A Superposition Model of the Spontaneous Activity of Cerebellar Purkinje Cells

Based on physiological evidence for multiple firing zones in the dendritic arborizations of cerebellar Purkinje cells, a superposition model is proposed for spike triggering in these cells. Spike trains from 10 Purkinje cells were analyzed in terms of independence of interspike intervals and the properties of their variance-time curves. The results of this analysis were found consistent with the hypothesis that the spike train of a cerebellar Purkinje cell is the pooled output of a relatively large number of independent component processes. Simplifying assumptions as to the statistical nature of these processes lead to a very rough estimate of the number of firing zones.     

Vegetation analysis,phenological patterns and chorological affinities in Wadi Qena,Eastern Desert,Egypt

The present study, which was conducted between 2009 and 2010, provides an analysis of the floristic composition, life forms, phenology, chorological spectrum and analysis of the vegetation in the deltaic part of Wadi Qena using multivariate analysis techniques. Twenty‐five stands were sampled to represent, as much as possible, the vegetation variation in the study area. A total of 54 species (nineteen annuals and 35 perennials) belonging to 47 genera and nineteen families were recorded. The largest families were Fabaceae and Brassicaceae (nine and seven, respectively), Asteraceae and Poaceae (six for each), Chenopodiaceae (five), and Zygophyllaceae (four). Therophytes are the predominant life form (37%) followed by chamaephytes (24%), phanerophytes (18.5%), hemicryptophytes (9.29%) and cryptophytes (5.5%). Chorological analysis revealed that Saharo‐Arabian (48%) and the Sudano‐Zambezian (19.2%) chorotypes constitute the main bulk (67.2%) of the total flora of the studied area. The majority of the perennial species behave similarly to each other in their phenology, and usually perennials sprout at the end of February, become leafy in March, flower in April and produce fruits between April and July. Three main vegetation groups resulted from classification of the dominant vegetation. Canonical correspondence analysis revealed that magnesium, potassium and pH were the most effective soil variables.     

Novel crown ethers on glucose based glycolipids

A series of crown ethers involving lauryl glucoside were synthesized and their assembly behavior in water was studied. The synthesis applied a simple protection scheme based on benzylidenation for the glycolipid, and cation templating for the macrocycle. A sequential build-up of the crown ether by bis-hydroxylethylation of the glucoside followed by reaction with di-, tri-, or tetraethylene glycol ditosylate provided better yields of the macrocycle compared to a single step cyclization with tetraethylene glycole ditosylate. The macrocycles containing up to six oxygens showed significantly higher affinity for sodium than for potassium, while more effective potassium complexation was found for the 21-crown-7 compound. The ion binding affinity leads to a slight but significant increase of the CMC of the crown ether containing surfactant in water upon the addition of sodium electrolyte.     

Integrating mental health into primary health care in Iraq

The Ministry of Health in Iraq is undertaking a systematic programme to integrate mental health into primary care in order to increase population access to mental health care. This paper reports the evaluation of the delivery of a ten day interactive training programme to 20% of primary care centres across Iraq. The multistage evaluation included a pre- and post-test questionnaire to assess knowledge, attitudes and practice in health workers drawn from 143 health centres, a course evaluation questionnaire and, in a random sample of 41 clinics, direct observation of health workers skills and exit interviews of patients, comparing health workers who had received the training programme with those from the same clinics who had not received the training. Three hundred andseventeen health workersparticipated in the training, which achieved an improvement in test scores from 42.3% to 59%. Trained health workers were observed by research psychiatrists to have a higher level of excellent skills than the untrained health workers, and patient exit interviews also reported better skills in the trained rather than untrained health workers. The two week course has thus been able to achieve significant change, not only in knowledge, but also in subsequent demonstration of trained practitioners practical skills in the workplace. Furthermore, it has been possible to implement the course and the evaluation despite a complex conflict situation.     

Expression and functional roles of angiopoietin-2 in skeletal muscles

Background

Angiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2) are angiogenesis factors that modulate endothelial cell differentiation, survival and stability. Recent studies have suggested that skeletal muscle precursor cells constitutively express ANGPT1 and adhere to recombinant ANGPT1 and ANGPT2 proteins. It remains unclear whether or not they also express ANGPT2, or if ANGPT2 regulates the myogenesis program of muscle precursors. In this study, ANGPT2 regulatory factors and the effects of ANGPT2 on proliferation, migration, differentiation and survival were identified in cultured primary skeletal myoblasts. The cellular networks involved in the actions of ANGPT2 on skeletal muscle cells were also analyzed.

Methodology/Principal Findings

Primary skeletal myoblasts were isolated from human and mouse muscles. Skeletal myoblast survival, proliferation, migration and differentiation were measured in-vitro in response to recombinant ANGPT2 protein and to enhanced ANGPT2 expression delivered with adenoviruses. Real-time PCR and ELISA measurements revealed the presence of constitutive ANGPT2 expression in these cells. This expression increased significantly during myoblast differentiation into myotubes. In human myoblasts, ANGPT2 expression was induced by H₂O₂, but not by TNFα, IL1β or IL6. ANGPT2 significantly enhanced myoblast differentiation and survival, but had no influence on proliferation or migration. ANGPT2-induced survival was mediated through activation of the ERK1/2 and PI-3 kinase/AKT pathways. Microarray analysis revealed that ANGPT2 upregulates genes involved in the regulation of cell survival, protein synthesis, glucose uptake and free fatty oxidation.

Conclusion/Significance

Skeletal muscle precursors constitutively express ANGPT2 and this expression is upregulated during differentiation into myotubes. Reactive oxygen species exert a strong stimulatory influence on muscle ANGPT2 expression while pro-inflammatory cytokines do not. ANGPT2 promotes skeletal myoblast survival and differentiation. These results suggest that muscle-derived ANGPT2 production may play a positive role in skeletal muscle fiber repair.     

A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.     

Identifying Darwinian Selection Acting on Different Human APOL1 Variants among Diverse African Populations

Disease susceptibility can arise as a consequence of adaptation to infectious disease. Recent findings have suggested that higher rates of chronic kidney disease (CKD) in individuals with recent African ancestry might be attributed to two risk alleles (G1 and G2) at the serum-resistance-associated (SRA)-interacting-domain-encoding region of APOL1. These two alleles appear to have arisen adaptively, possibly as a result of their protective effects against human African trypanosomiasis (HAT), or African sleeping sickness. In order to explore the distribution of potential functional variation at APOL1, we studied nucleotide variation in 187 individuals across ten geographically and genetically diverse African ethnic groups with exposure to two Trypanosoma brucei subspecies that cause HAT. We observed unusually high levels of nonsynonymous polymorphism in the regions encoding the functional domains that are required for lysing parasites. Whereas allele frequencies of G2 were similar across all populations (3%–8%), the G1 allele was only common in the Yoruba (39%). Additionally, we identified a haplotype (termed G3) that contains a nonsynonymous change at the membrane-addressing-domain-encoding region of APOL1 and is present in all populations except for the Yoruba. Analyses of long-range patterns of linkage disequilibrium indicate evidence of recent selection acting on the G3 haplotype in Fulani from Cameroon. Our results indicate that the G1 and G2 variants in APOL1 are geographically restricted and that there might be other functional variants that could play a role in HAT resistance and CKD risk in African populations.     

Effect of selenite and tellurite on the morphological growth and toxin production of Aspergillus parasiticus var. globosus IMI 120920

Aspergillus parasiticus var. globosus IMI 120920 was able to grow in presence of different concentrations tested (0.052–4.0%) of sodium selenite or concentrations up to 2.0% potassium tellurite. Growth of the fungus was decreased greatly by the increase of metals concentrations. Dark colour colony and black reverse were formed in presence of tellurite while reddish gray to grayish red colony colour and brownish red to orange red reverse were formed in presence of selenite. The fungal biomass was slightly decreased at lower concentrations and highly inhibited at higher concentrations of selenite or tellurite. Selenite slightly stimulated aflatoxin formation at lower concentrations and highly inhibited it at higher concentrations. Aflatoxin production was decreased greatly by increasing tellurite concentrations. Obvious malformations were observed in the morphological features of the fungus in presence of different levels of selenite or tellurite. This revised version was published online in June 2006 with corrections to the Cover Date.