bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photons guided by axons may enable backpropagation-based learning in the brain
Authors: Zarkeshian Parisa , Kergan Taylor , Ghobadi Roohollah , Nicola Wilten , Simon Christoph 
Published: March 2022

ABSTRACTDespite great advances in explaining synaptic plasticity and neuron function, a complete understanding of the brain’s learning algorithms is still missing. Artificial neural networks provide a powerful learning paradigm through the backpropagation algorithm which modifies synaptic weights by using feedback connections. Backpropagation requires extensive communication of information back through the layers of a network. This has been argued to be biologically implausible and it is not clear whether backpropagation can be realized in the brain. Here we suggest that biophotons guided by axons provide a potential channel for backward transmission of information in the brain. Biophotons have been experimentally shown to be produced in the brain, yet their purpose is not understood. We propose that biophotons can propagate from each post-synaptic neuron to its pre-synaptic one to carry the required information backward. To reflect the stochastic character of biophoton emissions, our model includes the stochastic backward transmission of teaching signals. We demonstrate that a three-layered network of neurons can learn the MNIST handwritten digit classification task using our proposed backpropagation-like algorithm with stochastic photonic feedback. We model realistic restrictions and show that our system still learns the task for low rates of biophoton emission, information-limited (one bit per photon) backward transmission, and in the presence of noise photons. Our results suggest a new functionality for biophotons and provide an alternate mechanism for backward transmission in the brain.
UniFuncNet: a flexible network annotation framework
Authors: Queirós Pedro , Hickl Oskar , Arbas Susana Martínez , Wilmes Paul , May Patrick 
Published: March 2022

AbstractSummaryFunctional annotation is an integral part in the analysis of organisms, as well as of multi-species communities. A common way to integrate such information is using biological networks. However, current data integration network tools are heavily dependent on a single source of information, which might strongly limit the amount of relevant data contained within the network. Here we present UniFuncNet, a network annotation framework that dynamically integrates data from multiple biological databases, thereby enabling data collection from various sources based on user preference. This results in a flexible and comprehensive data retrieval framework for network based analyses of omics data. Importantly, UniFuncNet’s data integration methodology allows for the output of a non-redundant composite network and associated metadata. In addition, a workflow exporting UniFuncNet’s output to the graph database management system Neo4j was implemented, which allows for efficient querying and analysis.AvailabilitySource code is available at https://github.com/PedroMTQ/UniFuncNet.
Microarray profiling of hypothalamic gene expression changes in Huntington’s disease mouse models
Authors: Dickson Elna , Dwijesha Amoolya Sai , Andersson Natalie , Lundh Sofia , Björkqvist Maria , Petersén Åsa , Soylu-Kucharz Rana 
Published: March 2022

AbstractStructural changes and neuropathology in the hypothalamus have been suggested to contribute to the non-motor manifestations of Huntington’s disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene. In the present study, we investigated whether transcriptional changes would be part of hypothalamic pathology induced by the disease-causing huntingtin (HTT) protein. We performed microarray analysis using the Affymetrix platform on total hypothalamic RNA isolated from two HD mouse models and their littermate controls; BACHD mice with ubiquitous expression of full-length mutant HTT (mHTT) and wild-type mice with targeted hypothalamic overexpression of either wild-type HTT (wtHTT) or mHTT fragments. To analyze microarray datasets (34760 variables) and obtain functional implications of differential expression patterns, we used Linear Models for Microarray Data (limma) followed by Gene Set Enrichment Analysis (GSEA) using ClusterProfiler. Limma identified 735 and 721 significantly differentially expressed genes (adjusted p < 0.05) in hypothalamus of AAV datasets wtHTT vs control and mHTT vs control. In contrast, for BACHD datasets and the AAV mHTT vs. wtHTT dataset, none of the genes were differentially expressed (adjusted p-value > 0.05 for all probe IDs). In AAV groups, from the combined limma with GSEA using ClusterProfiler, we found both shared and unique gene sets and pathways for mice with wtHTT overexpression compared to mice with mHTT overexpression. mHTT caused widespread suppression of neuroendocrine networks, as evident by GSEA enrichment of GO-terms related to neurons and/or specific neuroendocrine populations. Using qRT-PCR, we confirmed that mHTT overexpression caused significant downregulation of key enzymes involved in neuropeptide synthesis, including histidine and dopa decarboxylases, compared to wtHTT overexpression. Multiple biosynthetic pathways such as sterol synthesis were among the top shared processes, where both unique and shared genes constituted leading-edge subsets. In conclusion, mice with targeted overexpression of HTT (wtHTT or mHTT) in the hypothalamus show dysregulation of pathways, of which there are subsets of shared pathways and pathways unique to either wtHTT or mHTT overexpression.
Zika virus NS4A hijacks host ANKLE2 to promote viral replication
Authors: Fishburn Adam T , Kenaston Matthew W , Lopez Nicholas J , Hoang Vivian , Shiu Traci N , Haggard Arcé Sophia T , Khan Shahabal S , Shah Priya S 
Published: March 2022

AbstractZika virus (ZIKV) is infamous among flaviviruses for its unique association with congenital birth defects, notably microcephaly. We previously mapped ZIKV-host protein interactions and identified the interaction between ZIKV NS4A and host ANKLE2, which itself has established ties to congenital microcephaly. In fruit flies, NS4A induces microcephaly phenotypes in an ANKLE2-dependent manner. This suggests that NS4A interacts with ANKLE2 to dysregulate cell behavior and contributes to abnormal host neurodevelopment. Here, we explore the role of ANKLE2 in ZIKV replication to understand the biological significance of the interaction from the viral perspective. We show that knockdown of ANKLE2 reduces replication of two ZIKV strains, across multiple MOIs and timepoints. We observe that localization of ANKLE2 is drastically shifted to sites of NS4A accumulation during infection. We investigate which domains of ANKLE2 mediate this behavior and the interaction with NS4A. Using co-immunoprecipitation, we show that deletion of either the transmembrane or LEM domain has little impact on the interaction, but deletion of both significantly reduces interaction with NS4A. We show that the C-terminal transmembrane domains of NS4A stabilize the interaction with ANKLE2. Finally, we explore this interaction in other flaviviruses and observe ANKLE2 interacts with NS4A across four additional mosquito-borne flaviviruses. Together, these results suggest NS4A interacts with ANKLE2 through a combination of its transmembrane and LEM domains, bringing it to sites of ZIKV replication to promote replication through an unknown mechanism. Taken together with our previous results, our findings indicate that, in the process of hijacking ANKLE2 for replication, ZIKV disrupts its physiological function to cause disease.ImportanceThe ZIKV epidemic led to the astonishing revelation that congenital ZIKV infection is associated with devastating birth defects, including microcephaly. Microcephaly is the condition in which head and brain size are severely reduced, and is often accompanied by intellectual disability. The molecular mechanisms by which ZIKV replicates and causes microcephaly are still incompletely understood. We previously identified the protein interaction between ZIKV NS4A and host ANKLE2, which is associated with congenital microcephaly. In flies, NS4A induces microcephaly in an ANKLE2-dependent manner, suggesting this interaction is crucial for ZIKV pathogenesis. Here, we explore the relevance of this physical interaction for virus replication. We find that ANKLE2 promotes ZIKV replication, concentrates at sites of NS4A accumulation during infection, and interacts with NS4A via its N-terminal domain. Thus, this represents a rare example of a ZIKV-host protein interaction that impacts both disease and virus replication.
Molecular Dynamics simulation of TDP-43 RRM in the presence and absence of RNA
Authors: Scott David Donald , Mowrey David , Nagarajan Karthi , François-Moutal Liberty , Nair Anil , Khanna May 
Published: March 2022

AbstractStructural characterization of the prion prone TAR DNA Binding protein (TDP)-43 has been challenging since its intrinsically disordered regions represents 15-30% of the total protein. TDP-43 is a nucleic acid binding protein with an N-terminal domain, two RNA Recognition Motifs (RRM1 and RRM2) and the C-terminal domain. In this study, we seek to define possible new targetable sites on the apo structure of TDP-43 RRM domains. To do so, we used molecular dynamic (MD) simulations on the NMR solved TDP-43RRM1-2 structure bound to RNA to predict the apo structure. Contact analysis of TDP-43 showed that while the integrity of the individual domains was maintained upon RNA removal, a decrease in interdomain contacts was observed. Moreover, we compared apo TDP-43 structures obtained from MD to AlphaFold 2 (AF2) predicted TDP-43 structures and found differences in loop regions. A Sitemap analysis identified five druggable sites for the RNA bound structure solved by NMR, while fewer sites were identified following MD simulations and AF2 predicted apo structures.
Chlamydia trachomatis suppresses host cell store-operated Ca2+ entry and inhibits NFAT/calcineurin signaling
Authors: Chamberlain Nicholas B. , Hackstadt Ted 
Published: March 2022

AbstractThe obligate intracellular bacterium, Chlamydia trachomatis, replicates within a parasitophorous vacuole termed an inclusion. During development, host proteins critical for regulating intracellular calcium (Ca2+) homeostasis interact with the inclusion membrane. The inclusion membrane protein, MrcA, interacts with the inositol-trisphosphate receptor (IP3R), an ER cationic channel that conducts Ca2+. Stromal interaction molecule 1 (STIM1), an ER transmembrane protein important for regulating store-operated Ca2+ entry (SOCE), localizes to the inclusion membrane via an uncharacterized interaction. We therefore examined Ca2+ mobilization in C. trachomatis infected cells. Utilizing a variety of Ca2+ indicators to assess changes in cytosolic Ca2+ concentration, we demonstrate that C. trachomatis impairs host cell SOCE. Ca2+ regulates many cellular signaling pathways. We find that the SOCE-dependent NFAT/calcineurin signaling pathway is impaired in C. trachomatis L2 infected HeLa cells and likely has major implications on host cell physiology as it relates to C. trachomatis pathogenesis.
A novel conserved protein in Streptococcus agalactiae, BvaP, is important for vaginal colonization and biofilm formation
Authors: Thomas Lamar S. , Cook Laura C. 
Published: March 2022

ABSTRACTStreptococcus agalactiae (Group B Strep, GBS) infections in neonates are often fatal and strongly associated with maternal GBS vaginal colonization. Here, we investigated the role of a previously uncharacterized protein, BvaP, in GBS vaginal colonization. BvaP was previously identified as the most highly upregulated gene in the GBS A909 transcriptome when comparing vaginal colonization to growth in liquid culture. We found that expression of BvaP affects GBS adherence to extracellular matrix components and human vaginal epithelial cells and a ΔbvaP mutant was significantly decreased in its ability to colonize the murine vaginal tract. Cellular morphological alterations such as changes in cell shape, chain length, and clumping were also observed in a knockout mutant strain. Given its high expression in vivo, high degree of conservation among GBS strains, and role in vaginal colonization, BvaP may be an eligible target for GBS vaccination and/or drug therapy.IMPORTANCENeonatal GBS disease is a major cause of morbidity and mortality and maternal vaginal colonization is the leading risk factor for disease. Colonization prevention would greatly impact rates of disease transmission, but vaccine development has stalled as capsular polysaccharide vaccines have low immunogenicity in vivo. While these vaccines are still in development, addition of a protein conjugate may prove fruitful in increasing immunogenicity and strain coverage across GBS serotypes. Previous research identified sak_1753 as a gene very highly upregulated gene during murine vaginal colonization. This study reveals that Sak_1753 is required to maintain proper GBS cellular morphology and colonization phenotypes and is required for in vivo vaginal colonization in a murine model. We have renamed Sak_1753 Group B Strep vaginal adherence protein (BvaP). The findings of this study indicate that BvaP is important in GBS colonization of the vaginal tract and may be a candidate for vaccine development.
Plasma MIA, CRP, and albumin predict cognitive decline in Parkinson’s Disease
Authors: Shen Junchao , Amari Noor , Zack Rebecca , Skrinak R. Tyler , Unger Travis L. , Posavi Marijan , Tropea Thomas F. , Xie Sharon X. , Van Deerlin Vivianna M. , Dewey Richard B. , Weintraub Daniel , Trojanowski John Q. , Chen-Plotkin Alice S. 
Published: March 2022

ABSTRACTObjectiveUsing a multi-cohort, Discovery-Replication-Validation design, we sought new plasma biomarkers that predict which PD individuals will experience cognitive decline.MethodsIn 108 Discovery Cohort PD individuals and 83 Replication Cohort PD individuals, we measured 940 plasma proteins on an aptamer-based platform. Using proteins associating with subsequent cognitive decline in both cohorts, we trained a logistic regression model to predict which PD patients showed fast (>=1 point drop/year on Montreal Cognitive Assessment (MoCA)) vs. slow (<1 point drop/year on MoCA) cognitive decline in the Discovery Cohort, testing it in the Replication Cohort. We developed alternate assays for the top three proteins and confirmed their ability to predict cognitive decline – defined by change in MoCA or development of incident Mild Cognitive Impairment (MCI) or dementia – in a Validation Cohort of 118 PD individuals. We investigated the top plasma biomarker for causal influence by Mendelian randomization.ResultsA model with only three proteins (Melanoma Inhibitory Activity Protein (MIA), C-Reactive Protein (CRP), albumin) separated Fast vs. Slow cognitive decline subgroups with an AUC of 0.80 in the Validation Cohort. Validation Cohort PD individuals in the top quartile of risk for cognitive decline based on this model were 4.4 times more likely to develop incident MCI or dementia than those in the lowest quartile. Genotypes atMIASNP rs2233154 associated with MIA levels and cognitive decline, providing evidence for MIA’s causal influence.ConclusionsAn easily-obtained plasma-based predictor identifies PD individuals at risk for cognitive decline. MIA may participate causally in development of cognitive decline.
Longitudinal assessment of lung function in Swiss childhood cancer survivors
Authors: Kasteler Rahel , Otth Maria , Halbeisen Florian S , Mader Luzius , Singer Florian , Rössler Jochen , von der Weid Nicolas X , Ansari Marc , Kuehni Claudia E 
Published: March 2022

AbstractRationaleChildhood cancer survivors (CCSs) are at increased risk for pulmonary morbidity due to exposure to lung-toxic treatments, including specific chemotherapies, radiotherapy, and surgery. Longitudinal data on lung function, with information on how outcomes change over time, in CCSs are scarce.ObjectivesTo investigate lung function trajectories in childhood cancer survivors over time and investigate the association with lung-toxic treatment.MethodsThis retrospective, multi-center cohort study included CCSs, who were diagnosed between 1990 and 2013 in Switzerland and had been exposed to lung-toxic chemotherapeutics or thoracic radiotherapy. Pulmonary function tests (PFTs) were obtained from hospital charts. We assessed quality of PFTs systematically and calculated z-scores and percentage predicted of forced expiratory volume in first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, total lung capacity (TLC) and diffusion capacity for carbon-monoxide (DLCO) based on recommended reference equations. We described lung function over time and determined risk factors for change in FEV1 and FVC using multivariable linear regression.ResultsWe included 790 PFTs from 183 CCSs, with a median age of 12 years (IQR 7 – 14) at diagnosis. Common diagnoses were lymphoma (55%), leukemia (11%) and CNS tumors (12%). Median follow-up time was 5.5 years. Half (49%) of CCSs had at least one abnormal pulmonary function parameter, with restrictive impairment being common (22%). Trajectories of FEV1 and FVC started at z-scores of -1.5 at diagnosis and remained low throughout follow-up. CCSs treated with thoracic surgery started particularly low, with an FEV1 of -1.08 z-scores (−2.02 to -0.15) and an FVC of -1.42 z-scores (−2.27 to -0.57) compared to those without surgery. In CCS exposed to lung-toxic chemotherapeutics FEV1 z-scores increased slightly over time (0.12 per year; 95%CI 0.02 - 0.21).ConclusionThe large proportion of CCSs with reduced lung function identified in this study underlines the need for more research and long-term surveillance of this vulnerable population.
In depth exploration of the alternative proteome of Drosophila melanogaster
Authors: Fabre Bertrand , Choteau Sebastien A , Duboé Carine , Pichereaux Carole , Montigny Audrey , Korona Dagmara , Deery Michael J. , Camus Mylène , Brun Christine , Burlet-Schiltz Odile , Russell Steven , Combier Jean-Philippe , Lilley Kathryn S , Plaza Serge 
Published: March 2022

AbstractRecent studies have shown that hundreds of small proteins were occulted when protein coding genes were annotated. These proteins, called alternative proteins, have failed to be annotated notably due to the short length of their open reading frame (less than 100 codons) or the enforced rule establishing that messenger RNAs (mRNAs) are monocystronic. Several alternative proteins were shown to be biologically active molecules and seem to be involved in a wide range of biological functions. However, genome wide exploration of the alternative proteome is still limited to a few species. In the present article we describe a deep peptidomics workflow which enabled the identification of 401 alternative proteins in Drosophila melanogaster. Subcellular localization, protein domains and short linear motifs were predicted for 235 of the alternative proteins identified and point towards specific functions of these small proteins. Several alternative proteins had approximated abundances higher than their canonical counterparts, suggesting that these alternative proteins are actually the main products of their corresponding genes. Finally, we observed fourteen alternative proteins with developmentally regulated expression patterns and ten induced upon heat shock treatment of embryos, demonstrating stage or stress specific production of alternative proteins.
Assessing the moderating role of organizational culture in the relationship between organizational leadership and organizational efficiency in the banking sector
Authors: Omama Koranteng Francisca , Iddris Faisal , Dwomoh Gabriel , Kofi Dogbe Courage Simon 
Published: March 2022

PurposeThis study explored the moderating role of organizational culture in the relationship between organizational leadership and organizational culture in the banking sector.Design/methodology/approachThe sample comprised of 331 full-time bank employees in the Ashanti region of Ghana. The reliability and validity of the data was tested using confirmatory factor analysis, with structural equation modeling as the main means of analysis, run using Amos (V23) in the data analysis.FindingsThe study concluded that all four leadership styles (transformational, transactional, servant and sustainable leadership styles) had a positive effect on banks' efficiency. Organizational culture also had a direct positive effect on banks' efficiency in Ghana. The study concludes that organizational culture positively moderated the relationship between organizational leadership and organizational efficiency in the banking industry. This implies organizational culture strengthens the relationship between organizational leadership and organizational efficiency in the banking industry.Research limitations/implications– A limitation of this study was to consider organizational culture as a composite variable, instead of considering the effects of the individual dimensions (clan culture, adhocracy culture, hierarchy culture and market culture). Although using the composite variable was not theoretically wrong, each of the four dimensions had unique characteristics and may influence organizational outcomes differently, and should have been considered.Practical implicationsTo achieve strategic organizational outcomes, leaders are to comprehend the various leaderships styles and how they could be transformed to influence organizational outcomes.Originality/valuePast studies have paid limited attention to the interaction between organizational leadership and organizational culture, and how this affects organizational efficiency.
Risk events recognition using smartphone and machine learning in construction workers' material handling tasks
Authors: Duan Pinsheng , Zhou Jianliang , Tao Shiwei 
Published: March 2022

PurposeThe outbreak of the pandemic makes it more difficult to manage the safety or health of construction workers in infrastructure construction. Risk events in construction workers' material handling tasks are highly relevant to workers' work-related musculoskeletal disorders. However, there are still many problems to be resolved in recognizing risk events accurately. The purpose of this research is to propose an automatic and non-invasive recognition method for construction workers in material handling tasks during the pandemic based on smartphone and machine learning.Design/methodology/approachThis research proposes a method to recognize and classify four different risk events by collecting specific acceleration and angular velocity patterns through built-in sensors of smartphones. The events were simulated with anterior handling and shoulder handling methods in the laboratory. After data segmentation and feature extraction, five different machine learning methods are used to recognize risk events and the classification performances are compared.FindingsThe classification result of the shoulder handling method was slightly better than the anterior handling method. By comparing the accuracy of five different classifiers, cross-validation results showed that the classification accuracy of the random forest algorithm was the highest (76.71% in anterior handling method and 80.13% in shoulder handling method) when the window size was 0.64 s.Originality/valueLess attention has been paid to the risk events in workers' material handling tasks in previous studies, and most events are recorded by manual observation methods. This study provided a simple and objective way to judge the risk events in manual material handling tasks of construction workers based on smartphones, which can be used as a non-invasive way for managers to improve health and labor productivity during the pandemic.