bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of 8-mer Peptides that BlockClostridioides difficileToxin A in Intestinal Cells
Authors: Sarma Sudeep , Catella Carly M. , Pedro Ellyce T. San , Xiao Xingqing , Durmusoglu Deniz , Menegatti Stefano , Crook Nathan , Magness Scott T. , Hall Carol K. 
Published: January 2023

AbstractClostridioides difficile(C. diff.) is a bacterium that causes severe diarrhea and inflammation of the colon. The pathogenicity ofC. diff. infection is derived from two major toxins, toxins A (TcdA) and B (TcdB). Peptide inhibitors that can be delivered to the gut to inactivate these toxins are an attractive therapeutic strategy. In this work, we present a new approach that combines apeptidebindingdesign algorithm (PepBD), molecular-level simulations, rapid screening of candidate peptides for toxin binding, a primary human cell-based assay, and surface plasmon resonance (SPR) measurements to develop peptide inhibitors that block the glucosyltransferase activity of TcdA by targeting its glucosyltransferase domain (GTD). Using PepBD and explicit-solvent molecular dynamics simulations, we identified seven candidate peptides, SA1-SA7. These peptides were selected for specific TcdA GTD binding through a custom solid-phase peptide screening system, which eliminated the weaker inhibitors SA5-SA7. The efficacies of SA1-SA4 were then tested using a trans-epithelial electrical resistance (TEER) assay on monolayers of the human gut epithelial culture model. One peptide, SA1, was found to block TcdA toxicity in primary-derived human jejunum (small intestinal) and colon (large intestinal) epithelial cells. SA1 bound TcdA with a KDof 56.1 ± 29.8 nM as measured by surface plasmon resonance (SPR).Significance StatementInfections byClostridioides difficile, a bacterium that targets the large intestine (colon), impact a significant number of people worldwide. Bacterial colonization is mediated by two exotoxins: toxins A and B. Short peptides that can inhibit the biocatalytic activity of these toxins represent a promising strategy to prevent and treatC. diff. infection. We describe an approach that combines aPeptide BindingDesign (PepBD) algorithm, molecular-level simulations, a rapid screening assay to evaluate peptide:toxin binding, a primary human cell-based assay, and surface plasmon resonance (SPR) measurements to develop peptide inhibitors that block Toxin A in small intestinal and colon epithelial cells. Importantly, our designed peptide, SA1, bound toxin A with nanomolar affinity and blocked toxicity in colon cells.
Determining Best Practice for the Spatial Poisson Process in Species Distribution Modelling
Authors: Bellew Sean , Flint Ian , Wang Yan 
Published: January 2023

AbstractPoisson processes have become a prominent tool in species distribution modelling when analysing citizen science data based on presence records. This study examines four distinct statistical approaches, each of which utilises a different approximation to fit a Poisson point process. These include two Poisson regressions with either uniform weights or the more elaborate Berman-Turner device, as well as two logistic regressions, namely the infinitely weighted logistic regression method and Baddeley’s logistic regression developed in the context of spatial Gibbs processes. This last method has not been considered in depth in the context of Poisson point processes in the previous literature. A comprehensive comparison has been conducted on the performance of these four approaches using both simulated and actual presence data sets. When the number of dummy points is sufficiently large, all approaches converge, with the Berman-Turner device demonstrating the most consistent performance. A Poisson process model was developed to accurately predict the distribution of Arctotheca calendula, an invasive weed in Australia that does not appear to have been the subject of any species niche modelling analysis in the existing literature. Our findings are valuable for ecologists and other non-statistical experts who wish to implement the best practices for predicting species’ distribution using Poisson point processes.
Perilaryngeal Functional Muscle Network in Patients with Vocal Hyperfunction - A Case Study
Authors: O’Keeffe Rory , Shirazi Seyed Yahya , Mehrdad Sarmad , Crosby Tyler , Johnson Aaron M. , Atashzar S. Farokh 
Published: January 2023

AbstractPatients with both phonotraumatic and non-phonotraumatic dysphonia commonly present with vocal hyperfunction, defined as excessive perilaryngeal muscle activity and characterized by muscular pain and strain in the neck, increased vocal effort, and vocal fatigue. The inability to reliably measure vocal hyperfunction is a barrier to adequate evaluation and treatment of hyperfunctional voice disorders. We have recently demonstrated that the perilaryngeal functional muscle network can be a novel sensitive neurophysiological window to vocal performance in vocally healthy subjects. In this paper, for the first time, we evaluate the performance and symmetry of functional perilaryngeal muscle networks in three patients with voice disorders. Surface electromyography signals were recorded from twelve sensors (six on each side of the neck) using the wireless Trigno sEMG system (Delsys Inc., Natick, MA). Patient 1 was diagnosed with primary muscle tension dysphonia, Patient 2 was diagnosed with unilateral vocal fold paresis, and Patient 3 was diagnosed with age-related glottal insufficiency. This paper reports altered functional connectivity and asymmetric muscle network scan behavior in all three patients when compared with a cohort of eight healthy subjects. Our approach quantifies synergistic network activity to interrogate coordination of perilaryngeal and surrounding muscles during voicing and potentialdiscoordinationof the muscle network for dysphonic conditions. Asymmetry in muscle networks is proposed here as a biomarker for monitoring vocal hyperfunction.
OpaR exerts a dynamic control over c-di-GMP homeostasis andcpsAexpression inV. parahaemolyticusthrough its regulation of ScrC and the trigger phosphodiesterase TpdA
Authors: Zamorano-Sánchez David , Alejandre-Sixtos Jesús E. , Arredondo-Hernández Adilene , Martínez-Méndez Raquel 
Published: January 2023

AbstractThe second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) plays a central role in controlling decision making processes of vital importance for the environmental survival of the human pathogenVibrio parahaemolyticus. The mechanisms by which c-di-GMP levels are dynamically controlled inV. parahaemolyticusare poorly understood. Here we report our findings regarding the involvement of OpaR in controlling c-di-GMP metabolism in planktonic and surface-attached cells through controlling the expression of the trigger phosphodiesterase (PDE) TpdA and other PDEs such as ScrC. Our results revealed that OpaR negatively modulates the expression oftpdAby maintaining a baseline level of c-di-GMP. The OpaR-regulated PDEs ScrC, ScrG and VP0117 enable the upregulation oftpdA, to a different degree, in the absence of OpaR. We also found that TpdA plays the dominant role in c-di-GMP degradation under planktonic conditions compared to the other OpaR-regulated PDEs. In cells growing over solid media the dominant c-di-GMP degrader role is played by ScrC for 72 hours and passes to TpdA after 96 hours of growth. We also report negative and positive effects of the absence of OpaR oncpsAexpression in cells growing over solid media or forming biofilms over glass, respectively. These results suggest that OpaR can act as a double-edged sword to control c-di-GMP accumulation andcpsAexpression positively or negatively in response to poorly understood environmental factors. Finally, through anin-silicoanalysis we point out outlets of the OpaR regulatory module that can impact decision making during the motile to sessile transition inV. parahaemolyticus.ImportanceThe second messenger c-di-GMP is extensively used by bacterial cells to control crucial social adaptations such as biofilm formation. Here we explore the role of the quorum-sensing regulatorOpaR, from the human pathogenV. parahaemolyticus, on the dynamic control of c-di-GMP signaling. We found that OpaR can regulate positively or negatively c-di-GMP accumulation depending on the growth conditions. This dual role has not been reported for orthologues of OpaR, such as HapR fromV. cholerae. OpaR controls c-di-GMP homeostasis through PDEs that are absent inV. cholerae, pointing toward further differences in c-di-GMP signaling in these two pathogens. It is important to investigate the origins and consequences of these differences to better understand pathogenic bacterial behavior and its evolution.
Genomic characterization of multidrug-resistant extended spectrum β-lactamase-producingKlebsiella pneumoniaefrom clinical samples of a tertiary hospital in South Kivu Province, eastern Democratic Republic of Congo
Authors: Irenge Leonid M. , Ambroise Jérôme , Bearzatto Bertrand , Durant Jean-François , Bonjean Maxime , Gala Jean-Luc 
Published: January 2023

AbstractMultidrug-resistant (MDR) and Extended Spectrum β-Lactamase (ESBL)-producing extraintestinalK. pneumoniaeare associated with increased morbidity and mortality. This study aimed to characterize the resistance and virulence profiles of extra-intestinal MDR ESBL-producingK. pneumoniaeassociated with infections at a tertiary hospital in South-Kivu province, DRC. Whole-genome sequencing (WGS) was carried out on 37 K.pneumoniaeisolates displaying MDR, and ESBL-producing phenotype. The assembled genomes were analysed for phylogeny, virulence factors and antimicrobial resistance genes determinants. These isolates were compared to sub-Saharan counterparts.K. pneumoniaeisolates displayed a high genetic variability with up to 16 sequence types (ST). AMR was widespread against β-lactamases (including third and fourth-generation cephalosporins, but not carbapenems), aminoglycosides, ciprofloxacin, tetracycline, erythromycin, nitrofurantoin, and cotrimoxazole. TheblaCTXM-15gene was the most common β-lactamase gene amongK. pneumoniaeisolates. No carbapenemase gene was found. ARG for aminoglycosides, quinolones, phenicols, tetracyclines, sulfonamides, nitrofurantoin were widely distributed among the isolates. Nine isolates had the colistin-resistant R256G substitution in thepmrBefflux pump gene without displaying reduced susceptibility to colistin. Despite carrying virulence genes, none had hypervirulence genes. Our results highlight the genetic diversity of MDR ESBL-producingK. pneumoniaeisolates, and underscore the importance of monitoring simultaneously the evolution of phenotypic and genotypic AMR in Bukavu and DRC, while calling for caution in administering colistin and carbapenem to patients.
A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools
Authors: Morey-León Gabriel , Mejía-Ponce Paulina M. , Granda Pardo Juan Carlos , Muñoz-Mawyin Karen , Fernández-Cadena Juan Carlos , García-Moreira Evelyn , Andrade-Molina Derly , Licona-Cassani Cuauhtémoc , Berná Luisa 
Published: January 2023

AbstractTuberculosis (TB) is among the most deadly diseases that affect worldwide, its impact is mainly due to the continuous emergence of resistant isolates during treatment due to the laborious process of resistance diagnosis, non-adherence to treatment and circulation of previously resistant isolates ofMycobacterium tuberculosis. The aim in this study was evaluate the performance and functionalities of web-based tools: Mykrobe, TB-profiler, PhyReSse, KvarQ, and SAM-TB for detecting resistance in isolate ofMycobacterium tuberculosisin comparison with conventional drug susceptibility tests. We used 88M. tuberculosisisolates which were drug susceptibility tested and subsequently fully sequenced and web-based tools analysed. Statistical analysis was performed to determine the correlation between genomic and phenotypic analysis. Our data show that the main sub-lineage was LAM (44.3%) followed by X-type (23.0%) within isolates evaluated. Mykrobe has a higher correlation with DST (98% of agreement and 0.941Cohen’s Kappa) for global resistance detection, but SAM-TB, PhyReSse and Mykrobe had a better correlation with DST for first-line drug analysis individually. We have identified that 50% of mutations characterised by all web-based tools were canonical inrpoB, katG, embB, pncA, gyrAandrrsregions. Our findings suggest that SAM-TB, PhyReSse and Mykrobe were the web-based tools more efficient to determine canonical resistance-related mutations, however more analysis should be performed to improve second-line detection. The improvement of surveillance programs for the TB isolates applying WGS tools against first line drugs, MDR-TB and XDR-TB are priorities to discern the molecular epidemiology of this disease in the country.ImportanceTuberculosis, an infectious disease caused byMycobacterium tuberculosis, which most commonly affects the lungs and is often spread through the air when infected people cough, sneeze, or spit. However, despite the existence of effective drug treatment, the patient adherence, long duration of treatment, and late diagnosis, have reduced the effectiveness of therapy and raised the drug resistance. The increase in resistant cases, added to the impact of the COVID-19 pandemic, have highlighted the importance of implementing efficient and timely diagnostic methodologies worldwide. The significance of our research is in evaluating and identifying the more efficient and friendly web-based tool to characterise the resistance inMycobacterium tuberculosisby whole genome sequencing, which will allow apply it more routinely to improve TB strain surveillance programs locally.
“You have to add your own character”: Medical Student Perspectives on Observing Clinical Encounters
Authors: Poeppelman Rachel Stork , Fromme H Barrett , Yudkowsky Rachel , Lineberry Matthew , Hirshfield Laura 
Published: January 2023

AbstractIntroductionThe authors aimed to investigate how medical students interpret the observation of a more experienced clinician modeling both exemplaryandflawed behaviors as well as how that interpretation influences their subsequent clinical performance.MethodsWe presented a recorded patient sexual history to 11 medical students. The recording displayed both exemplary and flawed behaviors. Students then obtained a sexual history from a standardized patient themselves. Using an interview methodology and constructivist analytic approach, we explored the process of learning from clinical observations.ResultsStudents attended to flawed modeled behaviors, challenges specific to the task, and how areas of their own personal development were accomplished. They took a piecemeal approach to classifying modeled behaviors as done well or poorly based on previous instruction, experience, or perceived downstream effects. When applying their observations, students choose to copy, adapt, or avoid modeled behaviors based on their classification of the behavior.DiscussionTo optimize learning from observation, faculty can identify task-specific challenges and a student’s personal goals, which naturally draw the student’s attention, before observation in order to develop a shared mental model. When debriefing observed encounters, faculty may consider natural targets of learner attention, challenges specific to learning from observation, and factors likely to influence a learner’s judgement of modeled behaviors.
Deep learning prediction boosts phosphoproteomics-based discoveries through improved phosphopeptide identification
Authors: Yi Xinpei , Wen Bo , Ji Shuyi , Saltzman Alex , Jaehnig Eric J. , Lei Jonathan T. , Gao Qiang , Zhang Bing 
Published: January 2023

AbstractShotgun phosphoproteomics enables high-throughput analysis of phosphopeptides in biological samples, but low phosphopeptide identification rate in data analysis limits the potential of this technology. Here we present DeepRescore2, a computational workflow that leverages deep learning-based retention time and fragment ion intensity predictions to improve phosphopeptide identification and phosphosite localization. Using a state-of-the-art computational workflow as a benchmark, DeepRescore2 increases the number of correctly identified peptide-spectrum matches by 17% in a synthetic dataset and identifies 19%-46% more phosphopeptides in biological datasets. In a liver cancer dataset, 30% of the significantly altered phosphosites between tumor and normal tissues and 60% of the prognosis-associated phosphosites identified from DeepRescore2-processed data could not be identified based on the state-of-the-art workflow. Notably, DeepRescore2-processed data uniquely identifies EGFR hyperactivation as a new target in poor-prognosis liver cancer, which is validated experimentally. Integration of deep learning prediction in DeepRescore2 improves phosphopeptide identification and facilitates biological discoveries.
Major axes of variation in tree demography across global forests
Authors: Leite Melina de Souza , McMahon Sean M. , Prado Paulo Inácio , Davies Stuart J. , Oliveira Alexandre Adalardo de , De Deurwaerder Hannes P. , Aguilar Salomón , Anderson-Teixeira Kristina J. , Aqilah Nurfarah , Bourg Norman A. , Brockelman Warren Y. , Castaño Nicolas , Chang-Yang Chia-Hao , Chen Yu-Yun , Chuyong George , Clay Keith , Duque Álvaro , Ediriweera Sisira , Ewango Corneille E.N. , Gilbert Gregory , Gunatilleke I.A.U.N. , Gunatilleke C.V.S. , Howe Robert , Huasco Walter Huaraca , Itoh Akira , Johnson Daniel J. , Kenfack David , Král Kamil , Leong Yao Tze , Lutz James A. , Makana Jean-Remy , Malhi Yadvinder , McShea William J. , Mohamad Mohizah , Nasardin Musalmah , Nathalang Anuttara , Parker Geoffrey , Parmigiani Renan , Pérez Rolando , Phillips Richard P. , Šamonil Pavel , Sun I-Fang , Tan Sylvester , Thomas Duncan , Thompson Jill , Uriarte María , Wolf Amy , Zimmerman Jess , Zuleta Daniel , Visser Marco D. , Hülsmann Lisa 
Published: January 2023

AbstractThe future trajectory of global forests is closely intertwined with tree demography, and a major fundamental goal in ecology is to understand the key mechanisms governing spatial-temporal patterns in tree population dynamics. While historical research has made substantial progress in identifying the mechanisms individually, their relative importance among forests remains unclear mainly due to practical limitations. One approach is to group mechanisms according to their shared effects on the variability of tree vital rates and to quantify patterns therein. We developed a conceptual and statistical framework (variance partitioning of Bayesian multilevel models) that attributes the variability in tree growth, mortality, and recruitment to variation in species, space, and time, and their interactions, categories we refer to asorganising principles(OPs). We applied the framework to data from 21 forest plots covering more than 2.9 million trees of approximately 6,500 species. We found that differences among species, thespeciesOP, proved a major source of variability in tree vital rates, explaining 28-33% of demographic variance alone, and in interaction withspace14-17%, totalling 40-43%. The average variability among species declined with species richness across forests, indicating that diverse forests featured smaller interspecific differences in vital rates supporting the theory that the range of vital rates is similar across global forests. Decomposing the variance in vital rates into the proposed OPs showed that taxonomy is crucial to predicting and understanding tree demography on large forest plots. A focus on how variance is organized in forests can facilitate the construction of more targeted models with clearer expectations of which covariates might drive a vital rate. This study therefore highlights the most promising avenues for future research, both in terms of understanding the relative contributions of groups of mechanisms to forest demography and diversity, and for improving projections of forest ecosystems.
Warming-induced range expansion effects on the diversity and composition of the gut microbiome: a case study with two butterflies
Authors: Montoya Daniel , de Jong Maaike 
Published: January 2023

AbstractSpecies are the habitat of a diverse community of organisms, including bacteria, fungi and viruses – themicrobiome. Evidence shows that many species shift and/or expand their geographical ranges following warming climate; yet, the response of host-associated microbiome communities to species range shifts has received less attention, especially in observational studies. Here, we use two British butterfly species for which detailed long-term distributional data is available, and document for the first time a variety of effects of warming-induced range expansion on the diversity and composition of their microbiome. Our results show similar diversity and species-specific responses in the evenness of the gut microbial communities in the two butterflies. However, butterflies at the expanded ranges showed (i) a larger variability in the microbiome diversity, and (ii) a smaller core community of bacteria that is to a large extent a subset of the bacterial core community in the original range. The microbiome is responsible for many aspects of the host’s physiology and growth, and for ecosystem function, so if the changes in the gut microbial communities reported here apply to other species and taxonomic groups, the potential impact to biodiversity and functioning after range expansion could be severe.
Functional membrane microdomains and the hydroxamate siderophore transporter ATPase FhuC govern Isd-dependent heme acquisition inStaphylococcus aureus
Authors: Adolf Lea Antje , Müller-Jochim Angelika , Kricks Lara , Puls Jan-Samuel , Lopez Daniel , Grein Fabian , Heilbronner Simon 
Published: January 2023

AbstractSufficient access to transition metals such as iron is essential for bacterial proliferation and their active limitation within host tissues effectively restricts infection. To overcome iron limitation, the invasive pathogenStaphylococcus aureususes the iron-regulated surface determinant (Isd) system to acquire hemoglobin-derived heme. While heme transport over the cell wall is well understood, its transport over the membrane is hardly investigated. In this study, we show the heme-specific permease IsdF to be energized by the general ATPase FhuC. Additionally, we show that IsdF needs appropriate location within the membrane for functionality. The membrane ofS. aureuspossesses special compartments (functional membrane microdomains – FMMs) to organize membrane complexes. We show IsdF to be associated with FMMs, to directly interact with the FMM scaffolding protein flotillin A (FloA) and to co-localize with the latter on intact bacterial cells. Additionally, Isd-dependent bacterial growth required FMMs and FloA. Our study shows that Isd-dependent heme acquisition requires a highly structured cell envelope to allow coordinated transport over the cell wall and membrane and it gives the first example of a bacterial nutrient acquisition system that depends on FMMs.