bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavioral aspects and neurobiological properties underlying medical cannabis treatment in Shank3 mouse model of autism spectrum disorder
Authors: Poleg Shani , Kourieh Emad , Ruban Angela , Shapira Guy , Shomron Noam , Barak Boaz , Offen Daniel 
Published: October 2021

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disease with a wide spectrum of manifestation. The core symptoms of ASD are persistent deficits in social communication, and restricted and repetitive patterns of behavior, interests, or activities. These are often accompanied by intellectual disabilities. At present, there is no designated effective treatment for the core symptoms and co-morbidities of ASD. Recently, interest is rising in medical cannabis as a treatment for ASD, with promising clinical data. However, there is a notable absence of basic pre-clinical research in this field. In this study, we investigate the behavioral and biochemical effects of long-term oral treatment with CBD-enriched medical cannabis oil in a human mutation-basedShank3mouse model of ASD. Our findings show that this treatment alleviates anxiety and decreases repetitive grooming behavior by over 70% in treated mutant mice compared to non-treated mutant mice. Furthermore, we were able to uncover the involvement of CB1 receptor (CB1R) signaling in the Avidekel oil mechanism, alongside a mitigation of cerebrospinal fluid (CSF) glutamate concentrations. Subsequently, RNA sequencing (RNA seq) of cerebellar brain samples revealed changes in mRNA expression of several neurotransmission-related genes post-treatment. Finally, our results question the relevancy of CBD enrichment of medical cannabis for treating the core symptoms of ASD, and emphasize the importance of the THC component for alleviating deficits in repetitive and social behaviors in ASD.
LTBP4 affects renal fibrosis by influencing angiogenesis and altering mitochondrial structure
Authors: Su Chi-Ting , Jao Tzu-Ming , Urban Zsolt , Huang Yue-Jhu , See Daniel H. W. , Tsai Yao-Chou , Lin Wei-Chou , Huang Jenq-Wen 
Published: October 2021

AbstractTransforming growth factor beta (TGFβ) signalling regulates extracellular matrix accumulation known to be essential for the pathogenesis of renal fibrosis; latent transforming growth factor beta binding protein 4 (LTBP4) is an important regulator of TGFβ activity. To date, the regulation of LTBP4 in renal fibrosis remains unknown. Herein, we report that LTBP4 is upregulated in patients with chronic kidney disease and fibrotic mice kidneys created by unilateral ureteral obstruction (UUO). Mice lacking the short LTBP4 isoform (Ltbp4S−/−) exhibited aggravated tubular interstitial fibrosis (TIF) after UUO, indicating that LTBP4 potentially protects against TIF. Transcriptomic analysis of human proximal tubule cells overexpressing LTBP4 revealed that LTBP4 influences angiogenic pathways; moreover, these cells preserved better mitochondrial respiratory functions and expressed higher vascular endothelial growth factor A (VEGFA) compared to wild-type cells under hypoxia. Results of the tube formation assay revealed that additional LTBP4 in human umbilical vein endothelial cell supernatant stimulates angiogenesis with upregulated vascular endothelial growth factor receptors (VEGFRs). In vivo, aberrant angiogenesis, abnormal mitochondrial morphology and enhanced oxidative stress were observed in Ltbp4S−/− mice after UUO. These results reveal novel molecular functions of LTBP4 stimulating angiogenesis and potentially impacting mitochondrial structure and function. Collectively, our findings indicate that LTBP4 protects against disease progression and may be of therapeutic use in renal fibrosis.
PARK7 promotes repair in early steroid-induced osteonecrosis of the femoral head by enhancing resistance to stress-induced apoptosis in bone marrow mesenchymal stem cells via regulation of the Nrf2 signaling pathway
Authors: Zhang Fei , Yan Yanglin , Peng Wuxun , Wang Lei , Wang Tao , Xie Zhihong , Luo Hong , Zhang Jian , Dong Wentao 
Published: October 2021

AbstractNovel therapies for the treatment of early steroid-induced osteonecrosis of the femoral head (SONFH) are urgently needed in orthopedics. Transplantation of bone marrow mesenchymal stem cells (BMSCs) provides new strategies for treating this condition at the early stage. However, stress-induced apoptosis of BMSCs transplanted into the femoral head necrotic area limits the efficacy of BMSC transplantation. Inhibiting BMSC apoptosis is key to improving the efficacy of this procedure. In our previous studies, we confirmed that Parkinson disease protein 7 (PARK7) is active in antioxidant defense and can clear reactive oxygen species (ROS), protect the mitochondria, and impart resistance to stress-induced apoptosis in BMSCs. In this study, we investigated the mechanism driving this PARK7-mediated resistance to apoptosis in BMSCs. Our results indicate that PARK7 promoted the disintegration of nuclear factor (erythroid-derived 2)–like 2 (Nrf2)/Kelch-like echinacoside–associated protein 1 (Keap1) complex. The free Nrf2 then entered the nucleus and activated the genetic expression of manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), and other antioxidant enzymes that clear excessive ROS, thereby protecting BMSCs from stress-induced apoptosis. To further explore whether PARK7-mediated resistance to stress-induced apoptosis could improve the efficacy of BMSC transplantation in early-stage SONFH, we transplanted BMSCs-overexpressing PARK7 into rats with early-stage SONFH. We then evaluated the survival of transplanted BMSCs and bone regeneration in the femoral head necrotic area of these rats. The results indicated that PARK7 promoted the survival of BMSCs in the osteonecrotic area and improved the transplantation efficacy of BMSCs on early-stage SONFH. This study provides new ideas and methods for resisting the stress-induced apoptosis of BMSCs and improving the transplantation effect of BMSCs on early-stage SONFH.
m6A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability
Authors: Liu Hongjiang , Qin Shan , Liu Changqi , Jiang Le , Li Chen , Yang Jiankai , Zhang Shunyao , Yan Zhongjie , Liu Xiaopeng , Yang Jipeng , Sun Xiaofeng 
Published: October 2021

AbstractN6-methyladenosine (m6A) has been identified to exert critical roles in human cancer; however, the regulation of m6A modification on glioblastoma multiforme (GBM) and long non-coding RNA (lncRNA) CASC9 (cancer susceptibility 9) is still unclear. Firstly, MeRIP-Seq revealed the m6A profile in the GBM. Moreover, the m6A-related lncRNA CASC9 expression was significantly elevated in the GBM tissue and its ectopic high expression was associated with poor survival, acting as an independent prognostic factor for GBM patients. Functionally, the aerobic glycolysis was promoted in the CASC9 overexpression transfection, which was inhibited in CASC9 knockdown in GBM cells. Mechanistically, m6A reader IGF2BP2 (insulin-like growth factor 2 mRNA binding protein 2) could recognize the m6A site of CASC9 and enhance its stability, then CASC9 cooperated with IGF2BP2, forming an IGF2BP2/CASC9 complex, to increase the HK2 (Hexokinase 2) mRNA stability. Our findings reveal that CASC9/IGF2BP2/HK2 axis promotes the aerobic glycolysis of GBM.
Magneto-optical spectroscopy on Weyl nodes for anomalous and topological Hall effects in chiral MnGe
Authors: Hayashi Y. , Okamura Y. , Kanazawa N. , Yu T. , Koretsune T. , Arita R. , Tsukazaki A. , Ichikawa M. , Kawasaki M. , Tokura Y. , Takahashi Y. 
Published: October 2021

AbstractPhysics of Weyl electrons has been attracting considerable interests and further accelerated by recent discoveries of giant anomalous Hall effect (AHE) and topological Hall effect (THE) in several magnetic systems including non-coplanar magnets with spin chirality or small-size skyrmions. These AHEs/THEs are often attributed to the intense Berry curvature generated around the Weyl nodes accompanied by band anti-crossings, yet the direct experimental evidence still remains elusive. Here, we demonstrate an essential role of the band anti-crossing for the giant AHE and THE in MnGe thin film by using the terahertz magneto-optical spectroscopy. The low-energy resonance structures around ~ 1.2 meV in the optical Hall conductivity show the enhanced AHE and THE, indicating the emergence of at least two distinct anti-crossings near the Fermi level. The theoretical analysis demonstrates that the competition of these resonances with opposite signs is a cause of the strong temperature and magnetic-field dependences of observed DC Hall conductivity. These results lead to the comprehensive understanding of the interplay among the transport phenomena, optical responses and electronic/spin structures.
Primary visual cortex straightens natural video trajectories
Authors: Hénaff Olivier J. , Bai Yoon , Charlton Julie A. , Nauhaus Ian , Simoncelli Eero P. , Goris Robbe L. T. 
Published: October 2021

AbstractMany sensory-driven behaviors rely on predictions about future states of the environment. Visual input typically evolves along complex temporal trajectories that are difficult to extrapolate. We test the hypothesis that spatial processing mechanisms in the early visual system facilitate prediction by constructing neural representations that follow straighter temporal trajectories. We recorded V1 population activity in anesthetized macaques while presenting static frames taken from brief video clips, and developed a procedure to measure the curvature of the associated neural population trajectory. We found that V1 populations straighten naturally occurring image sequences, but entangle artificial sequences that contain unnatural temporal transformations. We show that these effects arise in part from computational mechanisms that underlie the stimulus selectivity of V1 cells. Together, our findings reveal that the early visual system uses a set of specialized computations to build representations that can support prediction in the natural environment.
Self-selective formation of ordered 1D and 2D GaBi structures on wurtzite GaAs nanowire surfaces
Authors: Liu Yi , Knutsson Johan V. , Wilson Nathaniel , Young Elliot , Lehmann Sebastian , Dick Kimberly A. , Palmstrøm Chris J. , Mikkelsen Anders , Timm Rainer 
Published: October 2021

AbstractScaling down material synthesis to crystalline structures only few atoms in size and precisely positioned in device configurations remains highly challenging, but is crucial for new applications e.g., in quantum computing. We propose to use the sidewall facets of larger III–V semiconductor nanowires (NWs), with controllable axial stacking of different crystal phases, as templates for site-selective growth of ordered few atoms 1D and 2D structures. We demonstrate this concept of self-selective growth by Bi deposition and incorporation into the surfaces of GaAs NWs to form GaBi structures. Using low temperature scanning tunneling microscopy (STM), we observe the crystal structure dependent self-selective growth process, where ordered 1D GaBi atomic chains and 2D islands are alloyed into surfaces of the wurtzite (Wz) $$\{11{\bar{2}}0\}$$

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crystal facets. The formation and lateral extension of these surface structures are controlled by the crystal structure and surface morphology uniquely found in NWs. This allows versatile high precision design of structures with predicted novel topological nature, by using the ability of NW heterostructure variations over orders of magnitude in dimensions with atomic-scale precision as well as controllably positioning in larger device structures.
Genome-wide detection of cytosine methylations in plant from Nanopore data using deep learning
Authors: Ni Peng , Huang Neng , Nie Fan , Zhang Jun , Zhang Zhi , Wu Bo , Bai Lu , Liu Wende , Xiao Chuan-Le , Luo Feng , Wang Jianxin 
Published: October 2021

AbstractIn plants, cytosine DNA methylations (5mCs) can happen in three sequence contexts as CpG, CHG, and CHH (where H = A, C, or T), which play different roles in the regulation of biological processes. Although long Nanopore reads are advantageous in the detection of 5mCs comparing to short-read bisulfite sequencing, existing methods can only detect 5mCs in the CpG context, which limits their application in plants. Here, we develop DeepSignal-plant, a deep learning tool to detect genome-wide 5mCs of all three contexts in plants from Nanopore reads. We sequence Arabidopsis thaliana and Oryza sativa using both Nanopore and bisulfite sequencing. We develop a denoising process for training models, which enables DeepSignal-plant to achieve high correlations with bisulfite sequencing for 5mC detection in all three contexts. Furthermore, DeepSignal-plant can profile more 5mC sites, which will help to provide a more complete understanding of epigenetic mechanisms of different biological processes.
Phorbol-12-myristate 13-acetate inhibits Nephronectin gene expression via Protein kinase C alpha and c-Jun/c-Fos transcription factors
Authors: Kinoshita Mitsuhiro , Yamada Atsushi , Sasa Kiyohito , Ikezaki Kaori , Shirota Tatsuo , Kamijo Ryutaro 
Published: October 2021

AbstractNephronectin (Npnt) is an extracellular matrix protein and ligand of integrin α8β1 known to promote differentiation of osteoblasts. A search for factors that regulate Npnt gene expression in osteoblasts revealed that phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), had a strong effect to suppress that expression. Research was then conducted to elucidate the signaling pathway responsible for regulation of Npnt gene expression by PMA in osteoblasts. Treatment of MC3T3-E1 cells with PMA suppressed cell differentiation and Npnt gene expression. Effects were noted at a low concentration of PMA, and were time- and dose-dependent. Furthermore, treatment with the PKC signal inhibitor Gö6983 inhibited down-regulation of Npnt expression, while transfection with small interfering RNA (siRNA) of PKCα, c-Jun, and c-Fos suppressed that down-regulation. The present results suggest regulation of Npnt gene expression via the PKCα and c-Jun/c-Fos pathway.
Effect of nocturnal oxygen therapy on exercise performance of COPD patients at 2048 m: data from a randomized clinical trial
Authors: Gutweniger Sophia , Latshang Tsogyal D. , Aeschbacher Sayaka S. , Huber Fabienne , Flueck Deborah , Lichtblau Mona , Ulrich Stefanie , Hasler Elisabeth D. , Scheiwiller Philipp M. , Ulrich Silvia , Bloch Konrad E. , Furian Michael 
Published: October 2021

AbstractThis trial evaluates whether nocturnal oxygen therapy (NOT) during a stay at 2048 m improves altitude-induced exercise intolerance in lowlanders with chronic obstructive pulmonary disease (COPD). 32 lowlanders with moderate to severe COPD, mean ± SD forced expiratory volume in the first second of expiration (FEV1) 54 ± 13% predicted, stayed for 2 days at 2048 m twice, once with NOT, once with placebo according to a randomized, crossover trial with a 2-week washout period at < 800 m in-between. Semi-supine, constant-load cycle exercise to exhaustion at 60% of maximal work-rate was performed at 490 m and after the first night at 2048 m. Endurance time was the primary outcome. Additional outcomes were cerebral tissue oxygenation (CTO), arterial blood gases and breath-by-breath measurements (http://www.ClinicalTrials.gov NCT02150590). Mean ± SE endurance time at 490 m was 602 ± 65 s, at 2048 m after placebo 345 ± 62 s and at 2048 m after NOT 293 ± 60 s, respectively (P < 0.001 vs. 490 m). Mean difference (95%CI) NOT versus placebo was − 52 s (− 174 to 70), P = 0.401. End-exercise pulse oximetry (SpO2), CTO and minute ventilation ($${\dot{\text{V}}}_{{\text{E}}}$$

V
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E

) at 490 m were: SpO2 92 ± 1%, CTO 65 ± 1%, $${\dot{\text{V}}}_{{\text{E}}}$$

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37.7 ± 2.0 L/min; at 2048 m with placebo: SpO2 85 ± 1%, CTO 61 ± 1%, $${\dot{\text{V}}}_{{\text{E}}}$$

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40.6 ± 2.0 L/min and with NOT: SpO2 84 ± 1%; CTO 61 ± 1%; $${\dot{\text{V}}}_{{\text{E}}}$$

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40.6 ± 2.0 L/min (P < 0.05, SpO2, CTO at 2048 m with placebo vs. 490 m; P = NS, NOT vs. placebo). Altitude-related hypoxemia and cerebral hypoxia impaired exercise endurance in patients with moderate to severe COPD and were not prevented by NOT.
Changes in "natural antibiotic" metabolite composition during tetraploid wheat domestication
Authors: Ben-Abu Yuval , Itsko Mark 
Published: October 2021

AbstractGramineous plants protect their seeds from a variety of biotic stresses by producing toxic and deterrent secondary metabolites such as benzoxazinoids. It is unclear how the composition and abundance of these natural toxins has changed over the course of crop-plant domestication. To address this uncertainty, we characterized differences in metabolic levels of benzoxazinoids and their derivatives, between four lines of tetraploid wheat: wild emmer wheat (WEW), the direct progenitor of modern wheat; non-fragile domesticated emmer wheat (DEW), which was first domesticated about 11,000 years ago; the subsequently developed non-fragile and free-threshing durum landraces (LD); and modern durum (MD) varieties. Three-dimensional principal component analysis of mass spectrometry data of wheat metabolites showed with high resolution clear differences between metabolic profiles of WEW, DEW, and durum (LD + MD) and similarity in the metabolic profiles of the two durum lines (LD and MD) that is coherent with the phylogenetic relationship between the corresponding wheat lines. Moreover, our results indicated that some secondary metabolites involved in plant defense mechanisms became significantly more abundant during wheat domestication, while other defensive metabolites decreased or were lost. These metabolic changes reflect the beneficial or detrimental roles the corresponding metabolites might play during the domestication of three taxonomic subspecies of tetraploid wheat (Triticum turgidum).
Estimates of country level temperature-related mortality damage functions
Authors: Bressler R. Daniel , Moore Frances C. , Rennert Kevin , Anthoff David 
Published: October 2021

AbstractMany studies project that climate change is expected to cause a significant number of excess deaths. Yet, in integrated assessment models that determine the social cost of carbon (SCC), human mortality impacts do not reflect the latest scientific understanding. We address this issue by estimating country-level mortality damage functions for temperature-related mortality with global spatial coverage. We rely on projections from the most comprehensive published study in the epidemiology literature of future temperature impacts on mortality (Gasparrini et al. in Lancet Planet Health 1:e360–e367, 2017), which estimated changes in heat- and cold-related mortality for 23 countries over the twenty-first century. We model variation in these mortality projections as a function of baseline climate, future temperature change, and income variables and then project future changes in mortality for every country. We find significant spatial heterogeneity in projected mortality impacts, with hotter and poorer places more adversely affected than colder and richer places. In the absence of income-based adaptation, the global mortality rate in 2080–2099 is expected to increase by 1.8% [95% CI 0.8–2.8%] under a lower-emissions RCP 4.5 scenario and by 6.2% [95% CI 2.5–10.0%] in the very high-emissions RCP 8.5 scenario relative to 2001–2020. When the reduced sensitivity to heat associated with rising incomes, such as greater ability to invest in air conditioning, is accounted for, the expected end-of-century increase in the global mortality rate is 1.1% [95% CI 0.4–1.9%] in RCP 4.5 and 4.2% [95% CI 1.8–6.7%] in RCP 8.5. In addition, we compare recent estimates of climate-change induced excess mortality from diarrheal disease, malaria and dengue fever in 2030 and 2050 with current estimates used in SCC calculations and show these are likely underestimated in current SCC estimates, but are also small compared to more direct temperature effects.
Genetic propensity for obesity, socioeconomic position, and trajectories of body mass index in older adults
Authors: Tommerup Kristiane , Ajnakina Olesya , Steptoe Andrew 
Published: October 2021

AbstractIdentifying how socioeconomic positioning and genetic factors interact in the development of obesity is imperative for population-level obesity prevention strategies. The current study investigated whether social positioning, either independently or through interaction with a polygenic score for Body Mass Index (BMI-PGS), influences BMI trajectories across older adulthood. Data were analysed from 7,183 individuals from the English Longitudinal Study of Aging (ELSA). Interactions between the BMI-PGS and; lower educational attainment, self-perceived social status (SSS), and income, on BMI trajectories over 12 years across older adulthood were investigated through linear mixed effects models. Lower educational attainment, SSS and income were each associated with a higher baseline BMI for women, but not for men. There were interaction effects between BMI-PGS and social positioning such that men aged > 65 with a lower educational attainment (β = 0.62; 95%CI 0.00 – 1.24, p < 0.05), men aged ≤ 65 of a lower income (β = − 0.72, 95%CI − 1.21 - − 0.23, p < 0.01) and women aged ≤ 65 of lower SSS (β = − 1.41; 95%CI − 2.46 – 0.36, p < 0.01) showed stronger associations between the BMI-PGS and baseline BMI. There were few associations between markers of socioeconomic position and rate of change in BMI over the follow-up period. In sum, lower socioeconomic positioning showed adverse associations with women’s BMI in older adulthood. Moreover, the expression of the BMI-PGS, or extent to which it translates to a higher BMI, was subtly influenced by socioeconomic standing in both women and in men.
Functional and structural analysis of catabolite control protein C that responds to citrate
Authors: Liu Wei , Chen Jinli , Jin Liming , Liu Zi-Yong , Lu Ming , Jiang Ge , Yang Qing , Quan Chunshan , Nam Ki Hyun , Xu Yongbin 
Published: October 2021

AbstractCatabolite control protein C (CcpC) belongs to the LysR-type transcriptional regulator (LTTR) family, which regulates the transcription of genes encoding the tricarboxylic acid branch enzymes of the TCA cycle by responding to a pathway-specific metabolite, citrate. The biological function of CcpC has been characterized several times, but the structural basis for the molecular function of CcpC remains elusive. Here, we report the characterization of a full-length CcpC from Bacillus amyloliquefaciens (BaCcpC-FL) and a crystal structure of the C-terminal inducer-binding domain (IBD) complexed with citrate. BaCcpC required both dyad symmetric regions I and II to recognize the citB promoter, and the presence of citrate reduced citB promoter binding. The crystal structure of CcpC-IBD shows two subdomains, IBD-I and IBD-II, and a citrate molecule buried between them. Ile100, two arginines (Arg147 and Arg260), and three serines (Ser129, Ser189, and Ser191) exhibit strong hydrogen-bond interactions with citrate molecules. A structural comparison of BaCcpC-IBD with its homologues showed that they share the same tail-to-tail dimer alignment, but the dimeric interface and the rotation between these molecules exhibit significant differences. Taken together, our results provide a framework for understanding the mechanism underlying the functional divergence of the CcpC protein.