bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single spectrum of neuronal identities across thalamus
Authors: Phillips James W. , Schulmann Anton , Hara Erina , Liu Chenghao , Wang Lihua , Shields Brenda C. , Korff Wyatt , Lemire Andrew L. , Dudman Joshua , Nelson Sacha B. , Hantman Adam 
Published: January 2018

ABSTRACTUncovering common principles by which diverse modalities of information are processed is a fundamental goal in neuroscience. In mammalian brain, thalamus is the central processing station for inputs from sensory systems, subcortical motor systems, and cortex; a function subserved by over 30 defined nuclei1,2. Multiple thalamic nuclei send convergent information to each region of the forebrain, but whether there is a conserved architecture across the set of thalamic pathways projecting to each forebrain area has remained unresolved3–5. To uncover organizational principles of thalamic pathways, we produced a near-comprehensive transcriptomic atlas of thalamus. This revealed a common logic for thalamic nuclei serving all major cortical modalities. We found that almost all nuclei belong to one of three major profiles, with a given cortical area getting input from each of these profiles. These profiles lie on a single axis of variance aligned with the mediolateral axis of thalamus, and this axis is strongly enriched in genes encoding receptors and ion channels. We further show that each projection profile exhibits different electrophysiological signatures. Single-cell profiling revealed that rather than forming discrete classes, thalamic neurons lie on a spectrum, with intermediate cells existing between profiles. Thus, in contrast to canonical models of thalamus that suggest it is a switchboard primarily concerned with routing distinct modalities of information to distinct cortical regions, we show that the thalamocortical system is more akin to a molecularly-defined ‘filter bank’ repeatedly applied across modality. Together, we reveal striking covariation in the organization of thalamic pathways serving all input modalities and output targets, establishing a simple and comprehensive thalamic functional architecture.
Binocular System with Asymmetric Eyes
Authors: Turski Jacek 
Published: January 2018

I elaborate binocular geometry with a novel eye model that incorporates the fovea’s temporalward displacement and the cornea and the lens’ misalignment. The formulated binocular correspondence results in longitudinal horopters that are conic sections resembling empirical horopters. When the eye model’s asymmetry parameters’ range is that which is observed in healthy eyes, abathic distance also falls within its experimentally observed range. This range in abathic distance is similar to that of the vergence resting position distance. Further, the conic’s orientation is specified by the eyes’ version angle, integrating binocular geometry with eye movement. This integration presents the possibility for modeling 3D perceptual stability during physiological eye movements.OCIS codes: (330.1400) Vision - binocular and stereopsis; (330.4060) Vision modeling
PRDM9 and an Epidemic of Gene Conversion and Non-Homologous Recombination among Alu Elements in Ancestral Gorillas
Authors: Wacholder Aaron C. , Pollock David D. 
Published: January 2018

AbstractWe performed a genome-wide scan for recombination-mediated interlocus gene conversion and deletion events among a set of orthologous Alu loci in the Great Apes, and were surprised to discover an extreme excess of such events in the gorilla lineage versus other lineages. Gorilla events, but not events in other Great Apes, are strongly associated with a 15 bp motif commonly found in Alu sequences. This result is consistent with evolutionarily transient targeting of the motif by PRDM9, which induces double strand breaks and crossovers during meiosis at specific but rapidly changing sequence motifs. The motif is preferentially found in conversion recipients but not donors, and is substantially depleted in gorillas, consistent with loss of PRDM9 targets by meiotic drive. Recombination probability falls of exponentially with distance between loci, is reduced slightly by sequence divergence, and drops substantially with recipient divergence from the target motif. We identified 16 other high-copy motifs in human, often associated with transposable elements, with lineage-specific depletion and nearby gene conversion signatures, consistent with transient roles as PRDM9 targets. This work strengthens our understanding of recombination-mediated events in evolution and highlights the potential for interactions between PRDM9 and repetitive sequences to cause rapid change in the genome.
Converting a broad matrix metalloproteinase family inhibitor into a specific inhibitor of MMP-9 and MMP-14
Authors: Shirian Jason , Arkadash Valeria , Cohen Itay , Sapir Tamila , Radisky Evette S. , Papo Niv , Shifman Julia M. 
Published: January 2018

AbstractMMP-14 and MMP-9 are two well established cancer targets for which no specific clinically relevant inhibitor is available. Using a powerful combination of computational design and yeast surface display technology, we engineered such an inhibitor starting from a non-specific MMP inhibitor, N-TIMP2. The engineered purified N-TIMP2 variants showed enhanced specificity towards MMP-14 and MMP-9 relative to a panel of off-target MMPs. MMP-specific N-TIMP2 sequence signatures were obtained that could be understood from the structural perspective of MMP/N-TIMP2 interactions. Our MMP-9 inhibitor exhibited 1000-fold preference for MMP-9 vs. MMP-14, which is likely to translate into significant differences under physiological conditions. Our results provide new insights regarding evolution of promiscuous proteins and optimization strategies for design of inhibitors with single-target specificities.
Multivariate analysis reveals environmental and genetic determinants of element covariation in the maize grain ionome
Authors: Asaro Alexandra , Dilkes Brian P. , Baxter Ivan 
Published: January 2018

AbstractPlants obtain elements from the soil through genetic and biochemical pathways responsive to physiological state and environment. Most perturbations affect multiple elements which leads the ionome, the full complement of mineral nutrients in an organism, to vary as an integrated network rather than a set of distinct single elements. To examine the genetic basis of covariation in the accumulation of multiple elements, we analyzed maize kernel ionomes from Intermated B73 × Mo17 (IBM) recombinant inbred populations grown in 10 environments. We compared quantitative trait loci (QTL) determining single-element variation to QTL that predict variation in principal components (PCs) of multiple-element covariance. Single-element and multivariate approaches detected partially overlapping sets of loci. In addition to loci co-localizing with single-element QTL, multivariate traits within environments were controlled by loci with significant multi-element effects not detectable using single-element traits. Gene-by-environment interactions underlying multiple-element covariance were identified through QTL analyses of principal component models of ionome variation. In addition to interactive effects, growth environment had a profound effect on the elemental profiles and multi-element phenotypes were significantly correlated with specific environmental variables.Author SummaryA multivariate approach to the analysis of element accumulation in the maize kernel shows that elements are not regulated independently. By describing relationships between element accumulation we identified new genetic loci invisible to single-element approaches. The mathematical combinations of elements distinguish groups of plants based on environment, demonstrating that observed variation derives from interactions between genetically controlled factors and environmental variables. These results suggest that successful application of ionomics to improve human nutrition and plant productivity requires simultaneous consideration of multiple-element effects and variation of such effects in response to environment.
A Suv39H1-low chromatin state drives migratory cell populations in cervical cancers
Authors: Rodrigues Calvin , Pattabiraman Chitra , Narayana Suma Mysore , Kumar Rekha V. , Notani Dimple , Varga-Weisz Patrick , Krishna Sudhir 
Published: January 2018

AbstractThe emergence of migratory cell populations within tumours represents a critical early stage during cancer metastasis. We have previously reported one such population, marked by CD66, in cervical cancers. It is unclear what broad mechanisms regulate such migratory populations. Here, we describe the role of a Suv39H1-low heterochromatin state as a driver of cervical cancer migratory populations. Cervical cancer cells sorted based on migratory ability in vitro show low Suv39H1, and Suv39H1 knockdown enhances cell migration. Histopathology shows the emergence of migratory Suv39H1low populations in advanced carcinoma progression. Meta-analysis of data from The Cancer Genome Atlas (TCGA) reveals that Suv39H1-low tumours show migration and CD66 expression signatures, and correlate with lower patient survival. Lastly, genome-wide profiling of migrated populations using RNA-Seq and H3K9me3 ChIP-Seq reveals Suv39H1-linked transcriptome alterations and a broad loss of H3K9me3, suggesting an increase in chromatin plasticity in migrated populations. The understanding of such chromatin based regulation in migratory populations may prove valuable in efforts to develop anti-metastatic strategies.
DeepGS: Predicting phenotypes from genotypes using Deep Learning
Authors: Ma Wenlong , Qiu Zhixu , Song Jie , Cheng Qian , Ma Chuang 
Published: January 2018

AbstractMotivationGenomic selection (GS) is a new breeding strategy by which the phenotypes of quantitative traits are usually predicted based on genome-wide markers of genotypes using conventional statistical models. However, the GS prediction models typically make strong assumptions and perform linear regression analysis, limiting their accuracies since they do not capture the complex, non-linear relationships within genotypes, and between genotypes and phenotypes.ResultsWe present a deep learning method, named DeepGS, to predict phenotypes from genotypes. Using a deep convolutional neural network, DeepGS uses hidden variables that jointly represent features in genotypic markers when making predictions; it also employs convolution, sampling and dropout strategies to reduce the complexity of high-dimensional marker data. We used a large GS dataset to train DeepGS and compare its performance with other methods. In terms of mean normalized discounted cumulative gain value, DeepGS achieves an increase of 27.70%~246.34% over a conventional neural network in selecting top-ranked 1% individuals with high phenotypic values for the eight tested traits. Additionally, compared with the widely used method RR-BLUP, DeepGS still yields a relative improvement ranging from 1.44% to 65.24%. Through extensive simulation experiments, we also demonstrated the effectiveness and robustness of DeepGS for the absent of outlier individuals and subsets of genotypic markers. Finally, we illustrated the complementarity of DeepGS and RR-BLUP with an ensemble learning approach for further improving prediction performance.AvailabilityDeepGS is provided as an open source R package available at https://github.com/cma2015/DeepGS.
Transcranial alternating current stimulation modulates auditory temporal resolution in elderly people
Authors: Baltus Alina , Herrmann Christoph Siegfried 
Published: January 2018

AbstractRecent research provides evidence for a functional role of brain oscillations for perception. For example, auditory temporal resolution seems to be linked to individual gamma frequency of auditory cortex. Individual gamma frequency not only correlates with performance in between-channel gap detection tasks but can be modulated via auditory transcranial alternating current stimulation. Modulation of individual gamma frequency is accompanied by an improvement in gap detection performance. Aging changes electrophysiological frequency components and sensory processing mechanisms. Therefore, we conducted a study to investigate the link between individual gamma frequency and gap detection performance in elderly people using auditory transcranial alternating current stimulation. In a within-subject design, nine participants were electrically stimulated with two individualized transcranial alternating current stimulation frequencies: 3 Hz above their individual gamma frequency (experimental condition) and 4 Hz below their individual gamma frequency (control condition) while they were performing a between-channel gap detection task. As expected, individual gamma frequencies correlated significantly with gap detection performance at baseline and in the experimental condition, transcranial alternating current stimulation modulated gap detection performance. In the control condition, stimulation did not modulate gap detection performance. In addition, in elderly, the effect of transcranial alternating current stimulation on auditory temporal resolution seems to be dependent on endogenous frequencies in auditory cortex: elderlies with slower individual gamma frequencies and lower auditory temporal resolution profit from auditory transcranial alternating current stimulation and show increased gap detection performance during stimulation. Our results strongly suggest individualized transcranial alternating current stimulation protocols for successful modulation of performance.
Polarization of Myosin II refines tissue material properties to buffer mechanical stress
Authors: Duda Maria , Khalilgharibi Nargess , Carpi Nicolas , Bove Anna , Piel Matthieu , Charras Guillaume , Baum Buzz , Mao Yanlan 
Published: January 2018

SummaryAs tissues develop, they are subjected to a variety of mechanical forces. Some of these forces, such as those required for morphogenetic movements, are instrumental to the development and sculpting of tissues. However, mechanical forces can also lead to accumulation of substantial tensile stress, which if maintained, can result in tissue damage and impair tissue function. Despite our extensive understanding of force-guided morphogenesis, we have only a limited understanding of how tissues prevent further morphogenesis, once shape is determined after development. Buffering forces to prevent cellular changes in response to fluctuations of mechanical stress is critical during the lifetime of an adult organism. Here, through the development of a novel tissue-stretching device, we uncover a mechanosensitive pathway that regulates tissue responses to mechanical stress through the polarization of Myosin II across the tissue. Mechanistically, this process is independent of conserved Rho-kinase signaling but is mediated by force-induced linear actin polymerization and depolymerization via the formin Diaphanous and actin severing protein Cofilin, respectively. Importantly, these stretch-induced actomyosin cables stiffen the tissue to limit changes in cell shape and to protect the tissue from further mechanical damage prior to stress dissipation. This tissue rigidification prevents fractures in the tissue from propagating by confining the damage locally to the injured cells. Overall this mechanism of force-induced changes in tissue mechanical properties provides a general model of force buffering that rapidly protects tissues from physical damage to preserve tissue shape.
A deep convolutional neural network approach for astrocyte detection
Authors: Suleymanova Ilida , Balassa Tamas , Tripathi Sushil , Molnar Csaba , Saarma Mart , Sidorova Yulia , Horvath Peter 
Published: January 2018

AbstractAstrocytes are involved in brain pathologies such as trauma or stroke, neurodegenerative disorders like Alzheimer’s and Parkinson’s disease, chronic pain, and many others. Determining cell density and timing of morphological and biochemical changes is important for a proper understanding of the role of astrocytes in physiological and pathological conditions. One of the most important of such analyses is astrocytes count within a complex tissue environment in microscopy images. The most widely used approaches for the quantification of microscopy images data are either manual stereological cell counting or semi-automatic segmentation techniques. Detecting astrocytes automatically is a highly challenging computational task, for which we currently lack efficient image analysis tools. In this study, we developed a fast and fully automated software that assesses the number of astrocytes using Deep Convolutional Neural Networks (DCNN). The method highly outperforms state-of-the-art image analysis and machine learning methods and provides detection accuracy and precision comparable to that of human experts. Additionally, the runtime of cell detection is significantly less than other three analyzed computational methods, and it is faster than human observers by orders of magnitude. We applied DCNN-based method to examine the number of astrocytes in different brain regions of rats with opioid-induced hyperalgesia/tolerance (OIH/OIT) as morphine tolerance is believed to activate glial cells in the brain. We observed strong positive correlation between manual cell detection and DCNN-based analysis method for counting astrocytes in the brains of experimental animals.
Identification of an arabinopyranosyltransferase fromPhyscomitrella patensinvolved in the synthesis of the hemicellulose xyloglucan
Authors: Zhu Lei , Dama Murali , Pauly Markus 
Published: January 2018

AbstractThe hemicellulose xyloglucan consists of a backbone of a β-1,4 glucan substituted with xylosyl moieties and many other, diverse sidechains that are important for its proper function. Many, but not all glycosyltransferases involved in the biosynthesis of xyloglucan have been identified. Here, we report the identification of an hitherto elusive xyloglucan:arabinopyranosyltransferase. This glycosyltransferase was isolated from the mossPhyscomitrella patens, where it acts as aXyloglucan “D”-side-chainTransferase (XDT). Heterologous expression ofXDTin theArabidopsis thalianadouble mutantmur3.1 xlt2, where xyloglucan consists of a xylosylated glucan without further glycosyl substituents, results in the production of the arabinopyranose-containing “D” side chain as characterized by oligosaccharide mass profiling, glycosidic linkage analysis, and NMR analysis. In addition, expression of a relatedPhyscomitrellaglycosyltransferase hortholog ofXLT2leads to the production of the galactose-containing “L” side chain. The presence of the “D” and “L” xyloglucan side chains inPpXDT mur3.1 xlt2andPpXLT2 mur3.1 xlt2transgenic plants, respectively, rescue the dwarfed phenotype of untransformedmur3.1 xlt2mutants to nearly wild-type height. Expression ofPpXDTandPpXLT2in the Arabidopsismur3.1 xlt2mutant also enhanced root growth.
Caffeine downregulates inflammatory pathways involved in autoimmunity
Authors: Iris Merve , Tsou Pei-Suen , Sawalha Amr H. 
Published: January 2018

ABSTRACTObjectivesCaffeine is a widely consumed pharmacologically active product. In the present study, we focused on characterizing immunomodulatory effects of caffeine on peripheral blood mononuclear cells (PMBCs).MethodsThe effect of caffeine on gene expression profiles was initially evaluated using RNA sequencing data. Validation experiments were performed to confirm the results and examine dose-dependent effects of caffeine on PBMCs from healthy subjects. Gene expression levels were measured by real-time quantitative PCR, and cytokine production was determined using a multiplex cytokine assay.ResultsCaffeine at high doses showed a robust downregulatory effect of immune-related genes in PBMCs. Functional annotation analysis of downregulated genes revealed significant enrichment in cytokine activity and in genes related to several autoimmune diseases including lupus and rheumatoid arthritis. Dose-dependent validation experiments showed significant downregulation at the mRNA levels of key inflammatory genes including STAT1, TNF, and PPARG. TNF and PPARG were suppressed even with the lowest caffeine dose tested, which corresponds to the serum concentration of caffeine after administration of one cup of coffee. Cytokine levels of IL-8, MIP-1β, IL-6, IFN-γ, GM-CSF, TNF, IL-2, IL-4, MCP-1, and IL-10 were decreased significantly with caffeine treatment.ConclusionOur findings indicate potential downregulatory effects of caffeine on key inflammatory genes and cytokines, which play important role in autoimmunity. Further studies exploring therapeutic or disease-modulating potential of caffeine in autoimmune diseases and exploring the mechanisms involved are warranted.
Disequilibrium in Gender Ratios among Authors who Contributed Equally
Authors: Broderick Nichole A. , Casadevall Arturo 
Published: January 2018

AbstractIn recent decades, the biomedical literature has witnessed an increasing number of authors per article together with a concomitant increase of authors claiming to have contributed equally. In this study, we analyzed over 3000 publications from 1995–2017 claiming equal contributions for authors sharing the first author position for author number, gender, and gender position. The frequency of dual pairings contributing equally was male-male > mixed gender > female-female. For mixed gender pairs males were more often at the first position although the disparity has lessened in the past decade. Among author associations claiming equal contribution and containing three or more individuals, males predominated in both the first position and number of gender exclusive groupings. Our results show a disequilibrium in gender ratios among authors who contributed equally from expected ratios had the ordering been done randomly or alphabetical. Given the importance of the first author position in assigning credit for a publication, the finding of fewer than expected females in associations involving shared contributions raises concerns about women not receiving their fair share of expected credit. The results suggest a need for journals to request clarity on the method used to decide author order among individuals claiming to have made equal contributions to a scientific publication.
Mesophotic Coral Ecosystems Inside and Outside a Caribbean Marine Protected Area
Authors: Gress Erika , Arroyo-Gerez Maria J , Wright Georgina , Andradi-Brown Dominic A 
Published: January 2018

AbstractRecent widespread shallow coral reef loss has led to calls for more holistic approaches to coral reef management, requiring inclusion of all ecosystems interacting with coral reefs in management plans. Yet almost all current reef management is biased towards shallow reefs, and overlooks that many reef species can also be found on mesophotic coral ecosystems (MCEs; reefs 30 −150 m). This study presents the first detailed quantitative characterisation of MCEs off Cozumel, in the Mexican Caribbean and provides insights into their general state. We investigate whether MCEs within the marine park have similar ecological communities to mesophotic reefs outside protection, despite widely recognised shallow reef impacts outside the protected area. Results show some taxon specific differences in MCE benthic communities between sites within the protected area and areas outside; although overall communities are similar. Regardless of protection and location, and in contrast to shallow reefs, all observed Cozumel MCEs were continuous reefs dominated by calcareous macroalgae, sponges, octocorals, and black corals. Hard corals were present on MCEs, but at low abundance. We found that 42.5 % of fish species recorded on Cozumel could be found on both shallow reefs and MCEs, including many commercially-important fish species. This suggest that MCEs may play a role in supporting fish populations. However, regardless of protection status and depth we found that large-body fishes (>500 mm) were nearly absent at all studied sites. MCEs should be incorporated into the existing shallow-reef focused management plan in Cozumel, with well informed and implemented fisheries and harvesting regulations.