Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations

Malaria has been a very strong selection pressure in recent human evolution, particularly in Africa. Of the one million deaths per year due to malaria, more than 90% are in sub-Saharan Africa, a region with high levels of genetic variation and population substructure. However, there have been few studies of nucleotide variation at genetic loci that are relevant to malaria susceptibility across geographically and genetically diverse ethnic groups in Africa. Invasion of erythrocytes by Plasmodium falciparum parasites is central to the pathology of malaria. Glycophorin A (GYPA) and B (GYPB), which determine MN and Ss blood types, are two major receptors that are expressed on erythrocyte surfaces and interact with parasite ligands. We analyzed nucleotide diversity of the glycophorin gene family in 15 African populations with different levels of malaria exposure. High levels of nucleotide diversity and gene conversion were found at these genes. We observed divergent patterns of genetic variation between these duplicated genes and between different extracellular domains of GYPA. Specifically, we identified fixed adaptive changes at exons 3-4 of GYPA. By contrast, we observed an allele frequency spectrum skewed toward a significant excess of intermediate-frequency alleles at GYPA exon 2 in many populations; the degree of spectrum distortion is correlated with malaria exposure, possibly because of the joint effects of gene conversion and balancing selection. We also identified a haplotype causing three amino acid changes in the extracellular domain of glycophorin B. This haplotype might have evolved adaptively in five populations with high exposure to malaria

Periodically Disturbing the Spatial Structure of Biofilms Can Affect the Production of an Essential Virulence Factor in Pseudomonas aeruginosa

Understanding the environmental factors that affect the production of virulence factors has major implications in evolution and medicine. While spatial structure is important in virulence factor production, observations of this relationship have occurred in undisturbed or continuously disturbed environments. However, natural environments are subject to periodic fluctuations, including changes in physical forces, which could alter the spatial structure of bacterial populations and impact virulence factor production. Using Pseudomonas aeruginosa PA14, we periodically applied a physical force to biofilms and examined production of pyoverdine. Intermediate frequencies of disturbance reduced the amount of pyoverdine produced compared to undisturbed or frequently disturbed conditions. To explore the generality of this finding, we examined how an intermediate disturbance frequency affected pyoverdine production in 21 different strains of P. aeruginosa. Periodic disturbance increased, decreased, or did not change the amount of pyoverdine produced relative to undisturbed populations. Mathematical modeling predicts that interactions between pyoverdine synthesis rate and biofilm density determine the amount of pyoverdine synthesized. When the pyoverdine synthesis rates are high, depletion of the biofilm due to disturbance reduces the accumulation of pyoverdine. At intermediate synthesis rates, production of pyoverdine increases during disturbance as bacteria dispersed into the planktonic state enjoy increased growth and pyoverdine production rates. At low synthesis rates, disturbance does not alter the amount of pyoverdine produced since disturbance-driven access to nutrients does not augment pyoverdine synthesis. Our results suggest that environmental conditions shape robustness in the production of virulence factors and may lead to novel approaches to treat infections

Limitations of Electromyography in the Assessment of Abdominal Wall Muscle Contractility Following Botulinum Toxin A Injection

Purpose: Pre-operative botulinum toxin A (BTA) injection of the lateral obliques aims to facilitate the closure of large ventral hernia defects and decrease the risk of repair breakdown during the critical healing phase. The exact duration of post-operative BTA effect and top-up timing in cases at high risk of recurrence remains uncertain. This study was designed to assess the value of electromyography (EMG) in determining the appropriate time for BTA top-up.Methods: 56 patients underwent ventral hernia repair with pre-operative BTA infiltration of the lateral obliques. Eleven patients at high risk of recurrence considered suitable for BTA top-up were assessed post-operatively with both functional computed tomography (CT) and EMG. CT assessed segmental contractility of each muscle layer. Single-point EMG assessed the activity of individual muscle layers bilaterally in the anterior axillary line.Results: CT showed (i) variable contractility of anterior and posterior muscle segments prior to BTA injection; (ii) absent or incomplete muscle paralysis in over half of all segments; (iii) increased BTA effect on progress scans; and (iv) non-uniform pattern of change in BTA effect between the anterior and posterior muscle. EMG demonstrated modest voluntary activity in most muscle layers. Compared to standard of reference (CT), EMG showed moderate sensitivity (0.62), poor specificity (0.48), poor accuracy (0.57), and incorrect grading in 71% of true positive results.Conclusions: As BTA effect wanes, single-point EMG cannot reliably determine functional muscle status. A novel finding is that BTA-induced paralysis of the abdominal muscles may be remarkably non-uniform in degree, distribution and duration

Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF–MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract’s effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF–MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2′-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress

Clinical and histopathological study on reproductive lesions caused by Pasteurella multocida type B2 immunogens in buffalo heifers

Haemorrhagic septicaemia (HS) is a globally renowned disease that affects cattle and buffaloes. Its effects on the reproductive system have not been previously studied. The present study evaluated the pathological responses in pre-pubertal female buffaloes infected with immunogens; lipopolysaccharide (LPS) and outer membrane protein (OMP) derived from P. multocida type B:2. Fifteen healthy pre-pubertal female buffaloes were divided into 5 equal groups. Buffaloes in groups 1 and 2 were intravenously and orally inoculated with P. multocida LPS, while those in groups 3 and 4 were sub-cutaneously and orally inoculated with P. multocida OMP. Buffaloes in group 5 were inoculated with sterile phosphate buffered saline (negative control). During the post infection period, all buffaloes were examined for clinical signs throughout 21 days and surviving animals were euthanised for postmortem evaluation. Histopathological evaluation of buffaloes inoculated intravenously with LPS showed a significantly higher occurrence (P<0.05) of necrosis and degeneration in the uterine horn and supramammary glands . Following inoculation with OMP, haemorrhage and congestion was significantly higher (P<0.05) in the ovaries, cervix, vagina, mammary and supra-mammary glands of buffaloes inoculated subcutaneously, while necrosis and degeneration and inflammatory cell infiltration in different organs was also significantly increased in the same group. The findings showed that both P. multocida bacterial LPS and OMP affected the uterine horn, ovaries, cervix, mammary gland and supramammary lymph nodes of buffalo calves inoculated either intravenously or subcutaneously, as compared to those inoculated orally

Lymphomas in sub-Saharan Africa - what can we learn and how can we help in improving diagnosis, managing patients and fostering translational research?

Approximately 30 000 cases of non-Hodgkin lymphoma (NHL) occur in the equatorial belt of Africa each year. Apart from the fact that Burkitt lymphoma (BL) is very common among children and adolescents in Africa and that an epidemic of human immunodeficiency virus (HIV) infection is currently ongoing in this part of the world, very little is known about lymphomas in Africa. This review provides information regarding the current infrastructure for diagnostics in sub-Saharan Africa. The results on the diagnostic accuracy and on the distribution of different lymphoma subsets in sub-Saharan Africa were based on a review undertaken by a team of lymphoma experts on 159 fine needle aspirate samples and 467 histological samples during their visit to selected sub- Saharan African centres is presented. Among children (age), BL accounted for 82% of all NHL, and among adults, diffuse large B-cell lymphoma accounted for 55% of all NHLs. Among adults, various lymphomas other than BL, including T-cell lymphomas, were encountered. The review also discusses the current strategies of the International Network of Cancer Treatment and Research on improving the diagnostic standards and management of lymphoma patients and in acquiring reliable clinical and pathology data in sub- Saharan Africa for fostering high-quality translational research

Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities

Clinical and histopathological study on reproductive lesions caused by Pasteurella multocida type B2 immunogens in buffalo heifers

Hemorrhagic septicemia (HS) is a globally renowned disease that affects cattle and buffaloes. Its effects on the reproductive system have not been previously studied. Thus, the present study aims to evaluate the pathological responses in pre-pubertal female buffalo infected with immunogens; lipopolysaccharide (LPS) and outer membrane protein (OMP) derived from P. multocida type B: 2. Fifteen healthy pre-pubertal female buffaloes of approximately 8 months old were selected and divided into five equal groups of 3 buffaloes each. Buffaloes in groups 1 and 2 were intravenously and orally inoculated with 10 mL of P. multocida LPS at 1× 1012 colony forming unit (cfu) ,while those in group 3 and group 4 were subcutaneously and orally inoculated with10 mL of P. multocida OMP at 1× 1012 colony forming unit (cfu). Buffaloes in group 5 were inoculated with 10mL of sterile phosphate buffered saline (PBS) PH7 and served as the negative control. During the post infection period, all buffaloes were examined for clinical signs throughout 21 days and surviving buffaloes were euthanized for postmortem evaluation. Histopathological evaluation of buffaloes inoculated with LPS showed a significantly higher occurrence (p<0.05) of necrosis and degeneration in the uterine horn and supramammary glands of buffaloes inoculated intravenously. Following inoculation with OMP, hemorrhage and congestion was significantly higher (p<0.05) in the ovaries, cervix, vagina, mammary and supra-mammary glands of buffaloes inoculated subcutaneously, while necrosis and degeneration and inflammatory cell infiltration in different organs was also significantly increased in the same inoculation group. The findings of this study have shown that both P. multocida bacterial LPS and OMP affect the uterine horn, ovaries, cervix, mammary gland and supramammary lymph nodes of buffalo calves inoculated either intravenously or subcutaneously, as compared to those inoculated orally