bluuebunny/crossref_metadata_2025_split huggingface dataset:
3‐D Tomography of the Ionospheric Anomalies Immediately Before and After the 2011 Tohoku‐Oki (Mw9.0) Earthquake
Authors: Muafiry Ihsan Naufal , Heki Kosuke 
Published: August 2020

AbstractA dense network of ground global navigation satellite system receivers detected ionospheric total electron content (TEC) changes starting ~40 min before the 2011 Tohoku‐oki (Mw9.0) earthquake around the ruptured fault, together with the long‐lasting postseismic TEC drop. In this paper, we robustly estimate three‐dimensional (3‐D) distribution of both preseismic and postseismic ionospheric anomalies of the 2011 Tohoku‐oki earthquake by tomographic inversions of electron density anomalies. We set up >6,000 blocks, as large as 1.0° (east‐west) × 0.9° (north‐south) × 60 km (vertical), over the Japanese Islands, the Sea of Japan, and the Korean Peninsula, up to 870 km altitude. By using TEC anomalies of pairs exceeding ~1,300 stations and eight satellites obtained using reference curves, we estimated electron density anomalies within individual blocks. The results showed that the preseismic and postseismic anomalies do not overlap in space. The preseismic anomalies are composed of low (~300 km height) positive and high (~600 km height) negative anomalies. They occurred above the land of NE Japan without extending offshore, suggesting its origin related to surface electric charges. On the other hand, the postseismic electron depletion occurred offshore above the region where large coseismic uplift took place. These results demonstrate that the preseismic and postseismic ionospheric anomalies are independent not only temporarily but also spatially and certainly in underlying physical mechanisms. We propose a simple model to explain how surface charges redistribute ionospheric electrons to make the observed preseismic electron density anomalies.
A 250‐Year, Decadally Resolved, Radiocarbon Time History in the Gulf of Maine Reveals a Hydrographic Regime Shift at the End of the Little Ice Age
Authors: Lower‐Spies Erin E. , Whitney Nina M. , Wanamaker Alan D. , Griffin Shelly M. , Introne Douglas S. , Kreutz Karl J. 
Published: August 2020

AbstractIn order to document relative changes in water mass contributions in the Gulf of Maine (GoM), we used the shell material of the long‐lived ocean quahog (Arctica islandica). A multicentury, crossdated master shell growth chronology facilitated the reconstruction of a radiocarbon Δ14C history prior to the radiocarbon bomb‐pulse of the 1950s. This reconstruction reveals a highly variable Δ14C series (mean = −56.6 ± 8.0‰ (1σ); N = 34) from CE 1685 to 1935. Δ14C values indicate a rapid shift ca. 1860 CE in source waters to the GoM. From CE 1685 to 1860, GoM waters were dominated by an admixture of Warm Slope Water primarily composed of tropical Atlantic surface waters/Gulf Stream Waters, and Scotian Shelf Water. This water regime was followed by a rapid Δ14C transition to a Labrador Slope Water endmember after CE 1860, with an apparent decrease in Scotian Shelf Water. Together, this shift is likely related to broader changes in the Arctic and the Labrador Sea, and a short‐term strengthening of the Atlantic meridional overturning circulation. Labrador Slope Water dominating GoM hydrography in the 1900s is verified by the similarities between this record and other coral‐ and shell‐derived Δ14C records influenced by waters with Labrador Sea origin. This suggests that GoM radiocarbon variability broadly reflects large‐scale ocean circulation processes in the Northwestern Atlantic. The lack of Δ14C values much below the Labrador Slope Water endmember suggests that the interior GoM gets very little to no Antarctic Intermediate Water as other studies had previously suggested.
Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation
Authors: Sharma Mohit , Fonseca Felipe Paiva , Hunter Keith D. , Radhakrishnan Raghu 
Published: August 2020

AbstractThe integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.
Chronic activation of 4-1BB signaling induces granuloma development in tumor-draining lymph nodes that is detrimental to subsequent CD8+ T cell responses
Authors: Kim Seon-Hee , Singh Rohit , Han Chungyong , Cho Eunjung , Kim Yu I. , Lee Don G. , Kim Young H. , Kim Sang Soo , Shin Dong Hoon , You Hye Jin , Lee Hyeon-Woo , Kwon Byoung S. , Choi Beom K. 
Published: August 2020

AbstractThe antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor immunotherapy. However, the adverse side effects associated with agonist antibodies have hindered their clinical development. Here, we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB mAbs. We show that chronic activation of 4-1BB signals induced the accumulation of IFN-γ-producing PD-1+CD8+ T cells in the secondary lymphoid organs of tumor-bearing mice by increasing the number of dividing CD8+ T cells, which was beneficial for suppressing tumor growth in the early phase of anti-4-1BB induction. However, repeated exposure to anti-4-1BB mAbs led to granuloma development in tumor-draining lymph nodes (TDLNs) of mice due to recruitment and accumulation of macrophages via the CD8+ T cell-IFN-γ axis. This was accompanied by excessive lymph node swelling, which impaired the sequential activation of CD8+ T cells. Our data provide insights into the immune-related adverse events of long-term agonist 4-1BB antibody dosing, which should be considered during the clinical development of immunomodulating therapy.
Inbred lab mice are not isogenic: genetic variation within inbred strains used to infer the mutation rate per nucleotide site
Authors: Chebib Jobran , Jackson Benjamin C. , López-Cortegano Eugenio , Tautz Diethard , Keightley Peter D. 
Published: August 2020

AbstractFor over a century, inbred mice have been used in many areas of genetics research to gain insight into the genetic variation underlying traits of interest. The generalizability of any genetic research study in inbred mice is dependent upon all individual mice being genetically identical, which in turn is dependent on the breeding designs of companies that supply inbred mice to researchers. Here, we compare whole-genome sequences from individuals of four commonly used inbred strains that were procured from either the colony nucleus or from a production colony (which can be as many as ten generations removed from the nucleus) of a large commercial breeder, in order to investigate the extent and nature of genetic variation within and between individuals. We found that individuals within strains are not isogenic, and there are differences in the levels of genetic variation that are explained by differences in the genetic distance from the colony nucleus. In addition, we employ a novel approach to mutation rate estimation based on the observed genetic variation and the expected site frequency spectrum at equilibrium, given a fully inbred breeding design. We find that it provides a reasonable per nucleotide mutation rate estimate when mice come from the colony nucleus (~7.9 × 10−9 in C3H/HeN), but substantially inflated estimates when mice come from production colonies.
Molecular layer interneurons in the cerebellum encode for valence in associative learning
Authors: Ma Ming , Futia Gregory L. , de Souza Fabio M. Simoes , Ozbay Baris N. , Llano Isabel , Gibson Emily A. , Restrepo Diego 
Published: August 2020

AbstractThe cerebellum plays a crucial role in sensorimotor and associative learning. However, the contribution of molecular layer interneurons (MLIs) to these processes is not well understood. We used two-photon microscopy to study the role of ensembles of cerebellar MLIs in a go-no go task where mice obtain a sugar water reward if they lick a spout in the presence of the rewarded odorant and avoid a timeout when they refrain from licking for the unrewarded odorant. In naive animals the MLI responses did not differ between the odorants. With learning, the rewarded odorant elicited a large increase in MLI calcium responses, and the identity of the odorant could be decoded from the differential response. Importantly, MLIs switched odorant responses when the valence of the stimuli was reversed. Finally, mice took a longer time to refrain from licking in the presence of the unrewarded odorant and had difficulty becoming proficient when MLIs were inhibited by chemogenetic intervention. Our findings support a role for MLIs in learning valence in the cerebellum.
Entropy of a bacterial stress response is a generalizable predictor for fitness and antibiotic sensitivity
Authors: Zhu Zeyu , Surujon Defne , Ortiz-Marquez Juan C. , Huo Wenwen , Isberg Ralph R. , Bento José , van Opijnen Tim 
Published: August 2020

AbstractCurrent approaches explore bacterial genes that change transcriptionally upon stress exposure as diagnostics to predict antibiotic sensitivity. However, transcriptional changes are often specific to a species or antibiotic, limiting implementation to known settings only. While a generalizable approach, predicting bacterial fitness independent of strain, species or type of stress, would eliminate such limitations, it is unclear whether a stress-response can be universally captured. By generating a multi-stress and species RNA-Seq and experimental evolution dataset, we highlight the strengths and limitations of existing gene-panel based methods. Subsequently, we build a generalizable method around the observation that global transcriptional disorder seems to be a common, low-fitness, stress response. We quantify this disorder using entropy, which is a specific measure of randomness, and find that in low fitness cases increasing entropy and transcriptional disorder results from a loss of regulatory gene-dependencies. Using entropy as a single feature, we show that fitness and quantitative antibiotic sensitivity predictions can be made that generalize well beyond training data. Furthermore, we validate entropy-based predictions in 7 species under antibiotic and non-antibiotic conditions. By demonstrating the feasibility of universal predictions of bacterial fitness, this work establishes the fundamentals for potentially new approaches in infectious disease diagnostics.
Single-cell RNA sequencing identifies shared differentiation paths of mouse thymic innate T cells
Authors: Lee Minji , Lee Eunmin , Han Seong Kyu , Choi Yoon Ha , Kwon Dong-il , Choi Hyobeen , Lee Kwanghwan , Park Eun Seo , Rha Min-Seok , Joo Dong Jin , Shin Eui-Cheol , Kim Sanguk , Kim Jong Kyoung , Lee You Jeong 
Published: August 2020

AbstractInvariant natural killer T (iNKT), mucosal-associated invariant T (MAIT), and γδ T cells are innate T cells that acquire memory phenotype in the thymus and share similar biological characteristics. However, how their effector differentiation is developmentally regulated is still unclear. Here, we identify analogous effector subsets of these three innate T cell types in the thymus that share transcriptional profiles. Using single-cell RNA sequencing, we show that iNKT, MAIT and γδ T cells mature via shared, branched differentiation rather than linear maturation or TCR-mediated instruction. Simultaneous TCR clonotyping analysis reveals that thymic maturation of all three types is accompanied by clonal selection and expansion. Analyses of mice deficient of TBET, GATA3 or RORγt and additional in vivo experiments corroborate the predicted differentiation paths, while human innate T cells from liver samples display similar features. Collectively, our data indicate that innate T cells share effector differentiation processes in the thymus.
ABHD4-dependent developmental anoikis safeguards the embryonic brain
Authors: László Zsófia I. , Lele Zsolt , Zöldi Miklós , Miczán Vivien , Mógor Fruzsina , Simon Gabriel M. , Mackie Ken , Kacskovics Imre , Cravatt Benjamin F. , Katona István 
Published: August 2020

AbstractA specialized neurogenic niche along the ventricles accumulates millions of progenitor cells in the developing brain. After mitosis, fate-committed daughter cells delaminate from this germinative zone. Considering the high number of cell divisions and delaminations taking place during embryonic development, brain malformations caused by ectopic proliferation of misplaced progenitor cells are relatively rare. Here, we report that a process we term developmental anoikis distinguishes the pathological detachment of progenitor cells from the normal delamination of daughter neuroblasts in the developing mouse neocortex. We identify the endocannabinoid-metabolizing enzyme abhydrolase domain containing 4 (ABHD4) as an essential mediator for the elimination of pathologically detached cells. Consequently, rapid ABHD4 downregulation is necessary for delaminated daughter neuroblasts to escape from anoikis. Moreover, ABHD4 is required for fetal alcohol-induced apoptosis, but not for the well-established form of developmentally controlled programmed cell death. These results suggest that ABHD4-mediated developmental anoikis specifically protects the embryonic brain from the consequences of sporadic delamination errors and teratogenic insults.
Inherited salt-losing tubulopathies are associated with immunodeficiency due to impaired IL-17 responses
Authors: Evans Rhys D. R. , Antonelou Marilina , Sathiananthamoorthy Sanchutha , Rega Marilena , Henderson Scott , Ceron-Gutierrez Lourdes , Barcenas-Morales Gabriela , Müller Christoph A. , Doffinger Rainer , Walsh Stephen B. , Salama Alan D. 
Published: August 2020

AbstractIncreased extracellular sodium activates Th17 cells, which provide protection from bacterial and fungal infections. Whilst high salt diets have been shown to worsen autoimmune disease, the immunological consequences of clinical salt depletion are unknown. Here, we investigate immunity in patients with inherited salt-losing tubulopathies (SLT). Forty-seven genotyped SLT patients (with Bartter, Gitelman or EAST Syndromes) are recruited. Clinical features of dysregulated immunity are recorded with a standardised questionnaire and immunological investigations of IL-17 responsiveness undertaken. The effects of altering extracellular ionic concentrations on immune responses are then assessed. Patients are hypokalaemic and hypomagnesaemic, with reduced interstitial sodium stores determined by 23Na-magnetic resonance imaging. SLT patients report increased mucosal infections and allergic disease compared to age-matched controls. Aligned with their clinical phenotype, SLT patients have an increased ratio of Th2:Th17 cells. SLT Th17 and Tc17 polarisation is reduced in vitro, yet STAT1 and STAT3 phosphorylation and calcium flux following T cell activation are unaffected. In control cells, the addition of extracellular sodium (+40 mM), potassium (+2 mM), or magnesium (+1 mM) reduces Th2:Th17 ratio and augments Th17 polarisation. Our results thus show that the ionic environment typical in SLT impairs IL-17 immunity, but the intracellular pathways that mediate salt-driven Th17 polarisation are intact and in vitro IL-17 responses can be reinvigorated by increasing extracellular sodium concentration. Whether better correction of extracellular ions can rescue the immunophenotype in vivo in SLT patients remains unknown.
Experience-dependent resonance in amygdalo-cortical circuits supports fear memory retrieval following extinction
Authors: Ozawa Minagi , Davis Patrick , Ni Jianguang , Maguire Jamie , Papouin Thomas , Reijmers Leon 
Published: August 2020

AbstractLearned fear and safety are associated with distinct oscillatory states in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC). To determine if and how these network states support the retrieval of competing memories, we mimicked endogenous oscillatory activity through optogenetic stimulation of parvalbumin-expressing interneurons in mice during retrieval of contextual fear and extinction memories. We found that exogenously induced 4 Hz and 8 Hz oscillatory activity in the BLA exerts bi-directional control over conditioned freezing behavior in an experience- and context-specific manner, and that these oscillations have an experience-dependent ability to recruit distinct functional neuronal ensembles. At the network level we demonstrate, via simultaneous manipulation of BLA and mPFC, that experience-dependent 4 Hz resonance across BLA-mPFC circuitry supports post-extinction fear memory retrieval. Our findings reveal that post-extinction fear memory retrieval is supported by local and interregional experience-dependent resonance, and suggest novel approaches for interrogation and therapeutic manipulation of acquired fear circuitry.
Plasticity of muscle synergies through fractionation and merging during development and training of human runners
Authors: Cheung Vincent C. K. , Cheung Ben M. F. , Zhang Janet H. , Chan Zoe Y. S. , Ha Sophia C. W. , Chen Chao-Ying , Cheung Roy T. H. 
Published: August 2020

AbstractComplex motor commands for human locomotion are generated through the combination of motor modules representable as muscle synergies. Recent data have argued that muscle synergies are inborn or determined early in life, but development of the neuro-musculoskeletal system and acquisition of new skills may demand fine-tuning or reshaping of the early synergies. We seek to understand how locomotor synergies change during development and training by studying the synergies for running in preschoolers and diverse adults from sedentary subjects to elite marathoners, totaling 63 subjects assessed over 100 sessions. During development, synergies are fractionated into units with fewer muscles. As adults train to run, specific synergies coalesce to become merged synergies. Presences of specific synergy-merging patterns correlate with enhanced or reduced running efficiency. Fractionation and merging of muscle synergies may be a mechanism for modifying early motor modules (Nature) to accommodate the changing limb biomechanics and influences from sensorimotor training (Nurture).
Asymmetric elastoplasticity of stacked graphene assembly actualizes programmable untethered soft robotics
Authors: Wang Shuai , Gao Yang , Wei Anran , Xiao Peng , Liang Yun , Lu Wei , Chen Chinyin , Zhang Chi , Yang Guilin , Yao Haimin , Chen Tao 
Published: August 2020

AbstractThere is ever-increasing interest yet grand challenge in developing programmable untethered soft robotics. Here we address this challenge by applying the asymmetric elastoplasticity of stacked graphene assembly (SGA) under tension and compression. We transfer the SGA onto a polyethylene (PE) film, the resulting SGA/PE bilayer exhibits swift morphing behavior in response to the variation of the surrounding temperature. With the applications of patterned SGA and/or localized tempering pretreatment, the initial configurations of such thermal-induced morphing systems can also be programmed as needed, resulting in diverse actuation systems with sophisticated three-dimensional structures. More importantly, unlike the normal bilayer actuators, our SGA/PE bilayer, after a constrained tempering process, will spontaneously curl into a roll, which can achieve rolling locomotion under infrared lighting, yielding an untethered light-driven motor. The asymmetric elastoplasticity of SGA endows the SGA-based bi-materials with great application promise in developing untethered soft robotics with high configurational programmability.
The fundamentals of cultural adaptation: implications for human adaptation
Authors: Fogarty Laurel , Kandler Anne 
Published: August 2020

AbstractThe process of human adaptation to novel environments is a uniquely complex interplay between cultural and genetic changes. However, mechanistically, we understand little about these processes. To begin to untangle these threads of human adaptation we use mathematical models to describe and investigate cultural selective sweeps. We show that cultural sweeps differ in important ways from the genetic equivalents. The models show that the dynamics of cultural selective sweeps and, consequently, their differences from genetic sweeps depend critically on cultural transmission mechanisms. Further, we consider the effect of processes unique to culture such as foresight and innovations in response to an environmental change on adaptation. Finally we show that a ‘cultural evolutionary rescue’, or the survival of an endangered population by means of cultural adaptation, is possible. We suggest that culture might make a true, genetic, evolutionary rescue plausible for human populations.
Spatiotemporal dynamics of hemorrhagic fever with renal syndrome in Jiangxi province, China
Authors: Yang Shu , Gao Yuan , Liu Xiaobo , Liu Xiaoqing , Liu Yangqing , Metelmann Soeren , Yuan Chenying , Yue Yujuan , Chen Shengen , Liu Qiyong 
Published: August 2020

AbstractHistorically, Jiangxi province has had the largest HFRS burden in China. However, thus far, the comprehensive understanding of the spatiotemporal distributions of HFRS is limited in Jiangxi. In this study, seasonal decomposition analysis, spatial autocorrelation analysis, and space–time scan statistic analyses were performed to detect the spatiotemporal dynamics distribution of HFRS cases from 2005 to 2018 in Jiangxi at the county scale. The epidemic of HFRS showed the characteristic of bi-peak seasonality, the primary peak in winter (November to January) and the second peak in early summer (May to June), and the amplitude and the magnitude of HFRS outbreaks have been increasing. The results of global and local spatial autocorrelation analysis showed that the HFRS epidemic exhibited the characteristic of highly spatially heterogeneous, and Anyi, Fengxin, Yifeng, Shanggao, Jing’an and Gao’an county were hot spots areas. A most likely cluster, and two secondary likely clusters were detected in 14-years duration. The higher risk areas of the HFRS outbreak were mainly located in Jiangxi northern hilly state, spreading to Wuyi mountain hilly state as time advanced. This study provided valuable information for local public health authorities to design and implement effective measures for the control and prevention of HFRS.