bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations
Authors: Thorpe Harry A. , Tourrette Elise , Yahara Koji , Vale Filipa F. , Liu Siqi , Oleastro Mónica , Alarcon Teresa , Perets Tsachi-Tsadok , Latifi-Navid Saeid , Yamaoka Yoshio , Martinez-Gonzalez Beatriz , Karayiannis Ioannis , Karamitros Timokratis , Sgouras Dionyssios N. , Elamin Wael , Pascoe Ben , Sheppard Samuel K. , Ronkainen Jukka , Aro Pertti , Engstrand Lars , Agreus Lars , Suerbaum Sebastian , Thorell Kaisa , Falush Daniel 
Published: November 2022

AbstractHelicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks by migration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.
Deep phenotyping and lifetime trajectories reveal limited effects of longevity regulators on the aging process in C57BL/6J mice
Authors: Xie Kan , Fuchs Helmut , Scifo Enzo , Liu Dan , Aziz Ahmad , Aguilar-Pimentel Juan Antonio , Amarie Oana Veronica , Becker Lore , da Silva-Buttkus Patricia , Calzada-Wack Julia , Cho Yi-Li , Deng Yushuang , Edwards A. Cole , Garrett Lillian , Georgopoulou Christina , Gerlini Raffaele , Hölter Sabine M. , Klein-Rodewald Tanja , Kramer Michael , Leuchtenberger Stefanie , Lountzi Dimitra , Mayer-Kuckuk Phillip , Nover Lena L. , Oestereicher Manuela A. , Overkott Clemens , Pearson Brandon L. , Rathkolb Birgit , Rozman Jan , Russ Jenny , Schaaf Kristina , Spielmann Nadine , Sanz-Moreno Adrián , Stoeger Claudia , Treise Irina , Bano Daniele , Busch Dirk H. , Graw Jochen , Klingenspor Martin , Klopstock Thomas , Mock Beverly A. , Salomoni Paolo , Schmidt-Weber Carsten , Weiergräber Marco , Wolf Eckhard , Wurst Wolfgang , Gailus-Durner Valérie , Breteler Monique M. B. , Hrabě de Angelis Martin , Ehninger Dan 
Published: November 2022

AbstractCurrent concepts regarding the biology of aging are primarily based on studies aimed at identifying factors regulating lifespan. However, lifespan as a sole proxy measure for aging can be of limited value because it may be restricted by specific pathologies. Here, we employ large-scale phenotyping to analyze hundreds of markers in aging male C57BL/6J mice. For each phenotype, we establish lifetime profiles to determine when age-dependent change is first detectable relative to the young adult baseline. We examine key lifespan regulators (putative anti-aging interventions; PAAIs) for a possible countering of aging. Importantly, unlike most previous studies, we include in our study design young treated groups of animals, subjected to PAAIs prior to the onset of detectable age-dependent phenotypic change. Many PAAI effects influence phenotypes long before the onset of detectable age-dependent change, but, importantly, do not alter the rate of phenotypic change. Hence, these PAAIs have limited effects on aging.
An opioid-gated thalamoaccumbal circuit for the suppression of reward seeking in mice
Authors: Vollmer Kelsey M. , Green Lisa M. , Grant Roger I. , Winston Kion T. , Doncheck Elizabeth M. , Bowen Christopher W. , Paniccia Jacqueline E. , Clarke Rachel E. , Tiller Annika , Siegler Preston N. , Bordieanu Bogdan , Siemsen Benjamin M. , Denton Adam R. , Westphal Annaka M. , Jhou Thomas C. , Rinker Jennifer A. , McGinty Jacqueline F. , Scofield Michael D. , Otis James M. 
Published: November 2022

AbstractSuppression of dangerous or inappropriate reward-motivated behaviors is critical for survival, whereas therapeutic or recreational opioid use can unleash detrimental behavioral actions and addiction. Nevertheless, the neuronal systems that suppress maladaptive motivated behaviors remain unclear, and whether opioids disengage those systems is unknown. In a mouse model using two-photon calcium imaging in vivo, we identify paraventricular thalamostriatal neuronal ensembles that are inhibited upon sucrose self-administration and seeking, yet these neurons are tonically active when behavior is suppressed by a fear-provoking predator odor, a pharmacological stressor, or inhibitory learning. Electrophysiological, optogenetic, and chemogenetic experiments reveal that thalamostriatal neurons innervate accumbal parvalbumin interneurons through synapses enriched with calcium permeable AMPA receptors, and activity within this circuit is necessary and sufficient for the suppression of sucrose seeking regardless of the behavioral suppressor administered. Furthermore, systemic or intra-accumbal opioid injections rapidly dysregulate thalamostriatal ensemble dynamics, weaken thalamostriatal synaptic innervation of downstream neurons, and unleash reward-seeking behaviors in a manner that is reversed by genetic deletion of thalamic µ-opioid receptors. Overall, our findings reveal a thalamostriatal to parvalbumin interneuron circuit that is both required for the suppression of reward seeking and rapidly disengaged by opioids.
dcHiC detects differential compartments across multiple Hi-C datasets
Authors: Chakraborty Abhijit , Wang Jeffrey G. , Ay Ferhat 
Published: November 2022

AbstractThe compartmental organization of mammalian genomes and its changes play important roles in distinct biological processes. Here, we introduce dcHiC, which utilizes a multivariate distance measure to identify significant changes in compartmentalization among multiple contact maps. Evaluating dcHiC on four collections of bulk and single-cell contact maps from in vitro mouse neural differentiation (n = 3), mouse hematopoiesis (n = 10), human LCLs (n = 20) and post-natal mouse brain development (n = 3 stages), we show its effectiveness and sensitivity in detecting biologically relevant changes, including those orthogonally validated. dcHiC reported regions with dynamically regulated genes associated with cell identity, along with correlated changes in chromatin states, subcompartments, replication timing and lamin association. With its efficient implementation, dcHiC enables high-resolution compartment analysis as well as standalone browser visualization, differential interaction identification and time-series clustering. dcHiC is an essential addition to the Hi-C analysis toolbox for the ever-growing number of bulk and single-cell contact maps. Available at: https://github.com/ay-lab/dcHiC.
Explosive percolation yields highly-conductive polymer nanocomposites
Authors: Meloni Manuela , Large Matthew J. , González Domínguez José Miguel , Victor-Román Sandra , Fratta Giuseppe , Istif Emin , Tomes Oliver , Salvage Jonathan P. , Ewels Christopher P. , Pelaez-Fernandez Mario , Arenal Raul , Benito Ana , Maser Wolfgang K. , King Alice A. K. , Ajayan Pulickel M. , Ogilvie Sean P. , Dalton Alan B. 
Published: November 2022

AbstractExplosive percolation is an experimentally-elusive phenomenon where network connectivity coincides with onset of an additional modification of the system; materials with correlated localisation of percolating particles and emergent conductive paths can realise sharp transitions and high conductivities characteristic of the explosively-grown network. Nanocomposites present a structurally- and chemically-varied playground to realise explosive percolation in practically-applicable systems but this is yet to be exploited by design. Herein, we demonstrate composites of graphene oxide and synthetic polymer latex which form segregated networks, leading to low percolation threshold and localisation of conductive pathways. In situ reduction of the graphene oxide at temperatures of <150 °C drives chemical modification of the polymer matrix to produce species with phenolic groups, which are known crosslinking agents. This leads to conductivities exceeding those of dense-packed networks of reduced graphene oxide, illustrating the potential of explosive percolation by design to realise low-loading composites with dramatically-enhanced electrical transport properties.
Protein control of photochemistry and transient intermediates in phytochromes
Authors: Salvadori Giacomo , Macaluso Veronica , Pellicci Giulia , Cupellini Lorenzo , Granucci Giovanni , Mennucci Benedetta 
Published: November 2022

AbstractPhytochromes are ubiquitous photoreceptors responsible for sensing light in plants, fungi and bacteria. Their photoactivation is initiated by the photoisomerization of the embedded chromophore, triggering large conformational changes in the protein. Despite numerous experimental and computational studies, the role of chromophore-protein interactions in controlling the mechanism and timescale of the process remains elusive. Here, we combine nonadiabatic surface hopping trajectories and adiabatic molecular dynamics simulations to reveal the molecular details of such control for the Deinococcus radiodurans bacteriophytochrome. Our simulations reveal that chromophore photoisomerization proceeds through a hula-twist mechanism whose kinetics is mainly determined by the hydrogen bond of the chromophore with a close-by histidine. The resulting photoproduct relaxes to an early intermediate stabilized by a tyrosine, and finally evolves into a late intermediate, featuring a more disordered binding pocket and a weakening of the aspartate-to-arginine salt-bridge interaction, whose cleavage is essential to interconvert the phytochrome to the active state.
Sexually dimorphic architecture and function of a mechanosensory circuit in C. elegans
Authors: Setty Hagar , Salzberg Yehuda , Karimi Shadi , Berent-Barzel Elisheva , Krieg Michael , Oren-Suissa Meital 
Published: November 2022

AbstractHow sensory perception is processed by the two sexes of an organism is still only partially understood. Despite some evidence for sexual dimorphism in auditory and olfactory perception, whether touch is sensed in a dimorphic manner has not been addressed. Here we find that the neuronal circuit for tail mechanosensation in C. elegans is wired differently in the two sexes and employs a different combination of sex-shared sensory neurons and interneurons in each sex. Reverse genetic screens uncovered cell- and sex-specific functions of the alpha-tubulin mec-12 and the sodium channel tmc-1 in sensory neurons, and of the glutamate receptors nmr-1 and glr-1 in interneurons, revealing the underlying molecular mechanisms that mediate tail mechanosensation. Moreover, we show that only in males, the sex-shared interneuron AVG is strongly activated by tail mechanical stimulation, and accordingly is crucial for their behavioral response. Importantly, sex reversal experiments demonstrate that the sexual identity of AVG determines both the behavioral output of the mechanosensory response and the molecular pathways controlling it. Our results present extensive sexual dimorphism in a mechanosensory circuit at both the cellular and molecular levels.
Impaired mitochondrial oxidative metabolism in skeletal progenitor cells leads to musculoskeletal disintegration
Authors: Lin Chujiao , Yang Qiyuan , Guo Dongsheng , Xie Jun , Yang Yeon-Suk , Chaugule Sachin , DeSouza Ngoc , Oh Won-Taek , Li Rui , Chen Zhihao , John Aijaz A. , Qiu Qiang , Zhu Lihua Julie , Greenblatt Matthew B. , Ghosh Sankar , Li Shaoguang , Gao Guangping , Haynes Cole , Emerson Charles P. , Shim Jae-Hyuck 
Published: November 2022

AbstractAlthough skeletal progenitors provide a reservoir for bone-forming osteoblasts, the major energy source for their osteogenesis remains unclear. Here, we demonstrate a requirement for mitochondrial oxidative phosphorylation in the osteogenic commitment and differentiation of skeletal progenitors. Deletion of Evolutionarily Conserved Signaling Intermediate in Toll pathways (ECSIT) in skeletal progenitors hinders bone formation and regeneration, resulting in skeletal deformity, defects in the bone marrow niche and spontaneous fractures followed by persistent nonunion. Upon skeletal fracture, Ecsit-deficient skeletal progenitors migrate to adjacent skeletal muscle causing muscle atrophy. These phenotypes are intrinsic to ECSIT function in skeletal progenitors, as little skeletal abnormalities were observed in mice lacking Ecsit in committed osteoprogenitors or mature osteoblasts. Mechanistically, Ecsit deletion in skeletal progenitors impairs mitochondrial complex assembly and mitochondrial oxidative phosphorylation and elevates glycolysis. ECSIT-associated skeletal phenotypes were reversed by in vivo reconstitution with wild-type ECSIT expression, but not a mutant displaying defective mitochondrial localization. Collectively, these findings identify mitochondrial oxidative phosphorylation as the prominent energy-driving force for osteogenesis of skeletal progenitors, governing musculoskeletal integrity.
Design and directed evolution of noncanonical β-stereoselective metalloglycosidases
Authors: Jeong Woo Jae , Song Woon Ju 
Published: November 2022

AbstractMetallohydrolases are ubiquitous in nearly all subclasses of hydrolases, utilizing metal elements to activate a water molecule and facilitate its subsequent dissociation of diverse chemical bonds. However, such a catalytic role of metal ions is rarely found with glycosidases that hydrolyze the glycosidic bonds in sugars. Herein, we design metalloglycosidases by constructing a hydrolytically active Zn-binding site within a barrel-shaped outer membrane protein OmpF. Structure- and mechanism-based redesign and directed evolution have led to the emergence of Zn-dependent glycosidases with catalytic proficiency of 2.8 × 109and high β-stereoselectivity. Biochemical characterizations suggest that the Zn-binding site constitutes a key catalytic motif along with at least one adjacent acidic residue. This work demonstrates that unprecedented metalloenzymes can be tailor-made, expanding the scope of inorganic reactivities in proteinaceous environments, resetting the structural and functional diversity of metalloenzymes, and providing the potential molecular basis of unidentified metallohydrolases and novel whole-cell biocatalysts.
Evaluation of telehealth support in an integrated respiratory clinic
Authors: Fox Lauren , Heiden Emily , Chauhan Milan A. J. , Longstaff Jayne M. , Balls Lara , De Vos Ruth , Neville Daniel M. , Jones Thomas L. , Leung Anthony W. , Morrison Lydia , Rupani Hitasha , Brown Thomas P. , Stores Rebecca , Chauhan Anoop J. 
Published: November 2022

AbstractSupporting self-management is key in improving disease control, with technology increasingly utilised. We hypothesised the addition of telehealth support following assessment in an integrated respiratory clinic could reduce unscheduled healthcare visits in patients with asthma and COPD. Following treatment optimisation, exacerbation-prone participants or those with difficulty in self-management were offered telehealth support. This comprised automated twice-weekly telephone calls, with a specialist nurse triaging alerts. We performed a matched cohort study assessing additional benefits of the telehealth service, matching by: confirmed diagnosis, age, sex, FEV1 percent predicted, smoking status and ≥1 exacerbation in the last year. Thirty-four telehealth participants were matched to twenty-nine control participants. The telehealth cohort generated 165 alerts, with 29 participants raising at least one alert; 88 (53.5%) alerts received a call discussing self-management, of which 35 (21%) received definitive advice that may otherwise have required an unscheduled healthcare visit. There was a greater reduction in median exacerbation rate across both telehealth groups at 6 months post-intervention (1 to 0, p < 0.001) but not in control groups (0.5 to 0.0, p = 0.121). Similarly, there was a significant reduction in unscheduled GP visits across the telehealth groups (1.5 to 0.0, p < 0.001), but not the control groups (0.5 to 0.0, p = 0.115). These reductions led to cost-savings across all groups, but greater in the telehealth cohorts. The addition of telehealth support to exacerbation-prone patients with asthma or COPD, following comprehensive assessment and treatment optimisation, proved beneficial in reducing exacerbation frequency and unscheduled healthcare visits and thus leads to significant cost-savings for the NHS.Clinical Trial Registration: ClinicalTrials.gov: NCT03096509
Sensory and metabolite migration from tilapia skin to soup during the boiling process: fast and then slow
Authors: Chen Jiahui , Nie Yinghua , Xu Jiamin , Huang Shudan , Sheng Jie , Wang Xichang , Zhong Jian 
Published: November 2022

AbstractThis study mainly studied sensory and metabolite migration from the skin to the soup in the boiling process of tilapia skin using content analysis, electronic nose technique, electronic tongue technique, and metabolomics technique based on ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry and gas chromatography-time-of-flight-mass spectrometry. The content changes, flavor changes, taste changes, metabolite numbers and differential metabolite numbers for both tilapia skin and soup mainly occurred in the initial 30 min. Moreover, the initial 10 min was the key period for the metabolite changes in the boiling process. Further, the differential metabolites in these three periods (0–10, 10–30, and 30–60 min) were identified to show the metabolites migration process. Six (adenine, gingerol, terephthalic acid, vanillin, pentanenitrile, and 2-pyrrolidinonede) and seven (butyramide, lysope(0:0/20:4(5z,8z,11z,14z)), lysope(22:6(4z,7z,10z,13z,16z,19z)/0:0), linoleic acid, N-acetylneuraminic acid, L-threose, and benzoin) chemicals were screened out in the differential metabolites of tilapia skin and soup, respectively, with Variable Importance in the Projection of >1 and p value of <0.05. This work would be beneficial to understand the sensory and metabolite migration in the preparation process of fish soup and provided a metabolomic analysis route to analyze metabolites migration in food.
Simulated redistricting plans for the analysis and evaluation of redistricting in the United States
Authors: McCartan Cory , Kenny Christopher T. , Simko Tyler , Garcia George , Wang Kevin , Wu Melissa , Kuriwaki Shiro , Imai Kosuke 
Published: November 2022

AbstractThis article introduces the 50stateSimulations, a collection of simulated congressional districting plans and underlying code developed by the Algorithm-Assisted Redistricting Methodology (ALARM) Project. The 50stateSimulationsallow for the evaluation of enacted and other congressional redistricting plans in the United States. While the use of redistricting simulation algorithms has become standard in academic research and court cases, any simulation analysis requires non-trivial efforts to combine multiple data sets, identify state-specific redistricting criteria, implement complex simulation algorithms, and summarize and visualize simulation outputs. We have developed a complete workflow that facilitates this entire process of simulation-based redistricting analysis for the congressional districts of all 50 states. The resulting 50stateSimulationsinclude ensembles of simulated 2020 congressional redistricting plans and necessary replication data. We also provide the underlying code, which serves as a template for customized analyses. All data and code are free and publicly available. This article details the design, creation, and validation of the data.
Integrative cross-species analysis of GABAergic neuron cell types and their functions in Alzheimer’s disease
Authors: Wang Shiyou , Ding Peiwen , Yuan Jingnan , Wang Haoyu , Zhang Xiuqing , Chen Dongsheng , Ma Dongli , Zhang Xingliang , Wang Fei 
Published: November 2022

AbstractUnderstanding the phenotypic and functional diversity of cerebral cortical GABAergic neurons requires a comprehensive analysis of key transcriptional signatures and neuronal subtype identity. However, the diversity and conservation of GABAergic neurons across multiple mammals remain unclear. Here, we collected the single-nucleus RNA sequencing (snRNA-seq) datasets of cerebral cortex from human, macaque, mouse, and pig to identify the conserved neuronal cell types across species. After systematic analysis of the heterogeneity of GABAergic neurons, we defined four major conserved GABAergic neuron subclasses (Inc SST, Inc LAMP5, Inc PVALB, and Inc VIP) across species. We characterized the species-enriched subclasses of GABAergic neurons from four mammals, such as Inc Meis2 in mouse. Then, we depicted the genetic regulatory network (GRNs) of GABAergic neuron subclasses, which showed the conserved and species-specific GRNs for GABAergic neuron cell types. Finally, we investigated the GABAergic neuron subclass-specific expression modules of Alzheimer’s disease (AD)-related genes in GABAergic neuron cell types. Overall, our study reveals the conserved and divergent GABAergic neuron subclasses and GRNs across multiple species and unravels the gene expression modules of AD-risk genes in GABAergic neuron subclasses, facilitating the GABAergic neurons research and clinical treatment.
Characterizing the effect of demographics, cardiorespiratory factors, and inter-subject variation on maternal heart rate variability in pregnancy with statistical modeling: a retrospective observational analysis
Authors: Bester M. , Joshi R. , Linders A. , Mischi M. , van Laar J. O. E. H. , Vullings R. 
Published: November 2022

AbstractPregnancy complications are associated with insufficient adaptation of the maternal autonomic nervous system to the physiological demands of pregnancy. Consequently, assessing maternal heart rate variability (mHRV)—which reflects autonomic regulation—is a promising tool for detecting early deterioration in maternal health. However, before mHRV can be used to screen for complications, an understanding of the factors influencing mHRV during healthy pregnancy is needed. In this retrospective observational study, we develop regression models to unravel the effects of maternal demographics (age, body mass index (BMI), gestational age (GA), and parity), cardiorespiratory factors (heart rate and breathing rate), and inter-subject variation on mHRV. We develop these models using two datasets which are comprised of, respectively, single measurements in 290 healthy pregnant women and repeated measurements (median = 8) in 29 women with healthy pregnancies. Our most consequential finding is that between one-third and two-thirds of the variation in mHRV can be attributed to inter-subject variability. Additionally, median heart rate dominantly affects mHRV (p < 0.001), while BMI and parity have no effect. Moreover, we found that median breathing rate, age, and GA all impact mHRV (p < 0.05). These results suggest that personalized, long-term monitoring would be necessary for using mHRV for obstetric screening.