No abstract

Although asexual reproduction via clonal propagation has been proposed as the principal reproductive mechanism across parasitic protozoa of the Leishmania genus, sexual recombination has long been suspected, based on hybrid marker profiles detected in field isolates from different geographical locations. The recent experimental demonstration of a sexual cycle in Leishmania within sand flies has confirmed the occurrence of hybridisation, but knowledge of the parasite life cycle in the wild still remains limited. Here, we use whole genome sequencing to investigate the frequency of sexual reproduction in Leishmania, by sequencing the genomes of 11 Leishmania infantum isolates from sand flies and 1 patient isolate in a focus of cutaneous leishmaniasis in the Çukurova province of southeast Turkey. This is the first genome-wide examination of a vector-isolated population of Leishmania parasites. A genome-wide pattern of patchy heterozygosity and SNP density was observed both within individual strains and across the whole group. Comparisons with other Leishmania donovani complex genome sequences suggest that these isolates are derived from a single cross of two diverse strains with subsequent recombination within the population. This interpretation is supported by a statistical model of the genomic variability for each strain compared to the L. infantum reference genome strain as well as genome-wide scans for recombination within the population. Further analysis of these heterozygous blocks indicates that the two parents were phylogenetically distinct. Patterns of linkage disequilibrium indicate that this population reproduced primarily clonally following the original hybridisation event, but that some recombination also occurred. This observation allowed us to estimate the relative rates of sexual and asexual reproduction within this population, to our knowledge the first quantitative estimate of these events during the Leishmania life cycle.

We conclude that supervised aerobic exercise training safely decreases fatigue, weight, BMI, subcutaneous fat and abdominal girth (central fat) in HIV-1-infected individuals. It did not appear to have an effect on dyspnea.

Aerobic exercise training may help prevent or reduce depressive symptoms experienced by persons living with HIV infection. However, the psychological effects of aerobic exercise have not been studied extensively. This study evaluated the effects of an aerobic exercise training program on self-reported symptoms of depression in HIV-infected adults and examined the convergent validity of two widely used depressive symptom scales. Sixty HIV-infected adults participated in a randomized, controlled trial of a supervised 12-week aerobic exercise training program. As compared to study controls, exercise participants showed reductions in depressive symptoms on all indices, and total depressive symptoms scores were highly correlated. Additional study of the psychological effects of aerobic exercise programs in the target population is recommended.

Fifteen different restriction fragment length polymorphisms (RFLPs) were detected in the human genome using 19 cloned DNA segments, derived from flow-sorted metaphase chromosomes or total genomic DNA, as hybridization probes. Since these clones were selected at random with respect to their coding potential, their analysis permitted an unbiased estimate of single-copy DNA sequence heterozygosity in the human genome. Since our estimate (h = 0.0037) is an order of magnitude higher than previous estimates derived from protein data, most of the polymorphic variation present in the genome must occur in non-coding sequences. In addition, it was confirmed that enzymes containing the dinucleotide CpG in their recognition sequence detect more polymorphic variation than those that do not contain CpG.

Adherence to exercise Adjuvant therapy Breast cancer Cardiopulmonary responsesCardiopulmonary responses to an 8-week moderate-intensity aerobic exercise intervention and adherence to exercise during and after intervention were assessed in 41 women newly diagnosed with breast cancer undergoing adjuvant therapy. The intervention was primarily aimed at minimizing deconditioning. Women were randomly assigned to the intervention or control group, completed graded exercise tests before and after intervention, and encouraged to continue their exercise postintervention. Over time, only the intervention group showed significant decreases in resting heart rate, resting systolic blood pressure (SBP), P G .05 each, and maximum SBP, P G .02, and an increase in VO 2 peak, P G .001, although resting SBP was higher in the intervention group at both timepoints, P G .05. The adherence rate to 8-week exercise intervention was 78.3% with average weekly attendance of 2.4 sessions and 42.7 minutes (27.8 minutes within target heart rate) exercise per session. Overall physical activity levels over 16 weeks postintervention did not differ between 2 groups. However, the within-group analysis indicated that only the intervention group showed a significant increase in voluntary activity, P G .02, and energy expenditure, P G .02, and a decrease in sedentary activity, P G .02. These findings indicate that moderate-intensity aerobic exercise is beneficial in reducing deconditioning of cardiopulmonary responses in newly diagnosed breast cancer women undergoing adjuvant therapy.156 n Cancer Nursing TM

The stage-regulated HASPB and SHERP proteins of Leishmania major are predominantly expressed in cultured metacyclic parasites that are competent for macrophage uptake and survival. The role of these proteins in parasite development in the sand fly vector has not been explored, however. Here, we confirm that expression of HASPB is detected only in vector metacyclic stages, correlating with the expression of metacyclic-specific lipophosphoglycan and providing the first definitive protein marker for this infective sand fly stage. Similarly, SHERP is expressed in vector metacyclics but is also detected at low levels in the preceding short promastigote stage. Using genetically modified parasites lacking or complemented for the LmcDNA16 locus on chromosome 23 that contains the HASP and SHERP genes, we further show that the presence of this locus is essential for parasite differentiation to the metacyclic stage in Phlebotomus papatasi. While wild-type and complemented parasites transform normally in late-stage infections, generating metacyclic promastigotes and colonizing the sand fly stomodeal valve, null parasites accumulate at the earlier elongated nectomonad stage of development within the abdominal and thoracic midgut of the sand fly. Complementation with HASPB or SHERP alone suggests that HASPB is the dominant effector molecule in this process.

We observed that in urothelium, both cornifying and noncornifying forms of squamous metaplasia are accompanied by changes in the localization of the nuclear hormone receptors, peroxisome proliferator activated receptor gamma (PPAR-gamma) and retinoid X receptor (RXR-alpha). To obtain objective evidence for a role for PPAR-gamma-mediated signaling in urothelial differentiation, we examined expression of the cytokeratin isotypes CK13, CK20, and CK14 as indicators of transitional, terminal transitional, and squamous differentiation, respectively, in cultures of normal human urothelial cells. In control culture conditions, normal human urothelial cells showed evidence of squamous differentiation (CK14+, CK13-, CK20-). Treatment with the high-affinity PPAR-gamma agonist, troglitazone (TZ), resulted in gain of CK13 and loss of CK14 protein expression. The effect of TZ was significantly augmented when the autocrine-stimulated epidermal growth factor receptor pathway was inhibited and this resulted in induction of CK20 expression. The RXR-specific inhibitors PA452, HX531, and HX603 inhibited the TZ-induced CK13 expression, supporting a role for RXR in the induction of CK13 expression. Thus, signaling through PPAR-gamma can mediate transitional differentiation of urothelial cells and this is modulated by growth regulatory programs.