bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychometric Properties and Measurement Invariance of a Short Form of	the Unified Multidimensional Calling Scale (UMCS)
Authors: Gerdel Sophie , Dalla Rosa Anna , Vianello Michelangelo 
Published: July 2022

Abstract: This paper reports on the development of a unidimensional short scale for measuring career calling (UMCS-7). The scale has been developed drawing from the theoretical model behind the Unified Multidimensional Calling Scale (UMCS; Vianello et al., 2018 ), according to which calling is composed of Passion, Prosociality, Purpose, Pervasiveness, Sacrifice, Transcendent Summons, and Identity. The UMCS-7 integrates classical and modern conceptualizations of career calling and can be used when time constraints prevent using the UMCS. The UMCS-7 has been validated in a sample of Italian workers ( N = 1,246) using exploratory and confirmatory factor analysis. A sample of US employees ( N = 165) was used to estimate measurement invariance across languages, establishing the equivalence of factor loadings, all but two intercepts, and all error variances. The UMCS-7 demonstrated nearly perfect convergent validity with the UMCS ( r = .97), excellent internal consistency (αItaly = .86; αUS = .87), and satisfactory concurrent validity with job satisfaction, life satisfaction, and turnover intentions.
High Spatial and Temporal Resolution Studies of Thermospheric Vector Wind Fields Derived From a Ground‐Based Network of All‐Sky Fabry‐Perot Interferometers
Authors: Elliott J. , Conde M. G. 
Published: July 2022

AbstractSimple scaling analysis of terms in the Navier‐Stokes momentum equation for Earth's atmosphere suggests that winds at heights above 120 km should be smooth and laminar, with little spatial variation over horizontal scale lengths smaller than several hundred kilometers. However, there is increasing evidence that this traditional understanding may fail to account for several important processes, including both waves and small‐scale ion‐neutral momentum coupling. Here, we examine the thermospheric neutral wind field over Alaska in unprecedented detail using observations from an array of four ground‐based all‐sky imaging Fabry‐Perot interferometers, processed using a new geophysical inverse algorithm, to derive high‐resolution maps of all three wind components, with a temporal cadence of 30 seconds. The reconstructed high‐resolution neutral winds showed synoptic‐scale agreement with prior observations and previously validated techniques, with all results exhibiting behavior in agreement with basic physics. However, stacked time‐series plots of vector wind components reveal significantly more spatial and temporal structure than previously reported. In particular, the observed responses included complex wave‐like behavior and highly geographically variable vertical winds. Local flow features were observed at spatial scales as small as 100 km at times, with temporal scales as short as a few tens of minutes. Instances of close spatial and temporal correlations were observed between the wind fields reconstructed from green‐line spectra and ionospheric flows observed independently by SuperDARN.
Effects of Mesoscale Dynamics on the Path of Fast‐Sinking Particles to the Deep Ocean: A Modeling Study
Authors: Wang Lu , Gula Jonathan , Collin Jérémy , Mémery Laurent 
Published: July 2022

AbstractThe gravitational sinking of organic particles is a vital component of the biological carbon pump. This sinking process is strongly modulated by the spatiotemporally varying eddy field, complicating the interpretation of particle flux measured by deep‐moored sediment traps. By backtracking particles to 200 m depth based on the outputs of a realistic eddy‐resolving simulation, we characterize the origins of particles collected at a long‐term observatory site in the Northeast Atlantic and focus on the impact of mesoscale dynamics on particle transport. Our results show that mesoscale dynamics between 200 and 1,000 m control the statistical funnel. Over the long term, the horizontal sampling scales of traps are estimated as hundreds of kilometers, with containment radius ranging from 90 to 490 km, depending on sinking velocities. Particle travel time suggests that overall vertical flow acts to facilitate the export, with estimated deviations up to 1 ± 2 days for particles sinking at 50 m d−1 to 1,000 m. Statistical analyses of horizontal displacements reveal that mesoscale eddies at the site confine particle sources in a more local area. On average, particles in anticyclonic eddies sink faster to depth than expected from purely gravitational sinking, contrary to their counterparts in cyclonic eddies. The results highlight the critical role of mesoscale dynamics in determining particle transport in a typical open ocean region with moderate eddy kinetic energy. This study provides implications for the sampling design of particle flux measurements during cruises and the interpretation of deep‐ocean mooring observations.
RBM47 inhibits hepatocellular carcinoma progression by targeting UPF1 as a DNA/RNA regulator
Authors: Guo Tao , You Ke , Chen Xi , Sun Yuqi , Wu Ying , Wu Ping , Jiang Yingying 
Published: July 2022

AbstractThe mechanisms by which the tumor behaviors of hepatocellular carcinoma (HCC) support growth and metastasis remain largely unknown, and it has become increasingly apparent that molecular dysregulation is of considerable importance for cellular signaling pathways. Recently, RNA-binding motif protein 47 (RBM47) has been suggested to function as a tumor regulator by acting as an RNA binding protein (RBP), but its role in HCC remains ambiguous. Here, in HCC, we identified that RBM47 had an inhibitory influence on tumor behaviors in vitro and accordingly suppressed the growth and metastasis of xenograft tumors in vivo. Additionally, RBM47 was verified to positively regulate Upframeshift 1 (UPF1), which is a crucial protein involved in the nonsense-mediated RNA decay (NMD) process and was previously determined to be an HCC suppressor. Mechanistically, the stability of UPF1 mRNA was demonstrated to be enhanced with its 3’UTR bound by RBM47, which acted as an RNA binding protein. Meanwhile, RBM47 was also proven to promote the transcription of UPF1 as a transcription factor. Taken together, we concluded that RBM47 functioned as a tumor suppressor by upregulating UPF1, acting as a DNA/RNA binding protein at the transcriptional and posttranscriptional levels.
Breaking photoswitch activation depth limit using ionising radiation stimuli adapted to clinical application
Authors: Guesdon-Vennerie Alban , Couvreur Patrick , Ali Fatoumia , Pouzoulet Frédéric , Roulin Christophe , Martínez-Rovira Immaculada , Bernadat Guillaume , Legrand François-Xavier , Bourgaux Claudie , Mazars Cyril Lucien , Marco Sergio , Trépout Sylvain , Mura Simona , Mériaux Sébastien , Bort Guillaume 
Published: July 2022

AbstractElectromagnetic radiation-triggered therapeutic effect has attracted a great interest over the last 50 years. However, translation to clinical applications of photoactive molecular systems developed to date is dramatically limited, mainly because their activation requires excitation by low-energy photons from the ultraviolet to near infra-red range, preventing any activation deeper than few millimetres under the skin. Herein we conceive a strategy for photosensitive-system activation potentially adapted to biological tissues without any restriction in depth. High-energy stimuli, such as those employed for radiotherapy, are used to carry energy while molecular activation is provided by local energy conversion. This concept is applied to azobenzene, one of the most established photoswitches, to build a radioswitch. The radiation-responsive molecular system developed is used to trigger cytotoxic effect on cancer cells upon gamma-ray irradiation. This breakthrough activation concept is expected to expand the scope of applications of photosensitive systems and paves the way towards the development of original therapeutic approaches.
Contrasting suitability and ambition in regional carbon mitigation
Authors: Liu Yu , Du Mingxi , Cui Qi , Lin Jintai , Liu Yawen , Liu Qiuyu , Tong Dan , Feng Kuishuang , Hubacek Klaus 
Published: July 2022

AbstractSubstantially enhancing carbon mitigation ambition is a crucial step towards achieving the Paris climate goal. Yet this attempt is hampered by poor knowledge on the potential cost and benefit of emission mitigation for each emitter. Here we use a global economic model to assess the mitigation costs for 27 major emitting countries and regions, and further contrast the costs against the potential benefits of mitigation valued as avoided social cost of carbon and the mitigation ambition of each region. We find a strong negative spatial correlation between cost and benefit of mitigating each ton of carbon dioxide. Meanwhile, the relative suitability of carbon mitigation, defined as the ratio of normalized benefit to normalized cost, also shows a considerable geographical mismatch with the mitigation ambition of emitters indicated in their first submitted nationally determined contributions. Our work provides important information to improve concerted climate action and formulate more efficient carbon mitigation strategies.
Structures of β1-adrenergic receptor in complex with Gs and ligands of different efficacies
Authors: Su Minfei , Paknejad Navid , Zhu Lan , Wang Jinan , Do Hung Nguyen , Miao Yinglong , Liu Wei , Hite Richard K. , Huang Xin-Yun 
Published: July 2022

AbstractG-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies, and transduce to heterotrimeric G-proteins to generate different degrees of physiological responses. Previous studies revealed how ligands with different efficacies activate GPCRs. Here, we investigate how a GPCR activates G-proteins upon binding ligands with different efficacies. We report the cryo-EM structures of β1-adrenergic receptor (β1-AR) in complex with Gs (GαsGβ1Gγ2) and a partial agonist or a very weak partial agonist, and compare them to the β1-AR–Gs structure in complex with a full agonist. Analyses reveal similar overall complex architecture, with local conformational differences. Cellular functional studies with mutations of β1-AR residues show effects on the cellular signaling from β1-AR to the cAMP response initiated by the three different ligands, with residue-specific functional differences. Biochemical investigations uncover that the intermediate state complex comprising β1-AR and nucleotide-free Gs is more stable when binding a full agonist than a partial agonist. Molecular dynamics simulations support the local conformational flexibilities and different stabilities among the three complexes. These data provide insights into the ligand efficacy in the activation of GPCRs and G-proteins.
Topology mediates transport of nanoparticles in macromolecular networks
Authors: Dai Xiaobin , Zhang Xuanyu , Gao Lijuan , Xu Ziyang , Yan Li-Tang 
Published: July 2022

AbstractDiffusion transport of nanoparticles in confined environments of macromolecular networks is common in diverse physical systems and regulates many biological responses. Macromolecular networks possess various topologies, featured by different numbers of degrees and genera. Although the network topologies can be manipulated from a molecular level, how the topology impacts the transport of nanoparticles in macromolecular networks remains unexplored. Here, we develop theoretical approaches combined with simulations to study nanoparticle transport in a model system consisting of network cells with defined topologies. We find that the topology of network cells has a profound effect on the free energy landscape experienced by a nanoparticle in the network cells, exhibiting various scaling laws dictated by the topology. Furthermore, the examination of the impact of cell topology on the detailed behavior of nanoparticle dynamics leads to different dynamical regimes that go beyond the particulars regarding the local network loop. The results might alter the conventional picture of the physical origin of transport in networks.
Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis
Authors: Kar Siddhartha P. , Quiros Pedro M. , Gu Muxin , Jiang Tao , Mitchell Jonathan , Langdon Ryan , Iyer Vivek , Barcena Clea , Vijayabaskar M. S. , Fabre Margarete A. , Carter Paul , Petrovski Slavé , Burgess Stephen , Vassiliou George S. 
Published: July 2022

AbstractClonal hematopoiesis (CH), the clonal expansion of a blood stem cell and its progeny driven by somatic driver mutations, affects over a third of people, yet remains poorly understood. Here we analyze genetic data from 200,453 UK Biobank participants to map the landscape of inherited predisposition to CH, increasing the number of germline associations with CH in European-ancestry populations from 4 to 14. Genes at new loci implicate DNA damage repair (PARP1, ATM, CHEK2), hematopoietic stem cell migration/homing (CD164) and myeloid oncogenesis (SETBP1). Several associations were CH-subtype-specific including variants at TCL1A and CD164 that had opposite associations with DNMT3A- versus TET2-mutant CH, the two most common CH subtypes, proposing key roles for these two loci in CH development. Mendelian randomization analyses showed that smoking and longer leukocyte telomere length are causal risk factors for CH and that genetic predisposition to CH increases risks of myeloproliferative neoplasia, nonhematological malignancies, atrial fibrillation and blood epigenetic ageing.
Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate
Authors: McCorvie Thomas J. , Loria Paula M. , Tu Meihua , Han Seungil , Shrestha Leela , Froese D. Sean , Ferreira Igor M. , Berg Allison P. , Yue Wyatt W. 
Published: July 2022

AbstractGlycogen synthase (GYS1) is the central enzyme in muscle glycogen biosynthesis. GYS1 activity is inhibited by phosphorylation of its amino (N) and carboxyl (C) termini, which is relieved by allosteric activation of glucose-6-phosphate (Glc6P). We present cryo-EM structures at 3.0–4.0 Å resolution of phosphorylated human GYS1, in complex with a minimal interacting region of glycogenin, in the inhibited, activated and catalytically competent states. Phosphorylations of specific terminal residues are sensed by different arginine clusters, locking the GYS1 tetramer in an inhibited state via intersubunit interactions. The Glc6P activator promotes conformational change by disrupting these interactions and increases the flexibility of GYS1, such that it is poised to adopt a catalytically competent state when the sugar donor UDP-glucose (UDP-glc) binds. We also identify an inhibited-like conformation that has not transitioned into the activated state, in which the locking interaction of phosphorylation with the arginine cluster impedes subsequent conformational changes due to Glc6P binding. Our results address longstanding questions regarding the mechanism of human GYS1 regulation.
Diagnosis of colonic dysmotility associated with autonomic dysfunction in patients with chronic refractory constipation
Authors: Liu Lijun , Milkova Natalija , Nirmalathasan Sharjana , Ali M. Khawar , Sharma Kartik , Huizinga Jan D. , Chen Ji-Hong 
Published: July 2022

AbstractWe report the first study assessing human colon manometric features and their correlations with changes in autonomic functioning in patients with refractory chronic constipation prior to consideration of surgical intervention. High-resolution colonic manometry (HRCM) with simultaneous heart rate variability (HRV) was performed in 14 patients, and the resulting features were compared to healthy subjects. Patients were categorized into three groups that had normal, weak, or no high amplitude propagating pressure waves (HAPWs) to any intervention. We found mild vagal pathway impairment presented as lower HAPW amplitude in the proximal colon in response to proximal colon balloon distention. Left colon dysmotility was observed in 71% of patients, with features of (1) less left colon HAPWs, (2) lower left colon HAPW amplitudes (69.8 vs 102.3 mmHg), (3) impaired coloanal coordination, (4) left colon hypertonicity in patients with coccyx injury. Patients showed the following autonomic dysfunction: (1) high sympathetic tone at baseline, (2) high sympathetic reactivity to active standing and meal, (3) correlation of low parasympathetic reactivity to the meal with absence of the coloanal reflex, (4) lower parasympathetic and higher sympathetic activity during occurrence of HAPWs. In conclusion, left colon dysmotility and high sympathetic tone and reactivity, more so than vagal pathway impairment, play important roles in refractory chronic constipation and suggests sacral neuromodulation as a possible treatment.
Social support correlates with glucocorticoid concentrations in wild African elephant orphans
Authors: Parker J. M. , Brown J. L. , Hobbs N. T. , Boisseau N. P. , Letitiya D. , Douglas-Hamilton I. , Wittemyer G. 
Published: July 2022

AbstractSocial relationships have physiological impacts. Here, we investigate whether loss of the mother/offspring relationship has lasting effects on fecal glucocorticoid metabolite (fGCM) concentrations in wild African elephant orphans several years following their mothers’ deaths. We find no difference in fGCM concentrations between orphans and nonorphans, but find lower fGCM concentrations in elephants with more age mates in their family. We also unexpectedly identify lower concentrations in orphans without their natal family versus nonorphans and natal orphans, which we speculate may be due to the development of hypocortisolism following a prolonged period without familial support. An index of plant productivity (i.e. food) shows the largest correlation with fGCM concentrations. Our findings indicate no lasting differences in glucocorticoid concentrations of surviving orphan elephants who are with their family, suggest the presence of age mates may reduce glucocorticoid concentrations in elephants, and emphasize that basic survival needs are the primary regulators of the stress response.
TCA cycle enhancement and uptake of monomeric substrates support growth of marine Roseobacter at low temperature
Authors: Wang Meng , Wang Huan , Wang Peng , Fu Hui-Hui , Li Chun-Yang , Qin Qi-Long , Liang Yantao , Wang Min , Chen Xiu-Lan , Zhang Yu-Zhong , Zhang Weipeng 
Published: July 2022

AbstractMembers of the marine Roseobacter group are ubiquitous in global oceans, but their cold-adaptive strategies have barely been studied. Here, as represented by Loktanella salsilacus strains enriched in polar regions, we firstly characterized the metabolic features of a cold-adapted Roseobacter by multi-omics, enzyme activities, and carbon utilization procedures. Unlike in most cold-adapted microorganisms, the TCA cycle is enhanced by accumulating more enzyme molecules, whereas genes for thiosulfate oxidation, sulfate reduction, nitrate reduction, and urea metabolism are all expressed at lower abundance when L. salsilacus was growing at 5 °C in comparison with higher temperatures. Moreover, a carbon-source competition experiment has evidenced the preferential use of glucose rather than sucrose at low temperature. This selective utilization is likely to be controlled by the carbon source uptake and transformation steps, which also reflects an economic calculation balancing energy production and functional plasticity. These findings provide a mechanistic understanding of how a Roseobacter member and possibly others as well counteract polar constraints.
Combined MEK and JAK/STAT3 pathway inhibition effectively decreases SHH medulloblastoma tumor progression
Authors: Zagozewski Jamie , Borlase Stephanie , Guppy Brent J. , Coudière-Morrison Ludivine , Shahriary Ghazaleh M. , Gordon Victor , Liang Lisa , Cheng Stephen , Porter Christopher J. , Kelley Rhonda , Hawkins Cynthia , Chan Jennifer A. , Liang Yan , Gong Jingjing , Nör Carolina , Saulnier Olivier , Wechsler-Reya Robert J. , Ramaswamy Vijay , Werbowetski-Ogilvie Tamra E. 
Published: July 2022

AbstractMedulloblastoma (MB) is the most common primary malignant pediatric brain cancer. We recently identified novel roles for the MEK/MAPK pathway in regulating human Sonic Hedgehog (SHH) MB tumorigenesis. The MEK inhibitor, selumetinib, decreased SHH MB growth while extending survival in mouse models. However, the treated mice ultimately succumbed to disease progression. Here, we perform RNA sequencing on selumetinib-treated orthotopic xenografts to identify molecular pathways that compensate for MEK inhibition specifically in vivo. Notably, the JAK/STAT3 pathway exhibits increased activation in selumetinib-treated tumors. The combination of selumetinib and the JAK/STAT3 pathway inhibitor, pacritinib, further reduces growth in two xenograft models and also enhances survival. Multiplex spatial profiling of proteins in drug-treated xenografts reveals shifted molecular dependencies and compensatory changes following combination drug treatment. Our study warrants further investigation into MEK and JAK/STAT3 inhibition as a novel combinatory therapeutic strategy for SHH MB.
Co-inhibition of ATM and ROCK synergistically improves cell proliferation in replicative senescence by activating FOXM1 and E2F1
Authors: Yang Eun Jae , Park Ji Hwan , Cho Hyun-Ji , Hwang Jeong-A , Woo Seung-Hwa , Park Chi Hyun , Kim Sung Young , Park Joon Tae , Park Sang Chul , Hwang Daehee , Lee Young-Sam 
Published: July 2022

AbstractThe multifaceted nature of senescent cell cycle arrest necessitates the targeting of multiple factors arresting or promoting the cell cycle. We report that co-inhibition of ATM and ROCK by KU-60019 and Y-27632, respectively, synergistically increases the proliferation of human diploid fibroblasts undergoing replicative senescence through activation of the transcription factors E2F1 and FOXM1. Time-course transcriptome analysis identified FOXM1 and E2F1 as crucial factors promoting proliferation. Co-inhibition of the kinases ATM and ROCK first promotes the G2/M transition via FOXM1 activation, leading to accumulation of cells undergoing the G1/S transition via E2F1 activation. The combination of both inhibitors increased this effect more significantly than either inhibitor alone, suggesting synergism. Our results demonstrate a FOXM1- and E2F1-mediated molecular pathway enhancing cell cycle progression in cells with proliferative potential under replicative senescence conditions, and treatment with the inhibitors can be tested for senomorphic effect in vivo.
Ultrafast interfacial carrier dynamics and persistent topological surface states of Bi2Se3 in heterojunctions with VSe2
Authors: Park Tae Gwan , Jeon Jae Ho , Chun Seung-Hyun , Lee Sunghun , Rotermund Fabian 
Published: July 2022

AbstractVanadium diselenide (VSe2) has recently been highlighted as an efficient 2D electrode owing to its extra-high conductivity, thickness controllability, and van der Waals contact. However, as the electrode, applications of VSe2 to various materials are still lacking. Here, by employing ultrafast time-resolved spectroscopy, we study VSe2-thickness-dependent interfacial effects in heterostructures with topological insulator Bi2Se3 that is severely affected by contact with conventional 3D electrodes. Our results show unaltered Dirac surface state of Bi2Se3 against forming junctions with VSe2, efficient ultrafast hot electron transfer from VSe2 to Bi2Se3 across the interface, shortened metastable carrier lifetimes in Bi2Se3 due to dipole interactions enabling efficient current flow, and the electronic level shift (~tens meV) of bulk states of Bi2Se3 by interfacial interactions, which is ~10 times lower compared to conventional electrodes, implying weak Fermi level pinning. Our observations confirm VSe2 as an ideal electrode for efficient Bi2Se3-based-applications with full utilization of topological insulator characteristics.