Macroautophagy is a degradative pathway that sequesters and transports cytosolic cargo in autophagosomes to lysosomes, its deterioration affects intracellular proteostasis. Membrane dynamics accompanying autophagy are mostly elusive depend on trafficking processes. RAB GTPase activating proteins (RABGAPs) important factors for the coordination of cellular vesicle transport systems, several TBC (TRE2-BUB2-CDC16) domain-containing RABGAPs associated with autophagy. Employing C. elegans human...

The transformation of cells generally involves multiple genetic lesions that undermine control both cell death and proliferation. We now report κB-Ras proteins act as regulators NF-κB Ral pathways, which inflammation/cell proliferation, respectively. Cells lacking therefore not only show increased activity, results in expression inflammatory mediators, but also exhibit elevated leads to enhanced anchorage-independent proliferation (AIP). deficiency consequently significantly tumor growth can...

Helicobacter pylori represents an important pathogen involved in diseases ranging from gastritis, peptic ulceration, to gastric malignancies. Prominent virulence factors comprise the vacuolating cytotoxin VacA and cytotoxin-associated genes pathogenicity island (cagPAI)-encoded type IV secretion system (T4SS). The T4SS effector protein CagA can be translocated into AGS other epithelial cells followed by phosphorylation through c-Src c-Abl tyrosin kinases hijack signalling networks. duodenal...

Monoclonal antibody (mAb) 6G5j is a novel anti-CEACAM monoclonal antibody. Our aim was to investigate mAb binding characteristics and validate fluorescence targeting of colorectal tumors metastases in patient derived orthotopic xenograft (PDOX) models with fluorescently labeled 6G5j.The MAb profile analyzed ELISA, Western blot immunohistochemistry. conjugated near-infrared dye IR800CW (LI-COR). blotting performed various colon cancer cell lysates determine CEACAM expression. Nude mice...

Streptococcus agalactiae, also known as group B (GBS), is the major cause of neonatal sepsis in humans.A critical step to infection adhesion bacteria epithelial surfaces.GBS adhesins have been identified bind extracellular matrix components and cellular receptors.However, several putative no host binding partner characterised.We report here that surfaceexpressed b protein GBS binds human CEACAM1 CEACAM5 receptors.A crystal structure complex showed an IgSF domain represents a novel Ig-fold...

Abstract The IL‐1 family member IL‐36α has proinflammatory and pathogenic properties in psoriasis. binds to the IL‐36 receptor leading nuclear factor kappa B/mitogen activated protein kinase mediated cytokine release. IL‐36R antagonist prevents recruitment of accessory therefore IL‐36‐dependent cell activation. In inflamed human tissue, we previously could show that resident B cells plasma (PC) express IL‐36α. Further, fibroblast‐like synoviocytes (FLS) produced cytokines upon...

Background: Development of brain metastases in advanced melanoma patients is a frequent event that limits patients’ quality life and survival. Despite recent insights into genetics, systematic analyses genetic alterations metastasis formation are lacking. Moreover, whether harbor distinct beyond those observed at different anatomic sites the same patient remains unknown. Experimental Design Results: In our study, 54 intracranial 18 corresponding extracranial were analyzed for mutations using...

Attachment to the host gastric mucosa is a key step in Helicobacter pylori infection. Recently, novel adhesin, HopQ, was shown bind distinct CEACAM proteins-an interaction that found be essential for translocation of CagA, virulence factor H. pylori. The HopQ-CEACAM1 co-crystal structure revealed binding mode dependent on loops HopQ are clasped by disulfide bonds. In this study, we investigated importance these cysteine residues CEACAM1 engagement We observed loss and CagA upon disruption...

The maintenance of cellular proteostasis is dependent on molecular chaperones and protein degradation pathways. Chaperones facilitate folding, maturation, degradation, the particular fate a misfolded determined by interaction with co-chaperones. co-factor CHIP (C-terminus HSP70-inteacting protein, STUB1) ubiquitinates chaperone substrates directs proteins to systems. activity regulated two co-chaperones, BAG2 HSPBP1, which are potent inhibitors E3 ubiquitin ligase activity. Here, we examined...

Helicobacter pylori typically colonizes the human stomach, but it can occasionally be detected in oral cavity of infected persons. Clinical outcome as a result gastric colonization depends on presence pathogenicity island cagPAI that encodes type-IV secretion system (T4SS) for translocation effector protein CagA and ADP-heptose. Upon injection into target cells, is phosphorylated, which demonstrated by vitro infection epithelial cell line AGS, resulting elongation. Here we investigated...

The incidence of gastrointestinal infections continues to increase, and infectious colitis contributes significantly morbidity mortality worldwide. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been discovered be strongly involved in the intestinal homeostasis. However, whether CEACAM1 expression an impact on control remains elusive. Citrobacter rodentium (C. rodentium) is a gram-negative enteric pathogen that induces colonic inflammation mice, with critical role...

The interleukin (IL)-1 family member IL-33 has been described as intracellular alarmin with broad roles in wound healing, skin inflammation but also autoimmunity. Its dichotomy between full length (fl) and the mature (m) form of its release by necrosis is still not fully understood. Here, we compare functional consequences both forms vivo, therefore generated two lines transgenic mice which selectively overexpress mmIL-33 flmIL-33 basal keratinocytes. Transgene mRNA was expressed at high...

Surgical adhesives are useful supplements in surgery, but their benefit tendon repair is uncertain. The purpose of this study was to evaluate the effect BioGlue™ on strength flexor repair. A total 60 porcine tendons were divided into three groups. In group one, a conventional core and peripheral suture used. two, three, We performed static cyclic axial load testing measured diameter site. found that did not improve tensile when added there an increase bulk at conclude application cannot...

Alpha synuclein (aSyn) and its aggregation are crucial for the neurodegeneration of Parkinson’s disease (PD). aSyn was initially described in nucleus presynaptic nerve terminals. However, biology nuclear link between subcellular compartments less understood. Current knowledge suggests existence various species with distinct structural biochemical properties. Here, we identified a C-terminal-targeting antibody (Nu-aSyn-C), which has high immunoaffinity towards nucleus. Comparing Nu-aSyn-C to...

HopQ is an outer-membrane protein of Helicobacter pylori that binds to human carcinoembryonic antigen-related cell-adhesion molecules (CEACAMs) with high specificity. We aimed investigate fluorescence targeting CEACAM-expressing colorectal tumors in patient-derived orthotopic xenograft (PDOX) models fluorescently labeled recombinant (rHopQ). Western blotting, flow cytometry and ELISA were performed determine the efficiency rHopQ binding CEACAMs. was conjugated IR800DyeCW (rHopQ-IR800). Nude...

Mycophenolate mofetil (MMF) is a prodrug active only after its hydrolysis to mycophenolic acid (MPA). The UGT1A9 enzyme of special interest since it the main involved in glucuronidation MPA. Single nucleotide polymorphisms (SNPs) gene may be responsible for individual differences pharmacokinetics MMF. Expression levels and activity depend on presence some SNPs located promoter region (-2152C>T -275T>A), as well changes coding (c.98T>C). objective this study was evaluate effect allelic...

________________________________________________________________________________treatment PSA was 7.2 ng/ml (range, 0.8 to 19.9).The overall 3-year biochemical relapse free survival (bRFS) 93.9%.Cox regression identified primary gleason pattern as the only significant predictor of with a HR 5.84 (1.92 17.8, 95% CI) for 4 vs. 3.There no difference in bRFS between patients classified having favorable unfavorable intermediate risk disease, 0.39 (0.11 1.41, CI).There were benefits observed...

Invasive candidiasis is a healthcare-associated fungal infection with high mortality rate. Neutrophils, the first line of defense during infections, express immunoregulatory Candida albicans receptors CEACAM1, CEACAM3, and CEACAM6. We analyzed effects specific antibodies on C. albicans-induced neutrophil responses. CEACAM6 ligation by 1H7-4B to some extent CEACAM1 B3-17, but not CEACAM3 308/3-3, resulted in immediate release stored CXCL8 altered transcriptional responses albicans-stimulated...

<h3>Background</h3> At the time, crystal arthropathies (CA) (e.g. calcium pyrophosphate deposition disease (CPPD) and gout (GA)) can be diagnosed definitely only by microscopic investigation of joint effusion with polarisation filter, especially if clinical aspect is atypical. <h3>Objectives</h3> It known that arthritis (GA) show a typical double contour (DC) sign in ultrasound. Previous studies investigated GA compared non (NCA). But there are no data about sensitivity specificity different...

Abstract Background Type 2 diabetes (T2DM) and obesity are characterized by altered insulin metabolism action. Reduced hepatic clearance is increasingly recognized as a key contributor to hyperinsulinemia resistance. CEACAM1 promotes clearance, its loss in hepatocytes associated with reduced mice men. This study examines whether circulating levels reflect compromised resistance the PREVADIAB2 cohort. Methods A total of 1019 individuals from cohort were evaluated for 75 g‐OGTT classified...

<h3>Background</h3> The cytokine interleukin 33 (IL-33), a member of the IL-1 family, is released in response to various types endothelial or epithelial cell damage. IL-33 constitutively expressed epidermal keratinocytes, upregulated inflamed skin and acts as an endogenous danger signal that mediates recruitment immune cells sites cellular Our preliminary data have shown psoriatic lesions express more nuclear compared perilesional biopsies from same patients mature induces inflammation mouse...