bluuebunny/crossref_metadata_2025_split huggingface dataset:
Staphylococcus aureusskin colonization is mediated by SasG lectin variation
Authors: Mills Krista B. , Maciag Joseph J. , Wang Can , Crawford John A. , Enroth Timothy J. , Keim Klara C. , Dufrêne Yves F. , Robinson D. Ashley , Fey Paul D. , Herr Andrew B. , Horswill Alexander R. 
Published: November 2023

AbstractStaphylococcus aureuscauses the majority of skin and soft tissue infections, but this pathogen only transiently colonizes healthy skin. However, this transient skin exposure enablesS. aureusto transition to infection. Initial adhesion ofS. aureusto skin corneocytes is mediated by surface protein G (SasG). Here, phylogenetic analyses reveal the presence of two major divergent SasG alleles inS. aureus, SasG-I and SasG-II. Structural analyses of SasG-II identified a unique non-aromatic arginine in the binding pocket of the lectin subdomain that mediates adhesion to corneocytes. Atomic force microscopy and corneocyte adhesion assays indicated SasG-II can bind to a broader variety of ligands than SasG-I. Glycosidase treatment resulted in different binding profiles between SasG-I and SasG-II on skin cells. Additionally, SasG-mediated adhesion was recapitulated using differentiated N/TERT keratinocytes. Our findings indicate that SasG-II has evolved to adhere to multiple ligands, conferring a distinct advantage toS. aureusduring skin colonization.
ColabFold predicts alternative protein structures from single sequences, coevolution unnecessary for AF-cluster
Authors: Porter Lauren L. , Chakravarty Devlina , Schafer Joseph W. , Chen Ethan A. 
Published: November 2023

AbstractThough typically associated with a single folded state, globular proteins are dynamic and often assume alternative or transient structures important for their functions1,2. Wayment-Steele, et al. steered ColabFold3to predict alternative structures of several proteins using a method they call AF-cluster4. They propose that AF-cluster “enables ColabFold to sample alternate states of known metamorphic proteins with high confidence” by first clustering multiple sequence alignments (MSAs) in a way that “deconvolves” coevolutionary information specific to different conformations and then using these clusters as input for ColabFold. Contrary to this Coevolution Assumption, clustered MSAs are not needed to make these predictions. Rather, these alternative structures can be predicted from single sequences and/or sequence similarity, indicating that coevolutionary information is unnecessary for predictive success and may not be used at all. These results suggest that AF-cluster’s predictive scope is likely limited to sequences with distinct-yet-homologous structures within ColabFold’s training set.
Revisiting Reddy: A DLBCL Do-over
Authors: Dreval Kostiantyn , Cruz Manuela , Rushton Christopher , Liuta Nina , Mirhosseini Houman Layegh , Brown Callum , Morin Ryan D. ,   the GAMBL consortium
Published: November 2023

AbstractThe 2017 study by Reddyet aldescribed the comprehensive characterization of somatic drivers of diffuse large B-cell lymphoma using whole exome sequencing.1After additional large studies relying on exome or whole genome sequencing were published, several oddities unique to the Reddy results have emerged. Seeking to explain the discrepancies, we reanalyzed their data using established open-source pipelines. This revealed thousands of mutations that could not be independently reproduced by these pipelines and a larger set of high-quality mutations that were not reported by Reddy. This caused an artificial under-representation of the mutation prevalence in many genes including clinically relevant hot spots affectingEZH2andCD79B. More generally, the study had an under-representation of mutations in DLBCL genes that disproportionately affected genes known to have the highest mutation rates. The missing variants and the spurious variants can be attributed to distinct problems with the analytical approaches employed in that study. Our analysis also identified strong associations between mutations and patient outcome includingTP53, KMT2DandPIM1, which were not found in the Reddy study. Overall, we demonstrate that this combination of errors influenced many of the central novel findings from their study rendering their results largely non-replicable. The full results of our analyses are included as supplemental items as a resource for other researchers with an interest in the genetics of B-cell lymphomas.
Intermolecular interactions between cysteine and aromatic amino acids with phenyl moiety in the DNA-binding domain of heat shock factor 1 regulate thermal stress-induced trimerization
Authors: Lee Chang-Ju , Choi Bo-Hee , So-Sun-Kim  , Kim David Nahm-Joon , Choi Jeong-Mo , Park Young-Shang , Park Jang-Su 
Published: November 2023

AbstractIn this study, we investigated the trimerization mechanism and structure of heat shock factor 1 (HSF1) in humans, goldfish, and walleye pollock at various temperatures. The trimerization of HSF1s were confirmed using western blotting using their respective antibodies. First, we examined the HSF1 DNA-binding domains of human (Homo sapiens), goldfish (Carassius auratus), and walleye pollock (Gadus chalcogrammus) by mutating key residues (36 and 103) that are thought to directly affect trimer generation. Humans, goldfish, and walleye pollock contain cysteine at residue 36, but cysteine (C), tyrosine (Y), and phenylalanine (F) at residue 103. Also, the trimer formation temperature of each species was found to be 42, 37, and 20 °C, respectively. In the mutation experiment, trimerization formed at 42 °C when residue 103 was C, at 37 °C it was Y, and at 20 °C it was F, regardless of the species. In addition, it was confirmed that when residue 103 of the three species was mutated to alanine (A), trimer was not formed. This suggest that, in addition to the previously identified C-C disulfide bonds in humans, C forms a trimer with a new type of bond with aromatic ring residues such as Y and F. Thus, HSF1 trimer formation temperature reveals the trimer creation mechanism through the fact that goldfish can have C-Y bonds at 37 °C, and walleye pollock can have C-F bonds at 20 °C. This study suggests that the trimer formation temperature and mechanism of HSF1 are regulated by the amino acid at residue 103.
Systems levels analysis of lipid metabolism in oxygen-induced retinopathy
Authors: Singh Charandeep 
Published: November 2023

AbstractHyperoxia induces glutamine-fueled anaplerosis in the Muller cells, endothelial cells, and retinal explants. Anaplerosis takes away glutamine from the biosynthetic pathway to the energy-producing TCA cycle. This process depletes biosynthetic precursors from newly proliferating endothelial cells. The induction of anaplerosis in the hyperoxic retina is a compensatory response, either to decreased glycolysis or decreased flux from glycolysis to the TCA cycle. We hypothesized that by providing substrates that feed into TCA, we could reverse or prevent glutamine-fueled anaplerosis, thereby abating the glutamine wastage for energy generation. Using an oxygen-induced retinopathy (OIR) mouse model, we first compared the difference in fatty acid metabolism between OIR-resistant BALB/cByJ and OIR susceptible C57BL/6J strains to understand if these strains exhibit metabolic difference that protects BALB/cByJ from the hyperoxic conditions and prevents their vasculature in oxygen-induced retinopathy model. Based on our findings from the metabolic comparison between two mouse strains, we hypothesized that the medium-chain fatty acid, octanoate, can feed into the TCA and serve as an alternative energy source in response to hyperoxia. Our systems levels analysis of OIR model shows that the medium chain fatty acid can serve as an alternative source to feed TCA. We here, for the first time, demonstrate that the retina can use medium-chain fatty acid octanoate to replenish TCA in normoxic and at a higher rate in hyperoxic conditions.
Neuroticism levels in severe depression may reveal association with higher levels of intelligence
Authors: Nitchie Frederick , Moore Tyler , Scott J. Cobb , Makhoul Walid , Sheline Yvette 
Published: November 2023

AbstractThe anxious-misery spectrum of disorders encompasses some of the most debilitating mental disorders that effect the population at-large. In addition, neuroticism is a trait that has been shown to correlate with higher levels of reported symptomatology for individuals diagnosed with anxious-misery disorders. However, it is less understood which of these might be more predictive of the cognitive impairments typically associated with mental illness. Therefore, we selected a group of participants with high trait neuroticism and comorbid anxious-misery symptoms. Using confirmatory factor analysis, we loaded the results of seventeen neuropsychological measures from each participant onto five distinct factors that exists on the anxious-misery spectrum: Depression, Anxiety, Impulsivity, Insomnia, and Somatizing. These factors were then compared to the results that participants had on to neurocognitive batteries: the University of Pennsylvania Computerized Neurocognitive Test Battery as well and the National Institute of Health Toolbox. Contrary to our expectations, we found that those in the top quartile of depressive symptom severity performed better than controls on working memory measures. These results are thought to be the result of correlations that have been shown previously between high levels of neuroticism and higher levels of intelligence.
IsoVEM: Isotropic Reconstruction for Volume Electron Microscopy Based on Transformer
Authors: He Jia , Zhang Yan , Sun Wenhao , Yang Ge , Sun Fei 
Published: November 2023

AbstractVolume electron microscopy (vEM) has become a rapidly developing technique for studying the 3D architecture of biological specimens, such as cells, tissues, and organs at nanometer resolution; this technique involves collecting a series of electron micrographs of axial sequential sections and reconstructing the 3D volume, providing useful information on the cellular ultrastructural spectrum. This technique currently suffers from anisotropic resolution between the lateral (x, y) and axial (z) directions and the loss/damage of sections. Here, we develop a new algorithm, IsoVEM, based on a video transformer model to boost the axial resolution and achieve isotropic reconstruction of vEM. By learning high-resolution axial structures and utilizing the 3D continuity of biological structures, IsoVEM can recover axial information and repair random lost/damaged sections based on a self-supervision strategy, achieving a higher resolution than existing methods, which has been validated for both simulated FIB-SEM datasets and experimental ssTEM datasets. In addition to visual validation, the segmentation efficiency and statistical precision of various ultrastructures, e.g., neurons, mitochondria, vesicles, and membrane bilayers, also prove the better performance of IsoVEM. Therefore, using IsoVEM, we achieve isotropic reconstruction via anisotropic axial sampling, which increases the vEM throughput for studying large-scale biological architectures.
Predicting phage-bacteria interactions at the strain level from genomes
Authors: Gaborieau Baptiste , Vaysset Hugo , Tesson Florian , Charachon Inès , Dib Nicolas , Bernier Juliette , Dequidt Tanguy , Georjon Héloïse , Clermont Olivier , Hersen Pascal , Debarbieux Laurent , Ricard Jean-Damien , Denamur Erick , Bernheim Aude 
Published: November 2023

AbstractPredicting how phages can selectively infect specific bacterial strains holds promise for developing novel approaches to combat bacterial infections and better understanding microbial ecology. Experimental studies on phage-bacteria interactions have been mostly focusing on a few model organisms to understand the molecular mechanisms which makes a particular bacterial strain susceptible to a given phage. However, both bacteria and phages are extremely diverse in natural contexts. How well the concepts learned from well-established experimental models generalize to a broad diversity of what is encountered in the wild is currently unknown. Recent advances in genomics allow to identify traits involved in phage-host specificity, implying that these traits could be utilized for the prediction of such interactions. Here, we show that we could predict outcomes of most phage-bacteria interactions at the strain level inEscherichianatural isolates based solely on genomic data. First, we established a dataset of experimental outcomes of phage-bacteria interactions of 403 natural, phylogenetically diverse,Escherichiastrains to 96 bacteriophages matched with fully sequenced and genomically characterized strains and phages. To predict these interactions, we set out to define genomic traits with predictive power. We show that most interactions in our dataset can be explained by adsorption factors as opposed to antiphage systems which play a marginal role. We then trained predictive algorithms to pinpoint which interactions could be accurately predicted and where future research should focus on. Finally, we show the application of such predictions by establishing a pipeline to recommend tailored phage cocktails to target pathogenic strains from their genomes only and show higher efficiency of tailored cocktails on a collection of 100 pathogenicE. coliisolates. Altogether, this work provides quantitative insights into understanding phage–host specificity at the strain level and paves the way for the use of predictive algorithms in phage therapy.
Tertiary folds of the SL5 RNA from the 5′ proximal region of SARS-CoV-2 and related coronaviruses
Authors: Kretsch Rachael C. , Xu Lily , Zheludev Ivan N. , Zhou Xueting , Huang Rui , Nye Grace , Li Shanshan , Zhang Kaiming , Chiu Wah , Das Rhiju 
Published: November 2023

AbstractCoronavirus genomes sequester their start codons within stem-loop 5 (SL5), a structured, 5′ genomic RNA element. In most alpha- and betacoronaviruses, the secondary structure of SL5 is predicted to contain a four-way junction of helical stems, some of which are capped with UUYYGU hexaloops. Here, using cryogenic electron microscopy (cryo-EM) and computational modeling with biochemically-determined secondary structures, we present three-dimensional structures of SL5 from six coronaviruses. The SL5 domain of betacoronavirus SARS-CoV-2, resolved at 4.7 Å resolution, exhibits a T-shaped structure, with its UUYYGU hexaloops at opposing ends of a coaxial stack, the T’s “arms.” Further analysis of SL5 domains from SARS-CoV-1 and MERS (7.1 and 6.4-6.9 Å resolution, respectively) indicate that the junction geometry and inter-hexaloop distances are conserved features across the studied human-infecting betacoronaviruses. The MERS SL5 domain displays an additional tertiary interaction, which is also observed in the non-human-infecting betacoronavirus BtCoV-HKU5 (5.9-8.0 Å resolution). SL5s from human-infecting alphacoronaviruses, HCoV-229E and HCoV-NL63 (6.5 and 8.4-9.0 Å resolution, respectively), exhibit the same coaxial stacks, including the UUYYGU-capped arms, but with a phylogenetically distinct crossing angle, an X-shape. As such, all SL5 domains studied herein fold into stable tertiary structures with cross-genus similarities, with implications for potential protein-binding modes and therapeutic targets.SignificanceThe three-dimensional structures of viral RNAs are of interest to the study of viral pathogenesis and therapeutic design, but the three-dimensional structures of viral RNAs remain poorly characterized. Here, we provide the first 3D structures of the SL5 domain (124-160 nt, 40.0-51.4 kDa) from the majority of human-infecting coronaviruses. All studied SL5s exhibit a similar 4-way junction, with their crossing angles grouped along phylogenetic boundaries. Further, across all species studied, conserved UUYYGU hexaloop pairs are located at opposing ends of a coaxial stack, suggesting that their three-dimensional arrangement is important for their as-of-yet defined function. These conserved tertiary features support the relevance of SL5 for pan-coronavirus fitness and highlight new routes in understanding its molecular and virological roles and in developing SL5-based antivirals.Classification:Biological Sciences, Biophysics and Computational Biology
The effect of clinically relevant beta-lactam, aminoglycoside, and quinolone antibiotics on bacterial extracellular vesicle release fromE. coli
Authors: Torabian Panteha , Singh Navraj , Crawford James , Gonzalez Gabriela , Burgado Nicholas , Videva Martina , Miller Aidan , Perdue Janai , Dinu Milena , Pietropaoli Anthony , Gaborski Thomas , Michel Lea Vacca 
Published: November 2023

AbstractSepsis, a leading cause of death in hospitals, can be defined as a dysregulated host inflammatory response to infection, which can lead to tissue damage, organ failure, and cardiovascular complications. Although there is no cure for sepsis, the condition is typically managed with broad spectrum antibiotics to eliminate any potential bacterial source of infection. However, a potential side-effect of antibiotic treatment is the enhanced release of bacterial extracellular vesicles (BEVs). BEVs are membrane-bound nanoparticles produced by a variety of mechanisms, one of which includes the pinching-off of the outer membrane (in Gram-negative bacteria) to enclose proteins and other biological molecules for transport and intercellular communication. Some of the Gram-negative EV cargo, including Peptidoglycan associated lipoprotein (Pal) and Outer membrane protein A (OmpA), have been shown to induce both acute and chronic inflammation in host tissue. We hypothesize that antibiotic concentration and its mechanism of action can have an effect on the amount of released BEVs, which could potentially exacerbate the host inflammatory response. In this study, we evaluated nine clinically relevant antibiotics for their effect on EV release fromEscherichia coli. EVs were characterized using immunoblotting, nanoparticle tracking analysis, and transmission electron microscopy. Several beta-lactam antibiotics caused significantly more EV release, while quinolone and aminoglycosides caused relatively less vesiculation. Further study is warranted to corroborate the correlation between an antibiotic’s mechanism of action and its effect on EV release, but these results underline the importance of antibiotic choice when treating sepsis patients.
Impact of electrodes design and insertion methods to surrounding cortical tissues from high-density arrays
Authors: McNamara Ingrid N. , Wellman Steven M. , Li Lehong , Eles James R. , Savya Sajishnu , Sohal Harbaljit S. , Angle Matthew R. , Kozai Takashi D. Y. 
Published: November 2023

AbstractObjectiveOver the past decade, neural electrodes have played a crucial role in bridging biological tissues with anthropomorphic devices. This study focuses on evaluating the optimal pitch, tip profile, and insertion speed for effectively implanting Paradromics’ high-density Fine Microwire Arrays (FμA) prototypes into the primary visual cortex (V1) of mice and rats, addressing the challenges associated with the “bed-of-nails” effect and tissue dimpling.ApproachTissue response was assessed by investigating the impact of electrodes on the blood-brain barrier (BBB) and cellular damage, with a specific emphasis on tailored insertion strategies to minimize tissue disruption during electrode implantation.Main ResultsElectro-sharpened arrays demonstrated a marked reduction in cellular damage within 50 μm of the electrode tip compared to blunt and angled arrays. Histological analysis revealed that slow insertion speeds led to greater BBB compromise than fast and pneumatic methods. Successful single-unit recordings validated the efficacy of the optimized electro-sharpened arrays in capturing neural activity.SignificanceThese findings underscore the critical role of tailored insertion strategies in minimizing tissue damage during electrode implantation, highlighting the suitability of electro-sharpened arrays for long-term neural recording applications. This research contributes to a deeper understanding of the complexities associated with high-channel-count microelectrode array implantation, emphasizing the importance of meticulous assessment and optimization of key parameters for effective integration and minimal tissue disruption. By elucidating the interplay between insertion parameters and tissue response, our study lays a strong foundation for the development of advanced implantable devices with a reduction in reactive gliosis and improved performance in neural recording applications.
Identification of Essential Temperature-Stressed Genes FromApis melliferaHypopharyngeal Glands Transcriptomes Under Variable Temperatures
Authors: Maigoro Abdulkadir Yusif , Lee Jeong Hyeon , Lee Sujin , Kwon Hyung Wook 
Published: November 2023

AbstractTemperature is one of the essential abiotic factors required for honey bee survival and pollination. It affects honey bee physiology, behavior, and expression of related genes. Also, considered one of the major factors contributing to colony collapse disease (CCD). In this research, RNA-seq analysis was performed using hypopharyngeal glands (HGs) tissue at low (18 °C), high (25 °C), and regular (22 °C) temperatures. Differentially expressed genes (DEGs) were identified after comparing the three groups with one another based on temperature differences using DESeq analysis. 5196 common DEGs (cDEGs) were identified among the groups. They are highly enriched in RNA processing and RNA metabolism process while the KEGG pathway enrichment analysis showed that the cDEGs are enriched in longevity regulating pathway, MAPK signaling pathway-fly, and Glycerophospholipid metabolism. Further, 360 temperature-stressed genes identified are highly enriched in translation, oxidative activity, and ribonucleoprotein complex. The enriched KEGG pathway includes ribosome, oxidative phosphorylation, fatty acid metabolism, and citrate cycle (TCA cycle). All the top ten (10) hub genes among the 360 temperature-stressed genes are found up-regulated. In addition, heat-shock protein 90 (HSP90) known as the stressed response gene, and Gr10, the amino acid response gene were up-regulated and down-regulated respectively in the temperature-stressed group. Low expression of Gr10 under temperature-stress can affect nursing behavior and bee development. Ultimately, these findings will help in identifying honeybee-temperature survival mechanisms under varying temperature effects.