bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison and Synthesis of Sea‐Level and Deep‐Sea Temperature Variations Over the Past 40 Million Years
Authors: Rohling Eelco J. , Foster Gavin L. , Gernon Thomas M. , Grant Katharine M. , Heslop David , Hibbert Fiona D. , Roberts Andrew P. , Yu Jimin 
Published: November 2022

AbstractGlobal ice volume (sea level) and deep‐sea temperature are key measures of Earth's climatic state. We synthesize evidence for multi‐centennial to millennial ice‐volume and deep‐sea temperature variations over the past 40 million years, which encompass the early glaciation of Antarctica at ∼34 million years ago (Ma), the end of the Middle Miocene Climate Optimum, and the descent into bipolar glaciation from ∼3.4 Ma. We compare different sea‐level and deep‐water temperature reconstructions to build a resource for validating long‐term numerical model‐based approaches. We present: (a) a new template synthesis of ice‐volume and deep‐sea temperature variations for the past 5.3 million years; (b) an extended template for the interval between 5.3 and 40 Ma; and (c) a discussion of uncertainties and limitations. We highlight key issues associated with glacial state changes in the geological record from 40 Ma to present that require attention in further research. These include offsets between calibration‐sensitive versus thermodynamically guided deep‐sea paleothermometry proxy measurements; a conundrum related to the magnitudes of sea‐level and deep‐sea temperature change at the Eocene‐Oligocene transition at 34 Ma; a discrepancy in deep‐sea temperature levels during the Middle Miocene; and a hitherto unquantified non‐linear reduction of glacial deep‐sea temperatures through the past 3.4 million years toward a near‐freezing deep‐sea temperature asymptote, while sea level stepped down in a more uniform manner. Uncertainties in proxy‐based reconstructions hinder further distinction of “reality” among reconstructions. It seems more promising to further narrow this using three‐dimensional ice‐sheet models with realistic ice‐climate‐ocean‐topography‐lithosphere coupling, as computational capacities improve.
Over 20‐Year Global Magnetohydrodynamic Simulation of Earth's Magnetosphere
Authors: Honkonen Ilja , van de Kamp Max , Hoppe Theresa , Kauristie Kirsti 
Published: November 2022

AbstractWe present our approach to modeling over 20 years of the solar wind‐magnetosphere‐ionosphere system using version 5 of the Grand Unified Magnetosphere‐Ionosphere Coupling Simulation (GUMICS‐5). As input we use 16‐s resolution magnetic field and 1‐min plasma measurements by Advanced Composition Explorer satellite from 1998 to 2020. The modeled interval is divided into 28 hr simulations including 4 hr overlap. We use maximum magnetospheric resolution of 0.5 Earth radii (RE) up to about 15 RE from Earth and decreasing resolution further away. In the ionosphere we use a maximum resolution of approximately 100 km poleward of ±58° magnetic latitude and decreasing resolution toward equator. With respect to previous version GUMICS‐4, we have parallelized the magnetosphere of GUMICS‐5 using the Message Passing Interface and have made several improvements which have for example, decreased its numerical diffusion. In total we have performed over 8,000 simulations which have produced over 10,000,000 ionospheric files and 2,000,000 magnetospheric files requiring over 100 TB of disk space. We compare these results to several empirical models and geomagnetic indices derived from ground magnetic field measurements. GUMICS‐5 reproduces observed solar cycle trends in magnetopause stand‐off distance and magnetospheric lobe field strength but consistency in plasma sheet pressure and ionospheric cross‐polar cap potential is lower. Comparisons with geomagnetic indices show better results for Kp index than for auroral electrojet index. Our extensive results can serve, for example, as a foundation for combined physics‐based and black‐box approach to real‐time prediction of near‐Earth space, or as input to other physics‐based models of the inner magnetosphere, upper and middle atmosphere, etc.
Oral prehabilitation for patients with head and neck cancer: getting it right - the Restorative Dentistry-UK consensus on a multidisciplinary approach to oral and dental assessment and planning prior to cancer treatment
Authors: McCaul Lorna K. , Barclay Stewart , Nixon Peter , Yule Pamela L. , Trainor Jenna , Stevenson Brian , Paterson Andrew , Nicol Ailsa , Keys Will , Donachie Martin , Barker Dean , Rollings Sam , Killough Simon , Ban James , Chatzipantelis Andreas , Gaitonde Pallavi , Ranka Meena , Ali Zaid , MacInnes Andrew , Taylor Carly , Gopakumar Ashish , Sharma Praveen , Harper Victoria , Rasaratnam Lakshmi , Toor Ishpinder , Rodriguez Jose M. 
Published: November 2022

AbstractHistorically, oral and dental issues for head and neck cancer patients were often not considered until after cancer treatment was complete. As a result, outcomes for oral rehabilitation were sometimes suboptimal. Inconsistencies in service delivery models and qualification, training and experience of staff delivering dental care often compounded this problem, making research and audit almost impossible. Collaborative working by consultants in restorative dentistry from all over the UK as part of a Restorative Dentistry-UK (RD UK) subgroup, renamed more recently as the RD-UK Head and Neck Cancer Clinical Excellence Network (CEN), has re-emphasised the importance of specialist restorative dentistry intervention at the outset of the head and neck cancer pathway to optimise outcomes of patient care. The CEN has driven several initiatives, reflecting Getting It Right First Time (GIRFT) principles aimed at reducing unwarranted variation. This improved consistency in approach and optimised collaborative working of the team now presents a better environment for multicentre audit and research. Ultimately, this should result in a continued improvement in patient and carer experience.
50 years on and still very much alive: ‘Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics’
Authors: Nössing Christoph , Ryan Kevin M. 
Published: November 2022

AbstractCell death is part of the lifecycle of every multicellular organism. Nineteenth-century pathologists already recognised that organised forms of cell death must exist to explain the demise and turnover of cells during metamorphosis (of insects), embryogenesis and normal tissue homoeostasis [1]. Nevertheless, Kerr, Wyllie and Currie in their seminal paper of 1972, were the first to collate and define the distinct morphological features of controlled cell death in different contexts [2]. To describe the processes of cell deletion observed under both physiological and pathological conditions, they coined the term ‘Apoptosis’ (derived from the Greek word ‘ἀπόπτωσις’, meaning ‘dropping off or falling off’ of petals from flowers). Kerr, Wyllie and Currie defined apoptosis as a mechanism ‘complementary to mitosis in the regulation of animal cell populations’. In addition, they already recognised the potential to use this programmed form of cell death for cancer therapy, but they also emphasised the occurrence of apoptosis during cancer development. In this article, some 50 years after its initial publication in The British Journal of Cancer, we revaluate and put the authors initial assumptions and general concepts about apoptosis into the context of modern-day biology
Evidence for late-glacial oceanic carbon redistribution and discharge from the Pacific Southern Ocean
Authors: Iwasaki Shinya , Lembke-Jene Lester , Nagashima Kana , Arz Helge W. , Harada Naomi , Kimoto Katsunori , Lamy Frank 
Published: November 2022

AbstractSouthern Ocean deep-water circulation plays a vital role in the global carbon cycle. On geological time scales, upwelling along the Chilean margin likely contributed to the deglacial atmospheric carbon dioxide rise, but little quantitative evidence exists of carbon storage. Here, we develop an X-ray Micro-Computer-Tomography method to assess foraminiferal test dissolution as proxy for paleo-carbonate ion concentrations ([CO32−]). Our subantarctic Southeast Pacific sediment core depth transect shows significant deep-water [CO32−] variations during the Last Glacial Maximum and Deglaciation (10-22 ka BP). We provide evidence for an increase in [CO32−] during the early-deglacial period (15-19 ka BP) in Lower Circumpolar Deepwater. The export of such low-carbon deep-water from the Pacific to the Atlantic contributed to significantly lowered carbon storage within the Southern Ocean, highlighting the importance of a dynamic Pacific-Southern Ocean deep-water reconfiguration for shaping late-glacial oceanic carbon storage, and subsequent deglacial oceanic-atmospheric CO2 transfer.
Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders
Authors: Hettwer M. D. , Larivière S. , Park B. Y. , van den Heuvel O. A. , Schmaal L. , Andreassen O. A. , Ching C. R. K. , Hoogman M. , Buitelaar J. , van Rooij D. , Veltman D. J. , Stein D. J. , Franke B. , van Erp T. G. M. ,   ENIGMA ADHD Working Group,   ENIGMA Autism Working Group, van Rooij D. ,   ENIGMA Bipolar Disorder Working Group,   ENIGMA Major Depression Working Group,   ENIGMA OCD Working Group, van den Heuvel O. A. ,   ENIGMA Schizophrenia Working Group, van Erp T. G. M. , Jahanshad N. , Thompson P. M. , Thomopoulos S. I. , Bethlehem R. A. I. , Bernhardt B. C. , Eickhoff S. B. , Valk S. L. 
Published: November 2022

AbstractNeuropsychiatric disorders are increasingly conceptualized as overlapping spectra sharing multi-level neurobiological alterations. However, whether transdiagnostic cortical alterations covary in a biologically meaningful way is currently unknown. Here, we studied co-alteration networks across six neurodevelopmental and psychiatric disorders, reflecting pathological structural covariance. In 12,024 patients and 18,969 controls from the ENIGMA consortium, we observed that co-alteration patterns followed normative connectome organization and were anchored to prefrontal and temporal disease epicenters. Manifold learning revealed frontal-to-temporal and sensory/limbic-to-occipitoparietal transdiagnostic gradients, differentiating shared illness effects on cortical thickness along these axes. The principal gradient aligned with a normative cortical thickness covariance gradient and established a transcriptomic link to cortico-cerebello-thalamic circuits. Moreover, transdiagnostic gradients segregated functional networks involved in basic sensory, attentional/perceptual, and domain-general cognitive processes, and distinguished between regional cytoarchitectonic profiles. Together, our findings indicate that shared illness effects occur in a synchronized fashion and along multiple levels of hierarchical cortical organization.
Computationally designed GPCR quaternary structures bias signaling pathway activation
Authors: Paradis Justine S. , Feng Xiang , Murat Brigitte , Jefferson Robert E. , Sokrat Badr , Szpakowska Martyna , Hogue Mireille , Bergkamp Nick D. , Heydenreich Franziska M. , Smit Martine J. , Chevigné Andy , Bouvier Michel , Barth Patrick 
Published: November 2022

AbstractCommunication across membranes controls critical cellular processes and is achieved by receptors translating extracellular signals into selective cytoplasmic responses. While receptor tertiary structures can be readily characterized, receptor associations into quaternary structures are challenging to study and their implications in signal transduction remain poorly understood. Here, we report a computational approach for predicting receptor self-associations, and designing receptor oligomers with various quaternary structures and signaling properties. Using this approach, we designed chemokine receptor CXCR4 dimers with reprogrammed binding interactions, conformations, and abilities to activate distinct intracellular signaling proteins. In agreement with our predictions, the designed CXCR4s dimerized through distinct conformations and displayed different quaternary structural changes upon activation. Consistent with the active state models, all engineered CXCR4 oligomers activated the G protein Gi, but only specific dimer structures also recruited β-arrestins. Overall, we demonstrate that quaternary structures represent an important unforeseen mechanism of receptor biased signaling and reveal the existence of a bias switch at the dimer interface of several G protein-coupled receptors including CXCR4, mu-Opioid and type-2 Vasopressin receptors that selectively control the activation of G proteins vs β-arrestin-mediated pathways. The approach should prove useful for predicting and designing receptor associations to uncover and reprogram selective cellular signaling functions.
Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation
Authors: Zhang Zheng , Sha Baoyong , Zhao Lingzhu , Zhang Huan , Feng Jinteng , Zhang Cheng , Sun Lin , Luo Meiqing , Gao Bin , Guo Hui , Wang Zheng , Xu Feng , Lu Tian Jian , Genin Guy M. , Lin Min 
Published: November 2022

AbstractDuring mesenchymal development, the sources of mechanical forces transduced by cells transition over time from predominantly cell-cell interactions to predominantly cell-extracellular matrix (ECM) interactions. Transduction of the associated mechanical signals is critical for development, but how these signals converge to regulate human mesenchymal stem cells (hMSCs) mechanosensing is not fully understood, in part because time-evolving mechanical signals cannot readily be presented in vitro. Here, we established a DNA-driven cell culture platform that could be programmed to present the RGD peptide from fibronectin, mimicking cell-ECM interactions, and the HAVDI peptide from N-cadherin, mimicking cell-cell interactions, through DNA hybridization and toehold-mediated strand displacement reactions. The platform could be programmed to mimic the evolving cell-ECM and cell-cell interactions during mesenchymal development. We applied this platform to reveal that RGD/integrin ligation promoted cofilin phosphorylation, while HAVDI/N-cadherin ligation inhibited cofilin phosphorylation. Cofilin phosphorylation upregulated perinuclear apical actin fibers, which deformed the nucleus and thereby induced YAP nuclear localization in hMSCs, resulting in subsequent osteogenic differentiation. Our programmable culture platform is broadly applicable to the study of dynamic, integrated mechanobiological signals in development, healing, and tissue engineering.
Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits
Authors: Liu Lili , Khan Atlas , Sanchez-Rodriguez Elena , Zanoni Francesca , Li Yifu , Steers Nicholas , Balderes Olivia , Zhang Junying , Krithivasan Priya , LeDesma Robert A. , Fischman Clara , Hebbring Scott J. , Harley John B. , Moncrieffe Halima , Kottyan Leah C. , Namjou-Khales Bahram , Walunas Theresa L. , Knevel Rachel , Raychaudhuri Soumya , Karlson Elizabeth W. , Denny Joshua C. , Stanaway Ian B. , Crosslin David , Rauen Thomas , Floege Jürgen , Eitner Frank , Moldoveanu Zina , Reily Colin , Knoppova Barbora , Hall Stacy , Sheff Justin T. , Julian Bruce A. , Wyatt Robert J. , Suzuki Hitoshi , Xie Jingyuan , Chen Nan , Zhou Xujie , Zhang Hong , Hammarström Lennart , Viktorin Alexander , Magnusson Patrik K. E. , Shang Ning , Hripcsak George , Weng Chunhua , Rundek Tatjana , Elkind Mitchell S. V. , Oelsner Elizabeth C. , Barr R. Graham , Ionita-Laza Iuliana , Novak Jan , Gharavi Ali G. , Kiryluk Krzysztof 
Published: November 2022

AbstractImmunoglobulin A (IgA) mediates mucosal responses to food antigens and the intestinal microbiome and is involved in susceptibility to mucosal pathogens, celiac disease, inflammatory bowel disease, and IgA nephropathy. We performed a genome-wide association study of serum IgA levels in 41,263 individuals of diverse ancestries and identified 20 genome-wide significant loci, including 9 known and 11 novel loci. Co-localization analyses with expression QTLs prioritized candidate genes for 14 of 20 significant loci. Most loci encoded genes that produced immune defects and IgA abnormalities when genetically manipulated in mice. We also observed positive genetic correlations of serum IgA levels with IgA nephropathy, type 2 diabetes, and body mass index, and negative correlations with celiac disease, inflammatory bowel disease, and several infections. Mendelian randomization supported elevated serum IgA as a causal factor in IgA nephropathy. African ancestry was consistently associated with higher serum IgA levels and greater frequency of IgA-increasing alleles compared to other ancestries. Our findings provide novel insights into the genetic regulation of IgA levels and its potential role in human disease.
Differential impact of ubiquitous and muscle dynamin 2 isoforms in muscle physiology and centronuclear myopathy
Authors: Gómez-Oca Raquel , Edelweiss Evelina , Djeddi Sarah , Gerbier Mathias , Massana-Muñoz Xènia , Oulad-Abdelghani Mustapha , Crucifix Corinne , Spiegelhalter Coralie , Messaddeq Nadia , Poussin-Courmontagne Pierre , Koebel Pascale , Cowling Belinda S. , Laporte Jocelyn 
Published: November 2022

AbstractDynamin 2 mechanoenzyme is a key regulator of membrane remodeling and gain-of-function mutations in its gene cause centronuclear myopathies. Here, we investigate the functions of dynamin 2 isoforms and their associated phenotypes and, specifically, the ubiquitous and muscle-specific dynamin 2 isoforms expressed in skeletal muscle. In cell-based assays, we show that a centronuclear myopathy-related mutation in the ubiquitous but not the muscle-specific dynamin 2 isoform causes increased membrane fission. In vivo, overexpressing the ubiquitous dynamin 2 isoform correlates with severe forms of centronuclear myopathy, while overexpressing the muscle-specific isoform leads to hallmarks seen in milder cases of the disease. Previous mouse studies suggested that reduction of the total dynamin 2 pool could be therapeutic for centronuclear myopathies. Here, dynamin 2 splice switching from muscle-specific to ubiquitous dynamin 2 aggravated the phenotype of a severe X-linked form of centronuclear myopathy caused by loss-of-function of the MTM1 phosphatase, supporting the importance of targeting the ubiquitous isoform for efficient therapy in muscle. Our results highlight that the ubiquitous and not the muscle-specific dynamin 2 isoform is the main modifier contributing to centronuclear myopathy pathology.
Female peer mentors early in college have lasting positive impacts on female engineering students that persist beyond graduation
Authors: Wu Deborah J. , Thiem Kelsey C. , Dasgupta Nilanjana 
Published: November 2022

AbstractExpanding the talent pipeline of students from underrepresented backgrounds in STEM has been a priority in the United States for decades. However, potential solutions to increase the number of such students in STEM academic pathways, measured using longitudinal randomized controlled trials in real-world contexts, have been limited. Here, we expand on an earlier investigation that reported results from a longitudinal field experiment in which undergraduate female students (N = 150) interested in engineering at college entry were randomly assigned a female peer mentor in engineering, a male peer mentor in engineering, or not assigned a mentor for their first year of college. While an earlier article presented findings from participants’ first two years of college, the current article reports the same participants’ academic experiences for each year in college through college graduation and one year post-graduation. Compared to the male peer mentor and no mentor condition, having a female peer mentor was associated with a significant improvement in participants’ psychological experiences in engineering, aspirations to pursue postgraduate engineering degrees, and emotional well-being. It was also associated with participants’ success in securing engineering internships and retention in STEM majors through college graduation. In sum, a low-cost, short peer mentoring intervention demonstrates benefits in promoting female students’ success in engineering from college entry, through one-year post-graduation.
Neural implementation of computational mechanisms underlying the continuous trade-off between cooperation and competition
Authors: Pisauro M. A. , Fouragnan E. F. , Arabadzhiyska D. H. , Apps M. A. J. , Philiastides M. G. 
Published: November 2022

AbstractSocial interactions evolve continuously. Sometimes we cooperate, sometimes we compete, while at other times we strategically position ourselves somewhere in between to account for the ever-changing social contexts around us. Research on social interactions often focuses on a binary dichotomy between competition and cooperation, ignoring people’s evolving shifts along a continuum. Here, we develop an economic game – the Space Dilemma – where two players change their degree of cooperativeness over time in cooperative and competitive contexts. Using computational modelling we show how social contexts bias choices and characterise how inferences about others’ intentions modulate cooperativeness. Consistent with the modelling predictions, brain regions previously linked to social cognition, including the temporo-parietal junction, dorso-medial prefrontal cortex and the anterior cingulate gyrus, encode social prediction errors and context-dependent signals, correlating with shifts along a cooperation-competition continuum. These results provide a comprehensive account of the computational and neural mechanisms underlying the continuous trade-off between cooperation and competition.
A nascent peptide code for translational control of mRNA stability in human cells
Authors: Burke Phillip C. , Park Heungwon , Subramaniam Arvind Rasi 
Published: November 2022

AbstractStability of eukaryotic mRNAs is associated with their codon, amino acid, and GC content. Yet, coding sequence motifs that predictably alter mRNA stability in human cells remain poorly defined. Here, we develop a massively parallel assay to measure mRNA effects of thousands of synthetic and endogenous coding sequence motifs in human cells. We identify several families of simple dipeptide repeats whose translation triggers mRNA destabilization. Rather than individual amino acids, specific combinations of bulky and positively charged amino acids are critical for the destabilizing effects of dipeptide repeats. Remarkably, dipeptide sequences that form extended β strands in silico and in vitro slowdown ribosomes and reduce mRNA levels in vivo. The resulting nascent peptide code underlies the mRNA effects of hundreds of endogenous peptide sequences in the human proteome. Our work suggests an intrinsic role for the ribosome as a selectivity filter against the synthesis of bulky and aggregation-prone peptides.
A simple denoising approach to exploit multi-fidelity data for machine learning materials properties
Authors: Liu Xiaotong , De Breuck Pierre-Paul , Wang Linghui , Rignanese Gian-Marco 
Published: November 2022

AbstractMachine-learning models have recently encountered enormous success for predicting the properties of materials. These are often trained based on data that present various levels of accuracy, with typically much less high- than low-fidelity data. In order to extract as much information as possible from all available data, we here introduce an approach which aims to improve the quality of the data through denoising. We investigate the possibilities that it offers in the case of the prediction of the band gap using both limited experimental data and density-functional theory relying on different exchange-correlation functionals. After analyzing the raw data thoroughly, we explore different ways to combine the data into training sequences and analyze the effect of the chosen denoiser. We also study the effect of applying the denoising procedure several times until convergence. Finally, we compare our approach with various existing methods to exploit multi-fidelity data and show that it provides an interesting improvement.