Study animal models with altered lipid storage to identify mechanisms of lipid droplet regulation

International audienc

Natural Proteolytic Processing of Hemofiltrate Cc Chemokine 1 Generates a Potent Cc Chemokine Receptor (Ccr)1 and Ccr5 Agonist with Anti-HIV Properties

Hemofiltrate CC chemokine (HCC)-1 is a recently described human chemokine that is constitutively expressed in numerous tissues and is present at high concentrations in normal plasma. Using a cell line expressing CC chemokine receptor (CCR)5 as a bioassay, we isolated from human hemofiltrate an HCC-1 variant lacking the first eight amino acids. HCC-1[9–74] was a potent agonist of CCR1, CCR3, and CCR5 and promoted calcium flux and chemotaxis of T lymphoblasts, monocytes, and eosinophils. It also blocked entry of HIV-1 strains using CCR5 as coreceptor. Limited tryptic digestion of HCC-1 generated the active variant. Conditioned media from several tumor cell lines activated HCC-1 with a high efficiency, and this activity could be inhibited by serine protease inhibitors. Our results indicate that HCC-1 represents a nonfunctional precursor that can be rapidly converted to the active chemokine by proteolytic processing. This process represents an additional mechanism by which tumor cells might generate chemoattractant molecules and recruit inflammatory cells. It might also affect HIV-1 replication in infected individuals and play an important role in AIDS pathogenesis

Практический опыт развития комплексной системы экологического просвещения в образовательной организации

В статье представлены разработанные и апробированные в образовательной организации новые подходы, механизмы и инструменты по одному из приоритетных направлений развития страны в части формирования экологического культуры вузовской молодежи с целью повышения познавательной активности, уровня экологических знаний в области гармоничного развития человека и природы, устойчивого интереса к экологическим проблемам современности, воспитания и привития бережного отношения к окружающей природе.The article presents new approaches, mechanisms and tools developed and tested in the educational organization in one of the priority directions of the country's development in terms of forming the ecological culture of university youth in order to increase cognitive activity, the level of ecological knowledge in the field of harmonious development of man and nature, and a steady interest in environmental problems of modernity, upbringing and inculcation of respect for nature

Aus Buchwerkstatt und Bibliothek. Manuskriptkulturen des Mittelalters in Orient und Okzident

Handschriften, seien sie Produkte des europäischen Mittelalters oder des vormodernen islamischen Orients, bergen eine Fülle von Informationen über grundlegende kulturelle Praktiken der Alten Welt, die aber auch entschlüsselt sein wollen. In den Fächern, die sich am Zentrum für Mittelalterstudien der Universität Bamberg beteiligen, hat die Beschäftigung mit Manuskripten ihren festen Platz. Unter dem Titel „Manuskriptkulturen des Mittelalters“ wurden im Rahmen der Ringvorlesung des Zentrums für Mittelalterstudien an der Universität Bamberg im Sommersemester 2011 zehn Vorträge gehalten, die sich ganz verschiedenen Aspekten des Themas widmeten. Chronologisch umspannten die Beiträge etwa ein Jahrtausend, geographisch sind sie zwischen dem Atlantik und dem Indischen Ozean angesiedelt. Die in den Vorträgen behandelten Handschriften repräsentieren die verschiedensten Inhalte und literarischen Formen – vom Epos bis zur juristisch-religiösen Traditionssammlung. Dennoch zeigen sich übergreifende Aspekte von Manuskriptkulturen, die sich im spezifischen Umgang mit den Texten und ihren Illustrationen, in den Anforderungen eines Layouts und grafischer Gestaltung niederschlagen. Diese wirkten sich bis weit in die Geschichte des gedruckten Buches aus. Der vorliegende Band enthält sieben Vorträge der Ringvorlesung, die zum Teil wesentlich überarbeitet wurden, sowie einen weiteren Beitrag, der aus einer Abschlussarbeit im Fach Iranistik hervorging

Safe cosmetics without animal testing? Contributions of the EU Project Sens-it-iv

The 7th Ammendment to the Cosmetics Directive of the European Commission (Directive 76/768/EEC2) bans the marketing of cosmetics containing animal-tested ingredients since March 2009. Excepted are only tests for repeated dose toxicity, for which the animal ban will come into effect by 2013. One major concern for cosmetics, i.e. the risk of containing skin (contact) sensitizers, has in the past been addressed almost exclusively by animal testing. It is this problem attracting the central interest of the integrated research project Sens-it-iv (Novel Testing Strategies for in vitro Assessment of Allergens, http://www.sens-it-iv.eu), funded by the EC within framework 6 since October 2005. Here, the 28 Sens-it-iv partners from 10 European States present the 5 most promising types of in vitro assays selected for further refinement. These are: (1) a human epidermal equivalent (EE) model to rank contact allergens according to their sensitizing potency, (2) identification of contact sensitizers, including pro-haptens, through intracellular production of IL-18 by the human keratinocyte cell line NCTC 2544, (3) determination of activation markers such as CD86, CD54 and most prominently CXCL8 (IL-8) on/in dendritic cell lines, (4) contact sensitizer-specific migration of MUTZ Langerhans cells towards the chemokine CXCL12, and (5) the allergen-specific activation and proliferation of na\uefve human T cells. Ongoing genomic and proteomic experiments are in the process of identifying larger sensitizer-specific biological marker signatures to be integrated into the above assays. We hope to supply the European control agencies with a basis for further validation of in vitro assays by the end of 2010

Effects of urodilatin on natriuresis in cirrhosis patients with sodium retention

BACKGROUND: Sodium retention and ascites are serious clinical problems in cirrhosis. Urodilatin (URO) is a peptide with paracrine effects in decreasing sodium reabsorption in the distal nephron. Our aim was to investigate the renal potency of synthetic URO on urine sodium excretion in cirrhosis patients with sodium retention and ascites. METHODS: Seven cirrhosis patients with diuretics-resistant sodium retention received a short-term (90 min) infusion of URO in a single-blind, placebo-controlled cross-over study. In the basal state after rehydration the patients had urine sodium excretion < 50 mmol/24 h. RESULTS: URO transiently increased urine sodium excretion from 22 ± 16 μmol/min (mean ± SD) to 78 ± 41 μmol/min (P < 0.05) and there was no effect of placebo (29 ± 14 to 44 ± 32). The increase of URO's second messenger after the receptor, cGMP, was normal. URO had no effect on urine flow or on blood pressure. Most of the patients had highly elevated plasma levels of renin, angiotensin II and aldosterone and URO did not change these. CONCLUSION: The short-term low-dose URO infusion increased the sodium excretion of the patients. The increase was small but systematic and potentially clinically important for such patients. The small response contrasts the preserved responsiveness of the URO receptors. The markedly activated systemic pressor hormones in cirrhosis evidently antagonized the local tubular effects of URO

MOS11: A New Component in the mRNA Export Pathway

Nucleocytoplasmic trafficking is emerging as an important aspect of plant immunity. The three related pathways affecting plant immunity include Nuclear Localization Signal (NLS)–mediated nuclear protein import, Nuclear Export Signal (NES)–dependent nuclear protein export, and mRNA export relying on MOS3, a nucleoporin belonging to the Nup107–160 complex. Here we report the characterization, identification, and detailed analysis of Arabidopsis modifier of snc1, 11 (mos11). Mutations in MOS11 can partially suppress the dwarfism and enhanced disease resistance phenotypes of snc1, which carries a gain-of-function mutation in a TIR-NB-LRR type Resistance gene. MOS11 encodes a conserved eukaryotic protein with homology to the human RNA binding protein CIP29. Further functional analysis shows that MOS11 localizes to the nucleus and that the mos11 mutants accumulate more poly(A) mRNAs in the nucleus, likely resulting from reduced mRNA export activity. Epistasis analysis between mos3-1 and mos11-1 revealed that MOS11 probably functions in the same mRNA export pathway as MOS3, in a partially overlapping fashion, before the mRNA molecules pass through the nuclear pores. Taken together, MOS11 is identified as a new protein contributing to the transfer of mature mRNA from the nucleus to the cytosol

An introduction to chemokines and their roles in transfusion medicine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74808/1/j.1423-0410.2008.01127.x.pd