bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocular disease mechanisms elucidated by genetics of human fetal retinal pigment epithelium gene expression
Authors: Liu Boxiang , Calton Melissa A. , Abell Nathan S. , Benchorin Gillie , Gloudemans Michael J. , Chen Ming , Hu Jane , Li Xin , Balliu Brunilda , Bok Dean , Montgomery Stephen B. , Vollrath Douglas 
Published: October 2018

AbstractThe eye is an intricate organ with limited representation in large-scale functional genomics datasets. The retinal pigment epithelium (RPE) serves vital roles in ocular development and retinal homeostasis. We interrogated the genetics of gene expression of cultured human fetal RPE (fRPE) cells under two metabolic conditions. Genes with disproportionately high fRPE expression are enriched for genes related to inherited ocular diseases. Variants near these fRPE-selective genes explain a larger fraction of risk for both age-related macular degeneration (AMD) and myopia than variants near genes enriched in 53 other human tissues. Increased mitochondrial oxidation of glutamine by fRPE promoted expression of lipid synthesis genes implicated in AMD. Expression and splice quantitative trait loci (e/sQTL) analysis revealed shared and metabolic condition-specific loci of each type and several eQTL not previously described in any tissue. Fine mapping of fRPE e/sQTL across AMD and myopia genome-wide association data suggests new candidate genes, and mechanisms by which the same common variant of RDH5 contributes to both increased AMD risk and decreased myopia risk. Our study highlights the unique transcriptomic characteristics of fRPE and provides a resource to connect e/sQTL in a critical ocular cell type to monogenic and complex eye disorders.
Automatic Single-Cell Discrimination by Cellular Appearance using Convolutional Neural Network
Authors: Matsuoka Yoshikazu , Nakatsuka Ryusuke , Fujioka Tatsuya 
Published: October 2018

AbstractMorphological images of cells contain extensive information, which help biologists to infer the type and state of cells to some degree based on their morphology. Convolutional Neural Network, a neural network architecture, is a powerful tool used for image recognition. However, whether it can be used to classify cells on the basis of their morphology remains unclear. In this study, we demonstrate that 10 different hematopoietic tumor cell lines with similar morphologies that biologists find difficult to distinguish can be classified with >90% accuracy using only their bright-field images when analyzed using a Convolutional Neural Network. This novel and simple system using bright-field images of cells could be a powerful analytical tool for cell type discrimination and could also be applied to the clinical diagnoses of hematopoietic tumors.
Structure and genome ejection mechanism of Podoviridae phage P68 infecting Staphylococcus aureus
Authors: Hrebík Dominik , Štveráková Dana , Škubník Karel , Füzik Tibor , Pantůček Roman , Plevka Pavel 
Published: October 2018

AbstractPhages infecting S. aureus have the potential to be used as therapeutics against antibiotic-resistant bacterial infections. However, there is limited information about the mechanism of genome delivery of phages that infect Gram-positive bacteria. Here we present the structures of S. aureus phage P68 in its native form, genome ejection intermediate, and empty particle. The P68 head contains seventy-two subunits of inner core protein, fifteen of which bind to and alter the structure of adjacent major capsid proteins and thus specify attachment sites for head fibers. Unlike in the previously studied phages, the head fibers of P68 enable its virion to position itself at the cell surface for genome delivery. P68 genome ejection is triggered by disruption of the interaction of one of the portal protein subunits with phage DNA. The inner core proteins are released together with the DNA and enable the translocation of phage genome across the bacterial membrane into the cytoplasm.
The molecular genetics of hand preference revisited
Authors: de Kovel Carolien G.F. , Francks Clyde 
Published: October 2018

AbstractHand preference is a prominent behavioural trait linked to human brain asymmetry. A handful of genetic variants have been reported to associate with hand preference or quantitative measures related to it. Most of these reports were on the basis of limited sample sizes, by current standards for genetic analysis of complex traits. Here we performed a genome-wide association analysis of hand preference in the large, population-based UK Biobank cohort (N=331,037). We used gene-set enrichment analysis to investigate whether genes involved in visceral asymmetry are particularly relevant to hand preference, following one previous report. We found no evidence implicating any specific candidate variants previously reported. We also found no evidence that genes involved in visceral laterality play a role in hand preference. It remains possible that some of the previously reported genes or pathways are relevant to hand preference as assessed in other ways, or else are relevant within specific disorder populations. However, some or all of the earlier findings are likely to be false positives, and none of them appear relevant to hand preference as defined categorically in the general population. Within the UK Biobank itself, a significant association implicates the geneMAP2in handedness.
Parallel systems for sound processing and functional connectivity among layer 5 and 6 auditory corticothalamic neurons
Authors: Williamson Ross S. , Polley Daniel B. 
Published: October 2018

AbstractCortical layers (L) 5 and 6 are populated by a spatially intermingled menagerie of neurons with distinct inputs and downstream targets. Here, we made optogenetically guided recordings from L5 and L6 corticothalamic (CT) neurons in the mouse auditory cortex to discern underlying patterns of functional connectivity and sensory processing in the largest sub-cerebral projection system. Whereas L5 CT neurons showed broad stimulus selectivity with sluggish response latencies and extended temporal non-linearities, L6 CTs exhibited sparse sound feature selectivity and rapid temporal processing. L5 CT spikes lagged behind neighboring units and imposed weak feedforward excitation within the local column. By contrast, L6 CT spikes drove robust and sustained activity in neighboring units. Our findings underscore a duality among CT projection neurons, where L5 CT units are canonical broadcast neurons that integrate sensory inputs for transmission to distributed downstream targets, while L6 CT neurons are positioned to regulate thalamocortical response gain and selectivity.
Managing river fish biodiversity generates substantial economic benefits in four European countries
Authors: Riepe Carsten , Meyerhoff Jürgen , Fujitani Marie , Fujitani Marie , Aas Øystein , Radinger Johannes , Kochalski Sophia , Arlinghaus Robert 
Published: October 2018

AbstractEcosystems and biodiversity produce benefits to society, but many of them are hard to quantify. For example, it is unclear whether European societies gain benefits from experiencing rivers that host high native biodiversity. Without such knowledge, monetary investments into ecologically oriented river management plans are difficult to justify. The objective of this study was to reveal how the public in four European countries values ecological characteristics of domestic rivers and the outcomes of hypothetical river basin management plans designed to improve river ecosystems, particularly fish biodiversity. We conducted a choice experiment among the populations in Norway, Sweden, Germany and France. We found similar preference structures in all countries with high marginal willingness-to-pay for improvements of abiotic river attributes (increased accessiblity of the river banks, improved bathing water quality, decreased river fragmentation). Citizens also benefited from certain fish species occurring in a river with native salmonid species being more valued than nonnatives, particularly in Norway, and from the degree of a river’s native biodiversity. Welfare measures calculated for selected river basin management plans (policy scenarios) revealed societal benefits that were primarily derived from ecological river management whereas a scenario focusing on hydroelectricity production generated the lowest utility. We conclude that ecological river management may produce high nonmarket economic benefits in all study countries, particularly through the management of abiotic river attributes and the restoration of declining or extinct fish species. Our results help to inform decisions on restoration efforts by showcasing the benefits that these measures have for the public.
Quantitative Proteomic Analysis of Prostate Tissue Specimens Identifies Deregulated Protein Complexes in Primary Prostate Cancer
Authors: Zhou Bo , Yan Yiwu , Wang Yang , You Sungyong , Freeman Michael R. , Yang Wei 
Published: October 2018

AbstractProstate cancer (PCa) is the most frequently diagnosed non-skin cancer and a leading cause of mortality among males in developed countries. However, our understanding of the global changes of protein complexes within PCa tissue specimens remains very limited, although it has been well recognized that protein complexes carry out essentially all major processes in living organisms and that their deregulation drives the pathogenesis and progression of various diseases. By coupling tandem mass tagging-synchronous precursor selection-mass spectrometry/mass spectrometry/mass spectrometry (TMT-SPSMS3) with differential expression and co-regulation analyses, the present study compared the differences between protein complexes in normal prostate, low-grade PCa, and high-grade PCa tissue specimens. Globally, a large downregulated putative protein-protein interaction (PPI) network was detected in both low-grade and high-grade PCa, yet a large upregulated putative PPI network was only detected in high-grade but not low-grade PCa, compared with normal controls. To identify specific protein complexes that are deregulated in PCa, quantified proteins were mapped to protein complexes in CORUM, a collection of experimentally verified mammalian protein complexes. Differential expression analysis suggested that mitochondrial ribosomes and the fibrillin-associated protein complex were significantly overexpressed, whereas the ITGA6-ITGB4-Laminin10/12 and the P2X7 receptor signaling complexes were significantly downregulated, in PCa compared with normal prostate. Moreover, differential co-regulation analysis indicated that the assembly levels of some nuclear protein complexes involved in RNA synthesis and processing were significantly increased in low-grade PCa, and those of mitochondrial complex I and its subcomplexes were significantly increased in high-grade PCa, compared with normal prostate. In summary, the study represents the first global and quantitative comparison of protein complexes in prostate tissue specimens. It is expected to enhance our understanding of the molecular mechanisms underlying PCa development and progression in human patients, as well as lead to the discovery of novel biomarkers and therapeutic targets for precision management of PCa.
Evolutionary couplings detect side-chain interactions
Authors: Hockenberry Adam J. , Wilke Claus O. 
Published: October 2018

Patterns of amino acid covariation in large protein sequence alignments can inform the prediction of de novo protein structures, binding interfaces, and mutational effects. While algorithms that detect these so-called evolutionary couplings between residues have proven useful for practical applications, less is known about how and why these methods perform so well, and what insights into biological processes can be gained from their application. Evolutionary coupling algorithms are commonly benchmarked by comparison to true structural contacts derived from solved protein structures. However, the methods used to determine true structural contacts are not standardized and different definitions of structural contacts may have important consequences for interpreting the results from evolutionary coupling analyses and understanding their overall utility. Here, we show that evolutionary coupling analyses are significantly more likely to identify structural contacts between side-chain atoms than between backbone atoms. We use both simulations and empirical analyses to highlight that purely backbone-based definitions of true residue–residue contacts (i.e., based on the distance between Cα atoms) may underestimate the accuracy of evolutionary coupling algorithms by as much as 40% and that a commonly used reference point (Cβ atoms) underestimates the accuracy by 10–15%. These findings show that co-evolutionary outcomes differ according to which atoms participate in residue–residue interactions and suggest that accounting for different interaction types may lead to further improvements to contact-prediction methods.Significance StatementEvolutionary couplings between residues within a protein can provide valuable information about protein structures, protein-protein interactions, and the mutability of individual residues. However, the mechanistic factors that determine whether two residues will co-evolve remains unknown. We show that structural proximity by itself is not sufficient for co-evolution to occur between residues. Rather, evolutionary couplings between residues are specifically governed by interactions between side-chain atoms. By contrast, intramolecular contacts between atoms in the protein backbone display only a weak signature of evolutionary coupling. These findings highlight that different types of stabilizing contacts exist within protein structures and that these types have a differential impact on the evolution of protein structures that should be considered in co-evolutionary applications.
Optical Sectioning of Live Mammal with Near-Infrared Light Sheet
Authors: Wang Feifei , Wan Hao , Yue Jingying , Zhang Mingxi , Ma Zhuoran , Sun Qinchao , Qu Liangqiong , Ma Huilong , Zhong Yeteng , Tian Ye , Hong Guosong , Jung Li Wen , Liang Yongye , Liu Lianqing , Dai Hongjie 
Published: October 2018

AbstractDeep-tissue three-dimensional optical imaging of live mammals in vivo with high spatiotemporal resolution in non-invasive manners has been challenging due to light scattering. Here, we developed near-infrared (NIR) light sheet microscopy (LSM) with optical excitation and emission wavelengths up to ~ 1320 nm and ~ 1700 nm respectively, far into the NIR-II (1000-1700 nm) region for 3D optical sectioning through live tissues. Suppressed scattering of both excitation and emission photons allowed one-photon optical sectioning at ~ 2 mm depth in highly scattering brain tissues. NIR-II LSM enabled non-invasive in vivo imaging of live mice, revealing never-before-seen dynamic processes such as highly abnormal tumor microcirculation, and 3D molecular imaging of an important immune checkpoint protein, programmed-death ligand 1 (PD-L1) receptors at the single cell scale in tumors. In vivo two-color near-infrared light sheet sectioning enabled simultaneous volumetric imaging of tumor vasculatures and PD-L1 proteins in live mammals.
Epigenome-wide association analysis of daytime sleepiness in the Multi-Ethnic Study of Atherosclerosis reveals African-American specific associations
Authors: Barfield Richard , Wang Heming , Liu Yongmei , Brody Jennifer A , Swenson Brenton , Li Ruitong , Bartz Traci M. , Sotoodehnia Nona , Chen Yii-der I. , Cade Brian E. , Chen Han , Patel Sanjay R. , Zhu Xiaofeng , Gharib Sina A. , Johnson W. Craig , Rotter Jerome I. , Saxena Richa , Purcell Shaun , Lin Xihong , Redline Susan , Sofer Tamar 
Published: October 2018

AbstractStudy ObjectivesExcessive daytime sleepiness (EDS) is a consequence of inadequate sleep, or of a primary disorder of sleep-wake control. Population variability in prevalence of EDS and susceptibility to EDS are likely due to genetic and biological factors as well as social and environmental influences. Epigenetic modifications (such as DNA methylation-DNAm) are potential influences on a range of health outcomes. Here, we explored the association between DNAm and daytime sleepiness quantified by the Epworth Sleepiness Scale (ESS).MethodsWe performed multi-ethnic and ethnic-specific epigenome-wide association studies for DNAm and ESS in 619 individuals from the Multi-Ethnic Study of Atherosclerosis. Replication was assessed in the Cardiovascular Health Study (CHS). Genetic variants in genes proximal to ESS-associated DNAm were analyzed to identify methylation quantitative trait loci and followed with replication of genotype-sleepiness associations in the UK Biobank.Results61 methylation sites were associated with ESS (FDR ≤ 0.1) in African Americans only, including an association inKCTD5, a gene strongly implicated in sleep. One association (cg26130090) replicated in CHS African Americans (p-value 0.0004). We identified a sleepiness-associated methylation site in the geneRAI1, a gene associated with sleep and circadian phenotypes. In a follow-up analysis, a genetic variant withinRAI1associated with both DNAm and sleepiness score. The variant’s association with sleepiness was replicated in the UK Biobank.ConclusionsOur analysis identified methylation sites in multiple genes that may be implicated in EDS. These sleepiness-methylation associations were specific to African Americans. Future work is needed to identify mechanisms driving ancestry-specific methylation effects.Statement of SignificanceExcessive daytime sleepiness is associated with negative health outcomes such as reduction in quality of life, increased workplace accidents, and cardiovascular mortality. There are race/ethnic disparities in excessive daytime sleepiness, however, the environmental and biological mechanisms for these differences are not yet understood. We performed an association analysis of DNA methylation, measured in monocytes, and daytime sleepiness within a racially diverse study population. We detected numerous DNA methylation markers associated with daytime sleepiness in African Americans, but not in European and Hispanic Americans. Future work is required to elucidate the pathways between DNA methylation, sleepiness, and related behavioral/environmental exposures.
Geometrical structure of perceptual color space: mental representations and adaptation invariance
Authors: Ennis Robert J , Zaidi Qasim 
Published: October 2018

AbstractA central issue in neuroscience is to understand how the brain builds structured representations of percepts that facilitate useful inferences about the world. Similarity between percepts is used to accomplish many everyday tasks, e.g. object identification, so is widely used to construct geometrical spaces that represent stimulus qualities, but the intrinsic validity of the geometry is not tested critically. We introduce an experimental approach to equating relative similarities by setting perceived midpoints between pairs of stimuli. Midpoint settings are used with Varignon’s Theorem to test the intrinsic geometry of a representation space, and its mapping to a physical space of stimuli. For perceptual color space, we demonstrate that geometrical structure depends on the mental representation used in judging similarity: an affine geometry is valid only when observers use an opponent-color mental representation. An affine geometry implies that similarity can be judged within straight lines and across parallel lines, and its neural coding could involve ratios of responses. We show that this perceptual space is invariant to changes in illumination color, providing a formal justification to generalize to all of color space, color constancy results measured for color categories. Our midpoint measurements deviate significantly from midpoints in the “uniform” color spaces CIELAB and CIELUV, used extensively in industry and research, so these spaces do not provide adequate metric representation of perceived colors. Our paradigm can thus test for intrinsic geometrical assumptions underlying the representation space for many perceptual modalities, and for the extrinsic perceptual geometry of the space of physical stimuli.SignificanceMathematical spaces based on similarity judgments are widely used to represent stimulus qualities in perception, cognition and neuroscience. We introduce a perceptual approach to equate relative similarities, and use them to test the geometry of a perceptual space and its mapping to a physical space of stimuli. For color perception, our results show that perceptual geometry depends on the mental representation used in judging similarity, and it has an affine structure when observers use an opponent-color representation. An affine geometry implies that neural coding of similarity could involve simple ratios of responses. Our measurements also reveal that the uniform color spaces CIELAB and CIELUV, used extensively in industrial applications, do not provide adequate representation of similarity between moderately spaced colors.
scFTD-seq: freeze-thaw lysis based, portable approach toward high-quality distributed single-cell 3’ mRNA profiling
Authors: Dura Burak , Choi Jin-Young , Zhang Kerou , Damsky William , Thakral Durga , Bosenberg Marcus , Craft Joe , Fan Rong 
Published: October 2018

ABSTRACTCellular barcoding of 3’ mRNAs enabled massively parallel profiling of single-cell gene expression and has been implemented in droplet and microwell based platforms. The latter further adds the value for compatibility with low input samples, optical imaging, scalability, and portability. However, cell lysis in microwells remains suboptimal despite the recently developed sophisticated solutions. Here, we present scFTD-seq, a microchip platform for performingsingle-cellfreeze-thaw lysisdirectly toward 3’ mRNAsequencing. It offers format flexibility with a simplified, widely adoptable workflow that reduces the number of preparation steps and hands-on time, with the quality of data and the cost per sample matching that of the state-of-the-art scRNA-seq platforms. Freeze-thaw, known as an unfavorable lysis method resulting in possible RNA fragmentation, turns out to be fully compatible with single-cell 3’ mRNA sequencing, which detects only ~50 bases at the 3’ end. We applied it to the profiling of mixed populations including whole tumors for distinguishing all major cell types and to the profiling of circulating follicular helper T cells implicated in systemic lupus erythematosus pathogenesis. Our results delineate the heterogeneity in the transcriptional programs and effector functions of these rare pathogenic T cells. As scFTD-seq decouples on-chip cell isolation and the following library preparation steps, we envision it to potentially allow the sampling (capture of cells/beads in microwells) at the distributed sites including small clinics or point-of-care settings and downstream processing at a centralized facility, which should enable wide-spread adoption beyond academic laboratories – for any users even with no experience in scRNA-seq library generation.