRNAs are differentially expressed between two conditions. We also obtain a high qPCR validation rate of 90% for DECs with a FDR of < 5%. Our results demonstrate that seekCRIT is a novel and efficient approach to detect DECs using rRNA depleted RNA-seq data. seekCRIT is freely downloadable at https://github.com/UofLBioinformatics/seekCRIT. The source code is licensed under the MIT License. seekCRIT is developed and tested on Linux CentOS-7., Competing Interests: The authors have declared that no competing interests exist.

We uncover a topological classification applicable to open fermionic systems governed by a general class of Lindblad master equations. These "quadratic Lindbladians" can be captured by a non-Hermitian single-particle matrix which describes internal dynamics as well as system-environment coupling. We show that this matrix must belong to one of ten non-Hermitian Bernard-LeClair symmetry classes which reduce to the Altland-Zirnbauer classes in the closed limit. The Lindblad spectrum admits a topological classification, which we show results in gapless edge excitations with finite lifetimes. Unlike previous studies of purely Hamiltonian or purely dissipative evolution, these topological edge modes are unconnected to the form of the steady state. We provide one-dimensional examples where the addition of dissipators can either preserve or destroy the closed classification of a model, highlighting the sensitivity of topological properties to details of the system-environment coupling.

Background: High-throughput RNA sequencing (RNA-seq) has evolved as an important analytical tool in molecular biology. Although the utility and importance of this technique have grown, uncertainties regarding the proper analysis of RNA-seq data remain. Of primary concern, there is no consensus regarding which normalization and statistical methods are the most appropriate for analyzing this data. The lack of standardized analytical methods leads to uncertainties in data interpretation and study reproducibility, especially with studies reporting high false discovery rates. In this study, we compared a recently developed normalization method, UQ-pgQ2, with three of the most frequently used alternatives including RLE (relative log estimate), TMM (Trimmed-mean M values) and UQ (upper quartile normalization) in the analysis of RNA-seq data. We evaluated the performance of these methods for gene-level differential expression analysis by considering the factors, including: 1) normalization combined with the choice of a Wald test from DESeq2 and an exact test/QL (Quasi-likelihood) F-Test from edgeR; 2) sample sizes in two balanced two-group comparisons; and 3) sequencing read depths., Results: Using the MAQC RNA-seq datasets with small sample replicates, we found that UQ-pgQ2 normalization combined with an exact test can achieve better performance in term of power and specificity in differential gene expression analysis. However, using an intra-group analysis of false positives from real and simulated data, we found that a Wald test performs better than an exact test when the number of sample replicates is large and that a QL F-test performs the best given sample sizes of 5, 10 and 15 for any normalization. The RLE, TMM and UQ methods performed similarly given a desired sample size., Conclusion: We found the UQ-pgQ2 method combined with an exact test/QL F-test is the best choice in order to control false positives when the sample size is small. When the sample size is large, UQ-pgQ2 with a QL F-test is a better choice for the type I error control in an intra-group analysis. We observed read depths have a minimal impact for differential gene expression analysis based on the simulated data.

Classical dynamical systems close to a critical point are known to act as efficient sensors due to a strongly nonlinear response. We explore such systems in the quantum regime by modeling a quantum version of a driven van der Pol oscillator. We find the classical response survives down to one excitation quantum. At very weak drives, genuine quantum features arise, including diverging and negative susceptibilities. Further, the linear response is greatly enhanced by using a strong incoherent pump. These results are largely generic and can be probed in current experimental platforms suited for quantum sensing.

Outer hair cells (OHCs) in the mammalian ear exhibit electromotility, electrically driven somatic length changes that are thought to mechanically amplify sound-evoked vibrations. For this amplification to work, OHCs must respond to sounds on a cycle-by-cycle basis even at frequencies that exceed the low-pass corner frequency of their cell membranes. Using in vivo optical vibrometry we tested this theory by measuring sound-evoked motility in the 13-25 kHz region of the gerbil cochlea. OHC vibrations were strongly rectified, and motility exhibited first-order low-pass characteristics with corner frequencies around 3 kHz- more than 2.5 octaves below the frequencies the OHCs are expected to amplify. These observations lead us to suggest that the OHCs operate more like the envelope detectors in a classical gain-control scheme than like high-frequency sound amplifiers. These findings call for a fundamental reconsideration of the role of the OHCs in cochlear function and the causes of cochlear hearing loss., Competing Interests: AV, NC, Mv No competing interests declared, (© 2019, Vavakou et al.)

High throughput RNA sequencing (RNA-seq) technology is increasingly used in disease-related biomarker studies. A negative binomial distribution has become the popular choice for modeling read counts of genes in RNA-seq data due to over-dispersed read counts. In this study, we propose two explicit sample size calculation methods for RNA-seq data using a negative binomial regression model. To derive these new sample size formulas, the common dispersion parameter and the size factor as an offset via a natural logarithm link function are incorporated. A two-sided Wald test statistic derived from the coefficient parameter is used for testing a single gene at a nominal significance level 0.05 and multiple genes at a false discovery rate 0.05. The variance for the Wald test is computed from the variance-covariance matrix with the parameters estimated from the maximum likelihood estimates under the unrestricted and constrained scenarios. The performance and a side-by-side comparison of our new formulas with three existing methods with a Wald test, a likelihood ratio test or an exact test are evaluated via simulation studies. Since other methods are much computationally extensive, we recommend our M1 method for quick and direct estimation of sample sizes in an experimental design. Finally, we illustrate sample sizes estimation using an existing breast cancer RNA-seq data.

We study the topological properties of one-dimensional systems undergoing unitary time evolution. We show that symmetries possessed both by the initial wave function and by the Hamiltonian at all times may not be present in the time-dependent wave function-a phenomenon which we dub "dynamically induced symmetry breaking." This leads to the possibility of a time-varying bulk index after quenching within noninteracting gapped topological phases. The consequences are observable experimentally through particle transport measurements. With reference to the entanglement spectrum, we explain how the topology of the wave function can change out of equilibrium, both for noninteracting fermions and for symmetry-protected topological phases protected by antiunitary symmetries.

Breast cancer (BC) is increasing in incidence and resistance to treatment worldwide. The challenges in limited therapeutic options and poor survival outcomes in BC subtypes persist because of its molecular heterogeneity and resistance to standard endocrine therapy. Recently, high throughput RNA sequencing (RNA-seq) has been used to identify biomarkers of disease progression and signaling pathways that could be amenable to specific therapies according to the BC subtype. However, there is no single generally accepted pipeline for the analysis of RNA-seq data in biomarker discovery due, in part, to the needs of simultaneously satisfying constraints of sensitivity and specificity. We proposed a combined approach using gene-wise normalization, UQ-pgQ2, followed by a Wald test from DESeq2. Our approach improved the analysis based on within-group comparisons in terms of the specificity when applied to publicly available RNA-seq BC datasets. In terms of identifying differentially expressed genes (DEGs), we combined an optimized log2 fold change cutoff with a nominal false discovery rate of 0.05 to further minimize false positives. Using this method in the analysis of two GEO BC datasets, we identified 797 DEGs uniquely expressed in triple negative BC (TNBC) and significantly associated with T cell and immune-related signaling, contributing to the immunotherapeutic efficacy in TNBC patients. In contrast, we identified 1403 DEGs uniquely expressed in estrogen positive and HER2 negative BC (ER+HER2-BC) and significantly associated with eicosanoid, notching and FAK signaling while a common set of genes was associated with cellular growth and proliferation. Thus, our approach to control for false positives identified two distinct gene expression profiles associated with these two subtypes of BC which are distinguishable by their molecular and functional attributes., Competing Interests: The authors have declared that no competing interests exist.

The micromechanical mechanisms that underpin tuning and dynamic range compression in the mammalian inner ear are fundamental to hearing, but poorly understood. Here, we present new, high-resolution optical measurements that directly map sound-evoked vibrations on to anatomical structures in the intact, living gerbil cochlea. The largest vibrations occur in a tightly delineated hotspot centering near the interface between the Deiters' and outer hair cells. Hotspot vibrations are less sharply tuned, but more nonlinear, than basilar membrane vibrations, and behave non-monotonically (exhibiting hyper-compression) near their characteristic frequency. Amplitude and phase differences between hotspot and basilar membrane responses depend on both frequency and measurement angle, and indicate that hotspot vibrations involve longitudinal motion. We hypothesize that structural coupling between the Deiters' and outer hair cells funnels sound-evoked motion into the hotspot region, under the control of the outer hair cells, to optimize cochlear tuning and compression.

We develop an analytic theory for the recently demonstrated Josephson junction laser [M. C. Cassidy et al., Science 355, 939 (2017)SCIEAS0036-807510.1126/science.aah6640]. By working in the time-domain representation (rather than the frequency domain), a single nonlinear equation is obtained for the dynamics of the device, which is fully solvable in some regimes of operation. The nonlinear drive is seen to lead to mode-locked output, with a period set by the round-trip time of the resonant cavity.

The goal of this study is to develop a model that explains the relationship between microRNAs, transcription factors, and their co-target genes. This relationship was previously reported in gene regulatory loops associated with 24 hour (24h) and 7 day (7d) time periods following ischemia-reperfusion injury in a rat's retina. Using a model system of retinal ischemia-reperfusion injury, we propose that microRNAs first influence transcription factors, which in turn act as mediators to influence transcription of genes via triadic regulatory loops. Analysis of the relative contributions of direct and indirect regulatory influences on genes revealed that a substantial fraction of the regulatory loops (69% for 24 hours and 77% for 7 days) could be explained by causal mediation. Over 40% of the mediated loops in both time points were regulated by transcription factors only, while about 20% of the loops were regulated entirely by microRNAs. The remaining fractions of the mediated regulatory loops were cooperatively mediated by both microRNAs and transcription factors. The results from these analyses were supported by the patterns of expression of the genes, transcription factors, and microRNAs involved in the mediated loops in both post-ischemic time points. Additionally, network motif detection for the mediated loops showed a handful of time specific motifs related to ischemia-reperfusion injury in a rat's retina. In summary, the effects of microRNAs on genes are mediated, in large part, via transcription factors.

Normalization is an essential step with considerable impact on high-throughput RNA sequencing (RNA-seq) data analysis. Although there are numerous methods for read count normalization, it remains a challenge to choose an optimal method due to multiple factors contributing to read count variability that affects the overall sensitivity and specificity. In order to properly determine the most appropriate normalization methods, it is critical to compare the performance and shortcomings of a representative set of normalization routines based on different dataset characteristics. Therefore, we set out to evaluate the performance of the commonly used methods (DESeq, TMM-edgeR, FPKM-CuffDiff, TC, Med UQ and FQ) and two new methods we propose: Med-pgQ2 and UQ-pgQ2 (per-gene normalization after per-sample median or upper-quartile global scaling). Our per-gene normalization approach allows for comparisons between conditions based on similar count levels. Using the benchmark Microarray Quality Control Project (MAQC) and simulated datasets, we performed differential gene expression analysis to evaluate these methods. When evaluating MAQC2 with two replicates, we observed that Med-pgQ2 and UQ-pgQ2 achieved a slightly higher area under the Receiver Operating Characteristic Curve (AUC), a specificity rate > 85%, the detection power > 92% and an actual false discovery rate (FDR) under 0.06 given the nominal FDR (≤0.05). Although the top commonly used methods (DESeq and TMM-edgeR) yield a higher power (>93%) for MAQC2 data, they trade off with a reduced specificity (<70%) and a slightly higher actual FDR than our proposed methods. In addition, the results from an analysis based on the qualitative characteristics of sample distribution for MAQC2 and human breast cancer datasets show that only our gene-wise normalization methods corrected data skewed towards lower read counts. However, when we evaluated MAQC3 with less variation in five replicates, all methods performed similarly. Thus, our proposed Med-pgQ2 and UQ-pgQ2 methods perform slightly better for differential gene analysis of RNA-seq data skewed towards lowly expressed read counts with high variation by improving specificity while maintaining a good detection power with a control of the nominal FDR level.

The de Haas-van Alphen effect describes the periodic oscillation of the magnetization in a material as a function of an inverse applied magnetic field. It forms the basis of a well established procedure for measuring Fermi surface properties, and its observation is typically taken as a direct signature of a system being metallic. However, certain insulators can show similar oscillations of the magnetization from quantization of the energies of electron states in filled bands. Recently, the theory of such an anomalous dHvAE (AdHvAE) was worked out, but there has not yet been a clear experimental observation. Here, we show that the inverted narrow gap regime of InAs/GaSb quantum wells is an ideal platform for the observation of the AdHvAE. From our microscopic calculations, we make quantitative predictions for the relevant magnetic field and temperature regimes, and we describe unambiguous experimental signatures.

Kondo insulating materials lie outside the usual dichotomy of weakly versus correlated-band versus Mott-insulators. They are metallic at high temperatures but resemble band insulators at low temperatures because of the opening of an interaction-induced band gap. The first discovered Kondo insulator (KI) SmB&#95;{6} has been predicted to form a topological KI (TKI). However, since its discovery thermodynamic and transport anomalies have been observed that have defied a theoretical explanation. Enigmatic signatures of collective modes inside the charge gap are seen in specific heat, thermal transport, and quantum oscillation experiments in strong magnetic fields. Here, we show that TKIs are susceptible to the formation of excitons and magnetoexcitons. These charge neutral composite particles can account for long-standing anomalies in SmB&#95;{6}.

Background: The volume of biomedical literature and its underlying knowledge base is rapidly expanding, making it beyond the ability of a single human being to read through all the literature. Several automated methods have been developed to help make sense of this dilemma. The present study reports on the results of a text mining approach to extract gene interactions from the data warehouse of published experimental results which are then used to benchmark an interaction network associated with glaucoma. To the best of our knowledge, there is, as yet, no glaucoma interaction network derived solely from text mining approaches. The presence of such a network could provide a useful summative knowledge base to complement other forms of clinical information related to this disease., Results: A glaucoma corpus was constructed from PubMed Central and a text mining approach was applied to extract genes and their relations from this corpus. The extracted relations between genes were checked using reference interaction databases and classified generally as known or new relations. The extracted genes and relations were then used to construct a glaucoma interaction network. Analysis of the resulting network indicated that it bears the characteristics of a small world interaction network. Our analysis showed the presence of seven glaucoma linked genes that defined the network modularity. A web-based system for browsing and visualizing the extracted glaucoma related interaction networks is made available at http://neurogene.spd.louisville.edu/GlaucomaINViewer/Form1.aspx., Conclusions: This study has reported the first version of a glaucoma interaction network using a text mining approach. The power of such an approach is in its ability to cover a wide range of glaucoma related studies published over many years. Hence, a bigger picture of the disease can be established. To the best of our knowledge, this is the first glaucoma interaction network to summarize the known literature. The major findings were a set of relations that could not be found in existing interaction databases and that were found to be new, in addition to a smaller subnetwork consisting of interconnected clusters of seven glaucoma genes. Future improvements can be applied towards obtaining a better version of this network.

We propose the use of optical lattice clocks operated with fermionic alkaline-earth atoms to study spin-orbit coupling (SOC) in interacting many-body systems. The SOC emerges naturally during the clock interrogation, when atoms are allowed to tunnel and accumulate a phase set by the ratio of the "magic" lattice wavelength to the clock transition wavelength. We demonstrate how standard protocols such as Rabi and Ramsey spectroscopy that take advantage of the sub-Hertz resolution of state-of-the-art clock lasers can perform momentum-resolved band tomography and determine SOC-induced s-wave collisions in nuclear-spin-polarized fermions. With the use of a second counterpropagating clock beam, we propose a method for engineering controlled atomic transport and study how it is modified by p- and s-wave interactions. The proposed spectroscopic probes provide clean and well-resolved signatures at current clock operating temperatures.

Dynamic aspects of cochlear mechanical compression were studied by recording basilar membrane (BM) vibrations evoked by tone pairs ("beat stimuli") in the 11-19 kHz region of the gerbil cochlea. The frequencies of the stimulus components were varied to produce a range of "beat rates" at or near the characteristic frequency (CF) of the BM site under study, and the amplitudes of the components were balanced to produce near perfect periodic cancellations, visible as sharp notches in the envelope of the BM response. We found a compressive relation between instantaneous stimulus intensity and BM response magnitude that was strongest at low beat rates (e.g., 10-100 Hz). At higher beat rates, the amount of compression reduced progressively (i.e. the responses became linearized), and the rising and falling flanks of the response envelope showed increasing amounts of hysteresis; the rising flank becoming steeper than the falling flank. This hysteresis indicates that cochlear mechanical compression is not instantaneous, and is suggestive of a gain control mechanism having finite attack and release times. In gain control terms, the linearization that occurs at higher beat rates occurs because the instantaneous gain becomes smoothened, or low-pass filtered, with respect to the magnitude fluctuations in the stimulus. In terms of peripheral processing, the linearization corresponds to an enhanced coding, or decompression, of rapid amplitude modulations. These findings are relevant both to those who wish to understand the underlying mechanisms and those who need a realistic model of nonlinear processing by the auditory periphery.

We propose a scheme for realizing lattice potentials of subwavelength spacing for ultracold atoms. It is based on spin-dependent optical lattices with a time-periodic modulation. We show that the atomic motion is well described by the combined action of an effective, time-independent lattice of small spacing, together with a micromotion associated with the time modulation. A numerical simulation shows that an atomic gas can be adiabatically loaded into the effective lattice ground state, for time scales comparable to the ones required for adiabatic loading of standard optical lattices. We generalize our scheme to a two-dimensional geometry, leading to Bloch bands with nonzero Chern numbers. The realization of lattices of subwavelength spacing allows for the enhancement of energy scales, which could facilitate the achievement of strongly correlated (topological) states.

The de Haas-van Alphen effect (dHvAE), describing oscillations of the magnetization as a function of magnetic field, is commonly assumed to be a definite sign for the presence of a Fermi surface (FS). Indeed, the effect forms the basis of a well-established experimental procedure for accurately measuring FS topology and geometry of metallic systems, with parameters commonly extracted by fitting to the Lifshitz-Kosevich (LK) theory based on Fermi liquid theory. Here we show that, in contrast to this canonical situation, there can be quantum oscillations even for band insulators of certain types. We provide simple analytic formulas describing the temperature dependence of the quantum oscillations in this setting, showing strong deviations from LK theory. We draw connections to recent experiments and discuss how our results can be used in future experiments to accurately determine, e.g., hybridization gaps in heavy-fermion systems.

The Harper-Hofstadter model provides a fractal spectrum containing topological bands of any integer Chern number C. We study the many-body physics that is realized by interacting particles occupying Harper-Hofstadter bands with |C|>1. We formulate the predictions of Chern-Simons or composite fermion theory in terms of the filling factor ν, defined as the ratio of particle density to the number of single-particle states per unit area. We show that this theory predicts a series of fractional quantum Hall states with filling factors ν=r/(r|C|+1) for bosons, or ν=r/(2r|C|+1) for fermions. This series includes a bosonic integer quantum Hall state in |C|=2 bands. We construct specific cases where a single band of the Harper-Hofstadter model is occupied. For these cases, we provide numerical evidence that several states in this series are realized as incompressible quantum liquids for bosons with contact interactions.

In two dimensions strongly interacting bosons in a magnetic field can realize a bosonic integer quantum Hall state, the simplest two-dimensional example of a symmetry-protected topological phase. We propose a realistic implementation of this phase using an optical flux lattice. Through exact diagonalization calculations, we show that the system exhibits a clear bulk gap and the topological signature of the bosonic integer quantum Hall state. In particular, the calculation of the many-body Chern number leads to a quantized Hall conductance in agreement with the analytical predictions. We also study the stability of the phase with respect to some of the experimentally relevant parameters.

Background: Retinal function is ordered by interactions between transcriptional and posttranscriptional regulators at the molecular level. These regulators include transcription factors (TFs) and posttranscriptional factors such as microRNAs (miRs). Some studies propose that miRs predominantly target the TFs rather than other types of protein coding genes and such studies suggest a possible interconnection of these two regulators in co-regulatory networks., Results: Our lab has generated mRNA and miRNA microarray expression data to investigate time-dependent changes in gene expression, following induction of ischemia-reperfusion (IR) injury in the rat retina. Data from different reperfusion time points following retinal IR-injury were analyzed. Paired expression data for miRNA-target gene (TG), TF-TG, miRNA-TF were used to identify regulatory loop motifs whose expressions were altered by the IR injury paradigm. These loops were subsequently integrated into larger regulatory networks and biological functions were assayed. Systematic analyses of the networks have provided new insights into retinal gene regulation in the early and late periods of IR. We found both overlapping and unique patterns of molecular expression at the two time points. These patterns can be defined by their characteristic molecular motifs as well as their associated biological processes. We highlighted the regulatory elements of miRs and TFs associated with biological processes in the early and late phases of ischemia-reperfusion injury., Conclusions: The etiology of retinal ischemia-reperfusion injury is orchestrated by complex and still not well understood gene networks. This work represents the first large network analysis to integrate miRNA and mRNA expression profiles in context of retinal ischemia. It is likely that an appreciation of such regulatory networks will have prognostic potential. In addition, the computational framework described in this study can be used to construct miRNA-TF interactive systems networks for various diseases/disorders of the retina and other tissues.

We show how spectroscopic experiments on a small Laughlin droplet of rotating bosons can directly demonstrate Haldane fractional exclusion statistics of quasihole excitations. The characteristic signatures appear in the single-particle excitation spectrum. We show that the transitions are governed by a "many-body selection rule" which allows one to relate the number of allowed transitions to the number of quasihole states on a finite geometry. We illustrate the theory with numerically exact simulations of small numbers of particles.

Purpose: Ischemia-reperfusion (IR) injury is involved in the pathology of many retinal disorders since it contributes to the death of retinal neurons and the subsequent decline in vision. We determined the molecular patterns of some of the principal molecules involved in necroptosis and investigated whether IR retinal injury is associated with the extracellular signal-regulated kinase-1/2- receptor-interacting protein kinase 3 (ERK1/2-RIP3) pathway., Methods: The cellular and subcellular localization of molecules involved in the cell death pathway, including RAGE, ERK1/2, FLIP, and RIP3, was determined with immunohistochemistry of cryosections of IR-injured retina from 2-month-old Long Evans rats. The total and phosphorylated protein levels were analyzed with quantitative western blots. ERK1/2 activity was inhibited by intravitreal injection of U0126, a highly selective inhibitor of mitogen-activated protein kinase 1/2 (MEK1/2)., Results: The IR-injured rat retinas expressed two RAGE isoforms with different intracellular localizations at early time points after injury. At that time point, frame inhibition of ERK activation decreased RIP3 accumulation and cell death. FLIP was detected in the IR-injured rat retinas at early time points after ischemia reperfusion., Conclusions: We report that the necroptotic cell death mechanism is executed by an ERK1/2-RIP3 pathway in the retinal ganglion cells in early stages after IR injury. Inhibition of ERK1/2 activity increased retinal ganglion cell (RGC) survival indicating that targeting of this pathway within the initial 12 h after IR injury can be used to inhibit the necroptosis pathway. We also provide evidence that a novel RAGE isoform is expressed in the early stages in rat retinal RGCs.

Ischemia/reperfusion (IR) injury has been associated with several retinal pathologies, and a few genes/gene products have been linked to IR injury. However, the big picture of temporal changes, regarding the affected gene networks, pathways, and processes remains to be determined. The purpose of the present study was to investigate initial, intermediate, and later stages to characterize the etiology of IR injury in terms of the pathways affected over time. Analyses indicated that at the initial stage, 0-hour reperfusion following the ischemic period, the ischemia-associated genes were related to changes in metabolism. In contrast, at the 24-hour time point, the signature events in reperfusion injury include enhanced inflammatory and immune responses as well as cell death indicating that this would be a critical period for the development of any interventional therapeutic strategies. Genes in the signal transduction pathways, particularly transmitter receptors, are downregulated at this time. Activation of the complement system pathway clearly plays an important role in the later stages of reperfusion injury. Together, these results demonstrate that the etiology of injury related to IR is characterized by the appearance of specific patterns of gene expression at any given time point during retinal IR injury. These results indicate that evaluation of treatment strategies with respect to time is very critical.

Acrolein is a major reactive component of vehicle exhaust, and cigarette and wood smoke. It is also present in several food substances and is generated endogenously during inflammation and lipid peroxidation. Although previous studies have shown that dietary or inhalation exposure to acrolein results in endothelial activation, platelet activation, and accelerated atherogenesis, the basis for these effects is unknown. Moreover, the effects of acrolein on microRNA (miRNA) have not been studied. Using AGILENT miRNA microarray high-throughput technology, we found that treatment of cultured human umbilical vein endothelial cells with acrolein led to a significant (>1.5-fold) upregulation of 12, and downregulation of 15, miRNAs. Among the miRNAs upregulated were members of the let-7 family and this upregulation was associated with decreased expression of their protein targets, β3 integrin, Cdc34, and K-Ras. Exposure to acrolein attenuated β3 integrin-dependent migration and reduced Akt phosphorylation in response to insulin. These effects of acrolein on endothelial cell migration and insulin signaling were reversed by expression of a let-7a inhibitor. Also, inhalation exposure of mice to acrolein (1 ppm x 6 h/day x 4 days) upregulated let-7a and led to a decrease in insulin-stimulated Akt phosphorylation in the aorta. These results suggest that acrolein exposure has broad effects on endothelial miRNA repertoire and that attenuation of endothelial cell migration and insulin signaling by acrolein is mediated in part by the upregulation of let-7a. This mechanism may be a significant feature of vascular injury caused by inflammation, oxidized lipids, and exposure to environmental pollutants., (© The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The health and function of the visual system rely on a collaborative interaction between diverse classes of molecular regulators. One of these classes consists of transcription factors, which are known to bind to DNA and control the transcription activities of their target genes. For a long time, it was thought that the transcription factors were the only regulators of gene expression. More recently, however, a novel class of regulators emerged. This class consists of a large number of small noncoding endogenous RNAs, namely, miRNAs. The miRNAs compose an essential component of posttranscriptional gene regulation, since they ultimately control the fate of gene transcripts. The retina, as a part of the central nervous system, is a well-established model for unraveling the molecular mechanisms underlying neuronal and glial functions. Numerous recent efforts have been made towards identification of miRNAs and their inferred roles in the visual pathway. In this review, we summarize the current state of our knowledge regarding the expression and function of miRNA in the neural retina and we discuss their potential uses as biomarkers for some retinal disorders.

Topological energy bands have important geometrical properties described by the Berry curvature. We show that the Berry curvature changes the hydrodynamic equations of motion for a trapped Bose-Einstein condensate, and causes significant modifications to the collective mode frequencies. We illustrate our results for the case of two-dimensional Rashba spin-orbit coupling in a Zeeman field. Using an operator approach, we derive the effects of Berry curvature on the dipole mode in very general settings. We show that the sizes of these effects can be large and readily detected in experiment. Collective modes therefore provide a sensitive way to measure geometrical properties of energy bands.

Engineered cardiac tissues (ECTs) are platforms to investigate cardiomyocyte maturation and functional integration, the feasibility of generating tissues for cardiac repair, and as models for pharmacology and toxicology bioassays. ECTs rapidly mature in vitro to acquire the features of functional cardiac muscle and respond to mechanical load with increased proliferation and maturation. ECTs are now being investigated as platforms for in vitro models for human diseases and for pharmacologic screening for drug toxicities. We tested the hypothesis that global ECT gene expression patterns are complex and sensitive to mechanical loading and tyrosine kinase inhibitors similar to the maturing myocardium. We generated ECTs from day 14.5 rat embryo ventricular cells, as previously published, and then conditioned constructs after 5 days in culture for 48 h with mechanical stretch (5%, 0.5 Hz) and/or the p38 MAPK (p38 mitogen-activated protein kinase) inhibitor BIRB796. RNA was isolated from individual ECTs and assayed using a standard Agilent rat 4 × 44k V3 microarray and Pathway Analysis software for transcript expression fold changes and changes in regulatory molecules and networks. Changes in expression were confirmed by quantitative-polymerase chain reaction (q-PCR) for selected regulatory molecules. At the threshold of a 1.5-fold change in expression, stretch altered 1559 transcripts, versus 1411 for BIRB796, and 1846 for stretch plus BIRB796. As anticipated, top pathways altered in response to these stimuli include cellular development, cellular growth and proliferation; tissue development; cell death, cell signaling, and small molecule biochemistry as well as numerous other pathways. Thus, ECTs display a broad spectrum of altered gene expression in response to mechanical load and/or tyrosine kinase inhibition, reflecting a complex regulation of proliferation, differentiation, and architectural alignment of cardiomyocytes and noncardiomyocytes within ECT.

Micro-RNAs regulate the expression of cellular and tissue phenotypes at a post-transcriptional level through a complex process involving complementary interactions between micro-RNAs and messenger-RNAs. Similar nucleotide interactions have been shown to occur as cross-kingdom events; for example, between plant viruses and plant micro-RNAs and also between animal viruses and animal micro-RNAs. In this study, this view is expanded to look for cross-kingdom similarities between plant virus and human micro-RNA sequences. A method to identify significant nucleotoide sequence similarities between plant viruses and hsa micro-RNAs was created. Initial analyses demonstrate that plant viruses contain nucleotide sequences which exactly match the seed sequences of human micro-RNAs in both parallel and anti-parallel directions. For example, the bean common mosaic virus strain NL4 from Colombia contains sequences that match exactly the seed sequence for micro-RNA of the hsa-mir-1226 in the parallel direction, which suggests a cross-kingdom conservation. Similarly, the rice yellow stunt viral cRNA contains a sequence that is an exact match in the anti-parallel direction to the seed sequence of hsa-micro-RNA let-7b. The functional implications of these results need to be explored. The finding of these cross-kingdom sequence similarities is a useful starting point in support of bench level investigations.

In the search for cochlear correlates of auditory masking by noise stimuli, we recorded basilar membrane (BM) vibrations evoked by either tone or click signals in the presence of varying levels of background noise. The BM vibrations were recorded from basal regions in healthy cochleae of anaesthetized chinchilla and gerbil. Non-linear interactions that could underpin various aspects of psychophysical masking data, including both compression and suppression at the BM level, were observed. The suppression effects, whereby the amplitude of the responses to each stimulus component could be reduced, depended on the relative intensities of the noise and the tones or clicks. Only stimulus components whose frequencies fell inside the non-linear region of the recording site, i.e. around its characteristic frequency (CF), were affected by presentation of the 'suppressing' stimulus (which could be either the tone or the noise). Mutual suppression, the simultaneous reduction of the responses to both tones and noise components, was observed under some conditions, but overall reductions of BM vibration were rarely observed. Moderate- to high-intensity tones suppressed BM responses to low-intensity Gaussian stimuli, including both broadband and narrowband noise. Suppression effects were larger for spectral components of the noise response that were closer to the CF. In this regime, the tone and noise stimuli became the suppressor and probe signals, respectively. This study provides the first detailed observations of cochlear mechanical correlates of the masking effects of noise. Mechanical detection thresholds for tone signals, which were arbitrarily defined using three criteria, are shown to increase in almost direct proportion to the noise level for low and moderately high noise levels, in a manner that resembles the findings of numerous psychophysical observations.

We present a robust scheme by which fractional quantum Hall states of bosons can be achieved for ultracold atomic gases. We describe a new form of optical flux lattice, suitable for commonly used atomic species with ground state angular momentum J(g) = 1, for which the lowest energy band is topological and nearly dispersionless. Through exact diagonalization studies, we show that, even for moderate interactions, the many-body ground states consist of bosonic fractional quantum Hall states, including the Laughlin state and the Moore-Read (Pfaffian) state. These phases are shown to have energy gaps that are larger than temperature scales achievable in ultracold gases.

At low stimulus levels, basilar-membrane (BM) mechanical transfer functions in sensitive cochleae manifest a quasiperiodic rippling pattern in both amplitude and phase. Analysis of the responses of active cochlear models suggests that the rippling is a mechanical interference pattern created by multiple internal reflection within the cochlea. In models, the interference arises when reverse-traveling waves responsible for stimulus-frequency otoacoustic emissions (SFOAEs) reflect off the stapes on their way to the ear canal, launching a secondary forward-traveling wave that combines with the primary wave produced by the stimulus. Frequency-dependent phase differences between the two waves then create the rippling pattern measurable on the BM. Measurements of BM ripples and SFOAEs in individual chinchilla ears demonstrate that the ripples are strongly correlated with the acoustic interference pattern measured in ear-canal pressure, consistent with a common origin involving the generation of SFOAEs. In BM responses to clicks, the ripples appear as temporal fine structure in the response envelope (multiple lobes, waxing and waning). Analysis of the ripple spacing and response phase gradients provides a test for the role of fast- and slow-wave modes of reverse energy propagation within the cochlea. The data indicate that SFOAE delays are consistent with reverse slow-wave propagation but much too long to be explained by fast waves.

Objectives: Presently available nonbehavioral methods to estimate auditory thresholds perform less well at frequencies below 1 kHz than at 1 kHz and above. For many uses, such as providing accurate infant hearing aid amplification for low-frequency vowels, an accurate nonbehavioral method to estimate low-frequency thresholds is needed. A novel technique was developed to estimate low-frequency cochlear thresholds based on the use of a previously reported waveform. It was determined how well the method worked by comparing the resulting thresholds to thresholds from onset-response compound action potentials (CAPs) and single-auditory-nerve (AN)- fibers in cats. A long-term goal is to translate this technique for use in humans., Design: An electrode near the cochlea records a combination of cochlear microphonic (CM) and neural responses. In response to low-frequency, near threshold-level tones, the CM is almost sinusoidal whereas the neural responses occur preferentially at one phase of the tone. If the tone is presented again but with its polarity reversed, the neural response keeps the same shape, but shifts ½ cycle in time. Averaging responses to tones presented separately at opposite polarities overlaps and interleaves the neural responses and yields a waveform in which the CM is canceled and the neural response appears twice each tone cycle, that is, the resulting neural response is mostly at twice the tone frequency. The resultant waveform is referred to as "the auditory nerve overlapped waveform" (ANOW). In this study, ANOW level functions were measured in anesthetized cats from 10 to 80 dB SPL in 10 dB steps using tones between 0.3 and 1 kHz. As a response metric, the magnitude of the ANOW component was calculated at twice the tone frequency (ANOW2f). The ANOW threshold was the sound level where the interpolated ANOW2f crossed a statistical criterion that was higher than 95% of the noise floor distribution. ANOW thresholds were compared with onset-CAP thresholds from the same recordings and single-AN-fiber thresholds from the same animals., Results: ANOW and onset-CAP level functions were obtained for 0.3 to 1 kHz tones, and single-AN-fiber responses from cats. Except at 1 kHz, typical ANOW thresholds were mostly 10 to 20 dB more sensitive than onset-CAP thresholds and 10 to 20 dB less sensitive than the most sensitive single-AN-fiber thresholds., Conclusions: ANOW provides frequency-specific estimates of cochlear neural thresholds over a frequency range that is important for hearing but is not well accessed by nonbehavioral, objective methods. Results suggest that with further targeted development, the ANOW low-frequency threshold estimation technique can be useful both clinically in humans and in basic-science animal experiments.

Various simple mathematical models of the dynamics of the organ of Corti in the mammalian cochlea are analyzed and their dynamics compared. The specific models considered are phenomenological Hopf and cusp normal forms, a recently proposed description combining active hair-bundle motility and somatic motility, a reduction thereof, and finally a model highlighting the importance of the coupling between the nonlinear transduction current and somatic motility. It is found that for certain models precise tuning to any bifurcation is not necessary and that a compressively nonlinear response over a range similar to experimental observations and that the normal form of the Hopf bifurcation is not the only description that reproduces compression and tuning similar to experiment.

Conditioned taste aversion (CTA) is an adaptive behavior that benefits survival of animals including humans and also serves as a powerful model to study the neural mechanisms of learning. Memory formation is a necessary component of CTA learning and involves neural processing and regulation of gene expression in the amygdala. Many studies have been focused on the identification of intracellular signaling cascades involved in CTA, but not late responsive genes underlying the long-lasting behavioral plasticity. In this study, we explored in silico experiments to identify persistent changes in gene expression associated with CTA in rats. We used oligonucleotide microarrays to identify 248 genes in the amygdala regulated by CTA. Pathway Studio and IPA software analyses showed that the differentially expressed genes in the amygdala fall in diverse functional categories such as behavior, psychological disorders, nervous system development and function, and cell-to-cell signaling. Conditioned taste aversion is a complex behavioral trait which involves association of visceral and taste inputs, consolidation of taste and visceral information, memory formation, retrieval of stored information, and extinction phase. In silico analysis of differentially expressed genes is therefore necessary to manipulate specific phase/stage of CTA to understand the molecular insight.

Ultracold atoms in Raman-dressed optical lattices allow for effective momentum-dependent interactions among single-species fermions originating from short-range s-wave interactions. These dressed-state interactions combined with the very flat bands encountered in the recently introduced optical flux lattices push the Stoner instability towards weaker repulsive interactions, making it accessible with current experiments. As a consequence of the coupling between spin and orbital degrees of freedom, the magnetic phase features Ising nematic order.

The present experiments investigated gene expression in the amygdala following contingent taste/LiCl treatment that supports development of conditioned taste aversion (CTA). The use of whole genome chips and stringent data set filtering led to the identification of 168 genes regulated by CTA compared to non-contingent LiCl treatment that does not support CTA learning. Seventy-six of these genes were eligible for network analysis. Such analysis identified "behavior" as the top biological function, which was represented by 15 of the 76 genes. These genes included several neuropeptides, G protein-coupled receptors, ion channels, kinases, and phosphatases. Subsequent qRT-PCR analyses confirmed changes in mRNA expression for 5 of 7 selected genes. We were able to demonstrate directionally consistent changes in protein level for 3 of these genes; insulin 1, oxytocin, and major histocompatibility complex class I-C. Behavioral analyses demonstrated that blockade of central insulin receptors produced a weaker CTA that was less resistant to extinction. Together, these results support the notion that we have identified downstream genes in the amygdala that contribute to CTA learning., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Unlike mammals, teleost fishes are capable of regenerating sensory inner ear hair cells that have been lost following acoustic or ototoxic trauma. Previous work indicated that immediately following sound exposure, zebrafish saccules exhibit significant hair cell loss that recovers to pre-treatment levels within 14 days. Following acoustic trauma in the zebrafish inner ear, we used microarray analysis to identify genes involved in inner ear repair following acoustic exposure. Additionally, we investigated the effect of growth hormone (GH) on cell proliferation in control zebrafish utricles and saccules, since GH was significantly up-regulated following acoustic trauma., Results: Microarray analysis, validated with the aid of quantitative real-time PCR, revealed several genes that were highly regulated during the process of regeneration in the zebrafish inner ear. Genes that had fold changes of ≥ 1.4 and P -values ≤ 0.05 were considered significantly regulated and were used for subsequent analysis. Categories of biological function that were significantly regulated included cancer, cellular growth and proliferation, and inflammation. Of particular significance, a greater than 64-fold increase in growth hormone (gh1) transcripts occurred, peaking at 2 days post-sound exposure (dpse) and decreasing to approximately 5.5-fold by 4 dpse. Pathway Analysis software was used to reveal networks of regulated genes and showed how GH affected these networks. Subsequent experiments showed that intraperitoneal injection of salmon growth hormone significantly increased cell proliferation in the zebrafish inner ear. Many other gene transcripts were also differentially regulated, including heavy and light chain myosin transcripts, both of which were down-regulated following sound exposure, and major histocompatability class I and II genes, several of which were significantly regulated on 2 dpse., Conclusions: Transcripts for GH, MHC Class I and II genes, and heavy- and light-chain myosins, as well as many others genes, were differentially regulated in the zebrafish inner ear following overexposure to sound. GH injection increased cell proliferation in the inner ear of non-sound-exposed zebrafish, suggesting that GH could play an important role in sensory hair cell regeneration in the teleost ear.