Annexin A8 Identifies a Subpopulation of Transiently Quiescent c-Kit Positive Luminal Progenitor Cells of the Ductal Mammary Epithelium

We have previously shown that Annexin A8 (ANXA8) is strongly associated with the basal-like subgroup of breast cancers, including BRCA1-associated breast cancers, and poor prognosis; while in the mouse mammary gland AnxA8 mRNA is expressed in low-proliferative isolated pubertal mouse mammary ductal epithelium and after enforced involution, but not in isolated highly proliferative terminal end buds (TEB) or during pregnancy. To better understand ANXA8’s association with this breast cancer subgroup we established ANXA8’s cellular distribution in the mammary gland and ANXA8’s effect on cell proliferation. We show that ANXA8 expression in the mouse mammary gland was strong during pre-puberty before the expansion of the rudimentary ductal network and was limited to a distinct subpopulation of ductal luminal epithelial cells but was not detected in TEB or in alveoli during pregnancy. Similarly, during late involution its expression was found in the surviving ductal epithelium, but not in the apoptotic alveoli. Double-immunofluorescence (IF) showed that ANXA8 positive (+ve) cells were ER-alpha negative (−ve) and mostly quiescent, as defined by lack of Ki67 expression during puberty and mid-pregnancy, but not terminally differentiated with ∼15% of ANXA8 +ve cells re-entering the cell cycle at the start of pregnancy (day 4.5). RT-PCR on RNA from FACS-sorted cells and double-IF showed that ANXA8+ve cells were a subpopulation of c-kit +ve luminal progenitor cells, which have recently been identified as the cells of origin of basal-like breast cancers. Over expression of ANXA8 in the mammary epithelial cell line Kim-2 led to a G₀/G₁ arrest and suppressed Ki67 expression, indicating cell cycle exit. Our data therefore identify ANXA8 as a potential mediator of quiescence in the normal mouse mammary ductal epithelium, while its expression in basal-like breast cancers may be linked to ANXA8’s association with their specific cells of origin.     

“It’s My Secret”: Fear of Disclosure among Sub-Saharan African Migrant Women Living with HIV/AIDS in Belgium

Patients with HIV not only have to deal with the challenges of living with an incurable disease but also with the dilemma of whether or not to disclose their status to their partners, families and friends. This study explores the extent to which sub-Saharan African (SSA) migrant women in Belgium disclose their HIV positive status, reasons for disclosure/non-disclosure and how they deal with HIV disclosure. A qualitative study consisting of interviews with twenty-eight SSA women with HIV/AIDS was conducted. Thematic content analysis was employed to identify themes as they emerged. Our study reveals that these women usually only disclose their status to healthcare professionals because of the treatment and care they need. This selective disclosure is mainly due to the taboo of HIV disease in SSA culture. Stigma, notably self-stigma, greatly impedes HIV disclosure. Techniques to systematically incorporate HIV disclosure into post-test counseling and primary care services are highly recommended.     

Historical Perspective and Risk of Multiple Neglected Tropical Diseases in Coastal Tanzania: Compositional and Contextual Determinants of Disease Risk

BackgroundIn the past decade, research on neglected tropical diseases (NTDs) has intensified in response to the need to enhance community participation in health delivery, establish monitoring and surveillance systems, and integrate existing disease-specific treatment programs to control overlapping NTD burdens and detrimental effects. In this paper, we evaluated the geographical distribution of NTDs in coastal Tanzania.ConclusionsNTD risks were inequitably distributed over geographic space, which has several important policy implications. First, it suggests that localities of high burden of NTDs are likely to diminish within statistical averages at higher (regional or national) levels. Second, it indicates that curative or preventive interventions will become more efficient provided they can be focused on the localities, particularly as populations in these localities are likely to be burdened by several NTDs simultaneously, further increasing the imperative of multi-disease interventions.     

Divergence in Female Duetting Signals in the Enchenopa binotata Species Complex of Treehoppers (Hemiptera: Membracidae)

Sexual communication often involves signal exchanges between the sexes, or duetting, in which mate choice is expressed through response signals. With both sexes acting as signalers and receivers, variation in the signals of males and females may be important for mate choice, reproductive isolation, and divergence. In the Enchenopa binotata species complex – a case study of sympatric speciation in which vibrational duetting may have an important role – male signals are species‐specific, females choose among males on the basis of signal traits that reflect species and individual differences, and female preferences have exerted divergent selection on male signals. Here, we describe variation in female signals in the E. binotata species complex. We report substantial species differences in the spectral and temporal features of female signals, and in their timing relative to male signals. These differences were similar in range to differences in male signals in the E. binotata complex. We consider processes that might contribute to divergence in female signals, and suggest that signal evolution in the E. binotata complex may be influenced by mate choice in both sexes.     

Complex life cycles of multicellular eukaryotes: new approaches based on the use of model organisms

A wide variety of life cycles can be found in the different groups of multicellular eukaryotes. Here we provide an overview of this variety, and review some of the theoretical arguments that have been put forward to explain the evolutionary stability of different life cycle strategies. We also describe recent progress in the analysis of the haploid-diploid life cycle of the model angiosperm Arabidopsis thaliana and show how new molecular data are providing a means to test some of the theoretical predictions. Finally, we describe an emerging model organism from the brown algae, Ectocarpus siliculosus, and highlight the potential of this system for the investigation of the mechanisms that regulate complex life cycles.     

Evolution of prokaryotic two-component system signaling pathways: gene fusions and fissions

Two-component systems (TCSs) are common signal transduction systems, typically comprising paired histidine protein kinase (HK) and response regulator (RR) proteins. In many examples, it appears RR and HK genes have fused, producing a "hybrid kinase " We have characterized a set of prokaryotic genes encoding RRs, HKs, and hybrid kinases, enabling characterization of gene fusion and fission. Primary factors correlating with fusion rates are the presence of transmembrane helices in HKs and the presence of DNA-binding domains in RRs, features that require correct (and separate) spatial location. In the absence of such features, there is a relative abundance of fused genes. The order of paired HK and RR genes and the nucleotide distance between encoded domains also correlate with apparent gene fusion rates. We propose that localization requirements and relative positioning of encoded domains within TCS genes affect the function (and therefore retention) of hybrid kinases resulting from gene fusion.     

Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration

Here, we show that the murine neurodegenerative disease mdf (autosomal recessive mouse mutant 'muscle deficient') is caused by a loss-of-function mutation in Scyl1, disrupting the expression of N-terminal kinase-like protein, an evolutionarily conserved putative component of the nucleocytoplasmic transport machinery. Scyl1 is prominently expressed in neurons, and enriched at central nervous system synapses and neuromuscular junctions. We show that the pathology of mdf comprises cerebellar atrophy, Purkinje cell loss and optic nerve atrophy, and therefore defines a new animal model for neurodegenerative diseases with cerebellar involvement in humans.