The Salmonella effector SseJ disrupts microtubule dynamics when ectopically expressed in Normal Rat Kidney cells

Salmonella effector protein SseJ is secreted by Salmonella into the host cell cytoplasm where it can then modify host cell processes. Whilst host cell small GTPase RhoA has previously been shown to activate the acyl-transferase activity of SseJ we show here an un-described effect of SseJ protein production upon microtubule dynamism. SseJ prevents microtubule collapse and this is independent of SseJ's acyl-transferase activity. We speculate that the effects of SseJ on microtubules would be mediated via its known interactions with the small GTPases of the Rho family

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Niclosamide Prevents the Formation of Large Ubiquitin-Containing Aggregates Caused by Proteasome Inhibition

Protein aggregation is a hallmark of many neurodegenerative diseases and has been linked to the failure to degrade misfolded and damaged proteins. In the cell, aberrant proteins are degraded by the ubiquitin proteasome system that mainly targets short-lived proteins, or by the lysosomes that mostly clear long-lived and poorly soluble proteins. Both systems are interconnected and, in some instances, autophagy can redirect proteasome substrates to the lysosomes.To better understand the interplay between these two systems, we established a neuroblastoma cell population stably expressing the GFP-ubiquitin fusion protein. We show that inhibition of the proteasome leads to the formation of large ubiquitin-containing inclusions accompanied by lower solubility of the ubiquitin conjugates. Strikingly, the formation of the ubiquitin-containing aggregates does not require ectopic expression of disease-specific proteins. Moreover, formation of these focused inclusions caused by proteasome inhibition requires the lysine 63 (K63) of ubiquitin. We then assessed selected compounds that stimulate autophagy and found that the antihelmintic chemical niclosamide prevents large aggregate formation induced by proteasome inhibition, while the prototypical mTORC1 inhibitor rapamycin had no apparent effect. Niclosamide also precludes the accumulation of poly-ubiquitinated proteins and of p62 upon proteasome inhibition. Moreover, niclosamide induces a change in lysosome distribution in the cell that, in the absence of proteasome activity, may favor the uptake into lysosomes of ubiquitinated proteins before they form large aggregates.Our results indicate that proteasome inhibition provokes the formation of large ubiquitin containing aggregates in tissue culture cells, even in the absence of disease specific proteins. Furthermore our study suggests that the autophagy-inducing compound niclosamide may promote the selective clearance of ubiquitinated proteins in the absence of proteasome activity

Liver alanine aminotransferase, insulin resistance and endothelial dysfunction in normotriglyceridaemic subjects with type 2 diabetes mellitus

and -0.31 [-0.58 to -0.03] respectively). Conclusions In metabolically well-controlled patients with DM2, ALT levels are related to decreased insulin-sensitivity and an impaired conduit vessel vascular function. Eur J Clin Invest 2005; 35(6): 369 -37

Efeito de um programa de condicionamento físico no broncoespasmo induzido pelo exercício em mulheres obesas Effect of a physical fitness program on the exercise-induced bronchospasm in obese women

O broncoespasmo induzido pelo exercício físico (BIE) é uma síndrome clínica caracterizada pelo estreitamento brônquico e ocorre mais frequentemente em indivíduos obesos. OBJETIVO: Avaliar o possível efeito de um programa de condicionamento físico em relação ao BIE em mulheres obesas. MÉTODOS: Trinta e duas mulheres foram divididas em três grupos: grupo A (obesidade ou sobrepeso + treinamento físico), grupo B (obesidade ou sobrepeso) e grupo C (controle). Foi aplicado um teste de caminhada de seis minutos antes e após um período de 12 semanas. O BIE foi verificado por meio de um monitor de pico de fluxo expiratório após a aplicação do teste de caminhada. Durante essas 12 semanas, para o grupo A um programa de atividade física foi conduzido três vezes por semana e cada sessão de 60 minutos foi composta por 10 minutos de alongamento, seguidos por 30 de exercícios aeróbios (50% da frequência cardíaca de reserva como intensidade), 15 de exercícios de força de baixa intensidade e cinco de relaxamento e alongamento. RESULTADOS: O programa de treinamento físico causou aumento significativo no pico de fluxo expiratório mínimo após o teste de esforço (pré: 379 ± 16l/min; pós: 405 ± 12l/min; p < 0,05) e reduziu em 50% (33% para 17%) a proporção de mulheres que apresentou BIE (p < 0,05). CONCLUSÃO: O programa de condicionamento físico de 12 semanas foi capaz de melhorar a função respiratória de mulheres obesas.<br>Exercise-induced bronchospasm (EIB) is a syndrome characterized by reduced bronchial lumen and happens more often in obese subjects. OBJECTIVE: To evaluate the possible effect of an exercise training program on EIB in obese women. METHODS: 32 women were divided in three groups: group A (obesity + exercise training), group B (obesity) and group C (control). A six-minute walking test was applied before and after 12 weeks. EIB was measured through a monitor of peak of expiratory flow used after the application of the walking test. During the12 weeks, an exercise training program was delivered to group A, three times a week, 60 minutes a day. Each exercise session consisted of 10 minutes of stretching exercises, followed by 30 minutes of aerobic exercise (50% of reserve heart rate as intensity), 15' of low-intensity strength training and 5' of stretching and relaxing exercises. RESULTS: Exercise training significantly increased minimum peak of expiratory flow after the walking test (before: 379±16 l/min; after: 405±12 l/min; p<0.05) and reduced in 50% (33% to 17%) the proportion of women who presented EIB (p<0.05). CONCLUSION: The 12-week exercise training increased the respiratory function of obese women