Islands and Stepping-Stones: Comparative Population Structure of Anopheles gambiae sensu stricto and Anopheles arabiensis in Tanzania and Implications for the Spread of Insecticide Resistance

Population genetic structures of the two major malaria vectors Anopheles gambiae s.s. and An. arabiensis, differ markedly across Sub-Saharan Africa, which could reflect differences in historical demographies or in contemporary gene flow. Elucidation of the degree and cause of population structure is important for predicting the spread of genetic traits such as insecticide resistance genes or artificially engineered genes. Here the population genetics of An. gambiae s.s. and An. arabiensis in the central, eastern and island regions of Tanzania were compared. Microsatellite markers were screened in 33 collections of female An. gambiae s.l., originating from 22 geographical locations, four of which were sampled in two or three years between 2008 and 2010. An. gambiae were sampled from six sites, An. arabiensis from 14 sites, and both species from two sites, with an additional colonised insectary sample of each species. Frequencies of the knock-down resistance (kdr) alleles 1014S and 1014F were also determined. An. gambiae exhibited relatively high genetic differentiation (average pairwise F_ST = 0.131), significant even between nearby samples, but without clear geographical patterning. In contrast, An. arabiensis exhibited limited differentiation (average F_ST = 0.015), but strong isolation-by-distance (Mantel test r = 0.46, p = 0.0008). Most time-series samples of An. arabiensis were homogeneous, suggesting general temporal stability of the genetic structure. An. gambiae populations from Dar es Salaam and Bagamoyo were found to have high frequencies of kdr 1014S (around 70%), with almost 50% homozygote but was at much lower frequency on Unguja Island, with no. An. gambiae population genetic differentiation was consistent with an island model of genetic structuring with highly restricted gene flow, contrary to An. arabiensis which was consistent with a stepping-stone model of extensive, but geographically-restricted gene flow.     

Hepatitis C virus genotype 3a with phylogenetically distinct origin is circulating in Pakistan

Background

Hepatitis C virus (HCV) is one of the leading causes of viral hepatitis worldwide and its genotype 3a is predominant in vast areas of Pakistan.

Findings

The present study reports the first full sequence of HCV 3a isolate PK-1 from Pakistan. This nucleotide sequence was compared with six other HCV genotype 3a full length sequences from different regions of the world by using statistical methods of phylogenetic analysis.

Conclusion

The nucleotide difference of these seven sequences shows that HCV genotype 3a of phylogenetically distinct origin is circulating in Pakistan.     

Evaluation of collaborative models of care in the management of patients with depression: protocol and progress

Introduction Depression is highly prevalent and has a considerable impact on the quality of life of affected individuals, and on healthcare resources. Evidence indicates that collaborative care models can improve patient outcomes within a primary care setting. The Primary Care Services Improvement Project (PCSIP) aims to investigate the costs and outcomes of different models of care for the management of patients with depression. These models have been defined based on the level of involvement of practice nurses in management processes within the primary care setting in Australia. This paper describes our study protocol and its progress.Methods PCSIP is an observational study that will link retrospective data from a range of sources to estimate costs and intermediate outcomes (such as relapse rate) over a 3-year time horizon. The main sources of primary data include the medical records of patients held at participating practices and Medicare Australia.Initial report We recruited 15 practices from a metropolitan area and allocated them to three models of care. Two hundred and sixty-one patients agreed to participate. Appropriate regression-based analyses will be used to evaluate the association between different models of care and patient-level outcomes while controlling for several covariates such as age and gender.Discussion/conclusions This project will generate the knowledge required to promote investment in the most cost-effective initiatives, and to ensure that waste of resources due to the implementation of comparatively inefficient interventions is minimised. Given the scarcity of resources, the increasing costs of providing healthcare and the increasing prevalence of chronic diseases, such research is essential.     

piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans

Transgenerational effects have wide-ranging implications for human health, biological adaptation, and evolution; however, their mechanisms and biology remain poorly understood. Here, we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain stable inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C. elegans. Using forward genetic screens and candidate approaches, we find that a core set of nuclear RNAi and chromatin factors is required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 ortholog HPL-2, and two putative histone methyltransferases, SET-25 and SET-32. piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present a multigenerational epigenetic inheritance mechanism induced by piRNAs.     

Characterization of in vitro cultured bone marrow and adipose tissue‐derived mesenchymal stem cells and their ability to express neurotrophic factors

MSCs (mesenchymal stem cells) have attracted attention as a promising tool for regenerative medicine and transplantation therapy. MSCs exert neuroprotective effects by secreting a number of factors in vitro and in vivo. Similar characteristics are found in ADSCs (adipose‐derived stem cells) and BMSCs (bone marrow stromal cells). Multipotent capability, easy accessibility and rapid proliferation of ADSCs have been established. Our main objective was to compare cell viability, growth rate, expression of neurotrophic factors and nestin genes in ADSCs and BMSCs. Cell doubling time and proliferation rate indicate that ADSCs has a higher proliferation rate than BMSCs. ADSCs and BMSCs express a similar pattern of CD71 and CD90 markers. Nestin immunostaining showed that ADSCs and BMSCs are immunopositive. The expression of neurotrophic factors genes in ADSCs proved similar to that of BMSCs genes. Thus adipose tissue stem cells with a high proliferation rate can express nestin and neurotrophic factor genes. Therefore ADSCs may be useful in future cell replacement therapies and help improve neurodegenerative diseases.     

Effect of aging on prolactin regulation of rat striatal dopamine receptor concentrations

Administration of highly purified rat prolactin by miniosmotic pump increases striatal dopamine receptor concentrations in both mature (4-6 months) and senescent (24 months) male Wistar rats. Although receptor levels in untreated rats are about 30% lower in the senescent group, elevated levels following prolactin are not significantly different between ages. Increases in circulating prolactin levels after 7 days of treatment were not detectable at the low concentrations used (150 ng/hr). In fact, there was a trend toward decreases in circulating prolactin concentrations to the same level in both groups after treatment, despite substantially elevated basal levels in many of the senescent rats.     

Cytomorphological spectrum in scar endometriosis: a study of eight cases

OBJECTIVE: Endometriosis due to ectopic endometrial tissue that responds to hormonal stimulation and is extremely rare in a surgical scar appearing in 0.1% of women who have undergone Caesarean section. Fine needle aspiration cytology (FNAC) can be a valuable diagnostic aid in the evaluation of these subcutaneous abdominal masses. METHODS: We present the cytomorphological spectrum in eight cases of abdominal wall endometriosis diagnosed by FNAC over a 6-year period (June 1998-June 2004) in Mubarak Al-Kabeer Hospital (Kuwait). The patients ranged from 27 to 56 years of age. Seven had a prior Caesarean section and one had a hysterectomy for fibroid. They presented 3-8 years later with nodules in/near the abdominal scar. Five cases presented with a painful nodule, fluctuant with the menstrual cycle. RESULTS: Cytological findings comprised epithelial clusters and fusiform stromal cells with numerous haemosiderin-laden macrophages. Mild to moderate epithelial atypia was observed in three cases. A diagnosis of endometriosis was rendered in all the eight cases and tissue was available in four cases. CONCLUSIONS: Endometriotic nodules need to be differentiated from other benign/malignant masses and evaluated for possible malignant transformation. FNAC provides a safe and effective tool for diagnosis thereby obviating the need for other procedures.     

Early Exposure of Infants to GI Nematodes Induces Th2 Dominant Immune Responses Which Are Unaffected by Periodic Anthelminthic Treatment

We have previously shown a reduction in anaemia and wasting malnutrition in infants <3 years old in Pemba Island, Zanzibar, following repeated anthelminthic treatment for the endemic gastrointestinal (GI) nematodes Ascaris lumbricoides, hookworm and Trichuris trichiura. In view of the low intensity of worm infections in this age group, this was unexpected, and it was proposed that immune responses to the worms rather than their direct effects may play a significant role in morbidity in infants and that anthelminthic treatment may alleviate such effects. Therefore, the primary aims of this study were to characterise the immune response to initial/early GI nematode infections in infants and the effects of anthelminthic treatment on such immune responses. The frequency and levels of Th1/Th2 cytokines (IL-5, IL-13, IFN-γ and IL-10) induced by the worms were evaluated in 666 infants aged 6–24 months using the Whole Blood Assay. Ascaris and hookworm antigens induced predominantly Th2 cytokine responses, and levels of IL-5 and IL-13 were significantly correlated. The frequencies and levels of responses were higher for both Ascaris positive and hookworm positive infants compared with worm negative individuals, but very few infants made Trichuris-specific cytokine responses. Infants treated every 3 months with mebendazole showed a significantly lower prevalence of infection compared with placebo-treated controls at one year following baseline. At follow-up, cytokine responses to Ascaris and hookworm antigens, which remained Th2 biased, were increased compared with baseline but were not significantly affected by treatment. However, blood eosinophil levels, which were elevated in worm-infected children, were significantly lower in treated children. Thus the effect of deworming in this age group on anaemia and wasting malnutrition, which were replicated in this study, could not be explained by modification of cytokine responses but may be related to eosinophil function.     

新疆圆柏化学成分研究

从新疆圆柏枝叶中分离得到9个化合物,经理化性质和光谱解析分别为扁柏双黄酮（hinokiflavone,1）、芹菜甙元（apigenin,2）、鬼臼毒素（podophyllotoxin,3）、苦松甙（coniferin,4）、肉豆蔻酸丙酯（propionic acetate myristic acid,5）、β-谷甾醇（β-sitosterol,6）、圆柏醇（sabinal,7）、反式璎珞酸（trans-communic acid,8）、蔗糖（sucrose,9）,其中化合物1～4为首次从该植物中提取分离得到.