bluuebunny/crossref_metadata_2025_split huggingface dataset:
A subpopulation of Talin 1 resides in the nucleus and regulates gene expression
Authors: Da Silva Alejandro J. , Hästbacka Hendrik S. E. , Puustinen Mikael C. , Pessa Jenny C. , Goult Benjamin T. , Jacquemet Guillaume , Henriksson Eva , Sistonen Lea 
Published: March 2022

AbstractTalin 1 (TLN1) is best known for its role at focal adhesions, where it activates β-integrin receptors and transmits mechanical stimuli to the actin cytoskeleton. Interestingly, the localization of TLN1 is not restricted to the focal adhesions, but its function in other cellular compartments remains poorly understood. By utilizing both biochemical and confocal microscopy analyses, we show that TLN1 localizes to the nucleus and that it strongly interacts with the chromatin. Importantly, depletion of endogenous TLN1 results in extensive changes in the gene expression profile of human breast epithelial cells. To determine the impact of nuclear TLN1 on gene regulation, we expressed a TLN1 fusion protein containing a nuclear localization signal. Our results revealed that nuclear TLN1 regulates a specific subset of the TLN1-dependent genes. Taken together, we show that apart from localizing at the plasma membrane and cytoplasm, TLN1 also resides in the nucleus where it functions in the regulation of gene expression.
High resolution reconstruction of a Jumbo bacteriophage infecting capsulated bacteria using hyperbranched tail fibers
Authors: Ouyang Ruochen , Costa Ana Rita , Cassidy C. Keith , Otwinowska Aleksandra , Williams Vera C. J. , Latka Agnieszka , Stansfeld Phill J. , Drulis-Kawa Zusanna , Briers Yves , Pelt Daan M. , Brouns Stan J. J. , Briegel Ariane 
Published: March 2022

SUMMARYTheKlebsiellajumbo myophage ϕKp24 displays an unusually complex arrangement of tail fibers interacting with a host cell. In this study, we combined cryo-electron microscopy methods, protein structure prediction methods, molecular simulations, and machine learning approaches to explore the capsid, tail, and tail fibers of this phage at high resolution. We determined the structure of the capsid and tail at 4.3Å and 4.1Å resolution. We observed that the tail fibers were highly branched and rearranged dramatically upon cell surface attachment. This complex configuration involves fourteen putative tail fibers with depolymerase activity that provide ϕKp24 with the ability to infect a broad panel of capsular polysaccharide (CPS) types ofKlebsiella pneumoniae. Taken together, our study provides structural and functional insight into how ϕKp24 adapts to the highly variable surfaces of capsulated bacterial pathogens, which will be useful for the development of phage therapy approaches against pan-drug resistantK. pneumoniaestrains.
Endogenous IL-10 Contributes to Wound Healing and Regulates Tissue Repair
Authors: Short Walker D. , Rae Meredith , Lu Thomas , Padon Benjamin , Prajapati Tanuj J. , Faruk Fayiz , Olutoye Oluyinka O. , Yu Ling , Bollyky Paul , Keswani Sundeep G. , Balaji Swathi 
Published: March 2022

AbstractBackgroundInterleukin-10 (IL-10) is essential in fetal regenerative wound healing and likewise promotes a regenerative phenotype in adult dermal wounds. However, the role of endogenous IL-10 in postnatal dermal wound healing is not well established. We sought to determine the role of IL-10 in murine full thickness, excisional wounds that are splinted to prevent contracture and mimic human patterns of wound closure.MethodsFull thickness, excisional wounds were made in wildtype (WT) and IL-10-/-mice on a C57BL/6J background (F/M, 8wks old). In a subset of wounds, contraction was prevented by splinting with silicone stents (stenting) and maintaining a moist wound microenvironment using a semi-occlusive dressing. Wounds were examined for re-epithelialization, granulation tissue deposition, and inflammatory cell infiltrate at day 7 and fibrosis and scarring at day 30 post-wounding.ResultsWe observed no difference in wound healing rate between WT and IL-10-/-mice in either the stented or unstented group. At day 7, unstented IL-10-/-wounds had a larger granulation tissue area and more inflammatory infiltrate than their WT counterparts. However, we did observe more F4/80+cell infiltrate in stented IL-10-/-wounds at day 7. At day 30, stented wounds had increased scar area and epithelial thickness compared to unstented wounds.ConclusionsThese data suggest that endogenous IL-10 expression does not alter closure of full thickness excisional wounds when wound hydration and excessive contraction are controlled. However, the loss of IL-10 leads to increased inflammatory cell infiltration and scarring. These data suggest that previous reports of increased rates of healing in IL-10-/-mice ought to be revisited considering recent advances in wound healing models. Moreover, these new findings suggest that IL-10 contributes to regulation of inflammation without compromising the healing response.
Characterisation of TbSmee1 indicates that endocytosis is required for access of surface-bound cargo to the trypanosome flagellar pocket
Authors: Schichler Daja , Konle Antonia , Spath Eva-Maria , Riegler Sina , Klein Alexandra , Seleznev Anna , Jung Sisco , Wuppermann Timothy , Wetterich Noah , Borges Alyssa , Meyer-Natus Elisabeth , Havlicek Katharina , Cabrera Sonia Pérez , Niedermüller Korbinian , Sajko Sara , Dohn Maximilian , Malzer Xenia , Riemer Emily , Tumurbaatar Tuguldur , Djinovic-Carugo Kristina , Dong Gang , Janzen Christian J. , Morriswood Brooke 
Published: March 2022

AbstractAll endo- and exocytosis in the African trypanosomeTrypanosoma bruceioccurs at a single subdomain of the plasma membrane. This subdomain, the flagellar pocket, is a small vase-shaped invagination containing the root of the cell’s single flagellum. Several cytoskeleton-associated multiprotein complexes are coiled around the neck of the flagellar pocket on its cytoplasmic face. One of these, the hook complex, was proposed to affect macromolecule entry into the flagellar pocket lumen. In previous work, knockdown of the hook complex component TbMORN1 resulted in larger cargo being unable to enter the flagellar pocket. In this study, the hook complex component TbSmee1 was characterised in bloodstream formTrypanosoma bruceiand was found to be essential for cell viability. TbSmee1 knockdown resulted in flagellar pocket enlargement and impaired access to the flagellar pocket membrane by surface-bound cargo, similar to depletion of TbMORN1. Unexpectedly, inhibition of endocytosis by knockdown of clathrin phenocopied TbSmee1 knockdown, suggesting that endocytic activity itself is a prerequisite for the entry of surface-bound cargo into the flagellar pocket.SummaryCharacterisation of the essential trypanosome protein TbSmee1 suggests that endocytosis is required for flagellar pocket access of surface-bound cargo.
Place cells are non-randomly clustered by field location in CA1 hippocampus
Authors: Wirtshafter Hannah S. , Disterhoft John F. 
Published: March 2022

AbstractA challenge in both modern and historic neuroscience has been achieving an understanding of neuron circuits, and determining the computational and organizational principles that underlie these circuits. Deeper understanding of the organization of brain circuits and cell types, including in the hippocampus, is required for advances in behavioral and cognitive neuroscience, as well as for understanding principles governing brain development and evolution. In this manuscript, we pioneer a new method to analyze the spatial clustering of active neurons in the hippocampus. We use calcium imaging and a rewarded navigation task to record from 100s of place cells in the CA1 of freely moving rats. We then use statistical techniques developed for and in widespread use in geographic mapping studies, global Moran’s I and local Moran’s I to demonstrate that cells that code for similar spatial locations tend to form small spatial clusters. We present evidence that this clustering is not the result of artifacts from calcium imaging, and show that these clusters are primarily formed by cells that have place field around previously rewarded locations. We go on to show that, although cells with similar place fields tend to form clusters, there is no obvious topographic mapping of environmental location onto the hippocampus, such as seen in the visual cortex. Insights into hippocampal organization, as in this study, can elucidate mechanisms underlying motivational behaviors, spatial navigation, and memory formation.
APOE ɛ2 vs APOE ɛ4 dosage shows sex-specific links to hippocampus-default network subregion co-variation
Authors: Savignac Chloé , Villeneuve Sylvia , Badhwar AmanPreet , Saltoun Karin , Shafighi Kimia , Zajner Chris , Sharma Vaibhav , Taliun Sarah A Gagliano , Farhan Sali , Poirier Judes , Bzdok Danilo 
Published: March 2022

AbstractAlzheimer’s disease and related dementias (ADRD) are marked by intracellular tau aggregates in the medial-temporal lobe (MTL) and extracellular amyloid aggregates in the default network (DN). Here, we sought to clarify ADRD-related co-dependencies between the MTL’s most vulnerable structure, the hippocampus (HC), and the highly associative DN at a subregion resolution. We confronted the effects of APOE ɛ2 and ɛ4, rarely investigated together, with their impact on HC-DN co-variation regimes at the population level. In a two-pronged decomposition of structural brain scans from ∼40,000 UK Biobank participants, we located co-deviating structural patterns in HC and DN subregions as a function of ADRD family risk. Across the disclosed HC-DN signatures, recurrent deviations in the CA1, CA2/3, molecular layer, fornix’s fimbria, and their cortical partners related to ADRD risk. Phenome-wide profiling of HC-DN co- variation expressions from these population signatures revealed male-specific associations with air-pollution, and female-specific associations with cardiovascular traits. We highlighted three main factors associated with brain-APOE associations across the different gene variants: happiness, and satisfaction with friendships, and with family. We further showed that APOE ɛ2/2 interacts preferentially with HC-DN co-variation patterns in estimating social lifestyle in males and physical activity in females. Our findings reinvigorate the often-neglected interplay between APOE ɛ2 dosage and sex, which we have linked to fine-grained structural divergences indicative of ADRD susceptibility.
The Use and Misuse of Composite Environmental Indices
Authors: Fischer Shelley M. , Joy Michael K. , Abrahamse Wokje , Milfont Taciano L. , Petherick Lynda M. 
Published: March 2022

AbstractComposite indices have been widely used to rank the environmental performance of nations. Such environmental indices can be useful in communicating complex information as a single value and have the potential to generate political and media awareness of environmental issues. However, indices that are poorly constructed can hinder efforts to identify environmental failings. Here, we provide a critical review of the theoretical and methodological foundations of environmental indices to enhance our understanding of the accuracy and applicability of such indices. In the present study we classify existing indices according to ranking goal, measurement components, and weighting methods. Using New Zealand and Niger as case studies, we examine correlations between ranks in ten national level indices to outline how measurement components and the goal of ranking itself may provide a more, or less, optimistic view of the state of a country’s environment. Our results suggest that environmental indices that include human health, socioeconomic, and policy indicators (such as human access to sanitation and clean drinking water) are positively correlated with each other, and that those excluding human health, socioeconomic, and policy indicators are also positively correlated with each other, while these two types of environmental indices are negatively correlated to each other. Our results demonstrate that the inclusion of indicators that do not relate to the actual state of natural environments can confound results. When choosing an existing environmental index – or developing a new one – it is important to assess whether the ranking goal and the included indicators are appropriate. This is important because the inclusion of confounding indicators in environmental indices may misrepresent the actual state of natural environments.
Improved sensitivity and resolution of ATAC-seq differential DNA accessibility analysis
Authors: Sheikh Ahmed Ali , Blais Alexandre 
Published: March 2022

AbstractEukaryotic genomes are packaged into chromatin, and the extent of its compaction must be modulated to allow several biological processes such as gene transcription. The regulatory elements of expressed genes are typically in relatively accessible chromatin, and several studies have revealed a reliable correlation between the abundance of mRNA transcripts and the degree of DNA accessibility at the regulatory elements of their coding genes. In consequence, the genome-wide profiling of DNA accessibility by methods such as ATAC-seq can help in the study of gene regulatory networks by serving as a proxy for gene expression and by helping identify important gene cis-regulatory elements and the trans-acting factors that bind them. The predominant approach used to identify differentially accessible genomic loci from ATAC-seq data obtained in two conditions of interest is comparable to that employed in RNA-seq gene expression profiling studies: accessible regions are identified through peak calling and treated like “genes”, then sequenced DNA fragments (originating from two neighboring transposase insertion events) that overlap them are counted and subjected to abundance modeling, which then allows to identify those that have a significant difference between the two conditions. We reasoned that this approach could be improved in terms of sensitivity and resolution by introducing two changes: bypassing peak calling, using instead a genome-wide sliding window quantification approach, and counting transposase insertion sites, instead of fragments originating from two neighboring insertion sites. We present the development of this approach, which we term “widaR”, for Window- and Insertion-based Differential Accessibility in R, using a murine skeletal myoblast differentiation dataset. Reproducible R code is provided.
CyberSco.Py: open-source software for event-based, conditional microscopy
Authors: Chiron Lionel , LeBec Matthias , Cordier Céline , Pouzet Sylvain , Milunov Dimitrije , Banderas Alvaro , Meglio Jean-Marc Di , Sorre Benoit , Hersen Pascal 
Published: March 2022

AbstractTimelapse fluorescence microscopy imaging is routinely used in quantitative cell biology. However, microscopes could become much more powerful investigation systems if they were endowed with simple unsupervised decision-making algorithms to transform them into fully responsive and automated measurement devices. Here, we report CyberSco.Py, Python software for advanced automated timelapse experiments. We provide proof-of-principle of a user-friendly framework that increases the tunability and flexibility when setting up and running fluorescence timelapse microscopy experiments. Importantly, CyberSco.Py combines real-time image analysis with automation capability, which allows users to create conditional, event-based experiments in which the imaging acquisition parameters and the status of various devices can be changed automatically based on the image analysis. We exemplify the relevance of CyberSco.Py to cell biology using several use case experiments with budding yeast. We anticipate that CyberSco.Py could be used to address the growing need for smart microscopy systems to implement more informative quantitative cell biology experiments.
Structural and functional analysis of the D-alanyl carrier protein ligase DltA from Staphylococcus aureus Mu50
Authors: Lee In-Gyun , Song Chiman , Yang Seoyeong , Jeon Hanul , Park Jingyeong , Yoon Hye-Jin , Im Hookang , Kang Sung-Min , Eun Hyun-Jong , Lee Bong-Jin 
Published: March 2022

D-Alanylation of the teichoic acids of the Gram-positive bacterial cell wall plays crucial roles in bacterial physiology and virulence. Deprivation of D-alanine from the teichoic acids of Staphylococcus aureus impairs biofilm and colony formation, induces autolysis and ultimately renders methicillin-resistant S. aureus highly susceptible to antimicrobial agents and host defense peptides. Hence, the D-alanylation pathway has emerged as a promising antibacterial target against drug-resistant S. aureus. D-Alanylation of teichoic acids is mediated via the action of four proteins encoded by the dlt operon, DltABCD, all four of which are essential for the process. In order to develop novel antimicrobial agents against S. aureus, the D-alanyl carrier protein ligase DltA, which is the first protein in the D-alanylation pathway, was focused on. Here, the crystal structure of DltA from the methicillin-resistant S. aureus strain Mu50 is presented, which reveals the unique molecular details of the catalytic center and the role of the P-loop. Kinetic analysis shows that the enantioselectivity of S. aureus DltA is much higher than that of DltA from other species. In the presence of DltC, the enzymatic activity of DltA is increased by an order of magnitude, suggesting a new exploitable binding pocket. This discovery may pave the way for a new generation of treatments for drug-resistant S. aureus.
Protein dynamics developments for the large scale and cryoEM: case study of ProDy 2.0
Authors: Krieger James Michael , Sorzano Carlos Oscar S. , Carazo Jose Maria , Bahar Ivet 
Published: March 2022

Cryo-electron microscopy (cryoEM) has become a well established technique with the potential to produce structures of large and dynamic supramolecular complexes that are not amenable to traditional approaches for studying structure and dynamics. The size and low resolution of such molecular systems often make structural modelling and molecular dynamics simulations challenging and computationally expensive. This, together with the growing wealth of structural data arising from cryoEM and other structural biology methods, has driven a trend in the computational biophysics community towards the development of new pipelines for analysing global dynamics using coarse-grained models and methods. At the centre of this trend has been a return to elastic network models, normal mode analysis (NMA) and ensemble analyses such as principal component analysis, and the growth of hybrid simulation methodologies that make use of them. Here, this field is reviewed with a focus on ProDy, the Python application programming interface for protein dynamics, which has been developed over the last decade. Two key developments in this area are highlighted: (i) ensemble NMA towards extracting and comparing the signature dynamics of homologous structures, aided by the recent SignDy pipeline, and (ii) pseudoatom fitting for more efficient global dynamics analyses of large and low-resolution supramolecular assemblies from cryoEM, revisited in the CryoDy pipeline. It is believed that such a renewal and extension of old models and methods in new pipelines will be critical for driving the field forward into the next cryoEM revolution.
Influence of social support on individual health knowledge adoption in online diabetes communities: the mediating role between cognition and emotion
Authors: Zhao Haibao , Wang Jianya , Zhang Huiqing 
Published: March 2022

PurposeTo address the problem of how to guide and promote health knowledge adoption, based on online diabetes communities, this study explores the impact mechanism of social support on users' individual health knowledge adoption to provide insights for online diabetes community management and personal health management.Design/methodology/approachIntegrating the theories of cognitive-affective personality system (CAPS) and social support, this study constructs a theoretical model, collects data through a questionnaire and uses a structural equation model to analyse 356 data.FindingsThe results show that: (1) Considering the online diabetes communities, it is reasonable to divide social support into emotional, information, network and respect support. (2) Social support affects individual health knowledge adoption through the intermediaries of knowledge argument quality, knowledge source credibility and positive emotions. (3) The order of the mediating effect of cognitive and emotional factors between social support and health knowledge adoption is knowledge argument quality > knowledge source credibility > positive emotions and rationality > sensibility. (4) Users pay more attention to the source credibility of professional health knowledge than that of experiential health knowledge.Originality/valueThis research expands the application scope of CAPS and opens the “black box” of the impact of social support on individual health knowledge adoption behaviour. Simultaneously, the dimensions of social support and the mediating effect between social support and the two types of health knowledge are discussed.
Towards blockchain led decentralized autonomous organization (DAO) business model innovations
Authors: Saurabh Kumar , Rani Neelam , Upadhyay Parijat 
Published: March 2022

PurposeToday, business model innovations leverage digital technologies to gain a competitive advantage and transform business processes. Blockchain is still gaining attention in specific fields and bringing value to business models. There is a dearth of research on how blockchain decentralized autonomous organizations impact organization business model innovations. This study attempts to contribute the body of knowledge based on a review of decentralized autonomous organizations and the business model innovation literature using the integrative and generative approach.Design/methodology/approachThe paper offers an analysis of decentralized autonomous organizations based on digital business models built on the well-established work by Osterwalder and Pigneur (2010). The practical multilayered decentralized autonomous organizations architectural implementation model design is achieved using practical archetypes depicted in the proposed decentralized autonomous organizations business model. The paper evaluates a marketplace comprising 13 decentralized autonomous organizations led platforms with core functionalities.FindingsThe paper delivers decentralized autonomous organizations led digital business model canvas elements to explain decentralized autonomous organization business model innovations. It presents the underlying multilayered decentralized autonomous organizations architectural implementation model required to conceptualize a practical business model with an enterprise-ready target operating model.Research limitations/implicationsThe paper contributes directly to the practical decentralized autonomous organizations business model canvas, exemplifying the nine elements of decentralized autonomous organizations’ characteristics for any organizational transformation. The tools and accelerators (business model, layered architecture, target operating model and product mapping) developed in the paper address the managerial challenges of redesigning the decentralized business models.Originality/valueThe proposed decentralized autonomous organizations smart contract powered business model provide a digital platform to adhere to rules, follow policies, preserve principles and develop consensus without human interventions. The paper shapes the first of its kind decentralized autonomous organizations marketplace evaluation while mapping it to decentralized autonomous organizations layered architecture product requirement considering business model dimension to adopt actionable target operating model.