bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inherited Heterogeneities Can Control Viscous Subduction Zone Deformation of Carbonates at Seismogenic Depths
Authors: Leah H. , Fagereng Å. 
Published: October 2022

AbstractThis work links mineral‐scale deformation mechanisms with structural evolution during subduction, providing examples showing how grain‐scale heterogeneities facilitated viscous creep in calcite at nominally seismogenic temperatures. Carbonates commonly enter subduction zones, either highly concentrated in irregularly distributed sediments or as more distributed precipitates in seafloor volcanics. We present shear zones, localized in calcite veins formed during shallow subduction of calcareous sediment and seafloor volcanics, with viscous shear strains of ≥5. Shear strain localized because secondary phases and chemical variations maintained fine grain sizes in calcite aggregates, activating relatively rapid grain size‐sensitive and frictional‐viscous creep at temperatures (260 ± 10°C), cooler than predicted from extrapolation of experimental data. Creep at increased strain rates may limit elastic strain accumulation during interseismic periods, reducing the likelihood of large megathrust earthquakes. As shown here for calcite, common inherited natural heterogeneities may induce weakening of viscous mechanisms in other rocks, or at larger scales in the lithosphere.
Amplification of the Temperature Seasonality in the Mediterranean Region Under Anthropogenic Climate Change
Authors: Feng Xiaofan , Qian Cheng , Materia Stefano 
Published: October 2022

AbstractAmplified warming in the Mediterranean region in summer, corresponding to strengthening temperature seasonality (Tseasonality), increases the frequency and intensity of heatwaves and endangers both human health and ecosystems. However, previous studies have not found a detectable signal of anthropogenic forcing in changes in Tseasonality in the Mediterranean and the contribution from human activities is unclear. Here, we show that signals of anthropogenic forcing and greenhouse gas forcing can be detected for the period 1950–2014, the signals of anthropogenic and natural forcing are separable, and the contribution of anthropogenic forcing is 74% using the optimal fingerprinting approach. Future projections based on attribution constraints indicated that Tseasonality will continue to strengthen by more than 2°C by 2100, which is much worse than predicted by direct model output. These results are important for understanding and projecting the impacts of human activities on Tseasonality and related summer heatwaves in the future.
Accelerated Transition Between Dry and Wet Periods in a Warming Climate
Authors: Chen Huijiao , Wang Shuo 
Published: October 2022

AbstractThe consecutive occurrence of meteorological dry and wet extremes has been receiving increasing attention due to potentially larger social and environmental impacts than single extremes. However, the changing characteristics of transitions between dry and wet periods remain poorly understood. Here we investigate the dynamic evolution of dry‐to‐wet transitions in response to climate warming, using the Standardized Precipitation Evapotranspiration Index as well as observations and general circulation models for the periods of 1954–2014 and 2040–2100. We find that approximately three‐fifths of global land area are projected to experience an accelerated dry‐to‐wet transition. Southern Asia has been experiencing the most severe dry‐to‐wet transitions and is projected to suffer more frequent, more intense, and accelerated dry‐to‐wet transitions. The increasing potential evapotranspiration (PET) variability plays an important role in accelerating the dry‐to‐wet transition in Southern Asia, while precipitation and PET variabilities contribute to the intensification of dry‐to‐wet transitions in Southern North America.
Analysis of the Hydrogeological Conditions Affecting Fault Response to Nearby Hydraulic Fracturing
Authors: Yehya A. , Basbous J. , Maalouf E. 
Published: October 2022

AbstractThe response of critically stressed dormant faults to fluid perturbation, by oil and gas production, has been a major public concern because of its link to induced seismicity. In this paper, we study the hydrogeological factors that affect a nearby fault response, during and after hydraulic fracturing (HF) operations, evaluated by the change in Coulomb Failure Stress (CFS) and the rate of seismicity (R) through coupling solid deformation and fluid flow. Our results show that the pore pressure increases rapidly in a fault that is close (hydraulically connected) to HF operations, which might lead to its activation when the injection rate is high. When the fault is adjacent to HF but distant from it, its shallow region is subjected to a stabilizing deformation‐induced normal compressive stress and its deeper region is destabilized under extension. In this case, the fault orientation and damage zone size have a significant effect on the fault's stability and response. On the other hand, decreasing the rate of injection can either increase or decrease the CFS values depending on the fault location and the dominant stresses. Therefore, serious attention should be given to the fault position, its architecture, and the injection rate to help reduce the potential for induced seismicity from HF. Our findings are verified and confirmed using the case of the Duvernay formation in Alberta, Canada, where the reported seismic data correlate with high CFS and R values.
Ferritin – a multifaceted protein scaffold for biotherapeutics
Authors: Lee Na Kyeong , Cho Seongeon , Kim In-San 
Published: October 2022

AbstractThe ferritin nanocage is an endogenous protein that exists in almost all mammals. Its hollow spherical structure that naturally stores iron ions has been diversely exploited by researchers in biotherapeutics. Ferritin has excellent biosafety profiles, and the nanosized particles exhibit rapid dispersion and controlled/sustained release pharmacokinetics. Moreover, the large surface-to-volume ratio and the disassembly/reassembly behavior of the 24 monomer subunits into a sphere allow diverse modifications by chemical and genetic methods on the surface and inner cage of ferritin. Here, we critically review ferritin and its applications. We (i) introduce the application of ferritin in drug delivery; (ii) present an overview of the use of ferritin in imaging and diagnosis for biomedical purposes; (iii) discuss ferritin-based vaccines; and (iv) review ferritin-based agents currently in clinical trials. Although there are no currently approved drugs based on ferritin, this multifunctional protein scaffold shows immense potential in drug development in diverse categories, and ferritin-based drugs have recently entered phase I clinical trials. This golden shortlist of recent developments will be of immediate benefit and interest to researchers studying ferritin and other protein-based biotherapeutics.
A genetics-first approach to understanding autism and schizophrenia spectrum disorders: the 22q11.2 deletion syndrome
Authors: Fiksinski Ania M. , Hoftman Gil D. , Vorstman Jacob A. S. , Bearden Carrie E. 
Published: October 2022

AbstractRecently, increasing numbers of rare pathogenic genetic variants have been identified that are associated with variably elevated risks of a range of neurodevelopmental outcomes, notably including Autism Spectrum Disorders (ASD), Schizophrenia Spectrum Disorders (SSD), and Intellectual Disability (ID). This review is organized along three main questions: First, how can we unify the exclusively descriptive basis of our current psychiatric diagnostic classification system with the recognition of an identifiable, highly penetrant genetic risk factor in an increasing proportion of patients with ASD or SSD? Second, what can be learned from studies of individuals with ASD or SSD who share a common genetic basis? And third, what accounts for the observed variable penetrance and pleiotropy of neuropsychiatric phenotypes in individuals with the same pathogenic variant? In this review, we focus on findings of clinical and preclinical studies of the 22q11.2 deletion syndrome (22q11DS). This particular variant is not only one of the most common among the increasing list of known rare pathogenic variants, but also one that benefits from a relatively long research history. Consequently, 22q11DS is an appealing model as it allows us to: (1) elucidate specific genotype–phenotype associations, (2) prospectively study behaviorally defined classifications, such as ASD or SSD, in the context of a known, well-characterized genetic basis, and (3) elucidate mechanisms underpinning variable penetrance and pleiotropy, phenomena with far-reaching ramifications for research and clinical practice. We discuss how findings from animal and in vitro studies relate to observations in human studies and can help elucidate factors, including genetic, environmental, and stochastic, that impact the expression of neuropsychiatric phenotypes in 22q11DS, and how this may inform mechanisms underlying neurodevelopmental expression in the general population. We conclude with research priorities for the field, which may pave the way for novel therapeutics.
Glutamate and GABAA receptor crosstalk mediates homeostatic regulation of neuronal excitation in the mammalian brain
Authors: Wen Ya , Dong Zhifang , Liu Jun , Axerio-Cilies Peter , Du Yehong , Li Junjie , Chen Long , Zhang Lu , Liu Lidong , Lu Jie , Zhou Ning , Chuan Wu Dong , Wang Yu Tian 
Published: October 2022

AbstractMaintaining a proper balance between the glutamate receptor-mediated neuronal excitation and the A type of GABA receptor (GABAAR) mediated inhibition is essential for brain functioning; and its imbalance contributes to the pathogenesis of many brain disorders including neurodegenerative diseases and mental illnesses. Here we identify a novel glutamate-GABAAR interaction mediated by a direct glutamate binding of the GABAAR. In HEK293 cells overexpressing recombinant GABAARs, glutamate and its analog ligands, while producing no current on their own, potentiate GABA-evoked currents. This potentiation is mediated by a direct binding at a novel glutamate binding pocket located at the α+/β− subunit interface of the GABAAR. Moreover, the potentiation does not require the presence of a γ subunit, and in fact, the presence of γ subunit significantly reduces the potency of the glutamate potentiation. In addition, the glutamate-mediated allosteric potentiation occurs on native GABAARs in rat neurons maintained in culture, as evidenced by the potentiation of GABAAR-mediated inhibitory postsynaptic currents and tonic currents. Most importantly, we found that genetic impairment of this glutamate potentiation in knock-in mice resulted in phenotypes of increased neuronal excitability, including decreased thresholds to noxious stimuli and increased seizure susceptibility. These results demonstrate a novel cross-talk between excitatory transmitter glutamate and inhibitory GABAAR. Such a rapid and short feedback loop between the two principal excitatory and inhibitory neurotransmission systems may play a critical homeostatic role in fine-tuning the excitation-inhibition balance (E/I balance), thereby maintaining neuronal excitability in the mammalian brain under both physiological and pathological conditions.
Regulation of KDM5C stability and enhancer reprogramming in breast cancer
Authors: Xiao Qiong , Wang Chen-Yu , Gao Chuan , Chen Ji-Dong , Chen Jing-Jing , Wang Zhen , Ju Lin-Gao , Tang Shan-Bo , Yao Jie , Li Feng , Li Lian-Yun , Wu Min 
Published: October 2022

AbstractAbnormality of enhancer regulation has emerged as one of the critical features for cancer cells. KDM5C is a histone H3K4 demethylase and frequently mutated in several types of cancer. It is critical for H3K4me3 and activity of enhancers, but its regulatory mechanisms remain elusive. Here, we identify TRIM11 as one ubiquitin E3 ligase for KDM5C. TRIM11 interacts with KDM5C, catalyzes K48-linked ubiquitin chain on KDM5C, and promotes KDM5C degradation through proteasome. TRIM11 deficiency in an animal model represses the growth of breast tumor and stabilizes KDM5C. In breast cancer patient tissues, TRIM11 is highly expressed and KDM5C is lower expressed, and their expression is negatively correlated. Mechanistically, TRIM11 regulates the enhancer activity of genes involved in cell migration and immune response by targeting KDM5C. TRIM11 and KDM5C regulate MCAM expression and cell migration through targeting H3K4me3 on MCAM enhancer. Taken together, our study reveals novel mechanisms for enhancer regulation during breast cancer tumorigenesis and development.
Assessing the digenic model in rare disorders using population sequencing data
Authors: Moreno-Ruiz Nerea ,   Genomics England Research Consortium, Ambrose J. C. , Arumugam P. , Baple E. L. , Bleda M. , Boardman-Pretty F. , Boissiere J. M. , Boustred C. R. , Brittain H. , Caulfield M. J. , Chan G. C. , Craig C. E. H. , Daugherty L. C. , de Burca A. , Devereau A. , Elgar G. , Foulger R. E. , Fowler T. , Furió-Tarí P. , Giess A. , Hackett J. M. , Halai D. , Hamblin A. , Henderson S. , Holman J. E. , Hubbard T. J. P. , Ibáñez K. , Jackson R. , Jones L. J. , Kasperaviciute D. , Kayikci M. , Kousathanas A. , Lahnstein L. , Lawson K. , Leigh S. E. A. , Leong I. U. S. , Lopez F. J. , Maleady-Crowe F. , Mason J. , McDonagh E. M. , Moutsianas L. , Mueller M. , Murugaesu N. , Need A. C. , Odhams C. A. , Orioli A. , Patch C. , Perez-Gil D. , Pereira M. B. , Polychronopoulos D. , Pullinger J. , Rahim T. , Rendon A. , Riesgo-Ferreiro P. , Rogers T. , Ryten M. , Savage K. , Sawant K. , Scott R. H. , Siddiq A. , Sieghart A. , Smedley D. , Smith K. R. , Smith S. C. , Sosinsky A. , Spooner W. , Stevens H. E. , Stuckey A. , Sultana R. , Tanguy M. , Thomas E. R. A. , Thompson S. R. , Tregidgo C. , Tucci A. , Walsh E. , Watters S. A. , Welland M. J. , Williams E. , Witkowska K. , Wood S. M. , Zarowiecki M. , Lao Oscar , Aróstegui Juan Ignacio , Laayouni Hafid , Casals Ferran 
Published: October 2022

AbstractAn important fraction of patients with rare disorders remains with no clear genetic diagnostic, even after whole-exome or whole-genome sequencing, posing a difficulty in giving adequate treatment and genetic counseling. The analysis of genomic data in rare disorders mostly considers the presence of single gene variants in coding regions that follow a concrete monogenic mode of inheritance. A digenic inheritance, with variants in two functionally-related genes in the same individual, is a plausible alternative that might explain the genetic basis of the disease in some cases. In this case, digenic disease combinations should be absent or underrepresented in healthy individuals. We develop a framework to evaluate the significance of digenic combinations and test its statistical power in different scenarios. We suggest that this approach will be relevant with the advent of new sequencing efforts including hundreds of thousands of samples.
HOXA9 has the hallmarks of a biological switch with implications in blood cancers
Authors: Talarmain Laure , Clarke Matthew A. , Shorthouse David , Cabrera-Cosme Lilia , Kent David G. , Fisher Jasmin , Hall Benjamin A. 
Published: October 2022

AbstractBlood malignancies arise from the dysregulation of haematopoiesis. The type of blood cell and the specific order of oncogenic events initiating abnormal growth ultimately determine the cancer subtype and subsequent clinical outcome. HOXA9 plays an important role in acute myeloid leukaemia (AML) prognosis by promoting blood cell expansion and altering differentiation; however, the function of HOXA9 in other blood malignancies is still unclear. Here, we highlight the biological switch and prognosis marker properties of HOXA9 in AML and chronic myeloproliferative neoplasms (MPN). First, we establish the ability of HOXA9 to stratify AML patients with distinct cellular and clinical outcomes. Then, through the use of a computational network model of MPN, we show that the self-activation of HOXA9 and its relationship to JAK2 and TET2 can explain the branching progression of JAK2/TET2 mutant MPN patients towards divergent clinical characteristics. Finally, we predict a connection between the RUNX1 and MYB genes and a suppressive role for the NOTCH pathway in MPN diseases.
Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis
Authors: Nakajima Kichitaro , Yamaguchi Keiichi , Noji Masahiro , Aguirre César , Ikenaka Kensuke , Mochizuki Hideki , Zhou Lianjie , Ogi Hirotsugu , Ito Toru , Narita Ichiei , Gejyo Fumitake , Naiki Hironobu , Yamamoto Suguru , Goto Yuji 
Published: October 2022

AbstractDialysis-related amyloidosis (DRA), a serious complication among long-term hemodialysis patients, is caused by amyloid fibrils of β2-microglobulin (β2m). Although high serum β2m levels and a long dialysis vintage are the primary and secondary risk factors for the onset of DRA, respectively, patients with these do not always develop DRA, indicating that there are additional risk factors. To clarify these unknown factors, we investigate the effects of human sera on β2m amyloid fibril formation, revealing that sera markedly inhibit amyloid fibril formation. Results from over 100 sera indicate that, although the inhibitory effects of sera deteriorate in long-term dialysis patients, they are ameliorated by maintenance dialysis treatments in the short term. Serum albumin prevents amyloid fibril formation based on macromolecular crowding effects, and decreased serum albumin concentration in dialysis patients is a tertiary risk factor for the onset of DRA. We construct a theoretical model assuming cumulative effects of the three risk factors, suggesting the importance of monitoring temporary and accumulated risks to prevent the development of amyloidosis, which occurs based on supersaturation-limited amyloid fibril formation in a crowded milieu.
Public attitudes value interpretability but prioritize accuracy in Artificial Intelligence
Authors: Nussberger Anne-Marie , Luo Lan , Celis L. Elisa , Crockett M. J. 
Published: October 2022

AbstractAs Artificial Intelligence (AI) proliferates across important social institutions, many of the most powerful AI systems available are difficult to interpret for end-users and engineers alike. Here, we sought to characterize public attitudes towards AI interpretability. Across seven studies (N = 2475), we demonstrate robust and positive attitudes towards interpretable AI among non-experts that generalize across a variety of real-world applications and follow predictable patterns. Participants value interpretability positively across different levels of AI autonomy and accuracy, and rate interpretability as more important for AI decisions involving high stakes and scarce resources. Crucially, when AI interpretability trades off against AI accuracy, participants prioritize accuracy over interpretability under the same conditions driving positive attitudes towards interpretability in the first place: amidst high stakes and scarce resources. These attitudes could drive a proliferation of AI systems making high-impact ethical decisions that are difficult to explain and understand.
Versatile self-assembled electrospun micropyramid arrays for high-performance on-skin devices with minimal sensory interference
Authors: Zhang Jia-Han , Li Zhengtong , Xu Juan , Li Jiean , Yan Ke , Cheng Wen , Xin Ming , Zhu Tangsong , Du Jinhua , Chen Sixuan , An Xiaoming , Zhou Zhou , Cheng Luyao , Ying Shu , Zhang Jing , Gao Xingxun , Zhang Qiuhong , Jia Xudong , Shi Yi , Pan Lijia 
Published: October 2022

AbstractOn-skin devices that show both high performance and imperceptibility are desired for physiological information detection, individual protection, and bioenergy conversion with minimal sensory interference. Herein, versatile electrospun micropyramid arrays (EMPAs) combined with ultrathin, ultralight, gas-permeable structures are developed through a self-assembly technology based on wet heterostructured electrified jets to endow various on-skin devices with both superior performance and imperceptibility. The designable self-assembly allows structural and material optimization of EMPAs for on-skin devices applied in daytime radiative cooling, pressure sensing, and bioenergy harvesting. A temperature drop of ~4 °C is obtained via an EMPA-based radiative cooling fabric under a solar intensity of 1 kW m–2. Moreover, detection of an ultraweak fingertip pulse for health diagnosis during monitoring of natural finger manipulation over a wide frequency range is realized by an EMPA piezocapacitive-triboelectric hybrid sensor, which has high sensitivity (19 kPa−1), ultralow detection limit (0.05 Pa), and ultrafast response (≤0.8 ms). Additionally, EMPA nanogenerators with high triboelectric and piezoelectric outputs achieve reliable biomechanical energy harvesting. The flexible self-assembly of EMPAs exhibits immense potential in superb individual healthcare and excellent human-machine interaction in an interference-free and comfortable manner.
Towards development of a high-strength stainless Mg alloy with Al-assisted growth of passive film
Authors: Zhu Qingchun , Li Yangxin , Cao Fuyong , Qiu Dong , Yang Yao , Wang Jingya , Zhang Huan , Ying Tao , Ding Wenjiang , Zeng Xiaoqin 
Published: October 2022

AbstractMagnesium alloys with high strength and excellent corrosion resistance are always sought-after in light-weighting structural components for automotive and aerospace applications. However, for most magnesium alloys that have a high specific strength, they usually have an inferior corrosion resistance and vice versa. In this work, we successfully develop a Mg-11Y-1Al (wt. %) alloy through conventional casting, solution treatment followed by extrusion. The overall properties of this alloy feature with a corrosion rate lower than 0.2 mm y−1, high yield strength of 350 MPa and moderate tensile elongation of 8%, the combination of which shows competitive advantage over other comparative magnesium alloys in the literature. It is found that a thin and dense protective film of Y2O3/Y(OH)3 can be fast developed with the aid of Al2O3/Al(OH)3 deposition to isolate this alloy from further attack of corrosion medium. Meanwhile, the refined grains, weak texture and activation of non-basal slip systems co-contribute to the high strength and good ductility. Our findings are expected to inspire the design of next-generation high performance magnesium alloys.
Real-space measurement of orbital electron populations for Li1-xCoO2
Authors: Shang Tongtong , Xiao Dongdong , Meng Fanqi , Rong Xiaohui , Gao Ang , Lin Ting , Tang Zhexin , Liu Xiaozhi , Li Xinyan , Zhang Qinghua , Wen Yuren , Xiao Ruijuan , Wang Xuefeng , Su Dong , Hu Yong-Sheng , Li Hong , Yu Qian , Zhang Ze , Petricek Vaclav , Wu Lijun , Gu Lin , Zuo Jian-Min , Zhu Yimei , Nan Ce-Wen , Zhu Jing 
Published: October 2022

AbstractThe operation of lithium-ion batteries involves electron removal from and filling into the redox orbitals of cathode materials, experimentally probing the orbital electron population thus is highly desirable to resolve the redox processes and charge compensation mechanism. Here, we combine quantitative convergent-beam electron diffraction with high-energy synchrotron powder X-ray diffraction to quantify the orbital populations of Co and O in the archetypal cathode material LiCoO2. The results indicate that removing Li ions from LiCoO2 decreases Co t2g orbital population, and the intensified covalency of Co–O bond upon delithiation enables charge transfer from O 2p orbital to Co eg orbital, leading to increased Co eg orbital population and oxygen oxidation. Theoretical calculations verify these experimental findings, which not only provide an intuitive picture of the redox reaction process in real space, but also offer a guidance for designing high-capacity electrodes by mediating the covalency of the TM–O interactions.