Loss of vesicular dopamine release precedes tauopathy in degenerative dopaminergic neurons in a Drosophila model expressing human tau.

While a number of genome-wide association studies have identified microtubule-associated protein tau as a strong risk factor for Parkinson's disease (PD), little is known about the mechanism through which human tau can predispose an individual to this disease. Here, we demonstrate that expression of human wild-type tau is sufficient to disrupt the survival of dopaminergic neurons in a Drosophila model. Tau triggers a synaptic pathology visualized by vesicular monoamine transporter-pHGFP that precedes both the age-dependent formation of tau-containing neurofibrillary tangle-like pathology and the progressive loss of DA neurons, thereby recapitulating the pathological hallmarks of PD. Flies overexpressing tau also exhibit progressive impairments of both motor and learning behaviors. Surprisingly, contrary to common belief that hyperphosphorylated tau could aggravate toxicity, DA neuron degeneration is alleviated by expressing the modified, hyperphosphorylated tau(E14). Together, these results show that impairment of VMAT-containing synaptic vesicle, released to synapses before overt tauopathy may be the underlying mechanism of tau-associated PD and suggest that correction or prevention of this deficit may be appropriate targets for early therapeutic intervention

Effects of insecticide-treated net access and use on infant mortality in Malawi: A pooled analysis of demographic health surveys

Malaria continues to be among the top causes of death in children and insecticide-treated nets (ITNs) are considered among the most effective malaria control methods. However, information on the association between universal ITN coverage and infant mortality is limited. A Cox proportional hazard model was applied to Malawi Demographic and Health Surveys to determine the association between ITN access and use and infant mortality between 2004 and 2015–2016. The overall infant mortality rate for the entire period was 47.9/1000 live births. Infants from the ITN-user households exhibited a lower risk of mortality [adjusted Hazard Ratio (aHR) = 0.61, 95% Confidence Interval (CI) = 0.44–0.85] than those from the ITN-nonuser households. Similarly, the infants from the high-access households exhibited a lower risk of death (aHR = 0.63, 95% CI = 0.46–0.86) than those from the no-access households. Infants from the ITN-user and high-access households exhibited a significantly lower risk of death (aHR = 0.57, 95% CI = 0.40–0.82) than those from the ITN-nonuser and no-access households. The relationship between ITN access and use and infant mortality was significant among female infants with a second or higher birth order and interval of ≥2 years. The findings of the present population-based study emphasized the importance of ITN access and use in providing optimal protection against malaria to infants in Malawi. Malaria control programs should ensure high ITN access and use in Malawi to reduce infant mortality

Multilevel analysis of factors associated with treatment-seeking behaviors among caregivers with febrile children in Malawi

Early diagnosis and treatment of childhood fever, an important sign of potentially serious infections such as malaria, is essential for controlling disease progression, and ultimately, preventing deaths. This study examined individual- and community-level factors associated with treatment-seeking behaviors and promptness in these behaviors among caregivers of febrile under-five children in Malawi. The 2015-2016 Malawi Demographic Health Survey was used to analyze a nationally representative sample of 4,133 under-five children who had fever within 2 weeks before the survey. A multilevel logistic regression model was used to examine the association between individual- and community-level factors and treatment-seeking behaviors. Approximately 67.3% of the caregivers reported seeking treatment for their febrile child, whereas only 46.3% reported promptly seeking treatment. Children from communities with moderate and high percentages of educated caregivers were more likely to be taken for treatment (adjusted odds ratio [aOR] = 1.26, 95% CI = 1.01-1.58 and aOR = 1.31, 95% CI = 1.02-1.70, respectively) than those from communities with a low percentage of educated caregivers. Children from communities with moderate and high percentages of caregivers complaining about the distance to a health facility were less likely to be taken for treatment (aOR = 0.74, 95% CI = 0.58-0.96 and aOR = 0.67, 95% CI = 0.51-0.88, respectively). At the individual level, having a cough in the last 2 weeks, region, religion, and having better health behaviors in other health dimensions were associated with fever treatment-seeking behaviors among Malawian caregivers. Programs aimed at improving treatment-seeking behaviors should consider these factors and the regional variations observed in this study

Influence of maternal exposure to malaria social and behavioral change messages and effectiveness of communication media on bed net use and malaria infection in Malawi.

Background: Malawi is a malaria-endemic country. A national malaria communication strategy was adopted to disseminate malaria messages with the aim of improving knowledge and adoption of malaria interventions. Objective: To examine the effect of maternal exposure to malaria messages and the medium through which such messages are delivered on insecticide-treated net (ITN) use and malaria infection among children under 5 years of age in Malawi. Methodology: Utilizing the data from the 2017 Malawi Malaria Indicator Survey, 2,055 children (aged under 5 years) and 1,886 children (aged 6–59 months) were analyzed for ITN use and malaria infection outcomes, respectively. Components of exposure to malaria messages were tested for association with ITN use and malaria infection outcomes using multiple logistic regression models. Results: Children whose mothers had reported hearing any malaria-related message in the past 6 months were more likely to sleep under an ITN and less likely to have malaria infection compared with those whose mothers had not heard any malaria-related message. Region and sex of the child were effect modifiers on the relationship between exposure to any malaria-related message and malaria infection. Knowledge regarding cause or protection methods partially mediated the relationship between exposure to any malaria message and malaria infection. Discussion and Conclusion: Health workers were an effective communication channel. Strengthening topic-specific malaria messages and building the capacity of health workers while alternately strengthening other message outlets may prove vital for effective malaria communication

Differentiation of fetal hematopoietic stem cells requires ARID4B to restrict autocrine KITLG/KIT-Src signaling.

Balance between the hematopoietic stem cell (HSC) duality to either possess self-renewal capacity or differentiate into multipotency progenitors (MPPs) is crucial for maintaining homeostasis of the hematopoietic stem/progenitor cell (HSPC) compartment. To retain the HSC self-renewal activity, KIT, a receptor tyrosine kinase, in HSCs is activated by its cognate ligand KITLG originating from niche cells. Here, we show that AT-rich interaction domain 4B (ARID4B) interferes with KITLG/KIT signaling, consequently allowing HSC differentiation. Conditional Arid4b knockout in mouse hematopoietic cells blocks fetal HSC differentiation, preventing hematopoiesis. Mechanistically, ARID4B-deficient HSCs self-express KITLG and overexpress KIT. As to downstream pathways of KITLG/KIT signaling, inhibition of Src family kinases rescues the HSC differentiation defect elicited by ARID4B loss. In summary, the intrinsic ARID4B-KITLG/KIT-Src axis is an HSPC regulatory program that enables the differentiation state, while KIT stimulation by KITLG from niche cells preserves the HSPC undifferentiated pool

Cryopreservation of Orchid Genetic Resources by Desiccation: A Case Study of Bletilla formosana

Many native orchid populations declined yearly due to economic development and climate change. This resulted in some wild orchids being threatened. In order to maintain the orchid genetic resources, development of proper methods for the long‐term preservation is urgent. Low temperature or dry storage methods for the preservation of orchid genetic resources have been implemented but are not effective in maintaining high viability of certain orchids for long periods. Cryopreservation is one of the most acceptable methods for long‐term conservation of plant germplasm. Orchid seeds and pollens are ideal materials for long‐term preservation (seed banking) in liquid nitrogen (LN) as the seeds and pollens are minute, enabling the storage of many hundreds of thousands of seeds or pollens in a small vial, and as most species germinate readily, making the technique very economical. This article describes cryopreservation of orchid genetic resources by desiccation and a case study of Bletilla formosana. We hope to provide a more practical potential cryopreservation method for future research needs

Spatial modelling and mapping of teen birth rates in Taiwan in the period 1995-2010

Geographical variations in teen birth rates (TBR) still persist despite controlling for contextual factors. The aim of this research was to identify spatial patterns of TBR in Taiwan and to examine spatial relationships among different contextual factors. Using townships as the unit of analysis (N=359), this research used social and demographic variables for the years 1995, 2000, 2005 and 2010 and conducted spatial modelling of TBR. Geographical maps of TBR were presented, and Local Indicator of Spatial Autocorrelations was used to identify TBR clustering. Comparisons were made between ordinary least-squares models and spatial lag models, in which township-level TBRs were regressed on other township-level contextual characteristics. Our study found that townships with a high TBR were mostly in eastern, central and some southern regions of Taiwan, while townships with a low TBR were in the vicinity of metropolitan areas. The significant spatial lag indicated that townships would have a higher expected prevalence rate if adjacent townships have had higher rates. Results also indicated that the percentage of aborigines and the percentage of college-educated people were consistently associated with TBR over the years. Interventions aimed at reducing TBR in Taiwan should consider the presence of spatial correlations and should incorporate neighbouring townships

Contextual factors and spatial patterns of childhood malnutrition in provinces of Burkina Faso

Background: Approximately 45% of all children's deaths are associated with malnutrition, and sub-Saharan Africa is hardest hit by this phenomenon. However, information on geographical variations of malnutrition in developing countries is limited. This study examined the geographical distribution and community characteristics associated with child malnutrition in Burkina Faso. Design: Data from the 2011 Burkina Faso Demographic Health Survey were analyzed. A general Kriging interpolation method was used to generate spatial malnutrition patterns. The global Moran's I test was used to identify significant malnutrition spatial patterns. Generalized estimating equations (GEEs) were fitted to examine the association between community level factors and malnutrition. Results: Average rates of stunting and wasting in the communities were 32.48% and 15.05%, respectively. Stunting hotspots were observed in the eastern and northeastern parts of Burkina Faso (i.e. Oudolan, Séno and Yagha, among others), while high rates of wasting were observed in the north-central part. The GEE results revealed lower stunting rates in communities with a higher percentage of households with improved sanitation. Communities with higher rates of professionally assisted births were associated with low wasting rates, while communities with higher rates of households with a low wealth index reported higher rates of wasting. Conclusions: Spatial statistical models of malnutrition prevalence are useful for indicating hotspots over wide areas and hence, for guiding intervention strategies. This study revealed significant geographical patterns and community factors associated with childhood malnutrition. These factors should be considered in future programs aimed at reducing malnutrition in Burkina Faso