On the vibron dressing in the α\alpha--helicoidal macromolecular chains

We present a study of the physical properties of the vibrational excitation in $\alpha$--helicoidal macromolecular chains, caused by the interaction with acoustical and optical phonon modes. The influence of the temperature and the basic system parameters on the vibron dressing has been analyzed by employing the simple mean--field approach based on the variational extension of the Lang--Firsov unitary transformation. Applied approach predicts a region in system parameter space where one takes place an abrupt transition from partially dressed (light and mobile) to fully dressed (immobile) vibron states. We found that the boundary of this region depends on system temperature and type of bond among structural elements in the macromolecular chain.Comment: 22 pages, 12 figures, title changed, the interaction with optical phonon modes jointly with acoustical ones added, consideration significantly enlarged, references added, the paper develops the results of arxiv:1210.3918, accepted for publication in Chinese Physics

Exercise training increases mitochondrial content and ex vivo mitochondrial function similarly in patients with type 2 diabetes and in control individuals

AIMS/HYPOTHESIS: We previously showed that type 2 diabetic patients are characterised by compromised intrinsic mitochondrial function. Here, we examined if exercise training could increase intrinsic mitochondrial function in diabetic patients compared with control individuals. METHODS: Fifteen male type 2 diabetic patients and 14 male control individuals matched for age, BMI and [Formula: see text] enrolled in a 12 week exercise intervention programme. Ex vivo mitochondrial function was assessed by high-resolution respirometry in permeabilised muscle fibres from vastus lateralis muscle. Before and after training, insulin-stimulated glucose disposal was examined during a hyperinsulinaemic-euglycaemic clamp. RESULTS: Diabetic patients had intrinsically lower ADP-stimulated state 3 respiration and lower carbonyl cyanide 4-(trifluoro-methoxy)phenylhydrazone (FCCP)-induced maximal oxidative respiration, both on glutamate and on glutamate and succinate, and in the presence of palmitoyl-carnitine (p < 0.05). After training, diabetic patients and control individuals showed increased state 3 respiration on the previously mentioned substrates (p < 0.05); however, an increase in FCCP-induced maximal oxidative respiration was observed only in diabetic patients (p < 0.05). The increase in mitochondrial respiration was accompanied by a 30% increase in mitochondrial content upon training (p < 0.01). After adjustment for mitochondrial density, state 3 and FCCP-induced maximal oxidative respiration were similar between groups after training. Improvements in mitochondrial respiration were paralleled by improvements in insulin-stimulated glucose disposal in diabetic patients, with a tendency for this in control individuals. CONCLUSIONS/INTERPRETATION: We confirmed lower intrinsic mitochondrial function in diabetic patients compared with control individuals. Diabetic patients increased their mitochondrial content to the same extent as control individuals and had similar intrinsic mitochondrial function, which occurred parallel with improved insulin sensitivity

Measurement properties of the Minimal Insomnia Symptom Scale (MISS) in an elderly population in Sweden

<p>Abstract</p> <p>Background</p> <p>Insomnia is common among elderly people and associated with poor health. The Minimal Insomnia Symptom Scale (MISS) is a three item screening instrument that has been found to be psychometrically sound and capable of identifying insomnia in the general population (20-64 years). However, its measurement properties have not been studied in an elderly population. Our aim was to test the measurement properties of the MISS among people aged 65 + in Sweden, by replicating the original study in an elderly sample.</p> <p>Methods</p> <p>Data from a cross-sectional survey of 548 elderly individuals were analysed in terms of assumptions of summation of items, floor/ceiling effects, reliability and optimal cut-off score by means of ROC-curve analysis and compared with self-reported insomnia criteria.</p> <p>Results</p> <p>Corrected item-total correlations ranged between 0.64-0.70, floor/ceiling effects were 6.6/0.6% and reliability was 0.81. ROC analysis identified the optimal cut-off score as ≥7 (sensitivity, 0.93; specificity, 0.84; positive/negative predictive values, 0.256/0.995). Using this cut-off score, the prevalence of insomnia in the study sample was 21.7% and most frequent among women and the oldest old.</p> <p>Conclusions</p> <p>Data support the measurement properties of the MISS as a possible insomnia screening instrument for elderly persons. This study make evident that the MISS is useful for identifying elderly people with insomnia-like sleep problems. Further studies are needed to assess its usefulness in identifying clinically defined insomnia.</p

Vulnerability to high risk sexual behaviour (HRSB) following exposure to war trauma as seen in post-conflict communities in eastern uganda: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Much of the literature on the relationship between conflict-related trauma and high risk sexual behaviour (HRSB) often focuses on refugees and not mass in-country displaced people due to armed conflicts. There is paucity of research about contexts underlying HRSB and HIV/AIDS in conflict and post-conflict communities in Uganda. Understanding factors that underpin vulnerability to HRSB in post-conflict communities is vital in designing HIV/AIDS prevention interventions. We explored the socio-cultural factors, social interactions, socio-cultural practices, social norms and social network structures that underlie war trauma and vulnerability to HRSB in a post-conflict population.</p> <p>Methods</p> <p>We did a cross-sectional qualitative study of 3 sub-counties in <it>Katakwi </it>district and 1 in <it>Amuria </it>in Uganda between March and May 2009. We collected data using 8 FGDs, 32 key informant interviews and 16 in-depth interviews. We tape-recorded and transcribed the data. We followed thematic analysis principles to manage, analyse and interpret the data. We constantly identified and compared themes and sub-themes in the dataset as we read the transcripts. We used illuminating verbatim quotations to illustrate major findings.</p> <p>Results</p> <p>The commonly identified HRSB behaviours include; transactional sex, sexual predation, multiple partners, early marriages and forced marriages. Breakdown of the social structure due to conflict had resulted in economic destruction and a perceived soaring of vulnerable people whose propensity to HRSB is high. Dishonour of sexual sanctity through transactional sex and practices like incest mirrored the consequence of exposure to conflict. HRSB was associated with concentration of people in camps where idleness and unemployment were the norm. Reports of girls and women who had been victims of rape and defilement by men with guns were common. Many people were known to have started to display persistent worries, hopelessness, and suicidal ideas and to abuse alcohol.</p> <p>Conclusions</p> <p>The study demonstrated that conflicts disrupt the socio-cultural set up of communities and destroy sources of people's livelihood. Post-conflict socio-economic reconstruction needs to encompass programmes that restructure people's morals and values through counselling. HIV/AIDS prevention programming in post-conflict communities should deal with socio-cultural disruptions that emerged during conflicts. Some of the disruptions if not dealt with, could become normalized yet they are predisposing factors to HRSB. Socio-economic vulnerability as a consequence of conflict seemed to be associated with HRSB through alterations in sexual morality. To pursue safer sexual health choices, people in post-conflict communities need life skills.</p

The Mycobacterium tuberculosis Drugome and Its Polypharmacological Implications

We report a computational approach that integrates structural bioinformatics, molecular modelling and systems biology to construct a drug-target network on a structural proteome-wide scale. The approach has been applied to the genome of Mycobacterium tuberculosis (M.tb), the causative agent of one of today's most widely spread infectious diseases. The resulting drug-target interaction network for all structurally characterized approved drugs bound to putative M.tb receptors, we refer to as the ‘TB-drugome’. The TB-drugome reveals that approximately one-third of the drugs examined have the potential to be repositioned to treat tuberculosis and that many currently unexploited M.tb receptors may be chemically druggable and could serve as novel anti-tubercular targets. Furthermore, a detailed analysis of the TB-drugome has shed new light on the controversial issues surrounding drug-target networks [1]–[3]. Indeed, our results support the idea that drug-target networks are inherently modular, and further that any observed randomness is mainly caused by biased target coverage. The TB-drugome (http://funsite.sdsc.edu/drugome/TB) has the potential to be a valuable resource in the development of safe and efficient anti-tubercular drugs. More generally the methodology may be applied to other pathogens of interest with results improving as more of their structural proteomes are determined through the continued efforts of structural biology/genomics

Bioprospecting the African Renaissance: The new value of muthi in South Africa

This article gives an overview of anthropological research on bioprospecting in general and of available literature related to bioprospecting particularly in South Africa. It points out how new insights on value regimes concerning plant-based medicines may be gained through further research and is meant to contribute to a critical discussion about the ethics of Access and Benefit Sharing (ABS). In South Africa, traditional healers, plant gatherers, petty traders, researchers and private investors are assembled around the issues of standardization and commercialization of knowledge about plants. This coincides with a nation-building project which promotes the revitalization of local knowledge within the so called African Renaissance. A social science analysis of the transformation of so called Traditional Medicine (TM) may shed light onto this renaissance by tracing social arenas in which different regimes of value are brought into conflict. When medicinal plants turn into assets in a national and global economy, they seem to be manipulated and transformed in relation to their capacity to promote health, their market value, and their potential to construct new ethics of development. In this context, the translation of socially and culturally situated local knowledge about muthi into global pharmaceuticals creates new forms of agency as well as new power differentials between the different actors involved

Extremely short duration high intensity interval training substantially improves insulin action in young healthy males

Background: Traditional high volume aerobic exercise training reduces cardiovascular and metabolic disease risk but involves a substantial time commitment. Extremely low volume high-intensity interval training (HIT) has recently been demonstrated to produce improvements to aerobic function, but it is unknown whether HIT has the capacity to improve insulin action and hence glycemic control. Methods: Sixteen young men (age: 21 ± 2 y; BMI: 23.7 ± 3.1 kg·m-2; VO2peak: 48 ± 9 ml·kg-1·min-1) performed 2 weeks of supervised HIT comprising of a total of 15 min of exercise (6 sessions; 4-6 × 30-s cycle sprints per session). Aerobic performance (250-kJ self-paced cycling time trial), and glucose, insulin and NEFA responses to a 75-g oral glucose load (oral glucose tolerance test; OGTT) were determined before and after training. Results: Following 2 weeks of HIT, the area under the plasma glucose, insulin and NEFA concentration-time curves were all reduced (12%, 37%, 26% respectively, all P < 0.001). Fasting plasma insulin and glucose concentrations remained unchanged, but there was a tendency for reduced fasting plasma NEFA concentrations post-training (pre: 350 ± 36 v post: 290 ± 39 μmol·l-1, P = 0.058). Insulin sensitivity, as measured by the Cederholm index, was improved by 23% (P < 0.01), while aerobic cycling performance improved by ∼6% (P < 0.01). Conclusion: The efficacy of a high intensity exercise protocol, involving only ∼250 kcal of work each week, to substantially improve insulin action in young sedentary subjects is remarkable. This novel time-efficient training paradigm can be used as a strategy to reduce metabolic risk factors in young and middle aged sedentary populations who otherwise would not adhere to time consuming traditional aerobic exercise regimes

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

Fat Oxidation, Fitness and Skeletal Muscle Expression of Oxidative/Lipid Metabolism Genes in South Asians: Implications for Insulin Resistance?

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; South Asians are more insulin resistant than Europeans, which cannot be fully explained by differences in adiposity. We investigated whether differences in oxidative capacity and capacity for fatty acid utilisation in South Asians might contribute, using a range of whole-body and skeletal muscle measures.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology/Principal Findings:&lt;/b&gt; Twenty men of South Asian ethnic origin and 20 age and BMI-matched men of white European descent underwent exercise and metabolic testing and provided a muscle biopsy to determine expression of oxidative and lipid metabolism genes and of insulin signalling proteins. In analyses adjusted for age, BMI, fat mass and physical activity, South Asians, compared to Europeans, exhibited; reduced insulin sensitivity by 26% (p = 0.010); lower VO2max (40.6±6.6 vs 52.4&#177;5.7 ml.kg−1.min−1, p = 0.001); and reduced fat oxidation during submaximal exercise at the same relative (3.77&#177;2.02 vs 6.55&#177;2.60 mg.kg−1.min−1 at 55% VO2max, p = 0.013), and absolute (3.46&#177;2.20 vs 6.00&#177;1.93 mg.kg−1.min−1 at 25 ml O2.kg−1.min−1, p = 0.021), exercise intensities. South Asians exhibited significantly higher skeletal muscle gene expression of CPT1A and FASN and significantly lower skeletal muscle protein expression of PI3K and PKB Ser473 phosphorylation. Fat oxidation during submaximal exercise and VO2max both correlated significantly with insulin sensitivity index and PKB Ser473 phosphorylation, with VO2max or fat oxidation during exercise explaining 10–13% of the variance in insulin sensitivity index, independent of age, body composition and physical activity.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; These data indicate that reduced oxidative capacity and capacity for fatty acid utilisation at the whole body level are key features of the insulin resistant phenotype observed in South Asians, but that this is not the consequence of reduced skeletal muscle expression of oxidative and lipid metabolism genes.&lt;/p&gt