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Forkhead box O transcriptional factors, especially FoxO1 and FoxO3a, play critical roles in physiologic and pathologic immune responses. However, the function of FoxO4, another main member of the FoxO family, in lymphoid cells is still poorly understood. Here, we showed that loss of FoxO4 in T cells augmented IFN-[gamma] production of Th1 cells in vitro. Correspondingly, conditional deletion of FoxO4 in CD4* T cells enhanced T cell-specific responses to Listeria monocytogenes infection in vivo. Genome-wide occupancy and transcriptomic analyses identified Dkk3 (encoding the Dickkopf-3 protein) as a direct transcriptional target of FoxO4. Consistent with the FoxO4-DKK3 relationship, recombinant DKK3 protein restored normal levels of IFN-[gamma] production in FoxO4-deficient Th1 cells through the downregulation of lymphoid enhancer-binding factor 1 (Left1) expression. Together, our data suggest a potential FoxO4/DKK3 axis in Th1 cell differentiation, providing what we believe to be an important insight and supplement for FoxO family proteins in T lymphocyte biology and revealing a promising target for the treatment of immune-related diseases., Introduction [CD4.sup.+] helper T cells are central regulators of adaptive immune responses. After encountering a specific antigen on antigen-presenting cells, [CD4.sup.+] T cells undergo clonal expansion and differentiate into functionally [...]

Acetaldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme detoxifying acetaldehyde and endogenous lipid aldehydes; previous studies suggest a protective role of ALDH2 against cardiovascular disease (CVD). Around 40% of East Asians carrying the single nucleotide polymorphism (SNP) ALDH2 rs671 have an increased incidence of CVD. However, the role of ALDH2 in CVD beyond alcohol consumption remains poorly defined. Here we report that ALDH2/LDLR double knockout (DKO) mice have decreased atherosclerosis compared with LDLR-KO mice, whereas ALDH2/APOE-DKO mice have increased atherosclerosis, suggesting an unexpected interaction of ALDH2 with LDLR. Further studies demonstrate that in the absence of LDLR, AMPK phosphorylates ALDH2 at threonine 356 and enables its nuclear translocation. Nuclear ALDH2 interacts with HDAC3 and represses transcription of a lysosomal proton pump protein ATP6V0E2, critical for maintaining lysosomal function, autophagy, and degradation of oxidized low-density lipid protein. Interestingly, an interaction of cytosolic LDLR C-terminus with AMPK blocks ALDH2 phosphorylation and subsequent nuclear translocation, whereas ALDH2 rs671 mutant in human macrophages attenuates this interaction, which releases ALDH2 to the nucleus to suppress ATP6V0E2 expression, resulting in increased foam cells due to impaired lysosomal function. Our studies reveal a novel role of ALDH2 and LDLR in atherosclerosis and provide a molecular mechanism by which ALDH2 rs671 SNP increases CVD., IntroductionAtherosclerosis is the major cause of cardiovascular disease (CVD), and macrophages play a central role in progression of atherosclerosis (1, 2). In the early stage of atherosclerosis, macrophages take up [...]

Feng Huang Nie Pan--Lv You Yu Jing Zhong De Zhe Xi Nan She Zu Wen Hua Bian Qian (Phoenix Nirvana--Cultural Changes of She Ethnic Group in Southwestern Zhejiang in the [...]

In this work, the influence of graphitization degree of carbon microspheres (CMSs) on flame retardancy of Polyethylene terephthalate) (PET) composites was examined. The graphitized CMSs (abbreviated as, TCMSs) were prepared through an annealing treatment, and both the CMSs/PET and TCMSs/PET composites with variable filler amounts were fabricated by the melt blending method. The results suggested that the graphitization degree of CMSs played an important role in the flame retardancy of PET. On the one hand, the TCMSs acted as effective heat shields to delay the ignition time (TTI), improve the initial thermal decomposition temperature of PET, decrease the heat absorption, and enhance the limiting oxygen index (LOI) values. On the other hand, the graphitized TCMSs decreased both the peak heat release rate (PHRR) and fire risk (FGI) through the formation of a more compact crosslinked carbon layer of graphitized carbon. With the addition of 2% TCMSs, the LOI of TCMSs/PET composites increased from 21% (neat PET) to 26.3%, the PHRR value decreased from 531.90 to 332.46 kW/[m.sup.2], and the residue amount increased from 9.31% to 19.31%. Compared to the CMSs, the dispersion of TCMSs in PET matrix and tensile strength of TCMSs/PET composites were also improved. Thus, these novel graphitized TCMSs show promise as efficient flame retardants for future applications. POLYM. ENG. SCI., 58:1399-1408, 2018. [C] 2017 Society of Plastics Engineers, INTRODUCTION Halogen-free flame retardants have gained increasing interest in recent years due to their numerous advantages over existing flame retardants. In this respect, carbon nanomaterials have excellent thermal properties, and [...]

BACKGROUND. Clear cell renal cell carcinoma (ccRCC) is the most common histologically defined renal cancer. However, it is not a uniform disease and includes several genetic subtypes with different prognoses. ccRCC is also characterized by distinctive metabolic reprogramming. Tobacco smoking (TS) is an established risk factor for ccRCC, with unknown effects on tumor pathobiology. METHODS. We investigated the landscape of ccRCCs and paired normal kidney tissues using integrated transcriptomic, metabolomic, and metallomic approaches in a cohort of white males who were long-term current smokers (LTS) or were never smokers (NS). RESULTS. All 3 Omics domains consistently identified a distinct metabolic subtype of ccRCCs in LTS, characterized by activation of oxidative phosphorylation (OXPHOS) coupled with reprogramming of the malate-aspartate shuttle and metabolism of aspartate, glutamate, glutamine, and histidine. Cadmium, copper, and inorganic arsenic accumulated in LTS tumors, showing redistribution among intracellular pools, including relocation of copper into the cytochrome c oxidase complex. A gene expression signature based on the LTS metabolic subtype provided prognostic stratification of The Cancer Genome Atlas ccRCC tumors that was independent of genomic alterations. CONCLUSION. The work identified the TS-related metabolic subtype of ccRCC with vulnerabilities that can be exploited for precision medicine approaches targeting metabolic pathways. The results provided rationale for the development of metabolic biomarkers with diagnostic and prognostic applications using evaluation of OXPHOS status. The metallomic analysis revealed the role of disrupted metal homeostasis in ccRCC, highlighting the importance of studying effects of metals from e- cigarettes and environmental exposures. FUNDING. Department of Defense, Veteran Administration, NIH, ACS, and University of Cincinnati Cancer Institute., Introduction Clear cell renal cell carcinoma (ccRCC) is characterized by loss of tumor suppressors localized to the short arm of chromosome 3, including the von Hippel Lindau gene (VHL), which [...]

Xiao Zhang, [phrase omitted] [Hua Jian Cheng Die-Xi Jiang Miao Zu Fu Nv Wen Hua Ji Yi; Reinvented as the butterfly-cultural memory of the Miao women of Xijiang] Beijing: The [...]

Abstract. In this paper, we study a multisourcing supply network design problem, in which each retailer faces uncertain demand and can source products from more than one distribution center (DC). [...]

The aim of this study was to detect mutations of the nuclear factor I/X (Nfix) gene and examine the association of its polymorphisms with growth traits in cattle. Six sequence variants (SVs) including five single-nucleotide mutations and an indel with multiple alleles were detected, among which four polymorphisms within the Nfix gene were identified in 1159 individuals of five cattle breeds by sequencing and forced PCR-RFLP methods. The results of haplotype analysis showed 14 haplotypes within the breeds. Three haplotypes were shared by the five cattle breeds. Hapl (ACAI) was extremely predominant in all test populations, which suggested that individuals with Hapl (ACAI) were more adapted to the steppe environment. Association analysis in Nanyang cattle showed that two SVs of the Nfix gene were significantly associated with growth traits at different ages. In addition, the locations of the SVs showed that the 3' terminal of the bovine Nfix gene was unstable. Combining this instability with its characteristic of multiple alternative splicing, we conjectured that some SVs might have a relationship with the formation of the splices through which growth traits are modulated. This study will provide useful information for the selection and detection of multiple forms of alternative splicing of the bovine Nfix gene. Key words: association, bovine, haplotype, Nfix gene, sequence variants. Le but de ce travail etait de detecter des mutations au sein du gene codant pour le facteur nucleaire I/X (Nfix)et d'examiner l'association entre ces polymorphismes et les parametres de croissance chez les bovins. Six variants dont cinq mutations d'un seul nucleotide et un indel avec plusieurs alleles ont ete detectes par sequencage ou par analyse PCR-RFLP parmi 1159 individus appartenant a cinq races de bovins et quatre de ces polymorphismes etaient situes au sein du gene Nfix. L'analyse des haplotypes a montre la presence de 14 haplotypes chez ces races. Trois haplotypes etaient presents chez les cinq races. Hap1 (ACAI) etait largement predominant chez toutes les populations ce qui suggere que les individus porteurs de Hap1 (ACAI) seraient mieux adaptes a l'environnement de la steppe. Une analyse d'association au sein des bovins Nanyang a montre que deux variants dans le gene Nfix etiaent significativement associes a des parametres de croissance a differents ages. Par ailleurs, la position des variants montre que l'extremite 3' du gene Nfix bovin serait instable et, conjointement a l'existence de plusieurs formes epissees alternatives, les auteurs postulent que certains variants pourraient jouer un role dans cet epissage alternatif et ainsi affecter la croissance. Cette etude fournit des informations utiles pour la selection et la detection des multiples formes d'epissage alternatif du gene Nfix chez les bovins. Mots-cles : association, bovin, haplotype, gene Nfix, variants., Introduction The nuclear factor I (Nfi) family is a group of genes coding for site-specific DNA-binding proteins involved in the control of gene expression in a variety of cell types [...]

The record of rabies in Chinese history dates back to 556 BC in Master Zuo's tradition of the Spring and Autumn annals. He wrote, "In the eleventh month, people in [...]

Expression of the Arabidopsis TRANSPARENT TESTA 2 (TT2) MYB family transcription factor leads to massive accumulation of proanthocyanidins (PAs) in hairy roots of Medicago truncatula. Microarray analysis showed that TT2 induces genes for flavonoid/PA biosynthesis, transcription factors, and a large number of genes of unknown function. A second microarray dataset identified genes that were preferentially expressed in the M. truncatula seed coat. Comparison of the two datasets defines target genes for steps that are yet unidentified in PA biosynthesis and accumulation. Of these genes, a glycosyltransferase, UGT72L1, was active specifically toward the PA precursor (-)--epicatechin, and its expression pattern in developing seeds correlated with the presence of epicatechin glucoside and accumulation of PA5. UGT72L1 may be involved in the production of epicatechin 3'-O-glucoside in the seed coat as a key step in PA biosynthesis or its regulation. glucosyltransferase | model legume | proanthocyanidin