Biology subjects

Ibrahim, M. A.

Publications and source records attributed to Ibrahim, M. A..

5 recordsLinked to original sources

bioRxiv2026

Full-length structure of the anti-viral and pro-tumor DNA deaminase APOBEC3B

Human APOBEC3B (A3B) restricts virus infections by catalyzing the deamination of cytosines to uracils in single-stranded DNA. A3B also contributes to mutagenesis and genome instability in cancer cells, driving tumor evolution and detrimental outcomes including therapy resistance and metastasis. A3B comprises tandem globular deaminase domains, with a multifunctional amino-terminal domain (NTD) and a catalytically active carboxy-terminal domain (CTD). Although individual domain structures have been studied, the structure of full-length A3B has remained elusive. Here, we report the cryoEM structure of wildtype A3B in complex with the natural antagonist BORF2 (the large subunit of the Epstein-Barr virus ribonucleotide reductase). The two domains of A3B bridge a novel BORF2 dimer interface, showing a unique domain positioning that distinguishes A3B from the related dual-domain retrovirus restriction factor APOBEC3G (A3G). Mutational analyses suggest that the unique NTD-CTD interaction regulates A3B deaminase activity. The BORF2 dimerization interface is stabilized by primary interactions with A3B-CTD and secondary contacts with A3B-NTD, as well as by A3B CTD-CTD dimerization. This matrix of interactions supports a molecular mechanism for A3B neutralization in which BORF2 binding leads to deaminase sequestration in large aggregates. The full-length wildtype A3B structure also provides a platform for future anti-viral and anti-cancer drug development efforts.

biochemistry↗

bioRxiv2025

Epidemiological Survey of Snail Intermediate Hosts of Schistosomiasis in Zaria, Northwest Nigeria and Molluscicidal Screening of Ficus exasperata Extracts

Schistosomiasis is a Snail-borne parasitic disease transmitted through water contact activities in endemic areas. It is associated with serious morbidities including anaemia, bladder cancer and infertility. Vector control efforts rely on the use of synthetic molluscicide (Niclosamide) which has been attributed to environmental toxicity. Snail intermediate hosts of schistosomiasis were obtained from water bodies and channels around Zaria, morphologically identified and screened for cercarial shedding. F. exasperata leaves and stem bark were obtained from natural habitat in Zaria, authenticated, dried under shade, ground into powder and subjected to extraction with distilled water, ethanol and methanol. The extracts were evaluated for phytochemical constituents, DPPH and FRAP radical scavenging activities and Molluscicidal efficacy against Bulinus spp. Higher percentage yield (8.62%) was obtained in Methanolic extract. Phytochemical analysis revealed the presence of compounds such as alkaloids, flavonoids, saponins, cardiac glycosides and steroids. Tannins and Phenolics have higher concentration compared to other phytochemicals detected in all the extracts. In vitro antioxidant analysis demonstrated moderate activity, with DPPH radical scavenging activity of 62%, 60% and 47% for methanolic, aqueous and ethanolic extracts, respectively. Molluscicidal screening of the extracts revealed dose dependent toxicity against Bulinus snails, with LC50 value of 23.59ppm, 28.96ppm, 31.51ppm for ethanolic, methanolic and aqueous extracts, respectively. These findings suggest that F. exasperata stem bark extracts could be exploited for development of eco-friendly botanical molluscicide. Further research is needed to identify the bioactive compounds responsible for Molluscicidal efficacy, elucidate the possible mechanisms of action, evaluate the efficacy in field trials and environmental impact.

pharmacology and toxicology↗

bioRxiv2025

Tobacco smoke carcinogens exacerbate APOBEC mutagenesis and carcinogenesis

Mutational processes are thought to act independently and additively. We challenge this view by demonstrating that DNA-adducting agents sensitize the genome to mutagenesis by APOBEC enzymes. A model tobacco carcinogen (NQO) triggers a 100-fold increase in APOBEC3B- catalyzed signature mutations and elevates oral carcinoma levels in vivo. A hallmark of this unidirectional synergy is strand-coordinated pairs of APOBEC signature mutations within 32nt of each other (didyma). Biochemical experiments show that APOBEC3B can catalyze didyma formation, and genetic studies demonstrate requirements for APOBEC3B and functional nucleotide excision repair (XPA in human cells and Rad14 in yeast). Analyses of lung and head & neck cancers show that APOBEC mutagenesis and didyma are elevated in tumors from smokers compared to non-smokers. Additional tumor types with links to DNA-adducting agents also exhibit didyma. These studies support a model in which DNA-adducting carcinogens activate nucleotide excision repair and amplify mutagenesis by APOBEC enzymes in cancer.

cancer biology↗

bioRxiv2023

Performing Roux-N Y Gastric Bypass on Rabbits: Perspective Report to Evaluate Body Weight Changes Food Consumption, And the Malabsorption of Vitamin D3

In 1998, Dr. Scopinaro published the first-ever known bariatric surgery, followed by reports by Buchwald and Oien in 2003 and 2013 [1,2]. Bariatric surgery (BS) is the most effective therapy against obesity, and recently it was recommended for type 2 diabetes as a therapeutic plan [3]. BS includes; Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy, and laparoscopic adjustable gastric banding has gained the attention of most healthcare providers in elevation of the issue of obesity for its ease and fast results, especially with patients with mobility problems and those with high risk to develop chronic diseases [1,2]. Gastric bypass is considered the most common BS and a gold standard for weight loss, also known as Roux-en-Y gastric bypass (RYGB). The procedure of this BS is by creating a small pouch of the stomach (300 mL capacity) connected directly to the jejunum by bypassing the duodenum. RYGB has many advantages, such as; the alteration of guts hormones, which reduces appetite and hunger feeling, increases energy expenditure, causes significant long-term weight loss (60-80% of the excess body weight), decreases the amount of food consumed, and preserves 50% of the weight loss during this procedure. However, RYGB has some disadvantages. The most critical issue regarding this BS is altering the absorption of many medicines and nutrients, such as; vitamin D3 (Vit D3) [4,5]. (American Society for Metabolic and Bariatric Surgery. Bariatric Surgery Procedures. https://asmbs.org/patients/bariatric-surgery-procedures (accessed Feb 15, 2020). RYGB was performed on rodents before [6] but was never applied to rabbits. To determine the malabsorption procedure after the RYGB, the pharmacokinetics of the substance must be attained, and data must be calculated, such as; Cmax and Tmax, to determine the absorption mutation. It was reported that pharmacokinetic studies on rodents could not be accurate due to the erratic absorption of the rodents [7]; thus, many studies have suggested using larger animals, such as rabbits, that do not address the same problem [8]. The current study investigates the ability to perform RYGB on rabbits and tests the effect of the surgery on body weight, food consumption, and the absorption of Vit D3.

pharmacology and toxicology↗

bioRxiv2022

Assessing biological network dynamics: Comparing numerical simulations with analytical decomposition of parameter space

Mathematical modeling of the emergent dynamics of gene regulatory networks (GRN) faces a double challenge of (a) dependence of model dynamics on parameters, and (b) lack of reliable experimentally determined parameters. In this paper we compare two complementary approaches for describing GRN dynamics across unknown parameters: (1) parameter sampling and resulting ensemble statistics used by RACIPE (RAndom CIrcuit PErturbation), and (2) use of rigorous analysis of combinatorial approximation of the ODE models by DSGRN (Dynamic Signatures Generated by Regulatory Networks). We find a very good agreement between RACIPE simulation and DSGRN predictions for four different 2- and 3-node networks typically observed in cellular decision making. This observation is remarkable since the DSGRN approach assumes that the Hill coefficients of the models are very high while RACIPE assumes the values in the range 1-6. Thus DSGRN parameter domains, explicitly defined by inequalities between systems parameters, are highly predictive of ODE model dynamics within a biologically reasonable range of parameters.

systems biology↗