RESULTS: Cluster-wide C19MC miRNA expression profiling by microarray analysis showed wholesome C19MC activation in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). However, in multipotent adipose-derived mesenchymal stem cells (MSCs) and a unipotent human white pre-adipocyte cell line, only selected C19MC miRNAs were expressed. MiRNA copy number analysis also showed selective C19MC expression in cancer cells with expression patterns highly similar to those in MSCs, suggesting similar miRNA regulatory mechanisms in these cells. Selective miRNA expression also suggests complex transcriptional mechanism(s) regulating C19MC expression under specific cellular and pathological conditions. Bioinformatics analysis showed that sixteen of the C19MC miRNAs share the same "AAGUGC" seed sequence with members of the miR-302/-372 family, which are known cellular reprogramming factors. In particular, C19MC-AAGUGC-miRNAs with the nucleotides 2-7 canonical seed position as in miR-302/-372 miRNAs, may play similar roles as miR-302/-372 in induced pluripotency. A biased 3p-arm selection of the C19MC-AAGUGC-miRNAs was observed indicating that targets of the 3p species of these miRNAs may be biologically significant in regulating stemness. Furthermore, bioinformatics analysis of the putative targets of the C19MC-AAGUGC-miRNAs predicted significant involvement of signaling pathways in reprogramming, many of which contribute to promoting apoptosis by indirect activation of the pro-apoptotic proteins BAK/BAX via suppression of genes of the cell survival pathways, or by enhancing caspase-8 activation through targeting inhibitors of TRAIL-inducing apoptosis.
CONCLUSIONS: This work demonstrated selective C19MC expression in MSCs and cancer cells, and, through miRNA profiling and bioinformatics analysis, predicted C19MC modulation of apoptosis in induced pluripotency and tumorigenesis.
METHODS: A total of 308 samples was collected and microscopically screened from the NHP in the wild (n = 163), urban (n = 76), and captive (n = 69) populations. The samples were taken from 12 species of local NHPs.
RESULTS: At least, 44 species of GI parasites comprising of protozoans (seven species), nematodes (26 species), cestodes (five species), trematodes (five species), and pentastomida (one species) were detected. There were no significant differences for the overall prevalence and no great differences in GI parasite species among the wild, urban, and captive NHP populations.
CONCLUSION: The most common GI parasite was Ascaris spp. (49.7%), followed by Oesophagostomum spp. (26.9%), and 31 species discovered in this study are of known public health importance.
RESULTS: Mosquitoes were collected from a total of 15 sites using gravid traps and a backpack aspirator around Kampong Puruh Karu, Sarawak, Malaysian Borneo, where sylvatic DENV spillover has been documented. A total of 2447 mosquitoes comprising 10 genera and 4 species of Aedes, were collected over the three years, 2013, 2014 and 2016, in the three major land cover types in the area, homestead, agriculture and forest. Mosquitoes were identified morphologically, pooled by species and gender, homogenized, and subject to DNA barcoding of each Aedes species and to arbovirus screening. As predicted, Ae. niveus was found almost exclusively in forests whereas Ae. albopictus was collected in all land cover types. Aedes albopictus was significantly (P = 0.04) more abundant in agricultural fields than forests. Sylvatic DENV was not detected in any Aedes mosquito pools, however genomes of 14 viruses were detected using next generation sequencing.
CONCLUSIONS: Land cover type affects the abundance and distribution of the most likely bridge vectors of sylvatic DENV in Malaysia Borneo. Conversion of forests to agriculture will likely decrease the range and abundance of Ae. niveus but enhance the abundance of Ae. albopictus.
METHODOLOGY/PRINCIPAL FINDINGS: After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region.
CONCLUSIONS/SIGNIFICANCE: We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment.
MAIN BODY: We argue that broader consideration of lactation, incorporating evolutionary, comparative and anthropological aspects, could provide new insights into breastfeeding practices and problems, enhance research and ultimately help to develop novel approaches to improve initiation and maintenance. Our current focus on breastfeeding as a strategy to improve health outcomes must engage with the evolution of lactation as a flexible trait under selective pressure to maximise reproductive fitness. Poor understanding of the dynamic nature of breastfeeding may partly explain why some women are unwilling or unable to follow recommendations.
CONCLUSIONS: We identify three key implications for health professionals, researchers and policymakers. Firstly, breastfeeding is an adaptive process during which, as in other mammals, variability allows adaptation to ecological circumstances and reflects mothers' phenotypic variability. Since these factors vary within and between humans, the likelihood that a 'one size fits all' approach will be appropriate for all mother-infant dyads is counterintuitive; flexibility is expected. From an anthropological perspective, lactation is a period of tension between mother and offspring due to genetic 'conflicts of interest'. This may underlie common breastfeeding 'problems' including perceived milk insufficiency and problematic infant crying. Understanding this - and adopting a more flexible, individualised approach - may allow a more creative approach to solving these problems. Incorporating evolutionary concepts may enhance research investigating mother-infant signalling during breastfeeding; where possible, studies should be experimental to allow identification of causal effects and mechanisms. Finally, the importance of learned behaviour, social and cultural aspects of primate (especially human) lactation may partly explain why, in cultures where breastfeeding has lost cultural primacy, promotion starting in pregnancy may be ineffective. In such settings, educating children and young adults may be important to raise awareness and provide learning opportunities that may be essential in our species, as in other primates.