bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climate Variations in the Past 250 Million Years and Contributing Factors
Authors: Li Xiang , Hu Yongyun , Yang Jun , Wei Mengyu , Guo Jiaqi , Lan Jiawenjing , Lin Qifan , Yuan Shuai , Zhang Jian , Wei Qiang , Liu Yonggang , Nie Ji , Xia Yan , Hu Shineng 
Published: February 2023

AbstractWe simulate climate variations in the past 250 million years (Myr), using the fully coupled Community Earth System Model version 1.2.2 (CESM1.2.2) with the Community Atmosphere Model version 4 (CAM4). Three groups of simulations are performed, each including 26 simulations, with a 10‐million‐year interval. The Control group is constrained by paleogeography, increasing solar radiation, and reconstructed global mean surface temperatures (GMSTs) by tuning CO2 concentrations. No ice sheets are prescribed for all simulations except for the pre‐industrial (PI) simulation in which modern geography, ice sheets and vegetation are used. Simulated zonal mean surface temperatures are always higher than those of proxy reconstructions in the tropics, but lower than those of proxy reconstructions at middle latitudes. The relative importance of individual contributing factors for surface temperature variations in the past 250 Myr is diagnosed, using the energy‐balance analysis. Results show that greenhouse gases are the major driver in regulating GMST variations, with a maximum contribution of 12.2°C. Varying surface albedo contributes to GMST variations by 3.3°C. Increasing solar radiation leads to GMST increases by 1.5°C. Cloud radiative effects have relatively weak impacts on GMST variations, less than ±0.8°C. For comparison, two groups of sensitivity simulations are performed. One group has the CO2 concentration fixed at 10 times the PI value, and the other group has fixed CO2 concentration of 10 times the PI value and fixed solar radiation at the present‐day value, showing that varying both paleogeography and solar constant and varying paleogeography alone result in GMST changes by 7.3°C and 5.6°C, respectively.
Neurocognitive effects of stress: a metaparadigm perspective
Authors: Kim Eun Joo , Kim Jeansok J. 
Published: February 2023

AbstractStressful experiences, both physical and psychological, that are overwhelming (i.e., inescapable and unpredictable), can measurably affect subsequent neuronal properties and cognitive functioning of the hippocampus. At the cellular level, stress has been shown to alter hippocampal synaptic plasticity, spike and local field potential activity, dendritic morphology, neurogenesis, and neurodegeneration. At the behavioral level, stress has been found to impair learning and memory for declarative (or explicit) tasks that are based on cognition, such as verbal recall memory in humans and spatial memory in rodents, while facilitating those that are based on emotion, such as differential fear conditioning in humans and contextual fear conditioning in rodents. These vertically related alterations in the hippocampus, procedurally observed after subjects have undergone stress, are generally believed to be mediated by recurrently elevated circulating hypothalamic-pituitary-adrenal (HPA) axis effector hormones, glucocorticoids, directly acting on hippocampal neurons densely populated with corticosteroid receptors. The main purposes of this review are to (i) provide a synopsis of the neurocognitive effects of stress in a historical context that led to the contemporary HPA axis dogma of basic and translational stress research, (ii) critically reappraise the necessity and sufficiency of the glucocorticoid hypothesis of stress, and (iii) suggest an alternative metaparadigm approach to monitor and manipulate the progression of stress effects at the neural coding level. Real-time analyses can reveal neural activity markers of stress in the hippocampus that can be used to extrapolate neurocognitive effects across a range of stress paradigms (i.e., resolve scaling and dichotomous memory effects issues) and understand individual differences, thereby providing a novel neurophysiological scaffold for advancing future stress research.
An old friend with a new face: tRNA-derived small RNAs with big regulatory potential in cancer biology
Authors: Di Fazio Arianna , Gullerova Monika 
Published: February 2023

AbstractTransfer RNAs (tRNAs) are small non-coding RNAs (sncRNAs) essential for protein translation. Emerging evidence suggests that tRNAs can also be processed into smaller fragments, tRNA-derived small RNAs (tsRNAs), a novel class of sncRNAs with powerful applications and high biological relevance to cancer. tsRNAs biogenesis is heterogeneous and involves different ribonucleases, such as Angiogenin and Dicer. For many years, tsRNAs were thought to be just degradation products. However, accumulating evidence shows their roles in gene expression: either directly via destabilising the mRNA or the ribosomal machinery, or indirectly via regulating the expression of ribosomal components. Furthermore, tsRNAs participate in various biological processes linked to cancer, including apoptosis, cell cycle, immune response, and retroviral insertion into the human genome. It is emerging that tsRNAs have significant therapeutic potential. Endogenous tsRNAs can be used as cancer biomarkers, while synthetic tsRNAs and antisense oligonucleotides can be employed to regulate gene expression. In this review, we are recapitulating the regulatory roles of tsRNAs, with a focus on cancer biology.
Cuproptosis: p53-regulated metabolic cell death?
Authors: Xiong Chen , Ling Hong , Hao Qian , Zhou Xiang 
Published: February 2023

AbstractCuproptosis is a novel type of copper-induced cell death that primarily occurs in cells that utilize oxidative phosphorylation as the main metabolic pathway to produce energy. Copper directly associates with the lipoylated proteins of the tricarboxylic acid cycle, leading to the disulfide-bond-dependent aggregation of these lipoylated proteins, destabilization of the iron-sulfur cluster proteins, and consequent proteotoxic stress. Cancer cells prefer glycolysis (Warburg effect) to oxidative phosphorylation for producing intermediate metabolites and energy, thereby achieving resistance to cuproptosis. Interestingly, the tumor suppressor p53 is a crucial metabolic regulator that inhibits glycolysis and drives a metabolic switch towards oxidative phosphorylation in cancer cells. Additionally, p53 regulates the biogenesis of iron-sulfur clusters and the copper chelator glutathione, which are two critical components of the cuproptotic pathway, suggesting that this tumor suppressor might play a role in cuproptosis. Furthermore, the possible roles of mutant p53 in regulating cuproptosis are discussed. In this essay, we review the recent progress in the understanding of the mechanism underlying cuproptosis, revisit the roles of p53 in metabolic regulation and iron-sulfur cluster and glutathione biosynthesis, and propose several potential mechanisms for wild-type and mutant p53-mediated cuproptosis regulation.
Views of healthcare professionals on the inclusion of genes associated with non-syndromic hearing loss in reproductive genetic carrier screening
Authors: Freeman Lucinda , Delatycki Martin B. , Scully Jackie Leach , Briggs Nancy , Kirk Edwin P. 
Published: February 2023

AbstractGenes associated with non-syndromic hearing loss (NSHL) are frequently included in panels for reproductive genetic carrier screening (RGCS), despite a lack of consensus on whether NSHL is a condition appropriate for inclusion in RGCS. We conducted a national online survey using a questionnaire to explore the views of clinicians who facilitate RGCS or provide care to deaf individuals in Australia and New Zealand regarding the inclusion of such genes in RGCS. Results were analysed descriptively, and free-text responses were analysed thematically. The questionnaire was completed by 386 respondents including genetic healthcare providers, obstetricians, ear nose and throat specialists, and general practitioners. The majority of respondents agreed that genes associated with NSHL should be included in RGCS, but there were differences between the groups. 74% of clinicians working in a hearing clinic agreed these genes should be included compared to 67% of genetic healthcare providers, 54% of reproductive care healthcare providers, and 44% of general practitioners. A majority of respondents agreed that moderate to profound deafness is a serious disability, although genetic healthcare providers were less likely to agree than other groups. Overall, respondents agreed that including NSHL in RGCS upholds prospective parents’ right to information. However, they also identified major challenges, including concern that screening may express a discriminatory attitude towards those living with deafness. They also identified the complexity of defining the severity of deafness.
Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo
Authors: Kulaj Konxhe , Harger Alexandra , Bauer Michaela , Caliskan Özüm S. , Gupta Tilak Kumar , Chiang Dapi Menglin , Milbank Edward , Reber Josefine , Karlas Angelos , Kotzbeck Petra , Sailer David N. , Volta Francesco , Lutter Dominik , Prakash Sneha , Merl-Pham Juliane , Ntziachristos Vasilis , Hauner Hans , Pfaffl Michael W. , Tschöp Matthias H. , Müller Timo D. , Hauck Stefanie M. , Engel Benjamin D. , Gerdes Jantje M. , Pfluger Paul T. , Krahmer Natalie , Stemmer Kerstin 
Published: February 2023

AbstractAdipocyte-derived extracellular vesicles (AdEVs) are membranous nanoparticles that convey communication from adipose tissue to other organs. Here, to delineate their role as messengers with glucoregulatory nature, we paired fluorescence AdEV-tracing and SILAC-labeling with (phospho)proteomics, and revealed that AdEVs transfer functional insulinotropic protein cargo into pancreatic β-cells. Upon transfer, AdEV proteins were subjects for phosphorylation, augmented insulinotropic GPCR/cAMP/PKA signaling by increasing total protein abundances and phosphosite dynamics, and ultimately enhanced 1st-phase glucose-stimulated insulin secretion (GSIS) in murine islets. Notably, insulinotropic effects were restricted to AdEVs isolated from obese and insulin resistant, but not lean mice, which was consistent with differential protein loads and AdEV luminal morphologies. Likewise, in vivo pre-treatment with AdEVs from obese but not lean mice amplified insulin secretion and glucose tolerance in mice. This data suggests that secreted AdEVs can inform pancreatic β-cells about insulin resistance in adipose tissue in order to amplify GSIS in times of increased insulin demand.
Climate-trait relationships exhibit strong habitat specificity in plant communities across Europe
Authors: Kambach Stephan , Sabatini Francesco Maria , Attorre Fabio , Biurrun Idoia , Boenisch Gerhard , Bonari Gianmaria , Čarni Andraž , Carranza Maria Laura , Chiarucci Alessandro , Chytrý Milan , Dengler Jürgen , Garbolino Emmanuel , Golub Valentin , Güler Behlül , Jandt Ute , Jansen Jan , Jašková Anni , Jiménez-Alfaro Borja , Karger Dirk Nikolaus , Kattge Jens , Knollová Ilona , Midolo Gabriele , Moeslund Jesper Erenskjold , Pielech Remigiusz , Rašomavičius Valerijus , Rūsiņa Solvita , Šibík Jozef , Stančić Zvjezdana , Stanisci Angela , Svenning Jens-Christian , Yamalov Sergey , Zimmermann Niklaus E. , Bruelheide Helge 
Published: February 2023

AbstractEcological theory predicts close relationships between macroclimate and functional traits. Yet, global climatic gradients correlate only weakly with the trait composition of local plant communities, suggesting that important factors have been ignored. Here, we investigate the consistency of climate-trait relationships for plant communities in European habitats. Assuming that local factors are better accounted for in more narrowly defined habitats, we assigned > 300,000 vegetation plots to hierarchically classified habitats and modelled the effects of climate on the community-weighted means of four key functional traits using generalized additive models. We found that the predictive power of climate increased from broadly to narrowly defined habitats for specific leaf area and root length, but not for plant height and seed mass. Although macroclimate generally predicted the distribution of all traits, its effects varied, with habitat-specificity increasing toward more narrowly defined habitats. We conclude that macroclimate is an important determinant of terrestrial plant communities, but future predictions of climatic effects must consider how habitats are defined.
The unprecedented Pacific Northwest heatwave of June 2021
Authors: White Rachel H. , Anderson Sam , Booth James F. , Braich Ginni , Draeger Christina , Fei Cuiyi , Harley Christopher D. G. , Henderson Sarah B. , Jakob Matthias , Lau Carie-Ann , Mareshet Admasu Lualawi , Narinesingh Veeshan , Rodell Christopher , Roocroft Eliott , Weinberger Kate R. , West Greg 
Published: February 2023

AbstractIn late June 2021 a heatwave of unprecedented magnitude impacted the Pacific Northwest region of Canada and the United States. Many locations broke all-time maximum temperature records by more than 5 °C, and the Canadian national temperature record was broken by 4.6 °C, with a new record temperature of 49.6 °C. Here, we provide a comprehensive summary of this event and its impacts. Upstream diabatic heating played a key role in the magnitude of this anomaly. Weather forecasts provided advanced notice of the event, while sub-seasonal forecasts showed an increased likelihood of a heat extreme with lead times of 10-20 days. The impacts of this event were catastrophic, including hundreds of attributable deaths across the Pacific Northwest, mass-mortalities of marine life, reduced crop and fruit yields, river flooding from rapid snow and glacier melt, and a substantial increase in wildfires—the latter contributing to landslides in the months following. These impacts provide examples we can learn from and a vivid depiction of how climate change can be so devastating.
Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection
Authors: Young Isabella C. , Massud Ivana , Cottrell Mackenzie L. , Shrivastava Roopali , Maturavongsadit Panita , Prasher Alka , Wong-Sam Andres , Dinh Chuong , Edwards Tiancheng , Mrotz Victoria , Mitchell James , Seixas Josilene Nascimento , Pallerla Aryani , Thorson Allison , Schauer Amanda , Sykes Craig , De la Cruz Gabriela , Montgomery Stephanie A. , Kashuba Angela D. M. , Heneine Walid , Dobard Charles W. , Kovarova Martina , Garcia J. Victor , Garcίa-Lerma J. Gerardo , Benhabbour S. Rahima 
Published: February 2023

AbstractUltra-long-acting delivery platforms for HIV pre-exposure prophylaxis (PrEP) may increase adherence and maximize public health benefit. We report on an injectable, biodegradable, and removable in-situ forming implant (ISFI) that is administered subcutaneously and can release the integrase inhibitor cabotegravir (CAB) above protective benchmarks for more than 6 months. CAB ISFIs are well-tolerated in female mice and female macaques showing no signs of toxicity or chronic inflammation. In macaques, median plasma CAB concentrations exceed established PrEP protection benchmarks within 3 weeks and confer complete protection against repeated rectal SHIV challenges. Implant removal via a small incision in 2 macaques at week 12 results in a 7- to 48-fold decrease in plasma CAB levels within 72 hours. Modeling to translate CAB ISFI dosing suggests that a 3 mL injection would exceed protective benchmarks in humans for over 5 months post administration. Our results support the clinical advancement of CAB ISFIs for ultra-long-acting PrEP in humans.
Identifying glycan consumers in human gut microbiota samples using metabolic labeling coupled with fluorescence-activated cell sorting
Authors: Dridi Lharbi , Altamura Fernando , Gonzalez Emmanuel , Lui Olivia , Kubinski Ryszard , Pidgeon Reilly , Montagut Adrian , Chong Jasmine , Xia Jianguo , Maurice Corinne F. , Castagner Bastien 
Published: February 2023

AbstractThe composition and metabolism of the human gut microbiota are strongly influenced by dietary complex glycans, which cause downstream effects on the physiology and health of hosts. Despite recent advances in our understanding of glycan metabolism by human gut bacteria, we still need methods to link glycans to their consuming bacteria. Here, we use a functional assay to identify and isolate gut bacteria from healthy human volunteers that take up different glycans. The method combines metabolic labeling using fluorescent oligosaccharides with fluorescence-activated cell sorting (FACS), followed by amplicon sequencing or culturomics. Our results demonstrate metabolic labeling in various taxa, such as Prevotella copri, Collinsella aerofaciens and Blautia wexlerae. In vitro validation confirms the ability of most, but not all, labeled species to consume the glycan of interest for growth. In parallel, we show that glycan consumers spanning three major phyla can be isolated from cultures of sorted labeled cells. By linking bacteria to the glycans they consume, this approach increases our basic understanding of glycan metabolism by gut bacteria. Going forward, it could be used to provide insight into the mechanism of prebiotic approaches, where glycans are used to manipulate the gut microbiota composition.
Tripodal Pd metallenes mediated by Nb2C MXenes for boosting alkynes semihydrogenation
Authors: Wei Zhongzhe , Zhao Zijiang , Qiu Chenglong , Huang Songtao , Yao Zihao , Wang Mingxuan , Chen Yi , Lin Yue , Zhong Xing , Li Xiaonian , Wang Jianguo 
Published: February 2023

Abstract2D metallene nanomaterials have spurred considerable attention in heterogeneous catalysis by virtue of sufficient unsaturated metal atoms, high specific surface area and surface strain. Nevertheless, the strong metallic bonding in nanoparticles aggravates the difficulty in the controllable regulation of the geometry of metallenes. Here we propose an efficient galvanic replacement strategy to construct Pd metallenes loaded on Nb2C MXenes at room temperature, which is triggered by strong metal-support interaction based on MD simulations. The Pd metallenes feature a chair structure of six-membered ring with the coordination number of Pd as low as 3. Coverage-dependent kinetic analysis based on first-principles calculations reveals that the tripodal Pd metallenes promote the diffusion of alkene and inhibit its overhydrogenation. As a consequence, Pd/Nb2C delivers an outstanding turnover frequency of 10372 h−1 and a high selectivity of 96% at 25 oC in the semihydrogenation of alkynes without compromising the stability. This strategy is general and scalable considering the plentiful members of the MXene family, which can set a foundation for the design of novel supported-metallene catalysts for demanding transformations.
Segmental motor recovery after cervical spinal cord injury relates to density and integrity of corticospinal tract projections
Authors: Balbinot Gustavo , Li Guijin , Kalsi-Ryan Sukhvinder , Abel Rainer , Maier Doris , Kalke Yorck-Bernhard , Weidner Norbert , Rupp Rüdiger , Schubert Martin , Curt Armin , Zariffa Jose 
Published: February 2023

AbstractCervical spinal cord injury (SCI) causes extensive impairments for individuals which may include dextrous hand function. Although prior work has focused on the recovery at the person-level, the factors determining the recovery of individual muscles are poorly understood. Here, we investigate the muscle-specific recovery after cervical spinal cord injury in a retrospective analysis of 748 individuals from the European Multicenter Study about Spinal Cord Injury (NCT01571531). We show associations between corticospinal tract (CST) sparing and upper extremity recovery in SCI, which improves the prediction of hand muscle strength recovery. Our findings suggest that assessment strategies for muscle-specific motor recovery in acute spinal cord injury are improved by accounting for CST sparing, and complement person-level predictions.
Two distinct binding modes provide the RNA-binding protein RbFox with extraordinary sequence specificity
Authors: Ye Xuan , Yang Wen , Yi Soon , Zhao Yanan , Varani Gabriele , Jankowsky Eckhard , Yang Fan 
Published: February 2023

AbstractSpecificity of RNA-binding proteins for target sequences varies considerably. Yet, it is not understood how certain few proteins achieve markedly higher sequence specificity than most others. Here we show that the RNA Recognition Motif of RbFox accomplishes extraordinary sequence specificity by employing functionally and structurally distinct binding modes. Affinity measurements of RbFox for all binding site variants reveal the existence of two distinct binding modes. The first exclusively accommodates cognate and closely related RNAs with high affinity. The second mode accommodates all other RNAs with reduced affinity by imposing large thermodynamic penalties on non-cognate sequences. NMR studies indicate marked structural differences between the two binding modes, including large conformational rearrangements distant from the RNA-binding site. Distinct binding modes by a single RNA-binding module explain extraordinary sequence selectivity and reveal an unknown layer of functional diversity, cross talk and regulation in RNA-protein interactions.
Comprehensive characterization of per- and polyfluoroalkyl substances in wastewater by liquid chromatography-mass spectrometry and screening algorithms
Authors: Tang Caiming , Liang Yutao , Wang Kai , Liao Jianbo , Zeng Yanhong , Luo Xiaojun , Peng Xianzhi , Mai Bixian , Huang Qingguo , Lin Hui 
Published: February 2023

AbstractPer- and polyfluoroalkyl substances (PFASs) constitute a large category of synthetic environmental pollutants, many of which remain unknown and warrant comprehensive investigation. This study comprehensively characterized PFASs in fluorinated-industrial wastewater by nontarget, quasi-target and target analyses using liquid chromatography-high-resolution mass spectrometry and data-processing algorithms. The algorithms based on characteristic in-source neutral losses and isotopologue distributions were applied to screening and identifying PFASs, while semiquantitative and quantitative analyses were utilized to determine their concentrations and distributions in the wastewater. In total, 175 formulae of PFASs, including traditional, little-known and unknown species were identified and further ascertained in terms of concentrations and distributions. The total concentrations of PFASs in the wastewater were 5.3–33.4 μg mL−1, indicating serious pollution of PFASs. This study not only provides an efficient approach for screening and identification of unknown PFASs, but also presents a practicable and simple way to comprehensively depict environmental pollution signatures of PFASs.