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Berlin Brandenburg

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  • Gene Expression
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  • 1
    In: PLoS ONE, 2016, Vol.11(10)
    Description: Phagocytes such as dendritic cells and macrophages, which are distributed in the small intestinal mucosa, play a crucial role in maintaining mucosal homeostasis by sampling the luminal gut microbiota. However, there is limited information regarding microbial uptake in a steady state. We investigated the composition of murine gut microbiota that is engulfed by phagocytes of specific subsets in the small intestinal lamina propria (SILP) and Peyer’s patches (PP). Analysis of bacterial 16S rRNA gene amplicon sequences revealed that: 1) all the phagocyte subsets in the SILP primarily engulfed Lactobacillus (the most abundant microbe in the small intestine), whereas CD11b hi and CD11b hi CD11c hi cell subsets in PP mostly engulfed segmented filamentous bacteria (indigenous bacteria in rodents that are reported to adhere to intestinal epithelial cells); and 2) among the Lactobacillus species engulfed by the SILP cell subsets, L . murinus was engulfed more frequently than L . taiwanensis , although both these Lactobacillus species were abundant in the small intestine under physiological conditions. These results suggest that small intestinal microbiota is selectively engulfed by phagocytes that localize in the adjacent intestinal mucosa in a steady state. These observations may provide insight into the crucial role of phagocytes in immune surveillance of the small intestinal mucosa.
    Keywords: Research Article ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Research And Analysis Methods ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: The Journal of nutrition, February 2002, Vol.132(2), pp.145-51
    Description: The relationship between nutritional status and insulin-like growth factor binding protein-2 (IGFBP-2) gene expression in chickens was studied. Chickens (6 wk old) were food deprived for 2 d and then refed. IGFBP-2 mRNA in the brain was significantly decreased by food deprivation and levels did not increase when birds were refed for 24 h. Gizzard and hepatic IGFBP-2 mRNA levels were significantly increased by food deprivation and decreased by refeeding. Any nutrients tested decreased hepatic IGFBP-2 gene expression. In kidney, IGFBP-2 mRNA was detected but not influenced by food deprivation and refeeding. In another study, the influence of dietary protein source [isolated soybean protein vs. casein; crude protein (CP) 20%] and the supplementation of essential amino acids on IGFBP-2 gene expression of young chickens (5 wk old) was examined. The influence of feeding a low soybean protein diet (CP 5%) on tissue IGFBP-2 gene expression was also investigated. Hepatic IGFBP-2 mRNA was not detected in any group. Feeding the low protein diet for 7 d decreased brain IGFBP-2 mRNA level and increased gizzard IGFBP-2 level compared with chickens fed 20% protein diets. A significant interaction between protein source and amino acid supplementation was observed in gizzard IGFBP-2 mRNA level. In both casein-fed groups and in chickens fed 20% soybean protein diet without supplemental amino acids, the levels did not differ from one another or from the low protein diet-fed birds. The level was lower in chickens fed the amino acid-supplemented, 20% soybean protein diet. In conclusion, the response of IGFBP-2 gene expression to variations in nutritional status was rapid and different in several tissues of young chickens, which would help modulate the growth-promoting effect of circulating IGF-I by making the IGF-IGFBP complex.
    Keywords: Gene Expression Regulation, Developmental ; Chickens -- Metabolism ; Food Deprivation -- Physiology ; Insulin-Like Growth Factor Binding Protein 2 -- Genetics
    ISSN: 0022-3166
    E-ISSN: 15416100
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  • 3
    Language: English
    In: Genes & development, May 2010, Vol.24(9), pp.887-92
    Description: VASA is an evolutionarily conserved RNA helicase essential for germ cell development. The mouse PIWI family proteins MILI and MIWI2 are involved in production of Piwi-interacting RNAs (piRNAs) in fetal male germ cells through a ping-pong amplification cycle. Expression of retrotransposons is elevated in MILI- and MIWI2-deficient male germ cells due to defective de novo DNA methylation, which is presumably caused by impaired piRNA expression. Here, we report that essentially the same abnormalities are observed in MVH (mouse VASA homolog)-deficient mice. Comprehensive analysis of piRNAs in MVH-deficient fetal male germ cells showed that MVH plays crucial roles in the early phase of the ping-pong amplification cycle.
    Keywords: Gene Silencing ; Dead-Box RNA Helicases -- Genetics ; Genes, Intracisternal A-Particle -- Genetics ; Long Interspersed Nucleotide Elements -- Genetics ; RNA, Small Interfering -- Metabolism
    ISSN: 08909369
    E-ISSN: 1549-5477
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  • 4
    Language: English
    In: The Journal of biological chemistry, 19 January 2007, Vol.282(3), pp.1998-2010
    Description: Molecular mechanisms underlying mineralocorticoid receptor (MR)-mediated gene expression are not fully understood. Various transcription factors are post-translationally modified by small ubiquitin-related modifier-1 (SUMO-1). We investigated the role of the SUMO-1-conjugating enzyme Ubc9 in MR transactivation. Yeast two-hybrid, GST-pulldown, and coimmunoprecipitation assays showed that Ubc9 interacted with N-terminal MR-(1-670). Endogenous Ubc9 is associated with stably expressing MR in 293-MR cells. Transient transfection assays in COS-1 cells showed that Ubc9 increased MR transactivation of reporter constructs containing MRE, ENaC, or MMTV promoter in a hormone-sensitive manner. Moreover, reduction of Ubc9 protein levels by small interfering RNA attenuated hormonal activation of a reporter construct as well as an endogenous target gene by MR. A sumoylation-inactive mutant Ubc9(C93S) similarly interacted with MR and potentiated aldosterone-dependent MR transactivation. An MR mutant in which four lysine residues within sumoylation motifs were mutated into arginine (K89R/K399R/K494R/K953R) failed to be sumoylated, but Ubc9 similarly enhanced transactivation by the mutant MR, indicating that sumoylation activity is dispensable for coactivation capacity of Ubc9. Coexpression of Ubc9 and steroid receptor coactivator-1 (SRC-1) synergistically enhanced MR-mediated transactivation in transient transfection assays. Indeed, chromatin immunoprecipitation assays demonstrated that endogenous MR, Ubc9, and SRC-1 were recruited to an endogenous ENaC gene promoter in a largely aldosterone-dependent manner. Coimmunoprecipitation assays showed a complex of MR, Ubc9, and SRC-1 in mammalian cells, and the endogenous proteins were colocalized in the nuclei of the mouse collecting duct cells. These findings support a physiological role of Ubc9 as a transcriptional MR coactivator, beyond the known SUMO E2-conjugating enzyme.
    Keywords: Transcriptional Activation ; Receptors, Mineralocorticoid -- Metabolism ; Ubiquitin-Conjugating Enzymes -- Chemistry
    ISSN: 0021-9258
    E-ISSN: 1083351X
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  • 5
    Language: English
    In: The Journal of biological chemistry, 22 July 2005, Vol.280(29), pp.27244-50
    Description: The Nrf2-Keap1 system coordinately regulates cytoprotective gene expression via the antioxidant responsive element (ARE). The expression of several ARE-regulated genes was found to be up-regulated in endothelial cells by laminar shear stress, suggesting that Nrf2 contributes to the anti-atherosclerosis response via the ARE. To gain further insight into the roles that Nrf2 plays in the development of atherosclerosis, we examined how Nrf2 regulates gene expression in response to anti-atherogenic laminar flow (L-flow) or pro-atherogenic oscillatory flow (O-flow). Exposure of human aortic endothelial cells (HAECs) to L-flow, but not to O-flow, induced the expression of cytoprotective genes, such as NAD(P)H quinone oxidoreductase 1 (NQO1) by 5-fold and heme oxygenase-1 by 8-fold. The critical contribution of Nrf2 to the expression induced by L-flow was ascertained in siRNA-mediated knock-down experiments. Two cyclooxygenase-2 (COX-2) specific inhibitors attenuated Nrf2 nuclear accumulation in the acute phase of L-flow exposure. A downstream product of COX-2, 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), activated the Nrf2 regulatory pathway in HAECs through binding to the cysteines of Keap1. These results demonstrate that 15d-PGJ2 is essential for L-flow to activate Nrf2 and induce anti-atherosclerotic gene expression. Whereas both L-flow and O-flow induced the nuclear accumulation of Nrf2 to comparable levels, chromatin immunoprecipitation analysis revealed that Nrf2 binding to the NQO1 ARE was significantly diminished in the case of O-flow compared with that of L-flow. These results suggest that O-flow inhibits Nrf2 activity at the DNA binding step, thereby suppressing athero-protective gene expression and hence predisposing the blood vessels to the formation of atherosclerosis.
    Keywords: DNA-Binding Proteins -- Physiology ; Endothelium, Vascular -- Cytology ; Proteins -- Physiology ; Trans-Activators -- Physiology
    ISSN: 0021-9258
    E-ISSN: 1083351X
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  • 6
    Language: English
    In: Cell Metabolism, 03 July 2012, Vol.16(1), pp.44-54
    Description: Although bacterial endotoxin, such as lipopolysaccharide (LPS), plays a key role in the pathogenesis of nonalcoholic steatohepatitis (NASH), detailed mechanisms of this pathogenesis remain unclear. Here, we demonstrate that upregulation of CD14 by leptin-mediated signaling is critical to hyperreactivity against endotoxin during NASH progression. Upregulation of CD14 in Kupffer cells and hyperreactivity against low-dose LPS were observed in high-fat diet (HFD)-induced steatosis mice, but not chow-fed-control mice. Hyperresponsivity against low-dose LPS led to accelerated NASH progression, including liver inflammation and fibrosis. Administering leptin in chow-fed mice caused increased hepatic expression of CD14 via STAT3 signaling, resulting in hyperreactivity against low-dose LPS without steatosis. In contrast, a marked decrease in hepatic CD14 expression was observed in leptin-deficient mice, despite severe steatosis. Our results indicate that obesity-induced leptin plays a crucial role in NASH progression via enhanced responsivity to endotoxin, and we propose a mechanism of bacteria-mediated progression of NASH. ► HFD-induced steatosis in mice promotes hyperresponsivity to low-dose LPS► CD14-positive Kupffer cells induced by feeding HFD regulate responsivity to LPS ► Leptin regulates CD14 expression in Kupffer cells via STAT3 signaling ► Leptin plays a critical role in NASH via control of responsivity to endotoxin
    Keywords: Biology
    ISSN: 1550-4131
    E-ISSN: 1932-7420
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  • 7
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 27 February 2001, Vol.98(5), pp.2199-2204
    Description: We have systematically characterized gene expression patterns in 49 adult and embryonic mouse tissues by using cDNA microarrays with 18,816 mouse cDNAs. Cluster analysis defined sets of genes that were expressed ubiquitously or in similar groups of tissues such as digestive organs and muscle. Clustering of expression profiles was observed in embryonic brain, postnatal cerebellum, and adult olfactory bulb, reflecting similarities in neurogenesis and remodeling. Finally, clustering genes coding for known enzymes into 78 metabolic pathways revealed a surprising coordination of expression within each pathway among different tissues. On the other hand, a more detailed examination of glycolysis revealed tissue-specific differences in profiles of key regulatory enzymes. Thus, by surveying global gene expression by using microarrays with a large number of elements, we provide insights into the commonality and diversity of pathways responsible for the development and maintenance of the mammalian body plan.
    ISSN: 00278424
    Source: Archival Journals (JSTOR)
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  • 8
    Language: English
    In: Molecular Reproduction and Development, April 2008, Vol.75(4), pp.632-640
    Description: Hexokinase is the first enzyme in the glycolytic pathway and utilizes ATP to convert glucose to glucose‐6‐phosphate (G6P). We previously identified three variant transcripts of that are expressed specifically in spermatogenic cells, have different 5′ untranslated regions, and encode a protein (HK1S, spermatogenic cell‐specific type 1 hexokinase) in which the porin‐binding domain (PBD) of HK1 is replaced by a novel ‐terminal spermatogenic cell‐specific region (SSR). However, the level of expression of the individual variant transcripts or of the other members of the hexokinase gene family (, and ) in spermatogenic cells remains uncertain. We show that , , and transcripts levels are quite low in spermatocytes and spermatids and transcripts are relatively abundant in spermatids, but that glucokinase (GCK) is not detected in spermatozoa. Using real time RT‐PCR (qPCR) with primers specific for each of the three variant forms and RNA from whole testis and isolated germ cells, we found that transcripts for and , but not for , are relatively high in spermatids. Similar results were seen using spermatogenic cells isolated by laser‐capture microdissection (LCM). Immunoblotting studies found that HK1S is abundant in sperm, and immunostaining confirmed that HK1S is located mainly in the principal piece of the sperm flagellum, where other spermatogenic cell‐specific glycolytic enzymes have been found. These results strongly suggest that HK1, HK2, HK3, and GCK are unlikely to have a role in glycolysis in sperm and that HK1S encoded by and serves this role. Mol. Reprod. Dev. 75: 632–640, 2008. © 2007 Wiley‐Liss, Inc.
    Keywords: Spermatogenesis ; Isozyme ; Gene Expression ; Glycolysis ; Testis
    ISSN: 1040-452X
    E-ISSN: 1098-2795
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  • 9
    Language: English
    In: Developmental Dynamics, November 2004, Vol.231(3), pp.518-526
    Description: The recent discovery of the gene (DM domain gene on Y chromosome and one of the family genes) as a key determinant of male development in the medaka () has led to its designation as the prime candidate gene for sex‐determination in this species. This study focused on the sites and pattern of expression of and genes during gonadal differentiation of medaka to further determine their roles in testis development. mRNA and protein are expressed specifically in the somatic cells surrounding primordial germ cells (PGCs) in the early gonadal primordium, before morphological sex differences are seen. However, somatic cells surrounding PGCs never express during the early migratory period. Expression of persists in Sertoli cell lineage cells, from PGC‐supporting cells to Sertoli cells, indicating that only ‐positive cells enclose PGCs during mitotic arrest after hatching. is expressed in spermatogonium‐supporting cells after testicular differentiation (20–30 days after hatching), and its expression is much higher than that of in mature testes. In XX sex‐reversed testes, is expressed in the Sertoli cell lineage, similar to the expression of in XY testes. These results suggest strongly that regulates PGC proliferation and differentiation sex‐specifically during early gonadal differentiation of XY individuals and that regulates spermatogonial differentiation. Developmental Dynamics 231:518–526, 2004. © 2004 Wiley‐Liss, Inc.
    Keywords: Dmy ; Dmrt1 ; Sex Determination ; Sex Differentiation ; Primordial Germ Cell ; Sertoli Cell ; Medaka
    ISSN: 1058-8388
    E-ISSN: 1097-0177
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  • 10
    Language: English
    In: Oncology letters, June 2019, Vol.17(6), pp.5139-5146
    Description: The prognostic impacts of preoperative C-reactive protein (CRP) and interleukin (IL)-6 expression levels in patients with breast cancer remain controversial. A total of 55 female patients with invasive breast cancer were enrolled, and preoperative prognostic parameters including IL-6 and CRP were analyzed. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method, and candidates' prognostic factors were examined using a Cox proportional hazard model. Using receiver operating characteristic curve analysis, IL-6 at 10.0 pg/ml and CRP at 0.12 mg/dl were determined as threshold values to predict OS and RFS, respectively. Patients with IL-6 ≥10.0 pg/ml had poorer OS compared with those with IL-6 〈10.0 pg/ml (P=0.003), and patients with CRP ≥0.12 mg/dl had poorer RFS compared with those with CRP 〈0.12 mg/dl (P〈0.001). Serum IL-6 level (hazard ratio, 13.230; 95% confidence interval, 1.285-136.214; P=0.030) and triple-negative subtype (hazard ratio, 11.739; 95% confidence interval, 1.415-97.362; P=0.023) were independent prognostic factors for OS, and CRP expression level was an independent prognostic factor for RFS in patients with breast cancer (hazard ratio, 18.571; 95% confidence interval, 2.240-153.949; P=0.007). In patients with invasive breast cancer, preoperative serum IL-6 and triple-negative subtype may be independent prognostic factors for OS, while for RFS, preoperative CRP may be a more accurate prognostic factor compared with those currently established.
    Keywords: Crp ; Il-6 ; Os ; Rfs ; Breast Cancer
    ISSN: 1792-1074
    E-ISSN: 17921082
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