bluuebunny/crossref_metadata_2025 huggingface dataset:
Murine models of IDH-wild-type glioblastoma exhibit spatial segregation of tumor initiation and manifestation during evolution
Authors: Li Yinghua , Li Bo , Li Wei , Wang Yuan , Akgül Seçkin , Treisman Daniel M. , Heist Kevin A. , Pierce Brianna R. , Hoff Benjamin , Ho Cheng-Ying , Ferguson David O. , Rehemtulla Alnawaz , Zheng Siyuan , Ross Brian D. , Li Jun Z. , Zhu Yuan
Published: July 2020

Recent characterization of spatiotemporal genomic architecture of IDH-wild-type multifocal glioblastomas (M-GBMs) suggests a clinically unobserved common-ancestor (CA) with a less aggressive phenotype, generating highly genetically divergent malignant gliomas/GBMs in distant brain regions. Using serial MRI/3D-reconstruction, whole-genome sequencing and spectral karyotyping-based single-cell phylogenetic tree building, we show two distinct types of tumor evolution in p53-mutant driven mouse models. Malignant gliomas/GBMs grow as a single mass (Type 1) and multifocal masses (Type 2), respectively, despite both exhibiting loss of Pten/chromosome 19 (chr19) and PI3K/Akt activation with sub-tetraploid/4N genomes. Analysis of early biopsied and multi-segment tumor tissues reveals no evidence of less proliferative diploid/2N lesions in Type 1 tumors. Strikingly, CA-derived relatively quiescent tumor precursors with ancestral diploid/2N genomes and normal Pten/chr19 are observed in the subventricular zone (SVZ), but are distantly segregated from multi focal Type 2 tumors. Importantly, PI3K/Akt inhibition by Rictor/mTORC2 deletion blocks distant dispersal, restricting glioma growth in the SVZ.
The Movember Prostate Cancer Landscape Analysis: an assessment of unmet research needs
Authors: Kouspou Michelle M. , Fong Jenna E. , Brew Nadine , Hsiao Sarah T. F. , Davidson Seanna L. , Choyke Peter L. , Crispino Tony , Jain Suneil , Jenster Guido W. , Knudsen Beatrice S. , Millar Jeremy L. , Mittmann Nicole , Ryan Charles J. , Tombal Bertrand , Buzza Mark
Published: July 2020

Prostate cancer is a heterogeneous cancer with widely varying levels of morbidity and mortality. Approaches to prostate cancer screening, diagnosis, surveillance, treatment and management differ around the world. To identify the highest priority research needs across the prostate cancer biomedical research domain, Movember conducted a landscape analysis with the aim of maximizing the effect of future research investment through global collaborative efforts and partnerships. A global Landscape Analysis Committee (LAC) was established to act as an independent group of experts across urology, medical oncology, radiation oncology, radiology, pathology, translational research, health economics and patient advocacy. Men with prostate cancer and thought leaders from a variety of disciplines provided a range of key insights through a range of interviews. Insights were prioritized against predetermined criteria to understand the areas of greatest unmet need. From these efforts, 17 research needs in prostate cancer were agreed on and prioritized, and 3 received the maximum prioritization score by the LAC: first, to establish more sensitive and specific tests to improve disease screening and diagnosis; second, to develop indicators to better stratify low-risk prostate cancer for determining which men should go on active surveillance; and third, to integrate companion diagnostics into randomized clinical trials to enable prediction of treatment response. On the basis of the findings from the landscape analysis, Movember will now have an increased focus on addressing the specific research needs that have been identified, with particular investment in research efforts that reduce disease progression and lead to improved therapies for advanced prostate cancer.
The effects of anthropogenic and volcanic aerosols and greenhouse gases on twentieth century Sahel precipitation
Authors: Herman Rebecca Jean , Giannini Alessandra , Biasutti Michela , Kushnir Yochanan
Published: July 2020

There is little scientific consensus on the importance of external climate forcings—including anthropogenic aerosols, volcanic aerosols, and greenhouse gases (GHG)—relative to each other and to internal variability in dictating past and future Sahel rainfall. We address this query by relating a 3-tiered multi-model mean (MMM) over the Climate Model Intercomparison Project phase 5 “twentieth century” and pre-Industrial control simulations to observations. The comparison of single-forcing and historical simulations highlights the importance of anthropogenic and volcanic aerosols over GHG in generating forced Sahel rainfall variability in models. However, the forced MMM only accounts for a small fraction of observed variance. A residual consistency test shows that simulated internal variability cannot explain the residual observed multidecadal variability, and points to model deficiency in simulating multidecadal variability in the forced response, internal variability, or both.
Variations in foliar carbon:nitrogen and nitrogen:phosphorus ratios under global change: a meta-analysis of experimental field studies
Authors: Xu Shan , Sardans Jordi , Zhang Jinlong , Peñuelas Josep
Published: July 2020

Foliar-level stoichiometry plays an important role in ecosystem elemental cycling. Shifts in foliar ratios of carbon to nitrogen (C:N) and nitrogen to phosphorus (N:P) in response to global change can therefore have a large impact upon ecosystem function. We conducted a meta-analysis with 2,236 paired observations from 123 published studies to investigate the responses of foliar C:N and N:P ratios to experimental global change treatments, i.e. warming, increased precipitation, drought, N addition and elevated carbon dioxide concentration (eCO2), in field conditions. Foliar C:N and N:P ratios were neither affected by warming nor by increased precipitation. Foliar C:N ratio increased with drought and eCO2, and decreased with N addition. Foliar N:P ratios declined with eCO2, and increased under drought and N addition. Our results suggested the responses of the C:N ratio to global change were mainly related to shifts in foliar [N], whereas changes in the N:P ratio were related to the responses of both [N] and [P]. Moreover, the response magnitude of foliar N:P ratio decreased with treatment duration under increased precipitation, N addition and eCO2. Our findings are important for our understanding of plant nutrient dynamic and modeling of nutrient biogeochemistry under global change.
Author Correction: New insights for understanding spatial patterning and formation processes of the Neanderthal occupation in the Amalda I cave (Gipuzkoa, Spain)
Authors: Sánchez-Romero Laura , Benito-Calvo Alfonso , Marín-Arroyo Ana B. , Agudo-Pérez Lucía , Karampaglidis Theodoros , Rios-Garaizar Joseba
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Emulating synaptic response in n- and p-channel MoS2 transistors by utilizing charge trapping dynamics
Authors: Bhattacharjee Shubhadeep , Wigchering Rient , Manning Hugh G. , Boland John. J. , Hurley Paul K.
Published: July 2020

Brain-inspired, neuromorphic computing aims to address the growing computational complexity and power consumption in modern von-Neumann architectures. Progress in this area has been hindered due to the lack of hardware elements that can mimic neuronal/synaptic behavior which form the fundamental building blocks for spiking neural networks (SNNs). In this work, we leverage the short/long term memory effects due to the electron trapping events in an atomically thin channel transistor that mimic the exchange of neurotransmitters and emulate a synaptic response. Re-doped (n-type) and Nb-doped (p-type) molybdenum di-sulfide (MoS2) field-effect transistors are examined using pulsed-gate measurements, which identify the time scales of electron trapping/de-trapping. The devices demonstrate promising trends for short/long term plasticity in the order of ms/minutes, respectively. Interestingly, pulse paired facilitation (PPF), which quantifies the short-term plasticity, reveal time constants (τ1 = 27.4 ms, τ2 = 725 ms) that closely match those from a biological synapse. Potentiation and depression measurements describe the ability of the synaptic device to traverse several analog states, where at least 50 conductance values are accessed using consecutive pulses of equal height and width. Finally, we demonstrate devices, which can emulate a well-known learning rule, spike time-dependent plasticity (STDP) which codifies the temporal sequence of pre- and post-synaptic neuronal firing into corresponding synaptic weights. These synaptic devices present significant advantages over iontronic counterparts and are envisioned to create new directions in the development of hardware for neuromorphic computing.
The hot sites of α-synuclein in amyloid fibril formation
Authors: Khammari Anahita , Arab Seyed Shahriar , Ejtehadi Mohammad Reza
Published: July 2020

The role of alpha-synuclein (αS) amyloid fibrillation has been recognized in various neurological diseases including Parkinson’s Disease (PD). In early stages, fibrillation occurs by the structural transition from helix to extended states in monomeric αS followed by the formation of beta-sheets. This alpha-helix to beta-sheet transition (αβT) speeds up the formation of amyloid fibrils through the formation of unstable and temporary configurations of the αS. In this study, the most important regions that act as initiating nuclei and make unstable the initial configuration were identified based on sequence and structural information. In this regard, a Targeted Molecular Dynamics (TMD) simulation was employed using explicit solvent models under physiological conditions. Identified regions are those that are in the early steps of structural opening. The trajectory was clustered the structures characterized the intermediate states. The findings of this study would help us to better understanding of the mechanism of amyloid fibril formation.
Hyperglycemia-stimulating diet induces liver steatosis in sheep
Authors: Kalyesubula Mugagga , Mopuri Ramgopal , Rosov Alexander , Alon Tamir , Edery Nir , Moallem Uzi , Dvir Hay
Published: July 2020

Hepatic steatosis is strongly associated with chronic liver disease and systemic metabolic disorder. Adipose lipolysis is a recognized principal source of intrahepatic fat in various metabolic disorders, including non-alcoholic fatty liver disease. We hypothesized that, in the premorbid state, hepatic de novo lipogenesis (DNL) driven by excess carbohydrates abundance might play a more significant role. We employed a novel nutritional model in sheep of two distinct carbohydrates abundances. During 4 months of the dietary treatment, lambs were monitored for metabolic and terminal liver parameters. Lambs grown on the high-calorie (HC) diet were consistently more hyperglycemic and hyperinsulinemic than lambs grown on the lower-calorie (LC) diet (P < 0.0001). As a result, the HC lambs developed systemic- (HOMA-IR of 7.3 vs. 3.1; P < 0.0001), and adipose- (ADIPO-IR of 342.7 vs. 74.4; P < 0.0001) insulin resistance, significant adiposity (P < 0.0001), and higher plasma triglycerides (P < 0.05). Circulating leukocytes in the HC lambs had higher mRNA expression levels of the proinflammatory markers CCL2 (P < 0.01) and TNF-alpha (P < 0.04), and IL1B trended higher (P < 0.1). Remarkably, lambs on the HC diet developed substantial liver steatosis (mean fat content of 8.1 vs. 5.3% in the LC group; P < 0.0001) with a higher histological steatosis score (2.1 vs. 0.4; P < 0.0002). Hepatic steatosis was most-strongly associated with blood glucose and insulin levels but negatively correlated with circulating fatty acids—indicating a more significant contribution from hepatic DNL than from adipose lipolysis. Sheep may prove an attractive large-animal model of fatty liver and metabolic comorbidities resulting from excess carbohydrate-based energy early in life.
A pooled genome-wide screening strategy to identify and rank influenza host restriction factors in cell-based vaccine production platforms
Authors: Sharon David M. , Nesdoly Sean , Yang Hsin J. , Gélinas Jean-François , Xia Yu , Ansorge Sven , Kamen Amine A.
Published: July 2020

Cell-derived influenza vaccines provide better protection and a host of other advantages compared to the egg-derived vaccines that currently dominate the market, but their widespread use is hampered by a lack of high yield, low cost production platforms. Identification and knockout of innate immune and metabolic restriction factors within relevant host cell lines used to grow the virus could offer a means to substantially increase vaccine yield. In this paper, we describe and validate a novel genome-wide pooled CRISPR/Cas9 screening strategy that incorporates a reporter virus and a FACS selection step to identify and rank restriction factors in a given vaccine production cell line. Using the HEK-293SF cell line and A/PuertoRico/8/1934 H1N1 influenza as a model, we identify 64 putative influenza restriction factors to direct the creation of high yield knockout cell lines. In addition, gene ontology and protein complex enrichment analysis of this list of putative restriction factors offers broader insights into the primary host cell determinants of viral yield in cell-based vaccine production systems. Overall, this work will advance efforts to address the public health burden posed by influenza.
RETRACTED ARTICLE: Novel green synthesis and antioxidant, cytotoxicity, antimicrobial, antidiabetic, anticholinergics, and wound healing properties of cobalt nanoparticles containing Ziziphora clinopodioides Lam leaves extract
Authors: Hou Huifang , Mahdavi Behnam , Paydarfard Sogand , Zangeneh Mohammad Mahdi , Zangeneh Akram , Sadeghian Nastaran , Taslimi Parham , Erduran Vildan , Sen Fatih
Published: July 2020

The aim of the experiment was a green synthesis of cobalt nanoparticles from the aqueous extract of Ziziphora clinopodioides Lam (CoNPs) and assessment of their cytotoxicity, antioxidant, antifungal, antibacterial, and cutaneous wound healing properties. The synthesized CoNPs were characterized using different techniques including UV–Vis., FT-IR spectroscopy, X‐ray diffraction (XRD), energy dispersive X-ray spectrometry (EDS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). According to the XRD analysis, 28.19 nm was measured for the crystal size of NPs. TEM and SEM images exhibited a uniform spherical morphology and average diameters of 29.08 nm for the biosynthesized nanoparticles. Agar diffusion tests were done to determine the antibacterial and antifungal characteristics. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) were specified by macro-broth dilution assay. CoNPs indicated higher antibacterial and antifungal effects than many standard antibiotics (p ≤ 0.01). Also, CoNPs prevented the growth of all bacteria at 2–4 mg/mL concentrations and removed them at 2–8 mg/mL concentrations (p ≤ 0.01). In the case of antifungal effects of CoNPs, they inhibited the growth of all fungi at 1–4 mg/mL concentrations and destroyed them at 2–16 mg/mL concentrations (p ≤ 0.01). The synthesized CoNPs had great cell viability dose-dependently and indicated this method was nontoxic. DPPH free radical scavenging test was done to assess the antioxidant potentials, which revealed similar antioxidant potentials for CoNPs and butylated hydroxytoluene. In vivo experiment, after creating the cutaneous wound, the rats were randomly divided into six groups: untreated control, treatment with Eucerin basal ointment, treatment with 3% tetracycline ointment, treatment with 0.2% Co(NO3)2 ointment, treatment with 0.2% Z. clinopodioides ointment, and treatment with 0.2% CoNPs ointment. These groups were treated for 10 days. For histopathological and biochemical analysis of the healing trend, a 3 × 3 cm section was prepared from all dermal thicknesses at day 10. Use of CoNPs ointment in the treatment groups substantially raised (p ≤ 0.01) the wound contracture, hydroxyl proline, hexosamine, hexuronic acid, fibrocyte, and fibrocytes/fibroblast rate and remarkably decreased (p ≤ 0.01) the wound area, total cells, neutrophil, and lymphocyte compared to other groups. In conclusion, CoNPs can be used as a medical supplement owing to their non-cytotoxic, antioxidant, antibacterial, antifungal, and cutaneous wound healing effects. Additionally, the novel nanoparticles (Co(NO3)2 and CoNPs) were good inhibitors of the α-glycosidase, and cholinesterase enzymes.
Trisk 95 as a novel skin mirror for normal and diabetic systemic glucose level
Authors: Ali Nsrein , Rezvani Hamid Reza , Motei Diana , Suleman Sufyan , Mahfouf Walid , Marty Isabelle , Ronkainen Veli-Pekka , Vainio Seppo J.
Published: July 2020

Developing trustworthy, cost effective, minimally or non-invasive glucose sensing strategies is of great need for diabetic patients. In this study, we used an experimental type I diabetic mouse model to examine whether the skin would provide novel means for identifying biomarkers associated with blood glucose level. We first showed that skin glucose levels are rapidly influenced by blood glucose concentrations. We then conducted a proteomic screen of murine skin using an experimental in vivo model of type I diabetes and wild-type controls. Among the proteins that increased expression in response to high blood glucose, Trisk 95 expression was significantly induced independently of insulin signalling. A luciferase reporter assay demonstrated that the induction of Trisk 95 expression occurs at a transcriptional level and is associated with a marked elevation in the Fluo-4AM signal, suggesting a role for intracellular calcium changes in the signalling cascade. Strikingly, these changes lead concurrently to fragmentation of the mitochondria. Moreover, Trisk 95 knockout abolishes both the calcium flux and the mitochondrial phenotype changes indicating dependency of glucose flux in the skin on Trisk 95 function. The data demonstrate that the skin reacts robustly to systemic blood changes, and that Trisk 95 is a promising biomarker for a glucose monitoring assembly.
Gene mapping and functional annotation of GWAS of oral ulcers using FUMA software
Authors: Jin Xiaoye , Wang Yijie , Zhang Xingru , Zhang Wenqing , Wang Hongdan , Chen Chuanliang
Published: July 2020

Oral ulcers not only influence the physical health of patients, but they also interfere with their quality of life. However, the exact etiology of oral ulcers is not clear. To explore the roles of genetic factors in oral ulcers, a genome-wide association study of the condition in European individuals was re-evaluated by the FUMA v1.3.5e online tool. A total of 380 independent significant single nucleotide polymorphisms (SNPs) and 89 lead SNPs were identified in 34 genomic risk loci. Out of these identified genomic risk loci, 280 possible causal genes were pinpointed by positional mapping and expression quantitative trait locus mapping. Among these genes, 216 novel genes were identified. Furthermore, some genomic loci were mapped to a single gene. Functional annotation of these prioritized genes revealed that the immune response pathway was implicated in the onset of oral ulcers. Overall, our findings revealed novel possible causal genes and demonstrated that the immune response has a crucial role in the occurrence of oral ulcers.
Iron acquisition system of Sphingobium sp. strain SYK-6, a degrader of lignin-derived aromatic compounds
Authors: Fujita Masaya , Sakumoto Taichi , Tanatani Kenta , Yu HongYang , Mori Kosuke , Kamimura Naofumi , Masai Eiji
Published: July 2020

Iron, an essential element for all organisms, acts as a cofactor of enzymes in bacterial degradation of recalcitrant aromatic compounds. The bacterial family, Sphingomonadaceae comprises various degraders of recalcitrant aromatic compounds; however, little is known about their iron acquisition system. Here, we investigated the iron acquisition system in a model bacterium capable of degrading lignin-derived aromatics, Sphingobium sp. strain SYK-6. Analyses of SYK-6 mutants revealed that FiuA (SLG_34550), a TonB-dependent receptor (TBDR), was the major outer membrane iron transporter. Three other TBDRs encoded by SLG_04340, SLG_04380, and SLG_10860 also participated in iron uptake, and tonB2 (SLG_34540), one of the six tonB comprising the Ton complex which enables TBDR-mediated transport was critical for iron uptake. The ferrous iron transporter FeoB (SLG_36840) played an important role in iron uptake across the inner membrane. The promoter activities of most of the iron uptake genes were induced under iron-limited conditions, and their regulation is controlled by SLG_29410 encoding the ferric uptake regulator, Fur. Although feoB, among all the iron uptake genes identified is highly conserved in Sphingomonad strains, the outer membrane transporters seem to be diversified. Elucidation of the iron acquisition system promises better understanding of the bacterial degradation mechanisms of aromatic compounds.
Insulin2Q104del (Kuma) mutant mice develop diabetes with dominant inheritance
Authors: Sakano Daisuke , Inoue Airi , Enomoto Takayuki , Imasaka Mai , Okada Seiji , Yokota Mutsumi , Koike Masato , Araki Kimi , Kume Shoen
Published: July 2020

Insulin gene mutations have been identified to cause monogenic diabetes, and most of which developed permanent neonatal diabetes at young ages before 6 months of age in humans. To establish an animal model of permanent diabetes, we performed genome editing using the CRISPR/Cas9 system. We generated a novel Kuma mutant mice with p.Q104del in the Insulin2 (Ins2) gene in a BRJ background that exhibits a severe immune deficiency. Kuma mutant mice are non-obese and developed hyperglycemia from 3 weeks after birth in both males and females, which are inherited in a dominant mode. Kuma mutant mice displayed reduced insulin protein levels from 3-weeks-old, which seem to be caused by the low stability of the mutant insulin protein. Kuma mutant showed a reduction in islet size and islet mass. Electron microscopic analysis revealed a marked decrease in the number and size of insulin granules in the beta-cells of the mutant mice. Hyperglycemia of the mutant can be rescued by insulin administration. Our results present a novel insulin mutation that causes permanent early-onset diabetes, which provides a model useful for islet transplantation studies.
Effects of cardiovascular medications on primary patency of hemodialysis arteriovenous fistula
Authors: Chang Te-I. , Chen Cheng-Hsien , Hsieh Hui-Ling , Chen Chun-You , Hsu Shih-Chang , Cheng Ho-Shun , Huang Wen-Cheng , Sue Yuh-Mou , Hsu Yung-Ho , Lin Feng-Yen , Shih Chun-Ming , Lin Shing-Jong , Huang Po-Hsun , Liu Chung-Te
Published: July 2020

While the patency of vascular access is essential for hemodialysis patients, optimal pharmaceutical treatment to maintain arteriovenous fistula (AVF) patency remains lacking. As cardiovascular diseases are highly prevalent in patients with end-stage renal disease, various cardiovascular medications have also been used to maintain AVF patency. However, previous studies revealed inconsistent therapeutic effects and a comprehensive evaluation of this issue is needed. The present retrospective, longitudinal cohort study included patients receiving successful AVF creation. The evaluated cardiovascular medications included antiplatelet agents, antihypertensive agents, nitrates and nitrites, statins, dipyridamole, and pentoxifylline. The outcome was AVF primary patency. All laboratory data and medication profiles were recorded at baseline and followed at 3-month interval, until the end of the 2-year study period. Cox proportional regression model with time-dependent covariates was used to evaluate the risk for AVF patency loss. A total of 349 patients were included in the present study, in which 57% were men and the mean age was 65 ± 14 years. Among the included patients, 40% used antiplatelet agents, 27% used dipyridamole and 36% used statins at baseline. Of all the evaluated cardiovascular medications, only dipyridamole showed significant association with a higher risk for loss of AVF patency. To evaluate the effect of combination of antiplatelet agents and dipyridamole, the patients were classified into four groups, I: combine use of antiplatelet agents and dipyridamole, II: antiplatelet only, III: dipyridamole only; IV: none of both were used. Of the four groups, group IV exhibited highest AVF patency (52.4%), which was followed by group III (42.7%), group II (40%), and group I (28.6%), respectively. Compared with group IV, only group I showed a significantly higher risk for AVF patency loss. None of the cardiovascular medications evaluated in the present study showed a beneficial effect on AVF patency. Furthermore, dipyridamole showed an association with a higher risk of AVF patency loss. We do not suggest a beneficial effect of dipyridamole on maintaining AVF patency, particularly in combination with antiplatelet agents.
Physical interpretation of shear-rate behaviour of soils and geotechnical solution to the coefficient of start-up friction with low inertial number
Authors: Fei Jianbo , Jie Yuxin , Sun Xiaohui , Xiong Hao
Published: July 2020

Shear experiments on soils have revealed the effects of shear rate, confining pressure, and grain size on the residual shear strength, but their nature is not well understood. To interpret these behaviours, a single dimensionless inertial number I from granular physics is introduced. A linear relationship between coefficient of residual friction μr and the natural logarithm of I was found by analysing geotechnical test data from other literature and helps to resolve the μ(aI)-rheology, which was proved invalid in the quasi-static regime. A method is proposed that introduces two three-dimensional yield criteria for soils to classify the frictional properties between grains in the quasi-static regime. The empirical coefficient of start-up friction is replaced by strength parameters of the soil. When compliant with the Mohr–Coulomb yield criterion, this coefficient is positively correlated with the internal angle of friction but negatively correlated with the Lode angle. Moreover from further analysis, the calculated strength is smallest in the pure tension state, largest in the pure compression state, and intermediate in the pure shearing state. This result is consistent with the properties of compressive endurable and tensive intolerable for natural geomaterials.
Ultralow power spin–orbit torque magnetization switching induced by a non-epitaxial topological insulator on Si substrates
Authors: Khang Nguyen Huynh Duy , Nakano Soichiro , Shirokura Takanori , Miyamoto Yasuyoshi , Hai Pham Nam
Published: July 2020

The large spin Hall effect in topological insulators (TIs) is very attractive for ultralow-power spintronic devices. However, evaluation of the spin Hall angle and spin–orbit torque (SOT) of TIs is usually performed on high-quality single-crystalline TI thin films grown on dedicated III-V semiconductor substrates. Here, we report on room-temperature ultralow power SOT magnetization switching of a ferrimagnetic layer by non-epitaxial BiSb TI thin films deposited on Si/SiO2 substrates. We show that non-epitaxial BiSb thin films outperform heavy metals and other epitaxial TI thin films in terms of the effective spin Hall angle and switching current density by one to nearly two orders of magnitude. The critical SOT switching current density in BiSb is as low as 7 × 104 A/cm2 at room temperature. The robustness of BiSb against crystal defects demonstrate its potential applications to SOT-based spintronic devices.
Altered active control of step width in response to mediolateral leg perturbations while walking
Authors: Reimold Nicholas K. , Knapp Holly A. , Henderson Rachel E. , Wilson Landi , Chesnutt Alyssa N. , Dean Jesse C.
Published: July 2020

During human walking, step width is predicted by mediolateral motion of the pelvis, a relationship that can be attributed to a combination of passive body dynamics and active sensorimotor control. The purpose of the present study was to investigate whether humans modulate the active control of step width in response to a novel mechanical environment. Participants were repeatedly exposed to a force-field that either assisted or perturbed the normal relationship between pelvis motion and step width, separated by washout periods to detect the presence of potential after-effects. As intended, force-field assistance directly strengthened the relationship between pelvis displacement and step width. This relationship remained strengthened with repeated exposure to assistance, and returned to baseline afterward, providing minimal evidence for assistance-driven changes in active control. In contrast, force-field perturbations directly weakened the relationship between pelvis motion and step width. Repeated exposure to perturbations diminished this negative direct effect, and produced larger positive after-effects once the perturbations ceased. These results demonstrate that targeted perturbations can cause humans to adjust the active control that contributes to fluctuations in step width.
11-Deoxycortisol controls hydromineral balance in the most basal osmoregulating vertebrate, sea lamprey (Petromyzon marinus)
Authors: Shaughnessy Ciaran A. , Barany Andre , McCormick Stephen D.
Published: July 2020

It is unknown whether and how osmoregulation is controlled by corticosteroid signaling in the phylogenetically basal vertebrate group Agnatha, including lampreys and hagfishes. It is known that a truncated steroid biosynthetic pathway in lampreys produces two predominant circulating corticosteroids, 11-deoxycortisol (S) and 11-deoxycorticosterone (DOC). Furthermore, lampreys express only a single, ancestral corticosteroid receptor (CR). Whether S and/or DOC interact with the CR to control osmoregulation in lampreys is still unknown. We examined the role of the endogenous corticosteroids in vivo and ex vivo in sea lamprey (Petromyzon marinus) during the critical metamorphic period during which sea lamprey increase osmoregulatory capacity and acquire seawater (SW) tolerance. We demonstrate in vivo that increases in circulating [S] and gill CR abundance are associated with increases in osmoregulatory capacity during metamorphosis. We further show that in vivo and ex vivo treatment with S increases activity and expression of gill active ion transporters and improves SW tolerance, and that only S (and not DOC) has regulatory control over active ion transport in the gills. Lastly, we show that the lamprey CR expresses an ancestral, spironolactone-as-agonist structural motif and that spironolactone treatment in vivo increases osmoregulatory capacity. Together, these results demonstrate that S is an osmoregulatory hormone in lamprey and that receptor-mediated discriminative corticosteroid regulation of hydromineral balance is an evolutionarily basal trait among vertebrates.
Racial/ethnic and geographic differences in polybrominated diphenyl ether (PBDE) levels across maternal, placental, and fetal tissues during mid-gestation
Authors: Varshavsky Julia R. , Sen Saunak , Robinson Joshua F. , Smith Sabrina Crispo , Frankenfield Julie , Wang Yunzhu , Yeh Greg , Park June-Soo , Fisher Susan J. , Woodruff Tracey J.
Published: July 2020

Prenatal polybrominated diphenyl ether (PBDE) exposures are a public health concern due to their persistence and potential for reproductive and developmental harm. However, we have little information about the extent of fetal exposures during critical developmental periods and the variation in exposures for groups that may be more highly exposed, such as communities of color and lower socioeconomic status (SES). To characterize maternal–fetal PBDE exposures among potentially vulnerable groups, PBDE levels were examined in the largest sample of matched maternal serum, placenta, and fetal liver tissues during mid-gestation among a geographically, racially/ethnically, and socially diverse population of pregnant women from Northern California and the Central Valley (n = 180; 2014–16). Maternal–fetal PBDE levels were compared to population characteristics using censored Kendall’s tau correlation and linear regression. PBDEs were commonly detected in all biomatrices. Before lipid adjustment, wet-weight levels of all four PBDE congeners were highest in the fetal liver (p < 0.001), whereas median PBDE levels were significantly higher in maternal serum than in the fetal liver or placenta after lipid-adjustment (p < 0.001). We also found evidence of racial/ethnic disparities in PBDE exposures (Non-Hispanic Black > Latina/Hispanic > Non-Hispanic White > Asian/Pacific Islander/Other; p < 0.01), with higher levels of BDE-100 and BDE-153 among non-Hispanic Black women compared to the referent group (Latina/Hispanic women). In addition, participants living in Fresno/South Central Valley had 34% (95% CI: − 2.4 to 84%, p = 0.07) higher wet-weight levels of BDE-47 than residents living in the San Francisco Bay Area. PBDEs are widely detected and differentially distributed in maternal–fetal compartments. Non-Hispanic Black pregnant women and women from Southern Central Valley geographical populations may be more highly exposed to PBDEs. Further research is needed to identify sources that may be contributing to differential exposures and associated health risks among these vulnerable populations.
Quality of main types of hunted red deer meat obtained in Spain compared to farmed venison from New Zealand
Authors: Serrano Martina Pérez , Maggiolino Aristide , Landete-Castillejos Tomás , Pateiro Mirian , Barbería Javier Pérez , Fierro Yolanda , Domínguez Rubén , Gallego Laureano , García Andrés , De Palo Pasquale , Lorenzo José Manuel
Published: July 2020

Deer venison is increasingly valued as a natural meat. This study examines the three main sources of venison: farmed venison from New Zealand (NZ), the world’s leading producer, and wild deer from Spain (SP), the second largest producer, which mainly supplies venison from traditional autumn–winter driven hunts (monteria), involving packs of dogs, and a smaller proportion culled through summer selective stalking. Meat from NZ contained more protein, lower shear force and lowern-6/n-3 ratio (P < 0.01). Spanish meat had a greater content of total, essential and non-essential amino acids (P < 0.01). Meat from deer culled in winter had lower intramuscular fat and saturated fatty acids (FA) but higher polyunsaturated FA (P < 0.01) and pH (P < 0.001) than meat from summer stalked deer. Therefore, venison presents differences by country of origin for composition, FA and texture that are likely to affect its health characteristics. Anomalies observed in meat between the winter driven hunt and non-stressful summer stalking may be attributed to the level of death stress in the case of variables such as pH. However, the effect on fat and mineral composition seems to be seasonal, depending respectively on wild diet or cyclic osteoporosis in males.
A DNA methylation signature discriminates between excellent and non-response to lithium in patients with bipolar disorder type 1
Authors: Marie-Claire C. , Lejeune F. X. , Mundwiller E. , Ulveling D. , Moszer I. , Bellivier F. , Etain B.
Published: July 2020

Lithium (Li) is the cornerstone maintenance treatment for bipolar disorders (BD), but response rates are highly variable. To date, no clinical or biological marker is available to reliably define eligibility criteria for a maintenance treatment with Li. We examined whether the prophylactic response to Li (assessed retrospectively) is associated with distinct blood DNA methylation profiles. Bisulfite-treated total blood DNA samples from individuals with BD type 1 (15 excellent-responders (LiERs) versus 11 non-responders (LiNRs)) were used for targeted enrichment of CpG rich genomic regions followed by high-resolution next-generation sequencing to identify differentially methylated regions (DMRs). After controlling for potential confounders we identified 111 DMRs that significantly differ between LiERs and LiNRs with a significant enrichment in neuronal cell components. Logistic regression and receiver operating curves identified a combination of 7 DMRs with a good discriminatory power for response to Li (Area Under the Curve 0.806). Annotated genes associated with these DMRs include Eukaryotic Translation Initiation Factor 2B Subunit Epsilon (EIF2B5), Von Willebrand Factor A Domain Containing 5B2 (VWA5B2), Ral GTPase Activating Protein Catalytic Alpha Subunit 1 (RALGAPA1). Although preliminary and deserving replication, these results suggest that biomarkers of response to Li may be identified through peripheral epigenetic measures.
Validation of a stroke model in rat compatible with rt-PA-induced thrombolysis: new hope for successful translation to the clinic
Authors: Arkelius Kajsa , Vivien Denis , Orset Cyrille , Ansar Saema
Published: July 2020

The recent clinical trial (DAWN) suggests that recanalization treatment may be beneficial up to 24 h after stroke onset, thus re-opening avenues for development of new therapeutic strategies. Unfortunately, there is a continuous failure of drugs in clinical trials and one of the major reasons proposed for this translational roadblock is the animal models. Therefore, the purpose of this study was to validate a new thromboembolic stroke rat model that mimics the human pathology, and that can be used for evaluating new strategies to save the brain in conditions compatible with recanalization. Stroke was induced by injection of thrombin into the middle cerebral artery. Recombinant tissue-type plasminogen activator (rt-PA) or saline was administrated at 1 h/4 h after stroke onset, and outcome was evaluated after 24 h. Induced ischemia resulted in reproducible cortical brain injuries causing a decrease in neurological function 24 h after stroke onset. Early rt-PA treatment resulted in recanalization, reduced infarct size and improved neurological functions, while late rt-PA treatment showed no beneficial effects and caused hemorrhagic transformation in 25% of the rats. This validated and established model’s resemblance to human ischemic stroke and high translational potential, makes it an important tool in the development of new therapeutic strategies for stroke.
MCD diet-induced steatohepatitis generates a diurnal rhythm of associated biomarkers and worsens liver injury in Klf10 deficient mice
Authors: Leclère Pierre S. , Rousseau Déborah , Patouraux Stéphanie , Guérin Sophie , Bonnafous Stéphanie , Gréchez-Cassiau Aline , Ruberto Anthony A. , Luci Carmelo , Subramaniam Malayannan , Tran Albert , Delaunay Franck , Gual Philippe , Teboul Michèle
Published: July 2020

A large number of hepatic functions are regulated by the circadian clock and recent evidence suggests that clock disruption could be a risk factor for liver complications. The circadian transcription factor Krüppel like factor 10 (KLF10) has been involved in liver metabolism as well as cellular inflammatory and death pathways. Here, we show that hepatic steatosis and inflammation display diurnal rhythmicity in mice developing steatohepatitis upon feeding with a methionine and choline deficient diet (MCDD). Core clock gene mRNA oscillations remained mostly unaffected but rhythmic Klf10 expression was abolished in this model. We further show that Klf10 deficient mice display enhanced liver injury and fibrosis priming upon MCDD challenge. Silencing Klf10 also sensitized primary hepatocytes to apoptosis along with increased caspase 3 activation in response to TNFα. This data suggests that MCDD induced steatohepatitis barely affects the core clock mechanism but leads to a reprogramming of circadian gene expression in the liver in analogy to what is observed in other experimental disease paradigms. We further identify KLF10 as a component of this transcriptional reprogramming and a novel hepato-protective factor.
Stress and behavioral correlates in the head-fixed method: stress measurements, habituation dynamics, locomotion, and motor-skill learning in mice
Authors: Juczewski Konrad , Koussa Jonathan A. , Kesner Andrew J. , Lee Jeong O. , Lovinger David M.
Published: July 2020

Manual restriction of head movement, or head-fixation, of awake rodents allows for sophisticated investigation of neural circuits in vivo, that would otherwise be impossible in completely freely moving animals. While it is known that head-fixation induces stress, the scale of this stress and habituation dynamics remain unclear. We used the Mobile HomeCage system (Neurotar Ltd, Finland) where animals have their heads fixed to an aluminum frame but are otherwise freely moving in an ultralight carbon container floating above an air-dispensing base. For 25 consecutive days, mice were head-fixed while standing on the air-lifted platform for 2 h per day and blood samples were taken periodically to measure variation in the stress-related hormone, corticosterone. We showed that the initial increase in corticosterone concentration is followed by a return to control level throughout the days of head-fixed training. We also found a locomotor correlate of this drop. We conducted a battery of stress-sensitive behavioral paradigms in freely-moving mice that revealed minor differences following chronic head-fixation. Finally, we analyzed motor-skill learning in the head-fixed setup with a floating container. We believe that our results may contribute to better interpretation of past literature and future in vivo experiments using head-fixed animals.
Identification of sequence polymorphisms at 58 STRs and 94 iiSNPs in a Tibetan population using massively parallel sequencing
Authors: Peng Dan , Zhang Yinming , Ren Han , Li Haixia , Li Ran , Shen Xuefeng , Wang Nana , Huang Erwen , Wu Riga , Sun Hongyu
Published: July 2020

Massively parallel sequencing (MPS) has rapidly become a promising method for forensic DNA typing, due to its ability to detect a large number of markers and samples simultaneously in a single reaction, and sequence information can be obtained directly. In the present study, two kinds of forensic genetic markers, short tandem repeat (STR) and identity-informative single nucleotide polymorphism (iiSNP) were analyzed simultaneously using ForenSeq DNA Signature Prep Kit, a commercially available kit on MPS platform. A total of 152 DNA markers, including 27 autosomal STR (A-STR) loci, 24 Y chromosomal STR (Y-STR) loci, 7 X chromosomal STR (X-STR) loci and 94 iiSNP loci were genotyped for 107 Tibetan individuals (53 males and 54 females). Compared with length-based STR typing methods, 112 more A-STR alleles, 41 more Y-STR alleles, and 24 more X-STR alleles were observed at 17 A-STRs, 9 Y-STRs, and 5 X-STRs using sequence-based approaches. Thirty-nine novel sequence variations were observed at 20 STR loci. When the flanking regions were also analyzed in addition to target SNPs at the 94 iiSNPs, 38 more alleles were identified. Our study provided an adequate genotype and frequencies data of the two types of genetic markers for forensic practice. Moreover, we also proved that this panel is highly polymorphic and informative in Tibetan population, and should be efficient in forensic kinship testing and personal identification cases.
Controlling a complex system near its critical point via temporal correlations
Authors: Chialvo Dante R. , Cannas Sergio A. , Grigera Tomás S. , Martin Daniel A. , Plenz Dietmar
Published: July 2020

Many complex systems exhibit large fluctuations both across space and over time. These fluctuations have often been linked to the presence of some kind of critical phenomena, where it is well known that the emerging correlation functions in space and time are closely related to each other. Here we test whether the time correlation properties allow systems exhibiting a phase transition to self-tune to their critical point. We describe results in three models: the 2D Ising ferromagnetic model, the 3D Vicsek flocking model and a small-world neuronal network model. We demonstrate that feedback from the autocorrelation function of the order parameter fluctuations shifts the system towards its critical point. Our results rely on universal properties of critical systems and are expected to be relevant to a variety of other settings.
Coffinite formation from UO2+x
Authors: Szenknect Stéphanie , Alby Delhia , López García Marta , Wang Chenxu , Podor Renaud , Miserque Frédéric , Mesbah Adel , Duro Lara , Zetterström Evins Lena , Dacheux Nicolas , Bruno Jordi , Ewing Rodney C.
Published: July 2020

Most of the highly radioactive spent nuclear fuel (SNF) around the world is destined for final disposal in deep-mined geological repositories. At the end of the fuel’s useful life in a reactor, about 96% of the SNF is still UO2. Thus, the behaviour of UO2 in SNF must be understood and evaluated under the weathering conditions of geologic disposal, which extend to periods of hundreds of thousands of years. There is ample evidence from nature that many uranium deposits have experienced conditions for which the formation of coffinite, USiO4, has been favoured over uraninite, UO2+x, during subsequent alteration events. Thus, coffinite is an important alteration product of the UO2 in SNF. Here, we present the first evidence of the formation of coffinite on the surface of UO2 at the time scale of laboratory experiments in a solution saturated with respect to amorphous silica at pH = 9, room temperature and under anoxic conditions.
Pollution characteristics and ecological risk assessment of heavy metals in paddy fields of Fujian province, China
Authors: Kang Zhiming , Wang Songliang , Qin Junhao , Wu Renyue , Li Huashou
Published: July 2020

To analyze the concentration, spatial distribution patterns, and ecological risks of heavy metals (Cd, Cr, Pb, As, Cu, Ni and Co), 272 topsoil samples (0–20 cm) were collected from paddy fields in Fujian province in July 2017. The results revealed that the mean concentration of all heavy metals exceeded the background values in Fujian province, with the mean concentration of Cd being 5.20 times higher than its background. However, these concentrations of heavy metals were lower than their corresponding national standards (GB 15618-1995). Spatially, for Cd, the high concentration areas were located mainly in southeast of Sanming city and northeast of Quanzhou city. For Pb and As, the places of highest concentration were mainly in southeast of Quanzhou city and Zhangzhou city, and the main areas of high Ni concentration were distributed southeast of Nanping city. The geo-accumulation index ($${I}_{geo}$$Igeo) of Cd and As were indicative of moderate contaminations, and the index of Co, Cu and Cr suggested that these were practically uncontaminated. The nemerow integrated pollution index ($${P}_{n}$$Pn) showed that the entire study area was prone to a low level of pollution, but at the county level, Yongcun county and Zhaoan county are in an warning line area of pollution. According to the potential ecological risk ($$RI$$RI), the ecological risk belongs to the low risk of paddy fields in Fujian province. However, Cd should be given attention ($${E}_{r}$$Er = 25.09), as it contributed to the majority of potential ecological risks in Fujian province.