bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis of central serous chorioretinopathy by deep learning analysis ofen faceimages of choroidal vasculature
Authors: Aoyama Yukihiro , Maruko Ichiro , Kawano Taizo , Yokoyama Tatsuro , Ogawa Yuki , Maruko Ruka , Iida Tomohiro 
Published: December 2020

AbstractPurposeTo classify central serous chorioretinopathy (CSC) by deep learning (DL) analyses ofen faceimages of choroidal vasculature obtained by optical coherence tomography (OCT) and to analyze the regions of interest for DL from heatmaps.MethodsOne-hundred eyes were studied; 53 eyes with CSC and 47 normal eyes. Volume scans of 12×12 mm square were obtained at the same time as the OCT angiographic (OCTA) scans (Plex Elite 9000 Swept-Source OCT®, Zeiss). High-qualityen faceimages of the choroidal vasculature of the segmentation slab of one-half of the subfoveal choroidal thickness were created for the analyses. The entire 100en faceimages were divided into 80 for training (100 times) and 20 for validation. The Neural Network Console (NNC) developed by Sony and the Keras-Tensorflow backend developed by Google were used as the software for the classification with 16 layers of convolutional neural networks. The active region of the heatmap based on the feature quantity extracted by DL was also evaluated as the percentages with gradient-weighted class activation mapping implementation in Keras.ResultsIn the 20 eyes used for validation including 8 eyes with CSC, the accuracy rate of the validation was 100% (20/20) for NNC and 95% (19/20) for Keras. This difference was not significant (P=0.33). The mean active region in the heatmap image was 12.5% in CSC eyes which was significantly lower than the 79.8% in normal eyes (P<0.01).ConclusionsCSC can be automatically classified with high accuracy fromen faceimages of the choroidal vasculature by DLs with different programs, convolutional layer structures, and small data sets. Heatmap analyses showed that DL focused on the area occupied by the choroidal vessels and their uniformity. We conclude that DL can help in the diagnosis of CSC.
High expression of JAM2 indicates better prognosis and immunotherapy response in breast cancer
Authors: Peng Yang , Qu Chi , Zhang Yingzi , Zong Beige , Jian Bin , Fu Yong , Xie Jian , Liu Shengchun 
Published: December 2020

AbstractIn our study, multiple databases were used to explore the potential role and underlying mechanism of junctional adhesion molecule B (JAM2) in breast cancer (BRCA). The data of JAM2 was downloaded from The Cancer Cell Line Encyclopedia (CCLE), the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Receiver operating characteristic (ROC) curve analysis was performed to analyze the area under the curve (AUC) of JAM2 expression correlated with normal breast tissue and breast cancer tissue. Gene set enrichment analysis (GSEA) was used to identify the potential biological mechanisms of the JAM2. The expression of JAM2 mRNA were downregulated In most tumors, including BRCA, which may be due to the hypermethylated status. The AUCs, which were 0.929 and 0.887 by the logistic regression and random forest algorithms, indicated that JAM2 mRNA expression have good diagnostic value in BRCA. Univariate and multivariate analyses indicated JAM2 as an independent prognostic factor for the overall survival of BRCA patients in both the TCGA cohort (HR = 0.62, P = 0.034) and METABRIC cohort (HR = 0.77, P = 0.001). GSEA showed that multiple tumor pathways were suppressed in the JAM2 high expression group. The expression of JAM2 was most positively related to the epithelial-mesenchymal transition (EMT) score (r = 0.38; P <0.01) by the reverse-phase protein array (RPPA) analysis. Patients with high JAM2 expression may be more sensitive to immunotherapy. 18 chemotherapy drugs that patients in the JAM2 low expression group were more sensitive to were identified. Our results demonstrated the diagnostic and prognostic value of JAM2. Analysis of the molecular mechanisms indicates the potential role of JAM2 as a tumor suppressor, and high JAM2 expression may predict a better immunotherapy response in BRCA.
Temporal scaling of human scalp-recorded potentials
Authors: Hassall Cameron D. , Harley Jack , Kolling Nils , Hunt Laurence T. 
Published: December 2020

AbstractMuch of human behaviour is governed by common processes that unfold over varying timescales. Standard event-related potential analysis assumesfixed-durationresponses relative to experimental events. However, recent single unit recordings in animals have revealed neural activityscalesto span different durations during behaviours demanding flexible timing. Here, we employed a general linear modelling approach using a novel combination of fixed-duration and variable-duration regressors to unmix fixed-time and scaled-time components in human magneto/electroencephalography (M/EEG) data. We use this to reveal consistent temporal scaling of human scalp-recorded potentials across four independent EEG datasets, including interval perception, production, prediction and value-based decision making. Between-trial variation in the temporally scaled response predicts between-trial variation in subject reaction times, demonstrating the relevance of this temporally scaled signal for temporal variation in behaviour. Our results provide a general approach for studying flexibly timed behaviour in the human brain.Significance StatementNeural activity is traditionally thought to occur over fixed time scales. However, recent animal work has suggested that some neural responses occur over varying timescales. We extended this animal result to humans by detecting temporally scaled signals non-invasively at the scalp in four different tasks. Our results suggest that temporal scaling is an important feature of cognitive processes known to unfold over varying timescales.
Pointing in depth is shaped by a natural grasping distance prior
Authors: Wiesing Michael , Kartashova Tatiana , Zimmermann Eckart 
Published: December 2020

AbstractVision in depth is distorted. A similar distortion can be observed for pointing to visual targets in depth. It has been suggested that pointing errors in depth reflect the visual distortion. However, much research has suggested that in case visual information is not rich enough, the sensorimotor system involves prior knowledge to optimally plan movement trajectories. Here, we show that pointing in depth is guided by a prior that biases movements toward the natural grasping distance at which object manipulation is usually performed. To dissociate whether pointing is guided by distorted vision only or whether it takes into account a natural grasping distance prior, we adapted pointing movements. Participants received visual feedback about the success of their pointing once the movement was finished. We distorted the feedback to signal either that pointing was not far enough or in separate sessions that pointing was too far. Participants adapted to this artificial error by either extending or shortening their pointing movements. The generalization of pointing adaptation revealed a bias in movement planning that is inconsistent with pointing being guided only by distorted vision but with the involvement of knowledge about the natural grasping distance. Adaptation was strongest for pointing movements to a middle position that corresponds to the natural grassing distance and it was weakest for movements leading away from it. It has been demonstrated that pointing adaptation in depth changes visual perception (Volcic et al., 2013). We also wondered how effects of pointing adaptation on visual space would generalize in depth.
Myogenin controls via AKAP6 non-centrosomal microtubule organizing center formation at the nuclear envelope
Authors: Becker Robert , Vergarajauregui Silvia , Billing Florian , Sharkova Maria , Lippolis Eleonora , Mamchaoui Kamel , Ferrazzi Fulvia , Engel Felix B. 
Published: December 2020

AbstractNon-centrosomal microtubule organizing centers (MTOC) are pivotal for the function of multiple cell types, but the processes initiating their formation are unknown. Here, we find that the transcription factor myogenin is required in myoblasts for the localization of MTOC proteins to the nuclear envelope. Moreover, myogenin is sufficient in fibroblasts for nuclear envelope MTOC (NE-MTOC) formation and centrosome attenuation. Bioinformatics combined with loss- and gain-of-function experiments identified induction of AKAP6 expression as one central mechanism for myogenin-mediated NE-MTOC formation. Promoter studies indicate that myogenin preferentially induces the transcription of muscle- and NE-MTOC-specific isoforms ofAkap6andSyne1, which encodes nesprin-1α, the NE-MTOC anchor protein in muscle cells. Overexpression of AKAP6β and nesprin-1α was sufficient to recruit endogenous MTOC proteins to the nuclear envelope of myoblasts in the absence of myogenin. Taken together, our results illuminate how mammals transcriptionally control the switch from a centrosomal MTOC to an NE-MTOC and identify AKAP6 as a novel NE-MTOC component in muscle cells.
Heavy metal pollutants have additive negative effects on honey bee cognition
Authors: Monchanin Coline , Drujont Erwann , Devaud Jean-Marc , Lihoreau Mathieu , Barron Andrew B. 
Published: December 2020

AbstractEnvironmental pollutants can exert sublethal deleterious effects on animals. These include disruption of cognitive functions underlying crucial behaviours. While agrochemicals have been identified as a major threat to pollinators, other compounds, such as heavy metals that are often found in complex mixtures, have largely been overlooked. Here, we assessed the impact of acute exposure to field-realistic concentrations of lead, copper, arsenic, and their combinations, on honey bee learning and memory. All treatments involving single metals slowed down appetitive learning and disrupted memory retrieval at 24 h. Importantly, combinations of these metals induced additive negative effects on both processes, suggesting common pathways of toxicity. Our results highlight the need to further assess the risks of heavy metal pollution on invertebrates and to their associated ecosystem services.Summary statementHoney bees displayed reduced learning and memory performances following acute exposure to arsenic, copper or lead. Exposure to combinations of these metals induced additive effects.
Autosomal recessive loci contribute significantly to quantitative variation of male fertility in a dairy cattle population
Authors: Hiltpold Maya , Kadri Naveen Kumar , Janett Fredi , Witschi Ulrich , Schmitz-Hsu Fritz , Pausch Hubert 
Published: December 2020

AbstractCattle are ideally suited to investigate the genetics of male fertility. Semen from individual bulls is used for thousands of artificial inseminations for which the fertilization success is monitored. In a cohort of 3881 bulls that had genotypes at 589,791 SNPs, we reveal four novel recessive QTL for male fertility using haplotype-based association testing. We detect either missense or nonsense variants inSPATA16,VWA3A, ENSBTAG00000006717andENSBTAG00000019919that are in linkage disequilibrium with the QTL. A QTL for bull fertility on BTA1 is also associated with sperm head shape anomalies. Using whole-genome sequence and transcriptome data, we prioritise a missense variant (p.Ile193Met) inSPATA16as candidate causal variant underlying this QTL. Our findings in a dairy cattle population provide evidence that recessive variants may contribute substantially to quantitative variation in male fertility in mammals.
Cytoplasmic physical state governs the influence of oxygen onPinus densifloraseed ageing
Authors: Gerna Davide , Ballesteros Daniel , Stöggl Wolfgang , Arc Erwann , Seal Charlotte E. , Na Chae Sun , Kranner Ilse , Roach Thomas 
Published: December 2020

AbstractDuring desiccation, the cytoplasm of orthodox seeds solidifies in a glass with highly restricted diffusion and molecular mobility, which extend longevity. Temperature and moisture determine seed cellular physical state, and oxygen can promote deteriorative reactions of seed ageing. However, whether seed physical state affects O2-mediated biochemical reactions during ageing remains unknown. Here, we answered this question using oil-richPinus densifloraseeds aged by controlled deterioration (CD) at 45 °C and distinct relative humidities (RHs), resulting in a glassy (9 and 33% RH) or fluid (64 and 85% RH) cytoplasm. Regardless of CD regimes, the cellular lipid domain remained always fluid. Hypoxia (0.4% O2) prevented seed deterioration only in the glassy state, limiting non-enzymatic lipid peroxidation, consumption of antioxidants (glutathione, tocopherols) and unsaturated fatty acids, accompanied by decreased lipid melt enthalpy and lower concentrations of aldehydes and reactive electrophile species (RES). In contrast, a fluid cytoplasm promoted faster seed deterioration and enabled the resumption of enzymatic activities implicated in glutathione metabolism and RES detoxification, regardless of O2availability. Furthermore, seeds stored under dry/cold seed bank conditions showed biochemical profiles similar to those of CD-aged seeds with glassy cytoplasm under normoxia. These findings are discussed in the context of germplasm management.Highlightlipid peroxidation occurred during seed ageing in the glassy state and, like viability loss, could be prevented by hypoxia. Seeds with fluid cytoplasm aged faster and irrespective of oxygen availability.
Osteoprotegerin expression in liver is induced by IL-13 through TGF-β
Authors: Adhyatmika Adhyatmika , Putri Kurnia S. S. , Gore Emilia , Mangnus Keri A. , Reker-Smit Catharina , Schuppan Detlef , Beljaars Leonie , Olinga Peter , Melgert Barbro N. 
Published: December 2020

1.AbstractBackgroundsOsteoprotegerin (OPG) is a profibrotic mediator produced by myofibroblasts under influence of transforming growth factor β (TGFβ). Its expression in experimental models of liver fibrosis correlates well with disease severity and treatment responses. The regulation of OPG in liver tissue is largely unknown and we therefore set out to elucidate which growth factors/interleukins associated with fibrosis induce OPG and through which pathways.MethodsPrecision-cut liver slices of wild type and STAT6-deficient mice and 3T3 fibroblasts were used to investigate the effects of TGFβ, interleukin (IL) 13 (IL13), IL1β, and platelet-derived growth factor BB (PDGF-BB) on expression of OPG.ResultsIn addition to TGFβ, only IL13 and not PDGF-BB or IL1β could induce OPG expression in 3T3 fibroblasts and liver slices. This IL13-dependent induction was not shown in liver slices of STAT6-deficient mice and when wild type slices were cotreated with TGFβ receptor 1 kinase inhibitor galunisertib, STAT6 inhibitor AS1517499, or AP1 inhibitor T5224. This suggests that the OPG-inducing effect of IL13 is mediated through IL13 receptor α1-activation and subsequent STAT6-dependent upregulation of IL13 receptor α2, which in turn activates AP1 and induces production of TGFβ and subsequent production of OPG.ConclusionWe have shown that IL13 induces OPG release by liver tissue through a TGFβ-dependent pathway involving both the α1 and the α2 receptor of IL13 and transcription factors STAT6 and AP1. OPG may therefore be a novel target for the treatment liver fibrosis as it is mechanistically linked to two important regulators of fibrosis in liver, namely IL13 and TGFβ1.
Overexpression ofEiKCSconfers paraquat-tolerance in rice(Oryza sativaL.) by promoting polyamine pathway
Authors: Luo Qiyu , Chen Shu , Zhu Jiazheng , Ye Laihua , Hall Nathan Daniel , Basak Suma , McElroy J. Scott , chen Yong 
Published: December 2020

AbstractParaquat is an important bipyridine herbicide by acting on the photosynthetic system of the plants and generating reactive oxygen species leading to cell death, whereas the mechanism of the paraquat resistance remains to be explored. In this study, a putative paraquat-resistant geneEiKCSfrom goosegrass(Eleusine indicaL.) was isolated and overexpressed in a transgenic rice(Oryza sativaL.). This transgenic rice (KCSox) was treated by exogenous spermidine and paraquat and then was analyzed by qualitative and quantitative proteomics. Overexpressing ofEiKCSenhanced paraquat tolerance in KCSox by the accumulation of endogenous polyamines whose dominant presences of polyamines benzoylation derivatizations in rice were C18H20N2O2, C28H31N3O3, and C38H42N4O4. The mechanism underlying the improving tolerance enhanced antioxidant capacity of ROS systems and light-harvesting in photosynthesis in KCSox rice leaves to reducing paraquat toxicity. The protein β-Ketoacyl-CoA Synthase (EiKCS) encoded by theEiKCSgene promoted the synthesis and metabolism of proteins of the polyamine pathway. Three cofactors CERs were identified and positively correlated with the function of EiKCS on very-long-chain fatty acids (VLCFAs) biosynthesis via promoting the polyamine pathway and inhibiting the links with the TCA pathway and fatty acid pathway to responding to the paraquat tolerance in the KCSox rice, which also caused the prolongation of the overproduction of spermine and a transient increase of intracellular malondialdehyde (MDA). These results expanded the polyamines pathway manipulated in cereals using genetic engineering to clarify the mechanism of paraquat-tolerance.One Sentence SummaryA putative paraquat-resistantEiKCSgene from the goosegrass overexpressing in the rice resulted in the accumulation of polyamines, especially the spermine, and promoted the proteins in polyamine pathways by its EiKCS protein under paraquat stress.
Basal G-protein-gated inwardly rectifying potassium (Kir3/GirK) channels activity governs synaptic plasticity that supports dorsal hippocampus-dependent cognitive functions
Authors: Temprano-Carazo Sara , Djebari Souhail , Iborra-Lázaro Guillermo , Sánchez-Rodríguez Irene , Nava-Mesa Mauricio O. , Múnera Alejandro , Gruart Agnès , Delgado-García José M. , Jiménez-Díaz Lydia , Navarro-López Juan D. 
Published: December 2020

AbstractG-protein-gated inwardly rectifying potassium (Kir3/GirK) channel is the effector of many G-protein-coupled receptors. Its dysfunction has been linked to the pathophysiology of Down syndrome, Alzheimer’s and Parkinson’s diseases, psychiatric disorders, epilepsy, drug addiction, or alcoholism. GirK channels are constitutively activated in the dorsal hippocampus contributing to resting membrane potential, and their synaptic activation compensates any excitation excess. Here, in order to elucidate the role of GirK channels activity in the maintenance of dorsal hippocampus-dependent cognitive functions, their involvement in controlling neuronal excitability at different levels of complexity was examined. For that purpose, basal GirK activity was pharmacologically modulated by two specific drugs: ML297, a GirK channel opener, and Tertiapin-Q, a GirK channel blocker.Ex vivo,using dorsal hippocampal slices, we studied pharmacological GirK modulation effect on synaptic plasticity processes induced in CA1 by Schaffer collateral stimulation.In vivo, we performed acute intracerebroventricular injections of both GirK modulators to study their contribution to CA3–CA1 synapse electrophysiological properties, synaptic plasticity, and learning and memory capabilities during hippocampal dependent tasks. We found that pharmacological disruption of basal GirK activity in dorsal hippocampus, causing either function gain or loss, induced learning and memory deficits by a mechanism involving neural excitability impairments and alterations in induction and maintenance of long-term synaptic plasticity processes. These results support the contention that an accurate control of GirK activity must take place in the hippocampus to sustain cognitive functions.Significance StatementThe dorsal hippocampus mostly performs cognitive functions related to contextual/spatial associations. These functions rely on synaptic plasticity processes that are critically ruled by a finely tuned neural excitability. Being the downstream physiological effectors of a variety of G-coupled receptors, activation of G protein-gated inwardly rectifying K+ (GirK) channels induces neurons to hyperpolarize, contributing to neural excitability throughout the control of excitatory excess. Here, we demonstrate that modulation of basal GirK channels activity, causing either function gain or loss, transforms HFS-induced LTP into LTD, inducing deficits in dorsal hippocampus-dependent learning and memory. Together, our data show a crucial GirK activity-mediated mechanism that governs synaptic plasticity direction and modulates subsequent hippocampal-dependent cognitive functions.
Target2DeNovoDrugPropMax : a novel programmatic tool incorporating deep learning andin silicomethods for automatedde novodrug design for any target of interest
Authors: Madaj Rafal , Geoffrey Ben , Sanker Akhil , Valluri Pavan Preetham 
Published: December 2020

AbstractThe past decade has seen a surge in the range of application data science, machine learning, deep learning, and AI methods to drug discovery. The presented work involves an assemblage of a variety of AI methods for drug discovery along with the incorporation of in silico techniques to provide a holistic tool for automated drug discovery. When drug candidates are required to be identified for a particular drug target of interest, the user is required to provide the tool target signatures in the form of an amino acid sequence or its corresponding nucleotide sequence. The tool collects data registered on PubChem required to perform an automated QSAR and with the validated QSAR model, prediction and drug lead generation are carried out. This protocol we call Target2Drug. This is followed by a protocol we call Target2DeNovoDrug wherein novel molecules with likely activity against the target are generated de novo using a generative LSTM model. It is often required in drug discovery that the generated molecules possess certain properties like drug-likeness, and therefore to optimize the generated de novo molecules toward the required drug-like property we use a deep learning model called DeepFMPO, and this protocol we call Target2DeNovoDrugPropMax. This is followed by the fast automated AutoDock-Vina based in silico modeling and profiling of the interaction of optimized drug leads and the drug target. This is followed by an automated execution of the Molecular Dynamics protocol that is also carried out for the complex identified with the best protein-ligand interaction from the AutoDock-Vina based virtual screening. The results are stored in the working folder of the user. The code is maintained, supported, and provide for use in the following GitHub repositoryhttps://github.com/bengeof/Target2DeNovoDrugPropMax