Tolerability and efficacy of single dose albendazole,diethylcarbamazine citrate (DEC) or co-administration of albendazole with DEC in the clearance of <Emphasis Type="Italic">Wuchereria bancrofti</Emphasis>in asymptomatic microfilaraemic volunteers in Pondicherry,South India: a hospital-based study

Background  

The tolerability and efficacy of single dose albendazole (400 mg), diethylcarbamazine citrate (DEC) (6 mg/kg bodyweight) or co-administration of albendazole (400 mg) + DEC (6 mg/kg bodyweight) was studied in 54 asymptomatic Wuchereria bancrofti microfilaraemic volunteers in a double blind hospital-based clinical study.     

Cyclin D in left ventricle hypertrophy

Left ventricle hypertrophy is induced by a number of stimuli and can lead to cardio-myopathy and heart failure. The hypertrophic response is achieved by enlargement of the cardiac myocytes and is regulated by multiple signaling pathways, with the D-type cyclins playing a crucial role. Induction of cyclin D in adult cardiac myocytes leads to activation of cyclin-dependent kinases 4 and 6 and a partial progress through the cell cycle. Therefore, these pathways are attractive therapeutic target for treatment of heart failure and hypertrophy. We discuss the activity of cyclin D and other cell cycle regulatory proteins in left ventricle hypertrophy and whether the hypertrophic signaling pathways converge at the D-type cyclins.     

Simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro

Background

The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect), which weakens the spatial linkage between hypoxia and acidosis.

Methods

Five different human squamous cell carcinoma cell lines (SiHa, FaDu_DD, UTSCC5, UTSCC14 and UTSCC15) were treated with hypoxia, acidosis (pH 6.3), or a combination, and gene expression analyzed using microarray. SiHa and FaDu_DD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of ³⁵S-labelled methionine and cysteine into protein.

Results

Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pH_e), genes induced at low oxygen at both normal and low pH_e, and genes induced at low pH_e independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2), and Ribosomal protein L37 (RPL37). Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa) and protein synthesis (both cell lines) was observed when hypoxia and low pH_e were combined.

Conclusions

We demonstrate here that the influence of hypoxia and acidosis causes different responses, both in gene expression and in de novo protein synthesis, depending on whether the two factors induced alone or overlapping, and as such it is important for in vivo studies to take this into account.     

Relationships between selected muscle endurance tasks and gender

The purpose of this research was to examine possible relationships between selected muscle endurance tasks and gender. Until 1990, girls' and women's programs infrequently contained activities such as sit-ups, push-ups, pull-ups, and exercises with resistance equipment. This lack of exposure may have, in turn, resulted in much poorer performance than men when examined in experimental settings. The results of a discriminant analysis indicated that the women (n = 31) in this study did not differ from men (n = 31) in the mean number of sit-ups, modified push-ups, and leg adductions performed, but that the men performed more lateral arm raises than the women (p < 0.05). When the influence of the age, height, and weight of the subjects (mean +/- SD; 24.13 +/- 7.50 years, 173.05 +/- 8.77 cm, 76.34 +/- 13.01 kg for men; 26.61 +/- 11.12 years, 161.82 +/- 6.47 cm, 58.89 +/- 10.91 kg for women) was examined, there were only small changes in the structure of the discriminant function generated in the first analysis. These findings should be approached with caution because of possible limitations related to the size and representativeness of the sample and lack of measurement equipment such as video cameras. The fact that the pattern of results in this study differed somewhat from patterns in earlier research may indicate that the findings in this study are: (a) a random result or comparison anomaly related to characteristics specific to this convenience sample of women and men or (b) suggestive that differences between women and men in the tests chosen may be representative of changes that are beginning to occur in the degree of differences between men and women in college resistance training or other fitness-related classes. Practical applications of the results of this study for teachers of resistance training or fitness-related classes in secondary school, college, and adult recreation might be that fitness programs should be individualized to meet needs specific to each student and that coeducational classes and programs should be expanded, especially offerings of fitness-related activities.     

A P Element Containing Suppressor of Hairy-Wing Binding Regions Has Novel Properties for Mutagenesis in Drosophila Melanogaster

P elements are widely used as insertional mutagens to tag genes, facilitating molecular cloning and analyses. We modified a P element so that it carried two copies of the suppressor of Hairy-wing [su(Hw)] binding regions isolated from the gypsy transposable element. This transposon was mobilized, and the genetic consequences of its insertion were analyzed. Gene expression can be altered by the su(Hw) protein as a result of blocking the interaction between enhancer/silencer elements and their promoter. These effects can occur over long distances and are general. Therefore, a composite transposon (SUPor-P for suppressor-P element) combines the mutagenic efficacy of the gypsy element with the controllable transposition of P elements. We show that, compared to standard P elements, this composite transposon causes an expanded repertoire of mutations and produces alleles that are suppressed by su(Hw) mutations. The large number of heterochromatic insertions obtained is unusual compared to other insertional mutagenesis procedures, indicating that the SUPor-P transposon may be useful for studying the structural and functional properties of heterochromatin.     

BAsE-Seq: a method for obtaining long viral haplotypes from short sequence reads

Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of pathogen genomes, together with date, location, clinical manifestation and other relevant data about sample origins, can contribute to describing nearly every aspect of transmission dynamics, including local transmission and global spread. The analyses of these data have implications for all levels of clinical and public health practice, from institutional infection control to policies for surveillance, prevention and treatment. This review highlights the range of epidemiological questions that can be addressed from the combination of genome sequence and traditional ‘line lists’ (tables of epidemiological data where each line includes demographic and clinical features of infected individuals). We identify opportunities for these data to inform interventions that reduce disease incidence and prevalence. By considering current limitations of, and challenges to, interpreting these data, we aim to outline a research agenda to accelerate the genomics-driven transformation in public health microbiology.