bluuebunny/crossref_metadata_2025 huggingface dataset:
Breaking Up Is Hard to Do: Magmatism During Oceanic Arc Breakup, Subduction Reversal, and Cessation
Authors: Gill James , Todd Erin , Hoernle Kaj , Hauff Folkmar , Price Allison Ann , Jackson Matthew G.
Published: November 2022

The formerly continuous Vitiaz Arc broke into its Vanuatu and Fijian portions during a reversal of subduction polarity in the Miocene. Basaltic volcanism in Fiji that accompanied the breakup ranged from shoshonitic to low‐K and boninitic with increasing distance from the broken edge of the arc that, presumably, marks the broken edge of the slab. The Sr‐Pb‐Nd isotope ratios of the slab‐derived component in the breakup basalts most closely match those of the isotopically most depleted part of the Samoan seamount chain on the Pacific Plate that was adjacent to the site of breakup at 4–8 Ma, and differ from those of subsequent basalts in spreading segments of the surrounding backarc North Fiji and Lau Basins. Subduction of the Samoan Chain along the Vitiaz Trench Lineament may have controlled the limit of polarity reversal and, hence, where the double saloon doors (Martin, 2013) opened. Prior to breakup, Fijian volcanics were more similar isotopically to the Louisville Seamount Chain.
Magnetospheric Field‐Aligned Current Generation by Foreshock Transients: Contribution by Flow Vortices and Pressure Gradients
Authors: Liu Terry Z. , Wang Chih‐Ping , Wang Xueyi , Angelopoulos Vassilis , Zhang Hui , Lu Xi , Lin Yu
Published: November 2022

Foreshock transients can result in significant dynamic pressure perturbations downstream, causing the magnetopause to move locally outward and inward. These near‐magnetopause phenomena in turn generate magnetospheric field‐aligned currents (FACs). FACs driven by solar wind impulses are commonly found to be due to flow vortices, but it remains unclear whether the FACs driven by those localized foreshock transients are contributed by flow vortices or pressure gradients. We report on a fortuitous conjunction between the Magnetospheric Multiscale (MMS) mission, which was observing a foreshock transient at the flank of the bow shock, and the Time History of Events and Macroscale Interactions during Substorms (THEMIS) mission, immediately downstream of MMS, which was observing magnetopause disturbances arising from that transient. Using observations from the three THEMIS spacecraft to calculate local current density perturbations within the outward motion region of the magnetosphere, we find that flow vortices play a dominant role in generating the current there; the contribution from pressure gradients is one order of magnitude smaller. Using a global hybrid simulation that reproduces the observed foreshock transient perturbations, we traced the simulated FACs generated by the transient's interaction with the magnetopause. We find that in the outward magnetopause motion region the simulated FACs are driven by flow vortices, in agreement with THEMIS observations. Deeper inside the magnetosphere, the faster convection of bipolar flow vortices than the local magnetospheric flow leads to reversal of the simulated FACs. Our results improve our understanding of how foreshock transients disturb and energize the magnetosphere‐ionosphere system.
Seasonally Discrepant Long‐Term Variations of the F2‐Layer Due To Geomagnetic Activity and Modulation to Linear Trend
Authors: Chen Yiding , Liu Libo , Le Huijun , Zhang Hui , Zhang Ruilong
Published: November 2022

Ionospheric long‐term variation has attracted wide attention since the upper atmosphere cooling due to increasing greenhouse gas was suggested. Observations of the lower ionosphere have indicated that cooling effect, whereas the F2 layer long‐term variation still remains controversial as multiple driving sources may cause it. It is crucial for investigating the F2 layer long‐term variation to distinguish contributions of different sources. foF2 records covering both long‐term increasing and decreasing phases of geomagnetic activity were selected for this study. foF2 long‐term component related to those increasing and decreasing phases is separable from the linear trend due to increasing greenhouse gas; it was identified and investigated. Geomagnetic activity induced long‐term component was found to be seasonally discrepant. With long‐term increasing geomagnetic activity, foF2 increases in winter while decreases in summer at middle and low latitudes; it decreases at higher latitudes while turns to increases with decreasing latitudes in equinox. In addition to the geomagnetic activity induced component, the linear component is dominated by long‐term decreasing trend, which is in line with the increasing greenhouse gas. Long‐term evolution of frequent weak geomagnetic activity was suggested to be primarily responsible for the seasonally discrepant long‐term variation of foF2 related to geomagnetic activity; it may change thermospheric composition by modulating average circulation. Moreover, geomagnetic activity has a decreasing trend as a whole. That may lead to misleading correlation between foF2 long‐term variation and geomagnetic activity if linear trend is dominant, and cause significant deviation when estimating greenhouse gas related decreasing trend using linear regression.
Seismic Fault Slip Behavior Predicted From Internal Microphysical Processes
Authors: Chen Jianye , Niemeijer Andre R. , Spiers Christopher J.
Published: November 2022

Earthquake simulation and hazard prediction are strongly hampered by insufficient physical knowledge of the constitutive behavior of faults. Laboratory studies of carbonate fault friction suggest that seismogenic rupture on faults in carbonate terrains can be explained by a transition from high friction at low initial sliding velocities (V) to low friction at seismic slip velocities, that is, by rapid dynamic weakening. One proposed explanation for this weakening, invokes frictional heating resulting in deformation by grain boundary sliding accommodated by solid‐state diffusion (sometimes referred to as “viscous” or “superplastic” flow). We recently added this dynamic weakening mechanism to a microphysically based model addressing the (rate‐and‐state) frictional behavior of granular gouges undergoing low V shear characteristic of rupture nucleation and arrest. In the present study, we applied the full model to simulate seismic slip in laboratory carbonate faults. Assuming that slip localizes in a principal shear band within the fault (gouge) zone, and accounting for grain size evolution with velocity and temperature, the model reproduces the frictional, thermal and (micro‐)structural evolution observed during seismic slip experiments. In particular, it predicts spatial and temporal evolutions of grain size, porosity, and dominant deformation mechanisms, within and outside the assumed shear band, consistent with trends identified in the laboratory and natural fault zones.
Micromechanics and Strain Localization in Sand in the Ductile Regime
Authors: Shahin G. , Hurley R. C.
Published: November 2022

Critical processes including seismic faulting, reservoir compartmentalization, and borehole failure involve high‐pressure mechanical behavior and strain localization of sedimentary rocks such as sandstone. Sand is often used as a model material to study the mechanical behavior of poorly lithified sandstone. Recent studies exploring the multi‐scale mechanics of sand have characterized the brittle, low‐pressure regime of behavior; however, limited work has provided insights into the ductile, high‐pressure regime of behavior via in‐situ measurements. Critical features of the ductile regime, including grain breakage, grain micromechanics, and volumetric strain behavior therefore remain under‐explored. Here, we use a new high‐pressure triaxial apparatus with in‐situ x‐ray tomography to provide new insights into deformation banding, grain breakage, and grain micromechanics in Ottawa sand subjected to triaxial compression under confining pressures between 10 and 45 MPa. We observed strain‐hardening at pressures above 15 MPa and strain‐neutral responses at pressures below 15 MPa. Compacting shear bands and grain breakage were observed at all pressures with no significant variation due to grain size, except for minor increases in breakage in less‐rounded sands. Grain breakage emerged at stress levels lower than the assumed yield threshold and more intense breakage was associated with thinner deformation bands. Contact sliding at inter‐grain contacts demonstrated a bifurcation into a bimodal distribution, with intense sliding within deformation bands and reduced but non‐negligible sliding outside of deformation bands, suggesting that off‐band zones remain mechanically active during strain hardening.
Interannual Variability of the 12‐hr Tide in the Mesosphere and Lower Thermosphere in 15 Years of Meteor‐Radar Observations Over Rothera (68°S, 68°W)
Authors: Dempsey Shaun M. , Noble Phoebe E. , Wright Corwin J. , Mitchell Nicholas J. , Moffat‐Griffin Tracy
Published: November 2022

The solar tides of the mesosphere and lower thermosphere (MLT) show great variability on time scales of days to years, with significant variability at interannual time scales. However, the nature and causes of this variability remain poorly understood. Here, we present measurements made over the interval 2005–2020 of the interannual variability of the 12‐hr tide as measured at heights of 80–100 km by a meteor radar over Rothera (68°S, 68°W). We use a linear regression analysis to investigate correlations between the 12‐hr tidal amplitudes and several climate indices, specifically the solar cycle (as measured by F10.7 solar flux), El Niño Southern Oscillation (ENSO), the Quasi‐Biennial Oscillation (QBO) at 10 and 30 hPa and the Southern Annular Mode (SAM). Our observations reveal that the 12‐hr tide has a large amplitude and a clearly defined seasonal cycle with monthly mean values as large as 35 m s−1. We observe substantial interannual variability, with monthly mean 12‐hr tidal amplitudes at 95 km exhibiting a two standard‐deviation range (2σ) in spring of 13.4 m s−1, 11.2 m s−1 in summer, 18.6 m s−1 in autumn, and 7.0 m s−1 in winter. We find that F10.7, QBO10, QBO30, and SAM all have significant correlations to the 12‐hr tidal amplitudes at the 95% level, with a linear trend also present. Whereas we detect very minimal correlation with ENSO. These results suggest that variations in F10.7, the QBO and SAM may contribute significantly to the interannual variability of 12‐hr tidal amplitudes in the Antarctic MLT.
Bi‐Linear Laws Govern the Impacts of Debris Flows, Debris Avalanches, and Rock Avalanches on Flexible Barrier
Authors: Kong Yong , Guan Mingfu , Li Xingyue , Zhao Jidong , Yan Haochen
Published: November 2022

Geophysical mass flows impacting flexible barriers can create complex flow patterns and multiway solid‐fluid‐structure interactions, wherein estimates of impact loads rely predominantly on analytical or simplified solutions. However, an examination of the fundamental relations, applicability, and underlying mechanisms of these solutions has been so far elusive. Here, using a coupled continuum‐discrete method, we systematically examine the physical laws of multiphase, multiway interactions between geophysical flows of variable natures, and a permeable flexible ring net barrier system. This model well captures the essential physics observed in experiments and field investigations. Our results reveal for the first time that unified bi‐linear laws underpin widely used analytical and simplified solutions, with inflection points caused by the transitions from trapezoid‐shaped to triangle‐shaped dead zones. Specifically, the peak impact load increases bi‐linearly with increasing Froude number, peak cable force, or maximum barrier deformation. Flow materials (wet vs. dry) and impact dynamics (slow vs. fast) jointly drive the patterns of identified bi‐linear correlations. These findings offer a physics‐based, significant improvement over existing solutions to impact problems for geophysical flows.
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

Global 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

We 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

Historically, 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

Cell 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

Southern 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

Neuropsychiatric 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

Communication 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

During 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

Immunoglobulin 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

Dynamin 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

Expanding 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

Social 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

Stability 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

Machine-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.
A dataset of a proxy variable for the poultry trade flows in China
Authors: Kong Lingcai , Zhou Xuan , Duan Mengwei , Yang Xinyi , Zhou Caifeng , Liao Yilan
Published: November 2022

Understanding the intercity poultry trading network is crucial for assessing the risk of avian influenza prevalence. Unfortunately, the poultry trading network in China has rarely been described. Here, with a modified radiation model, we obtain values for a proxy variable for poultry trade flows among 318 prefecture-level cities in China in 2015 utilizing the product capacity and demand quantity of poultry of the cities. The results are validated by comparing the proxy variable values with the trade volumes investigated in the literature, and it is found that the modified radiation model can accurately predict the main poultry trade flows among cities. This is the first dataset on China’s poultry trade pattern, and it can be used to analyze the production and consumption structure of poultry in prefecture-level cities within China. The dataset can be a tool for avian influenza epidemic risk assessment as well as a basis to develop prevention and control measures during an epidemic.
Co-axial acoustic-based optical coherence vibrometry probe for the quantification of resonance frequency modes in ocular tissue
Authors: McAuley Ryan , Nolan A. , Curatolo A. , Alexandrov S. , Zvietcovich F. , Varea Bejar A. , Marcos S. , Leahy M. , Birkenfeld J. S.
Published: November 2022

We present a co-axial acoustic-based optical coherence vibrometry probe (CoA-OCV) for vibro-acoustic resonance quantification in biological tissues. Sample vibrations were stimulated via a loudspeaker, and pre-compensation was used to calibrate the acoustic spectrum. Sample vibrations were measured via phase-sensitive swept-source optical coherence tomography (OCT). Resonance frequencies of corneal phantoms were measured at varying intraocular pressures (IOP), and dependencies on Young´s Modulus (E), phantom thickness and IOP were observed. Cycling IOP revealed hysteresis. For E = 0.3 MPa, resonance frequencies increased with IOP at a rate of 3.9, 3.7 and 3.5 Hz/mmHg for varied thicknesses and 1.7, 2.5 and 2.8 Hz/mmHg for E = 0.16 MPa. Resonance frequencies increased with thickness at a rate of 0.25 Hz/µm for E = 0.3 MPa, and 0.40 Hz/µm for E = 0.16 MPa. E showed the most predominant impact in the shift of the resonance frequencies. Full width at half maximum (FWHM) of the resonance modes increased with increasing thickness and decreased with increasing E. Only thickness and E contributed to the variance of FWHM. In rabbit corneas, resonance frequencies of 360–460 Hz were observed. The results of the current study demonstrate the feasibility of CoA-OCV for use in future OCT-V studies.
Self-reported sleep quality and mental health mediate the relationship between chronic diseases and suicidal ideation among Chinese medical students
Authors: Gui Zhen , Sun Long , Zhou Chengchao
Published: November 2022

High prevalence and strong associations of chronic disease, poor sleep quality, poor mental health, and suicidal ideation (SI) have been reported worldwide. However, the underlying mechanism remains unexamined. The participants were 2646 Chinese medical college students with an average age of 20.13 years. Pittsburgh Sleep Quality Index, the Kessler Psychological Distress Scale, and SI was evaluated. The lifetime SI, past 12-month SI, and chronic disease prevalence rates were 10.0%, 8.4%, and 4.6%, respectively. The results of logistic regression analysis in this study found that chronic disease, self-reported poor sleep quality, poor mental health, gender and scholarship were associated with lifetime SI. Similar results were also found for 12-month SI with an exception of region. This result indicated that the effects of chronic diseases on the SI were mediated by self-reported sleep quality and mental health. Physical diseases, sleep-related concerns, and mental health issues need to be addressed through a multidisciplinary team approach and various delivery systems to prevent SI among medical college students.
Identifying plastics with photoluminescence spectroscopy and machine learning
Authors: Lotter Benjamin , Konde Srumika , Nguyen Johnny , Grau Michael , Koch Martin , Lenz Peter
Published: November 2022

A quantitative understanding of the worldwide plastics distribution is required not only to assess the extent and possible impact of plastic litter on the environment but also to identify possible counter measures. A systematic collection of data characterizing amount and composition of plastics has to be based on two crucial components: (i) An experimental approach that is simple enough to be accessible worldwide and sensible enough to capture the diversity of plastics; (ii) An analysis pipeline that is able to extract the relevant parameters from the vast amount of experimental data. In this study, we demonstrate that such an approach could be realized by a combination of photoluminescence spectroscopy and a machine learning-based theoretical analysis. We show that appropriate combinations of classifiers with dimensional reduction algorithms are able to identify specific material properties from the spectroscopic data. The best combination is based on an unsupervised learning technique making our approach robust to alternations of the input data.
Functional connectivity response to acute pain assessed by fNIRS is associated with BDNF genotype in fibromyalgia: an exploratory study
Authors: de Oliveira Franco Álvaro , de Oliveira Venturini Guilherme , da Silveira Alves Camila Fernanda , Alves Rael Lopes , Vicuña Paul , Ramalho Leticia , Tomedi Rafaela , Bruck Samara Machado , Torres Iraci L. S. , Fregni Felipe , Caumo Wolnei
Published: November 2022

Fibromyalgia is a heterogenous primary pain syndrome whose severity has been associated with descending pain modulatory system (DPMS) function and functional connectivity (FC) between pain processing areas. The brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism has been linked to vulnerability to chronic pain. In this cross-sectional imaging genetics study, we investigated fibromyalgia, the relationship between BDNF Val66Met heterozygous genotypes (Val/Met), and the functional connectivity (FC) response pattern to acute pain stimulus in the motor (MC) and prefrontal (PFC) cortex assessed by near-infrared spectroscopy (fNIRS) before and after a cold pressor test utilizing water (0–1 °C). Also, we assessed the relationship between this genotype with the DPMS function and quality of life. We included 42 women (Val/Val = 30; Val/Met = 12) with fibromyalgia, ages 18–65. The MANCOVA comparing Val/Met to Val/Val genotypes showed higher ΔFC between left(l)-PFC—l-MC (β = 0.357, p = 0.048), l-PFC—right(r)-PFC (β = 0.249, p = 0.012), l-PFC—r-MC (β = 0.226, p = 0.022), and l-MC—r-PFC (β = 0.260, p = 0.016). Val/Met genotypes showed higher efficiency of the DPMS and lower disability due to pain. Here we show that fibromyalgia patients carrying the Val/Met BDNF genotype presented an increased ΔFC across MC and PFC in response to acute pain associated with differences in acute pain perception and fibromyalgia symptoms.
Simulated global warming affects endophytic bacterial and fungal communities of Antarctic pearlwort leaves and some bacterial isolates support plant growth at low temperatures
Authors: Perazzolli Michele , Vicelli Bianca , Antonielli Livio , Longa Claudia M. O. , Bozza Elisa , Bertini Laura , Caruso Carla , Pertot Ilaria
Published: November 2022

Antarctica is one of the most stressful environments for plant life and the Antarctic pearlwort (Colobanthus quitensis) is adapted to the hostile conditions. Plant-associated microorganisms can contribute to plant survival in cold environments, but scarce information is available on the taxonomic structure and functional roles ofC. quitensis-associated microbial communities. This study aimed at evaluating the possible impacts of climate warming on the taxonomic structure ofC. quitensisendophytes and at investigating the contribution of culturable bacterial endophytes to plant growth at low temperatures. The culture-independent analysis revealed changes in the taxonomic structure of bacterial and fungal communities according to plant growth conditions, such as the collection site and the presence of open-top chambers (OTCs), which can simulate global warming. Plants grown inside OTCs showed lower microbial richness and higher relative abundances of biomarker bacterial genera (Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium,Aeromicrobium,Aureimonas,Hymenobacter,Novosphingobium,Pedobacter,PseudomonasandSphingomonas) and fungal genera (Alternaria,Cistella,andVishniacozyma) compared to plants collected from open areas (OA), as a possible response to global warming simulated by OTCs. Culturable psychrotolerant bacteria ofC. quitensiswere able to endophytically colonize tomato seedlings and promote shoot growth at low temperatures, suggesting their potential contribution to plant tolerance to cold conditions.
Quantification of receptor binding from response data obtained at different receptor levels: a simple individual sigmoid fitting and a unified SABRE approach
Authors: Buchwald Peter
Published: November 2022

Methods that allow quantification of receptor binding (occupancy) by measuring response (effect) data only are of interest as they can be used to allow characterization of binding properties (e.g., dissociation constant, Kd) without having to perform explicit ligand binding experiments that require different setups (e.g., use of labeled ligands). However, since response depends not just on the binding affinity-determined receptor occupancy, but also on receptor activation, which is affected by ligand efficacy (plus constitutive activity, if present), and downstream pathway amplification, this requires the acquisition and fitting of multiple concentration-response data. Here, two alternative methods, which both are straightforward to implement using nonlinear regression software, are described to fit such multiple responses measured at different receptor levels that can be obtained, for example, by partial irreversible receptor inactivation (i.e., Furchgott method) or different expression levels. One is a simple method via straightforward fitting of each response with sigmoid functions and estimation of Kd from the obtained Emax and EC50 values as Kd = (Emax·EC′50 − E′max·EC50)/(Emax − E′max). This is less error-prone than the original Furchgott method of double-reciprocal fit and simpler than alternatives that require concentration interpolations, thus, should allow more widespread use of this so-far underutilized approach to estimate binding properties. Relative efficacies can then be compared using Emax·Kd/EC50 values. The other is a complex method that uses the SABRE receptor model to obtain a unified fit of the multiple concentration-response curves with a single set of parameters that include binding affinity Kd, efficacy ε, amplification γ, and Hill coefficient n. Illustrations with simulated and experimental data are presented including with activity data of three muscarinic agonists measured in rabbit myocardium.