Evolution of a supergene that regulates a trans-species social polymorphism

Supergenes are clusters of linked genetic loci that jointly affect the expression of complex phenotypes, such as social organization. Little is known about the origin and evolution of these intriguing genomic elements. Here we analyse whole-genome sequences of males from native populations of six fire ant species and show that variation in social organization is under the control of a novel supergene haplotype (termed Sb), which evolved by sequential incorporation of three inversions spanning half of a 'social chromosome'. Two of the inversions interrupt protein-coding genes, resulting in the increased expression of one gene and modest truncation in the primary protein structure of another. All six socially polymorphic species studied harbour the same three inversions, with the single origin of the supergene in their common ancestor inferred by phylogenomic analyses to have occurred half a million years ago. The persistence of Sb along with the ancestral SB haplotype through multiple speciation events provides a striking example of a functionally important trans-species social polymorphism presumably maintained by balancing selection. We found that while recombination between the Sb and SB haplotypes is severely restricted in all species, a low level of gene flux between the haplotypes has occurred following the appearance of the inversions, potentially mitigating the evolutionary degeneration expected at genomic regions that cannot freely recombine. These results provide a detailed picture of the structural genomic innovations involved in the formation of a supergene controlling a complex social phenotype

Restriction associated DNA-genotyping at multiple spatial scales in Arabidopsis lyrata reveals signatures of pathogen-mediated selection

Background: Genome scans based on outlier analyses have revolutionized detection of genes involved in adaptive processes, but reports of some forms of selection, such as balancing selection, are still limited. It is unclear whether high throughput genotyping approaches for identification of single nucleotide polymorphisms have sufficient power to detect modes of selection expected to result in reduced genetic differentiation among populations. In this study, we used Arabidopsis lyrata to investigate whether signatures of balancing selection can be detected based on genomic smoothing of Restriction Associated DNA sequencing (RAD-seq) data. We compared how different sampling approaches (both within and between subspecies) and different background levels of polymorphism (inbreeding or outcrossing populations) affected the ability to detect genomic regions showing key signatures of balancing selection, specifically elevated polymorphism, reduced differentiation and shifts towards intermediate allele frequencies. We then tested whether candidate genes associated with disease resistance (R-gene analogs) were detected more frequently in these regions compared to other regions of the genome. Results: We found that genomic regions showing elevated polymorphism contained a significantly higher density of R-gene analogs predicted to be under pathogen-mediated selection than regions of non-elevated polymorphism, and that many of these also showed evidence for an intermediate site-frequency spectrum based on Tajima’s D. However, we found few genomic regions that showed both elevated polymorphism and reduced FST among populations, despite strong background levels of genetic differentiation among populations. This suggests either insufficient power to detect the reduced population structure predicted for genes under balancing selection using sparsely distributed RAD markers, or that other forms of diversifying selection are more common for the R-gene analogs tested. Conclusions: Genome scans based on a small number of individuals sampled from a wide range of populations were sufficient to confirm the relative scarcity of signatures of balancing selection across the genome, but also identified new potential disease resistance candidates within genomic regions showing signatures of balancing selection that would be strong candidates for further sequencing efforts

Controlled Trial of Transfusions for Silent Cerebral Infarcts in Sickle Cell Anemia

BACKGROUND Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular bloodtransfusion therapy than among those who received standard care. METHODS In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct. RESULTS A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04). CONCLUSIONS Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.

Phytocompounds and modulatory effects of Anacardium microcarpum (cajui) on antibiotic drugs used in clinical infections

Valter M Barbosa-Filho,1,2 Emily P Waczuk,2 Nadghia F Leite,3 Irwin RA Menezes,1 José GM da Costa,1 Sírleis R Lacerda,1 Isaac A Adedara,2 Henrique Douglas Melo Coutinho,4 Thais Posser,5 Jean P Kamdem2,6 1Departamento de Ciências Biológicas, Centro de Ciências Biológicas e da Saúde (CCBS), Universidade Regional do Cariri (URCA), Crato, CE, Brazil; 2Programa de Pós-Graduação em Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil; 3Departamento de Química Biológica, Centro de Ciências Biológicas e da Saúde (CCBS), 4Laboratory of Microbiology and Molecular Biology, Universidade Regional do Cariri (URCA), Crato, CE, Brazil; 5Campus São Gabriel, Universidade Federal do Pampa, São Gabriel, RS, Brazil; 6Departamento de Bioquímica, Instituto de Ciências Básica da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil Background: The challenge of antibiotic resistance and the emergence of new infections have generated considerable interest in the exploration of natural products from plant origins as combination therapy. In this context, crude ethanolic extract (CEE), ethyl acetate fraction (EAF), and methanolic fraction (MF) from Anacardium microcarpum were tested alone or in combination with antibiotics (amikacin, gentamicin, ciprofloxacin, and imipenem) against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Methods: Antibiotic resistance-modifying activity was performed using the microdilution method by determining the minimal inhibitory concentration (MIC). In addition, phytochemical prospecting analyses of tested samples were carried out. Results: Our results indicated that all the extracts showed low antibacterial activity against multidrug-resistant strains (MIC =512 µg/mL). However, addition of CEE, EAF, and MF to the growth medium at the subinhibitory concentration (MIC/8=64 µg/mL) significantly modulated amikacin- and gentamicin-resistant E. coli 06. CEE and EAF also demonstrated a significant (P<0.001) synergism with imipenem against S. aureus. In contrast, MF antagonized the antibacterial effect of ciprofloxacin and gentamicin against P. aeruginosa 03 and S. aureus 10, respectively. Qualitative phytochemical analysis of the extracts revealed the presence of secondary metabolites including phenols, flavonoids, xanthones, chalcones, and tannin pyrogallates. Conclusion: Taken together, our results suggest that A. microcarpum is a natural resource with resistance-modifying antibacterial activity that needs to be further investigated to overcome the present resistant-infection problem. Keywords: multidrug-resistant, A. microcarpum, antibacterial activit

Prevalence and risk factors of peripheral artery disease in black Africans with HIV infection: a cross-sectional hospital-based study

Félicité Kamdem,1,2 Yacouba Mapoure,1,2 Ba Hamadou,3 Fanny Souksouna,2 Marie Solange Doualla,1,3 Ahmadou Musa Jingi,3 Caroline Kenmegne,1 Fernando Kemta Lekpa,1,4 Jaff Kweban Fenkeu,1 Gisèle Imandy,5 Jean Pierre Nda Mefo’o,2,5 Henry Luma1,3 1Internal Medicine Service, Douala General Hospital, Douala, Cameroon; 2Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon; 3Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaounde 1, Yaounde, Cameroon; 4Faculty of Health Sciences, University of Buea, Buea, Cameroon; 5Chemical Pathology Laboratory, Douala General Hospital, Douala, Cameroon Background: The prevalence of peripheral artery disease (PAD) is not well known among HIV-infected patients in Africa. The aim of this study was to determine the prevalence and associated risk factors of PAD among HIV-infected patients at the Douala General Hospital (DGH).Methods: This was a cross-sectional descriptive and analytic study between November 2015 and April 2016. We recruited patients aged ≥21 years, diagnosed with HIV infection, and who were receiving care at the DGH. We collected sociodemographic data and past medical history of patients. We measured their ankle-brachial index (ABI). We defined PAD as an ABI <0.9. We also measured their fasting blood glucose and lipid profile.Results: We recruited 144 patients for this study. The mean age was 46±9 years, and 72.2% were females. Of which, 89% were on antiretroviral treatment (ARV). Their mean CD4+ T lymphocytes count was 451±306 cells/mm3. Their mean ABI was 1.12±0.17 and 1.07±0.11, respectively, on the left and right legs (P>0.05). The prevalence of PAD was 6.9% (95% CI: 3.4–12.4), and 60% of patients with PAD were symptomatic. After adjusting for age, sex and ARV, ARV treatment was protective (aOR: 0.18, [95% CI: 0.04–0.82], P=0.034), while WHO stages III or IV was associated with PAD (aOR: 11.1, [95% CI: 2.19–55.92], P=0.004).Conclusion: The prevalence of PAD was not as high as expected in this group of patients with high cardiovascular risk infected with HIV. Advanced HIV disease was associated with PAD, while ARV was protective. Keywords: HIV, peripheral artery disease, prevalence, risk factors, Afric