bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proto-oncoprotein Zbtb7c and SIRT1 repression: implications in high-fat diet-induced and age-dependent obesity
Authors: Choi Won-Il , Yoon Jae-Hyun , Choi Seo-Hyun , Jeon Bu-Nam , Kim Hail , Hur Man-Wook 
Published: May 2021

AbstractZbtb7c is a proto-oncoprotein that controls the cell cycle and glucose, glutamate, and lipid metabolism. Zbtb7c expression is increased in the liver and white adipose tissues of aging or high-fat diet-fed mice. Knockout or knockdown of Zbtb7c gene expression inhibits the adipocyte differentiation of 3T3-L1 cells and decreases adipose tissue mass in aging mice. We found that Zbtb7c was a potent transcriptional repressor of SIRT1 and that SIRT1 was derepressed in various tissues of Zbtb7c-KO mice. Mechanistically, Zbtb7c interacted with p53 and bound to the proximal promoter p53RE1 and p53RE2 to repress the SIRT1 gene, in which p53RE2 was particularly critical. Zbtb7c induced p53 to interact with the corepressor mSin3A-HADC1 complex at p53RE. By repressing the SIRT1 gene, Zbtb7c increased the acetylation of Pgc-1α and Pparγ, which resulted in repression or activation of Pgc-1α or Pparγ target genes involved in lipid metabolism. Our study provides a molecular target that can overexpress SIRT1 protein in the liver, pancreas, and adipose tissues, which can be beneficial in the treatment of diabetes, obesity, longevity, etc.
Genome-wide association study of early-onset bipolar I disorder in the Han Taiwanese population
Authors: Wu Lawrence Shih-Hsin , Huang Ming-Chyi , Fann Cathy Shen-Jang , Lane Hsien-Yuan , Kuo Chian-Jue , Chiu Wei-Che , Kwok Pui-Yan , Cheng Andrew Tai-Ann 
Published: May 2021

AbstractThe search for susceptibility genes underlying the heterogeneous bipolar disorder has been inconclusive, often with irreproducible results. There is a hope that narrowing the phenotypes will increase the power of genetic analysis. Early-onset bipolar disorder is thought to be a genetically homogeneous subtype with greater symptom severity. We conducted a genome-wide association study (GWAS) for this subtype in bipolar I (BPI) disorder. Study participants included 1779 patients of Han Chinese descent with BPI disorder recruited by the Taiwan Bipolar Consortium. We conducted phenotype assessment using the Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry and prepared a life chart with graphic depiction of lifetime clinical course for each of the BPI patient recruited. The assessment of onset age was based on this life chart with early onset defined as ≤20 years of age. We performed GWAS in a discovery group of 516 early-onset and 790 non-early-onset BPI patients, followed by a replication study in an independent group of 153 early-onset and 320 non-early-onset BPI patients and a meta-analysis with these two groups. The SNP rs11127876, located in the intron of CADM2, showed association with early-onset BPI in the discovery cohort (P = 7.04 × 10−8) and in the test of replication (P = 0.0354). After meta-analysis, this SNP was demonstrated to be a new genetic locus in CADM2 gene associated with early-onset BPI disorder (P = 5.19 × 10−8).
Characterization of gut microbiome in mice model of depression with divergent response to escitalopram treatment
Authors: Duan Jiajia , Huang Yu , Tan Xunmin , Chai Tingjia , Wu Jing , Zhang Hanping , Li Yifan , Hu Xi , Zheng Peng , Ji Ping , Zhao Libo , Yang Deyu , Fang Liang , Song Jinlin , Xie Peng 
Published: May 2021

AbstractDepression is a common and heterogeneous mental disorder. Although several antidepressants are available to treat the patients with depression, the factors which could affect and predict the treatment response remain unclear. Here, we characterize the longitudinal changes of microbial composition and function during escitalopram treatment in chronic unpredictable mild stress (CUMS) mice model of depression based on 16 S rRNA sequencing and metabolomics. Consequently, we found that escitalopram (ESC) administration serves to increase the alpha-diversity of the gut microbiome in ESC treatment group. The microbial signatures between responder (R) and non-responder (NR) groups were significantly different. The R group was mainly characterized by increased relative abundances of genus Prevotellaceae_UCG-003, and depleted families Ruminococcaceae and Lactobacillaceae relative to NR group. Moreover, we identified 15 serum metabolites responsible for discriminating R and NR group. Those differential metabolites were mainly involved in phospholipid metabolism. Significantly, the bacterial OTUs belonging to family Lachnospiraceae, Helicobacteraceae, and Muribaculaceae formed strong co-occurring relationships with serum metabolites, indicating alternations of gut microbiome and metabolites as potential mediators in efficiency of ESC treatment. Together, our study demonstrated that the alterations of microbial compositions and metabolic functions might be relevant to the different response to ESC, which shed new light in uncovering the mechanisms of differences in efficacy of antidepressants.
Is the worst of the COVID-19 global pandemic yet to come? Application of financial mathematics as candidate predictive tools
Authors: Dogra Prashant , Koay Eugene J. , Wang Zhihui , Vahidy Farhaan S. , Ferrari Mauro , Pasqualini Renata , Arap Wadih , Boom Marc L. , Dirk Sostman H. , Cristini Vittorio 
Published: May 2021

AbstractThe Elliott Wave principle is a time-honored, oft-used method for predicting variations in the financial markets. It is based on the notion that human emotions drive financial decisions. In the fight against the COVID-19 global pandemic, human emotions are similarly decisive, for instance in that they determine one’s willingness to be vaccinated, and/or to follow preventive measures including the personal wearing of masks, the application of social distancing protocols, and frequent handwashing. On this basis, we postulated that the Elliott Wave Principle may similarly be used to predict the future evolution of the COVID-19 pandemic. We demonstrated that this method reproduces the data pattern for various countries and the world (daily new cases). Potential scenarios were then extrapolated, from the best-case corresponding to a rapid, full vaccination of the population, to the utterly disastrous case of slow vaccination, and poor adherence to preventive protocols.
Opposite alterations of 5­HT2A receptor brain density in subjects with schizophrenia: relevance of radiotracers pharmacological profile
Authors: Diez-Alarcia Rebeca , Muguruza Carolina , Rivero Guadalupe , García-Bea Aintzane , Gómez-Vallejo Vanessa , Callado Luis F. , Llop Jordi , Martín Abraham , Meana J. Javier 
Published: May 2021

AbstractThe status of serotonin 5­HT2A receptors (5­HT2ARs) in schizophrenia has been controversial. In vivo positron emission tomography neuroimaging and in vitro post-mortem binding studies have reported conflicting results about 5­HT2AR density. Radiotracers bind different receptor conformations depending on their agonist, antagonist or inverse agonist properties. This study investigates 5­HT2AR density in the post-mortem prefrontal cortex from subjects with schizophrenia and controls using three radiotracers with a different pharmacological profile. The specific binding parameters of the inverse agonist [18F]altanserin, the agonist [3H]lysergic acid diethylamide (LSD) and the antagonist [3H]MDL100907 to brain cortex membranes from 20 subjects with schizophrenia and 20 individually matched controls were evaluated under similar methodological conditions. Ten schizophrenia subjects were antipsychotic-free at death. Saturation curve analyses were performed by non-linear regression to obtain a maximal density of binding sites (Bmax) and the affinity of the respective radiotracers (Kd). In schizophrenia subjects, 5-HT2AR density was decreased when quantified by [18F]altanserin binding, whereas increased when evaluated by [3H]LSD binding. However, [3H]MDL100907 binding was unaltered. A slight loss of affinity (higher Kd) was observed exclusively in [3H]LSD binding. The findings were more evident in antipsychotic-free subjects than in antipsychotic-treated subjects. In conclusion, a higher proportion of the 5-HT2AR-active functional conformation, which is rather identified by agonist radiotracers, was observed in schizophrenia patients. A consequent reduction of the inactive 5-HT2AR conformation, which is preferentially identified by inverse agonist radiotracers, was also obtained. Antagonist radiotracers do not distinguish between molecular conformations of the receptor, and accordingly, the absence of changes was shown. These results are compatible with the proposed increased functional activity of brain cortical 5-HT2ARs in schizophrenia.
A bioinformatic study revealed serotonergic neurons are involved in the etiology and therapygenetics of anxiety disorders
Authors: Liu Han-Kui , He Si-Jie , Zhang Jian-Guo 
Published: May 2021

AbstractGenetic factors contribute to the susceptibility of anxiety disorders (ADs) and responses to associated cognitive-behavioral therapy (CBT). However, the type of brain cell affected by the related genes remains unclear. Previous studies have indicated various important brain neurons associated with psychiatric disorders, highlighting the necessity to study the cellular basis of anxiety. We assembled 37 AD-related genes and 23 CBT-related genes from recent large-scale genome-wide association studies, and then investigated their cell-type specificity in single-cell transcriptome data via an expression weighted cell type enrichment method. Additionally, to investigate the cellular differences between ADs and other psychiatric disorders, we excluded the genes associated with major depressive disorder, bipolar disorder, and neuroticism, resulting in 29 AD-specific genes. Remarkably, results indicate that serotonergic neurons are significantly associated with both AD-related and CBT-related genes, despite the two gene sets showing no overlap. These observations provide evidence that serotonergic neurons are involved in the etiology and therapygenetics of ADs. Moreover, results also showed that serotonergic neurons are associated with AD-specific genes, providing a supplementary finding that is in opposition to previous studies that found no evidence for the association between serotonergic neurons and psychiatric disorders via the same strategy. In summary, the current study found that serotonergic neurons are involved in the etiology and therapygenetics of ADs, providing insights into their genetic and cellular basis. Further, this cellular difference study may deepen our understanding of ADs and other psychiatric disorders.
Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release
Authors: Egea Virginia , Kessenbrock Kai , Lawson Devon , Bartelt Alexander , Weber Christian , Ries Christian 
Published: May 2021

AbstractBone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.
Regulation of sarcomagenesis by the empty spiracles homeobox genes EMX1 and EMX2
Authors: Jimenez-García Manuel Pedro , Lucena-Cacace Antonio , Otero-Albiol Daniel , Carnero Amancio 
Published: May 2021

AbstractThe EMX (Empty Spiracles Homeobox) genesEMX1andEMX2are two homeodomain gene members of the EMX family of transcription factors involved in the regulation of various biological processes, such as cell proliferation, migration, and differentiation, during brain development and neural crest migration. They play a role in the specification of positional identity, the proliferation of neural stem cells, and the differentiation of certain neuronal cell phenotypes. In general, they act as transcription factors in early embryogenesis and neuroembryogenesis from metazoans to higher vertebrates. TheEMX1andEMX2’s potential as tumor suppressor genes has been suggested in some cancers. Our work showed thatEMX1/EMX2act as tumor suppressors in sarcomas by repressing the activity of stem cell regulatory genes (OCT4,SOX2,KLF4,MYC,NANOG,NES, andPROM1). EMX protein downregulation, therefore, induced the malignance and stemness of cells both in vitro and in vivo. In murine knockout (KO) models lackingEmxgenes, 3MC-induced sarcomas were more aggressive and infiltrative, had a greater capacity for tumor self-renewal, and had higher stem cell gene expression andnestinexpression than those in wild-type models. These results showing that EMX genes acted as stemness regulators were reproduced in different subtypes of sarcoma. Therefore, it is possible that the EMX genes could have a generalized behavior regulating proliferation of neural crest-derived progenitors. Together, these results indicate that theEMX1andEMX2genes negatively regulate these tumor-altering populations or cancer stem cells, acting as tumor suppressors in sarcoma.
Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue
Authors: Georgiadi Anastasia , Lopez-Salazar Valeria , Merahbi Rabih El- , Karikari Rhoda Anane , Ma Xiaochuan , Mourão André , Klepac Katarina , Bühler Lea , Alfaro Ana Jimena , Kaczmarek Isabell , Linford Adam , Bosma Madeleen , Shilkova Olga , Ritvos Olli , Nakamura Nobuhiro , Hirose Shigehisa , Lassi Maximilian , Teperino Raffaele , Machado Juliano , Scheideler Marcel , Dietrich Arne , Geerlof Arie , Feuchtinger Annette , Blutke Andreas , Fischer Katrin , Müller Timo Dirk , Kessler Katharina , Schöneberg Torsten , Thor Doreen , Hornemann Silke , Kruse Michael , Nawroth Peter , Pivovarova-Ramich Olga , Pfeiffer Andreas Friedrich Hermann , Sattler Michael , Blüher Matthias , Herzig Stephan 
Published: May 2021

AbstractThe proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.
Event generation and statistical sampling for physics with deep generative models and a density information buffer
Authors: Otten Sydney , Caron Sascha , de Swart Wieske , van Beekveld Melissa , Hendriks Luc , van Leeuwen Caspar , Podareanu Damian , Ruiz de Austri Roberto , Verheyen Rob 
Published: May 2021

AbstractSimulating nature and in particular processes in particle physics require expensive computations and sometimes would take much longer than scientists can afford. Here, we explore ways to a solution for this problem by investigating recent advances in generative modeling and present a study for the generation of events from a physical process with deep generative models. The simulation of physical processes requires not only the production of physical events, but to also ensure that these events occur with the correct frequencies. We investigate the feasibility of learning the event generation and the frequency of occurrence with several generative machine learning models to produce events like Monte Carlo generators. We study three processes: a simple two-body decay, the processes e+e− → Z → l+l− and $$pp\to t\bar{t}$$
p
p
→
t

t

¯

including the decay of the top quarks and a simulation of the detector response. By buffering density information of encoded Monte Carlo events given the encoder of a Variational Autoencoder we are able to construct a prior for the sampling of new events from the decoder that yields distributions that are in very good agreement with real Monte Carlo events and are generated several orders of magnitude faster. Applications of this work include generic density estimation and sampling, targeted event generation via a principal component analysis of encoded ground truth data, anomaly detection and more efficient importance sampling, e.g., for the phase space integration of matrix elements in quantum field theories.
Self-association of MreC as a regulatory signal in bacterial cell wall elongation
Authors: Martins Alexandre , Contreras-Martel Carlos , Janet-Maitre Manon , Miyachiro Mayara M. , Estrozi Leandro F. , Trindade Daniel Maragno , Malospirito Caíque C. , Rodrigues-Costa Fernanda , Imbert Lionel , Job Viviana , Schoehn Guy , Attrée Ina , Dessen Andréa 
Published: May 2021

AbstractThe elongasome, or Rod system, is a protein complex that controls cell wall formation in rod-shaped bacteria. MreC is a membrane-associated elongasome component that co-localizes with the cytoskeletal element MreB and regulates the activity of cell wall biosynthesis enzymes, in a process that may be dependent on MreC self-association. Here, we use electron cryo-microscopy and X-ray crystallography to determine the structure of a self-associated form of MreC from Pseudomonas aeruginosa in atomic detail. MreC monomers interact in head-to-tail fashion. Longitudinal and lateral interfaces are essential for oligomerization in vitro, and a phylogenetic analysis of proteobacterial MreC sequences indicates the prevalence of the identified interfaces. Our results are consistent with a model where MreC’s ability to alternate between self-association and interaction with the cell wall biosynthesis machinery plays a key role in the regulation of elongasome activity.
Observed interannual changes beneath Filchner-Ronne Ice Shelf linked to large-scale atmospheric circulation
Authors: Hattermann Tore , Nicholls Keith W. , Hellmer Hartmut H. , Davis Peter E. D. , Janout Markus A. , Østerhus Svein , Schlosser Elisabeth , Rohardt Gerd , Kanzow Torsten 
Published: May 2021

AbstractFloating ice shelves are the Achilles’ heel of the Antarctic Ice Sheet. They limit Antarctica’s contribution to global sea level rise, yet they can be rapidly melted from beneath by a warming ocean. At Filchner-Ronne Ice Shelf, a decline in sea ice formation may increase basal melt rates and accelerate marine ice sheet mass loss within this century. However, the understanding of this tipping-point behavior largely relies on numerical models. Our new multi-annual observations from five hot-water drilled boreholes through Filchner-Ronne Ice Shelf show that since 2015 there has been an intensification of the density-driven ice shelf cavity-wide circulation in response to reinforced wind-driven sea ice formation in the Ronne polynya. Enhanced southerly winds over Ronne Ice Shelf coincide with westward displacements of the Amundsen Sea Low position, connecting the cavity circulation with changes in large-scale atmospheric circulation patterns as a new aspect of the atmosphere-ocean-ice shelf system.
Inorganic-organic competitive coating strategy derived uniform hollow gradient-structured ferroferric oxide-carbon nanospheres for ultra-fast and long-term lithium-ion battery
Authors: Xia Yuan , Zhao Tiancong , Zhu Xiaohang , Zhao Yujuan , He Haili , Hung Chin-te , Zhang Xingmiao , Chen Yan , Tang Xinlei , Wang Jinxiu , Li Wei , Zhao Dongyuan 
Published: May 2021

AbstractThe gradient-structure is ideal nanostructure for conversion-type anodes with drastic volume change. Here, we demonstrate an inorganic-organic competitive coating strategy for constructing gradient-structured ferroferric oxide-carbon nanospheres, in which the deposition of ferroferric oxide nanoparticles and polymerization of carbonaceous species are competitive and well controlled by the reaction thermodynamics. The synthesized gradient-structure with a uniform size of ~420 nm consists of the ferroferric oxide nanoparticles (4–8 nm) in carbon matrix, which are aggregated into the inner layer (~15 nm) with high-to-low component distribution from inside to out, and an amorphous carbon layer (~20 nm). As an anode material, the volume change of the gradient-structured ferroferric oxide-carbon nanospheres can be limited to ~22% with ~7% radial expansion, thus resulting in stable reversible specific capacities of ~750 mAh g−1 after ultra-long cycling of 10,000 cycles under ultra-fast rate of 10 A g−1. This unique inorganic-organic competitive coating strategy bring inspiration for nanostructure design of functional materials in energy storage.
Covalency does not suppress O2 formation in 4d and 5d Li-rich O-redox cathodes
Authors: House Robert A. , Marie John-Joseph , Park Joohyuk , Rees Gregory J. , Agrestini Stefano , Nag Abhishek , Garcia-Fernandez Mirian , Zhou Ke-Jin , Bruce Peter G. 
Published: May 2021

AbstractLayered Li-rich transition metal oxides undergo O-redox, involving the oxidation of the O2− ions charge compensated by extraction of Li+ ions. Recent results have shown that for 3d transition metal oxides the oxidized O2− forms molecular O2 trapped in the bulk particles. Other forms of oxidised O2− such as O22− or (O–O)n− with long bonds have been proposed, based especially on work on 4 and 5d transition metal oxides, where TM–O bonding is more covalent. Here, we show, using high resolution RIXS that molecular O2 is formed in the bulk particles on O2‒ oxidation in the archetypal Li-rich ruthenates and iridate compounds, Li2RuO3, Li2Ru0.5Sn0.5O3 and Li2Ir0.5Sn0.5O3. The results indicate that O-redox occurs across 3, 4, and 5d transition metal oxides, forming O2, i.e. the greater covalency of the 4d and 5d compounds still favours O2. RIXS and XAS data for Li2IrO3 are consistent with a charge compensation mechanism associated primarily with Ir redox up to and beyond the 5+ oxidation state, with no evidence of O–O dimerization.