Myosin Va phosphorylated on ser(1650) is found in nuclear speckles and redistributes to nucleoli upon inhibition of transcription

Nuclear actin and nuclear myosins have been implicated in the regulation of geneexpression in vertebrate cells. Myosin V is a class of actin-based motor proteins involved in cytoplasmic vesicle transport and anchorage, spindle-pole alignment and mRNA translocation. In this study, myosin-Va, phosphorylated on a conserved serine in the tail domain (phospho-ser(1650) MVa), was localized to subnuclear compartments. A monoclonal antibody, 9E6, raised against a peptide corresponding to phosphoserine(1650) and flanking regions of the murine myosin Va sequence, was immunoreactive to myosin Va heavy chain in cellular and nuclear extracts of HeLa cells, PC12 cells and B16-F10 melanocytes. Immunofluorescence microscopy with this antibody revealed discrete irregular spots within the nucleoplasm that colocalized with SC35, a splicing factor that earmarks nuclear speckles. Phospho-ser(1650) MVa was not detected in other nuclear compartments, such as condensed chromatin, Cajal bodies, gems and perinucleolar caps. Although nucleoli also were not labeled by 9E6 under normal conditions, inhibition of transcription in HeLa cells by actinomycin D caused the redistribution of phospho-ser(1650) MVa to nucleoli, as well as separating a fraction of phosphoser(1650) MVa from SC35 into near-neighboring particles. These observations indicate a novel role for myosin Va in nuclear compartmentalization and offer a new lead towards the understanding of actomyosin-based gene regulation.

Protein Intake during Weight Loss Influences the Energy Required for Weight Loss and Maintenance in Cats

The effects of 2 diets with different protein contents on weight loss and subsequent maintenance was assessed in obese cats. The control group [Cc; n = 8; body condition score (BCS) = 8.6 +/- 0.2] received a diet containing 21.4 g crude protein (CP)/MJ of metabolizable energy and the high-protein group (HP; n = 7; BCS = 8.6 +/- 0.2) received a diet containing 28.4 g CP/MJ until the cats achieved a 20% controlled weight loss (0.92 +/- 0.2%/wk). After the weight loss, the cats were all fed a diet containing 28.0 g CP/MJ at an amount sufficient to maintain a constant body weight (MAIN) for 120 d. During weight loss, there was a reduction of lean mass in Cc (P < 0.01) but not in HIP cats and a reduction in leptinemia in both groups (P < 0.01). Energy intake per kilogram of metabolic weight (kg(-0.40)) to maintain the same rate of weight loss was lower (P < 0.04) in the Co (344 +/- 15.9 kJ.kg(-0.40).d(-1)) than in the HP group (377 +/- 12.4 kJ.kg-(0.40).d(-1)). During the first 40 d of MAIN, the energy requirement for weight maintenance was 398.7 +/- 9.7 kJ.kg(-0.40).d(-1) for both groups, corresponding to 73% of the NRC recommendation. The required energy gradually increased in both groups (P < 0.05) but at a faster rate in HP; therefore, the energy consumption during the last 40 d of the MAIN was higher (P < 0.001) for the HP cats (533.8 +/- 7.4 kJ.kg(-0.40).d(-1)) than for the control cats (462.3 +/- 9.6 kJ.kg(-0.40).d(-1)). These findings suggest that HIP diets allow a higher energy intake to weight loss in cats, reducing the intensity of energy restriction. Protein intake also seemed to have long-term effects so that weight maintenance required more energy after weight loss. J. Nutr, 139: 855-860, 2009.

Muscle mass gain observed in patients with short bowel syndrome subjected to resistance training

Few studies are available about the evaluation of resistance training in patients with protein-energy malnutrition. To assess the effects of resistance training on the recovery of nutritional status of patients with short bowel syndrome, with a small bowel remnant of less than 100 cm, 9 patients of both sexes with protein-energy malnutrition after extensive resection of the small bowel were submitted to resistance training of progressive intensity consisting of concentric and eccentric work exercises for the upper limbs, trunk, and lower limbs, with the individuality and limitations of each patients being respected. Food consumption was monitored by 24-hour food recall performed during the initial phase of the study, before and 7 and 14 weeks after physical training, and by a dietary record for a period of 3 days of oral feeding. The nutrients administered by the enteral and parenteral route were recorded. A significant increase in total arm area (P <= .01) and fat-free mass (P <= .01) was observed as determined by computed tomography. An increase in total energy ingestion and carbohydrate consumption (P <= .01) was also observed. In addition, the activity of the enzyme carnosinase was increased after resistance training (P <= .01). The present results show that resistance training in patients with short bowel syndrome and protein-energy malnutrition can be considered to be a part of the nonmedicamentous treatment of these patients, leading to better nutrient use and to a gain of lean mass. (c) 2008 Elsevier Inc. All rights reserved.

Adenosine actions are preserved in corpus cavernosum from obese and type II diabetic db/db mouse

Introduction. Erectile dysfunction (ED) in diabetes is associated with autonomic neuropathy and endothelial dysfunction. Whereas the nonadrenergic-noncholinergic (NANC)/neurogenic nitric oxide pathway has received great attention in diabetes-associated ED, few studies have addressed sympathetic overactivity. Aim. To test the hypothesis that adenosine-induced inhibition of adrenergic-mediated contractile responses in mouse corpus cavernosum is impaired in the presence of diabetes. Methods. The db/db (obesity and type II diabetes caused by a leptin receptor mutation) mouse strain was used as a model of obesity and type II diabetes, and standard procedures were performed to evaluate functional cavernosal responses. Main Outcome Measures. Increased cavernosal responses to sympathetic stimulation in db/db mice are not associated with impaired prejunctional actions of adenosine. Results. Electrical field stimulation (EFS)-, but not phenylephrine (PE)-, induced contractions are enhanced in cavernosal strips from db/db mice in comparison with those from lean littermates. Direct effects of adenosine, 2-chloro-adenosine, A(1) receptor agonist C-8031 (N6 cyclopentyladenosine), and sodium nitroprusside are similar between the strips from lean and db/db mice, whereas relaxant responses to acetylcholine and NANC stimulation are significantly impaired in the cavernosal strips from db/db mice. 5`-Iodotubercidin (adenosine kinase inhibitor) and dipyridamole (inhibitor of adenosine transport), as well as the A(1) agonist C-8031, significantly and similarly inhibit contractions induced by stimulation of adrenergic nerves in the cavernosal strips from lean and db/db mice. Conclusions. Results from this study suggest that corpora cavernosa from obese and diabetic db/db mice display altered neural-mediated responses that would favor penile detumescence, i.e., increased contractile response to adrenergic nerve stimulation and decreased relaxant responses upon activation of NANC nerves. However, increased cavernosal responses to adrenergic nerve stimulation are not due to impaired negative modulation of sympathetic neurotransmission by adenosine in this diabetic model.

Experimental autoimmune encephalomyelitis evolution was not modified by multiple infections with Strongyloides venezuelensis

P>According to the hygiene hypothesis, the increased incidence of allergic and autoimmune diseases in developed countries is mainly explained by the decreased contact between the human population and certain environmental agents as lactobacillus, mycobacteria and helminths. In this study, we evaluated the effect of multiple infections with Strongyloides venezuelensis on the development of experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Multiple infections before EAE induction were not able to change the evolution of the disease. No alterations were observed in weight loss, clinical score and inflammation intensity at the central nervous system. The presence of significant levels of parasite-specific IgG1 but not IgG2b suggested a Th2 polarization. However, the percentage and absolute number of CD4+CD25+Foxp3+ T cells were not changed, being their levels in the spleen and lymph nodes of infected rats comparable to the ones found in normal animals. These results suggest that a Th2-polarized response without concomitant expansion of Foxp3+ regulatory T cells was not able to modify EAE progression. Even though these results do not threaten the hygiene hypothesis, they suggest that this paradigm might be an oversimplification. They also emphasize the need of a study to compare the immunoregulatory ability associated with different helminth spp.

Notes on market failure and the Paretian (Kaldor-Hicks) relevance and irrelevance of unfavourable externalities

The following are notes that have been distributed by me over the last few years to students in Environmental Economics at The University of Queensland. They give particular attention to whether externalities are Pareto or Kaldor-Hicks relevant from a policy point of view. Externalities are Kaldor-Hicks or Pareto irrelevant if no change is possible for which gainers could compensate losers. Both absolute and marginal externalities may be Kaldor-Hicks relevant. Infra-marginal negative externalities are often, but not always, Kaldor-Hicks irrelevant. There are at least two cases where such externalities can be relevant. First, the absolute impact of the negative externality may be so great that the source of the externality should be eliminated. Secondly, if the externality arises from production, its nature may depend on the type of production technique adopted. Although for the technique adopted, an infra-marginal negative externality occurs. That is Paretian irrelevant given that choice of this technique is the only available possibility, alternative techniques may actually be available in practice. Some of these may generate even smaller total external effects and be socially preferable. Both cases are outlined and illustrated in these notes. The analysis reveals the dangers of relying on marginalism for deciding on environmental policy. Total (external) effects are often of great social and economic importance and appropriate social choices cannot be made on the basis of marginalism alone.

Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment

OBJECTIVE: To observe the chronic effects of human growth hormone (hGH) and AOD9604 (a C-terminal fragment of hGH) on body weight, energy balance, and substrate oxidation rates in obese (ob/ob) and lean C57BL/6Jmice. In vitro assays were used to confirm whether the effects of AOD9604 are mediated through the hGH receptor, and if this peptide is capable of cell proliferation via the hGH receptor. METHOD: Obese and lean mice were treated with hGH, AOD or saline for 14 days using mini-osmotic pumps. Body weight, caloric intake, resting energy expenditure, fat oxidation, glucose oxidation, and plasma glucose, insulin and glycerol were measured before and after treatment. BaF-BO3 cells transfected with the hGH receptor were used to measure in Vitro I-125-hGH receptor binding and cell proliferation. RESULTS: Both hGH and AOD significantly reduced body weight gain in obese mice. This was associated with increased in vivo fat oxidation and increased plasma glycerol levels (an index of lipolysis). Unlike hGH, however, AOD9604 did not induce hyperglycaemia or reduce insulin secretion. AOD9604 does not compete for the hGH receptor and nor does it induce cell proliferation, unlike hGH. CONCLUSIONS: Both hGH and its C-terminal fragment reduce body weight gain, increase fat oxidation, and stimulate lipolysis in obese mice, yet AOD9604 does not interact with the hGH receptor. Thus, the concept of hGH behaving as a pro-hormone is further confirmed. This data shows that fragments of hGH can act in a manner novel to traditional hGH-stimulated pathways.

beta-hydroxy-beta-methylbutyrate (HMB) supplementation does not affect changes in strength or body composition during resistance training in trained men

This investigation evaluated the effects of oral beta -Hydroxy-beta -Methylbutyrate (HMB) supplementation on training responses in resistance-trained male athletes who were randomly administered HMB in standard encapsulation (SH), HMB in time release capsule (TRH), or placebo (P) in a double-blind fashion. Subjects ingested 3 g (.) day(-1) of HMB; or placebo for 6 weeks. Tests were conducted pre-supplementation and following 3 and 6 weeks of supplementation. The testing battery assessed body mass, body composition (using dual energy x-ray absorptiometry), and 3-repetition maximum isoinertial strength, plus biochemical parameters, including markers of muscle damage and muscle protein turnover. While the training and dietary intervention of the investigation resulted in significant strength gains (p < .001) and an increase in total lean mass (p =.01), HMB administration had no influence on these variables. Likewise, biochemical markers of muscle protein turnover and muscle damage were also unaffected by HMB supplementation. The data indicate that 6 weeks of HMB supplementation in either SH or TRH form does not influence changes in strength and body composition in response to resistance training in strength-trained athletes.

Timing and magnitude of peak height velocity and peak tissue velocities for early, average, and late maturing boys and girls

Height, weight, and tissue accrual were determined in 60 male and 53 female adolescents measured annually over six years using standard anthropometry and dual-energy X-ray absorptiometry (DXA). Annual velocities were derived, and the ages and magnitudes of peak height and peak tissue velocities were determined using a cubic spline fit to individual data. Individuals were rank ordered on the basis of sex and age at peak height velocity (PHV) and then divided into quartiles: early (lowest quartile), average (middle two quartiles), and late (highest quartile) maturers. Sex- and maturity-related comparisons in ages and magnitudes of peak height and peak tissue velocities were made. Males reached peak velocities significantly later than females for all tissues and had significantly greater magnitudes at peak. The age at PHV was negatively correlated with the magnitude of PHV in both sexes. At a similar maturity point (age at PHV) there were no differences in weight or fat mass among maturity groups in both sexes. Late maturing males, however, accrued more bone mineral and lean mass and were taller at the age of PHV compared to early maturers. Thus, maturational status (early, average, or late maturity) as indicated by age at PHV is inversely related to the magnitude and late maturers for weight and fat mass in boys and girls. Am. J. Hum. Biol. 13:1-8, 2001. (C) 2001 Wiley-Liss, Inc.

Numerical investigations of flow and energy fields near a thermoacoustic couple

The flow field and the energy transport near thermoacoustic couples are simulated using a 2D full Navier-Stokes solver. The thermoacoustic couple plate is maintained at a constant temperature; plate lengths, which are short and long compared with the particle displacement lengths of the acoustic standing waves, are tested. Also investigated are the effects of plate spacing and the amplitude of the standing wave. Results are examined in the form of energy vectors, particle paths, and overall entropy generation rates. These show that a net heat-pumping effect appears only near the edges of thermoacoustic couple plates, within about a particle displacement distance from the ends. A heat-pumping effect can be seen even on the shortest plates tested when the plate spacing exceeds the thermal penetration depth. It is observed that energy dissipation near the plate increases quadratically as the plate spacing is reduced. The results also indicate that there may be a larger scale vortical motion outside the plates which disappears as the plate spacing is reduced. (C) 2002 Acoustical Society of America.

The medicine and epidemiology of bovine respiratory disease in feedlots

Bovine Respiratory Disease (BRD) results from a complex, multifactorial interaction of stressors, animal susceptibility, and respiratory pathogens. The infectious agents associated with BRD are ubiquitous among cattle populations. Typically, one or a combination of stressors are necessary to initiate BRD. Prevention of BRD should, therefore, address management procedures to minimise stressors. Administration of vaccines against BRD agents may help reduce the incidence of BRD but is unlikely to eliminate the condition. The effectiveness of antimicrobials in the treatment of BIRD depends primarily on early recognition and treatment. The use of antioxidant vitamins, minerals or other agents in the prevention and treatment of BRD warrants further research.

In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy

Background/Aims: Host factors such as increased body mass index (BMI) and genotype-specific viral factors contribute to the development of steatosis in patients with chronic hepatitis C (HCV). We hypothesized that host metabolic factors associated with increased BMI may play a role in disease progression. Methods: Fasting serum was collected from 160 patients with chronic HCV at the time of liver biopsy and 45 age, gender and BMI matched controls, and assessed for levels of insulin, c-peptide and leptin. Results: Patients with viral genotype 3 had more severe steatosis (P = 0.0001) and developed stages 1 and 2 fibrosis at a younger age (P < 0.05) than patients with genotype 1. For both genotypes, overweight patients had significantly more steatosis and increased insulin and leptin levels. In contrast to lean patients, there was a statistically significant increase in circulating insulin levels with increasing fibrosis in overweight patients with chronic HCV (P = 0.03). Following multivariate analysis, insulin was independently associated with fibrosis (P = 0.046) but not inflammation (P = 0.83). There was no association between serum leptin levels and stage of fibrosis. Conclusions: Increasing circulating insulin levels may be a factor responsible for the association between BMI and fibrosis in patients with HCV, irrespective of viral genotype. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A pol??tica social que queremos: um embate entre universalismo e focaliza????o

A id??ia de que crescimento econ??mico por si s?? ?? necess??rio, mas n??o suficiente para o desenvolvimento ?? quest??o j?? bastante discutida e acertada no Brasil. Desenvolvimento implica crescimento econ??mico, como tamb??m mudan??as de estrutura n??o apenas no ??mbito econ??mico e produtivo, mas tamb??m no social. ?? nesse contexto que se torna clara a import??ncia da pol??tica social na redu????o das desigualdades e na promo????o do desenvolvimento social do pa??s. Fortemente presente na agenda do atual governo, a quest??o que se coloca para os gestores de pol??ticas p??blicas hoje ??: Qual pol??tica social desejamos? Trata-se de pergunta abrangente que envolve escolhas institucionais, a partir das quais as estruturas de incentivos s??o criadas e condicionam todo o processo de formula????o, implementa????o e avalia????o de pol??ticas.

Análise da fibrose do tecido adiposo de mulheres submetidas à abdominoplastia e cirurgia bariátrica

A fibrose é um acúmulo demasiado de matriz extracelular, resultante de um desequilíbrio entre a síntese e a degradação dos seus componentes. É associada às alterações metabólicas do tecido adiposo, contudo sua ocorrência nos diferentes depósitos e repercussões clínicas ainda não são totalmente compreendidas. O objetivo deste estudo foi analisar a fibrose no tecido adiposo em relação à presença de obesidade, localização do depósito [tecido adiposo subcutâneo abdominal (TASA) e visceral (TAV)] e sua associação a variáveis clínicas. Amostras de gordura do TASA e TAV foram obtidas de 21 mulheres submetidas à cirurgia bariátrica (IMC>40Kg/m2) e 25 amostras de TASA das submetidas à abdominoplastia (IMC<30Kg/m2). As amostras foram processadas para histologia convencional. O corante picrosirius foi utilizado para avaliação das fibras colágenas totais. As imagens obtidas foram analisadas no ADIPOSOFT®. O percentual de fibrose no TASA e no TAV foi analisado com testes estatísticos não paramétricos, adotando-se um valor de p<0,05. A fibrose no TASA foi maior em mulheres com obesidade (p<0.0006). A fibrose entre os depósitos de TASA e de TAV foi observada apenas em mulheres pardas e negras com obesidade (p<0,012). A fibrose no TASA não foi correlacionada com as variáveis clínicas nas mulheres sem obesidade. No entanto, nas submetidas à cirurgia bariátrica, foram observadas correlações da fibrose no TASA com Índice de Massa Corpórea (IMC), hemoglobina glicada (A1c), LDL e triglicerídeos; e no TAV com porcentagem de perda gordura pré-operatório, % de perda de gordura total, % de massa magra pré, Taxa Metabólica Basal (TBM) e Gasto Energético Basal (GEB). Os parâmetros metabólicos e de perfil antropométrico antes da cirurgia bariátrica foram associados à fibrose no TASA, enquanto os parâmetros após a cirurgia foram associados à fibrose no TAV.

A economia da informação : rumo a um programa de pesquisa alternativo

Este trabalho tem por objetivo discutir o surgimento de um programa de pesquisa na Ciência Econômica, no que concerne a análise das assimetrias de informação, as diferenças epistemológicas e as implicações em termos de equilíbrio ótimo de Pareto, em contraponto à abordagem neoclássica standard. Em busca de tal objetivo, foi necessário destacar o método de ambos os paradigmas; todavia, era igualmente necessário discutir a filosofia/epistemologia da ciência envolvida e que serviria de base para uma abordagem relacionada a mudanças paradigmáticas na ciência. No capítulo 1, discutimos a epistemologia da ciência, a partir de três autores: Popper, Kuhn e Lakatos. Definimos o conjunto de hipóteses que podem ser associadas ao método empregado pela Escola Neoclássica, a partir da filosofia da ciência proposta por Lakatos. Em seguida, no capítulo 2, fizemos uma longa exposição do método neoclássico, definindo os axiomas inerentes às preferências bem-comportadas, apresentando algebricamente o equilíbrio geral walrasiano, exemplificando o relaxamento de hipóteses auxiliares do modelo neoclássico a partir de Friedman e, por fim, aplicando o instrumental neoclássico ao relaxamento da hipótese auxiliar de perfeição da informação, a partir do modelo desenvolvido por Grossman & Stiglitz (1976), bem como da expansão matemática desenvolvida pelo presente trabalho. Finalmente, encerramos a presente dissertação com o capítulo 3, no qual, basicamente, expomos as principais contribuições de autores como Stiglitz, Akerlof e Arrow, no que concerne a mercados permeados por informações assimétricas e comportamentos oportunistas. Procuramos mostrar as consequências para o próprio mercado, chegando a resultados em que o mesmo era extinto. Apresentamos a segunda parte do modelo de Grossman & Stiglitz, enfatizando a natureza imperfeita do sistema de preços, sua incapacidade de transmitir todas as informações sobre os bens ao conjunto dos agentes, e, por fim, discutimos tópicos variados ligados à Economia da Informação.