bluuebunny/crossref_metadata_2025_split huggingface dataset:
CellDepot: A unified repository for scRNA-seq data and visual exploration
Authors: Lin Dongdong , Chen Yirui , Negi Soumya , Cheng Derrick , Ouyang Zhengyu , Sexton David , Li Kejie , Zhang Baohong 
Published: October 2021

AbstractCellDepot serves as an integrated web application to assist users in exploring single-cell RNA-seq (scRNA-seq) datasets and comparing the datasets among various studies through a user-friendly interface with advanced visualization and analytical tools. To begin with, it provides an efficient data management system that users can upload single cell datasets and query the database by multiple attributes such as species and cell types. In addition, the advanced query function incorporated in MySQL database system and its conditional filtering, allows users to quickly query and compare the expression of gene(s) across the datasets of interest. Moreover, by embedding the cellxgene VIP tool, CellDepot enables fast exploration of individual dataset in the manner of interactivity and scalability to gain more refined insights such as cell composition, gene expression profiles, and differentially expressed genes among cell types. In summary, the web portal allows large scale single cell data sharing, analysis and visualization for supporting decision-making, and encouraging scientists to contribute to the single-cell community in a tractable and collaborative way. Finally, CellDepot is released as open-source software to motivate crowd contribution, broad adoption, and local deployment for private data.
Plausible Mechanistic Insights in Biofilm Eradication Potential of against Candida spp. using In Situ Synthesized Tyrosol Functionalized Chitosan Gold Nanoparticles as a versatile Antifouling Coating on Implant Surfaces
Authors: Yadav Tara Chand , Gupta Payal , Saini Saakshi , Pruthi Vikas , Prasad Ramasare 
Published: October 2021

ABSTRACTIn the present study, tyrosol functionalized chitosan gold nanoparticles (Chi-TY-AuNP’s) were prepared as an alternative treatment strategy to combat fungal infections. Various biophysical techniques were used to characterize the synthesized Chi-TY-AuNP’s. The antifungal and antibiofilm activities of Chi-TY-AuNP’s were evaluated against C. albicans and C. glabrata and efforts have been made to elucidate the possible mechanism of action. Chi-TY-AuNP’s showed a high fungicidal effect against both sessile and planktonic cells of Candida spp. Additionally, Chi-TY-AuNP’s completely eradicated (100%) the mature biofilms of both the Candida spp. FESEM analysis highlighted the morphological alterations in Chi-TY-AuNP’s treated Candida biofilm cells. Effect of Chi-TY-AuNP’s on the ECM components showed significant reduction in protein content in C. glabrata biofilm and substantial decrease in extracellular DNA (eDNA) content of both the Candida spp. ROS generation analysis using DCFDA-PI staining showed high ROS levels in both the Candida spp., whereas pronounced ROS production was observed in Chi-TY-AuNP’s treated C. glabrata biofilm. Biochemical analysis revealed decreased ergosterol content in Chi-TY-AuNP’s treated C. glabrata cells, while inconsequential changes were observed in C. albicans. Furthermore, the transcriptional expression of selected genes (ergosterol biosynthesis, efflux, sterol importer, and glucan biogenesis) was reduced in C. glabrata in response to Chi-TY-AuNP’s except ERG11 and CDR1. Conclusively the result showed the biofilm inhibition and biofilm eradication efficacy of Chi-TY-AuNP’s in both the Candida spp. Findings of the present study manifest Chi-TY-AuNP’s as a potential therapeutic solution to Candida biofilm-related chronic infections and overcome biofilm antifungal resistance.
Integrative modelling of reported case numbers and seroprevalence reveals time-dependent test efficiency and infectious contacts
Authors: Contento Lorenzo , Castelletti Noemi , Raimúndez Elba , Le Gleut Ronan , Schälte Yannik , Stapor Paul , Hinske Ludwig Christian , Hoelscher Michael , Wieser Andreas , Radon Katja , Fuchs Christiane , Hasenauer Jan ,   the KoCo19 study group
Published: October 2021

AbstractMathematical models have been widely used during the ongoing SARS-CoV-2 pandemic for data interpretation, forecasting, and policy making. However, most models are based on officially reported case numbers, which depend on test availability and test strategies. The time dependence of these factors renders interpretation difficult and might even result in estimation biases.Here, we present a computational modelling framework that allows for the integration of reported case numbers with seroprevalence estimates obtained from representative population cohorts. To account for the time dependence of infection and testing rates, we embed flexible splines in an epidemiological model. The parameters of these splines are estimated, along with the other parameters, from the available data using a Bayesian approach.The application of this approach to the official case numbers reported for Munich (Germany) and the seroprevalence reported by the prospective COVID-19 Cohort Munich (KoCo19) provides first estimates for the time dependence of the under-reporting factor. Furthermore, we estimate how the effectiveness of non-pharmaceutical interventions and of the testing strategy evolves over time. Overall, our results show that the integration of temporally highly resolved and representative data is beneficial for accurate epidemiological analyses.
Neural Correlates of Eye Contact and Social Function in Autism Spectrum Disorder
Authors: Hirsch Joy , Zhang Xian , Adam Noah J. , Dravida Swethasri , Naples Adam , Tiede Mark , Wolf Julie M. , McPartland James C. 
Published: October 2021

AbstractReluctance to make eye contact during natural interactions is a central diagnostic criterion for autism spectrum disorder (ASD). However, the underlying neural correlates for natural eye contacts in ASD are unknown, and diagnostic biomarkers are active areas of investigation. Here, neuroimaging, eye-tracking, and pupillometry data were acquired simultaneously using two-person functional near-infrared spectroscopy (fNIRS) during live eye-to-eye contact and eye-gaze at a video face in typically developed (TD) and ASD participants to identify the neural correlates of live eye-to-eye contact in both groups. Direct comparisons between ASD and TD participants showed decreased right dorsal parietal activity and increased right ventral temporal-parietal activity for ASD relative to TD during live eye-to-eye contact (p≤0.05, FDR-corrected) consistent with the hypothesis of alternative neural systems for live eye contact. The additional hypothesis that hypoactivity of the right dorsal-parietal regions during eye contact is associated with social performance in ASD was supported by the correlation of right dorsal parietal activity with individual measures of social function: ADOS-2, Autism Diagnostic Observation Schedule, 2nd Edition (r = -0.69); and SRS-2, Social Responsiveness Scale, Second Edition (r = -0.58). That is, as social ability decreased, the neural responses in the right dorsal parietal region to real eye-contact also decreased consistent with a neural correlate for social characteristics in ASD.
Spatial distribution of erector spinae activity is related to task-specific pain-related fear during a repetitive object lifting task
Authors: Liechti Melanie , Von Arx Michael , Eichelberger Patric , Bangerter Christian , Meier Michael L. , Schmid Stefan 
Published: October 2021

ABSTRACTFear-avoidance beliefs, particularly the fear of lifting an object with a flexed spine, were shown to be associated with reduced spinal motion during object lifting in both individuals with and without low back pain (LBP). LBP patients thereby also showed potentially clinically relevant changes in the spatial distribution of back muscle activity, but it remains unknown whether such associations are also present in pain-free individuals. The aim of this study was therefore to investigate the relationship between fear-avoidance beliefs and the change in spatial distribution of lumbar paraspinal muscle activity in pain-free individuals during a repetitive object lifting task. Thirty participants completed two pain-related fear questionnaires and performed 25 repetitions of lifting a 5kg-box from a lower to an upper shelf and back, while multi-channel electromyographic signals were recorded bilaterally from the lumbar erector spinae muscles. Changes in spatial distribution were determined by calculating the differences in vertical position of the weighted centroids of muscle activity (centroid shift) between the first and last few repetitions. Multiple linear regression analyses were performed to examine the relationship between the centroid shift and fear-avoidance belief scores. The analyses showed that the fear of lifting an object with a flexed spine was negatively associated with erector spinae activity centroid shift (R2 adj. = 0.1832; p = 0.045), which might be an expression of behavioral alterations in order to prevent the back from possible harm.
ViralFlow: an automated workflow for SARS-CoV-2 genome assembly, lineage assignment, mutations and intrahost variants detection
Authors: Dezordi Filipe Zimmer , de Lima Campos Túlio , Carneiro Jeronimo Pedro Miguel , Aksenen Cleber Furtado , Almeida Suzana Porto , Wallau Gabriel Luz 
Published: October 2021

ABSTRACTThe COVID-19 pandemic, a disease caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), emerged in 2019 and quickly spread worldwide. Genomic surveillance has become the gold standard methodology to monitor and study this emerging virus. The current deluge of SARS-CoV-2 genomic data being generated worldwide has put additional pressure on the urgent need for streamlined bioinformatics workflows for data analysis. Here, we describe a workflow developed by our group to process and analyze large-scale SARS-CoV-2 Illumina amplicon sequencing data. This workflow automates all the steps involved in SARS-CoV-2 genomic analysis: data processing, genome assembly, PANGO lineage assignment, mutation analysis and the screening of intrahost variants. The workflow presented here (https://github.com/dezordi/ViralFlow) is available through Docker or Singularity images, allowing implementation in laptops for small scale analyses or in high processing capacity servers or clusters. Moreover, the low requirements for memory and CPU cores makes it a versatile tool for SARS-CoV-2 genomic analysis.
New insights into the architecture and dynamics of archaella
Authors: Gambelli Lavinia , Isupov Michail N. , Conners Rebecca , McLaren Mathew , Bellack Annett , Gold Vicki , Rachel Reinhard , Daum Bertram 
Published: October 2021

AbstractArchaea swim by means of a unique molecular machine called the archaellum. The archaellum consists of an ATP-powered intracellular motor that drives the rotation of an extracellular filament, allowing the cell to rapidly propel itself through liquid media.The archaellum filament comprises multiple copies of helically organised subunits named archaellins. While in many species several archaellin homologs are encoded in the same operon, structural studies conducted to date have suggested that archaella consist of only one protein species. Thus, the role of the remaining archaellin genes remains elusive.Here we present the structure of the Methanocaldococcus villosus archaellum filament at 3.08 Å resolution. We find that the filament is composed of two alternating archaellins - ArlB1 and ArlB2, suggesting that the architecture and assembly of archaella is more complex than previously thought. Moreover, we identify two major structural elements that enable the archaellum filament to move.Our findings provide new insights into archaeal motility and challenge the current view on the archaellum architecture and assembly.
Alkaline phosphatase activity of serum affects osteogenic differentiation cultures
Authors: Ansari Sana , Ito Keita , Hofmann Sandra 
Published: October 2021

AbstractFetal bovine serum (FBS) is a widely used supplement in cell culture medium, despite its known variability in composition which greatly affects cellular function and consequently the outcome of studies. In bone tissue engineering, the deposited mineralized matrix is one of the main outcome parameters, but using different brands of FBS can result in large variations. Alkaline phosphatase (ALP) is present in FBS. Not only is ALP used to judge the osteogenic differentiation of bone cells, it may affect deposition of mineralized matrix. The present study focused on the enzymatic activity of ALP in FBS of different suppliers and its contribution to mineralization in osteogenic differentiation cultures. It was hypothesized that culturing cells in a medium with high intrinsic ALP activity of FBS will lead to higher mineral deposition compared to media with lower ALP activity. The used FBS types were shown to have significant differences in enzymatic ALP activity. Our results indicate that the ALP activity of the medium not only affected the deposited mineralized matrix but also the osteogenic differentiation of cells as measured by a changed cellular ALP activity of human bone marrow derived mesenchymal stromal cells (hBMSC). In media with low inherent ALP activity, the cellular ALP activity was increased and played the major role in the mineralization process; while, in media with high intrinsic ALP activity contribution from the serum, less cellular ALP activity was measured and the ALP activity of the medium also contributed to mineral formation substantially. Our results highlight the diverse effects of ALP activity intrinsic to FBS on osteogenic differentiation and matrix mineralization and how FBS can determine the experimental outcomes, in particular for studies investigating matrix mineralization. Once again, the need to replace FBS with more controlled and known additives is highlighted.Graphical abstract
Synthetic glabridin derivatives mitigate steatohepatitis in a diet-induced biopsy-confirmed non-alcoholic steatosis hepatitis mouse model through paraoxonase-2
Authors: Shin Gu-Choul , Lee Hyeong Min , Kim Na Yeon , Yoo Sang-Ku , Park Yun Sun , Park Hyung Soon , Ryu Dongryeol , Kim Kwang Pyo , Kim Kyun-Hwan 
Published: October 2021

AbstractLimited therapeutic agents have been developed for non-alcoholic steatohepatitis (NASH), a common immunometabolic disease that can progress to hepatic cirrhosis and cancer. Glabridin and its derivatives are potential therapeutics for some metabolic diseases. However, the therapeutic effects of glabridin and its derivatives on NASH and their biological functions are unclear. This study demonstrated the role of synthetic glabridin derivatives (SGDs) in alleviating hepatic steatosis and inflammation in a biopsy-confirmed rodent NASH model. SGDs exerted therapeutic effects by activating autophagy and the antioxidant defense system, which mitigate NASH pathogenesis. The cellular target of HSG4112, an SGD, was paraoxonase 2. These findings will enable the development of novel therapeutics for NASH in the future.
JADE family proteins regulate proteasome abundance and activity
Authors: Ebert Lena Kathrin , Bargfrede Sebastian , Bohl Katrin , Müller Roman-Ulrich , Benzing Thomas , Schermer Bernhard 
Published: October 2021

AbstractJADE family proteins (JADE1/2/3) have been implicated in diverse cellular functions and signaling pathways ranging from WNT signaling and cell cycle control to cell death and complex transcriptional regulation through histone acetyl-transferase complexes. JADE proteins show a high degree of sequence similarity and share two PHD zinc finger domains. JADE1 interacts with cilia-associated proteins and has been implicated in cilia-related genetic disorders with kidney phenotypes. However, the function of the widely expressed JADE proteins at the molecular level is still elusive. Here we show that JADE proteins regulate proteasome abundance and activity. Using kidney cells as a model, we demonstrate that loss of either JADE protein resulted in increased expression of almost all components of the 26S proteasome. Regulation occurred at the post-translational level and was not the consequence of transcriptional activation. Consistent with a role for JADE proteins in regulating overall proteasomal abundance, proteasomal activity was elevated in Jade-deficient cells, while exogenous expression of JADE1/2/3 decreased the level of proteasome activity. Coimmunoprecipitation experiments confirmed the interaction of proteasomal subunits with Jade1 suggesting a direct role of JADE proteins in regulating turnover, stability and abundance of the 26s proteasome. These data may now explain the plethora of cellular roles that have been attributed to JADE proteins.
The Human STAT2 Coiled-Coil Domain Contains a Degron for Zika Virus Interferon Evasion
Authors: Parisien Jean-Patrick , Lenoir Jessica J. , Alvarado Gloria , Horvath Curt M. 
Published: October 2021

AbstractThe ability of viruses to evade the host antiviral immune system determines their level of replication fitness, species specificity, and pathogenic potential. Flaviviruses rely on the subversion of innate immune barriers including the type I and type III IFN antiviral systems. Zika virus infection induces the degradation of STAT2, an essential component of the IFN stimulated gene transcription factor, ISGF3. The mechanisms that lead to STAT2 degradation by Zika virus are poorly understood, but it is known to be mediated by the viral NS5 protein that binds to STAT2 and targets it for proteasome-mediated destruction. To better understand how NS5 engages and degrades STAT2, functional analysis of the protein interactions that lead to Zika virus and NS5-dependent STAT2 proteolysis were investigated. Data implicate the STAT2 coiled-coil domain as necessary and sufficient for NS5 interaction and proteasome degradation after Zika virus infection. Molecular dissection reveals that the first two α-helices of the STAT2 coiled-coil contain a specific targeting region for IFN antagonism. These functional interactions provide a more complete understanding of the essential protein-protein interactions needed for Zika virus evasion of the host antiviral response, and identifies new targets for antiviral therapeutic approaches.ImportanceZika virus infection can cause mild fever, rash, and muscle pain, and in rare cases lead to brain or nervous system diseases including Guillain–Barré syndrome. Infections in pregnant women can increase the risk of miscarriage or serious birth defects including brain anomalies and microcephaly. There are no drugs or vaccines for Zika disease. Zika virus is known to break down the host antiviral immune response, and this research project reveals how the virus suppresses interferon signaling, and may reveal therapeutic vulnerabilities.
Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma
Authors: Guetta-Terrier Charlotte , Karambizi David , Akosman Bedia , Chen Jia-Shu , Kamle Suchitra , Fajardo Eduardo , Fiser Andras , Singh Ritambhara , Toms Steven A. , Lee Chun Geun , Elias Jack A. , Tapinos Nikos 
Published: October 2021

SummaryChi3l1 (Chitinase 3-like 1) is a secreted protein highly expressed in glioblastoma. Here, we show that exposure of glioma stem cells (GSCs) to Chi3l1 reduces the CD133+/SOX2+ cells and increases the CD44+/Chi3l1+ cells. Chi3l1 binds to CD44 and induces phosphorylation and nuclear translocation of beta-catenin, Akt and STAT3. Single cell RNA-seq and RNA velocity following incubation of GSCs with Chi3l1 show significant changes in GSC state dynamics driving GSCs towards a mesenchymal expression profile and reducing transition probabilities towards terminal cellular states. ATAC-seq reveals that Chi3l1 increases accessibility of promoters containing MAZ transcription factor footprint. Inhibition of MAZ directly regulates genes with highest expression in cellular clusters exhibiting significant cell state transitions. Finally, targeting Chi3l1 in vivo with a blocking antibody, resets the transcriptomic profile of glioblastoma and inhibits tumor growth. Our work implicates Chi3l1 as modulator of GSC cellular states and demonstrates pre-clinical efficacy of anti-Chi3l1 antibody treatment.
Neutrophils contribute to ER stress in lung epithelial cells in the pristane-induced diffuse alveolar hemorrhage mouse model
Authors: Tumurkhuu Gantsetseg , Laguna Duygu Ercan , Moore Richard E. , Contreras Jorge , De Los Santos Gabriela , Akaveka Luisa , Montano Erica N. , Wang Yizhou , Ishimori Mariko , Venuturupalli Swamy , Forbess Lindsy , Stripp Barry R. , Wallace Daniel J. , Jefferies Caroline A. 
Published: October 2021

AbstractDiffuse alveolar hemorrhage (DAH), although rare, is a life-threatening complication of systemic lupus erythematosus (SLE). Little is known about the pathophysiology of DAH in humans, although increasingly neutrophils, NETosis and inflammatory monocytes have been shown to play an important role in the pristane-induced model of SLE which develops lung hemorrhage and recapitulates many of the pathologic features of human DAH. Using this experimental model, we asked whether endoplasmic reticulum (ER) stress played a role in driving the pathology of pulmonary hemorrhage and what role infiltrating neutrophils had in this process. Analysis of lung tissue from pristane-treated mice showed genes associated with ER stress and NETosis were increased in a time-dependent manner and reflected the timing of CD11b+Ly6G+ neutrophil accumulation in the lung. Using precision cut lung slices from untreated mice we observed that neutrophils isolated from the peritoneal cavity of pristane-treated mice could directly induce the expression of genes associated with ER stress, namely Chop and Bip. Mice which had myeloid-specific deletion of PAD4 were generated and treated with pristane to assess the involvement of PAD4 and PAD4-dependent NET formation in pristane-induced lung inflammation. Specific deletion of PAD4 in myeloid cells resulted in decreased expression of ER stress genes in the pristane model, with accompanying reduction in IFN-driven genes and pathology. Lastly, coculture experiments of human neutrophils and human lung epithelial cell line (BEAS-2b) showed neutrophils from SLE patients induced significantly more ER stress and interferon-stimulated genes in epithelial cells compared to healthy control neutrophils. These results support a pathogenic role of neutrophils and NETs in lung injury during pristane-induced DAH through the induction of ER stress response and suggest that overactivation of neutrophils in SLE and NETosis may underlie development of DAH.
Molecular structure and conformation of stereocilia tip-links elucidated by cryo-electron tomography
Authors: Elferich Johannes , Clark Sarah , Ge Jingpeng , Goehring April , Matsui Aya , Gouaux Eric 
Published: October 2021

AbstractMechanosensory transduction (MT), the conversion of mechanical stimuli into electrical signals, underpins hearing and balance and is carried out within hair cells in the inner ear. Hair cells harbor actin-filled stereocilia, arranged in rows of descending heights, where the tips of stereocilia are connected to their taller neighbors by a filament composed of protocadherin 15 (PCDH15) and cadherin 23 (CDH23), deemed the ‘tip-link’. Tension exerted on the tip-link opens an ion channel at the tip of the shorter stereocilia, thus converting mechanical force into an electrical signal. While biochemical and structural studies have provided insights into the molecular composition and structure of isolated portions of the tip-link, the architecture, location and conformational states of intact tip-links, on stereocilia, remains unknown. Here we report in situ cryo-electron microscopy imaging of the tip-link in mouse stereocilia. We observe individual PCDH15 molecules at the tip and shaft of stereocilia and determine their stoichiometry, conformational heterogeneity, and their complexes with CDH23. The PCDH15/CDH23 complexes occur in clusters, frequently with more than one copy of PCDH15 at the tip of stereocilia, suggesting that tip-links might consist of more than one copy of the PCDH15/CDH23 heterotetramer and by extension, might include multiple MT complexes.