bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depdc5 deficiency exacerbates alcohol-induced hepatic steatosis via suppression of PPARα pathway
Authors: Xu Lin , Zhang Xinge , Xin Yue , Ma Jie , Yang Chenyan , Zhang Xi , Hou Guoqing , Dong Xiaocheng Charlie , Sun Zhaoli , Xiong Xiwen , Cao Xuan 
Published: July 2021

AbstractAlcohol-related liver disease (ALD), a condition caused by alcohol overconsumption, occurs in three stages of liver injury including steatosis, hepatitis, and cirrhosis. DEP domain-containing protein 5 (DEPDC5), a component of GAP activities towards Rags 1 (GATOR1) complex, is a repressor of amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. In the current study, we found that aberrant activation of mTORC1 was likely attributed to the reduction of DEPDC5 in the livers of ethanol-fed mice or ALD patients. To further define the in vivo role of DEPDC5 in ALD development, we generated Depdc5 hepatocyte-specific knockout mouse model (Depdc5-LKO) in which mTORC1 pathway was constitutively activated through loss of the inhibitory effect of GATOR1. Hepatic Depdc5 ablation leads to mild hepatomegaly and liver injury and protects against diet-induced liver steatosis. In contrast, ethanol-fed Depdc5-LKO mice developed severe hepatic steatosis and inflammation. Pharmacological intervention with Torin 1 suppressed mTORC1 activity and remarkably ameliorated ethanol-induced hepatic steatosis and inflammation in both control and Depdc5-LKO mice. The pathological effect of sustained mTORC1 activity in ALD may be attributed to the suppression of peroxisome proliferator activated receptor α (PPARα), the master regulator of fatty acid oxidation in hepatocytes, because fenofibrate (PPARα agonist) treatment reverses ethanol-induced liver steatosis and inflammation in Depdc5-LKO mice. These findings provide novel insights into the in vivo role of hepatic DEPDC5 in the development of ALD.
Mutant p53-reactivating compound APR-246 synergizes with asparaginase in inducing growth suppression in acute lymphoblastic leukemia cells
Authors: Ceder Sophia , Eriksson Sofi E. , Liang Ying Yu , Cheteh Emarndeena H. , Zhang Si Min , Fujihara Kenji M. , Bianchi Julie , Bykov Vladimir J. N. , Abrahmsen Lars , Clemons Nicholas J. , Nordlund Pär , Rudd Sean G. , Wiman Klas G. 
Published: July 2021

AbstractAsparaginase depletes extracellular asparagine in the blood and is an important treatment for acute lymphoblastic leukemia (ALL) due to asparagine auxotrophy of ALL blasts. Unfortunately, resistance occurs and has been linked to expression of the enzyme asparagine synthetase (ASNS), which generates asparagine from intracellular sources. Although TP53 is the most frequently mutated gene in cancer overall, TP53 mutations are rare in ALL. However, TP53 mutation is associated with poor therapy response and occurs at higher frequency in relapsed ALL. The mutant p53-reactivating compound APR-246 (Eprenetapopt/PRIMA-1Met) is currently being tested in phase II and III clinical trials in several hematological malignancies with mutant TP53. Here we present CEllular Thermal Shift Assay (CETSA) data indicating that ASNS is a direct or indirect target of APR-246 via the active product methylene quinuclidinone (MQ). Furthermore, combination treatment with asparaginase and APR-246 resulted in synergistic growth suppression in ALL cell lines. Our results thus suggest a potential novel treatment strategy for ALL.
Revealing the widespread potential of forests to increase low level cloud cover
Authors: Duveiller Gregory , Filipponi Federico , Ceglar Andrej , Bojanowski Jędrzej , Alkama Ramdane , Cescatti Alessandro 
Published: July 2021

AbstractForests play a key role in humanity’s current challenge to mitigate climate change thanks to their capacity to sequester carbon. Preserving and expanding forest cover is considered essential to enhance this carbon sink. However, changing the forest cover can further affect the climate system through biophysical effects. One such effect that is seldom studied is how afforestation can alter the cloud regime, which can potentially have repercussions on the hydrological cycle, the surface radiation budget and on planetary albedo itself. Here we provide a global scale assessment of this effect derived from satellite remote sensing observations. We show that for 67% of sampled areas across the world, afforestation would increase low level cloud cover, which should have a cooling effect on the planet. We further reveal a dependency of this effect on forest type, notably in Europe where needleleaf forests generate more clouds than broadleaf forests.
The active sites of Cu–ZnO catalysts for water gas shift and CO hydrogenation reactions
Authors: Zhang Zhenhua , Chen Xuanye , Kang Jincan , Yu Zongyou , Tian Jie , Gong Zhongmiao , Jia Aiping , You Rui , Qian Kun , He Shun , Teng Botao , Cui Yi , Wang Ye , Zhang Wenhua , Huang Weixin 
Published: July 2021

AbstractCu–ZnO–Al2O3catalysts are used as the industrial catalysts for water gas shift (WGS) and CO hydrogenation to methanol reactions. Herein, via a comprehensive experimental and theoretical calculation study of a series of ZnO/Cu nanocrystals inverse catalysts with well-defined Cu structures, we report that the ZnO–Cu catalysts undergo Cu structure-dependent and reaction-sensitive in situ restructuring during WGS and CO hydrogenation reactions under typical reaction conditions, forming the active sites of CuCu(100)-hydroxylated ZnO ensemble and CuCu(611)Zn alloy, respectively. These results provide insights into the active sites of Cu–ZnO catalysts for the WGS and CO hydrogenation reactions and reveal the Cu structural effects, and offer the feasible guideline for optimizing the structures of Cu–ZnO–Al2O3catalysts.
Large parental differences in chromatin organization in pancreatic beta cell line explaining diabetes susceptibility effects
Authors: Jian Xing , Felsenfeld Gary 
Published: July 2021

AbstractPrevious GWAS studies identified non-coding loci with parent-of-origin-specific effects on Type 2 diabetes susceptibility. Here we report the molecular basis for one such locus near the KRTAP5-6 gene on chromosome 11. We determine the pattern of long-range contacts between an enhancer in this locus and the human INS promoter 460 kb away, in the human pancreatic β-cell line, EndoC-βH1. 3C long range contact experiments distinguish contacts on the two sister chromosomes. Coupling with allele-specific SNPs allows construction of maps revealing marked differences in organization of the two sister chromosomes in the entire region between KRTAP5-6 and INS. Further mapping distinguishes maternal and paternal alleles. This reveals a domain of parent-of-origin-specific chromatin structure extending in the telomeric direction from the INS locus. This suggests more generally that imprinted loci may extend their influence over gene expression beyond those loci through long range chromatin structure, resulting in parent-of-origin-biased expression patterns over great distances.
Routine sub-2.5 Å cryo-EM structure determination of GPCRs
Authors: Danev Radostin , Belousoff Matthew , Liang Yi-Lynn , Zhang Xin , Eisenstein Fabian , Wootten Denise , Sexton Patrick M. 
Published: July 2021

AbstractCryo-electron microscopy (cryo-EM) of small membrane proteins, such as G protein-coupled receptors (GPCRs), remains challenging. Pushing the performance boundaries of the technique requires quantitative knowledge about the contribution of multiple factors. Here, we present an in-depth analysis and optimization of the main experimental parameters in cryo-EM. We combined actual structural studies with methods development to quantify the effects of the Volta phase plate, zero-loss energy filtering, objective lens aperture, defocus magnitude, total exposure, and grid type. By using this information to carefully maximize the experimental performance, it is now possible to routinely determine GPCR structures at resolutions better than 2.5 Å. The improved fidelity of such maps enables the building of better atomic models and will be crucial for the future expansion of cryo-EM into the structure-based drug design domain. The optimization guidelines given here are not limited to GPCRs and can be applied directly to other small proteins.
Reduced stress-associated FKBP5 DNA methylation together with gut microbiota dysbiosis is linked with the progression of obese PCOS patients
Authors: Chen Fu , Chen Zhangran , Chen Minjie , Chen Guishan , Huang Qingxia , Yang Xiaoping , Yin Huihuang , Chen Lan , Zhang Weichun , Lin Hong , Ou Miaoqiong , Wang Luanhong , Chen Yongsong , Lin Chujia , Xu Wencan , Yin Guoshu 
Published: July 2021

AbstractPolycystic ovary syndrome (PCOS) is a common endocrine disease in females that is characterized by hyperandrogenemia, chronic anovulation, and polycystic ovaries. However, the exact etiology and pathogenesis of PCOS are still unknown. The aim of this study was to clarify the bacterial, stress status, and metabolic differences in the gut microbiomes of healthy individuals and patients with high body mass index (BMI) PCOS (PCOS-HB) and normal BMI PCOS (PCOS-LB), respectively. Here, we compared the gut microbiota characteristics of PCOS-HB, PCOS-LB, and healthy controls by 16S rRNA gene sequencing, FK506-binding protein 5 (FKBP5) DNA methylation and plasma metabolite determination. Clinical parameter comparisons indicated that PCOS patients had higher concentrations of total testosterone, androstenedione, dehydroepiandrosterone sulfate, luteinizing hormone, and HOMA-IR while lower FKBP5 DNA methylation. Significant differences in bacterial diversity and community were observed between the PCOS and healthy groups but not between the PCOS-HB and PCOS-LB groups. Bacterial species number was negatively correlated with insulin concentrations (both under fasting status and 120 min after glucose load) and HOMA-IR but positively related to FKBP5 DNA methylation. Compared to the healthy group, both PCOS groups had significant changes in bacterial genera, including Prevotella_9, Dorea, Maihella, and Slackia, and plasma metabolites, including estrone sulfate, lysophosphatidyl choline 18:2, and phosphatidylcholine (22:6e/19:1). The correlation network revealed the complicated interaction of the clinical index, bacterial genus, stress indices, and metabolites. Our work links the stress responses and gut microbiota characteristics of PCOS disease, which might afford perspectives to understand the progression of PCOS.
High temperature oxidation of corrosion resistant alloys from machine learning
Authors: Taylor Christopher D. , Tossey Brett M. 
Published: July 2021

AbstractParabolic rate constants, kp, were collected from published reports and calculated from corrosion product data (sample mass gain or corrosion product thickness) and tabulated for 75 alloys exposed to temperatures between ~800 and 2000 K (~500–1700 oC; 900–3000 oF). Data were collected for environments including lab air, ambient and supercritical carbon dioxide, supercritical water, and steam. Materials studied include low- and high-Cr ferritic and austenitic steels, nickel superalloys, and aluminide materials. A combination of Arrhenius analysis, simple linear regression, supervised and unsupervised machine learning methods were used to investigate the relations between composition and oxidation kinetics. The supervised machine learning techniques produced the lowest mean standard errors. The most significant elements controlling oxidation kinetics were Ni, Cr, Al, and Fe, with Mo and Co composition also found to be significant features. The activation energies produced from the machine learning analysis were in the correct distributions for the diffusion constants for the oxide scales expected to dominate in each class.
Influenza colloidal gold method and blood routine tests combination for rapid diagnosis of influenza: a decision tree-based analysis
Authors: Li Xiaoguang , Chen Jing , Lin Fei , Wang Wei , Xu Jie , Li Nan 
Published: July 2021

AbstractRapid influenza diagnosis can facilitate targeted treatment and reduce antibiotic misuse. However, diagnosis efficacy remains unclear. This study examined the efficacy of a colloidal gold rapid test for rapid influenza diagnosis. Clinical characteristics of 520 patients with influenza-like illness presenting at a fever outpatient clinic during two influenza seasons (2017–2018; 2018–2019) were evaluated. The clinical manifestations and results of routine blood, colloidal gold, and nucleic acid tests were used to construct a decision tree with three layers, nine nodes, and five terminal nodes. The combined positive predictive value of a positive colloidal gold test result and monocyte level within 10.95–12.55% was 88.2%. The combined negative predictive value of a negative colloidal gold test result and white blood cell count > 9.075 × 109/L was 84.9%. The decision-tree model showed the satisfactory accuracy of an early influenza diagnosis based on colloidal gold and routine blood test results.
Haplotype-resolved genome assembly provides insights into evolutionary history of the tea plant Camellia sinensis
Authors: Zhang Xingtan , Chen Shuai , Shi Longqing , Gong Daping , Zhang Shengcheng , Zhao Qian , Zhan Dongliang , Vasseur Liette , Wang Yibin , Yu Jiaxin , Liao Zhenyang , Xu Xindan , Qi Rui , Wang Wenling , Ma Yunran , Wang Pengjie , Ye Naixing , Ma Dongna , Shi Yan , Wang Haifeng , Ma Xiaokai , Kong Xiangrui , Lin Jing , Wei Liufeng , Ma Yaying , Li Ruoyu , Hu Guiping , He Haifang , Zhang Lin , Ming Ray , Wang Gang , Tang Haibao , You Minsheng 
Published: July 2021

AbstractTea is an important global beverage crop and is largely clonally propagated. Despite previous studies on the species, its genetic and evolutionary history deserves further research. Here, we present a haplotype-resolved assembly of an Oolong tea cultivar, Tieguanyin. Analysis of allele-specific expression suggests a potential mechanism in response to mutation load during long-term clonal propagation. Population genomic analysis using 190 Camellia accessions uncovered independent evolutionary histories and parallel domestication in two widely cultivated varieties, var. sinensis and var. assamica. It also revealed extensive intra- and interspecific introgressions contributing to genetic diversity in modern cultivars. Strong signatures of selection were associated with biosynthetic and metabolic pathways that contribute to flavor characteristics as well as genes likely involved in the Green Revolution in the tea industry. Our results offer genetic and molecular insights into the evolutionary history of Camellia sinensis and provide genomic resources to further facilitate gene editing to enhance desirable traits in tea crops.
Scenarios of future Indian electricity demand accounting for space cooling and electric vehicle adoption
Authors: Barbar Marc , Mallapragada Dharik S. , Alsup Meia , Stoner Robert 
Published: July 2021

AbstractIndia is expected to witness rapid growth in electricity use over the next two decades. Here, we introduce a custom regression model to project electricity consumption in India over the coming decades, which includes a bottom-up estimate of electricity consumption for two major growth drivers, air conditioning, and vehicle electrification. The model projections are available at a customizable level of spatial aggregation at an hourly temporal resolution, which makes them useful as inputs to long-term electricity infrastructure planning studies. The approach is used to develop electricity consumption data sets spanning various technology adoption and growth scenarios up to the year 2050 in five-year increments. The aim of the data is to provide a range of scenarios for India’s demand growth given new technology adoption. With long-term hourly demand projections serving as an essential input for electricity infrastructure modeling, this data publication enables further work on energy efficiency, generation, and transmission expansion planning for a fast-growing and increasingly important region from a global climate mitigation perspective.
Temporal transcriptomic profiling reveals dynamic changes in gene expression of Xenopus animal cap upon activin treatment
Authors: Satou-Kobayashi Yumeko , Kim Jun-Dal , Fukamizu Akiyoshi , Asashima Makoto 
Published: July 2021

AbstractActivin, a member of the transforming growth factor-β (TGF-β) superfamily of proteins, induces various tissues from the amphibian presumptive ectoderm, called animal cap explants (ACs) in vitro. However, it remains unclear how and to what extent the resulting cells recapitulate in vivo development. To comprehensively understand whether the molecular dynamics during activin-induced ACs differentiation reflect the normal development, we performed time-course transcriptome profiling of Xenopus ACs treated with 50 ng/mL of activin A, which predominantly induced dorsal mesoderm. The number of differentially expressed genes (DEGs) in response to activin A increased over time, and totally 9857 upregulated and 6663 downregulated DEGs were detected. 1861 common upregulated DEGs among all Post_activin samples included several Spemann’s organizer genes. In addition, the temporal transcriptomes were clearly classified into four distinct groups in correspondence with specific features, reflecting stepwise differentiation into mesoderm derivatives, and a decline in the regulation of nuclear envelop and golgi. From the set of early responsive genes, we also identified the suppressor of cytokine signaling 3 (socs3) as a novel activin A-inducible gene. Our transcriptome data provide a framework to elucidate the transcriptional dynamics of activin-driven AC differentiation, reflecting the molecular characteristics of early normal embryogenesis.
Investigating PLGA microparticle swelling behavior reveals an interplay of expansive intermolecular forces
Authors: Rapier Crystal E. , Shea Kenneth J. , Lee Abraham P. 
Published: July 2021

AbstractThis study analyzes the swelling behavior of native, unmodified, spherically uniform, monodisperse poly(lactic-co-glycolic acid) (PLGA) microparticles in a robust high-throughput manner. This work contributes to the complex narrative of PLGA microparticle behavior and release mechanisms by complementing and extending previously reported studies on intraparticle microenvironment, degradation, and drug release. Microfluidically produced microparticles are incubated under physiological conditions and observed for 50 days to generate a profile of swelling behavior. Microparticles substantially increase in size after 15 days, continue increasing for 30 days achieving size dependent swelling indices between 49 and 83%. Swelling capacity is found to correlate with pH. Our study addresses questions such as onset, duration, swelling index, size dependency, reproducibility, and causal mechanistic forces surrounding swelling. Importantly, this study can serve as the basis for predictive modeling of microparticle behavior and swelling capacity, in addition to providing clues as to the microenvironmental conditions that encapsulated material may experience.
Medial prefrontal cortex (A32 and A25) projections in the common marmoset: a subcortical anterograde study
Authors: Ríos-Flórez Jorge Alexander , Lima Ruthnaldo R. M. , Morais Paulo Leonardo A. G. , de Medeiros Helder Henrique Alves , Cavalcante Jeferson Souza , Junior Expedito S. Nascimento 
Published: July 2021

AbstractThis study was aimed at establishing the subcorticals substrates of the cognitive and visceromotor circuits of the A32 and A25 cortices of the medial prefrontal cortex and their projections and interactions with subcortical complexes in the common marmoset monkey (Callithrix jacchus). The study was primarily restricted to the nuclei of the diencephalon and amygdala. The common marmoset is a neotropical primate of the new world, and the absence of telencephalic gyrus favors the mapping of neuronal fibers. The biotinylated dextran amine was employed as an anterograde tracer. There was an evident pattern of rostrocaudal distribution of fibers within the subcortical nuclei, with medial orientation. Considering this distribution, fibers originating from the A25 cortex were found to be more clustered in the diencephalon and amygdala than those originating in the A32 cortex. Most areas of the amygdala received fibers from both cortices. In the diencephalon, all regions received projections from the A32, while the A25 fibers were restricted to the thalamus, hypothalamus, and epithalamus at different densities. Precise deposits of neuronal tracers provided here may significantly contribute to expand our understanding of specific connectivity among the medial prefrontal cortex with limbic regions and diencephalic areas, key elements to the viscerocognitive process.
Sex and age bias viral burden and interferon responses during SARS-CoV-2 infection in ferrets
Authors: Francis Magen E. , Richardson Brian , Goncin Una , McNeil Mara , Rioux Melissa , Foley Mary K. , Ge Anni , Pechous Roger D. , Kindrachuk Jason , Cameron Cheryl M. , Richardson Christopher , Lew Jocelyne , Machtaler Steven , Cameron Mark J. , Gerdts Volker , Falzarano Darryl , Kelvin Alyson A. 
Published: July 2021

AbstractSARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and older ages. Here we investigated the impact of male sex and age comparing sex-matched or age-matched ferrets infected with SARS-CoV-2. Differences in temperature regulation was identified for male ferrets which was accompanied by prolonged viral replication in the upper respiratory tract after infection. Gene expression analysis of the nasal turbinates indicated that 1-year-old female ferrets had significant increases in interferon response genes post infection which were delayed in males. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.