bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobiome analyses of critically ill COVID-19 patients
Authors: Weaver Danielle , Gago Sara , Bassetti Matteo , Giacobbe Daniele Roberto , Prattes Juergen , Hoenigl Martin , Reizine Florian , Guegan Hélène , Gangneux Jean-Pierre , Bromley Michael John , Bowyer Paul 
Published: June 2023

AbstractRationaleCOVID-19-associated pulmonary aspergillosis (CAPA) is a life-threatening complication in patients with severe COVID-19. Previously, acute respiratory distress syndrome in patients with COVID-19 has been associated with lung fungal dysbiosis, evidenced by reduced microbial diversity andCandidacolonisation. Increased fungal burden in the lungs of critically ill COVID-19 patients is linked to prolonged mechanical ventilation and increased mortality. However, specific mycobiome signatures associated with severe COVID-19 in the context of survival and antifungal drug prophylaxis have not yet been determined and such knowledge could have an important impact on treatment.ObjectivesTo understand the composition of the respiratory mycobiome in critically ill COVID-19 patients with and without CAPA and the impact of antifungal use in patient outcome.MethodsWe performed a multi-national study of 39 COVID-19 patients in intensive care units (ICU) with and without CAPA. Respiratory mycobiome was profiled using ITS1 sequencing andAspergillus fumigatusburden was further validated using qPCR. Fungal communities were investigated using alpha diversity, beta diversity, taxa predominance and taxa abundances.ResultsRespiratory mycobiomes of COVID-19 patients were dominated byCandidaandAspergillus.There was no significant association with corticosteroid use or CAPA diagnosis and respiratory fungal communities. IncreasedA. fumigatusburden was associated with mortality and, the use of azoles at ICU admission was linked with an absence ofA. fumigatus.ConclusionsOur findings suggest that mould-active antifungal treatment at ICU admission may be linked with reducedA. fumigatus-associated mortality in severe COVID-19. However, further studies are warranted on this topic.
Demographic inference for spatially heterogeneous populations using long shared haplotypes
Authors: Forien Raphaël , Ringbauer Harald , Coop Graham 
Published: June 2023

AbstractWe introduce a modified spatial Λ-Fleming-Viot process to model the ancestry of individuals in a population occupying a continuous spatial habitat divided into two areas by a sharp discontinuity of the dispersal rate and effective population density. We derive an analytical formula for the expected number of shared haplotype segments between two individuals depending on their sampling locations. This formula involves the transition density of a skew diffusion which appears as a scaling limit of the ancestral lineages of individuals in this model. We then show that this formula can be used to infer the dispersal parameters and the effective population density of both regions, using a composite likelihood approach, and we demonstrate the efficiency of this method on a range of simulated data sets.
Dynamics in the assembly of the 30S ribosomal subunit investigated by coarse-grained simulations
Authors: Liu Xin , Zhang Zhiyong 
Published: June 2023

AbstractThe ribosome is a large biomolecular complex responsible for protein synthesis. InEscherichia coli(E. coli), a complete ribosome is composed of a 30S small subunit and a 50S large subunit. For about half a century, the 30S subunit has been a key model system for studying thein vitroassembly of the ribosome, and an assembly map has been proposed. However, structural details in the assembly of this protein-RNA complex remain elusive. In this paper, we have conducted a series of coarse-grained simulations following the order of the assembly map, in order to investigate conformational dynamics during the assembly process of the 30S subunit. It has been found that, the tertiary structure of the naked 16S rRNA is very unstable, and that is the case after binding of the early-assembly proteins. The mid-assembly proteins can significantly restrict the mobility of the 16S rRNA and make the latter close to the native structure. The final binding of the late-assembly proteins would fully obtain the collective motion of the 16S rRNA. In particular, proteins S9 and S3 may have more important contributions to the assembly of the 30S subunit than other S proteins. Our strategy of coarse-grained simulations can be generally used to study assembly dynamics of large biomolecular complexes as long as the assembly map is available.
Biologically-informed self-supervised learning for segmentation of subcellular spatial transcriptomics data
Authors: Fu Xiaohang , Lin Yingxin , Lin David M , Mechtersheimer Daniel , Wang Chuhan , Ameen Farhan , Ghazanfar Shila , Patrick Ellis , Kim Jinman , Yang Jean YH 
Published: June 2023

AbstractRecent advances in subcellular imaging transcriptomics platforms have enabled high-resolution spatial mapping of gene expression, while also introducing significant analytical challenges in accurately identifying cells and assigning transcripts. Existing methods grapple with cell segmentation, frequently leading to fragmented cells or oversized cells that capture contaminated expression. To this end, we present BIDCell, a self-supervised deep learning-based framework with biologically-informed loss functions that learn relationships between spatially resolved gene expression and cell morphology. BIDCell incorporates cell-type data, including single-cell transcriptomics data from public repositories, with cell morphology information. Using a comprehensive evaluation framework consisting of metrics in five complementary categories for cell segmentation performance, we demonstrate that BIDCell outperforms other state-of-the-art methods according to many metrics across a variety of tissue types and technology platforms. Our findings underscore the potential of BIDCell to significantly enhance single-cell spatial expression analyses, including cell-cell interactions, enabling great potential in biological discovery.
Cortical Activity Associated With Acute Development of Phantom Auditory Percepts via Unilateral Deprivation
Authors: Ginnan Gregory , Rampp Stefan , Schaette Roland , Buchfelder Michael , Müller-Voggel Nadia 
Published: June 2023

ABSTRACTSubjective tinnitus describes the experience of hearing phantom sounds (e.g., tones, buzzing, noise). While the majority of those who report having experienced phantom sounds claim that these percepts have not lasted but are transient, some experience this chronically, with others even describing their tinnitus as severe enough to negatively impact their well-being and daily lives. Currently, no permanent solution has been discovered for preventing or curing tinnitus. This is due to several factors, including an insufficient understanding of the mechanisms at play that give rise to such auditory sensations, as well as a lack of research investigating the corresponding changes in neural activity associated with the onset and development of tinnitus. Taking advantage of the high spatial and temporal resolution of magnetoencephalography (MEG), we measured cortical activity associated with the development of acute tinnitus-like percepts induced via unilateral auditory deprivation. Over the course of four days, participants continuously wore a silicone earplug in one ear, which led to the experience of phantom sounds in 15 of 16 participants. Frequency analysis of source-localized continuous MEG data revealed a significant increase of gamma power in primary auditory cortices (A1) during the tinnitus condition (p=0.02), which most likely reflects the neuronal processing correlated with tinnitus perception.
Label-free quantification LC-mass spectrometry proteomic analysis of blood plasma in healthy dogs
Authors: Doulidis Pavlos G. , Kuropka Benno , Frizzo Ramos Carolina , Rodríguez-Rojas Alexandro , Burgener Iwan A. 
Published: June 2023

AbstractBloodwork is a widely used diagnostic tool in veterinary medicine, as diagnosis and therapeutic interventions often rely on blood biomarkers. However, biomarkers available in veterinary medicine often lack sensitivity or specificity. Mass spectrometry (MS)-based proteomics technology has been extensively used in biological fluids and offers excellent potential for a more comprehensive characterization of the plasma proteome in veterinary medicine. In this study, we aimed to identify and quantify plasma proteins in a cohort of healthy dogs and compare two techniques for depleting high-abundance plasma proteins to enable the detection of lower-abundance proteins. We utilized surplus lithium-heparin plasma from 30 healthy dogs, which were subdivided into five groups of pooled plasma from 6 randomly selected individuals each. Our goal was to identify and quantify plasma proteins via label-free quantification LC-mass spectrometry. Additionally, we employed different methods to deplete the most abundant proteins. Firstly, we used a commercial kit for the depletion of high-abundance plasma proteins. Secondly, we employed an in-house method to remove albumin using Blue-Sepharose. Among all the samples, some of the most abundant proteins identified were apolipoprotein A and B, albumin, alpha-2-macroglobulin, fibrinogen beta chain, fibronectin, complement C3, serotransferrin, and coagulation Factor V. However, neither of the depletion techniques achieved significant depletion of high-abundant proteins. Nevertheless, the two different depletion methods exhibited substantial differences in the fold-change of many proteins, suggesting partial depletion that did not contribute to an increase in the number of detected proteins. Despite this limitation, we were able to detect and quantify many clinically relevant proteins. The determination of the healthy canine proteome is a crucial first step in establishing a reference proteome for canine plasma. This reference proteome can later be utilized to identify protein markers associated with different diseases, thereby contributing to the diagnosis and prognosis of various pathologies.
A large-scale sORF screen identifies putative microproteins and provides insights into their interaction partners, localisation and function
Authors: Schlesinger Dörte , Dirks Christopher , Luzon Carmen Navarro , Lafranchi Lorenzo , Eirich Jürgen , Elsässer Simon J 
Published: June 2023

AbstractThe human genome contains thousands of potentially coding short open reading frames (sORFs). A growing set of microproteins translated from these sORFs are known to have important cellular functions. However, the majority remains uncharacterised. Thus, larger screens to find functional microproteins have become more vital. Here, we performed a high-throughput CRISPR/Cas9 knock-out screen with a customised library of 11,776 sORFs, curated from literature and databases to identify microproteins essential for cancer cell line growth. 16/17 tested candidates displayed a reproducible knockout phenotype. We selected our top six hits, consisting of 11 to 63 amino acids. Various of these candidates localised to distinct subcellular compartments and the majority showed specific interaction partners. Endogenous tagging demonstrated translation of an sORF in the CENPBD2P pseudogene that bears no resemblance to the CENPBD2P name-giving CENPB DNA binding domains. For two candidates, uORFs in the DSE and NUTF2 genes, the microprotein suppliedin transameliorated the growth defect of the respective knock-out. RNA-seq analysis revealed however that gene expression changes in the knock-out could only partially be rescued. Overall, we identified various putative microproteins and a microprotein-producing pseudogene that might be involved in cancer cell growth, but also illustrate the limitations and caveats of sORF functional screening and characterisation.
The effects of prefrontal tDCS on working memory associate with the magnitude of the individual electric field in the brain
Authors: Razza Lais B. , De Smet Stefanie , Van Hoornweder Sybren , De Witte Sara , Luethi Matthias S. , Baeken Chris , Brunoni Andre R. , Vanderhasselt Marie-Anne 
Published: June 2023

AbstractTranscranial direct current stimulation (tDCS) over the prefrontal cortex has the potential to enhance working memory by means of a weak direct current applied to the scalp. However, its effects are highly variable and possibly dependent on individual variability in cortical architecture and head anatomy. Unveiling sources of heterogeneity might improve fundamental and clinical application of tDCS in the field. Therefore, we investigated sources of tDCS variability of prefrontal 1.5mA tDCS, 3mA tDCS and sham tDCS in 40 participants (67.5% women, mean age 24.7 years) by associating simulated electric field (E-field) magnitude in brain regions of interest (dorsolateral prefrontal cortex, anterior cingulate cortex (ACC) and subgenual ACC) and working memory performance. Emotional and non-emotional 3-back paradigms were used. In the tDCS protocol analysis, effects were only significant for the 3mA group, and only for the emotional tasks. In the individual E-field magnitude analysis, faster responses in non-emotional, but not in the emotional task, were associated with stronger E-fields in all brain regions of interest. A follow-up analysis showed that people with higher (vs. lower) E-fields magnitude in the left DLPFC were faster in the both tasks, and more accurate in the emotional task. Concluding, individual E-field distribution might explain part of the variability of prefrontal tDCS effects on working memory performance and in clinical samples. Our results suggest that tDCS effects can be more consistent or improved by applying personalizing current intensity, although this hypothesis should be confirmed by further studies.
The homeodomain drives favorable DNA binding energetics of prostate cancer target ONECUT2
Authors: Chatterjee Avradip , Gallent Brad , Katiki Madhusudhanarao , Qian Chen , Harter Matthew R. , Freeman Michael R. , Murali Ramachandran 
Published: June 2023

AbstractThe ONECUT transcription factors feature a CUT and a homeodomain, evolutionarily conserved elements that bind DNA cooperatively, but the process remains mechanistically enigmatic. Using an integrative DNA binding analysis of ONECUT2, a driver of aggressive prostate cancer, we show that the homeodomain energetically stabilizes the ONECUT2-DNA complex through allosteric modulation of CUT. Further, evolutionarily conserved base-interactions in both the CUT and homeodomain are necessary for the favorable thermodynamics. We have identified a novel arginine pair unique to the ONECUT family homeodomain that can adapt to DNA sequence variations. Base interactions in general, including by this arginine pair, are critical for optimal DNA binding and transcription in a prostate cancer model. These findings provide fundamental insights into DNA binding by CUT-homeodomain proteins with potential therapeutic implications.One-Sentence SummaryBase-specific interactions regulate homeodomain-mediated stabilization of DNA binding by the ONECUT2 transcription factor.
Structure-based virtual screening identifies small molecule inhibitors of O-fucosyltransferase SPINDLY
Authors: Aizezi Yalikunjiang , Zhao Hongming , Zhang Zhenzhen , Bi Yang , Yang Qiuhua , Guo Guangshuo , Zhang Hongliang , Guo Hongwei , Jiang Kai , Wang Zhi-Yong 
Published: June 2023

AbstractProtein O-glycosylation is a nutrient-signaling mechanism that plays essential roles in maintaining cellular homeostasis across different species. In plants, SPINDLY (SPY) and SECRET AGENT (SEC) catalyze posttranslational modifications of hundreds of intracellular proteins by O-fucose and O-linked N-acetylglucosamine, respectively. SPY and SEC play overlapping roles in cellular regulation and loss of both SPY and SEC causes embryo lethality in Arabidopsis. Using structure-based virtual screening of chemical libraries followed byin vitroandin plantaassays, we identified aSPYO-fucosyltransferaseinhibitor (SOFTI). Computational analyses predicted that SOFTI binds to the GDP-fucose-binding pocket of SPY and competitively inhibits GDP-fucose binding.In vitroassays confirmed that SOFTI interacts with SPY and inhibits its O-fucosyltransferase activity. Docking analysis identified additional SOFTI analogs that showed stronger inhibitory activities. SOFTI treatment of Arabidopsis seedlings decreased protein O-fucosylation and caused phenotypes similar to thespymutants, including early seed germination, increased root hair density, and defect in sugar-dependent growth. By contrast, SOFTI had no visible effect on thespymutant. Similarly, SOFTI inhibited sugar-dependent growth of tomato seedlings. These results demonstrate that SOFTI is a specific SPY O-fucosyltransferase inhibitor and a useful chemical tool for functional studies of O-fucosylation and potentially for agricultural management.
Population ecology and potential biogeochemical impacts of ssDNA and dsDNA soil viruses along a permafrost thaw gradient
Authors: Trubl Gareth , Roux Simon , Borton Mikayla A. , Varsani Arvind , Li Yueh-Fen , Sun Christine , Jang Ho Bin , Woodcroft Ben J. , Tyson Gene W. , Wrighton Kelly C. , Saleska Scott R. , Eloe-Fadrosh Emiley A. , Sullivan Matthew B. , Rich Virginia I. 
Published: June 2023

AbstractClimate change is disproportionately warming northern peatlands, which may release large carbon stores via increased microbial activity. While there are many unknowns about such microbial responses, virus roles are especially poorly characterized with studies to date largely restricted to “bycatch” from bulk metagenomes. Here, we used optimized viral particle purification techniques on 20 samples along a highly contextualized peatland permafrost thaw gradient, extracted and sequenced viral particle DNA using two library kits to capture single-stranded (ssDNA) and double-stranded (dsDNA) virus genomes (40 total viromes), and explored their diversity and potential ecosystem impacts. Both kits recovered similar dsDNA virus numbers, but only one also captured thousands of ssDNA viruses. Combining these data, we explored population-level ecology using genomic representation from 9,560 viral operational taxonomic units (vOTUs); nearly a 4-fold expansion from permafrost-associated soils, and 97% of which were novel when compared against large datasets from soils, oceans, and the human gut.In silicopredictions identified putative hosts for 44% (4,149 dsDNA + 17 ssDNA) of the identified vOTUs spanning 2 eukaryotic, 12 archaeal, and 30 bacterial phyla. The recovered vOTUs encoded 1,684 putative auxiliary metabolic genes (AMGs) and other metabolic genes carried by ∼10% of detected vOTUs, of which 46% were related to carbon processing and 644 were novel. These AMGs grouped into five functional categories and 11 subcategories, and nearly half (47%) of the AMGs were involved in carbon utilization. Of these, 112 vOTUs encoded 123 glycoside hydrolases spanning 15 types involved in the degradation of polysaccharides (e.g., cellulose) to monosaccharides (e.g., galactose), or further monosaccharide degradation, which suggests virus involvement in myriad metabolisms including fermentation and central carbon metabolism. These findings expand the scope of viral roles in microbial carbon processing and suggest viruses may be critical for understanding the fate of soil organic carbon in peatlands.
Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses
Authors: Jiang Kaiyi , Lim Justin , Sgrizzi Samantha , Trinh Michael , Kayabolen Alisan , Yutin Natalya , Koonin Eugene V. , Abudayyeh Omar O. , Gootenberg Jonathan S. 
Published: June 2023

AbstractTnpB proteins are RNA-guided nucleases that are broadly associated with IS200/605 family transposons in prokaryotes. TnpB homologs, named Fanzors, have been detected in genomes of some eukaryotes and large viruses, but their activity and functions in eukaryotes remain unknown. We searched genomes of diverse eukaryotes and their viruses for TnpB homologs and identified numerous putative RNA-guided nucleases that are often associated with various transposases, suggesting they are encoded in mobile genetic elements. Reconstruction of the evolution of these nucleases, which we rename Horizontally-transferred Eukaryotic RNA-guided Mobile Element Systems (HERMES), revealed multiple acquisitions of TnpBs by eukaryotes and subsequent diversification. In their adaptation and spread in eukaryotes, HERMES proteins acquired nuclear localization signals, and genes captured introns, indicating extensive, long term adaptation to functioning in eukaryotic cells. Biochemical and cellular evidence show that HERMES employ non-coding RNAs encoded adjacent to the nuclease for RNA-guided cleavage of double-stranded DNA. HERMES nucleases contain a re-arranged catalytic site of the RuvC domain, similar to a distinct subset of TnpBs, and lack collateral cleavage activity. We demonstrate that HERMES can be harnessed for genome editing in human cells, highlighting the potential of these widespread eukaryotic RNA-guided nucleases for biotechnology applications.
Implicit motor adaptation patterns in a redundant motor task manipulating a stick with both hands
Authors: Kobayashi Toshiki , Nozaki Daichi 
Published: June 2023

AbstractThe remarkable ability of the motor system to adapt to novel environments has traditionally been investigated using kinematically non-redundant tasks, such as planar reaching movements. This limitation prevents the study of how the motor system achieves adaptation by altering the movement patterns of our redundant body. To address this issue, we developed a redundant motor task in which participants reached for targets with the tip of a virtual stick held with both hands. Despite the redundancy of the task, participants consistently employed a stereotypical strategy of flexibly changing the tilt angle of the stick depending on the direction of tip movement. Thus, this baseline relationship between tip-movement direction and stick-tilt angle constrained both the physical and visual movement patterns of the redundant system. Our task allowed us to systematically investigate how the motor system implicitly changed both the tip-movement direction and the stick-tilt angle in response to imposed visual perturbations. Both types of perturbations, whether directly affecting the task (tip-movement direction) or not (stick-tilt angle around the tip), drove adaptation, and the patterns of implicit adaptation were guided by the baseline relationship. Consequently, tip-movement adaptation was associated with changes in stick-tilt angle, and intriguingly, even seemingly ignorable stick-tilt perturbations significantly influenced tip-movement adaptation, leading to tip-movement direction errors. These findings provide a new understanding that the baseline relationship plays a crucial role not only in how the motor system controls movement of the redundant system, but also in how it implicitly adapts to modify movement patterns.