Determinants of expression variability

The amount of tissue-specific expression variability (EV) across individuals is an essential characteristic of a gene and believed to have evolved, in part, under functional constraints. However, the determinants and functional implications of EV are only beginning to be investigated. Our analyses based on multiple expression profiles in 41 primary human tissues show that a gene’s EV is significantly correlated with a number of features pertaining to the genomic, epigenomic, regulatory, polymorphic, functional, structural and network characteristics of the gene. We found that (i) EV of a gene is encoded, in part, by its genomic context and is further influenced by the epigenome; (ii) strong promoters induce less variable expression; (iii) less variable gene loci evolve under purifying selection against copy number polymorphisms; (iv) genes that encode inherently disordered or highly interacting proteins exhibit lower variability; and (v) genes with less variable expression are enriched for house-keeping functions, while genes with highly variable expression tend to function in development and extra-cellular response and are associated with human diseases. Thus, our analysis reveals a number of potential mediators as well as functional and evolutionary correlates of EV, and provides new insights into the inherent variability in eukaryotic gene expression.     

Malaria Infection Has Spatial,Temporal, and Spatiotemporal Heterogeneity in Unstable Malaria Transmission Areas in Northwest Ethiopia

Background

Malaria elimination requires successful nationwide control efforts. Detecting the spatiotemporal distribution and mapping high-risk areas are useful to effectively target pockets of malaria endemic regions for interventions.

Objective

The aim of the study was to identify patterns of malaria distribution by space and time in unstable malaria transmission areas in northwest Ethiopia.

Methods

Data were retrieved from the monthly reports stored in the district malaria offices for the period between 2003 and 2012. Eighteen districts in the highland and fringe malaria areas were included and geo-coded for the purpose of this study. The spatial data were created in ArcGIS10 for each district. The Poisson model was used by applying Kulldorff methods using the SaTScan™ software to analyze the purely temporal, spatial and space-time clusters of malaria at a district levels.

Results

The study revealed that malaria case distribution has spatial, temporal, and spatiotemporal heterogeneity in unstable transmission areas. Most likely spatial malaria clusters were detected at Dera, Fogera, Farta, Libokemkem and Misrak Este districts (LLR =197764.1, p<0.001). Significant spatiotemporal malaria clusters were detected at Dera, Fogera, Farta, Libokemkem and Misrak Este districts (LLR=197764.1, p<0.001) between 2003/1/1 and 2012/12/31. A temporal scan statistics identified two high risk periods from 2009/1/1 to 2010/12/31 (LLR=72490.5, p<0.001) and from 2003/1/1 to 2005/12/31 (LLR=26988.7, p<0.001).

Conclusion

In unstable malaria transmission areas, detecting and considering the spatiotemporal heterogeneity would be useful to strengthen malaria control efforts and ultimately achieve elimination.     

Increasing Trends of Diabetes Mellitus and Body Weight: A Ten Year Observation at Gondar University Teaching Referral Hospital,Northwest Ethiopia

Background

Diabetes mellitus is becoming one of the major causes of premature adult mortality in developing countries. However, there is a very little documentation of the morbidity trend in such countries.

Objective

To assess the ten-year trend of diabetes mellitus at Gondar University Teaching Referral Hospital, northwest Ethiopia.

Methods

A hospital-based retrospective record review was done at the main referral hospital in northwest Ethiopia. Data were obtained from medical records of all registered diabetic patients in the Diabetic Follow up Clinic between 2000 and 2009. An Extended Mantel-Haenzel chi-square test for the linear trend was used to examine the trend over time.

Result

Out of the total 354,524 patients who visited the Outpatient Department of the hospital during the study period, 1553 (4.4/1000) were diabetes patients, of which 50.1% was type 1 and 49.9% type 2 diabetes mellitus. The average increase in the proportion of both Type 1 and Type 2 diabetes mellitus cases between 2000 and 2009 was 125%. The mean (±SD) age for Type 1 diabetes mellitus was 29.1 (±12), and 53.5 (±12) for Type 2 diabetes. Overall 42.5% of the diabetes mellitus patients were female and 31.7% were rural residents. The mean body mass index for both type of diabetes mellitus increased from 15.9 to 18.3 kg for type 1 and from 23.8 to 24.6 for type 2 between 2000 and 2009, respectively.

Conclusion

The number of diabetes mellitus cases seen at Gondar Referral Hospital is rising steadily. A comprehensive diabetes prevention, treatment, and care program is needed to improve the quality of life of the increasing diabetes mellitus cases in Ethiopia.     

High Prevalence of Cryptococcal Antigenemia among HIV-infected Patients Receiving Antiretroviral Therapy in Ethiopia

Background

Cryptococcal disease is estimated to be responsible for significant mortality in Sub-Saharan Africa; however, only scarce epidemiology data exists. We sought to evaluate the prevalence of and risk factors for cryptococcal antigenemia in Ethiopia.

Methods

Consecutive adult HIV-infected patients from two public HIV clinics in Addis Ababa, Ethiopia were enrolled into the study. A CD4 count ≤200 cells/μl was required for study participation. Patients receiving anti-retroviral therapy (ART) were not excluded. A cryptococcal antigen test was performed for all patients along with an interview, physical exam, and medical chart abstraction. Logistic regression analysis was used to assess risk factors for cryptococcal antigenemia.

Results

369 HIV-infected patients were enrolled; mean CD4 123 cells/μl and 74% receiving ART. The overall prevalence of cryptococcal antigenemia was 8.4%; 11% in patients with a CD4 count <100 cells/μl, 8.9% with CD4 100 to 150 cells/μl and 5.7% with CD4150-200 cell/μl. 84% of patients with cryptococcal antigenemia were receiving ART. In multivariable analysis, increasing age, self reported fever, CD4 count <100 cells/μl, and site of screening were associated with an increased risk of cryptococcal antigenemia. No individual or combination of clinical symptoms had optimal sensitivity or specificity for cryptococcal antigenemia.

Conclusion

Cryptococcal antigenemia is high in Ethiopia and rapid scale up of screening programs is needed. Screening should be implemented for HIV-infected patients with low CD4 counts regardless of symptoms or receipt of ART. Further study into the effect of location and environment on cryptococcal disease is warranted.     

Dog Demography,Animal Bite Management and Rabies Knowledge-Attitude and Practices in the Awash Basin,Eastern Ethiopia

Background

Rabies is a viral zoonosis that has been described in limited numbers of studies in Ethiopia at large and among pastoralists in particular. This study assessed dog demography, bite wound prevalence and management, potential risk factors of disease transmission and knowledge attitude practice towards rabies among urban dwellers, pastoralists and health workers in Awash, Eastern Ethiopia.

Methodology

Information was collected by means of structured questionnaires and interviews and through medical and official records from the Agricultural and Health bureaus.

Principal Findings

Respondents totaled 539 (471 urban, 49 pastoralists, 19 medical). Dog(s) were owned in 33% urban and 75.5% pastoralist households respectively. Mean dog number per dog owning household was 1.50 (95%CI: 1.40–1.60) in urban and 2.05 (95%CI: 1.51–2.60) in pastoralists sites. Human Dog Ratio in Metahara was 4.7:1. No bite wounds records were kept in medical facilities, where staff recalled around 100 bites per year, 2/3 being in adults. Over 90% of the respondents claimed knowing rabies but up to 79.2% pastoralist did not know how dogs acquire the disease; 37.3% urban and 23% pastoralist did not know the symptoms of rabies in dogs; 36% urban and 44% pastoralists did not know rabies symptoms in people. Eighty percent of pastoralists did not know that the disease was fatal in people if untreated. Over half (58.7%) of pastoralist respondents go to traditional healers if bitten, despite a health extension worker program in place in the study area. Knowledge gaps were also shown amidst medical staff.

Conclusions

The study highlighted overall poor disease knowledge, severe under-reporting of human rabies cases, lack of record keeping and poor collaboration between the public and animal health sectors and communities in rabies control.     

Satellite detection of cumulative and lagged effects of drought on autumn leaf senescence over the Northern Hemisphere

Climate change has substantial influences on autumn leaf senescence, that is, the end of the growing season (EOS). Relative to the impacts of temperature and precipitation on EOS, the influence of drought is not well understood, especially considering that there are apparent cumulative and lagged effects of drought on plant growth. Here, we investigated the cumulative and lagged effects of drought (in terms of the Standardized Precipitation–Evapotranspiration Index, SPEI) on EOS derived from the normalized difference vegetation index (NDVI3g) data over the Northern Hemisphere extra‐tropical ecosystems (>30°N) during 1982–2015. The cumulative effect was determined by the number of antecedent months at which SPEI showed the maximum correlation with EOS (i.e., R_max‐cml) while the lag effect was determined by a month during which the maximum correlation between 1‐month SPEI and EOS occurred (i.e., R_max‐lag). We found cumulative effect of drought on EOS for 27.2% and lagged effect for 46.2% of the vegetated land area. For the dominant time scales where the R_max‐cml and R_max‐lag occurred, we observed 1–4 accumulated months for the cumulative effect and 2–6 lagged months for the lagged effect. At the biome level, drought had stronger impacts on EOS in grasslands, savannas, and shrubs than in forests, which may be related to the different root functional traits among vegetation types. Considering hydrological conditions, the mean values of both R_max‐cml and R_max‐lag decreased along the gradients of annual SPEI and its slope, suggesting stronger cumulative and lagged effects in drier regions as well as in areas with decreasing water availability. Furthermore, the average accumulated and lagged months tended to decline along the annual SPEI gradient but increase with increasing annual SPEI. Our results revealed that drought has strong cumulative and lagged effects on autumn phenology, and considering these effects could provide valuable information on the vegetation response to a changing climate.     

Evidence for contemporary and historical gene flow between guppy populations in different watersheds,with a test for associations with adaptive traits

In dendritic river systems, gene flow is expected to occur primarily within watersheds. Yet, rare cross‐watershed transfers can also occur, whether mediated by (often historical) geological events or (often contemporary) human activities. We explored these events and their potential evolutionary consequences by analyzing patterns of neutral genetic variation (microsatellites) and adaptive phenotypic variation (male color) in wild guppies (Poecilia reticulata) distributed across two watersheds in northern Trinidad. We found the expected signatures of within‐watershed gene flow; yet we also inferred at least two instances of cross‐watershed gene flow—one in the upstream reaches and one further downstream. The upstream cross‐watershed event appears to be very recent (41 ± 13 years), suggesting dispersal via recent flooding or undocumented human‐mediated transport. The downstream cross‐watershed event appears to be considerably older (577 ± 265 years), suggesting a role for rare geological or climatological events. Alongside these strong signatures of both contemporary and historical gene flow, we found little evidence of impacts on presumably adaptive phenotypic differentiation, except perhaps in the one instance of very recent cross‐watershed gene flow. Selection in this system seems to overpower gene flow—at least on the spatiotemporal scales investigated here.     

Helminthiasis: Hookworm Infection Remains a Public Health Problem in Dera District,South Gondar,Ethiopia

Background

Intestinal parasitic infections are significant cause of morbidity and mortality in endemic countries. In Ethiopia, helminthiasis was the third leading cause of outpatient visits. Despite the health extension program was launched to address this problem, there is limited information on the burden of intestinal parasites after implementation of the program in our setting. Therefore, the aim of this study was to assess the intestinal helminthic infections among clients attending at Anbesame health center, South Gondar, Ethiopia.

Methods

A cross sectional study was conducted at Anbesame health center from March to June 2015. A structured questionnaire was used to collect data from 464 study participants selected consecutively. Stool specimen collection, processing through formol-ether concentration technique and microscopic examination for presence of parasites were carried out. Data were entered, cleaned and analyzed using SPSS Version 20.

Results

Among the total 464 study participants with median (±IQR) age of 25.0 (±21.75) years, 262 (56.5%) were females. Helminthic infection was found in 97 (20.9%) participants. Hookworm (68 [14.7%]) was the predominant parasite followed by S. mansoni (11 [2.4%]), E. vermicularis (9 [1.9%]) and S. stercoralis (5 [1.1%]). Patients with age group ≥15 years (AOR: 5.26; 95% CI: 2.05–13.46; P: 0.001) and walking barefoot (AOR: 2.20; 95% CI: 1.08–4.48; P: 0.031) were more vulnerable from the hookworm infections.

Conclusions

There was a high burden of hookworm infections in our setting. Hence, regular shoes wearing, considering all age groups in the albendazole deworming as mass treatment and environmental hygiene are important interventions to reduce the burden of such neglected tropical disease.