Probing the different chaperone activities of the bacterial HSP70-HSP40 system using a thermolabile luciferase substrate.

During mild heat-stress, a native thermolabile polypeptide may partially unfold and transiently expose water-avoiding hydrophobic segments that readily tend to associate into a stable misfolded species, rich in intra-molecular non-native beta-sheet structures. When the concentration of the heat-unfolded intermediates is elevated, the exposed hydrophobic segments tend to associate with other molecules into large stable insoluble complexes, also called "aggregates." In mammalian cells, stress- and mutation-induced protein misfolding and aggregation may cause degenerative diseases and aging. Young cells, however, effectively counteract toxic protein misfolding with a potent network of molecular chaperones that bind hydrophobic surfaces and actively unfold otherwise stable misfolded and aggregated polypeptides. Here, we followed the behavior of a purified, initially mostly native thermolabile luciferase mutant, in the presence or absence of the Escherichia coli DnaK-DnaJ-GrpE chaperones and/or of ATP, at 22 °C or under mild heat-stress. We concomitantly measured luciferase enzymatic activity, Thioflavin-T fluorescence, and light-scattering to assess the effects of temperature and chaperones on the formation, respectively, of native, unfolded, misfolded, and/or of aggregated species. During mild heat-denaturation, DnaK-DnaJ-GrpE+ATP best maintained, although transiently, high luciferase activity and best prevented heat-induced misfolding and aggregation. In contrast, the ATP-less DnaK and DnaJ did not maintain optimal luciferase activity and were less effective at preventing luciferase misfolding and aggregation. We present a model accounting for the experimental data, where native, unfolded, misfolded, and aggregated species spontaneously inter-convert, and in which DnaK-DnaJ-GrpE+ATP specifically convert stable misfolded species into unstable unfolded intermediates.

Health for life : annual report of activities for the period January-December 2013

In Seychelles, cardiovascular diseases (CVD), notably stroke, ischemic heart disease and hypertensive heart disease has become the largest contributor of deaths (40%) in the entire population. CVD also results in a large burden of disability and also has subsequent social and economic impact. The Unit for Prevention and Control of Cardiovascular Diseases (UPCCD) provides leadership, expertise and capacity at national level for the surveillance, prevention and control of cardiovascular diseases through education, programs and input into policy.

Structure-function analyses point to a polynucleotide-accommodating groove essential for APOBEC3A restriction activities.

Members of the human APOBEC3 family of editing enzymes can inhibit various mobile genetic elements. APOBEC3A (A3A) can block the retrotransposon LINE-1 and the parvovirus adeno-associated virus type 2 (AAV-2) but does not inhibit retroviruses. In contrast, APOBEC3G (A3G) can block retroviruses but has only limited effects on AAV-2 or LINE-1. What dictates this differential target specificity remains largely undefined. Here, we modeled the structure of A3A based on its homology with the C-terminal domain of A3G and further compared the sequence of human A3A to those of 11 nonhuman primate orthologues. We then used these data to perform a mutational analysis of A3A, examining its ability to restrict LINE-1, AAV-2, and foreign plasmid DNA and to edit a single-stranded DNA substrate. The results revealed an essential functional role for the predicted single-stranded DNA-docking groove located around the A3A catalytic site. Within this region, amino acid differences between A3A and A3G are predicted to affect the shape of the polynucleotide-binding groove. Correspondingly, transferring some of these A3A residues to A3G endows the latter protein with the ability to block LINE-1 and AAV-2. These results suggest that the target specificity of APOBEC3 family members is partly defined by structural features influencing their interaction with polynucleotide substrates.

Activities of daily living with reverse prostheses: importance of scapular compensation for functional mobility of the shoulder.

HYPOTHESIS: The nonanatomical design of reverse shoulder prostheses induce medial displacement of the center of rotation, impingements and may reduce the mobility of the shoulder. The aim of this study is to test the hypothesis that during activities of daily living functional mobility of the shoulder can be restored by scapular compensation. MATERIAL AND METHODS: A numerical 3-dimensional model was developed to reproduce the movement of the scapula and humerus, during 4 activities of daily living measured experimentally. This hypothesis was tested in 4 configurations of the aequalis reverse prosthesis (standard 36-mm glenosphere, 42-mm glenosphere, lateralized 36-mm glenosphere, lateralized Bony Increased-Offset Reverse Shoulder Arthroplasty [BIO-RSA]), which were implanted in the virtual model. All impingement positions were evaluated, as the required scapular compensation to avoid impingements. RESULTS: With the 36-mm glenosphere, impingements occurred only for rest of hand to back-pocket positions. The 42-mm partly improved the mobility. The 2 lateralized glenospheres were free of impingement. When impingements occurred, the scapular compensation was less than 10°. CONCLUSION: Most reverse prostheses impingements reported in clinical and biomechanical studies can be avoided, either by scapular compensation or by a glenosphere lateralization. After reverse shoulder arthroplasty, a fraction of the mobility of the gleno-humeral is transferred to the scapulo-thoracic joint.

Ambulatory monitoring of physical activities in patients with Parkinson's disease.

A new ambulatory method of monitoring physical activities in Parkinson's disease (PD) patients is proposed based on a portable data-logger with three body-fixed inertial sensors. A group of ten PD patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) and ten normal control subjects followed a protocol of typical daily activities and the whole period of the measurement was recorded by video. Walking periods were recognized using two sensors on shanks and lying periods were detected using a sensor on trunk. By calculating kinematics features of the trunk movements during the transitions between sitting and standing postures and using a statistical classifier, sit-to-stand (SiSt) and stand-to-sit (StSi) transitions were detected and separated from other body movements. Finally, a fuzzy classifier used this information to detect periods of sitting and standing. The proposed method showed a high sensitivity and specificity for the detection of basic body postures allocations: sitting, standing, lying, and walking periods, both in PD patients and healthy subjects. We found significant differences in parameters related to SiSt and StSi transitions between PD patients and controls and also between PD patients with and without STN-DBS turned on. We concluded that our method provides a simple, accurate, and effective means to objectively quantify physical activities in both normal and PD patients and may prove useful to assess the level of motor functions in the latter.

Troubles gastro-intestinaux et activités sportives [Lower intestinal distress during sports activities].

This article reviews the literature regarding gastrointestinal disturbances in particular in runners. The lower intestinal problems of motility and blood loss are discussed. These problems are directly related to running. These symptoms, especially diarrhea are common and can impact adversely both performance and the health of the athlete. Most cases are relatively benign. The sport medicine clinician should be familiar with the management of these problems in order to optimize the treatment and facilitate return to sport.

Nursing Activities Score (NAS) como instrumento para medir carga de trabalho de enfermagem em UTI adulto

Pesquisa de campo, prospectiva, quantitativa, descritiva-exploratória, realizada na UTI geral/adulto de um hospital privado do município de São Paulo. Objetivos: avaliar o NAS - Nursing Activities Score - como medida de carga de trabalho de enfermagem; sua aplicabilidade por turnos e sua correspondência com o quantitativo de enfermagem efetivo. Classificados 33 pacientes: idade média: 70,4 anos (+/-16,5), 66,7% do sexo masculino; permanência média na UTI: 17 dias (+/- 20,4); SAPSII: 41,7 (+/-17,9); risco de morte: (RM) 33,5% (+/- 26,8); 63,6% transferidos para Unidades de Cuidados Semi-Intensivos, 18,2% evoluíram a óbito. Obtiveram-se 396 medidas por turnos (134-manhã; 132-tarde; 130-noturno), média de 55,4 (+/-12,3) e 147 medidas de NAS de 24h, média de 69,6 (+/-18,2). O instrumento mostrou-se mais adequado à aplicação em 24 horas que por turnos, tendendo a refletir o número de profissionais efetivo, revelando-se interessante instrumento de classificação de pacientes e carga de trabalho de enfermagem em terapia intensiva.

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