bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineered cross-feeding creates inter- and intra-species synthetic yeast communities with enhanced bioproduction
Authors: Park Young-Kyoung , Peng Huadong , Hapeta Piotr , Sellés Vidal Lara , Ledesma-Amaro Rodrigo 
Published: October 2024

AbstractMicroorganisms can be engineered to sustainably produce a variety of products including fuels, pharmaceuticals, materials, and food. However, highly engineered strains often result in low production yield, due to undesired effects such as metabolic burden and the toxicity of intermediates. Drawing inspiration from natural ecosystems, the construction of a synthetic community with division of labor can offer advantages for bioproduction. This approach involves dividing specific tasks among community members, thereby enhancing the functionality of each member. In this study, we identify six pairs out of fifteen composed of six auxotrophs of Yarrowia lipolytica that spontaneously form robust syntrophic and synergistic communities. We characterize the stability and growth dynamics of these communities. Furthermore, we validate the existence of syntrophic interactions between two yeast species, Y. lipolytica and Saccharomyces cerevisiae, and find a strain combination, Δtrp2 and Δtrp4, forming a stable syntrophic community between two species. Subsequently, we introduce a 3-hydroxypropionic acid (3-HP) biosynthesis pathway into the syntrophic community by dividing the pathway among different strains. Our results demonstrate improved production of 3-HP in both intra- and interspecies communities compared to monocultures. Our results show the stable formation of synthetic syntrophic communities, and their potential in improving bioproduction processes.
Active state structures of a bistable visual opsin bound to G proteins
Authors: Tejero Oliver , Pamula Filip , Koyanagi Mitsumasa , Nagata Takashi , Afanasyev Pavel , Das Ishita , Deupi Xavier , Sheves Mordechai , Terakita Akihisa , Schertler Gebhard F. X. , Rodrigues Matthew J. , Tsai Ching-Ju 
Published: October 2024

AbstractOpsins are G protein-coupled receptors (GPCRs) that have evolved to detect light stimuli and initiate intracellular signaling cascades. Their role as signal transducers is critical to light perception across the animal kingdom. Opsins covalently bind to the chromophore 11-cis retinal, which isomerizes to the all-trans isomer upon photon absorption, causing conformational changes that result in receptor activation. Monostable opsins, responsible for vision in vertebrates, release the chromophore after activation and must bind another retinal molecule to remain functional. In contrast, bistable opsins, responsible for non-visual light perception in vertebrates and for vision in invertebrates, absorb a second photon in the active state to return the chromophore and protein to the inactive state. Structures of bistable opsins in the activated state have proven elusive, limiting our understanding of how they function as bidirectional photoswitches. Here we present active state structures of a bistable opsin, jumping spider rhodopsin isoform-1 (JSR1), in complex with its downstream signaling partners, the Gi and Gq heterotrimers. These structures elucidate key differences in the activation mechanisms between monostable and bistable opsins, offering essential insights for the rational engineering of bistable opsins into diverse optogenetic tools to control G protein signaling pathways.
Streamlined analysis of drug targets by proteome integral solubility alteration indicates organ-specific engagement
Authors: Batth Tanveer Singh , Locard-Paulet Marie , Doncheva Nadezhda T. , Lopez Mendez Blanca , Jensen Lars Juhl , Olsen Jesper Velgaard 
Published: October 2024

AbstractProteins are the primary targets of almost all small molecule drugs. However, even the most selectively designed drugs can potentially target several unknown proteins. Identification of potential drug targets can facilitate design of new drugs and repurposing of existing ones. Current state-of-the-art proteomics methodologies enable screening of thousands of proteins against a limited number of drug molecules. Here we report the development of a label-free quantitative proteomics approach that enables proteome-wide screening of small organic molecules in a scalable, reproducible, and rapid manner by streamlining the proteome integral solubility alteration (PISA) assay. We used rat organs ex-vivo to determine organ specific targets of medical drugs and enzyme inhibitors to identify drug targets for common drugs such as Ibuprofen. Finally, global drug profiling revealed overarching trends of how small molecules affect the proteome through either direct or indirect protein interactions.
Rumicidins are a family of mammalian host-defense peptides plugging the 70S ribosome exit tunnel
Authors: Panteleev Pavel V. , Pichkur Eugene B. , Kruglikov Roman N. , Paleskava Alena , Shulenina Olga V. , Bolosov Ilia A. , Bogdanov Ivan V. , Safronova Victoria N. , Balandin Sergey V. , Marina Valeriya I. , Kombarova Tatiana I. , Korobova Olga V. , Shamova Olga V. , Myasnikov Alexander G. , Borzilov Alexander I. , Osterman Ilya A. , Sergiev Petr V. , Bogdanov Alexey A. , Dontsova Olga A. , Konevega Andrey L. , Ovchinnikova Tatiana V. 
Published: October 2024

AbstractThe antimicrobial resistance crisis along with challenges of antimicrobial discovery revealed the vital necessity to develop new antibiotics. Many of the animal proline-rich antimicrobial peptides (PrAMPs) inhibit the process of bacterial translation. Genome projects allowed to identify immune-related genes encoding animal host defense peptides. Here, using genome mining approach, we discovered a family of proline-rich cathelicidins, named rumicidins. The genes encoding these peptides are widespread among ruminant mammals. Biochemical studies indicated that rumicidins effectively inhibited the elongation stage of bacterial translation. The cryo-EM structure of the Escherichia coli 70S ribosome in complex with one of the representatives of the family revealed that the binding site of rumicidins span the ribosomal A-site cleft and the nascent peptide exit tunnel interacting with its constriction point by the conservative Trp23-Phe24 dyad. Bacterial resistance to rumicidins is mediated by knockout of the SbmA transporter or modification of the MacAB-TolC efflux pump. A wide spectrum of antibacterial activity, a high efficacy in the animal infection model, and lack of adverse effects towards human cells in vitro make rumicidins promising molecular scaffolds for development of ribosome-targeting antibiotics.
Ex vivo imaging reveals the spatiotemporal control of ovulation
Authors: Thomas Christopher , Marx Tabea Lilian , Penir Sarah Mae , Schuh Melina 
Published: October 2024

AbstractDuring ovulation, an egg is released from an ovarian follicle, ready for fertilization. Ovulation occurs inside the body, impeding direct studies of its progression. Therefore, the exact mechanisms that control ovulation have remained unclear. Here we devised live imaging methods to study the entire process of ovulation in isolated mouse ovarian follicles. We show that ovulation proceeds through three distinct phases, follicle expansion (I), contraction (II) and rupture (III), culminating in the release of the egg. Follicle expansion is driven by hyaluronic acid secretion and an osmotic gradient-directed fluid influx into the follicle. Then, smooth muscle cells in the outer follicle drive follicle contraction. Follicle rupture begins with stigma formation, followed by the exit of follicular fluid and cumulus cells and the rapid release of the egg. These results establish a mechanistic framework for ovulation, a process of fundamental importance for reproduction.
The dynamics of blaTEM resistance genes in Salmonella Typhi
Authors: Nuanmuang Narong , Leekitcharoenphon Pimlapas , Njage Patrick Murigu Kamau , Thorn Alix Vincent , Aarestrup Frank M. 
Published: October 2024

AbstractSalmonella Typhi (S. Typhi) is an important pathogen causing typhoid fever worldwide. The emergence of antibiotic resistance, including that of blaTEM genes encoding to TEM $$\:\beta\:$$-lactamases has been observed. This study aimed to investigate the dynamics of blaTEM genes in S. Typhi by analyzing the phylogeny and flanking region patterns and phylogenetic associating them with metadata (year, country) and genomic data (genotypes, antibiotic resistance genes (ARGs), plasmids). Genomic sequences of publicly available S. Typhi harboring blaTEM (n = 6079), spanning from 1983 to 2023, were downloaded and analyzed using CSIPhylogeny for phylogeny, Flankophile for identifying genetic contexts around blaTEM genes and GenoTyphi for determining genotypes, ARGs and plasmid replicons. We found that blaTEM-positive isolates occurred most commonly in specific location, especially in Asia and Africa and clustered among a limited number of genotypes. Flankophile identified 740 isolates (12.2%) with distinct flanking region patterns, which were categorized into 13 patterns. Notably, 7 patterns showed a predominantly phylogenetic association with genotypes. Additionally, these 7 patterns exhibited relation to the country, ARGs and plasmid replicons. Further examination of the flanking region patterns provided association with mobile genetic elements (MGEs). Taken together, this study suggests that blaTEM has been acquired by S. Typhi isolates a limited number of times and subsequently spread clonally with specific genotypes.
The value of systemic immune inflammation index, white blood cell to platelet ratio, and homocysteine in predicting the instability of small saccular intracranial aneurysms
Authors: Zhang Wanwan , Xiang Chao , Liu Boliang , Hou Fandi , Zheng Zhanqiang , Chen Zhongcan , Suo Lina , Feng Guang , Gu Jianjun 
Published: October 2024

AbstractInflammation has a destructive effect on the homeostasis of the vascular wall, which is involved in the formation, growth, and rupture of human intracranial aneurysms (IAs) disease progression. However, inflammation-related markers have not been well studied in the risk stratification of unruptured IAs. The purpose of this study was to investigate the predictive value of serum inflammatory markers in the unstable progression of small saccular intracranial aneurysms (SIAs). This study retrospectively included 275 patients with small SIAs (aneurysm diameter less than or equal to 7 mm), to compare the level difference of serum inflammatory complex marker systemic immune-inflammatory index (SII), white blood cell to platelet ratio (WPR), and homocysteine (Hcy) in patients with stable (asymptomatic unruptured) and unstable (symptomatic unruptured, ruptured) small SIAs. 187 patients (68%) had aneurysm-related compression symptoms and rupture outcomes. In the multivariate logistic regression after adjusting for baseline differences, SII, WPR, and Hcy were independent risk factors for the instability of small SIAs, the prediction model combined with other risk factors (previous stroke history, aneurysm irregularity) showed good predictive ability for the instability of small SIAs, with an area under the curve of 0.905. In addition, correlation analysis showed that SII, WPR, and Hcy also had significant differences in patients with symptomatic unruptured and ruptured small SIAs, and higher inflammation levels often promoted the disease progression of small SIAs. Higher levels of SII, WPR and Hcy can be used as independent predictors of instability of small SIAs. As an economical and convenient biomarker, it is crucial for clinical treatment strategies of stable small SIAs.
Lessons learned from 12 years using the Woven Endobridge for the treatment of cerebral aneurysms in a multi-center series
Authors: Goertz Lukas , Liebig Thomas , Siebert Eberhard , Zopfs David , Pennig Lenhard , Pflaeging Muriel , Schlamann Marc , Radomi Alexandra , Dorn Franziska , Kabbasch Christoph 
Published: October 2024

AbstractIntrasaccular flow disruption with the Woven Endobridge (WEB) has become a well-established endovascular technique for the treatment of intracranial aneurysms. This study presents our 12-year experience with the WEB and evaluates its evolving indications, procedures, and outcomes. A consecutive series of 324 aneurysms treated with WEB between 2011 and 2023 at three neurovascular centers was retrospectively analyzed and the study group was divided into four treatment periods. Uni- and multivariate analyses were performed to evaluate factors associated with technical success, thromboembolic complications, and angiographic outcome. The mean aneurysm size was 7.0 ± 3.6 mm and decreased during the study period, while the proportion of atypical sites for WEB implantation increased. WEB implantation was technically successful in 96.0%, and the ratio of WEB width to dome width increased during the study period, indicating oversizing. The neurological complication rate was 4.9% (1.5% major, 3.4% minor) and the mid-term complete occlusion rate was 60.6% (81.9% adequate occlusion), with no statistical differences in either outcome measure between the study periods. In multivariate analyses, the use of WEB 17 was associated with increased technical success (HR: 7.4, 95%CI: 2.4-23.6, p<0.01), whereas ruptured aneurysm status (HR: 2.5, 95%CI: 1.0-6.0, p=0.04) and the use of additional stents (HR: 4.8, 95%CI: 1.6-14.4, p<0.01) predicted thromboembolic complications. Appropriate oversizing of the WEB favored mid-term complete occlusion (HR: 10.5, 95%CI: 1.3-83.3, p=0.03). The results suggest an expansion of the indications for WEB implantation and highlight the importance of oversizing for treatment efficacy.
Effects of inorganic phosphate on stem cells isolated from human exfoliated deciduous teeth
Authors: Suwittayarak Ravipha , Nowwarote Nunthawan , Kornsuthisopon Chatvadee , Sukarawan Waleerat , Foster Brian L , Egusa Hiroshi , Osathanon Thanaphum 
Published: October 2024

AbstractCalcium phosphate-based materials (CaP) are introduced as potential dental pulp capping materials for deciduous teeth. The present study investigated the influence of inorganic phosphate (Pi) on regulating stem cells isolated from human exfoliated deciduous teeth (SHED). SHEDs were treated with Pi. Cell cycle progression and apoptosis were examined using flow cytometry analysis. Osteo/odontogenic and adipogenic differentiation were analyzed using alizarin red S and oil red O staining, respectively. The mRNA expression profile was investigated using a high-throughput RNA sequencing technique. Pi increased the late apoptotic cell population while cell cycle progression was not altered. Pi upregulated osteo/odontoblastic gene expression and enhanced calcium deposition. Pi-induced mineralization was reversed by pretreatment of cells with Foscarnet, or p38 inhibitor. Pi treatment inhibited adipogenic differentiation as determined by decreased PPARγ expression and reduced intracellular lipid accumulation. Bioinformatic analysis of gene expression profiles demonstrated several involved pathways, including PI3K/AKT, MAPK, EGFR, and VEGF signaling. In conclusion, Pi enhanced osteo/odontogenic but inhibited adipogenic differentiation in SHED.
Acceptance as a possible link between past psychedelic experiences and psychological flexibility
Authors: Krabbe Andreas , Sikka Pilleriin , Jylkkä Jussi 
Published: October 2024

AbstractIncreased psychological flexibility (PF) may underlie the lasting positive effects of psychedelic experiences on mental well-being. The associations between different components of PF, psychological inflexibility (PI), and well-being with psychedelic use are not well understood. We conducted a cross-sectional internet survey of participants (N = 629) with experience of classical psychedelics. Using network analysis, we examined how aspects of a single psychedelic experience (mystical-type features and psychological insights) and the frequency of past psychedelic use, were associated with current PF and PI components, as well as with mental well-being and ill-being. Mediation analyses explored whether PF mediated the relationship between past psychedelic use and well-being or ill-being. The network analysis linked psychological insight to the PF component Acceptance, with no association found between the frequency of past use and PF. Mediation analyses showed PF mediates the association between past psychedelic use and well-being and ill-being. These results suggest that the quality and depth of the psychedelic experience, rather than the frequency of use, are primarily linked to psychological flexibility, particularly Acceptance, and overall well-being. This underscores the importance of treating PF as a multidimensional construct to better understand the long-term mental health benefits of psychedelics.
Immunomodulatory effect of IFN-γ licensed adipose-mesenchymal stromal cells in an in vitro model of inflammation generated by SARS-CoV-2 antigens
Authors: Bispo Elizabete Cristina Iseke , Argañaraz Enrique Roberto , Neves Franscisco de Assis Rocha , de Carvalho Juliana Lott , Saldanha-Araujo Felipe 
Published: October 2024

AbstractIn recent years, clinical studies have shown positive results of the application of Mesenchymal Stromal Cells (MSCs) in severe cases of COVID-19. However, the mechanisms of immunomodulation of IFN-γ licensed MSCs in SARS-CoV-2 infection are only partially understood. In this study, we first tested the effect of IFN-γ licensing in the MSC immunomodulatory profile. Then, we established an in vitro model of inflammation by exposing Calu-3 lung cells to SARS-CoV-2 nucleocapsid and spike (NS) antigens, and determined the toxicity of SARS-CoV-2 NS antigen and/or IFN-γ stimulation to Calu-3. The conditioned medium (iCM) generated by Calu-3 cells exposed to IFN-γ and SARS-CoV-2 NS antigens was used to stimulate T-cells, which were then co-cultured with IFN-γ-licensed MSCs. The exposure to IFN-γ and SARS-CoV-2 NS antigens compromised the viability of Calu-3 cells and induced the expression of the inflammatory mediators ICAM-1, CXCL-10, and IFN-β by these cells. Importantly, despite initially stimulating T-cell activation, IFN-γ-licensed MSCs dramatically reduced IL-6 and IL-10 levels secreted by T-cells exposed to NS antigens and iCM. Moreover, IFN-γ-licensed MSCs were able to significantly inhibit T-cell apoptosis induced by SARS-CoV-2 NS antigens. Taken together, our data show that, in addition to reducing the level of critical cytokines in COVID-19, IFN-γ-licensed MSCs protect T-cells from SARS-CoV-2 antigen-induced apoptosis. Such observations suggest that MSCs may contribute to COVID-19 management by preventing the lymphopenia and immunodeficiency observed in critical cases of the disease.
Impacts of testing and immunity acquired through vaccination and infection on covid-19 cases in Massachusetts elementary and secondary students
Authors: Branch-Elliman Westyn , Ertem Melissa Zeynep , Nelson Richard E. , Danesharasteh Anseh , Berlin David , Fisher Lloyd , Schechter-Perkins Elissa M. 
Published: October 2024

Abstract
Background
During the 2021–22 academic year, Massachusetts supported several in-school testing programs to facilitate in-person learning. Additionally, COVID-19 vaccines became available to all school-aged children and many were infected with SARS-CoV-2. There are limited studies evaluating the impacts of these testing programs on SARS-CoV-2 cases in elementary and secondary school settings. The aim of this state-wide, retrospective cohort study was to assess the impact of testing programs and immunity on SARS-CoV-2 case rates in elementary and secondary students.

Methods
Community-level vaccination and cumulative incidence rates were combined with data about participation in and results of in-school testing programs (test-to-stay, pooled surveillance testing). School-level impacts of surveillance testing programs on SARS-CoV-2 cases in students were estimated using generalized estimating equations within a target trial emulation approach stratified by school type (elementary/middle/high). Impacts of immunity and vaccination were estimated using random effects linear regression.

Results
Here we show that among N = 652,353 students at 2141 schools participating in in-school testing programs, surveillance testing is associated with a small but measurable decrease in in-school positivity rates. During delta, pooled testing positivity rates are higher in communities with higher cumulative incidence of infection. During omicron, when immunity from prior infection became more prevalent, the effect reversed, such that communities with lower burden of infection during the earlier phases of the pandemic had higher infection rates.

Conclusions
Testing programs are an effective strategy for supporting in-person learning. Fluctuating levels of immunity acquired via natural infection or vaccination are a major determinant of SARS-CoV-2 cases in schools.
Changing epidemiology and antimicrobial susceptibility of bloodstream infections at a Vietnamese infectious diseases hospital (2010–2020)
Authors: Nguyen Hoang Thu Trang , Chau Vinh , Nguyen Phu Huong Lan , Du Hong Duc , Nguyen Luong Nha Phuong , Le Thi Quynh Ngan , Huynh Phuong Thao , Nguyen Thi Nguyen To , Tran Thi Ngoc Dung , Voong Vinh Phat , Ha Thanh Tuyen , Nguyen Pham Nhu Quynh , Baker Stephen , Thwaites Guy , Rabaa Maia , Pham Duy Thanh 
Published: October 2024

AbstractBloodstream infection (BSI) poses a global health problem, with diverse organisms and rising antimicrobial resistance (AMR). Here, we characterized trends in BSI prevalence, AMR, and antibiotic use at a Vietnamese infectious diseases hospital from 2010 to 2020. Among 108,303 cultured blood samples, 8.8% were positive, yielding 7995 pathogens. Of 7553 BSI cases, 86.4% were community-acquired. BSI prevalence varied from 17 to 35 cases/1000 admissions/year, highest in HIV/hepatitis wards and patients >60. The in-hospital mortality or hospice discharge outcome was 21.3%. The top three pathogens, E. coli (24%), K. pneumoniae (8.7%) and S. aureus (8.5%) exhibited increasing prevalence and multidrug resistance. Pathogens like Cryptococcus neoformans (8.4%), Talaromyces marneffei (6.7%), and Salmonella enterica (6.5%) declined. E. coli and K. pneumoniae were prevalent in older adults with community-acquired BSIs. Antibiotic use reached 842.6 DOT/1000 PD and significantly reduced after an antibiotic control policy. Enhanced surveillance and antimicrobial stewardship are crucial for managing BSIs in Vietnam.