Virtual screening and in vitro evaluation of putative positive allosteric modulators of the GABAB receptor

-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter of the central nervous system (CNS). GABA exhibits its function by binding to either the ionotropic GABAA receptor or the metabotropic GABAB receptor, causing a decrease in activity in the nervous system. Disruption in the GABAergic system has been associated with various neurological conditions, including Alzheimer’s disease, anxiety, depressive disorders, and epilepsy. Currently, there is only one marketed drug that work on the GABAB – receptor, on the orthosteric site to be more specific. The discovery of allosteric modulators for the G-protein coupled receptors provides a promising new strategy with potential for developing novel treatments for a variety of CNS disorders, as they allow for increased drug selectivity and potentially decreased adverse side effects. Homology models of the GABAB receptor were built due to the lack of an experimentally solved three-dimensional structure, and they were used to screen for potentially new allosteric modulators using a combination of structure-based and ligand based virtual screening (in silico) with compounds from the Molport database and DrugBank. 16 compounds were purchased for testing – 8 from each database, and were further investigated and evaluated by experimental in vitro testing. Our results indicate that we have four hits, two from each database (DrugBank: I-4 = Mefloquine and I-10 = Rivaroxaban, Molport: I-23 and I-24) where it seems like I-4, I-23 and I-24 acts like PAMs whereas I-10 acts like a NAM/antagonist. The compounds from DrugBank, especially Mefloquine is of interest due to its well-known adverse effect profile which may be linked to the GABAergic system. Further investigation and confirmation of activity at the GABAB receptor could potentially lead to development of novel drugs as well as important tools for studying the structure and function of the GABAB receptor. And at the same time be used to explain the side effects seen when using Mefloquine

Policy and Institutional effects on market participation by smallholder rice farmers: case studies in Burkina Faso, Mali and Niger

Rice sector contributes significantly to secure households with regard to their food needs but also to the creation of employments and income generation. The sector development and its evolution over the years have been marked by various policies and approaches. These development stages of the sector constitute nothing but the impact of the number of factors such as the rice policies put in place. A collaborative multi-country pilot study on policy and institutional arrangements effects on irrigated rice production and commercialization was conducted by WARDA and its country partners of Burkina Faso, Mali, and Niger. In-depth surveys were carried out at both village and household levels to collect qualitative and quantitative data on irrigated rice production, commercialization, and irrigated schemes governance. A common critical constrain cited by the producers in these countries is the commercialization of their product and their inability to take advantage of the market opportunities. Using village and household levels survey data on irrigated rice production and commercialization, this paper attempts to examine the impact of policy and institutional factors in market participation by smallholder rice producers. A farm level supply is estimated using the quantity of rice marketed as the dependant variable and factors such as output and inputs price, and policy and institutional variables as independent ones. The preliminary results indicate that most significant explanatory variable is the average irrigated rice plot (Mali and Niger) and total area of other crops grown by the producer.Agribusiness, Agricultural and Food Policy, Community/Rural/Urban Development, Environmental Economics and Policy, Farm Management, Food Consumption/Nutrition/Food Safety, Food Security and Poverty, Institutional and Behavioral Economics, International Relations/Trade, Labor and Human Capital, Marketing, Production Economics, Research and Development/Tech Change/Emerging Technologies, Research Methods/ Statistical Methods,

Recovery of floristic diversity, composition and structure of regrowth forests on fallow lands: implications for conservation and restoration of degraded forest lands in Laos

In Laos, there are extensive shifting cultivation areas and regrowth forests spontaneously established on fallow lands. The aims of the study were to conduct a comparative study of old-growth and regrowth forests in terms of structure, woody species diversity and composition as well as to investigate the potential role of regrowth forests in the conservation and restoration of degraded forest lands in Laos and the tropics in general. Systematic plot sampling was used to survey the floristic diversity, species composition and structure of old-growth and regrowth forests. Concentric circular plots with an area of 200 m2 and 500 m2 were laid on line transects. A total of 24 plots were sampled from two sites. In comparison to regrowth forests, old-growth forests had higher structural heterogeneity because of higher canopy height variations, vertical stratification, and tree sizes and their variations. Species richness and diversity indices values were similar, but abundance and species composition were significantly different between old-growth and regrowth forests. It appears that species richness recovers first followed by forest structure and species composition. Regrowth forests are important for in situ conservation of tropical biodiversity and they can also serve as a conduit for the restoration of degraded lands and forests. Regrowth forests provide habitats, serve as buffer zones around the fragmented old-growth forests, function as source of propagules, and enhance landscape connectivity. Utilization of regrowth forests for restoration purposes is comparatively inexpensive. Regrowth forests should be given the due considerations in the national forest conservation and restoration policy of Laos.Peer reviewe

Genetic Diversity of Simulium damnosum complex Onchocerciasis Vector and its Influence on Entomological Monitoring in the West of Côte d'Ivoire

In West Africa, Onchocerca volvulus, the causative pathogen of human onchocerciasis, is transmitted by sibling species of the Simulium damnosum complex. Little is known about blackfly intraspecific variability and its consequences on vectorial capacity in Côte d’Ivoire. This study reports the use of microsatellite markers to study the genetic profile and evaluate the gene flow between populations of S. damnosum s.l from three (3) different epidemiological facies in western Côte d’Ivoire, fifteen years after the end of onchocerciasis control program. Adult flies were collected on human attractants from 07 : 00 to 18 : 00 hours for three consecutive days by site, from December 2016 to October 2017. Four (4) microsatellite loci were used to characterize individuals from these populations. The four (4) loci were polymorphic with 13.25 alleles per locus. Two (2) specific alleles (190 bp and 290 bp), were reveal abundant with respective frequencies of 0.46 % and 0.58 %. Asignificant heterozygosity deficiency and low genetic differentiation (FST = 0.046, P = 0.024) have been observed for all the populations. The genetic analysis showed significant deviation from Hardy-Weinberg and significant heterozygosity deficiencies. Then, the great interspecific variability would be a general characteristic in S. damnosum s.l. At last, a probable evolution of the invasive strains of S. damnosum would have occurred in these localities. This study has shown significant deviation from Hardy-Weinberg and significant heterozygosity deficiencies in the populations of the three localities. The loci give independent estimate genetic parameters. The H3-4 locus to a low genetic differentiation between the populations. &nbsp

Apport des moyens endoscopiques dans la dilatation des sténoses caustiques de l’oesophage

Introduction: The aim of this work was to present the contribution of the endoscopy in the management of esophageal dilatation for caustic esophageal stenosis (CES). Methods: This was a descriptive and prospective study in the thoracic surgery department at the Hospital of Mali. A total of 46 cases of CES is recorded and divided into 4 groups according to the topography of the esophageal lesions. For the different methods of dilatation the number of performed endoscopic support was determined to understand the contribution of endoscopic means in the success of dilatation for CES. The outcome, complications and mortality in the two methods were compared. Results: Fibroscopy was used in 41.30% of patients with Savary Guillard dilators and in 47.82% of patients with Lerut dilators. Video laryngoscopy was used in 58.69% of patients who underwent dilatation with Lerut dilators. The passage of the guide wire was performed in 39.13% under video laryngoscopy and 58.68% under fibroscopy. In comparison of the two methods, there is a significant difference in the occurrence of complications (p = 0.04075), general anesthesia (p = 0.02287), accessibility (p = 0.04805) and mortality (p = 0.00402). Conclusion: The CES is a serious disease and under evaluated in Mali. The endoscopies contribute significantly to the success of esophageal dilatation for caustic stenosis in the different methods we used.Keywords: Esophagus, caustic stenosis, dilatation, endoscopicPan African Medical Journal 2016; 2

Caractérisation Physico-Chimique Et Minéralogique Des Argiles De La Carrière De Mirriah, Région De Zinder, Utilisées Dans La Poterie

In order to contribute to the valuation of clay materials from the Zinder Region, the clays taken from the quarry and used for the pottery of Mirriah have been characterized from a physico-chemical and mineralogical point of view. So the five samples were taken and the composite sample representative of the quarry were subjected to chemical and mineralogical analyzes.The chemical analysis showed that the six samples all consisted of more than 60% aluminosilicates with a high silica/alumina ratio estimated at 2.5 on average. This report shows that the samples of this study are rich in clay minerals; this is in agreement with the estimate of the fine or clay fraction which is 39.5% of the initial mass of the raw sample. This chemical analysis also made it European Scientific Journal, ESJ ISSN: 1857-7881 (Print) e - ISSN 1857-7431 January 2021 edition Vol.17, No.3 www.eujournal.org 122 possible to highlight, at the level of these Mirriah clays, a significant iron oxide content of 32%, which gives them a brick red color. The main mineralogical phases detected by X-ray diffraction in the raw sample and its fine fraction are kaolinite, a mica structure close to illite and quartz, all weathering products of granite. This characterization indicates that the clays mined at the Mirriah quarry are very favorable materials for formulations of pottery products. Dans le but de contribuer à la valorisation des matériaux argileux de la Région de Zinder, les argiles prélevées à la carrière et utilisées pour la poterie de Mirriah ont été caractérisées du point de vue physico-chimique et minéralogique. Ainsi les cinq échantillons ont été prélevés et l’échantillon composite représentatif de la carrière, ont été soumis à des analyses chimiques et minéralogiques. Il ressort de l’analyse chimique que les six échantillons sont tous constitués à plus de 60 % d’aluminosilicates avec un rapport silice/alumine élevé estimé à 2,5 en moyenne. Ce rapport montre que les échantillons de cette étude sont riches en minéraux argileux ceci est en accord avec l’estimation de la fraction fine ou argileuse qui est de 39,5 % de la masse initiale de l’échantillon brut. Cette analyse chimique a aussi permis de mettre European Scientific Journal, ESJ ISSN: 1857-7881 (Print) e - ISSN 1857-7431 January 2021 edition Vol.17, No.3 www.eujournal.org 121 en évidence, au niveau de ces argiles de Mirriah, une teneur importante en oxyde de fer de 32% ceci leur induit une couleur rouge brique. Les phases minéralogiques principales détectées par diffraction des rayons X dans l’échantillon brut et sa fraction fine sont de la kaolinite, une structure de mica proche de l’illite et du quartz, tous des produits d’altération du granite. Cette caractérisation indique que les argiles exploitées à la carrière de Mirriah sont des matériaux très favorables aux formulations des produits de poterie

The Internet of Responsibilities-Connecting Human Responsibilities using Big Data and Blockchain

Accountability in the workplace is critically important and remains a challenging problem, especially with respect to workplace safety management. In this paper, we introduce a novel notion, the Internet of Responsibilities, for accountability management. Our method sorts through the list of responsibilities with respect to hazardous positions. The positions are interconnected using directed acyclic graphs (DAGs) indicating the hierarchy of responsibilities in the organization. In addition, the system detects and collects responsibilities, and represents risk areas in terms of the positions of the responsibility nodes. Finally, an automatic reminder and assignment system is used to enforce a strict responsibility control without human intervention. Using blockchain technology, we further extend our system with the capability to store, recover and encrypt responsibility data. We show that through the application of the Internet of Responsibility network model driven by Big Data, enterprise and government agencies can attain a highly secured and safe workplace. Therefore, our model offers a combination of interconnected responsibilities, accountability, monitoring, and safety which is crucial for the protection of employees and the success of organizations

Effects of incorporation levels of Pueraria phaseoloides leaf flour on carcass characteristics and chemical composition of meat from local rabbit (Oryctolagus cuniculus) in South-East Gabon

The objective of this study was to contribute in improving knowledge on rabbit feeding in Gabon. This work was conducted with the aim of studying carcass characteristics and chemical composition of meat from rabbit induced by feeds containing P. phaseoloides. To that effect, 20 young female rabbits from local breed, weighing averagely 611 ± 33.20 g and aged about 6 weeks were randomly distributed in 4 groups of 5 animals each. The groups R0, R15, R20 and R25 were fed rations containing respectively 0%, 15%, 20% and 25% of P. phaseoloides. At the end of the trial, animals were slaughtered then eviscerated in order to evaluate carcass characteristics. Muscles were taken, ground and mixed for chemical analysis. No matter the ration, carcass characteristics showed no significant difference (p > 0.05). Highest protein contents in meat were recorded in animals from R15 (23.90% DM) and R20 (22.46% DM). The lowest fat content (5.41% DM) was that of animals from R25, followed by that from R20 (6.67% DM). Based on these results obtained, the ration containing 20% Pueraria phaseolides (R20) could be recommended

Health facility-based prevalence and potential risk factors of autism spectrum disorders in Mali

Background: The prevalence of autism spectrum disorders (ASD) is 1-2% worldwide, 1 in 68 in the U.S, and unknown in Africa. ASD is under-diagnosed in Mali due to stigma and the lack of appropriate human resources and infrastructure.Objective: To determine the ASD frequency and potential risk factors in Mali.Methods: We identified all the health facilities and community-based organizations involved in the ASD diagnosis and management in Bamako. We established an ASD research and awareness platform in Mali, which encompasses community-based organizations and a multidisciplinary team including psychiatrists, psychologists, pediatricians, geneticists, and public health and social science specialists. Through this platform, we performed a survey in health facilities and organizations where patients with ASD are likely to seek care in Bamako. We reviewed the psychiatric patient registry to obtain basic epidemiological profiles of children with ASD, epilepsy and other psychiatric disorders.Results: We found a health facility-based prevalence of ASD of 4.5% (105/2,343) in Bamako. The mean age at the first outpatient visit was 7.64 ± 3.85 years old. First degree consanguinity of 29.5% (31/105) was more frequent in parents of ASD children versus age and sex matched controls OR= 4.37 [1.96-9.76] p=0.0001.Conclusion: Our data suggest that ASD is more common than expected in Mali. The established ASD awareness and research platform may improve the diagnosis and management of ASD by raising ASD awareness, training of Malian clinicians and researchers in early ASD screening and diagnosis, and strengthening research capacity in genomics of ASD and other mental disorders.Keywords: ASD, prevalence, consanguinity, health facilit