bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying essential genes across eukaryotes by machine learning
Authors: Beder Thomas , Aromolaran Olufemi , Dönitz Jürgen , Tapanelli Sofia , Adedeji Eunice O. , Adebiyi Ezekiel , Bucher Gregor , Koenig Rainer 
Published: April 2021

AbstractIdentifying essential genes on a genome scale is resource intensive and has been performed for only a few eukaryotes. For less studied organisms essentiality might be predicted by gene homology. However, this approach cannot be applied to non-conserved genes. Additionally, divergent essentiality information is obtained from studying single cells or whole, multi-cellular organisms, and particularly when derived from human cell line screens and human population studies. We employed machine learning across six model eukaryotes and 60,381 genes, using 41,635 features derived from sequence, gene functions and network topology. Within a leave-one-organism-out cross-validation, the classifiers showed a high generalizability with an average accuracy close to 80% in the left-out species. As a case study, we applied the method toTribolium castaneumand validated predictions experimentally yielding similar performance. Finally, using the classifier based on the studied model organisms enabled linking the essentiality information of human cell line screens and population studies.
Endothelial metastasis-associated protein 1 (MTA1) is an essential molecule for angiogenesis
Authors: Ishikawa Mizuho , Osaki Mitsuhiko , Uno Narumi , Ohira Takahito , Kugoh Hiroyuki , Okada Futoshi 
Published: April 2021

AbstractOur previous study revealed that metastasis-associated protein 1 (MTA1), expressed in endothelial cells acts as a factor promoting tube formation. In this study, we aimed to clarify the importance of MTA1 in tube formation usingMTA1-knockout endothelial cells (MTA1-KO MSS31 cells). Tube formation was strongly suppressed in MTA1-KO MSS31 cells, whereas MTA1-overexpressed MTA1-KO MSS31 cells regained the ability to form tube-like structures. Furthermore, MTA1-KO MSS31 cells showed higher phosphorylation of non-muscle myosin heavy chain IIa (NMIIa), which resulted in suppression of tube formation; this was attributed to a decrease of MTA1– S100 calcium-binding protein A4 (S100A4) complex formation. Moreover, inhibition of tube formation in MTA1-KO MSS31 cells could not be rescued by stimulation with vascular endothelial growth factor (VEGF). These results demonstrated that MTA1 is an essential molecule for angiogenesis, and that it may be involved in different steps of the angiogenic process compared to the VEGF–VEGF receptor 2 (VEGFR2) pathway. Our findings showed that endothelial MTA1 and its pathway are promising targets for inhibiting tumor angiogenesis, supporting the development of MTA1-based anti-angiogenic therapies.
Smell-induced gamma oscillations in human olfactory cortex are required for accurate perception of odor identity
Authors: Yang Qiaohan , Zhou Guangyu , Noto Torben , Templer Jessica , Schuele Stephan , Rosenow Joshua , Lane Gregory , Zelano Christina 
Published: April 2021

AbstractStudies of neuronal oscillations have contributed substantial insight into the mechanisms of visual, auditory and somatosensory perception. However, progress in such research in the human olfactory system has lagged behind. As a result, the electrophysiological properties of the human olfactory system are poorly understood, and in particular, whether stimulus-driven high frequency oscillations play a role in odor processing is unknown. Here, we used direct intracranial recordings from human piriform cortex during an odor identification task to show that three key oscillatory rhythms are an integral part of the human olfactory cortical response to smell: odor induces theta, beta and gamma rhythms in human piriform cortex. We further show that these rhythms have distinct relationships with perceptual behavior. Odor-elicited gamma oscillations occur only during trials in which the odor is accurately perceived, and features of gamma oscillations predict odor identification accuracy, suggesting they are critical for odor identity perception in humans. We also found that the amplitude of high-frequency oscillations is organized by the phase of low frequency signals shortly following sniff onset, only when odor is present. Our findings reinforce previous work on theta oscillations, suggest that gamma oscillations in human piriform cortex are important for perception of odor identity, and constitute a robust identification of the characteristic electrophysiological response to smell in the human brain. Future work will determine whether the distinct oscillations we identified reflect distinct perceptual features of odor stimuli.
Behavioral clusters revealed by end-to-end decoding from microendoscopic imaging
Authors: Chang Chia-Jung , Guo Wei , Zhang Jie , Newman Jon , Sun Shao-Hua , Wilson Matt 
Published: April 2021

AbstractIn vivocalcium imaging using head-mounted miniature microscopes enables tracking activity from neural populations over weeks in freely behaving animals. Previous studies focus on inferring behavior from a population of neurons, yet it is challenging to extract neuronal signals given out-of-focus fluorescence in endoscopic data. Existing analysis pipelines include regions of interest (ROIs) identification, which might lose relevant information from false negatives or introduce unintended bias from false positives. Moreover, these methods often require prior knowledge for parameter tuning and are time-consuming for implementation. Here, we develop an end-to-end decoder to predict the behavioral variables directly from the raw microendoscopic images. Our framework requires little user input and outperforms existing decoders that need ROI extraction. We show that neuropil/background residuals carry additional behaviorally relevant information. Video analysis further reveals an optimal decoding window and dynamics between residuals and cells. Critically, saliency maps reveal the emergence of video-decomposition across our decoder, and identify distinct clusters representing different behavioral aspects. Together, we present a framework that is efficient for decoding behavior from microendoscopic imaging, and may help discover functional clustering for a variety of imaging studies.
The Expression of Angiopoietin-1 and −2 in the Osteogenesis of Mesenchymal Stem Cells
Authors: Chen Jinwen , Yang Guangchan , Guo Jie , Liu Yuqin , Guo Jinchen , Suo Jiatao , Yu Hongyou 
Published: April 2021

AbstractObjectiveThe objectives of this study are to clarify whether rat bone marrow derived Mesenchymal stem cells (MSCs) express Ang1 and Ang2 and their expression in the process of osteogenesis in vitro.Material and MethodsMSCs were cultured from rat tibia bone marrow cells and the hemopoietic stem cells were deplete by consistently replacement of the culture medium. The MSCs were induced osteogenesis with mineralization conditional medium and Immunohistochemical and immunofluorescent staining were performed to assess the expression of Ang1 and Ang2.ResultsThe method used to expand rat MSCs in vitro was applicable, and the cell morphology is spindle-like shape that is consistent with the privous reports. The immunohistochemical staining results showed that both Ang1 and Ang2 were expressed by rat MSCs. Both Ang1 and Ang2 were up-regulated in the process of osteogenesis of rat MSCs.ConclusionRat MSCs express both Ang1 and Ang2 which might play critical roles in the osteogenesis in vitro.
Cytoplasmic zinc regulates IL-1β production by monocytes/macrophages via mTORC1-induced glycolysis in rheumatoid arthritis (RA)
Authors: Kim Bonah , Kim Hee Young , Yoon Bo Ruem , Yeo Jina , Yu Kyung-Sang , Kim Hyeon Chang , Park Jin Kyun , Kang Seong Wook , Lee Won-Woo 
Published: April 2021

ABSTRACTThe essential micronutrient zinc plays regulatory roles in immune responses through its ability to affect signaling pathways. In activated monocytes/macrophages, signaling networks mediate metabolic reprogramming in order to meet the demands of participating in immune responses. Despite its known immunoregulatory roles, the effect of zinc on metabolic reprogramming in monocytes/macrophages remains unclear. Here, we demonstrate that cytoplasmic bioavailable zinc is essential for regulating IL-1β production in activated human monocytes/macrophages downstream of mTORC1-induced glycolysis. The cytoplasmic zinc level was influenced by extracellular zinc concentration through a zinc-specific importer, Zip8, which was markedly increased in monocytes of patients with rheumatoid arthritis (RA), a chronic inflammatory disease, and even in LPS-stimulated monocytes/macrophages of healthy individuals. Mechanically, phosphorylation of S6 kinase, a substrate of mTORC1, was significantly enhanced by zinc-mediated inhibition of PP2A, an S6 kinase phosphatase. As a result, IL-1β production was increased due to the activation of mTORC1-induced glycolysis. The expression of Zip8 and MT2A, a zinc-inducible gene, and the phosphorylation of S6 kinase by monocytes of RA patients was significantly enhanced compared with those of HCs and Zip8 levels positively correlated with RA clinical parameters, suggesting that Zip8-mediated zinc influx is related to inflammatory conditions. These results provide insight into the role of cytoplasmic bioavailable zinc in the metabolic reprogramming of human monocytes/macrophages which is an essential process for inflammatory responses.One Sentence SummaryCytoplasmic zinc regulates IL-1β production in monocytes/macrophages downstream of mTORC1-S6K-induced glycolysisviazinc-mediated inhibition of PP2A.
Validation and Application of a Protocol for the Extraction and Quantitative Analysis of Sphingomyelin in Erythrocyte Membranes of Patients with NAFLD
Authors: Papadopoulos Charalampos , Mimidis Konstantinos , Tentes Ioannis , Tente Thaleia , Anagnostopoulos Konstantinos 
Published: April 2021

ABSTRACTA set of constituents of the erythrocyte membrane lipidome has been proposed to serve as biomarkers for liver disease and acute coronary syndrome. In erythrocytes, sphingomyelin hydrolysis provides ceramide, a signaling lipid necessary for phosphatidylserine exposure and eryptosis. Phosphatidylserine exposure further amplifies hepatic inflammation and fibrosis during non-alcoholic fatty liver disease (NAFLD). In this study, we developed and applied a quantitative TLC for erythrocyte membrane sphingomyelin of NAFLD patients. We also compared 10 extraction methods for the isolation of sphingomyelin from erythrocytes. For quantitative TLC, lipids were separated in Silica gel 60 F254 using a mixture of chloroform/methanol/acetic acid/water (60/50/1/4) (v/v/v/v). The separated lipids were stained in a chamber containing iodine, and the intensity of each of the primary colors (red, green, blue) and the sum of the Red plus Green colors (R+G) was analyzed. The method was linear over a wide range of concentrations, presented acceptable precision (inter-day CV(%) 0.34, 0.006 and 0.44 for 2.5, 5.0 and 10 μg, respectively), good accuracy (recovery range 85.2-97.1%), and excellent limit of detection (0.137 μg/spot) and limit of quantification (0.41 μg/spot). Using this quantitation method, we compared various lipid extraction methods and found that lipid extraction with methanol led to higher yield of erythrocyte sphingomyelin (135.35±1.04% recovery, compared to the Folch method). Application of these methods showed that erythrocytes from NAFLD patients (9 men, 15 women, 57.95±11.11 years old) contained statistically significantly less sphingomyelin (829.82±511.60 vs 1892.08±606.25 μg/ml of packed erythrocytes) compared to healthy controls (4 men, 6 women, 39.3±15.55 years old).
How the Zebra got its Rump Stripes: Salience at Distance and in Motion
Authors: Muhl-Richardson Alex , Parker Maximilian G. , Davis Greg 
Published: April 2021

SummaryZebras’ stripes cannot protect them from predators, Darwin concluded, and current consensus tends to support his view1,2. In principle, stripes could support crypsis or aposematism, could dazzle, confuse or disrupt predators’ perception3–8, yet no such effects are manifest in predator-prey interactions9–11. Instead, narrow stripes covering zebras’ head, neck, limbs and flanks are an effective deterrent to tabanids12, vectors for equine disease13,14. Accordingly, while other potential benefits, e.g., thermoregulation15,16and intraspecific communication17, cannot be excluded, zebra stripes likely evolved primarily to deter parasites18–20. Rump stripes, however, do not fit this, or any extant view. Typically horizontal and broader in sub-species with width variation, they are ill-suited to crypsis or parasite-deterrence12and vary with hyaena threat18, perhaps shaped by an additional selective pressure. We observed that rump (and rear-flank) stripes remain highly conspicuous when viewed in motion or at distance, while other stripes do not. To study this striking effect, we filtered images of zebra to simulate acuity limitations in lion and hyaena photopic and mesopic vision. For mountain zebra and plains zebra without shadow striping, rump stripes were the most conspicuous image regions according to computational salience models, corroborated by human observers’ judgements of maximally attention-capturing image locations, which were strongly biased toward the rear. By hijacking exogenous attention mechanisms to force predator attention to the rear, salient rump stripes confer benefits to zebra, estimated here in pursuit simulations. Benefits of rump stripe salience may counteract anti-parasite benefits and costs of conspicuity to shape rump and shadow stripe variation.1HighlightsZebra stripes likely evolved to deter biting flies, but rump stripes are ill-suited to this.Rump-stripes remain highly conspicuous when viewed at distance or in motion.Computational models and human observers’ judge rump stripes are most salient stripes.Salient rump stripes drive predator attention to rear, hindering capture by predators.Observe this striking effect in moving zebra at: viscog.psychol.cam.ac.uk/resources-and-downloads
Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage
Authors: Morini Elisabetta , Gao Dadi , Logan Emily M. , Salani Monica , Krauson Aram J. , Chekuri Anil , Chen Yei-Tsung , Ragavendran Ashok , Chakravarty Probir , Erdin Serkan , Stortchevoi Alexei , Svejstrup Jesper Q. , Talkowski Michael E. , Slaugenhaupt Susan A. 
Published: April 2021

AbstractElongator is a highly conserved protein complex required for transcriptional elongation, intracellular transport and translation. Elongator complex protein 1 (ELP1) is the scaffolding protein of Elongator and is essential for its assembly and stability. Familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy, is caused by a mutation inELP1that lead to a tissue-specific reduction of ELP1 protein. Our work to generate a phenotypic mouse model for FD led to the discovery that homozygous deletion of the mouseElp1gene leads to embryonic lethality prior to mid-gestation. Given that FD is caused by a reduction, not loss, of ELP1, we generated two new mouse models by introducing different copy numbers of the human FDELP1transgene into theElp1knockout mouse (Elp1-/-) and observed that humanELP1expression rescues embryonic development in a dose dependent manner. We then conducted a comprehensive transcriptome analysis in mouse embryos to identify genes and pathways whose expression correlates with the amount ofELP1. We found thatELP1is essential for the expression of genes responsible for the formation and development of the nervous system. Further, gene length analysis of the differentially expressed genes showed that the loss ofElp1mainly impacts the expression of long genes and that by gradually restoring Elongator their expression is progressively rescued. Finally, through evaluation of co-expression modules, we identified gene sets with unique expression patterns that depended onELP1expression. Overall, this study highlights the crucial role ofELP1during early embryonic neuronal development and reveals gene networks and biological pathways that are regulated by Elongator.
State and stimulus dependence reconcile motion computation and the Drosophila connectome
Authors: Kohn Jessica R. , Portes Jacob P. , Christenson Matthias P. , Abbott LF , Behnia Rudy 
Published: April 2021

AbstractSensory systems dynamically optimize their processing properties in order to process a wide range of environmental and behavioral conditions. However, attempts to infer the function of these systems via modeling often treat system components as having static processing properties. This is particularly evident in the Drosophila motion detection circuit, where the core algorithm for motion detection is still debated, and where inputs to motion detecting neurons remain underdescribed. Using whole-cell patch clamp electrophysiology, we measured the state- and stimulus-dependent filtering properties of inputs to the OFF motion-detecting T5 cell in Drosophila. Simply summing these inputs within the framework of a connectomic-constrained model of the circuit demonstrates that changes in the shape of input temporal filters are sufficient to explain conflicting theories of T5 function. Therefore, with our measurements and our model, we reconcile motion computation with the anatomy of the circuit.
MDH2 is a metabolic switch rewiring the fuelling of respiratory chain and TCA cycle
Authors: Molinié Thibaut , Cougouilles Elodie , David Claudine , Cahoreau Edern , Portais Jean-Charles , Mourier Arnaud 
Published: April 2021

ABSTRACTThe mitochondrial respiratory chain (RC) enables many metabolic processes by regenerating both mitochondrial and cytosolic NAD+and ATP. The oxidation by the RC of the NADH metabolically produced in the cytosol involves redox shuttles as the malate-aspartate shuttle (MAS) and is of paramount importance for cell fate. However, the specific metabolic regulations allowing mitochondrial respiration to prioritize NADH oxidation in response to high NADH/NAD+redox stress have not been elucidated. Our work demonstrates the crucial role played by MDH2 in orchestrating the electron fuelling of the RC. On one hand, MDH2 mediated oxaloacetate (OAA) production allows mitochondria to metabolize pyruvate and glutamate and to feed complex I with NADH, whereas on the other hand, OAA inhibits complex II. This regulatory mechanism synergistically increases RC’s NADH oxidative capacity and rewires MDH2 driven anaplerosis of the TCA favouring the oxidation of malate produced by the MAS.
Neural correlates of alcohol use disorder severity among nontreatment‐seeking heavy drinkers: An examination of the incentive salience and negative emotionality domains of the alcohol and addiction research domain criteria
Authors: Al‐Khalil Kareem , Vakamudi Kishore , Witkiewitz Katie , Claus Eric D. 
Published: April 2021

AbstractBackgroundThe Alcohol and Addiction Research Domain Criteria (AARDoC) propose that alcohol use disorder is associated with neural dysfunction in three primary domains: incentive salience, negative emotionality, and executive function. Prior studies in heavy drinking samples have examined brain activation changes associated with alcohol and negative affect cues, representing the incentive salience and negative emotionality domains, respectively. Yet studies examining such cue‐induced changes in functional connectivity (FC) are relatively sparse.MethodsNontreatment‐seeking heavy drinking adults (N = 149, 56.0% male, 48.6% non‐white, mean age 34.8 years (SD = 10.0)) underwent functional magnetic resonance imaging during presentation of alcohol, negative, and neutral pictures. We focused on FC changes involving the nucleus accumbens and amygdala in addition to activation and FC correlations with self‐reported AUD severity.ResultsFor alcohol cues versus neutral cues, we observed accumbens FC changes in the cerebellum and prefrontal cortex (PFC), and amygdala FC changes with occipital, parietal, and hippocampal regions. AUD severity correlated positively with activation in the cerebellum (p < 0.05), accumbens FC in the cingulate gyri, somatosensory gyri, and cerebellum (p < 0.05), and with amygdala FC in the PFC and inferior parietal lobule (p < 0.05) for alcohol cues versus neutral cues. For negative cues versus neutral cues, we observed accumbens FC changes in the lateral temporal, occipital, and parietal regions, and amygdala FC changes in the fusiform and lingual gyri (p < 0.05).ConclusionsThe present findings provide empirical support for the AARDoC domains of incentive salience and negative emotionality and indicate that AUD severity is associated with salience and response control for reward cues. When covarying for differences in nonalcohol substance use and mood disorder diagnoses, AUD severity was also associated with emotional reactivity for negative cues.
The impact of removing former drinkers from genome‐wide association studies of AUDIT‐C
Authors: Dao Cecilia , Zhou Hang , Small Aeron , Gordon Kirsha S. , Li Boyang , Kember Rachel L. , Ye Yixuan , Gelernter Joel , Xu Ke , Kranzler Henry R. , Zhao Hongyu , Justice Amy C. 
Published: April 2021

AbstractBackground and aimsThe Alcohol Use Disorders Identification Test‐Consumption (AUDIT‐C) questionnaire screens for harmful drinking using a 12‐month timeframe. A score of 0 is assigned to individuals who report abstaining from alcohol in the past year. However, many middle‐age individuals reporting current abstinence are former drinkers (FDs). Because FDs may be more genetically prone to harmful alcohol use than lifelong abstainers (LAs) and are often combined with LAs, we evaluated the impact of differentiating them on the identification of genetic association.Design and SettingThe United Kingdom Biobank (UKBB) includes AUDIT‐C and alcohol drinker status.Participants131 510 Europeans, including 5135 FDs.MeasurementsWe compared three genome‐wide association (GWAS) analyses to explore the effects of removing FDs: the full AUDIT‐C data, AUDIT‐C data without FDs, and data from a random sample numerically matched to the data without FDs. Because prior studies show a consistent association of the ADH1B polymorphism rs1229984 with both alcohol consumption and alcohol use disorder, we compared allele frequencies for rs1229984 stratified by AUDIT‐C value and FD versus LA status. Additionally, we calculated polygenic risk scores (PRS) of related diseases.FindingsThe rs1229984 allele frequencies among FDs were numerically comparable to those with high AUDIT‐C scores and very different from those of LAs. Removing FDs from GWAS yielded a stronger association with rs1229984 (P value after removal: 1.9 × 10−70 vs 1.7 × 10−65 and 2.5 × 10−62), more statistically significant single nucleotide polymorphisms (SNPs) (after removal: 11 vs 9 and 8), and genomic loci (after removal: 11 vs 9 and 7). Additional independent SNPs were identified after removal of FDs: rs2817866 (PTGER3), rs7105867 (ANO3), and rs17601612 (DRD2). For PRS of alcohol use disorder and major depressive disorder, there are statistically significant differences between FDs and LAs.ConclusionsDifferentiating between former drinkers and lifelong abstainers can improve Alcohol Use Disorders Identification Test‐Consumption (AUDIT‐C) genome‐wide association results.