Upper gastrointestinal Crohn's disease

Symptomatic gastroduodenal manifestations of Crohn's disease are rare, with less than 4% of patients being clinically symptomatic. Gastroduodenal involvement may, however, be found endoscopically in 20% and in up to 40% of cases histologically, most frequently as Helicobacter pylori-negative focal gastritis, usually in patients with concomitant distal ileal disease. In practice, the activity of concomitant distal Crohn's disease usually determines the indication for therapy, except in the presence of obstructive gastroduodenal symptoms. With the few data available, it seems correct to say that localized gastroduodenal disease should be treated with standard medical therapy used for more distal disease, with the exception of the galenic formulation of sulfasalazine and mesalazine with pH-dependent release. The presence of symptoms of obstruction needs aggressive therapy. If medical therapy with steroids and immunomodulatory drugs does not alleviate the symptoms, balloon dilation and surgery are the options to consider. [Ed.]]]> oai:serval.unil.ch:BIB_5E8B8CEC2A7F 2022-05-07T01:18:50Z openaire documents urnserval <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_5E8B8CEC2A7F Agniṣṭoma and the nature of sacrifice Bronkhorst, Johannes info:eu-repo/semantics/bookPart incollection 2016 On Meaning and Mantras: Essays in Honor of Frits Staal, pp. 79-99 Thompson, George (ed.) Payne, Richard K. (ed.) info:eu-repo/semantics/altIdentifier/isbn/978-1-886439-64-1 eng https://serval.unil.ch/resource/serval:BIB_5E8B8CEC2A7F.P001/REF.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_5E8B8CEC2A7F4 info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_5E8B8CEC2A7F4 info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/openAccess Copying allowed only for non-profit organizations https://serval.unil.ch/disclaimer application/pdf oai:serval.unil.ch:BIB_5E8C17A3E220 2022-05-07T01:18:50Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_5E8C17A3E220 Selective regulation of acid-sensing ion channel 1 by serine proteases. info:doi:10.1074/jbc.M407381200 info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M407381200 info:eu-repo/semantics/altIdentifier/pmid/15247234 Poirot, O. Vukicevic, M. Boesch, A. Kellenberger, S. info:eu-repo/semantics/article article 2004 Journal of Biological Chemistry, vol. 279, no. 37, pp. 38448-38457 info:eu-repo/semantics/altIdentifier/pissn/0021-9258[print], 0021-9258[linking] <![CDATA[Acid-sensing ion channels (ASICs) are neuronal Na(+) channels that belong to the epithelial Na(+) channel/degenerin family. ASICs are transiently activated by a rapid drop in extracellular pH. Conditions of low extracellular pH, such as ischemia and inflammation in which ASICs are thought to be active, are accompanied by increased protease activity. We show here that serine proteases modulate the function of ASIC1a and ASIC1b but not of ASIC2a and ASIC3. We show that protease exposure shifts the pH dependence of ASIC1a activation and steady-state inactivation to more acidic pH. As a consequence, protease exposure leads to a decrease in current response if ASIC1a is activated by a pH drop from pH 7.4. If, however, acidification occurs from a basal pH of approximately 7, protease-exposed ASIC1a shows higher activity than untreated ASIC1a. We provide evidence that this bi-directional regulation of ASIC1a function also occurs in neurons. Thus, we have identified a mechanism that modulates ASIC function and may allow ASIC1a to adapt its gating to situations of persistent extracellular acidification

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Terrestrial support of lake food webs: Synthesis reveals controls over cross-ecosystem resource use

Widespread evidence that organic matter exported from terrestrial into aquatic ecosystems supports recipient food webs remains controversial. A pressing question is not only whether high terrestrial support is possible but also what the general conditions are under which it arises. We assemble the largest data set, to date, of the isotopic composition (δ$^{2}$H, δ$^{13}$C, and δ$^{15}$N) of lake zooplankton and the resources at the base of their associated food webs. In total, our data set spans 559 observations across 147 lakes from the boreal to subtropics. By predicting terrestrial resource support from within-lake and catchment-level characteristics, we found that half of all consumer observations that is, the median were composed of at least 42% terrestrially derived material. In general, terrestrial support of zooplankton was greatest in lakes with large physical and hydrological connections to catchments that were rich in aboveground and belowground organic matter. However, some consumers responded less strongly to terrestrial resources where within-lake production was elevated. Our study shows that multiple mechanisms drive widespread cross-ecosystem support of aquatic consumers across Northern Hemisphere lakes and suggests that changes in terrestrial landscapes will influence ecosystem processes well beyond their boundaries.Support to organize the working group that produced this manuscript came from Natural Environment Research Council grant NE/M005968/1. B.W.K. also received travel support from the Natural Sciences and Engineering Research Council of Canada Collaborative Research and Training Experiencein Biodiversity Research at the University of British Columbia. J.K. received funding from the Swedish Research Council (2012–2015, funding number 621-2011-3908). M.L.P. acknowledges funding from the NSF Division of Environmental Biology (grant number 1456151)

Terrestrial support of lake food webs: Synthesis reveals controls over cross-ecosystem resource use

Widespread evidence that organic matter exported from terrestrial into aquatic ecosystems supports recipient food webs remains controversial. A pressing question is not only whether high terrestrial support is possible but also what the general conditions are under which it arises. We assemble the largest data set, to date, of the isotopic composition (δ$^{2}$H, δ$^{13}$C, and δ$^{15}$N) of lake zooplankton and the resources at the base of their associated food webs. In total, our data set spans 559 observations across 147 lakes from the boreal to subtropics. By predicting terrestrial resource support from within-lake and catchment-level characteristics, we found that half of all consumer observations that is, the median were composed of at least 42% terrestrially derived material. In general, terrestrial support of zooplankton was greatest in lakes with large physical and hydrological connections to catchments that were rich in aboveground and belowground organic matter. However, some consumers responded less strongly to terrestrial resources where within-lake production was elevated. Our study shows that multiple mechanisms drive widespread cross-ecosystem support of aquatic consumers across Northern Hemisphere lakes and suggests that changes in terrestrial landscapes will influence ecosystem processes well beyond their boundaries.Support to organize the working group that produced this manuscript came from Natural Environment Research Council grant NE/M005968/1. B.W.K. also received travel support from the Natural Sciences and Engineering Research Council of Canada Collaborative Research and Training Experiencein Biodiversity Research at the University of British Columbia. J.K. received funding from the Swedish Research Council (2012–2015, funding number 621-2011-3908). M.L.P. acknowledges funding from the NSF Division of Environmental Biology (grant number 1456151)

Culture-Independent Microbiological Analysis of Foley Urinary Catheter Biofilms

Background: Prevention of catheter-associated urinary tract infection (CAUTI), a leading cause of nosocomial disease, is complicated by the propensity of bacteria to form biofilms on indwelling medical devices [1,2,3,4,5]. Methodology/Principal Findings: To better understand the microbial diversity of these communities, we report the results of a culture-independent bacterial survey of Foley urinary catheters obtained from patients following total prostatectomy. Two patient subsets were analyzed, based on treatment or no treatment with systemic fluoroquinolone antibiotics during convalescence. Results indicate the presence of diverse polymicrobial assemblages that were most commonly observed in patients who did not receive systemic antibiotics. The communities typically contained both Gram-positive and Gramnegative microorganisms that included multiple potential pathogens. Conclusion/Significance: Prevention and treatment of CAUTI must take into consideration the possible polymicrobial nature of any particular infection

Critical Early Roles for col27a1a and col27a1b in Zebrafish Notochord Morphogenesis, Vertebral Mineralization and Post-embryonic Axial Growth

Fibrillar collagens are well known for their links to human diseases, with which all have been associated except for the two most recently identified fibrillar collagens, type XXIV collagen and type XXVII collagen. To assess functions and potential disease phenotypes of type XXVII collagen, we examined its roles in zebrafish embryonic and post-embryonic development.We identified two type XXVII collagen genes in zebrafish, col27a1a and col27a1b. Both col27a1a and col27a1b were expressed in notochord and cartilage in the embryo and early larva. To determine sites of type XXVII collagen function, col27a1a and col27a1b were knocked down using morpholino antisense oligonucleotides. Knockdown of col27a1a singly or in conjunction with col27a1b resulted in curvature of the notochord at early stages and formation of scoliotic curves as well as dysmorphic vertebrae at later stages. These defects were accompanied by abnormal distributions of cells and protein localization in the notochord, as visualized by transmission electron microscopy, as well as delayed vertebral mineralization as detected histologically.Together, our findings indicate a key role for type XXVII collagen in notochord morphogenesis and axial skeletogenesis and suggest a possible human disease phenotype

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation

<p>Abstract</p> <p>Background</p> <p>Ribonucleases are promising agents for use in anticancer therapy. Among the different ribonucleases described to be cytotoxic, a paradigmatic example is onconase which manifests cytotoxic and cytostatic effects, presents synergism with several kinds of anticancer drugs and is currently in phase II/III of its clinical trial as an anticancer drug against different types of cancer. The mechanism of cytotoxicity of PE5, a variant of human pancreatic ribonuclease carrying a nuclear localization signal, has been investigated and compared to that of onconase.</p> <p>Methods</p> <p>Cytotoxicity was measured by the MTT method and by the tripan blue exclusion assay. Apoptosis was assessed by flow cytometry, caspase enzymatic detection and confocal microscopy. Cell cycle phase analysis was performed by flow cytometry. The expression of different proteins was analyzed by western blot.</p> <p>Results</p> <p>We show that the cytotoxicity of PE5 is produced through apoptosis, that it does not require the proapoptotic activity of p53 and is not prevented by the multiple drug resistance phenotype. We also show that PE5 and onconase induce cell death at the same extent although the latter is also able to arrest the cell growth. We have compared the cytotoxic effects of both ribonucleases in the NCI/ADR-RES cell line by measuring their effects on the cell cycle, on the activation of different caspases and on the expression of different apoptosis- and cell cycle-related proteins. PE5 increases the number of cells in S and G₂/M cell cycle phases, which is accompanied by the increased expression of cyclin E and p21^WAF1/CIP1together with the underphosphorylation of p46 forms of JNK. Citotoxicity of onconase in this cell line does not alter the cell cycle phase distribution and it is accompanied by a decreased expression of XIAP</p> <p>Conclusions</p> <p>We conclude that PE5 kills the cells through apoptosis associated with the p21^WAF1/CIP1induction and the inactivation of JNK. This mechanism is significantly different from that found for onconase.</p

The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder

Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study