bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward One-Shot Learning in Neuroscience-Inspired Deep Spiking Neural Networks
Authors: Faghihi Faramarz , Molhem Hossein , Moustafa Ahmed A. 
Published: November 2019

AbstractConventional deep neural networks capture essential information processing stages in perception. Deep neural networks often require very large volume of training examples, whereas children can learn concepts such as hand-written digits with few examples. The goal of this project is to develop a deep spiking neural network that can learn from few training trials. Using known neuronal mechanisms, a spiking neural network model is developed and trained to recognize hand-written digits with presenting one to four training examples for each digit taken from the MNIST database. The model detects and learns geometric features of the images from MNIST database. In this work, a novel biological back-propagation based learning rule is developed and used to a train the network to detect basic features of different digits. For this purpose, randomly initialized synaptic weights between the layers are being updated. By using a neuroscience inspired mechanism named ‘synaptic pruning’ and a predefined threshold, some of the synapses through the training are deleted. Hence, information channels are constructed that are highly specific for each digit as matrix of synaptic connections between two layers of spiking neural networks. These connection matrixes named ‘information channels’ are used in the test phase to assign a digit class to each test image. As similar to humans’ abilities to learn from small training trials, the developed spiking neural network needs a very small dataset for training, compared to conventional deep learning methods checked on MNIST dataset.
Foreign body reaction is triggeredin vivoby cellular mechanosensing of implants stiffer than host tissue
Authors: Carnicer-Lombarte Alejandro , Barone Damiano G. , Dimov Ivan B. , Hamilton Russell S. , Prater Malwina , Zhao Xiaohui , Rutz Alexandra L. , Malliaras George G. , Lacour Stephanie P. , Bryant Clare E. , Fawcett James W. , Franze Kristian 
Published: November 2019

AbstractMedical implants offer a unique and powerful therapeutic approach in many areas of medicine. However, their lifetime is often limited as they may cause a foreign body reaction (FBR) leading to their encapsulation by scar tissue1–4. Despite the importance of this process, how cells recognise implanted materials is still poorly understood5, 6.Here, we show how the mechanical mismatch between implants and host tissue leads to FBR. Fibroblasts and macrophages, which are both crucially involved in mediating FBR, became activated when cultured on materials just above the stiffness of healthy tissue. Coating stiff implants with a thin layer of hydrogel or silicone with a tissue-like elastic modulus (∼20 kPa in subcutaneous and ∼2 kPa in peripheral nerve implants) or softer significantly reduced inflammation and fibrosis three months after implantation. Materials stiffer than the host tissue led to nuclear localisation of the mechanosensitive transcriptional regulator YAP in neighbouring cellsin vivo, confirming mechanotransduction. The alleviation of FBR by soft coatings not exceeding the stiffness of the host tissue provides a strategy to achieve long-term implant stability without extensive modification of current implant manufacturing techniques, facilitating clinical translation.
Semi-supervised machine learning facilitates cell colocalization and tracking in intravital microscopy
Authors: Pizzagalli Diego Ulisse , Thelen Marcus , Gonzalez Santiago Fernandez , Krause Rolf 
Published: November 2019

Abstract2-photon intravital microscopy (2P-IVM) is a key technique to investigate cell migration and cell-to-cell interactions in organs and tissues of living organisms. Focusing on immunology, 2P-IVM allowed recording videos of leukocytes during the immune response, highlighting unprecedented mechanisms of the immune system. However, the automatic analysis of the acquired videos remains challenging and poorly reproducible. In fact, both manual curation of results and tuning of bioimaging software parameters among different experiments, are required. One of the most difficult tasks for a user is transferring to a computer the knowledge on what a cell is and how it should appear with respect to the background, other objects, or other cell types. This is possibly due to the low specificity of acquisition channels which may include multiple cell populations and the presence of similar objects in the background.In this work, we propose a method based on semi-supervised machine learning to facilitate colocalization. In line with recently proposed approaches for pixel classification, the method requires the user to draw some lines on the cells of interest and some line on the other objects/background. These lines embed knowledge, not only on which pixel belongs to a class or which pixel belongs to another class but also on how pixels in the same object are connected. Hence, the proposed method exploits the information from the lines to create an additional imaging channel that is specific for the cells fo interest. The usage of this method increased tracking accuracy on a dataset of challenging 2P-IVM videos of leukocytes. Additionally, it allowed processing multiple samples of the same experiment keeping the same mathematical model.
Development of Dynamic Functional Architecture during Early Infancy
Authors: Wen Xuyun , Wang Rifeng , Lin Weili , Zhang Han , Shen Dinggang 
Published: November 2019

AbstractUnderstanding the moment-to-moment dynamics of functional connectivity (FC) in the human brain during early development is crucial for uncovering neuro-mechanisms of the emerging complex cognitive functions and behaviors. Instead of calculating FC in a static perspective, we leveraged a longitudinal resting-state functional magnetic resonances imaging dataset from fifty-one typically developing infants and, for the first time, thoroughly investigated how the temporal variability of the FC architecture develops at theglobal(entire brain),meso- (functional system) andlocal(brain region) levels in the first two years of age. Our results revealed that, in such a pivotal stage,1)the whole-brain FC dynamics is linearly increased;2)the high-order functional systems display increased FC dynamics for both within- and between-network connections, while the primary systems show the opposite trajectories;3)many frontal regions have increasing FC dynamics despite large heterogeneity in developmental trajectories and velocities. All these findings indicate that the brain is gradually reconfigured towards a more flexible, dynamic, and adaptive system with globally increasing but locally heterogeneous trajectories in the first two postnatal years, explaining why infants have emerging and rapidly developing high-order cognitive functions and complex behaviors.
Expansion Microscopy of Lipid Membranes
Authors: Karagiannis Emmanouil D. , Kang Jeong Seuk , Shin Tay Won , Emenari Amauche , Asano Shoh , Lin Leanne , Costa Emma K. ,   IMAXT Grand Challenge Consortium, Marblestone Adam H. , Kasthuri Narayanan , Boyden Edward S. 
Published: November 2019

AbstractLipids are fundamental building blocks of cells and their organelles, yet nanoscale resolution imaging of lipids has been largely limited to electron microscopy techniques. We introduce and validate a chemical tag that enables lipid membranes to be imaged optically at nanoscale resolution via a lipid-optimized form of expansion microscopy, which we call membrane expansion microscopy (mExM). mExM, via a novel post-expansion antibody labeling protocol, enables protein-lipid relationships to be imaged in organelles such as mitochondria, the endoplasmic reticulum, the nuclear membrane, and the Golgi apparatus. mExM may be of use in a variety of biological contexts, including the study of cell-cell interactions, intracellular transport, and neural connectomics.
Parallel Bimodal Single-cell Sequencing of Transcriptome and Chromatin Accessibility
Authors: Xing Qiao Rui , Farran Chadi EL , Yi Yao , Warrier Tushar , Gautam Pradeep , Collins James J. , Xu Jian , Li Hu , Zhang Li-Feng , Loh Yuin-Han 
Published: November 2019

SUMMARYWe developed ASTAR-Seq (Assay for Single-cell Transcriptome and Accessibility Regions) integrated with automated microfluidic chips, which allows for parallel sequencing of transcriptome and chromatin accessibility within the same single-cell. Using ASTAR-Seq, we profiled 192 mESCs cultured in serum+LIF and 2i medium, 424 human cell lines including BJ, K562, JK1, and Jurkat, and 480 primary cells undergoing erythroblast differentiation. Integrative analysis using Coupled NMF identified the distinct sub-populations and uncovered sets of regulatory regions and the respective target genes determining their distinctions. Analysis of epigenetic regulomes further unravelled the key transcription factors responsible for the heterogeneity observed.
Genetic structure at national and regional scale in a long-distance dispersing pest organism, the bird cherry–oat aphidRhopalosiphum padi
Authors: Morales-Hojas Ramiro , Gonzalez-Uriarte Asier , Iraizoz Fernando Alvira , Jenkins Todd , Alderson Lynda , Kruger Tracey , Hall Mike J. , Greenslade Alex , Shortall Chris R. , Bell James R. 
Published: November 2019

AbstractGenetic diversity is determinant for pest species’ success and vector competence. Understanding the ecological and evolutionary processes that determine the genetic diversity is fundamental to help identify the spatial scale at which pest populations are best managed. In the present study, we present the first comprehensive analysis of the genetic diversity and evolution ofRhopalosiphum padi, a major pest of cereals and a main vector of the barley yellow dwarf virus (BYDV), in Great Britain. We have used a genotype by sequencing approach to study whether i) there is any underlying population genetic structure in this long distant disperser pest at a national and regional scale; ii) the populations evolve as a response to environmental change and selective pressures, and; iii) the populations comprise anholocyclic lineages. IndividualR. padiwere collected using the Rothamsted Insect Survey’s suction-trap network at several sites across England between 2004 and 2016 as part of the RIS long-term nationwide surveillance. Results identified two genetic clusters in Great Britain that mostly paralleled a North – South division, although gene flow is ongoing between the two subpopulations. These different groups do not correspond to sexual and asexual types, sexual reproduction being predominant in Great Britain, and could correspond to ecotypes. Results also show that there is migration with gene flow across Great Britain, although there is a reduction between the northern and southern sites with the Southwestern population being the most genetically differentiated. There is no evidence for isolation-by-distance and other factors like primary host distribution could influence the migration patterns. Finally, results also show no evidence for the evolution of theR. padipopulation, and it is demographically stable despite the ongoing environmental change. These results are discussed in view of their relevance to pest management and the transmission of BYDV.
Dentate gyrus somatostatin cells are required for contextual discrimination during episodic memory encoding
Authors: Morales Cristian , Morici Juan Facundo , Espinosa Nelson , Sacson Agostina , Lara-Vasquez Ariel , Garcia-Perez M. Alexandra , Bekinschtein Pedro , Weisstaub Noelia V. , Fuentealba Pablo 
Published: November 2019

AbstractEpisodic memory establishes and stores relations among the different elements of an experience, which are often similar and difficult to distinguish. Pattern separation, implemented by the dentate gyrus, is a neural mechanism that allows the discrimination of similar experiences by orthogonalizing synaptic inputs. Granule cells support such disambiguation by sparse rate coding, a process tightly controlled by highly diversified GABAergic neuronal populations, such as somatostatin-expressing cells which directly target the dendritic arbor of granule cells, massively innervated by entorhinal inputs reaching the molecular layer and conveying contextual information. Here, we tested the hypothesis that somatostatin neurons regulate the excitability of the dentate gyrus, thus controlling the efficacy of pattern separation during memory encoding in mice. Indeed, optogenetic suppression of dentate gyrus somatostatin neurons increased spiking activity in putative excitatory neurons and triggered dentate spikes. Moreover, optical inhibition of somatostatin neurons impaired both contextual and spatial discrimination of overlapping episodic-like memories during task acquisition. Importantly, effects were specific for similar environments, suggesting that pattern separation was selectively engaged when overlapping conditions ought to be distinguished. Overall, our results suggest that somatostatin cells regulate excitability in the dentate gyrus and are required for effective pattern separation during episodic memory encoding.Significance statementMemory systems must be able to discriminate stored representations of similar experiences in order to efficiently guide future decisions. This is solved by pattern separation, implemented in the dentate gyrus by granule cells to support episodic memory formation. The tonic inhibitory bombardment produced by multiple GABAergic cell populations maintains low activity levels in granule cells, permitting the process of pattern separation. Somatostatin-expressing cells are one of those interneuron populations, selectively targeting the distal dendrites of granule cells, where cortical multimodal information reaches the dentate gyrus. Hence, somatostatin cells constitute an ideal candidate to regulate pattern separation. Here, by using optogenetic stimulation in mice, we demonstrate that somatostatin cells are required for the acquisition of both contextual and spatial overlapping memories.
Natural naphthoquinones isolated from Lithospermum erythrorhizon suppress dextran sulfate sodium-induced murine experimental colitis
Authors: Sun Wenxue , Han Hongwei , Wang Zhaoyue , Wen Zhongling , Yang Minkai , Wang Yinsong , Fu Jiangyan , Feng Lu , Xu Xinhong , Yin Tongming , Wang Xiaoming , Lu Guihua , Qi Jinliang , Lin Hongyan , Yang Yonghua 
Published: November 2019

AbstractThe purpose of this study was to explore the effects of natural shikonin and its derivatives on mice experimental colitis induced by dextran sulfate sodium, and to investigate the underlying mechanisms in vivo. Our results suggested that, intragastric administration of single compound like shikonin and its derivatives contributed to attenuating symptoms of malignant induced by DSS. Meanwhile, shikonin or its derivatives could also remarkably reduce the disease activity index and histopathological scores, suppress the levels of pro-inflammatory cytokines (including IL-6, IL-1β and TNF-α), while increase that of inflammatory cytokine IL-10 in serum. Additionally, both shikonin and alkanin were found to restrain the levels of COX-2, MPO and iNOS in serum and colonic tissues. Moreover, western blotting results demonstrated that shikonin and its derivatives could inhibit the activation of the NLRP3 inflammasome and the NF-κB signaling pathway, relieve the DSS-induced disruption of colonic epithelial tight junction (TJ) in colonic tissues. Further, docking simulation had been performed to prove that shikonin and its derivatives could bind to the active sites of NLRP3 inflammasome and the NF-κB to generate an effective inflammatory effect. Taken together, our experimental data can provide some evidence for the potential use of shikonin and its derivatives to treat the inflammatory bowel disease (IBD).
Two common disease-associated TYK2 variants impact exon splicing and TYK2 dosage
Authors: Li Zhi , Rotival Maxime , Patin Etienne , Michel Frédérique , Pellegrini Sandra 
Published: November 2019

AbstractTYK2 belongs to the JAK protein tyrosine kinase family and mediates signaling of numerous antiviral and immunoregulatory cytokines (type I and type III IFNs, IL-10, IL-12, IL-22, IL-23) in immune and non-immune cells. After many years of genetic association studies, TYK2 is recognized as a susceptibility gene for some inflammatory and autoimmune diseases (AID). Seven TYK2 variants have been associated with AIDs in Europeans, and establishing their causality remains challenging. Previous work showed that a protective variant (P1104A) is hypomorphic and also a risk allele for mycobacterial infection. Here, we have studied two AID-associated common TYK2 variants: rs12720270 located in intron 7 and rs2304256, a non-synonymous variant in exon 8 that causes a valine to phenylalanine substitution (c.1084 G > T, Val362Phe). We found that this amino acid substitution does not alter TYK2 expression, catalytic activity or ability to relay signaling in EBV-B cell lines or in reconstituted TYK2-null cells. Based on in silico predictions that these variants may impact splicing of exon 8, we: i) analyzed TYK2 transcripts in genotyped EBV-B cells and in CRISPR/Cas9-edited cells, ii) measured splicing using minigene assays, and iii) performed eQTL (expression quantitative trait locus) analysis of TYK2 transcripts in primary monocytes and whole blood cells. Our results reveal that the two variants promote the inclusion of exon 8, which, we demonstrate, is essential for TYK2 binding to cognate receptors. In addition and in line with GTEx (Genetic Tissue Expression) data, our eQTL results show that rs2304256 mildly enhances TYK2 expression in whole blood. In all, these findings suggest that these TYK2 variants are not neutral but instead have a potential impact in AID.
In silico analysis of Missense Variants in Human MPL Gene Associated with Essential Thrombocythemia
Authors: Elbager Sahar G. , Makkawi Abier A. , Mohamed Hadeel A. , Abdelrahman Fauzia A. , Osman Lamia H. , Hameed Moroj F. , Elrashid Asia M. , Basher Mohamed Y. , Khalil Safinaz I. , Bayoumi Magdi 
Published: November 2019

AbstractIntroductionThe proto-oncogene (MPL) gen encodes the receptor for thrombopoietin (TPO-R), a member of hematopoietic receptor superfamily. Thrombopoietin (TPO), the primary cytokine regulating self-renewal of hematopoietic stem cells, thrombopoiesis and megakaryocytopoiesis. TPO binding to TPO-R induces activation of Janus Kinase 2 (JAK2). Activated JAK2 triggers the activation of downstream positive signaling pathways, leading to the survival, proliferation, and differentiation of hematopoietic cells. Mutations in MPL gene possibly will alter the normal regulatory mechanisms. Numerous MPL mutations have been observed in various hematopoietic cancers such as essential thrombocythemia and primary myelofibrosis and leukemias. In this study, we performed a comprehensive in silico analysis of the functional and structural impact of non-synonymous (nsSNP) that are deleterious to TPO-R structure and function.MethodologyThe data on human MPL gene was retrieved from dbSNP/NCBI. Nine prediction algorithms; SIFT, Polyphen, PROVEAN, SNAP2, Condel, PhD-SNP, I-Mutant, Mutpred. RaptorX and Chimera were used to analyzing the effect of nsSNPs on functions and structure of the TPO-R. STRING and KEGG database were used for TPO-R protein-protein interaction.Results and DiscussionAs per dbSNP database, the human MPL gene contained 445 missense mutations. A total 5 nsSNPs (D295G, R257C, Y252H, R537W and D128Y) were predicted to have the most damaging effects on TPO-R structure and function. STRING and KEGG revealed that MPL had strong interactions with proteins that involved in cell growth, apoptosis, signal transduction pathway, some cancers pathways such as colorectal cancer, lung cancer, pancreas cancers, and skin cancer. A literature search revealed that Y252H has contribute to the development of essential thrombocythemia.ConclusionThese in silico predictions will provide useful information in selecting the target SNPs that are likely to have functional impact on the TPO-R and moreover could act as potential targets in genetic association studies. Keywords: In Silico analyses; JAK2; Missense Variants; MPL gene; Thrombopoietin (TPO); Single nucleotide polymorphism (SNP).
Decoding and encoding models reveal the role of mental simulation in the brain representation of meaning
Authors: Soto David , Sheikh Usman Ayub , Mei Ning , Santana Roberto 
Published: November 2019

AbstractHow the brain representation of conceptual knowledge vary as a function of processing goals, strategies and task-factors remains a key unresolved question in cognitive neuroscience. Here we asked how the brain representation of semantic categories is shaped by the depth of processing during mental simulation. Participants were presented with visual words during functional magnetic resonance imaging (fMRI). During shallow processing, participants had to read the items. During deep processing, they had to mentally simulate the features associated with the words. Multivariate classification, informational connectivity and encoding models were used to reveal how the depth of processing determines the brain representation of word meaning. Decoding accuracy in putative substrates of the semantic network was enhanced when the depth processing was high, and the brain representations were more generalizable in semantic space relative to shallow processing contexts. This pattern was observed even in association areas in inferior frontal and parietal cortex. Deep information processing during mental simulation also increased the informational connectivity within key substrates of the semantic network. To further examine the properties of the words encoded in brain activity, we compared computer vision models - associated with the image referents of the words - and word embedding. Computer vision models explained more variance of the brain responses across multiple areas of the semantic network. These results indicate that the brain representation of word meaning is highly malleable by the depth of processing imposed by the task, relies on access to visual representations and is highly distributed, including prefrontal areas previously implicated in semantic control.
Clofarabine commandeers the RNR-α—ZRANB3 nuclear signaling axis
Authors: Long Marcus J. C. , Zhao Yi , Aye Yimon 
Published: November 2019

SummaryRibonucleotide reductase (RNR) is an essential enzyme in DNA-biogenesis and a target of several chemotherapeutics. Here we investigate how anti-leukemic drugs [e.g., clofarabine (ClF)] that target one of the two subunits of RNR, RNR-α, affect non-canonical RNR-α functions. We discovered that these clinically-approved RNR-inhibiting dATP-analogs inhibit growth by also targeting ZRANB3—a newly-identified DNA-synthesis promoter and nuclear-localized interactor of RNR-α. Remarkably, in early time points following drug treatment, ZRANB3-targeting accounted for most of the drug-induced DNA-synthesis suppression and multiple cell types featuring ZRANB3-knockout/knockdown were resistant to these drugs. Additionally, ZRANB3 plays a major role in regulating tumor-invasion and H-rasG12V-promoted transformation in a manner dependent on the recently-discovered interactome of RNR-α involving select cytosolic-/nuclear-localized protein-players. The H-rasG12V-promoted transformation—which we show requires ZRANB3-supported DNA-synthesis—was efficiently suppressed by ClF. Such overlooked mechanisms-of-action of approved drugs and a new example of non-oncogene addiction, which is suppressed by RNR-α, may advance cancer interventions.