bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long term vaccination strategies to mitigate the impact of SARS-CoV-2 transmission: a modelling study
Authors: Hogan Alexandra B , Wu Sean L , Toor Jaspreet , Mesa Daniela Olivera , Doohan Patrick , Watson Oliver J , Winskill Peter , Charles Giovanni , Barnsley Gregory , Riley Eleanor M , Khoury David S , Ferguson Neil M , Ghani Azra C 
Published: February 2023

AbstractBackgroundVaccines have reduced severe disease and death from COVID-19. However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity.Methods and findingsWe developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated SARS-CoV-2 transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both original and variant-adapted vaccine products, in the presence of both continuing transmission of Omicron subvariants and considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is the most efficient strategy, although large numbers of hospitalisations and deaths can be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups is more effective than continuing primary vaccination into younger ages. These findings hold if even if virus drift results in a gradual reduction in vaccine effectiveness over time due to immune escape. In a worst-case scenario where a new variant emerges that is 10% more transmissible, as severe as Delta, and exhibits substantial further immune escape, demand on health services could be similar to that experienced during 2020.ConclusionsRegular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. The cost-effectiveness of boosting is difficult to assess given the ongoing uncertainty in the likelihood of future variants and their properties but focusing vaccination in the highest-risk cohorts remains the most efficient strategy to reduce morbidity and mortality.
The genetic architecture of human cerebellar morphology supports a key role for the cerebellum in human evolution and psychopathology
Authors: Moberget Torgeir , van der Meer Dennis , Bahrami Shahram , Roelfs Daniel , Frei Oleksandr , Kaufmann Tobias , Fernandez-Cabello Sara , Kim Milin , Wolfers Thomas , Diedrichsen Joern , Smeland Olav B. , Shadrin Alexey , Dale Anders , Andreassen Ole A. , Westlye Lars T. 
Published: February 2023

AbstractThe functional domain of the cerebellum has expanded beyond motor control to also include cognitive and affective functions. In line with this notion, cerebellar volume has increased over recent primate evolution, and cerebellar alterations have been linked to heritable mental disorders. To map the genetic architecture of human cerebellar morphology, we here studied a large imaging genetics sample from the UK Biobank (n discovery = 27,302; n replication: 11,264) with state-of-the art neuroimaging and biostatistics tools. Multivariate GWAS on regional cerebellar MRI features yielded 351 significant genetic loci (228 novel, 94% replicated). Lead SNPs showed positive enrichment for relatively recent genetic mutations over the last 20-40k years (i.e., overlapping the Upper Paleolithic, a period characterized by rapid cultural evolution), while gene level analyses revealed enrichment for human-specific evolution over the last ∼6-8 million years. Finally, we observed genetic overlap with major mental disorders, supporting cerebellar involvement in psychopathology.TeaserGenome-wide analysis of cerebellar morphology reveals links to recent human evolution and psychopathology
Low Antibody Titers Demonstrate Significantly Increased Rate of SARS-CoV-2 Infection in a Highly Vaccinated Population from the National Basketball Association
Authors: Tai Caroline G. , Haviland Miriam J. , Kissler Steven M. , Lucia Rachel M. , Merson Michael , Maragakis Lisa L. , Ho David D. , Anderson Deverick J. , DiFiori John , Grubaugh Nathan D. , Grad Yonatan H. , Mack Christina DeFilippo 
Published: February 2023

AbstractSARS-CoV-2 antibody titers may serve as a correlate for immunity and could inform optimal booster timing. The relationship between antibody titer and protection from infection was evaluated in 2,323 vaccinated individuals from the National Basketball Association who had antibody levels measured from 9/12/2021—12/31/2021. Cox-proportional hazards models were used to estimate risk of infection within 90-days of serologic testing by titer level (<250, 250-800, and >800 AU/mL) and individuals were censored on date of booster receipt. The cohort was 78.2% male, 68.1% aged ≤ 40 years, and 56.4% vaccinated (primary series) with the Pfizer-BioNTech mRNA vaccine. Among the 2,248 individuals not yet boosted at testing, those with titers <250 AU/mL (adj HR: 2.4; 95% CI: 1.5, 3.7) and 250-800 800 AU/mL (adj HR: 1.5; 95% CI: 0.98, 2.4) had greater infection risk compared to those with titers >800 AU/mL. Serologic titers could inform individual COVID-19 risk and booster scheduling.
Glutathione supports lipid abundancein vivo
Authors: Asantewaa Gloria , Tuttle Emily T. , Ward Nathan P. , Kang Yun Pyo , Kim Yumi , Kavanagh Madeline E. , Girnius Nomeda , Chen Ying , Duncan Renae , Rodriguez Katherine , Hecht Fabio , Zocchi Marco , Smorodintsev-Schiller Leonid , Scales TashJaé Q. , Taylor Kira , Alimohammadi Fatemeh , Sechrist Zachary R , Agostini-Vulaj Diana , Schafer Xenia L. , Chang Hayley , Smith Zachary , O’Connor Thomas N. , Whelan Sarah , Selfors Laura M. , Crowdis Jett , Gray G. Kenneth , Bronson Roderick T. , Brenner Dirk , Rufini Alessandro , Dirksen Robert T. , Hezel Aram F. , Huber Aaron R. , Munger Josh , Cravatt Benjamin F. , Vasiliou Vasilis , Cole Calvin L , DeNicola Gina M. , Harris Isaac S. 
Published: February 2023

SUMMARYCells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we developed a series ofin vivomodels to induceGclcdeletion in adult animals. We find that GSH is essential to lipid abundancein vivo. GSH levels are reported to be highest in liver tissue, which is also a hub for lipid production. While the loss of GSH did not cause liver failure, it decreased lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we found that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver’s balance of redox buffering and triglyceride production.
Phylogenetic distance and structural diversity directing a reclassification of glycopeptide antibiotics
Authors: Gavriilidou Athina , Adamek Martina , Rodler Jens-Peter , Kubach Noel , Kramer Susanna , Huson Daniel H. , Cryle Max J. , Stegmann Evi , Ziemert Nadine 
Published: February 2023

AbstractAntibiotics have been an essential part of modern medicine since their initial discovery. The continuous search for new antibiotic candidates remains a necessity given the increasing emergence of resistance to antimicrobial compounds among pathogens. The glycopeptide antibiotics (GPAs) represent an important group of last resort antibiotics which inhibit bacterial growth through non-covalent binding to the cell wall precursor lipid II. The so far reported GPAs exhibit an enormous diversity in the biosynthetic gene clusters that encode their production, which is in turn reflected in the variety of their structures. GPAs are typically composed of seven amino acids, which are highly crosslinked and decorated with a variable collection of sugar moieties as well as other modifications. Based on their structural characteristics, they have been classified into four main types. More recently, atypical GPAs have been identified that differ from type I-IV GPAs in both their structure and function and have consequently been classified as type V GPAs. Given these differences, we studied the phylogeny of all gene sequences related to the biosynthesis of the GPAs and observed a clear evolutionary diversification between the lipid II binding GPA classes and the so-called type V GPAs. Here we suggest the adoption of a phylogeny-driven reclassification and a separation of classical lipid II binding GPAs from type V GPAs, which we propose to identify instead as glycopeptide- related peptides (GRPs).
Habitat restoration and the recovery of metacommunities
Authors: Gawecka Klementyna A. , Bascompte Jordi 
Published: February 2023

AbstractEcosystem restoration is becoming a widely recognised solution to the biodiversity crisis. However, there is a gap between restoration science and practice. Specifically, we lack a theoretical framework which would improve our understanding of ecosystems’ recovery and allow us to optimise restoration design. Here, we narrow this gap by developing spatially explicit metacommunity models and studying the recovery dynamics of communities during restoration. We show that community response depends on how damaged the landscape is prior to restoration, with highly fragmented landscapes imposing greater challenges to community recovery. In such cases, we found that the recovery depends on the type of interaction and the structure of the interaction network. Finally, we demonstrate that community recovery can be maximised with careful spatial planning. When recovering communities composed of antagonistic interactions, restoration should target areas adjacent to the most species-rich sites. In the case of mutualistic communities, the same strategy should be adopted in the short-term, whereas in the long-term, restoration should be extended to sites that improve the overall connectivity of the landscape. Our results highlight the importance of considering interactions between species and spatial planning in restoration projects.
Mechanical control of neural plate folding by apical domain alteration
Authors: Matsuda Miho , Rozman Jan , Ostvar Sassan , Kasza Karen E. , Sokol Sergei Y. 
Published: February 2023

AbstractVertebrate neural tube closure is associated with complex changes in cell shape and behavior, however, the relative contribution of these processes to tissue folding is not well understood. In this study, we evaluated morphology of the superficial cell layer in theXenopusneural plate. At the stages corresponding to the onset of tissue folding, we observed the alternation of cells with apically constricting and apically expanding apical domains. The cells had a biased orientation along the anteroposterior (AP) axis. This apical domain heterogeneity required planar cell polarity (PCP) signaling and was especially pronounced at neural plate hinges. Vertex model simulations suggested that spatially dispersed isotropically constricting cells cause the elongation of their non-constricting counterparts along the AP axis. Consistent with this hypothesis, cell-autonomous induction of apical constriction inXenopusectoderm cells was accompanied by the expansion of adjacent non-constricting cells. Our observations indicate that a subset of isotropically constricting cells can initiate neural plate bending, whereas a ‘tug-of-war’ contest between the force-generating and responding cells reduces its shrinking along the AP axis. This mechanism is an alternative to anisotropic shrinking of cell junctions that are perpendicular to the body axis. We propose that neural folding relies on PCP-dependent transduction of mechanical signals between neuroepithelial cells.
Conserved Chamber-Specific Polyploidy Maintains Heart Function inDrosophila
Authors: Chakraborty Archan , Peterson Nora G. , King Juliet S. , Gross Ryan T. , Pla Michelle Mendiola , Thennavan Aatish , Zhou Kevin C. , DeLuca Sophia , Bursac Nenad , Bowles Dawn E. , Wolf Matthew J. , Fox Donald T. 
Published: February 2023

SUMMARYDevelopmentally programmed polyploidy (whole-genome-duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, we reveal roles for precise polyploidy levels in cardiac tissue. We highlight a conserved asymmetry in polyploidy level between cardiac chambers inDrosophilalarvae and humans. InDrosophila, differential Insulin Receptor (InR) sensitivity leads the heart chamber to reach a higher ploidy/cell size relative to the aorta chamber. Cardiac ploidy-reduced animals exhibit reduced heart chamber size, stroke volume, cardiac output, and acceleration of circulating hemocytes. TheseDrosophilaphenotypes mimic systemic human heart failure. Using human donor hearts, we reveal asymmetry in nuclear volume (ploidy) and insulin signaling between the left ventricle and atrium. Our results identify productive and likely conserved roles for polyploidy in cardiac chambers and suggest precise ploidy levels sculpt many developing tissues. These findings of productive cardiomyocyte polyploidy impact efforts to block developmental polyploidy to improve heart injury recovery.
Aldehyde accumulation inMycobacterium tuberculosiswith defective proteasomal degradation results in copper sensitivity
Authors: Limón Gina , Samhadaneh Nora M. , Pironti Alejandro , Darwin K. Heran 
Published: February 2023

ABSTRACTMycobacterium tuberculosisis a major human pathogen and the causative agent of tuberculosis disease.M. tuberculosisis able to persist in the face of host-derived antimicrobial molecules nitric oxide and copper. However,M. tuberculosiswith defective proteasome activity is highly sensitive to nitric oxide and copper, making the proteasome an attractive target for drug development. Previous work linked nitric oxide susceptibility with the accumulation ofpara-hydroxybenzaldehyde inM. tuberculosismutants with defective proteasomal degradation. In this study, we found thatpara-hydroxybenzaldehyde accumulation was also responsible for copper sensitivity in these strains. We showed that exogenous addition ofpara-hydroxybenzaldehyde to wild-typeM. tuberculosiscultures sensitized bacteria to copper to a degree similar to that of a proteasomal degradation mutant. We determined thatpara-hydroxybenzaldehyde reduced the production and function of critical copper resistance proteins of the regulated in copper repressor (RicR) regulon. Further, we extended these Cu-sensitizing effects to an aldehyde thatM. tuberculosismay face within the macrophage. Collectively, this study is the first to mechanistically propose how aldehydes can renderM. tuberculosissusceptible to an existing host defense and could support a broader role for aldehydes in controllingM. tuberculosisinfections.IMPORTANCEM. tuberculosisis a leading cause of death by a single infectious agent, causing 1.5 million deaths annually. An effective vaccine forM. tuberculosisinfections is currently lacking, and prior infection does not typically provide robust immunity to subsequent infections. Nonetheless, immunocompetent humans can controlM. tuberculosisinfections for decades. For these reasons, a clear understanding of how mammalian immunity inhibits mycobacterial growth is warranted. In this study, we show aldehydes can increaseM. tuberculosissusceptibility to copper, an established antibacterial metal used by immune cells to controlM. tuberculosisand other microbes. Given that activated macrophages produce increased amounts of aldehydes during infection, we propose host-derived aldehydes may help control bacterial infections, making aldehydes a previously unappreciated antimicrobial defense.
Insight into the central and nodal cells transcriptome of the streptophyte green algaChara brauniiS276
Authors: Heß Daniel , Holzhausen Anja , Hess Wolfgang R. 
Published: February 2023

ABSTRACTChara brauniiis an emerging model system for streptophyte terrestrialization and early land plant evolution. In this study, tissue containing nodal cells was prepared under the stereomicroscope and an RNA-seq dataset generated and compared to transcriptome data from whole plantlets. In both samples, transcript coverage was high for genes encoding ribosomal proteins and a homolog of the putative PAX3- and PAX7-binding protein 1. Gene ontology-based functional assignments revealed for the nodal cell sample main upregulated molecular functions related to protein binding, nucleic acid binding and DNA binding. Looking at specific genes, several signalling-related genes and genes encoding sugar-metabolizing enzymes were found to be expressed at a higher level in the nodal cell sample, while photosynthesis-and chloroplast-related genes were expressed at a comparatively lower level. We detected the transcription of 21 different genes encoding DUF4360-containing cysteine-rich proteins. The data contribute to the growing understanding of charophyte developmental genetics by providing a first insight into the transcriptome composition ofCharacentral and nodal cells.
Quantum entropy reveals chromosomal disorder of ancestry tracts in genetic admixture
Authors: Xiong Tianzhu , Bu Kaifeng 
Published: February 2023

AbstractAncestry tracts are contiguous haplotype blocks inherited from distinct groups of common ancestors. The genomic distribution of ancestry tracts (or local ancestry) provides rich information about evolutionary mechanisms shaping the genetic composition of hybrids. The correlation structure of ancestry tracts has been particularly useful in both empirical and theoretical studies, but there is a lack ofdescriptivemeasures operating on arbitrarily large genomic blocks to summarize this correlation structure without imposing too many assumptions about admixture. We here develop an approach inspired by quantum information theory to quantify this correlation structure. The key innovation is to represent local ancestry as quantum states, where less correlation in local ancestry leads to elevated quantum entropy. By leveraging a variety of entropy measures on local ancestry signals, we show that entropy is deeply connected to co-ancestry probabilities between and within haplotypes, so that ancestral recombination graphs become pivotal to the study of entropy dynamics in admixture. We use this approach to characterize a standard neutral admixture model with an arbitrary number of sources, and recover entropic laws governing the dynamics of ancestry tracts under recombination and genetic drift, which resembles the second law of thermodynamics. In application, entropy is well-defined on arbitrarily large genomic blocks with either phased or unphased local ancestry, and is insensitive to a small amount of noise. These properties are superior to simple statistics on ancestry tracts such as tract length and junction density. Finally, we construct an entropic index reflecting the degree of intermixing among ancestry tracts over a chromosomal block. This index confirms that the Z chromosome in a previously studied butterfly hybrid zone has the least potential of ancestry mixing, thus conforming to the “large-X/Z” effect in speciation. Together, we show that quantum entropy provides a useful framework for studying ancestry tract dynamics in both theories and real systems.
Vutiglabridin Alleviates Cellular Senescence Process of Dysfunctional Replication, Metabolic Regulation, and Circadian Clock in Primary Human Dermal Fibroblasts
Authors: Heo Jin-Woong , Lee Hye Eun , Lee Jimin , Choi Leo Sungwong , Shin Jaejin , Mun Ji Young , Park Hyung Soon , Park Sang Chul , Nam Chang-Hoon 
Published: February 2023

AbstractThe process of cellular senescence, which is characterized by stable cell cycle arrest, is strongly associated with dysfunctional cellular metabolism and circadian rhythmicity, both of which are reported to result from and also be causal to cellular senescence. As a result, modifying any of them - senescence, metabolism, or the circadian clock - may affect all three simultaneously. Obesity accelerates aging by disrupting the homeostasis of reactive oxygen species (ROS) via an increased mitochondrial burden of fatty acid oxidation. As a result, if senescence, metabolism, and circadian rhythm are all linked, anti-obesity treatments may improve metabolic regulation while also alleviating senescence and circadian rhythm. Vutiglabridin is a small molecule in clinical trials that improves obesity by enhancing mitochondrial function. We found that chronic treatment of senescent primary human dermal fibroblasts (HDFs) with vutiglabridin alleviates all investigated markers of cellular senescence (SA-β-gal,CDKN1A, CDKN2A) and dysfunctional cellular circadian rhythm (BMAL1), while remarkably preventing the alterations of mitochondrial function and structure that occur during the process of cellular senescence. Our results demonstrate the significant senescence-alleviating effects of vutiglabridin, specifically with the restoration of cellular circadian rhythmicity and metabolic regulation. These data support the potential development of vutiglabridin against aging-associated diseases and corroborate the intricate link between cellular senescence, metabolism, and the circadian clock.
Comparative analysis between two GT4 glycosyltransferases related to polysaccharide biosynthesis inRhodococcus jostiiRHA1
Authors: Cereijo Antonela E. , Ferretti María V. , Iglesias Alberto A. , Álvarez Héctor M. , Asencion Diez Matías D. 
Published: February 2023

AbstractThe bacterial genusRhodococcuscomprises organisms that perform an oleaginous behavior under certain growth conditions and the ratio of carbon and nitrogen availability. Thus,Rhodococcusspp have outstanding biotechnological features as microbial producers of biofuel precursors, which would be used instead of lipids from crops. It was postulated that lipid and glycogen metabolism inRhodococciare closely related. Thus, a better understanding of rhodococcal carbon partitioning requires identifying the catalytic steps redirecting sugar moieties to temporal storage molecules, such as glycogen and trehalose. In this work, we analyzed two glycosyl-transferases GT4 fromR. jostii,RjoGlgAb andRjoGlgAc, which were annotated as α-glucan-α-1,4-glucosyl transferases, putatively involved in glycogen synthesis. Both enzymes were recombinantly produced inE. coliBL21 (DE3) cells, purified to near homogeneity, and kinetically characterized.RjoGlgAb andRjoGlgAc presented the “canonical” glycogen synthase (EC 2.4.1.21) activity. Besides, both enzymes were actives as maltose-1P synthases (GlgM, EC 2.4.1.342), although to a different extent. In this scenario,RjoGlgAc is a homologous enzyme to the mycobacterial GlgM, with similar behavior regarding kinetic parameters and glucosyl-donor (ADP-glucose) preference.RjoGlgAc was two orders of magnitude more efficient to glucosylate glucose-1P than glycogen. Also, this rhodococcal enzyme used glucosamine-1P as a catalytically efficient aglycon. On the other hand, both activities exhibited byRjoGlgAb depicted similar kinetic efficiency and a preference for short-branched α-1,4-glucans. Curiously,RjoGlgAb presented a super-oligomeric conformation (higher than 15 subunits), representing a novel enzyme with a unique structure to function relationships. Results presented herein constitute a milestone regarding polysaccharide biosynthesis in Actinobacteria, leading to (re)discovery of methyl-glucose lipo-polysaccharide metabolism inRhodococci.