Absence of N-terminal acetyltransferase diversification during evolution of eukaryotic organisms

Protein N-terminal acetylation is an ancient and ubiquitous co-translational modification catalyzed by a highly conserved family of N-terminal acetyltransferases (NATs). Prokaryotes have at least 3 NATs, whereas humans have six distinct but highly conserved NATs, suggesting an increase in regulatory complexity of this modification during eukaryotic evolution. Despite this, and against our initial expectations, we determined that NAT diversification did not occur in the eukaryotes, as all six major human NATs were most likely present in the Last Eukaryotic Common Ancestor (LECA). Furthermore, we also observed that some NATs were actually secondarily lost during evolution of major eukaryotic lineages; therefore, the increased complexity of the higher eukaryotic proteome occurred without a concomitant diversification of NAT complexes

Mapping Genetic Diversity of Cherimoya (Annona cherimola Mill.): Application of Spatial Analysis for Conservation and Use of Plant Genetic Resources

There is a growing call for inventories that evaluate geographic patterns in diversity of plant genetic resources maintained on farm and in species' natural populations in order to enhance their use and conservation. Such evaluations are relevant for useful tropical and subtropical tree species, as many of these species are still undomesticated, or in incipient stages of domestication and local populations can offer yet-unknown traits of high value to further domestication. For many outcrossing species, such as most trees, inbreeding depression can be an issue, and genetic diversity is important to sustain local production. Diversity is also crucial for species to adapt to environmental changes. This paper explores the possibilities of incorporating molecular marker data into Geographic Information Systems (GIS) to allow visualization and better understanding of spatial patterns of genetic diversity as a key input to optimize conservation and use of plant genetic resources, based on a case study of cherimoya (Annona cherimola Mill.), a Neotropical fruit tree species. We present spatial analyses to (1) improve the understanding of spatial distribution of genetic diversity of cherimoya natural stands and cultivated trees in Ecuador, Bolivia and Peru based on microsatellite molecular markers (SSRs); and (2) formulate optimal conservation strategies by revealing priority areas for in situ conservation, and identifying existing diversity gaps in ex situ collections. We found high levels of allelic richness, locally common alleles and expected heterozygosity in cherimoya's putative centre of origin, southern Ecuador and northern Peru, whereas levels of diversity in southern Peru and especially in Bolivia were significantly lower. The application of GIS on a large microsatellite dataset allows a more detailed prioritization of areas for in situ conservation and targeted collection across the Andean distribution range of cherimoya than previous studies could do, i.e. at province and department level in Ecuador and Peru, respectively

Frequent, Geographically Structured Heteroplasmy in the Mitochondria of a Flowering Plant, Ribwort Plantain (Plantago lanceolata)

Recent research has convincingly documented cases of mitochondrial heteroplasmy in a small set of wild and cultivated plant species. Heteroplasmy is suspected to be common in flowering plants and investigations of additional taxa may help understand the mechanisms generating heteroplasmy as well as its effects on plant phenotypes. The role of mitochondrial heteroplasmy is of particular interest in plants as cytoplasmic male sterility is controlled by mitochondrial genotypes, sometimes leading to co-occurring female and hermaphroditic individuals (gynodioecy). Paternal leakage may be important in the evolution of mating systems in such populations. We conducted a genetic survey of the gynodioecious plant Plantago lanceolata, in which heteroplasmy has not previously been reported, and estimated the frequencies of mitochondrial genotypes and heteroplasmy. Sanger sequence genotyping of 179 individuals from 15 European populations for two polymorphic mitochondrial loci, atp6 and rps12, identified 15 heteroplasmic individuals. These were distributed among 6 of the 10 populations that had polymorphisms in the target loci and represented 8% of all sampled individuals and 15% of the individuals in those 6 populations. The incidence was highest in Northern England and Scotland. Our results are consistent with geographic differences in the incidence of paternal leakage and/or the rates of nuclear restoration of male fertility

Incidence and risk factors for community-acquired acute gastroenteritis in north-west Germany in 2004

In developed countries, acute gastroenteritis (AGE) is a major source of morbidity. However, only a few studies have estimated its incidence and the associated medical burden. This population-based study determined the incidence of community-acquired AGE patients seeking medical care and the relative role of various pathogens. Stool samples from patients with AGE presenting to a general practitioner (GP), pediatrician, or specialist in internal medicine for that reason were screened for various bacterial and viral enteropathogens. A control group was established as well. Incidences were calculated by the number of positive patients divided by the general population. The study was performed in north-west Germany in 2004. The incidence of AGE patients requiring medical consultation was 4,020/100,000 inhabitants. Children (<5 years of age) were at the highest risk (13,810/100,000 inhabitants). Of the patients, 6.6% were tested positive for an enteropathogenic bacteria and 17.7% for a viral agent. The predominant pathogens were norovirus (626/100,000) and rotavirus (270/100,000). Salmonella was the most frequently detected bacteria (162/100,000). The results presented confirm AGE and, specifically, AGE of viral origin as a major public health burden in developed countries

Motor performance in chronic low back pain: is there an influence of pain-related cognitions? A pilot study

Background: Chronic low back pain (CLBP) is often accompanied by an abnormal motor performance. However, it has not been clarified yet whether these deviations also occur during motor tasks not involving the back and whether the performance is influenced by pain and pain-related cognitions. Therefore, the aim of the present study is to get insight in the contribution of both pain experience and pain-related cognitions to general motor task performance in CLBP. Methods. 13 CLBP patients and 15 healthy subjects performed a hand-function task in three conditions: sitting, lying prone (lying) and lying prone without trunk support (provoking). The last condition was assumed to provoke pain-related cognitions, which was considered successful when a patients' pain expectancy on a numeric rating scale was at least 1 point higher than actual pain experienced. Subjects' performance was expressed in reaction time and movement time. Repeated measures analysis of variance was performed to detect main effect for group and condition. Special interest was given to group*condition interaction, since significant interaction would indicate that patients and healthy subjects performed differently throughout the three conditions. Results: Patients were slower throughout all conditions compared to healthy subjects. With respect to the provoking condition, patients showed deteriorated performance compared to lying while healthy subjects' performance remained equal between these two conditions. Further analysis of patients' data showed that provocation was successful in 54% of the patients. Especially this group showed deteriorated performance in the provoking condition. Conclusion: It can be concluded that CLBP patients in general have worse motor task performance compared to healthy subjects and that provoking pain-related cognitions further worsened performanc

Task shifting: the answer to the human resources crisis in Africa?

Ever since the 2006 World Health Report advocated increased community participation and the systematic delegation of tasks to less-specialized cadres, there has been a great deal of debate about the expediency, efficacy and modalities of task shifting

Reproductive health for refugees by refugees in Guinea III: maternal health

BACKGROUND: Maternal mortality can be particularly high in conflict and chronic emergency settings, partly due to inaccessible maternal care. This paper examines associations of refugee-led health education, formal education, age, and parity on maternal knowledge, attitudes, and practices among reproductive-age women in refugee camps in Guinea. METHODS: Data comes from a 1999 cross-sectional survey of 444 female refugees in 23 camps. Associations of reported maternal health outcomes with exposure to health education (exposed versus unexposed), formal education (none versus some), age (adolescent versus adult), or parity (nulliparous, parous, grand multiparous), were analysed using logistic regression. RESULTS: No significant differences were found in maternal knowledge or attitudes. Virtually all respondents said pregnant women should attend antenatal care and knew the importance of tetanus vaccination. Most recognised abdominal pain (75%) and headaches (24%) as maternal danger signs and recommended facility attendance for danger signs. Most had last delivered at a facility (67%), mainly for safety reasons (99%). Higher odds of facility delivery were found for those exposed to RHG health education (adjusted odds ratio 2.03, 95%CI 1.23-3.01), formally educated (adjusted OR 1.93, 95%CI 1.05-3.92), or grand multipara (adjusted OR 2.13, 95%CI 1.21-3.75). Main reasons for delivering at home were distance to a facility (94%) and privacy (55%). CONCLUSIONS: Refugee-led maternal health education appeared to increase facility delivery for these refugee women. Improved knowledge of danger signs and the importance of skilled birth attendance, while vital, may be less important in chronic emergency settings than improving facility access where quality of care is acceptable

Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

Background. Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design. A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion. This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration. Netherlands Trial Register (NTR1636)

Immunoelectron Microscopic Evidence for Tetherin/BST2 as the Physical Bridge between HIV-1 Virions and the Plasma Membrane

Tetherin/BST2 was identified in 2008 as the cellular factor responsible for restricting HIV-1 replication at a very late stage in the lifecycle. Tetherin acts to retain virion particles on the plasma membrane after budding has been completed. Infected cells that express large amounts of tetherin display large strings of HIV virions that remain attached to the plasma membrane. Vpu is an HIV-1 accessory protein that specifically counteracts the restriction to virus release contributed by tetherin. Tetherin is an unusual Type II transmembrane protein that contains a GPI anchor at its C-terminus and is found in lipid rafts. The leading model for the mechanism of action of tetherin is that it functions as a direct physical tether bridging virions and the plasma membrane. However, evidence that tetherin functions as a physical tether has thus far been indirect. Here we demonstrate by biochemical and immunoelectron microscopic methods that endogenous tetherin is present on the viral particle and forms a bridge between virion particles and the plasma membrane. Endogenous tetherin was found on HIV particles that were released by partial proteolytic digestion. Immunoelectron microscopy performed on HIV-infected T cells demonstrated that tetherin forms an apparent physical link between virions and connects patches of virions to the plasma membrane. Linear filamentous strands that were highly enriched in tetherin bridged the space between some virions. We conclude that tetherin is the physical tether linking HIV-1 virions and the plasma membrane. The presence of filaments with which multiple molecules of tetherin interact in connecting virion particles is strongly suggested by the morphologic evidence

Treating childhood pneumonia in hard-to-reach areas: A model-based comparison of mobile clinics and community-based care

BACKGROUND: Where hard-to-access populations (such as those living in insecure areas) lack access to basic health services, relief agencies, donors, and ministries of health face a dilemma in selecting the most effective intervention strategy. This paper uses a decision mathematical model to estimate the relative effectiveness of two alternative strategies, mobile clinics and fixed community-based health services, for antibiotic treatment of childhood pneumonia, the world's leading cause of child mortality. METHODS: A "Markov cycle tree" cohort model was developed in Excel with Visual Basic to compare the number of deaths from pneumonia in children aged 1 to 59 months expected under three scenarios: 1) No curative services available, 2) Curative services provided by a highly-skilled but intermittent mobile clinic, and 3) Curative services provided by a low-skilled community health post. Parameter values were informed by literature and expert interviews. Probabilistic sensitivity analyses were conducted for several plausible scenarios. RESULTS: We estimated median pneumonia-specific under-5 mortality rates of 0.51 (95% credible interval: 0.49 to 0.541) deaths per 10,000 child-days without treatment, 0.45 (95% CI: 0.43 to 0.48) with weekly mobile clinics, and 0.31 (95% CI: 0.29 to 0.32) with CHWs in fixed health posts. Sensitivity analyses found the fixed strategy superior, except when mobile clinics visited communities daily, where rates of care-seeking were substantially higher at mobile clinics than fixed posts, or where several variables simultaneously differed substantially from our baseline assumptions. CONCLUSIONS: Current evidence does not support the hypothesis that mobile clinics are more effective than CHWs. A CHW strategy therefore warrants consideration in high-mortality, hard-to-access areas. Uncertainty remains, and parameter values may vary across contexts, but the model allows preliminary findings to be updated as new or context-specific evidence becomes available. Decision analytic modelling can guide needed field-based research efforts in hard-to-access areas and offer evidence-based insights for decision-makers