Roles of a Trypanosoma brucei 5'->3' exoribonuclease homolog in mRNA degradation

The genome of the kinetoplastid parasite Trypanosoma brucei encodes four homologs of the Saccharomyces cerevisiae 5'-->3' exoribonucleases Xrn1p and Xrn2p/Rat1p, XRNA, XRNB, XRNC, and XRND. In S. cerevisiae, Xrn1p is a cytosolic enzyme involved in degradation of mRNA, whereas Xrn2p is involved in RNA processing in the nucleus. Trypanosome XRND was found in the nucleus, XRNB and XRNC were found in the cytoplasm, and XRNA appeared to be in both compartments. XRND and XRNA were essential for parasite growth. Depletion of XRNA increased the abundances of highly unstable developmentally regulated mRNAs, perhaps by delaying a deadenylation-independent decay pathway. Degradation of more stable or unregulated mRNAs was not affected by XRNA depletion although a slight decrease in average poly(A) tail length was observed. We conclude that in trypanosomes 5'-->3' exonuclease activity is important in degradation of highly unstable, regulated mRNAs, but that for other mRNAs another step is more important in determining the decay rate.     

Species composition and diversity of small Afromontane forest fragments in northern Ethiopia

In the highlands of northern Ethiopia, remnants of the original Afromontane forest vegetation are largely restricted to church yards and other sacred groves in a matrix of cropland and semiarid degraded savanna. To assess the potential for natural forest regeneration, species composition and diversity of all forest fragments (10) in a study area of 13,000 ha were analyzed in relation to environmental and soil variables. Using a random design and a density of approximately one plot per 2 ha in all fragments, 31 20×20 m plots were sampled. Indicator species analysis and MRPP tests yielded five communities representing two forest types and one degraded savanna habitat. The forest fragments had a species-poor tree and shrub community in which plots were rather homogeneous and most species abundant. NMDS and analysis of variance indicated that a topographical gradient correlated to soil phosphorus, soil depth, stoniness and the proximity to the river system explained the major differences in species composition and separated moist and dry Afromontane forest communities. The grazing intensity further partitioned the habitats. Present communities and their environmental correlates indicate that the secondary climax forest in the area probably consisted of dry Afromontane forest interlaced by broad strips of moist Afromontane forest along rivers and streams and not a continuous, mono-dominant Juniperus forest as is often presumed. Negative effects of the degraded matrix on forest fragments increased with decreasing patch area and increasing shape irregularity. Nevertheless, all remaining fragments are important for their role in the landscape ecology of the region as refuges and species pools and should be protected and managed accordingly. If seed dispersal from forest fragments into exclosures and subsequent tree recruitment are both successful, the vegetation type most likely to establish is Afromontane savanna woodland, and if managed properly, eventually dry Afromontane forest may arise. Increasing the size of small patches and placing forest plantations and exclosures in the vicinity of small forest fragments is expected to yield the most immediate results. This approach may increase the likelihood of patch colonisation by frugivorous forest birds and thus foster the regeneration of native woody species.     

Human Resource and Funding Constraints for Essential Surgery in District Hospitals in Africa: A Retrospective Cross-Sectional Survey

Background

There is a growing recognition that the provision of surgical services in low-income countries is inadequate to the need. While constrained health budgets and health worker shortages have been blamed for the low rates of surgery, there has been little empirical data on the providers of surgery and cost of surgical services in Africa. This study described the range of providers of surgical care and anesthesia and estimated the resources dedicated to surgery at district hospitals in three African countries.

Methods and Findings

We conducted a retrospective cross-sectional survey of data from eight district hospitals in Mozambique, Tanzania, and Uganda. There were no specialist surgeons or anesthetists in any of the hospitals. Most of the health workers were nurses (77.5%), followed by mid-level providers (MLPs) not trained to provide surgical care (7.8%), and MLPs trained to perform surgical procedures (3.8%). There were one to six medical doctors per hospital (4.2% of clinical staff). Most major surgical procedures were performed by doctors (54.6%), however over one-third (35.9%) were done by MLPs. Anesthesia was mainly provided by nurses (39.4%). Most of the hospital expenditure was related to staffing. Of the total operating costs, only 7% to 14% was allocated to surgical care, the majority of which was for obstetric surgery. These costs represent a per capita expenditure on surgery ranging from US$0.05 to US$0.14 between the eight hospitals.

Conclusion

African countries have adopted different policies to ensure the provision of surgical care in their respective district hospitals. Overall, the surgical output per capita was very low, reflecting low staffing ratios and limited expenditures for surgery. We found that most surgical and anesthesia services in the three countries in the study were provided by generalist doctors, MLPs, and nurses. Although more information is needed to estimate unmet need for surgery, increasing the funds allocated to surgery, and, in the absence of trained doctors and surgeons, formalizing the training of MLPs appears to be a pragmatic and cost-effective way to make basic surgical services available in underserved areas. Please see later in the article for the Editors'' Summary     

Enhanced selectivity profile of pyrazole-urea based DFG-out p38α inhibitors

By targeting an extended region of the conventional ‘DFG-out’ pocket of p38α, while minimizing interactions with the specificity pocket and eliminating interactions with the adenine binding site, we are able to design and synthesize a number of pyrazole-urea based DFG-out p38α inhibitors with good potencies, and excellent selectivity.     

Inland fisheries development versus aquatic biodiversity conservation in China and its global implications

Reviews in Fish Biology and Fisheries - China is unique among nations on account of its rich aquatic biodiversity (1443 inland fish species comprising 10% of those worldwide), status as the...     

Genetic Variation in the Base Excision Repair Pathway,Environmental Risk Factors,and Colorectal Adenoma Risk

Cigarette smoking, high alcohol intake, and low dietary folate levels are risk factors for colorectal adenomas. Oxidative damage caused by these three factors can be repaired through the base excision repair pathway (BER). We hypothesized that genetic variation in BER might modify colorectal adenoma risk. In a sigmoidoscopy-based study, we examined associations between 182 haplotype tagging SNPs in 14 BER genes, and colorectal adenoma risk, and examined their potential role as modifiers of the effect cigarette smoking, alcohol intake, and dietary folate levels. Among all individuals, no statistically significant associations between BER SNPs and adenoma risk persisted after correction for multiple comparisons. However, among Asian-Pacific Islanders we observed two SNPs in FEN1 and one in NTHL1, and among African-Americans one SNP in APEX1 that were associated with colorectal adenoma risk. Significant associations were also observed between SNPs in the NEIL2 gene and rectal adenoma risk. Three SNPS modified the effect of smoking (MUTYH interaction p = 0.002; OGG1 interaction p = 0.013); FEN1 interaction p = 0.013)), one SNP in LIG3 modified the effect of alcohol consumption (interaction p = 0.024) and two SNPs in LIG3 modified the effect of dietary folate (interaction p = 0.001 and p = 0.08) on colorectal adenoma risk. These findings support a role for genetic variants in the BER pathway as potential modifiers of colorectal adenoma risk. Our findings strengthen the role of oxidative damage induced by key lifestyle and dietary risk factors in colorectal adenoma formation.     

Molecular‐ and pollen‐based vegetation analysis in lake sediments from central Scandinavia

Plant and animal biodiversity can be studied by obtaining DNA directly from the environment. This new approach in combination with the use of generic barcoding primers (metabarcoding) has been suggested as complementary or alternative to traditional biodiversity monitoring in ancient soil sediments. However, the extent to which metabarcoding truly reflects plant composition remains unclear, as does its power to identify species with no pollen or macrofossil evidence. Here, we compared pollen‐based and metabarcoding approaches to explore the Holocene plant composition around two lakes in central Scandinavia. At one site, we also compared barcoding results with those obtained in earlier studies with species‐specific primers. The pollen analyses revealed a larger number of taxa (46), of which the majority (78%) was not identified by metabarcoding. The metabarcoding identified 14 taxa (MTUs), but allowed identification to a lower taxonomical level. The combined analyses identified 52 taxa. The barcoding primers may favour amplification of certain taxa, as they did not detect taxa previously identified with species‐specific primers. Taphonomy and selectiveness of the primers are likely the major factors influencing these results. We conclude that metabarcoding from lake sediments provides a complementary, but not an alternative, tool to pollen analysis for investigating past flora. In the absence of other fossil evidence, metabarcoding gives a local and important signal from the vegetation, but the resulting assemblages show limited capacity to detect all taxa, regardless of their abundance around the lake. We suggest that metabarcoding is followed by pollen analysis and the use of species‐specific primers to provide the most comprehensive signal from the environment.     

Optimization of selection for growth in Menz Sheep while minimizing inbreeding depression in fitness traits

The genetic trends in fitness (inbreeding, fertility and survival) of a closed nucleus flock of Menz sheep under selection during ten years for increased body weight were investigated to evaluate the consequences of selection for body weight on fitness. A mate selection tool was used to optimize in retrospect the actual selection and matings conducted over the project period to assess if the observed genetic gains in body weight could have been achieved with a reduced level of inbreeding. In the actual selection, the genetic trends for yearling weight, fertility of ewes and survival of lambs were 0.81 kg, –0.00026% and 0.016% per generation. The average inbreeding coefficient remained zero for the first few generations and then tended to increase over generations. The genetic gains achieved with the optimized retrospective selection and matings were highly comparable with the observed values, the correlation between the average breeding values of lambs born from the actual and optimized matings over the years being 0.99. However, the level of inbreeding with the optimized mate selections remained zero until late in the years of selection. Our results suggest that an optimal selection strategy that considers both genetic merits and coancestry of mates should be adopted to sustain the Menz sheep breeding program.     

Population dynamics of Walia ibex (Capra walie) at Simien Mountains National Park,Ethiopia

Intensive total direct counts of Walia ibex (Capra walie) population were performed at Simien Mountains National Park (SMNP) in 2009. Historical data were collected from SMNP and literature reviews. Different models were suited to determine population growth rates and intrinsic rate of increase. The population size estimated was 745 animals. The correlation between the two repeated counts was significant (r = 0.99 and P < 0.01). Mean instantaneous growth rate (r), growth rate per capita (λ) and population annual growth rate (Λ) were 2.6 ± 2.6, 0.03 ± 0.18 and 19.5 ± 50.4, respectively. Instantaneous growth rate and growth rate per capita were positively correlated (r = 0.958, P < 0.01). Average growth rate (rΛ) and intrinsic rate of increase (rr) under ideal (r = 0.950, P < 0.01) and random environments (r = 0.810, P < 0.01) were positively correlated. The population grows by 2.5% under ideal environments with an intrinsic increase of 0.04 (0.006%) and by 0.13% under random environments with intrinsic rate of decrease of ?0.184 or ?0.025% per year, respectively. The mean rank of the flock structure of whole population was 3.13, 3.88, 2.00 and 1.00 for males, females, juveniles and unidentified, respectively.