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Type 3 secretion

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https://www.readbyqxmd.com/read/28642776/regulation-involved-in-colonization-of-intercellular-spaces-of-host-plants-in-ralstonia-solanacearum
#1
REVIEW
Yasufumi Hikichi, Yuka Mori, Shiho Ishikawa, Kazusa Hayashi, Kouhei Ohnishi, Akinori Kiba, Kenji Kai
A soil-borne bacterium Ralstonia solanacearum invading plant roots first colonizes the intercellular spaces of the root, and eventually enters xylem vessels, where it replicates at high levels leading to wilting symptoms. After invasion into intercellular spaces, R. solanacearum strain OE1-1 attaches to host cells and expression of the hrp genes encoding components of the type III secretion system (T3SS). OE1-1 then constructs T3SS and secrets effectors into host cells, inducing expression of the host gene encoding phosphatidic acid phosphatase...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28642028/discovery-of-novel-5-oxa-2-6-diazaspiro-3-4-oct-6-ene-derivatives-as-potent-selective-and-orally-available-somatostatin-receptor-subtype-5-sstr5-antagonists-for-treatment-of-type-2-diabetes-mellitus
#2
Hideki Hirose, Takeshi Yamasaki, Masaki Ogino, Ryo Mizojiri, Yumiko Tamura-Okano, Hiroaki Yashiro, Yo Muraki, Yoshihide Nakano, Jun Sugama, Akito Hata, Shinji Iwasaki, Masanori Watanabe, Tsuyoshi Maekawa, Shizuo Kasai
Somatostatin receptor subtype 5 (SSTR5) has emerged as a novel attractive drug target for type 2 diabetes mellitus. Starting from N-benzyl azetidine derivatives 1 and 2 as in-house hit compounds, we explored the introduction of a carboxyl group into the terminal benzene of 1 to enhance SSTR5 antagonistic activity by the combination of the substituents at the 3-position of the isoxazoline. Incorporation of a carboxyl group at the 4-position of the benzene ring resulted in a significant enhancement in potency, however, the 4-benzoic acid derivative 10c exhibited moderate human ether-a-go-go related gene (hERG) inhibitory activity...
June 9, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28640446/c1q-tnf-related-protein-3-ctrp3-function-and-regulation
#3
Ying Li, Gary L Wright, Jonathan M Peterson
As the largest endocrine organ, adipose tissue secretes many bioactive molecules that circulate in blood, collectively termed adipokines. Efforts to identify such metabolic regulators have led to the discovery of a family of secreted proteins, designated as C1q tumor necrosis factor (TNF)-related proteins (CTRPs). The CTRP proteins, adiponectin, TNF-alpha, as well as other proteins with the distinct C1q domain are collectively grouped together as the C1q/TNF superfamily. Reflecting profound biological potency, the initial characterization of these adipose tissue-derived CTRP factors finds wide-ranging effects upon metabolism, inflammation, and survival-signaling in multiple tissue types...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28636871/pregnane-glycosides-from-cynanchum-menarandrense
#4
Michail Tsoukalas, Arianna Psichas, Frank Reimann, Fiona M Gribble, Annelise Lobstein, Aurélie Urbain
Five new pregnane-type steroidal glycosides, named menarandrosides A-E (1-2, 5-7) were isolated from the aerial parts of Cynanchum menarandrense, together with three known compounds, carumbelloside I (3), carumbelloside II (4), and pregnenolone-3-O-gentiobioside (8). Their structures were determined on the basis of spectroscopic analyses including NMR and mass spectrometry, reporting C-21 steroids glycosylated only by one or two glucose moieties. Compounds were then investigated for their potential to stimulate glucagon-like peptide-1 (GLP-1) secretion in intestinal cells; although none of the pure compounds had any influence, the fraction enriched in pregnanes exhibited a significant activity, suggesting a possible synergistic effect...
June 18, 2017: Steroids
https://www.readbyqxmd.com/read/28636781/discovery-of-two-bombinin-peptides-with-antimicrobial-and-anticancer-activities-from-the-skin-secretion-of-oriental-fire-bellied-toad-bombina-orientalis
#5
Chang Zhou, Zhengming Wang, Xin Peng, Yao Liu, Yangjun Lin, Zhe Zhang, Yuling Qiu, Meihua Jin, Ran Wang, Dexin Kong
Amphibian skin secretions are known to contain numerous peptides with a large array of biological activities. Bombinins are a group of amphibian derived peptides with broad spectrum antimicrobial activities that have been only identified from the ancient toad species, Bombina. In this study, we described the identification and characterization of a novel bombinin precursor which encoded a bombinin like peptide (BLP-7) and a novel bombinin H type peptide (named as Bombinin H-BO) from the skin secretion of Oriental fire-bellied toad, Bombina orientalis...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28635176/genetic-loss-of-the-muscarinic-m3-receptor-m3-r-markedly-alters-bile-formation-and-cholestatic-liver-injury-in-mice
#6
Franziska Durchschein, Elisabeth Krones, Marion J Pollheimer, Gernot Zollner, Martin Wagner, Jean-Pierre Raufman, Peter Fickert
Hepatic innervation represents a potentially underestimated regulator of liver function and regeneration. The muscarinic 3 receptor (M3 -R) is the primary cholangiocyte receptor for the afferent parasympathetic innervation of bile ducts. We aimed to determine the specific role of the M3 -R in bile formation and models for cholestatic liver disease in mice. We compared bile flow and composition in M3 -R knock-out mice (M3 -R(-/-) ) and wild type littermates (WT). M3 -R(-/-) mice showed significantly reduced bile flow compared to WT mice, most likely due to decreased biliary HCO3(-) secretion...
June 21, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28634815/autoimmune-diabetes-induced-by-pd-1-inhibitor-retrospective-analysis-and-pathogenesis-a-case-report-and-literature-review
#7
Marie-Léa Gauci, Pauline Laly, Tiphaine Vidal-Trecan, Barouyr Baroudjian, Jérémy Gottlieb, Nika Madjlessi-Ezra, Laetitia Da Meda, Isabelle Madelaine-Chambrin, Martine Bagot, Nicole Basset-Seguin, Cécile Pages, Samia Mourah, Philippe Boudou, Céleste Lebbé, Jean-François Gautier
Anti-PD-1 antibody treatment is approved in advanced melanoma and provides median overall survival over 24 months. The main treatment-related side effects are immune-related adverse events, which include rash, pruritus, vitiligo, thyroiditis, diarrhoea, hepatitis and pneumonitis. We report a case of autoimmune diabetes related to nivolumab treatment. A 73-year-old man was treated in second line with nivolumab at 3 mg/kg every two weeks for metastatic melanoma. At 6 weeks of treatment, he displayed diabetic ketoacidosis...
June 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28634242/type-ii-secretion-substrates-of-legionella-pneumophila-translocate-out-of-the-pathogen-occupied-vacuole-via-a-semipermeable-membrane
#8
Hilary K Truchan, Harry D Christman, Richard C White, Nakisha S Rutledge, Nicholas P Cianciotto
Legionella pneumophila replicates in macrophages in a host-derived phagosome, termed the Legionella-containing vacuole (LCV). While the translocation of type IV secretion (T4S) effectors into the macrophage cytosol is well established, the location of type II secretion (T2S) substrates in the infected host cell is unknown. Here, we show that the T2S substrate ProA, a metalloprotease, translocates into the cytosol of human macrophages, where it associates with the LCV membrane (LCVM). Translocation is detected as early as 10 h postinoculation (p...
June 20, 2017: MBio
https://www.readbyqxmd.com/read/28633807/differential-induction-of-atf3-and-ho-1-in-myeloid-cells-and-keratinocytes-via-dimethylfumarate-or-cyclosporine-a
#9
Stefanie Müller, Nikola Smatlik, Marc Burian, Kamran Ghoreschi, Martin Röcken, Amir S Yazdi
BACKGROUND: Chronic inflammatory skin diseases are characterized by controlled proliferation of keratinocytes. Here, activating transcription factor 3 (ATF3) might play a fundamental role. In these inflammatory diseases, proliferation is controlled and only rarely leads to cancer development which can be supported by an inflammatory microenvironment. ATF3 is a dual function protein as it suppresses pro-inflammatory IL-6 and IL-8, but also acts as a pro-oncogenic factor by the suppression of p53...
June 12, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28633071/structural-characterization-of-the-immunostimulatory-exopolysaccharide-produced-by-leuconostoc-mesenteroides-strain-ntm048
#10
Chiaki Matsuzaki, Chikahiro Takagaki, Yusuke Tomabechi, Lennart S Forsberg, Christian Heiss, Parastoo Azadi, Kenji Matsumoto, Toshihiko Katoh, Koji Hosomi, Jun Kunisawa, Kenji Yamamoto, Keiko Hisa
The exopolysaccharide (EPS) produced by probiotic Leuconostoc mesenteroides subsp. mesenteroides strain NTM048 has been reported to be an immunostimulant that enhances mucosal IgA production. In this study, we found that intranasal administration of mice with the EPS and an antigen (ovalbumin) resulted in secretion of antigen-specific IgA and IgG in the airway mucosa and the serum, suggesting that the EPS has the adjuvant activity for use with mucosal vaccination. Methylation analysis coupled to GC-MS, and 1D and 2D NMR spectroscopy revealed that 94% of the EPS consists of an α-(1 → 6) glucan containing 4% of 1→3-linked α-glucose branches...
June 15, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28631500/pancreatic-%C3%AE-cell-survival-and-proliferation-are-promoted-by-protein-kinase-g-type-i%C3%AE-and-downstream-regulation-of-akt-foxo1
#11
Janica C Wong, Van Vo, Priyatham Gorjala, Ronald R Fiscus
Early studies showed nitric oxide as a pro-inflammatory-cytokine-induced toxin involved in pancreatic β-cell destruction during pathogenesis of type-1 diabetes. However, nitric oxide has both cytotoxic and cytoprotective effects on mammalian cells, depending on concentration and micro-environmental surroundings. Our studies have shown that low/physiological-level nitric oxide selectively activates protein kinase G type Iα isoform, promoting cytoprotective/pro-cell-survival effects in many cell types. In bone marrow-derived stromal/mesenchymal stem cells, protein kinase G type Iα mediates autocrine effects of nitric oxide and atrial natriuretic peptide, promoting DNA-synthesis/proliferation and cell survival...
June 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28630662/sex-differences-in-endogenous-cortical-network-activity-spontaneously-recurring-up-down-states
#12
Charalambos Sigalas, Eleni Konsolaki, Irini Skaliora
BACKGROUND: Several molecular and cellular processes in the vertebrate brain exhibit differences between males and females, leading to sexual dimorphism in the formation of neural circuits and brain organization. While studies on large-scale brain networks provide ample evidence for both structural and functional sex differences, smaller-scale local networks have remained largely unexplored. In the current study, we investigate sexual dimorphism in cortical dynamics by means of spontaneous Up/Down states, a type of network activity that is exhibited during slow-wave sleep, quiet wakefulness, and anesthesia and is thought to represent the default activity of the cortex...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28630067/sipa-activation-of-caspase-3-is-a-decisive-mediator-of-host-cell-survival-at-early-stages-of-salmonella-typhimurium-infection
#13
Anne McIntosh, Lynsey M Meikle, Michael Ormsby, Beth A McCormick, John M Christie, James M Brewer, Mark Roberts, Daniel M Wall
Salmonella invasion protein A (SipA) is a dual function effector protein that plays roles in both actin polymerization and caspase-3 activation in intestinal epithelial cells. To date its function in other cell types has remained largely unknown despite its expression in multiple cell types and its extracellular secretion during infection. Here we show that in macrophages SipA induces increased caspase-3 activation early in infection. This activation required a threshold level of SipA linked to multiplicity of infection and may be a limiting factor controlling bacterial numbers in infected macrophages...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28630062/the-transcription-factor-nfat1-participates-in-the-induction-of-cd4-t-cell-functional-exhaustion-during-plasmodium-yoelii-infection
#14
Rachel Y Ames, Li-Min Ting, Inessa Gendlina, Kami Kim, Fernando Macian
Repeated stimulation of T cells that occurs in the context of chronic infection results in progressively reduced responsiveness of T cells to pathogen-derived antigens. This phenotype, known as T cell exhaustion, occurs during chronic infections caused by a variety of pathogens, from persistent viruses to parasites. Unlike the memory cells that typically form after successful pathogen clearance following an acute infection, exhausted T cells secrete lower levels of effector cytokines, proliferate less in response to cognate antigen, and up-regulate cell-surface inhibitory molecules such as PD-1 and LAG-3...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28627870/encapsulation-of-autoinducer-sensing-reporter-bacteria-in-reinforced-alginate-based-microbeads
#15
Ping Li, Mareike Müller, Matthew Wook Chang, Martin Frettlöh, Holger Schönherr
Quorum sensing, in which bacteria communities use signaling molecules for inter- and intracellular communication, has been intensively studied in recent decades. In order to fabricate highly sensitive easy-to-handle point of care biosensors that detect quorum sensing molecules, we have developed, as is reported here, reporter bacteria entrapped alginate-methacrylate (alginate-MA) hydrogel beads. The alginate-MA beads, which were obtained by electrostatic extrusion, were reinforced by photo-crosslinking to increase stability and thereby to reduce bacteria leaching...
June 19, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28627741/proteomics-approach-to-identify-novel-metastatic-bone-markers-from-the-secretome-of-pc-3-prostate-cancer-cells
#16
EunJi Sung, Oh Kwang Kwon, Jae-Mok Lee, Sangkyu Lee
Prostate cancer is the leading type of cancer diagnosed, and the most frequent cause of worldwide male cancer-related deaths annually. The limitations of current prostate cancer screening tests demand the identification of novel biomarkers for the early diagnosis of prostate cancer bone metastasis. In the present study, we performed a proteomic analysis of secreted proteins from the prostate cancer bone metastasis cell line, PC-3, and the normal prostate cell line, RWPE-1. We thus quantified 917 proteins, of which 68 were found to be secreted at higher levels by PC-3 than by RWPE-1 cells via LC-MS/MS...
June 19, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28626803/estimation-of-insulin-secretion-glucose-uptake-by-tissues-and-liver-handling-of-glucose-using-a-mathematical-model-of-glucose-insulin-homeostasis-in-lean-and-obese-mice
#17
Michael Brenner, Sakineh Esmaeili Mohsen Abadi, Ramin Balouchzadeh, H Felix Lee, Hoo Sang Ko, Michael Johns, Nehal Malik, Joshua J Lee, Guim Kwon
Destruction of the insulin-producing β-cells is the key determinant of diabetes mellitus regardless of their types. Due to their anatomical location within the islets of Langerhans scattered throughout the pancreas, it is difficult to monitor β-cell function and mass clinically. To this end, we propose to use a mathematical model of glucose-insulin homeostasis to estimate insulin secretion, glucose uptake by tissues, and hepatic handling of glucose. We applied the mathematical model by Lombarte et al. (2013) to compare various rate constants representing glucose-insulin homeostasis between lean (11% fat)- and high fat diet (HFD; 45% fat)-fed mice...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28624550/comparative-genome-analysis-of-fish-pathogen-flavobacterium-columnare-reveals-extensive-sequence-diversity-within-the-species
#18
Pattanapon Kayansamruaj, Ha Thanh Dong, Ikuo Hirono, Hidehiro Kondo, Saengchan Senapin, Channarong Rodkhum
Flavobacterium columnare is one of the deadliest fish pathogens causing devastating mortality in various freshwater fish species globally. To gain an insight into bacterial genomic contents and structures, comparative genome analyses were performed using the reference and newly sequenced genomes of F. columnare including genomovar I, II and I/II strains isolated from Thailand, Europe and the USA. Bacterial genomes varied in size from 3.09 to 3.39Mb (2714 to 3101 CDSs). The pan-genome analysis revealed open pan-genome nature of F...
June 15, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28623344/an-essential-role-of-pi3k-in-the-control-of-west-nile-virus-infection
#19
Leilei Wang, Long Yang, Erol Fikrig, Penghua Wang
The phosphatidyl-inositol-3 kinases (PI3K) pathway regulates a variety of cellular processes, including cell proliferation, RNA processing, protein translation, autophagy, apoptosis and antiviral immunity. Many viruses depend on PI3K signaling for replication. However, its role in flaviviral infection has not been clearly defined. Here we report that PI3K signaling is critical for the control of West Nile virus (WNV) infection by regulating type I IFN (IFN-I) response. Inhibition of PI3K activity by 3-methyl adenine (3-MA), Wortmannin (WM) and LY294002 (LY) increased viral titers by 3-16 folds in primary mouse macrophages, embryonic fibroblasts and human cell lines...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622658/how-effectors-promote-beneficial-interactions
#20
REVIEW
Hiroki Miwa, Shin Okazaki
Beneficial microbes such as rhizobia possess effector proteins that are secreted into the host cytoplasm where they modulate host-signaling pathways. Among these effectors, type 3 secreted effectors (T3Es) of rhizobia play roles in promoting nitrogen-fixing nodule symbiosis, suppressing host defenses and directly activating symbiosis-related processes. Rhizobia use the same strategy as pathogenic bacteria to suppress host defenses such as targeting the MAPK cascade. In addition, rhizobial T3E can promote root nodule symbiosis by directly activating Nod factor signaling, which bypasses Nod factor perception...
June 13, 2017: Current Opinion in Plant Biology
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