bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of overweight and its associated factors among Malaysian adults: findings from a nationally representative survey
Authors: Tat Chong Chean , Kent Lai Wai , Sallehuddin Syafinaz Mohd , Ganapathy Shubash Shander 
Published: March 2023

AbstractThe World Health Organization has reported that the prevalence of overweight is a growing problem in many countries, including middle- and lower-income countries like Malaysia. This study aimed to determine the prevalence of overweight and its associated factors among Malaysian adults. A total of 9782 Malaysian adults aged 18 and above were included in this study, representing states and federal territories from the National Health and Morbidity Survey 2019. Sociodemographic data (sex, locality, age, marital status, ethnicity, educational level, income level, and health literacy), non-communicable disease status (hypertension, diabetes, and hypercholesterolemia), and lifestyle behaviours (physical activity level, smoking status, and also fruit and vegetable consumption) were collected and analysed to identify factors associated with overweight. The study found that the prevalence of overweight among Malaysian adults was 50.1%. Multivariate analyses showed that several factors, including female gender, ages 30-59 years, being Malay, Indian or other Bumiputeras, being married, and having adequate health literacy, were significantly associated with an increased risk of overweight. Additionally, overweight individuals had a significantly higher risk of non-communicable diseases such as diabetes and hypertension. The study suggests that intervention programs should be implemented in an equitable and cost-effective manner to target these high-risk populations and address the burden of overweight in Malaysia.
Mind the viscous modulus: The mechanotransductive response to the viscous nature of isoelastic matrices regulates stem cell chondrogenesis
Authors: Walker Matthew , Pringle Eonan William , Ciccone Giuseppe , Tassieri Manlio , Gourdon Delphine , Cantini Marco 
Published: March 2023

AbstractThe design of hydrogels as mimetics of tissues’ matrices typically disregards the viscous nature of native tissues and focuses only on their elastic properties. In the case of stem cell chondrogenesis, this has led to contradictory results, likely due to unreported changes of the matrices’ viscous modulus. Here, by employing isoelastic matrices with a Young’s modulus of ~12 kPa, we demonstrate that variations in viscous properties alone (i.e., loss tangent between 0.1-0.25) are sufficient to drive efficient growth factor-free chondrogenesis of human mesenchymal stem cells, both in 2D and 3D cultures. The increase of the viscous component of RGD-functionalised polyacrylamide or polyethylene glycol maleimide hydrogels promotes a phenotype with reduced adhesion, alters mechanosensitive signalling, and boosts cell-cell contacts. In turn, this upregulates the chondrogenic transcription factor SOX9 and supports neocartilage formation, demonstrating that the mechanotransductive response to the viscous nature of the matrix can be harnessed to direct cell fate.
Water chlorination increases the relative abundance of an antibiotic resistance marker in developing sourdough starters
Authors: Lau Pearson , Jain Swapan , Perron Gabriel G. 
Published: March 2023

AbstractMultiple factors explain the proper development of sourdough starters. While the role of raw ingredients and geography, among other things, have been widely studied recently, the possible effect of water chlorination on the overall bacterial communities associated with sourdough remains to be explored. Here, using16s rRNAamplicon sequencing, we show that water chlorination at levels commonly found in drinking water systems has a limited impact on the overall bacterial communities developing in sourdough starters. However, using targeted sequencing, we found that the abundance of integron 1, a genetic mechanism responsible for the horizontal exchange of antibiotic resistance genes in spoilage and pathogenic bacteria, increased significantly with the level of water chlorination. While our results suggest that water chlorination might not impact sourdough starters at a deep phylogenetic level, they indicate that it can favor the growth of key spoilage bacteria.
Stuck in the weeds: Invasive grasses reduce tiger snake movement
Authors: Cornelis Jari , Cooper Christine E , Lettoof Damian C , Mayer Martin , Marshall Benjamin M 
Published: March 2023

ABSTRACTWetlands are particularly vulnerable to degradation in urban environments, partially due to the introduction of non-native plants. Invasive weeds in wetlands can replace native plants leading to alterations in habitat composition and vegetation, in turn, animal movements and ultimately population dynamics might be affected. Here we investigate how home range size and movements of western tiger snakes (Notechis scutatus occidentalis) differ in wetlands dominated by invasive kikuyu grass (Cenchrus clandestinus) compared to wetlands dominated by native vegetation to understand if and how the movement ecology of this top-order predator is altered by vegetation homogenization. To do so, we used Autocorrelated Kernel Density Estimators (AKDE) to estimate home range size, dynamic Brownian Bridge Movement Models to document movement trajectory confidence areas, and compared movement distances using a Bayesian regression model. Home range sizes by tiger snakes were 14.59 ± 9.35 ha smaller in areas dominated by invasive versus native vegetation. Moreover, within-day movement distances tended to be smaller in areas dominated by invasive versus native vegetation (mean ± SD: 9 ± 3 m versus 18 ± 6 m), but there was considerable overlap between the 95% credible intervals between these two groups. Smaller home ranges by tiger snakes in areas dominated by invasive kikuyu grass were likely driven by thermoregulation, with snakes moving vertically between basking locations on top of kikuyu and shelter sites at the base, rather than travelling horizontally along the ground to open basking areas in sites dominated by native vegetation. Additionally, fragmentation of sites dominated by invasive vegetation might have contributed to the comparatively smaller home ranges of snakes there. These findings add to our understanding how changes in habitat composition driven by invasive vegetation can affect animal space use and emphasise the need for further studies to understand how these changes affect population dynamics.
Efficient clathrin-mediated entry of enteric adenoviruses in human duodenal cells
Authors: Becker Miriam , Dorma Noemi , Conca Dario Valter , Mistry Nitesh , Bally Marta , Arnberg Niklas , Gerold Gisa 
Published: March 2023

AbstractEnteric adenovirus types F40 and 41 (EAdVs) are a leading cause of diarrhea and diarrhea-associated death in young children and have recently been proposed to cause acute hepatitis in children. Unlike other adenoviruses, EAdVs exhibit hitherto a strict tropism for gastrointestinal tissues with, to date, unknown infection mechanism and target cells. In this study, we turn to potentially limiting host factors by comparison of EAdV entry in cell lines with respiratory and intestinal origin by cellular perturbation, virus particle tracking and transmission electron microscopy. Our analyses highlight kinetic advantages in duodenal HuTu80 cell infection and reveal a larger fraction of mobile particles, faster virus uptake and infectious particle entry in intestinal cells. Moreover, EAdVs display a dependence on clathrin- and dynamin-dependent pathways in intestinal cells. Detailed knowledge of virus entry routes and host factor requirements is essential to understand pathogenesis and develop new countermeasures. Hence, this study provides novel insights into the entry mechanisms of a medically important virus with emerging tropism in a physiologically relevant cell line.Author SummaryEnteric adenoviruses have historically been difficult to grow in cell culture, which resulted in lack of knowledge of host factors and pathways required for infection of these medically relevant viruses. Previous studies in non-intestinal cell lines showed slow infection kinetics and generated comparatively low virus yields compared to other adenovirus types. We suggest duodenum derived HuTu80 cells as a superior cell line for studies to complement efforts using complex intestinal tissue models. We show that viral host cell factors required for virus entry differ between cell lines from distinct origins and demonstrate the importance of clathrin-mediated endocytosis.
The minimal intrinsic stochasticity of constitutively expressed eukaryotic genes is sub-Poissonian
Authors: Weidemann Douglas E. , Singh Abhyudai , Grima Ramon , Hauf Silke 
Published: March 2023

AbstractStochastic variation in gene products (“noise”) is an inescapable by-product of gene expression. Noise must be minimized to allow for the reliable execution of cellular functions. However, noise cannot be suppressed beyond an intrinsic lower limit. For constitutively expressed genes, this limit is believed to be Poissonian, meaning that the variance in mRNA numbers cannot be lower than their mean. Here, we show that several cell division genes in fission yeast have mRNA variances significantly below this limit, which cannot be explained by the classical gene expression model for low-noise genes. Our analysis reveals that multiple steps in both transcription and mRNA degradation are essential to explain this sub-Poissonian variance. The sub-Poissonian regime differs qualitatively from previously characterized noise regimes, a hallmark being that cytoplasmic noise is reduced when the mRNA export rate increases. Our study re-defines the lower limit of eukaryotic gene expression noise and identifies molecular requirements for ultra-low noise which are expected to support essential cell functions.
The role of size in biostability of DNA tetrahedra
Authors: Vilcapoma Javier , Patel Akul , Chandrasekaran Arun Richard , Halvorsen Ken 
Published: March 2023

AbstractThe potential for using DNA nanostructures for drug delivery applications requires understanding and ideally tuning their biostability. Here we investigate how biological degradation varies with size of a DNA nanostructure. We designed DNA tetrahedra of three edge lengths ranging from 13 to 20 bp and analyzed nuclease resistance for two nucleases and biostability in fetal bovine serum. We found that DNase I had similar digestion rates across sizes but appeared to incompletely digest the smallest tetrahedron, while T5 exonuclease was notably slower to digest the largest tetrahedron. In fetal bovine serum, the 20 bp tetrahedron was degraded ~four times faster than the 13 bp. These results show that DNA nanostructure size can influence nuclease degradation, but suggest a complex relationship that is nuclease specific.
Tat-fimbriae (“tafi”) – novel type of haloarchaeal surface structures
Authors: Galeva Anna V. , Syutkin Alexey S. , Zhao Dahe , Kireev Igor I. , Surin Alexey K. , Pavlova Elena Yu. , Liu Jingfang , Xiang Hua , Pyatibratov Mikhail G. 
Published: March 2023

SUMMARYIn present study, we describe “tat-fimbriae (tafi)” – a novel type of archaeal surface appendages isolated from haloarchaeonHaloarcula hispanica. Thesefilamental structures are unique because they are formed of protein subunits secreted through thetwin-arginine translocation pathway (Tat-pathway), in contrast to well-known archaeal surface filamentous structures secreted by the general secretory pathway (Sec-pathway). No cases of the role of Tat-pathway in the assembly of archaeal and bacterial filamentous structures have been described to date. “Tafi” are the first example of such structures. The precursor of the major tafi protein subunit TafA contains the N-terminal signal peptide carrying a twin-arginine consensus motif and fimbria-forming mature TafA lacks this signal peptide. We analyzed the gene neighborhood of thetafAhomologues in the known haloarchaeal genomes and found a conservative cluster of seven associated genestafA, B, C, D, E, F, G. We assume that all of them take part in the tafi synthesis. TafC and TafE proteins, whose precursor sequences also contain twin-arginine motifs, were detected as minor components of tafi. TafE protein is structurally similar to TafA, while TafC contains a TafA-like N-terminal domain and a C-terminal “laminin G-like” domain capable of functioning as an adhesin. TafD is annotated as a signal peptidase I. The functions of TafB, TafF and TafG are not known yet. This study demonstrated that ΔtafAand ΔtafDdeletion mutant strains synthesized archaella and not tafi, and only tafi were detected in ΔarlK(gene of common archaellin/pilin signal peptidase) deletion strain. It was shown that the expression of completeHar. hispanica taf-gene cluster in a heterologous hostHaloferax volcaniithat does not have similar genes leads to synthesis of recombinant tafi structures similar to the native ones. The tafi function remains elusive, but our preliminary data suggest that these structures may be involved in cell adhesion to different surfaces or substrates.
State-Level Excess Mortality in US Adults During the Delta and Omicron Waves of COVID-19
Authors: Renton Benjamin , Du Chengan , Chen Alexander Junxiang , Li Shu-Xia , Lin Zhenqiu , Krumholz Harlan M. , Faust Jeremy Samuel 
Published: March 2023

AbstractIntroductionThe US has continued to see excess mortality through the Delta and Omicron periods. We sought to quantify excess mortality on a state level and calculate potential deaths averted if all states matched the excess mortality rates of those with the 10 lowest excess mortality rates.MethodsObservational cohort, US and state-level data. Expected monthly deaths were modeled using pre-pandemic US and state-level data (2015-2020). Mortality data was accessed from CDC public reporting.ResultsWe find that during the Delta and Omicron waves, the US recorded over 596,000 excess deaths. 60% of the nation’s total excess mortality during these periods could have been averted if all states had excess mortality rates equal to those with the 10 lowest excess mortality rates.ConclusionWith large differences in excess mortality across US states in this 15-month study period, we note that a significant portion of deaths could have been averted with higher vaccination rates, improved mitigation policies, and adherence to other behaviors.
Spatial and Amplitude Dynamics of Neurostimulation: Insights from the Acute Intrahippocampal Kainate Seizure Mouse Model
Authors: Foutz Thomas J. , Rensing Nicholas , Han Lirong , Durand Dominique M. , Wong Michael 
Published: March 2023

AbstractObjectiveNeurostimulation is an emerging treatment for patients with medically refractory epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model.MethodsWe performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of temporal lobe epilepsy. We evaluated combinations of six anatomic targets and three stimulus amplitudes.ResultsWe found that the spike-suppressive effects of high-frequency neurostimulation are highly dependent on the stimulation amplitude and location, with higher amplitude stimulation being significantly more effective. Epileptiform spiking activity was significantly reduced with ipsilateral 250 μA stimulation of the CA1 and CA3 hippocampal regions with 21.5% and 22.2% reductions, respectively. In contrast, we found that spiking frequency and amplitude significantly increased with stimulation of the ventral hippocampal commissure. We further found spatial differences with broader effects from CA1 versus CA3 stimulation.SignificanceThese findings demonstrate that the effects of therapeutic neurostimulation in an acute hippocampal seizure model are highly dependent on the location of stimulation and stimulus amplitude. We provide a platform to optimize the anti-seizure effects of neurostimulation, and demonstrate that an exploration of the large electrical parameter and location space can improve current modalities for treating epilepsy.Key PointsEvaluated spatial and temporal parameters of neurostimulation in a mouse model of acute seizuresBrief bursts of high-frequency (100 Hz) stimulation effectively interrupted epileptiform activity.The suppressive effect was highly dependent on stimulation amplitude and was maximal at the ipsilateral CA1 and CA3 regions.Pro-excitatory effects were identified with high-amplitude high-frequency stimulation at the ventral hippocampal commissure and contralateral CA1.
Early transcriptional responses of human nasal epithelial cells to infection with Influenza A and SARS-CoV-2 virus differ and are influenced by physiological temperature
Authors: Resnick Jessica D. , Beer Michael A. , Pekosz Andrew 
Published: March 2023

ABSTRACTInfluenza A (IAV) and SARS-CoV-2 (SCV2) viruses represent an ongoing threat to public health. Both viruses target the respiratory tract, which consists of a gradient of cell types, receptor expression, and temperature. Environmental temperature has been an un-derstudied contributor to infection susceptibility and understanding its impact on host responses to infection could help uncover new insights into severe disease risk factors. As the nasal passageways are the initial site of respiratory virus infection, in this study we investigated the effect of temperature on host responses in human nasal epithelial cells (hNECs) utilizing IAV and SCV2in vitroinfection models. We demonstrate that temperature affects SCV2, but not IAV, viral replicative fitness and that SCV2 infected cultures are slower to mount an infection-induced response, likely due to suppression by the virus. Additionally, we show that that temperature not only changes the basal transcriptomic landscape of epithelial cells, but that it also impacts the response to infection. The induction of interferon and other innate immune responses were not drastically affected by temperature, suggesting that while the baseline antiviral response at different temperatures remains consistent, there may be metabolic or signaling changes that affect how well the cultures are able to adapt to new pressures such as infection. Finally, we show that hNECs respond differently to IAV and SCV2 infection in ways that give insight into how the virus is able to manipulate the cell to allow for replication and release. Taken together, these data give new insight into the innate immune response to respiratory infections and can assist in identifying new treatment strategies for respiratory infections.
Structural insights into the allosteric inhibition of P2X4 receptors
Authors: Shen Cheng , Cui WenWen , Zhang Yuqing , Zhao Yimeng , Sheng Danqi , Teng Xinyu , Wang Jin , Hattori Motoyuki 
Published: March 2023

AbstractP2X receptors are ATP-activated cation channels involved in a variety of physiological functions. Among the seven subtypes of P2X receptors, the P2X4 subtype plays important roles in both the immune system and the central nervous system, particularly in neuropathic pain. Therefore, P2X4 receptors are of increasing interest as potential drug targets, and several P2X4 subtype-specific inhibitors have been developed. However, the mechanism of allosteric inhibition of P2X4 receptors remains largely unclear due to the lack of structural information.Here, we report the cryo-EM structures of the zebrafish P2X4 receptor in complex with two P2X4 subtype-specific antagonists, BX430 and BAY-1797. Both antagonists bind to the same allosteric site located at the subunit interface at the top of the extracellular domain. Structure-based mutational analysis by electrophysiology identified the important residues for the allosteric inhibition of both zebrafish and human P2X4 receptors.Interestingly, in the previously reported apo structure, the binding pocket is closed and too narrow to accommodate allosteric modulators. Structural comparison revealed the ligand-dependent structural rearrangement of the binding pocket to stabilize the binding of allosteric modulators, which in turn would prevent the structural changes of the extracellular domain associated with channel activation. Furthermore, comparison with the previously reported P2X structures of other subtypes provided mechanistic insights into subtype-specific allosteric inhibition.Overall, the present work provides structural insights into the allosteric inhibition mechanism of P2X4 receptors, facilitating the design and optimization of specific modulators for P2X4 receptors.
Proteomic analysis shows decreased Type I fibers and ectopic fat accumulation in skeletal muscle from women with PCOS
Authors: Stener-Victorin E , Eriksson G , Shrestha M Mohan , Paris V Rodriguez , Lu H , Banks J , Samad M , Perian C , Jude B , Engman V , Boi R , Nilsson E , Ling C , Nyström J , Asterholm I Wernstedt , Turner N , Lanner J T , Benrick A 
Published: March 2023

AbstractBackgroundPolycystic ovary syndrome’s (PCOS) main feature is hyperandrogenism, which is linked to a higher risk of metabolic disorders in women. Gene expression analyses in adipose tissue and skeletal muscle reveal dysregulated metabolic pathways in women with PCOS, but these differences do not necessarily lead to changes in protein levels and biological function.MethodsTo advance our understanding of the molecular alterations in PCOS, we performed global proteomic and phosphorylation site analysis using tandem mass spectrometry. Adipose tissue and skeletal muscle were collected at baseline from 10 women with and without PCOS, and in women with PCOS after 5 weeks of treatment with electrical stimulation.ResultsPerilipin-1, a protein that typically coats the surface of lipid droplets in adipocytes, was increased whereas proteins involved in muscle contraction and type I muscle fiber function were downregulated in PCOS muscle. Proteins in the thick and thin filaments had many altered phosphorylation sites, indicating differences in protein activity and function. The upregulated proteins in muscle post treatment were enriched in pathways involved in extracellular matrix organization and wound healing, which may reflect a protective adaptation to repeated contractions and tissue damage due to needling. A similar, albeit less pronounced, upregulation in extracellular matrix organization pathways was also seen in adipose tissue.ConclusionsOur results suggest that hyperandrogenic women with PCOS have higher levels of extramyocellular lipids and fewer oxidative insulin-sensitive type I muscle fibers. These could be key factors leading insulin resistance in PCOS muscle while electric stimulation-induced tissue remodeling may be protective.FundingA.B. holds funding from the Swedish Research Council (2020-02485), E.SV. holds funding from the Swedish Research Council (2022-00550), the Novo Nordisk Foundation (NNF22OC0072904), and I.W.A. holds funding from the Swedish Research Council (2020-01463), Mary von Sydow Foundation, Diabetes Wellness Sverige, and EFSD//European Research Programme on ‘New Targets for Diabetes or Obesity-related Metabolic Diseases’ supported by MSD 2022, and J.N. holds funding from IngaBritt and Arne Lundberg Research Foundation.