bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Basigin (CD147)-CD98 protein complex is involved in Chikungunya virus attachment and entry in human cells
Authors: Caluwé Lien De , Coppens Sandra , Daled Simon , Dhaenens Maarten , Deforce Dieter , Ostade Xaveer Van , Ariën Kevin , Bartholomeeusen Koen 
Published: December 2019

Chikungunya virus (CHIKV), a positive stranded RNA alphavirus, recently reemerged causing multiple outbreaks around the world. Generally, alphaviruses enter the cell via clathrin-mediated endocytosis. Entry is supported by the structural envelope proteins E2 and E1. Different experimental approaches have been applied previously to identify receptor(s) molecules responsible for CHIKV binding and entry in human and mosquito cells. However they cannot account for all CHIKV entry events in all susceptible cell types.
We performed affinity purification coupled to mass spectrometry to identify entry factors of CHIKV in both human and mosquito cells. We transiently expressed the N-terminally Strep-tagged, full-length envelope gene in 293T and C6/36 cells. Affinity purifications were digested on-bead and analyzed by mass spectrometry. MiST analysis allowed the identification of 39 human proteins with a confidence score above 0.8. Twelve proteins were selected for validation with CRISPR/Cas9 knock-out cells. Three separate AP-MS experiments in C6/36 cells led to the identification of 31, 58 and 11 proteins with a MiST score higher than 0.7, of which 19 proteins were chosen for further analysis.
Using knock-out experiments in 293T cells and a reporter CHIKV (ECSA strain) resulted in the identification of the CD147-CD98 protein complex on human cells as possible entry factor. Repetition of this knock-out experiment using an Asian CHIKV strain combined with E2 staining, confirmed these results. CD147 contains 2 immunoglobulin domains which is similar to MXRA8, a previously identified alphavirus entry factor. The interaction of CD147 with E2 was validated on Western Blot after affinity purification.
Diverse demographic histories in a guild of hymenopteran parasitoids
Authors: Walton William , Stone Graham N , Lohse Konrad 
Published: December 2019

AbstractSignatures of changes in population size have been detected in genome-wide variation in many species. However, the causes of such changes and the extent to which they are shared across co-distributed species remain poorly understood. During Pleistocene glacial maxima, many temperate European species were confined to southern refugia. While vicariance and range expansion processes associated with glacial cycles have been widely studied, little is known about the demographic history of refugial populations, and the extent and causes of demographic variation among codistributed species. We used whole genome sequence data to reconstruct and compare demographic histories during the Quaternary for Iberian refuge populations in a single ecological guild (seven species of chalcid parasitoid wasps associated with oak cynipid galls). We find support for large changes in effective population size (Ne) through the Pleistocene that coincide with major climate change events. However, there is little evidence that the timing, direction and magnitude of demographic change are shared across species, suggesting that demographic histories are largely idiosyncratic. Our results are compatible with the idea that specialist parasitoids attacking a narrow range of hosts experience greater fluctuations inNethan generalists.
PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis
Authors: Danileviciute Egle , Zeng Ni , Capelle Christophe , Paczia Nicole , Gillespie Mark A. , Kurniawan Henry , Coowar Djalil , Vogt Weisenhorn Daniela Maria , Giro Gemma Gomez , Grusdat Melanie , Baron Alexandre , Guerin Coralie , Franchina Davide G. , Léonard Cathy , Domingues Olivia , Delhalle Sylvie , Wurst Wolfgang , Schwamborn Jens Christian , Krüger Rejko , Ranish Jeff , Brenner Dirk , Linster Carole L. , Balling Rudi , Ollert Markus , He Feng Q. 
Published: December 2019

AbstractPyruvate dehydrogenase (PDH) is the gatekeeper enzyme into the tricarboxylic acid (TCA) cycle. Here we show that PARK7/DJ-1, a key familial Parkinson’s disease (PD) gene, is a pacemaker controlling PDH activity in CD4 regulatory T cells (Tregs). DJ-1 bound to PDH-E1 beta (PDHB), inhibiting the phosphorylation of PDH-E1 alpha (PDHA), thus promoting PDH activity and oxidative phosphorylation (OXPHOS).Dj-1depletion impaired Treg proliferation and cellularity maintenance in older mice, increasing the severity during the remission phase of experimental autoimmune encephalomyelitis (EAE). The compromised proliferation and differentiation of Tregs inDj-1knockout mice were caused via regulating PDH activity. These findings provide novel insight into the already complicated regulatory machinery of the PDH complex and demonstrate that the DJ-1-PDHB axis represents a potent target to maintain Treg homeostasis, which is dysregulated in many complex diseases.
SSnet: A Deep Learning Approach for Protein-Ligand Interaction Prediction
Authors: Verma Niraj , Qu Xingming , Trozzi Francesco , Elsaied Mohamed , Karki Nischal , Tao Yunwen , Zoltowski Brian , Larson Eric C. , Kraka Elfi 
Published: December 2019

AbstractComputational prediction of Protein-Ligand Interaction (PLI) is an important step in the modern drug discovery pipeline as it mitigates the cost, time, and resources required to screen novel therapeutics. Deep Neural Networks (DNN) have recently shown excellent performance in PLI prediction. However, the performance is highly dependent on protein and ligand features utilized for the DNN model. Moreover, in current models, the deciphering of how protein features determine the underlying principles that govern PLI is not trivial. In this work, we developed a DNN framework named SSnet that utilizes secondary structure information of proteins extracted as the curvature and torsion of the protein backbone to predict PLI. We demonstrate the performance of SSnet by comparing against a variety of currently popular machine and non-machine learning models using various metrics. We visualize the intermediate layers of SSnet to show a potential latent space for proteins, in particular to extract structural elements in a protein that the model finds influential for ligand binding, which is one of the key features of SSnet. We observed in our study that SSnet learns information about locations in a protein where a ligand can bind including binding sites, allosteric sites and cryptic sites, regardless of the conformation used. We further observed that SSnet is not biased to any specific molecular interaction and extracts the protein fold information critical for PLI prediction. Our work forms an important gateway to the general exploration of secondary structure based deep learning, which is not just confined to protein-ligand interactions, and as such will have a large impact on protein research while being readily accessible forde novodrug designers as a standalone package.
Real-time monitoring of cotranscriptional riboswitch folding and switching
Authors: Hua Boyang , Jones Christopher P. , Mitra Jaba , Murray Peter J. , Rosenthal Rebecca , Ferré-D’Amaré Adrian R. , Ha Taekjip 
Published: December 2019

SummaryRiboswitches function through cotranscriptional conformation switching governed by cognate ligand concentration, RNA folding and transcription elongation kinetics. To investigate how these parameters influence riboswitch folding, we developed a novel vectorial folding assay (VF) in which the superhelicase Rep-X sequentially liberates the RNA strand from a heteroduplex in a 5’-to-3’ direction, mimicking the nascent chain emergence during transcription. The RNA polymerase (RNAP)-free VF recapitulates the kinetically controlled cotranscriptional folding of a ZTP riboswitch, whose activation is favored by slower transcription, strategic pausing, or a weakened transcriptional terminator. New methods to observe positions and local rates of individual helicases show an average Rep-X unwinding rate similar to bacterial RNAP elongation (~60 nt/s). Real-time single-molecule monitoring captured folding riboswitches in multiple states, including an intermediate responsible for delayed terminator formation. These methods allow observation of individual folding RNAs as they occupy distinct folding channels within the landscape that controls gene expression and showed that riboswitch fate control is encoded in its sequence and is readily interpreted by a directionally moving protein even in the absence of an RNA polymerase.
Genotyping and functional regression trees reveals environmental preferences of toxic cyanobacteria (Microcystis aeruginosacomplex) along a wide spatial gradient
Authors: Martínez de la Escalera Gabriela , Segura Angel M. , Kruk Carla , Ghattas Badih , Piccini Claudia 
Published: December 2019

AbstractAddressing ecological and evolutionary processes explaining biodiversity patterns is essential to identify the mechanisms driving community assembly. In the case of bacteria, the formation of new ecologically distinct populations or ecotypes is proposed as one of the main drivers of diversification. New ecotypes arise when mutation in key functional genes or acquisition of new metabolic pathways by horizontal gene transfer allow the population to exploit new resources, making possible their coexistence with parental population. Recently, we have reported the presence of toxic, microcystin-producing organisms from theMicrocystis aeruginosacomplex (MAC) through a wide environmental gradient (800 km) in South America, ranging from freshwater to estuarine-marine waters. In order to explain this finding, we hypothesize that the success of toxic organisms of MAC in such array of environmental conditions is due to the existence of ecotypes having different environmental preferences. So, we analysed the genetic diversity of microcystin-producing populations ofMicrocystis aeruginosacomplex (MAC) by qPCR and high resolution melting analysis (HRMA) of a functional gene (mcyJ, involved in microcystin synthesis) and explored its relationship with the environmental conditions through the gradient by functional classification and regression trees (fCART). Six groups ofmcyJgenotypes were distinguished and selected by different combinations of water temperature, conductivity and turbidity, determining the environmental preferences of each group. Since these groups were based on the basis of similar sequence and ecological characteristics they were defined as ecotypes of toxic MAC. Taking into account that the role of microcystins in MAC biology and ecology has not yet been elucidated, we propose that the toxin might have a role in MAC fitness that would be mainly controlled by the physical environment in a way such that the ecotypes that thrive in the riverine zone of the gradient would be more stable and less influenced by salinity fluctuations than those living at the marine limit of the estuary. These would periodically disappear or being eliminated by salinity increases, depending on the estuary dynamics. Thus, ecotypes generation would be an important mechanism allowing toxic MAC adapting to and succeed in a wide array of environmental conditions.
Niacin Stimulates Mammary Gland Development in Pubertal Mice through Activation of the AKT/mTOR and ERK1/2 Signaling Pathways
Authors: Cao Yu , Liu Juxiong , Ma Lijun , Zhang Qing , Wang Jiaxin , Guo Wenjin , Li Yanwei , Cheng Ji , Fu Shoupeng 
Published: December 2019

ABSTRACTPrevious studies have shown the effects of vitamins on the development of the mammary gland. However, the role of niacin in this process has not been reported. Therefore, the aim of this study was to investigate the effects of niacin on mammary gland development in pubertal mice and to use a mouse mammary epithelial cell line to study the underlying mechanism. The results showed that niacin could activate the AKT/mTOR and ERK signaling pathways by the Gi protein-coupled receptor and increase phosphorylation of 4EBP1 to promote the synthesis of cell proliferation markers, leading to the dissociation of the Rb-E2F1 complex in mMECs. In addition, 0.5% niacin promoted mammary duct development, increased the expression of cyclin D1/D3 and PCNA, and activated Akt/mTOR and ERK1/2 in the mammary glands of pubertal mice. These results strongly suggest that niacin stimulates mammary gland development in pubertal mice through the Akt/mTOR and ERK1/2 signaling pathways and that the Gi protein-coupled receptor is essential for this function.
A dynamic normalization model of temporal attention
Authors: Denison Rachel N. , Carrasco Marisa , Heeger David J. 
Published: December 2019

AbstractVision is dynamic, handling a continuously changing stream of input, yet most models of visual attention are static. Here, we develop a dynamic normalization model of visual temporal attention and constrain it with new psychophysical human data. We manipulated temporal attention–the prioritization of visual information at specific points in time–to a sequence of two stimuli separated by a variable time interval. Voluntary temporal attention improved perceptual sensitivity only over a specific interval range. To explain these data, we modeled voluntary and involuntary attentional gain dynamics. Voluntary gain enhancement took the form of a limited resource over short time intervals, which recovered over time. Taken together, our theoretical and experimental results formalize and generalize the idea of limited attentional resources across space at a single moment to limited resources across time at a single location.
Distinct relations of microtubules and actin filaments with dendritic architecture
Authors: Nanda Sumit , Bhattacharjee Shatabdi , Cox Daniel N. , Ascoli Giorgio A. 
Published: December 2019

SummaryMicrotubules and F-actin have long been recognized as key regulators of dendritic morphology. Nevertheless, precisely ascertaining their distinct influences on dendritic trees have been hampered until now by the lack of direct, arbor-wide cytoskeletal quantification. We pair live confocal imaging of fluorescently labeled dendritic arborization (da) neurons in Drosophila larvae with complete multi-signal neural tracing to separately measure microtubules and F-actin. We demonstrate that dendritic arbor length is highly interrelated with local microtubule quantity, whereas local F-actin enrichment is associated with dendritic branching. Computational simulation of arbor structure solely constrained by experimentally observed subcellular distributions of these cytoskeletal components generated synthetic morphological and molecular patterns statistically equivalent to those of real da neurons, corroborating the efficacy of local microtubule and F-actin in describing dendritic architecture. The analysis and modeling outcomes hold true for the simplest (Class I), most complex (Class IV), and genetically altered (Formin3 overexpression) da neuron types.SUPPORT: NIH R01 NS39600 and NS086082 and BICCN U01 MH114829.
Detection of genome-wide low-frequency mutations with Paired-End and Complementary Consensus Sequencing (PECC-Seq) revealed end-repair derived artifacts as residual errors
Authors: You Xinyue , Thiruppathi Suresh , Liu Weiying , Cao Yiyi , Naito Mikihiko , Furihata Chie , Honma Masamitsu , Luan Yang , Suzuki Takayoshi 
Published: December 2019

ABSTRACTTo improve the accuracy and the cost-efficiency of next-generation sequencing in ultralow-frequency mutation detection, we developed the Paired-End and Complementary Consensus Sequencing (PECC-Seq), a PCR-free duplex consensus sequencing approach. PECC-Seq employed shear points as endogenous barcodes to identify consensus sequences from the overlap in the shortened, complementary DNA strands-derived paired-end reads for sequencing error correction. With the high accuracy of PECC-Seq, we identified the characteristic base substitution errors introduced by the end-repair process of mechanical fragmentation-based library preparations, which were prominent at the terminal 6 bp of the library fragments in the 5’-NpCpA-3’ or 5’-NpCpT-3’ trinucleotide context. As demonstrated at the human genome scale (TK6 cells), after removing these potential end-repair artifacts from the terminal 6 bp, PECC-Seq could reduce the sequencing error frequency to mid-10−7with a relatively low sequencing depth. For TA base pairs, the background error rate could be suppressed to mid-10−8. In mutagen-treated TK6, slight increases in mutagen treatment-related mutant frequencies could be detected, indicating the potential of PECC-Seq in detecting genome-wide ultra-rare mutations. In addition, our finding on the patterns of end-repair artifacts may provide new insights in further reducing technical errors not only for PECC-Seq, but also for other next-generation sequencing techniques.
The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification
Authors: Wells Carrow I. , Al-Ali Hassan , Andrews David M. , Asquith Christopher R. M. , Axtman Alison D. , Chung Mirra , Dikic Ivan , Ebner Daniel , Elkins Jonathan M. , Ettmayer Peter , Fischer Christian , Frederiksen Mathias , Gray Nathanael S. , Hatch Stephanie , Knapp Stefan , Lee Shudong , Lücking Ulrich , Michaelides Michael , Mills Caitlin E. , Müller Susanne , Owen Dafydd , Picado Alfredo , Ramadan Kristijan , Saikatendu Kumar S. , Schröder Martin , Stolz Alexandra , Tellechea Mariana , Treiber Daniel K. , Turunen Brandon J. , Vilar Santiago , Wang Jinhua , Zuercher William J. , Willson Timothy M. , Drewry David H. 
Published: December 2019

AbstractWe describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS) is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
Discovery of dual inhibitors of KPC-3 and KPC-15 of Klebsiella pneumoniae – an in-silico molecular docking and dynamics study
Authors: Sharma Sony , Kumar-M Praveen , Singh Santa , Sohal Ajay , Yadav Rohitash , Gupta Nitin 
Published: December 2019

AbstractBackgroundThe development of carbapenem resistance against Klebsiella pneumoniae is a situation of grave concern and requires urgent attention. Among the KPC produced by K.pneumoniae, KPC-3, and KPC-15, play a significant role in the development of resistance to carbapenem.Materials and methodsThe binding sites of KPC-3 and KPC-15 were predicted by the COACH server. Drug-like ligands from ZINC were then screened by ligand-based drug screening (LBVS) by keeping Relebactam as a template. The top 50,000 selected ligands were then screened by structure-based virtual screening using idock. For keeping an account of the dual inhibitors’ stability in complex with KPC-3 and KPC-15, MDS were carried out for each complex.ResultsBased on consensus weighted ranks, the top 3 ligands with the dual inhibitory property are ZINC76060350 (consensus weighted rank - 1.5), ZINC05528590 (2), ZINC72290395 (3.5). All the top 3 dual inhibitors have a reasonable probability of passing through the blood-brain barrier. The RDKit and Morgan fingerprint scores between Relebactam and the top three ligands were 0.24, 0.22, 0.23, and 0.26, 0.19, 0.25, respectively (showing only 20% similarity). The MD simulation result revealed good binding stability of ligand ZINC05528590 with both KPC-3 and KPC-15, whereas ligand ZINC76060350 showed good binding stability to KPC-3.ConclusionThe ligand ZINC05528590 could be taken forward to develop a new drug against a multi-resistant- Klebsiella pneumoniae infection. At the same time, ZINC76060350 can be considered to develop a new drug against KPC-15 resistant Klebsiella pneumoniae.
An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of a-synuclein
Authors: Kara Eleanna , Crimi Alessandro , Wiedmer Anne , Emmenegger Marc , Manzoni Claudia , Bandres-Ciga Sara , D’Sa Karishma , Reynolds Regina H , Botía Juan A , Losa Marco , Lysenko Veronika , Carta Manfredi , Heinzer Daniel , Avar Merve , Chincisan Andra , Blauwendraat Cornelis , Ruiz Sonia Garcia , Pease Daniel , Mottier Lorene , Carrella Alessandra , Schneider Dezirae , Magalhaes Andreia , Aemisegger Caroline , Theocharides Alexandre P A , Fan Zhanyun , Marks Jordan D , Hopp Sarah C , Lewis Patrick , Ryten Mina , Hardy John , Hyman Bradley T , Aguzzi Adriano 
Published: December 2019

SummaryNeuropathological and experimental evidence suggests that the cell-to-cell transfer of a-synuclein has an important role in the pathogenesis of Parkinson’s disease (PD). However, the mechanism underlying this phenomenon is not fully understood. We undertook an siRNA, genome-wide high throughput screen to identify genes regulating the cell-to-cell transfer of a-synuclein. We transiently transfected HEK cells stably overexpressing a-synuclein with a construct encoding GFP-2a-aSynuclein-RFP. The cells expressing a-synuclein-RFP through transfection were double positive for GFP and RFP fluorescence, whereas the cells receiving it through transfer were positive only for RFP fluorescence. The amount of a-synuclein transfer was quantified by high content microscopy. A series of unbiased screens confirmed the involvement of 38 genes in the regulation of a-synuclein-RFP transfer. One of those hits wasITGA8, a candidate gene recently identified through a large PD genome wide association study (GWAS). Weighted gene co-expression network analysis (WGCNA) and weighted protein-protein network interaction analysis (WPPNIA) showed that the hits clustered in networks that included known PD Mendelian and GWAS risk genes more frequently than expected than random chance. Given the genetic overlap between a-synuclein transfer and PD, those findings provide supporting evidence for the importance of the cell-to-cell transfer of a-synuclein in the pathogenesis of PD, and expand our understanding of the mechanism of a-synuclein spread.
Towards innovation, co-creation and customers’ satisfaction: a banking sector perspective
Authors: Malik Muhammad Imran , Ahsan Rizwan 
Published: December 2019

PurposeCo-creation fosters customer’s involvement for innovation in products/services and is used as a tool to develop competitive edge for better entrepreneurship. Based on limited evidence, the study aims to examine the factors contributing to the co-creation and the relationship of co-creation with customer satisfaction.Design/methodology/approachA sample of 384 customers from selected banks in Pakistan was selected. The study adopted quantitative, explanatory and cross-sectional research design. Structural equation modeling is used for analysis.FindingsThe results revealed a positive and significant relationship between co-creation with customer satisfaction. Further results revealed that access to information, risk assessment and transparency have a positive relationship with co-creation for innovation. The study is significant for customers and management of banks to understand the implications of co-creation to increase customer satisfaction.Research limitations/implicationsFew banks with a small number of customers were selected for the study.Practical implicationsManagers must consider customer’s access to information, risk assessment and transparency of information as necessary factors for co-creation that foster innovation and entrepreneurial opportunities because co-creation strengthens customer satisfaction.Social implicationsAdopting the co-creation process brings long-lasting harmony between customers and banks, and customers may consider the banks as being socially responsible by inviting the opinions of their customers.Originality/valueModel is re-tested in the context of Pakistani banks with selected variables affecting co-creation for innovation. Moreover, the relationship of co-creation with customer satisfaction is examined.