Genomic Reference Resource for African Cattle: Genome Sequences and High-Density Array Variants.

The diversity in genome resources is fundamental to designing genomic strategies for local breed improvement and utilisation. These resources also support gene discovery and enhance our understanding of the mechanisms of resilience with applications beyond local breeds. Here, we report the genome sequences of 555 cattle (208 of which comprise new data) and high-density (HD) array genotyping of 1,082 samples (537 new samples) from indigenous African cattle populations.

Whole-genome sequencing across 449 samples spanning 47 ethnolinguistic groups provides insights into genetic diversity in Nigeria.

African populations have been drastically underrepresented in genomics research, and failure to capture the genetic diversity across the numerous ethnolinguistic groups (ELGs) found on the continent has hindered the equity of precision medicine initiatives globally. Here, we describe the whole-genome sequencing of 449 Nigerian individuals across 47 unique self-reported ELGs. Population structure analysis reveals genetic differentiation among our ELGs, consistent with previous findings.

The African Goat Improvement Network: a scientific group empowering smallholder farmers.

The African Goat Improvement Network (AGIN) is a collaborative group of scientists focused on genetic improvement of goats in small holder communities across the African continent. The group emerged from a series of workshops focused on enhancing goat productivity and sustainability. Discussions began in 2011 at the inaugural workshop held in Nairobi, Kenya.

A Mendelian randomization study of genetic liability to post-traumatic stress disorder and risk of ischemic stroke.

Observational studies have shown an association between post-traumatic stress disorder (PTSD) and ischemic stroke (IS) but given the susceptibility to confounding it is unclear if these associations represent causal effects. Mendelian randomization (MR) facilitates causal inference that is robust to the influence of confounding. Using two sample MR, we investigated the causal effect of genetic liability to PTSD on IS risk.

Livestock phenomics and genetic evaluation approaches in Africa: current state and future perspectives.

The African livestock sector plays a key role in improving the livelihoods of people through the supply of food, improved nutrition and consequently health. However, its impact on the economy of the people and contribution to national GDP is highly variable and generally below its potential. This study was conducted to assess the current state of livestock phenomics and genetic evaluation methods being used across the continent, the main challenges, and to demonstrate the effects of various genetic models on the accuracy and rate of genetic gain that could be achieved.

Benzimidazole compound abrogates SARS-COV-2 receptor-binding domain (RBD)/ACE2 interaction In vitro.

The development of clinically actionable pharmaceuticals against coronavirus disease (COVID-19); an infectious disease caused by the SARS-CoV-2 virus is very important for ending the pandemic. Coronavirus spike glycoprotein (GP)-Receptor Binding Domain (RBD) and its interaction with host receptor angiotensin converting enzyme 2 (ACE2) is one of the most structurally understood but therapeutically untapped aspect of COVID-19 pathogenesis. Binding interface based on previous x-ray structure of RBD/ACE2 were virtually screened to identify fragments with high-binding score from 12,000 chemical building blocks.

Lipid traits and type 2 diabetes risk in African ancestry individuals: A Mendelian Randomization study.

Background: Dyslipidaemia is highly prevalent in individuals with type 2 diabetes mellitus (T2DM). Numerous studies have sought to disentangle the causal relationship between dyslipidaemia and T2DM liability. However, conventional observational studies are vulnerable to confounding.

SARS-CoV-2 Omicron spike glycoprotein receptor binding domain exhibits super-binder ability with ACE2 but not convalescent monoclonal antibody.

SARS-CoV-2, the causative virus for COVID-19 has now super-mutated into the Omicron (Om) variant. On its spike (S) glycoprotein alone, more than 30 substitutions have been characterized with 15 within the receptor binding domain (RBD); It therefore calls to question the transmissibility and antibody escapability of Omicron. This study was setup to investigate the Omicron RBD's interaction with ACE2 (host receptor) and a SARS-CoV-2 neutralizing monoclonal antibody (mAb).

One-year impact of a bowel management program in treating fecal incontinence in patients with anorectal malformations.

Background: Many patients with anorectal malformations (ARM) need a bowel management program (BMP) to manage lifelong problems of fecal incontinence or severe constipation. We aimed to evaluate the sustainability of the results in such a program.

Methods: A single-institution retrospective review was performed in children with ARM who attended our BMP (2015-2019).

flavonoids attenuate experimental nephropathy: Involvement of pro-inflammatory genes downregulation.

Nephropathy is a serious complication comorbid with a number of life-threatening diseases such as diabetes. Flavonoids are well known cytoprotective phytochemicals. Here, nephropathy associated with streptozotocin (STZ) treatment in experimental animals was challenged by flavonoids (CoF) isolated from Experimental animals were divided into control (n = 5), STZ (40 .

Comparative analyses of copy number variations between Bos taurus and Bos indicus.

Background: Bos taurus and Bos indicus are two main sub-species of cattle. However, the differential copy number variations (CNVs) between them are not yet well studied.

Results: Based on the new high-quality cattle reference genome ARS-UCD1.

Aframomum melegueta secondary metabolites exhibit polypharmacology against SARS-CoV-2 drug targets: in vitro validation of furin inhibition.

COVID-19 pandemic is currently decimating the world's most advanced technologies and largest economies and making its way to the continent of Africa. Weak medical infrastructure and over-reliance on medical aids may eventually predict worse outcomes in Africa. To reverse this trend, Africa must re-evaluate the only area with strategic advantage; phytotherapy.

Atomistic simulation reveals structural mechanisms underlying D614G spike glycoprotein-enhanced fitness in SARS-COV-2.

D614G spike glycoprotein (sgp) mutation in rapidly spreading severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) is associated with enhanced fitness and higher transmissibility in new cases of COVID-19 but the underlying mechanism is unknown. Here, using atomistic simulation, a plausible mechanism has been delineated. In G614 sgp but not wild type, increased D(G)614-T859 Cα-distance within 65 ns is interpreted as S1/S2 protomer dissociation.

Total Colonic Hirschsprung's Disease: The Hypermotility and Skin Rash Protocol.

Introduction:  Total colonic Hirschsprung's disease (TCHD) presents a postoperative challenge due to multiple stools and perineal rash. We propose a protocol developed by pediatric surgeons and ostomy nurses to help prevent and treat hypermotility and severe perineal rash, especially in younger children who are not toilet trained.

Materials And Methods:  We retrospectively reviewed our TCHD patients' charts from 2014 to 2017.

Methanolic extract of Kigelia africana exhibits antiatherosclerotic effects in endothelial cells by downregulating RAGE and adhesion molecules.

The Kigelia plant is used in African countries for its medicinal properties. Kigelia africana is an interesting example of a medicinal plant due to its pharmacological activities, including its anti-inflammatory effect. Atherosclerosis, the primary cause of cardiovascular disease, is related to lipoprotein oxidation, inflammation and immune responses involving the vascular endothelium and immune cells.

T-705-modified ssRNA in complex with Lassa virus nucleoprotein exhibits nucleotide splaying and increased water influx into the RNA-binding pocket.

Lassa virus infection is clinically characterized by multiorgan failure in humans. Without an FDA-approved vaccine, ribavirin is the frontline drug for the treatment but with attendant toxicities. 6-Fluoro-3-hydroxy-2-pyrazinecarboxamide (T-705) is an emerging alternative drug with proven anti-Lassa virus activity in experimental model.

A descriptive model for a multidisciplinary unit for colorectal and pelvic malformations.

Introduction: Patients with anorectal malformations (ARM), Hirschsprung disease (HD), and colonic motility disorders often require care from specialists across a variety of fields, including colorectal surgery, urology, gynecology, and GI motility. We sought to describe the process of creating a collaborative process for the care of these complex patients.

Methods: We developed a model of a devoted center for these conditions that includes physicians, psychologists, social workers, nurses, and advanced practice nurses.

A structured bowel management program for patients with severe functional constipation can help decrease emergency department visits, hospital admissions, and healthcare costs.

Background: Published health-care costs related to constipation in children in the USA are estimated at $3.9 billion/year. We sought to assess the effect of a bowel management program (BMP) on health-care utilization and costs.

Flavonoid-rich extract of modulate circulating GLP-1 in Wistar rats: computational evaluation of TGR5 involvement.

Unlabelled: is a major bio-resource in folkloric treatment of diabetes. In the present study, its anti-diabetic component and underlying mechanism were investigated. A library containing 140 phytocompounds previously characterized from was generated and docked (Autodock Vina) into homology models of dipeptidyl peptidase (DPP)-4, Takeda-G-protein-receptor-5 (TGR5), glucagon-like peptide 1 (GLP1) receptor, renal sodium dependent glucose transporter (SGLUT)-1/2 and nucleotide-binding oligomerization domain (NOD) proteins 1&2.

Are Senna based laxatives safe when used as long term treatment for constipation in children?

Background And Aim: Senna is a stimulant laxative commonly used by pediatricians, pediatric gastroenterologists, and pediatric surgeons. Many clinicians avoid Senna for reasons such as tolerance or side effects but this has little scientific justification. We recently found several patients we were caring for developed perineal blistering during the course of Senna treatment.

Geranylnaringenin (CG902) inhibits constitutive and inducible STAT3 activation through the activation of SHP-2 tyrosine phosphatase.

The roles and significance of signal transducer and activator of transcription 3 (STAT3) in human cancers have been extensively studied and STAT3 is a promising therapeutic target for cancer drug discovery. During the screening of natural products to identify STAT3 inhibitors, we identified geranylnaringenin (CG902), which decreased luciferase activity in a dose-dependent manner. CG902 specifically inhibited STAT3 phosphorylation at Tyr-705 in DU145 prostate cancer cells and decreased the expression levels of STAT3 target genes, such as cyclin D1, cyclin A, and survivin.

Signatures of Selection for Environmental Adaptation and Zebu × Taurine Hybrid Fitness in East African Shorthorn Zebu.

The East African Shorthorn Zebu (EASZ) cattle are ancient hybrid between Asian zebu × African taurine cattle preferred by local farmers due to their adaptability to the African environment. The genetic controls of these adaptabilities are not clearly understood yet. Here, we genotyped 92 EASZ samples from Kenya (KEASZ) with more than 770,000 SNPs and sequenced the genome of a pool of 10 KEASZ.