ABSTRACT
UM171 is a potent small molecule agonist of ex vivo human hematopoietic stem cell (HSC) self-renewal, a process that is tightly controlled by epigenetic regulation. By co-opting KBTBD4, a substrate receptor of the CULLIN3-RING E3 ubiquitin ligase complex, UM171 promotes the degradation of members of the CoREST transcriptional corepressor complex, thereby limiting HSC attrition. However, the direct target and mechanism of action of UM171 remain unclear. Here, we reveal that UM171 acts as a molecular glue to induce high-affinity interactions between KBTBD4 and HDAC1 to promote the degradation of select HDAC1/2 corepressor complexes. Through proteomics and chemical inhibitor studies, we discover that the principal target of UM171 is HDAC1/2. Cryo-electron microscopy (cryo-EM) analysis of dimeric KBTBD4 bound to UM171 and the LSD1-HDAC1-CoREST complex unveils an unexpected asymmetric assembly, in which a single UM171 molecule enables a pair of KBTBD4 KELCH-repeat propeller domains to recruit HDAC1 by clamping on its catalytic domain. One of the KBTBD4 propellers partially masks the rim of the HDAC1 active site pocket, which is exploited by UM171 to extend the E3-neo-substrate interface. The other propeller cooperatively strengthens HDAC1 binding via a separate and distinct interface. The overall neomorphic interaction is further buttressed by an endogenous cofactor of HDAC1-CoREST, inositol hexakisphosphate, which makes direct contacts with KBTBD4 and acts as a second molecular glue. The functional relevance of the quaternary complex interaction surfaces defined by cryo-EM is demonstrated by in situ base editor scanning of KBTBD4 and HDAC1. By delineating the direct target of UM171 and its mechanism of action, our results reveal how the cooperativity offered by a large dimeric CRL E3 family can be leveraged by a small molecule degrader and establish for the first time a dual molecular glue paradigm.
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As one of the 17 sustainable development goals, the United Nations (UN) has prioritized "clean water and sanitation" (Goal 6) to reduce the discharge of emerging pollutants and disease-causing agents into the environment. Contamination of water by pathogenic microorganisms and their existence in treated water is a global public health concern. Under natural conditions, water is frequently prone to contamination by invasive microorganisms, such as bacteria, viruses, and protozoa. This circumstance has therefore highlighted the critical need for research techniques to prevent, treat, and get rid of pathogens in wastewater. Membrane systems have emerged as one of the effective ways of removing contaminants from water and wastewater However, few research studies have examined the synergistic or conflicting effects of operating conditions on newly developing contaminants found in wastewater. Therefore, the efficient, dependable, and expeditious examination of the pathogens in the intricate wastewater matrix remains a significant obstacle. As far as it can be ascertained, much attention has not recently been given to optimizing membrane processes to develop optimal operation design as related to pathogen removal from water and wastewater. Therefore, this state-of-the-art review aims to discuss the current trends in removing pathogens from wastewater by membrane techniques. In addition, conventional techniques of treating pathogenic-containing water and wastewater and their shortcomings were briefly discussed. Furthermore, derived mathematical models suitable for modelling, simulation, and control of membrane technologies for pathogens removal are highlighted. In conclusion, the challenges facing membrane technologies for removing pathogens were extensively discussed, and future outlooks/perspectives on optimizing and modelling membrane processes are recommended.
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The incorporation of phytoactive compounds in the management of malarial vectors holds promise for the development of innovative and efficient alternatives. Nevertheless, the molecular and physiological responses that these bioactive substances induce remain underexplored. This present study investigated the toxicity of different concentrations of aqueous and methanol extracts of Ocimum tenuiflorum against larvae of Anopheles gambiae (sensu stricto) and unraveled the possible underlying molecular pathways responsible for the observed physiological effects. FTIR and GCMS analyses of phytoactive compounds in aqueous and methanol crude extracts of O. tenuiflorum showed the presence of OH stretching vibration, C = C stretching modes of aromatics and methylene rocking vibration; ring deformation mode with high levels of trans-ß-ocimene, 3,7-dimethyl-1,3,6-octatriene in aqueous extract and 4-methoxy-benzaldehyde, 1,3,5-trimethyl-cyclohexane and o-cymene in methanol extract. The percentage mortality upon exposure to methanol and aqueous extracts of O. tenuiflorum were 21.1% and 26.1% at 24 h, 27.8% and 36.1% at 48 h and 36.1% and 45% at 72 h respectively. Using reverse transcription quantitative polymerase chain reaction (RT-qPCR), down-regulation of ABC transporter, overexpression of CYP6M2, Hsp70, and α-esterase, coupled with significantly increased levels of SOD, CAT, and GSH, were observed in An. gambiae (s.s.) exposed to aqueous and methanol extracts of O. tenuiflorum as compared to the control. Findings from this study have significant implications for our understanding of how An. gambiae (s.s.) larvae detoxify phytoactive compounds.
Subject(s)
ATP-Binding Cassette Transporters , Anopheles , Antioxidants , HSP70 Heat-Shock Proteins , Ocimum , Plant Extracts , Animals , Anopheles/drug effects , Anopheles/genetics , Anopheles/metabolism , Plant Extracts/pharmacology , Antioxidants/metabolism , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , HSP70 Heat-Shock Proteins/metabolism , HSP70 Heat-Shock Proteins/genetics , Cytochrome P-450 Enzyme System/metabolism , Cytochrome P-450 Enzyme System/genetics , Larva/drug effects , Larva/metabolism , Insect Proteins/metabolism , Insect Proteins/genetics , Stress, Physiological/drug effectsABSTRACT
This report presents a comprehensive investigation into the synthesis and characterization of Schiff base compounds derived from benzenesulfonamide. The synthesis process, involved the reaction between N-cycloamino-2-sulfanilamide and various substituted o-salicylaldehydes, resulted in a set of compounds that were subjected to rigorous characterization using advanced spectral techniques, including 1H NMR, 13C NMR and FT-IR spectroscopy, and single-crystal X-ray diffraction. Furthermore, an in-depth assessment of the synthesized compounds was conducted through Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis, in conjunction with docking studies, to elucidate their pharmacokinetic profiles and potential. Impressively, the ADMET analysis showcased encouraging drug-likeness properties of the newly synthesized Schiff bases. These computational findings were substantiated by molecular properties derived from density functional theory (DFT) calculations using the B3LYP/6-31G* method within the Jaguar Module of Schrödinger 2023-2 from Maestro (Schrodinger LLC, New York, USA). The exploration of frontier molecular orbitals (HOMO and LUMO) enabled the computation of global reactivity descriptors (GRDs), encompassing charge separation (Egap) and global softness (S). Notably, within this analysis, one Schiff base, namely, 4-bromo-2-{N-[2-(pyrrolidine-1-sulfonyl)phenyl]carboximidoyl}phenol, 20, emerged with the smallest charge separation (ΔEgap = 3.5780â eV), signifying heightened potential for biological properties. Conversely, 4-bromo-2-{N-[2-(piperidine-1-sulfonyl)phenyl]carboximidoyl}phenol, 17, exhibited the largest charge separation (ΔEgap = 4.9242â eV), implying a relatively lower propensity for biological activity. Moreover, the synthesized Schiff bases displayed remarkeable inhibition of tankyrase poly(ADP-ribose) polymerase enzymes, integral in colon cancer, surpassing the efficacy of a standard drug used for the same purpose. Additionally, their bioavailability scores aligned closely with established medications such as trifluridine and 5-fluorouracil. The exploration of molecular electrostatic potential through colour mapping delved into the electronic behaviour and reactivity tendencies intrinsic to this diverse range of molecules.
Subject(s)
Colonic Neoplasms , Schiff Bases , Humans , Schiff Bases/chemistry , Models, Molecular , Molecular Conformation , Crystallography, X-Ray , Spectroscopy, Fourier Transform Infrared , Hydrogen Bonding , PhenolsABSTRACT
Every year, 10 million people fall ill with tuberculosis (TB). Despite being a preventable and curable disease, 1.5 million people die from TB each year -making it the world's top infectious disease. TB is the leading cause of death of people with HIV and also a major contributor to antimicrobial resistance. Its presumed that TB was the cause of 1% of the total deaths among inpatients in Sudan in 2017. The current study is aimed to provide pooled prevalence of Mycobacterium tuberculosis among Sudanese as well as to determine any socio-cultural risk factors associated. A systematic review of the literature was conducted and regulated in accordance with the PRISMA Statement. After abstract and full text screening only twenty-six articles met our inclusion criteria and passed the quality assessment procedure. Pulmonary tuberculosis prevalence was assessed in sixteen included studies among participants from Khartoum, Gezira, Kassala, Blue Nile, River Nile, White Nile, Gadarif, Red sea, North Kordofan, Northern State, Sennar and West Darfur States, representing a total sample size of 11,253 participants of suspected individuals such as febrile outpatients, TB patients' contacts and other groups such as HIV/AIDS patients, hemodialysis patients, School adolescents as well as pregnant women. The pooled prevalence was 30.72% [CI: 30.64, 30.81]. Moreover, Khartoum State recorded the highest pooled prevalence as 41.86% [CI: 14.69, 69.02] based on a total sample size of 2,737 participants. Furthermore, male gender and rural residence were found to be significantly associated with TB infection. Further research with larger sample sizes targeting prevalence and risk factors of TB among Sudanese population is needed to be conducted.
Subject(s)
Acquired Immunodeficiency Syndrome , Latent Tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Pregnancy , Adolescent , Humans , Female , Male , SudanABSTRACT
It is estimated that more than 4% of the causes of inpatient deaths in 2017 were due to diarrheal diseases. The current study is aimed to provide pooled prevalence of microorganisms causing diarrhea among Sudanese as well as determine any socio-cultural risk factors associated. A systematic review of the literature was conducted and regulated in accordance to PRISMA. After abstract and full text screening Twenty-one research articles were recruited to the study. Among witch eighteen research articles determined prevalence of causative microorganisms of Diarrhea; eight research articles determining prevalence of causative microorganisms of Diarrhea were conducted in Khartoum State, five in Gezira State, two in White Nile State, one in Kordofan State while two studies were conducted in several States. Moreover, majority of studies were concerned of prevalence among children while two studies were toward general population as well as mothers of children. The pooled prevalence of viral diarrhea in less than five years old children was 22.90% [15.37, 30.43] among more than 14 thousands' participants, the pooled prevalence of parasitic diarrhea was 31.40% [19.53, 43.27] among participants from different age groups while the pooled prevalence of bacterial diarrhea was 36.20% [14.00, 58.40]. No associated risk factors were able to be synthesized from included studies.
Subject(s)
Diarrhea , Mothers , Child, Preschool , Female , Humans , Diarrhea/epidemiology , Diarrhea/etiology , Prevalence , Risk Factors , Sudan/epidemiologyABSTRACT
In addition to excessive burden of non-communicable diseases, natural and manmade disasters, and internal conï¬icts, Sudan is predominantly susceptible to communicable diseases, such as malaria, tuberculosis, and pneumonia, which bring about an extra burden of demand for high-quality healthcare. According to the WHO and the Sudan Health Observatory, pneumonia is one of the leading causes of death in Sudan. This study therefore aimed to illustrate pneumonia literature in Sudan, estimate infection prevalence regardless of the cause among Sudanese children and adults, and demonstrate its related risk factors. A systematic and scoping review of the literature was conducted and regulated in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). After abstract and full-text screening, only 15 articles met our inclusion criteria and passed the quality assessment procedure. Seven included studies determined prevalence of pneumonia; the overall pooled prevalence was around 30%. Furthermore, 12 research articles investigated risk factors related to pneumonia among Sudanese population. Further research with larger sample sizes targeting risk factors of pneumonia among Sudanese population is needed to be conducted.
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Introduction Hereditary bleeding disorders, such as hemophilia and von Willebrand disease (VWD), result from specific deficiencies or malformations in the coagulation cascade proteins. These disorders can significantly impact both physical and psychological health. Complications such as depression, anxiety, and stress (DAS) can further exacerbate these impacts. Despite their significance, detailed prevalence data remain limited, especially for regions such as Madinah province in Saudi Arabia. This study aimed to determine the prevalence of DAS and their associated risk factors among patients with hereditary bleeding disorders in Madinah province, Saudi Arabia. Methods We conducted a cross-sectional study using telephonic interviews involving patients diagnosed with severe hemophilia A or B or VWD attending a hematology clinic in Madinah. Patients over 10 were included, and the study excluded those with central nervous system insults and platelet count concerns. The validated and reliable Depression Anxiety Stress Scale-21-item questionnaire and Statistical Product and Service Solutions (SPSS), version 26.0 (IBM SPSS Statistics for Windows, Armonk, NY), facilitated data collection and analysis, respectively. Results Of the 44 patients studied, 25% exhibited symptoms of depression, 45.5% showed signs of anxiety, and 29.5% had stress symptoms. Regarding symptom severity, 9.1% of patients experienced extremely severe depression, 15.9% had moderate anxiety, and 13.6% reported moderate stress. The prevalence of these psychological issues varied with patients' age and economic status. Notably, a significantly higher rate of depression was observed in patients over 15 years (42.9% vs. 8.7%; p=0.009). Additionally, while not statistically significant, patients with a high economic status reported increased rates of DAS. Conclusions Patients with inherited bleeding disorders, particularly those older than 15, manifest significant psychological distress. There is a pressing need for enhanced awareness, specialized screenings, and tailored counseling services to improve treatment adherence and overall quality of life. Given the findings, a comprehensive national study in Saudi Arabia is highly recommended, alongside the integration of specialized psychological services.
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This study takes a new look at the stock price-exchange rate nexus and attempts contributions to the extant studies in a number of intuitive ways. First, we analyze the reverse relationships given the theory-backed two-way causality between the two variables. We reassess the nexus across the First, Second and Third Waves of the COVID-19 pandemic, as well as comparison between advanced and emerging economies. Third, we adopt a panel modeling approach that simultaneously takes nonstationarity, cross sectional dependence, and asymmetry into account. The data analyses show that the relationship is statistically negative for the two nexuses. The magnitudes were higher during the crisis (the COVID-19 pandemic) although the relationship broke down during the Second Wave as the Delta variant surged. We identify relevant investment and policy implications of the findings.
ABSTRACT
In the search for new `sulfa drugs' with therapeutic properties, o-nitrosulfonamides and N-cycloamino-o-sulfanilamides were synthesized and characterized using techniques including 1H NMR, 13C NMR and FT-IR spectroscopy, and single-crystal X-ray diffraction (SC-XRD). The calculated density functional theory (DFT)-optimized geometry of the molecules showed similar conformations to those obtained by SC-XRD. Molecular docking of N-piperidinyl-o-sulfanilamide and N-indolinyl-o-sulfanilamide supports the notion that o-sulfanilamides are able to bind to human carbonic anhydrase II and IX inhibitors (hCA II and IX; PDB entries 4iwz and 5fl4). Hirshfeld surface analyses and DFT studies of three o-nitrosulfonamides {1-[(2-nitrophenyl)sulfonyl]pyrrolidine, C10H12N2O4S, 1, 1-[(2-nitrophenyl)sulfonyl]piperidine, C11H14N2O4S, 2, and 1-[(2-nitrophenyl)sulfonyl]-2,3-dihydro-1H-indole, C14H12N2O4S, 3} and three N-cycloamino-o-sulfanilamides [2-(pyrrolidine-1-sulfonyl)aniline, C10H14N2O2S, 4, 2-(piperidine-1-sulfonyl)aniline, C11H16N2O2S, 5, and 2-(2,3-dihydro-1H-indole-1-sulfonyl)aniline, C14H14N2O2S, 6] suggested that forces such as hydrogen bonding and π-π interactions hold molecules together and further showed that charge transfer could promote bioactivity and the ability to form biological interactions at the piperidinyl and phenyl moieties.
Subject(s)
Aniline Compounds , Carbonic Anhydrase II , Humans , Sulfanilamide , Molecular Docking Simulation , Spectroscopy, Fourier Transform Infrared , Crystallography, X-Ray , Hydrogen Bonding , Piperidines , PyrrolidinesABSTRACT
Neural stem cells (NSCs) are immature progenitor cells that are found in developing and adult brains that have the potential of dividing actively and renewing themselves, with a complex form of gene expression. The generation of new brain cells in adult individuals was initially considered impossible, however, the landmark discovery of human neural stem cells in the hippocampus has been followed by further discoveries in other discreet regions of the brain. Investigation into the current state in Africa of the research and use of NSCs shows relatively limited activities on the continent. Information on the African application of NSCs for modelling disease mechanisms, drug discovery, and therapeutics is still limited. The International Brain Research Organization (IBRO)-African Regional Committee (ARC), with support from the Company of Biologists, and the Movement Disorder Society, sponsored the first African Basic School on NSC in Ibadan, Nigeria, with the vision of bringing together young neuroscientists and physicians across different fields in neuroscience to learn from leaders who have applied NSCs in stem cell research, the pathophysiology of neurodegenerative diseases, neuroanatomy, and neurotherapeutics. Twenty early-career researchers in academic institutions at junior and senior faculty cadres were selected from South Africa, Uganda and Nigeria. The students and organizer of the school, who wrote this review on the state of NSCs research in Africa, recommended the following: (1) other African countries can take a cue from South Africa and Nigeria in probing the phenomena of adult neurogenesis in unique animal species on the continent; (2) Africa should leverage the expertise and facilities of South African scientists and international collaborators in scaling up NSC research into these unique species and (3) Centers of Excellence should be established on the continent to serve as research hubs for training postgraduate students, and facilities for African scientists who trained overseas on NSCs.
Subject(s)
Neural Stem Cells , Stem Cell Research , Animals , Adult , Humans , Nigeria , Neurogenesis/genetics , Hippocampus/metabolismABSTRACT
BACKGROUND: Nigeria has an estimated TB prevalence of 219 per 100,000 population. In 2019, Nigeria diagnosed and notified 27% of the WHO-estimated cases of all forms of TB and contributed 11% of the missing TB cases globally. OBJECTIVE: To assess TB underreporting by type and level of health facility (HF), and associated factors in Lagos State, Nigeria. METHODOLOGY: Quantitative secondary data analysis of TB cases was conducted in 2015. χ2 test was used to assess the association between treatment initiation, TB underreporting, local government area (LGA) and HF characteristics. RESULTS: Overall, 2,064 persons with bacteriologically confirmed TB (15.5%) were not matched to patients in sampled TB registers. Treatment status was unknown for 86 cases (IQR 55-97) per LGA. LGAs with higher case-loads had higher proportions of cases with unknown TB status. Discrepant reporting of treated TB was also common (60% HFs). Primary-level TB treatment facilities and unengaged private facilities were less likely to notify. CONCLUSION: There was TB under-reporting across all types and levels of HFs and LGAs. There is a need to revise or strengthen the process of supervision and data quality assurance system at all levels.
CONTEXTE: Le Nigeria a une prévalence de la TB estimée à 219 pour 100 000 habitants. En 2019, le Nigéria a diagnostiqué et notifié 27% des cas estimés par l'OMS de toutes les formes de TB et a contribué à 11% des cas de TB manquants dans le monde. OBJECTIF: Évaluer la sous-déclaration de la TB par type et niveau d'établissement de santé (HF), et les facteurs associés dans l'État de Lagos, au Nigeria. MÉTHODES: Une analyse quantitative des données secondaires des cas de TB a été réalisée en 2015. Le test χ2 a été utilisé pour évaluer l'association entre l'initiation du traitement, la sous-déclaration de la TB, la zone de gouvernement local (LGA) et les caractéristiques des HF. RÉSULTATS: Dans l'ensemble, 2 064 personnes ayant une TB confirmée par épreuve bactériologique (15,5%) n'ont pas été appariées à des patients dans les registres de TB échantillonnés. Le statut de traitement était inconnu pour 86 cas (IQR 5597) par LGA. Les LGA ayant un plus grand nombre de cas avaient une plus grande proportion de cas dont le statut de traitement était inconnu. La déclaration discrète de la TB traitée était également fréquente (60% des HF). Les établissements de traitement de la TB de premier niveau et les établissements privés non engagés étaient moins susceptibles de faire des déclarations. CONCLUSION: Il y avait une sous-déclaration de la TB dans tous les types et niveaux d'HF et de LGA. Il est nécessaire de réviser ou de renforcer le processus de supervision et le système d'assurance qualité des données à tous les niveaux.
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Objective: To describe how seizure severity in children with epilepsy may be affected by certain socio-demographic and clinical variables. Design: A cross-sectional study. Setting: At the Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria. Participants: Sixty children and adolescents who were being followed up for seizure disorder at the child neurology clinic. Intervention: Information on socio-demographic characteristics was obtained with a questionnaire, details of neurological co-morbidities were extracted from the participants' records, and seizure severity was assessed with the National Hospital Seizure Severity Score 3 tool. Main Outcome Measure: Chi-square test was used to establish the relationship between categorical variables, while the Independent t-test was used in describing the differences between means. Simple linear regression was calculated to assess the predictability of seizure severity. Result: The median age was ten years (IQR = 6-13 years), with a male dominance (1.5:1). The Seizure Severity Score (SSS) ranged between 3 and 24 units, with a mean of 12.22 ± 4.29 units. The only characteristic that had a significant association with SSS on bivariate analysis was the "presence of co-morbidities" (p=0.019). A simple linear regression revealed that the presence of a neurological co-morbidity predicted an increase in the SSS by 2.67 units. [R2 = 0.091, F (1, 58)= 5.837, p = 0.019. ß = 2.67, t= 2.42, p= 0.019.]. Conclusion: This study shows that neurological co-morbidities predict worsening seizure severity. This knowledge may influence prognostication and the charting of a treatment trajectory. Funding: No external funding.
Subject(s)
Epilepsy , Adolescent , Child , Cross-Sectional Studies , Epilepsy/complications , Epilepsy/drug therapy , Epilepsy/epidemiology , Humans , Male , Nigeria/epidemiology , Seizures/complications , Seizures/epidemiology , Surveys and QuestionnairesABSTRACT
Rabies is an endemic, highly fatal, and vaccine-preventable disease with severe socio-economic implications. Most (99%) human rabies cases are transmitted through dog bites. Children under 15 years account for 40% of all dog bite victims and 35-50% of all rabies deaths. Rabies awareness among this vulnerable group is critical to rabies prevention. However, there is a paucity of data on rabies awareness among pupils under 15. Hence, this study assessed the awareness and attitude of pupils under 15 years towards canine rabies in Kwara state in Nigeria. The study was conducted as a cross-sectional survey of 1,388 pupils across the state using a structured questionnaire that was administered as a one-on-one interview using the Open Data Kit on Android phones in December 2019. Of the 1388 pupils included in this study, only 21.7% (n = 301) of them were aware of rabies. The mean rabies score was 1.7±0.8 and only 29.2% (n = 88/301) of the pupils had adequate knowledge of canine rabies. The dog ownership rate was 18.7% (n = 259) with an average of 1.93 dogs per household. Approximately 5% (n = 66) of the pupils have been previously bitten by a dog. One-third of the dog bite victims (35%, n = 23/66) were managed and treated at home and only 12% (n = 8/66) were treated in a health facility. The result of the multivariable logistic regression showed that students aged between 13-15 years were more likely (OR: 1.93; 95% CI: 0.72-3.01; p < 0.001) to have adequate knowledge of rabies than the younger pupils. Similarly, pupils that have dogs in their households (OR: 2.09; 95%CI: 1.49-2.75; p < 0.001) and those that reside in Kwara South (OR:1.78 95% CI:1.29, 2.44; p < 0.001) were more likely to be aware and have adequate knowledge of canine rabies respectively. Finally, Pupils from non-dog-owning households were more likely (OR:2.2; 95% CI: 1.45, 4.42; p < 0.001) to have been bitten by dogs than those from dog-owning households. The awareness and attitude of pupils under 15 to canine rabies was poor. We advocate the introduction of rabies lessons into the school curriculum in Kwara State to reduce the incidence of dog bites and prevent dog-mediated human rabies.
Subject(s)
Bites and Stings , Dog Diseases , Rabies Vaccines , Rabies , Adolescent , Animals , Bites and Stings/epidemiology , Child , Cross-Sectional Studies , Dog Diseases/epidemiology , Dog Diseases/prevention & control , Dogs , Health Knowledge, Attitudes, Practice , Humans , Nigeria/epidemiology , Perception , Rabies/epidemiology , Rabies/prevention & control , Rabies/veterinary , Surveys and QuestionnairesABSTRACT
Neuropeptides are secretory peptides characterized by small chains of amino acids linked by peptide bonds. They are majorly found in some mammalian neurons and glial cells, where they modulate a variety of physiological homeostasis. In the male genital tract, they are mostly found in the neuronal fibers supplying the vasculature, smooth muscle layer, interstitium, and lamina propria of the tunica mucosa of the various reproductive organs. Functionally, neuropeptides are strongly implicated in vascular temperature regulations, spermatozoa extrusion, epididymal content transportation, and movement of accessory gland secretions. This review provides an overview of neuropeptides with respect to their synthesis, release, and mechanism of actions, with emphasis on the locally acting neuropeptides, such as substance P (SP), neuropeptide Y (NPY), vasoactive intestinal peptides (VIP), calcitonin gene-related peptide (CGRP), galanin (GAL), cholecystokinin (CCK), C-terminal flanking peptide of NPY (CPON), peptide histidine isoleucine (PHI), and met- and leu-enkephalins (M-ENK and L-ENK) along the male genital tract (i.e., the spermatic cord, testis, epididymis, ductus deferens, and accessory sex organs) of 14 species of mammals and their marked influence on reproduction. This review also revealed from documented reports that the vast majority of neuropeptides present in the autonomic nerve supply to the male genital tract probably coexist with other peptides or with various neurotransmitters (tyrosine hydroxylase, dopamine beta hydroxylase, and 5-hydroxytryptamine). In addition, documented evidence of variation in age, season, and intraspecies differences were identified as notable factors of influence in peptidergic nerve fiber distribution.
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Cardiovascular diseases and metabolic complications caused by hyperlipidemia are the leading cause of death globally. In this study, the hypolipidemic potency of Sesamum indicum (SI) seeds was investigated. Of the thirty-five (35) male rats used in the study, five (5) were randomly selected for baseline measurements and thirty (30) were fed high fat diet (HFD) for four (4) weeks before random assignment into three (3) groups. The experimental group was treated with 50% SI seed, the positive control group was given a hypolipidemic drug, atorvastatin (5 mg/kg/day) while the untreated group served as the negative control. With SI administration, the dyslipidemia induced by the HFD consumption in the plasma and the investigated body organs was reversed to a comparable degree with that of atorvastatin treatment. Taken together, this study demonstrates the hypolipidemic potency of SI in ameliorating hyperlipidemia and its associated complications, facilitated by the inhibition of HMG-CoA reductase activity.
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Vector control strategies have focused on the development of effective and ecofriendly alternatives. In the present study, investigation of larvicidal and genotoxic effects of leaves of Hyptis suaveolens from four different extraction solvents (aqueous, hexane, methanol and acetone) on fourth instar larvae of Culex quinquefasciatus was carried out. Extraction was done using soxhlet apparatus and the characteristics functional group of active constituents were identified using Fourier Transform Infrared spectrophotometer. Larvicidal activities were screened using three different concentrations (50, 150 and 250 mg/mL) following WHO standard protocol and mortality was recorded after 24, 48 and 72 hr. Hexane extract showed the highest mortality (27.92, 38.75, 90.42 %; LC50: 272.5, 191.3, 114.8 mg/mL), followed by aqueous extract (20.83, 34.58, 59.58 %; LC50: 496.6, 392.9, 208.1 mg/mL) and acetone extract (20.83, 32.08, 59.58 %; LC50: 1111.2, 393.6, 266.1 mg/mL) and methanol extract (17.92, 29.17, 52.92 %; LC50: 466.0, 400.1, 272.3 mg/mL). Enzyme profile such as superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase (CAT), glutathione (GSH) and alkaline phosphatase (ALP) were significantly altered in the larvae exposed to the four extracts. Phytochemical screening of all solvents extract revealed the presence of saponins, flavonoids, terpenoids and alkaloids as common constituents. Random Amplified Polymorphic DNA-Polymerase Chain Reaction (RAPD-PCR) profile implied hexane and aqueous extracts altered the DNA of larvae. Furthermore, FTIR Spectroscopic analysis revealed phenols, alcohols, aliphatic primary amines and saponins as the major groups in the extracts. Conclusively, this study established the lethal potential of extracts of H. suaveolens as alternative plant-based and eco-friendly larvicide against Cx. quinquefasciatus.
Subject(s)
Aedes , Anopheles , Culex , Hyptis , Insecticides , Animals , DNA Damage , Insecticides/chemistry , Insecticides/pharmacology , Larva , Mosquito Vectors , Plant Extracts/chemistry , Plant Leaves/chemistry , Random Amplified Polymorphic DNA TechniqueABSTRACT
Africa is lagging in infrastructural development including Information and Communication Technology (ICT). As there are rising employment opportunities in the ICT-intensive industries globally including Africa, enhanced knowledge and use of ICT may tend to reduce youth unemployment in Africa. Thus, this study investigates the effect of ICT on youth unemployment in Africa using a sample of 41 African countries between 2003 and 2018. The study employs a dynamic Generalized Method of Moment (GMM) approach and constructs a composite ICT index to combine key indicators of ICT, using the principal component approach. We also account for the interactive role of education in the ICT-youth unemployment nexus. Relying on the Phillip curve theoretical model, the effect of inflation, physical capital accumulation, level of corruption, and economic growth are also examined. The results show that youth unemployment in Africa can be reduced by higher ICT deployment and usage, which confirms our hypothesis in this study. There is also evidence that education enhances the potential of ICT usage to reduce youth unemployment. Furthermore, we find that the Phillip curve hypothesis holds, as the inflation rate has a negative effect on youth unemployment. More so, there is evidence that youth unemployment in Africa can be reduced by higher physical capital accumulation, lower level of corruption, and higher economic growth. With falling economic growth and looming economic recession in many African countries, governments would need to revise educational curricula to include ICT-based training to reduce the level of youth unemployment in the medium to long term period.
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Tropical goat breeds often have at least modest resistance to gastrointestinal nematode parasites (GIN), but enhancement of GIN resistance is important for breed improvement. This study compared changes in fecal egg count (FEC), packed cell volume, and body weight in Red Sokoto (RS) and Sahelian (SH) male and female weaner kids and adult goats. The RS is found throughout Nigeria, but the SH is found only in the arid Sahel. Goats were evaluated fortnightly for 20 times (MT) under normal grazing conditions and natural GIN infection over 9.5 months, beginning in the dry season (November) and ending at the end of the subsequent wet season (August). Animals were dewormed at the start of the study and during the rainy season (MT 18). Breed differences in FEC and PCV were not observed in weaners. Weaner females had lower FEC than males but were rapidly re-infected after deworming, perhaps in association with attainment of puberty. Adult SH goats of both sexes had lower FEC than RS goats in MT 8 through 17, suggesting a stronger acquired immune response. The FEC in lactating females of both breeds increased rapidly after deworming, to ≥ 3000 eggs per gram of feces at MT 19 and 20. The optimal time to evaluate GIN resistance in weaners was during the early rainy season, but the decision to focus on the initial high FEC near MT 15 or wait until mobilization of the acquired immune response near MT 17 requires further consideration.
Subject(s)
Goat Diseases , Nematoda , Nematode Infections , Animals , Feces , Female , Goat Diseases/genetics , Goats , Lactation , Male , Nematode Infections/veterinary , Nigeria , Ovum , Parasite Egg Count/veterinary , Sexual MaturationABSTRACT
Orexin (hypocretin), is a neuropeptide produced by a subset of neurons in the lateral hypothalamus. From the lateral hypothalamus, the orexin-containing neurons project their fibres extensively to other brain structures, and the spinal cord constituting the central orexinergic system. Generally, the term ''orexinergic system'' usually refers to the orexin peptides and their receptors, as well as to the orexin neurons and their projections to different parts of the central nervous system. The extensive networks of orexin axonal fibres and their terminals allow these neuropeptidergic neurons to exert great influence on their target regions. The hypothalamic neurons containing the orexin neuropeptides have been implicated in diverse functions, especially related to the control of a variety of homeostatic functions including feeding behaviour, arousal, wakefulness stability and energy expenditure. The broad range of functions regulated by the orexinergic system has led to its description as ''physiological integrator''. In the last two decades, the orexinergic system has been a topic of great interest to the scientific community with many reports in the public domain. From the documentations, variations exist in the neuroanatomical profile of the orexinergic neuron soma, fibres and their receptors from animal to animal. Hence, this review highlights the distinct variabilities in the morphophysiological aspects of the orexinergic system in the vertebrate animals, mammals and non-mammals, its presence in other brain-related structures, including its involvement in ageing and neurodegenerative diseases. The presence of the neuropeptide in the cerebrospinal fluid and peripheral tissues, as well as its alteration in different animal models and conditions are also reviewed.