REST/NRSF governs the expression of dense-core vesicle gliosecretion in astrocytes.

Astrocytes are the brain nonnerve cells that are competent for gliosecretion, i.e., for expression and regulated exocytosis of clear and dense-core vesicles (DCVs). We investigated whether expression of astrocyte DCVs is governed by RE-1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), the transcription repressor that orchestrates nerve cell differentiation. Rat astrocyte cultures exhibited high levels of REST and expressed neither DCVs nor their markers (granins, peptides, and membrane proteins). Transfection of a dominant-negative construct of REST induced the appearance of DCVs filled with secretogranin 2 and neuropeptide Y (NPY) and distinct from other organelles. Total internal reflection fluorescence analysis revealed NPY-monomeric red fluorescent protein-labeled DCVs to undergo Ca(2+)-dependent exocytosis, which was largely prevented by botulinum toxin B. In the I-II layers of the human temporal brain cortex, all neurons and microglia exhibited the expected inappreciable and high levels of REST, respectively. In contrast, astrocyte REST was variable, going from inappreciable to high, and accompanied by a variable expression of DCVs. In conclusion, astrocyte DCV expression and gliosecretion are governed by REST. The variable in situ REST levels may contribute to the well-known structural/functional heterogeneity of astrocytes.

Immune response to hepatitis B vaccination in HIV-positive adults with isolated antibodies to HBV core antigen.

OBJECTIVE: To investigate the merits of vaccination against hepatitis B virus (HBV) in HIV-positive individuals with isolated antibodies to hepatitis B core antigen (anti-HBc). METHODS: HIV-positive patients with isolated anti-HBc and CD4 counts >200 cells/mm(3) received HBV vaccination. An antibody titre to hepatitis B surface antigen (anti-HBs titres) ≥10 IU/L one month post-vaccination was termed an anamnestic response; a titre <10 IU/L was termed a primary response. Patients with primary responses received a 3-dose vaccine course. Anti-HBs titres in all responders were measured 12 and 24 months post-vaccination. RESULTS: 37 patients were studied: 19 (51%) were co-infected with hepatitis C; median CD4 count was 443 cells/mm(3). 8/37 patients (22%) elicited an anamnestic response. 29/37 patients (78%) elicited a primary response. After a 3-dose vaccine course, 15/25 primary responders (60%) achieved anti-HBs titres ≥10 IU/L. HIV acquisition through injecting drug use was the only independent predictor of an anamnestic response (OR 22.9, CI 1.71-306.74, P=0.018). Median anti-HBs titres for anamnestic and primary responders were 51 IU/L (13-127) and 157 IU/L (25-650) respectively. Of all responders, 12/23 (52%) retained anti-HBs titres ≥10 IU/L at 24 months. Anti-HBs duration was not significantly different between anamnestic and primary responders. CONCLUSIONS: 23/37 HIV-positive patients (62%) with isolated anti-HBc achieved anti-HBs titres ≥10 IU/L after 1-3 vaccine doses. However, duration of this immune response was short-lived (

Regulation of c-fos expression by RNA polymerase elongation competence.

The molecular mechanisms underlying transcription elongation and their role in gene regulation are poorly characterized in eukaryotes. A number of genes, however, have been proposed to be regulated at the level of transcription elongation, including c-myc, c-fos and c-myb. Here, we analyze the control of transcription elongation at the mouse c-fos gene at the nucleotide level in intact cells. We find that RNA polymerases are engaged in the promoter-proximal part of the gene in the absence of gene activation signals and mRNA synthesis. Importantly, we determine that the engaged RNA polymerases originate from a continuous initiation of transcription which, in the absence of gene activation signals, terminate close to the promoter. We also observe that the c-fos gene presents an active chromatin conformation, with the promoter and upstream regulatory sequences constitutively occupied by proteins, accounting for the continuous initiation of RNA polymerase complexes. We propose that activation of c-fos gene expression results primarily from the assembly of elongation-competent RNA polymerases that can transcribe the complete gene. Our results suggest that the engaged RNA polymerases found downstream of a number of other eukaryotic promoters may be associated with transcription termination of elongation-incompetent polymerases in the absence of activating signals.

Aprendiendo coreano : Desenvolupament d'una aplicació Android per a l'aprenentatge de coreà

Aquest projecte consisteix en el desenvolupament d'una aplicació per a dispositius mòbils que facilita l'aprenentatge de coreà per a estudiants castellanoparlants.

Correlates of frailty, prediction of functional decline and preventative approaches - selected results from the lausanne cohort 65+ (lc65+) study (Switzerland) (Lausanne) and the longitudinal urban cohort ageing study (Lucas) (Germany)

Overall introduction.- Longitudinal studies have been designed to investigate prospectively, from their beginning, the pathway leading from health to frailty and to disability. Knowledge about determinants of healthy ageing and health behaviour (resources) as well as risks of functional decline is required to propose appropriate preventative interventions. The functional status in older people is important considering clinical outcome in general, healthcare need and mortality. Part I.- Results and interventions from lucas (longitudinal urban cohort ageing study). Authors.- J. Anders, U. Dapp, L. Neumann, F. Pröfener, C. Minder, S. Golgert, A. Daubmann, K. Wegscheider,. W. von Renteln-Kruse Methods.- The LUCAS core project is a longitudinal cohort of urban community-dwelling people 60 years and older, recruited in 2000/2001. Further LUCAS projects are cross-sectional comparative and interventional studies (RCT). Results.- The emphasis will be on geriatric medical care in a population-based approach, discussing different forms of access, too. (Dapp et al. BMC Geriatrics 2012, 12:35; http://www.biomedcentral.com/1471-2318/12/35): - longitudinal data from the LUCAS urban cohort (n = 3.326) will be presented covering 10 years of observation, including the prediction of functional decline, need of nursing care, and mortality by using a self-filling screening tool; - interventions to prevent functional decline do focus on first (pre-clinical) signs of pre-frailty before entering the frailty-cascade ("Active Health Promotion in Old Age", "geriatric mobility centre") or disability ("home visits"). Conclusions.- The LUCAS research consortium was established to study particular aspects of functional competence, its changes with ageing, to detect pre-clinical signs of functional decline, and to address questions on how to maintain functional competence and to prevent adverse outcome in different settings. The multidimensional data base allows the exploration of several further questions. Gait performance was exmined by GAITRite®-System. Supported by the Federal Ministry for Education and Research (BMBF Funding No. 01ET1002A). Part II.- Selected results from the lausanne cohort 65+ (Lc65 + ) Study (Switzerland). Authors.- Prof Santos-Eggimann Brigitte, Dr Seematter-Bagnoud Laurence, Prof Büla Christophe, Dr Rochat Stéphane. Methods.- The Lc65+ cohort was launched in 2004 with the random selection of 3054 eligible individuals aged 65 to 70 (birth year 1934-1938) in the non-institutionalized population of Lausanne (Switzerland). Results.- Information is collected about life course social and health-related events, socio-economics, medical and psychosocial dimensions, lifestyle habits, limitations in activities of daily living, mobility impairments, and falls. Gait performance are objectively measured using body-fixed sensors. Frailty is assessed using Fried's frailty phenotype. Follow-up consists in annual self-completed questionnaires, as well as physical examination and physical and mental performance tests every three years. - Lausanne cohort 65+ (Lc65 + ): design and longitudinal outcomes. The baseline data collection was completed among 1422 participants in 2004-2005 through self-completed questionnaires, face-to-face interviews, physical examination and tests of mental and physical performances. Information about institutionalization, self-reported health services utilization, and death is also assessed. An additional random sample (n = 1525) of 65-70 years old subjects was recruited in 2009 (birth year 1939-1943). - lecture no 4: alcohol intake and gait parameters: prevalent and longitudinal association in the Lc65+ study. The association between alcohol intake and gait performance was investigated.

Stress reaction of kidney epithelial cells to inorganic solid-core nanoparticles.

A route of accumulation and elimination of therapeutic engineered nanoparticles (NPs) may be the kidney. Therefore, the interactions of different solid-core inorganic NPs (titanium-, silica-, and iron oxide-based NPs) were studied in vitro with the MDCK and LLC-PK epithelial cells as representative cells of the renal epithelia. Following cell exposure to the NPs, observations include cytotoxicity for oleic acid-coated iron oxide NPs, the production of reactive oxygen species for titanium dioxide NPs, and cell depletion of thiols for uncoated iron oxide NPs, whereas for silica NPs an apparent rapid and short-lived increase of thiol levels in both cell lines was observed. Following cell exposure to metallic NPs, the expression of the tranferrin receptor/CD71 was decreased in both cells by iron oxide NPs, but only in MDCK cells by titanium dioxide NPs. The tight association, then subsequent release of NPs by MDCK and LLC-PK kidney epithelial cells, showed that following exposure to the NPs, only MDCK cells could release iron oxide NPs, whereas both cells released titanium dioxide NPs. No transfer of any solid-core NPs across the cell layers was observed.

Scientific value of systematic reviews: survey of editors of core clinical journals.

BACKGROUND: Synthesizing research evidence using systematic and rigorous methods has become a key feature of evidence-based medicine and knowledge translation. Systematic reviews (SRs) may or may not include a meta-analysis depending on the suitability of available data. They are often being criticised as 'secondary research' and denied the status of original research. Scientific journals play an important role in the publication process. How they appraise a given type of research influences the status of that research in the scientific community. We investigated the attitudes of editors of core clinical journals towards SRs and their value for publication.¦METHODS: We identified the 118 journals labelled as "core clinical journals" by the National Library of Medicine, USA in April 2009. The journals' editors were surveyed by email in 2009 and asked whether they considered SRs as original research projects; whether they published SRs; and for which section of the journal they would consider a SR manuscript.¦RESULTS: The editors of 65 journals (55%) responded. Most respondents considered SRs to be original research (71%) and almost all journals (93%) published SRs. Several editors regarded the use of Cochrane methodology or a meta-analysis as quality criteria; for some respondents these criteria were premises for the consideration of SRs as original research. Journals placed SRs in various sections such as "Review" or "Feature article". Characterization of non-responding journals showed that about two thirds do publish systematic reviews.¦DISCUSSION: Currently, the editors of most core clinical journals consider SRs original research. Our findings are limited by a non-responder rate of 45%. Individual comments suggest that this is a grey area and attitudes differ widely. A debate about the definition of 'original research' in the context of SRs is warranted.

On the monotonic core

The monotonic core of a cooperative game with transferable utility (T.U.-game) is the set formed by all its Population Monotonic Allocation Schemes. In this paper we show that this set always coincides with the core of a certain game associated to the initial game.

On the dimension of the core of the assignment game

The set of optimal matchings in the assignment matrix allows to define a reflexive and symmetric binary relation on each side of the market, the equal-partner binary relation. The number of equivalence classes of the transitive closure of the equal-partner binary relation determines the dimension of the core of the assignment game. This result provides an easy procedure to determine the dimension of the core directly from the entries of the assignment matrix and shows that the dimension of the core is not as much determined by the number of optimal matchings as by their relative position in the assignment matrix.

Multi-sided Böhm-Bawerk assignment markets: the nucleolus and the core-center

En aquest treball mostrem que, a diferència del cas bilateral, per als mercats multilaterals d'assignació coneguts amb el nom de Böhm-Bawerk assignment games, el nucleolus i el core-center, i. e. el centre de masses del core, no coincideixen en general. Per demostrar-ho provem que donant un m-sided Böhm-Bawerk assignment game les dues solucions anteriors poden obtenir-se respectivament del nucleolus i el core-center d'un joc convex definit en el conjunt format pels m sectors. Encara més, provem que per calcular el nucleolus d'aquest últim joc només les coalicions formades per un jugador o m-1 jugadors són importants. Aquests resultats simplifiquen el càlcul del nucleolus d'un multi-sided ¿¿ohm-Bawerk assignment market amb un número molt elevat d'agents.

The Lorenz-maximal core allocations and the kernel in some classes of assignment games

En aquest treball demostrem que en la classe de jocs d'assignació amb diagonal dominant (Solymosi i Raghavan, 2001), el repartiment de Thompson (que coincideix amb el valor tau) és l'únic punt del core que és maximal respecte de la relació de dominància de Lorenz, i a més coincideix amb la solucié de Dutta i Ray (1989), també coneguda com solució igualitària. En segon lloc, mitjançant una condició més forta que la de diagonal dominant, introduïm una nova classe de jocs d'assignació on cada agent obté amb la seva parella òptima almenys el doble que amb qualsevol altra parella. Per aquests jocs d'assignació amb diagonal 2-dominant, el repartiment de Thompson és l'únic punt del kernel, i per tant el nucleolo.