Biology subjects

Ibrahim, N.

Publications and source records attributed to Ibrahim, N..

10 recordsLinked to original sources

bioRxiv2026

Bioelectricity Generation from Acidogenic Palm Oil Mill Effluents using Microbial Fuel Cells

Microbial fuel cell offers a promising approach to improve wastewater quality and generate bioenergy from dark fermented effluents. In this study, the use of dark-fermented palm oil mill effluent as an electron donor for bioelectricity generation was investigated using a double-chambered microbial fuel cell (MFC). The MFCs were operated at room temperature (29 {+/-} 2{degrees}C), anode electrolytes adjusted to pH 7, and a chemical catholyte as the oxidizing agent. The maximum power {+/-} 8.07 mW/m2 and 155.16 {+/-} 12.88 mA/m2, respectively, were generated from the MFCs inoculated with sludge, which was 5.9 times higher than control without inoculum. Microbial community analysis revealed the enrichment of fermentative and electrogenic representative taxa from the phyla Bacillota, Bacteroidota and Pseudomonadota on the anode electrodes. Optimizations of the running conditions were carried out, suggesting the optimum parameters of 0.5 k{Omega} external resistance, anolyte initial pH 9, and 75% DFPOME substrate concentration. Operation under the optimized conditions increased current production, wastewater treatment, and Coulombic efficiency compared to the non-optimized conditions. Multiple configurations were also evaluated, showing higher cumulative voltage, power, and current densities with the stacked MFC connections, compared to single MFC units. Parallel circuit connection produced higher power and current density than serial connection. This study demonstrated the feasibility of MFC as a promising downstream treatment for biohydrogen production processes, towards higher treatment efficiency and resource recovery.

microbiology↗

bioRxiv2025

Edited Filamin A in myeloid cells reduces intestinal inflammation and protects from colitis

Patho-mechanistic origins and disease dynamics of ulcerative colitis are still poorly understood. The actin-crosslinker Filamin A (FLNA) impacts cellular responses through interaction with cytosolic proteins. FLNA exists in two forms that differ only in one amino acid: genome-encoded FLNAQ and FLNAR - generated by post-transcriptional A-to-I editing. FLNA is edited in fibroblasts, smooth muscle- and endothelial cells in the colon. We identified the FLNA editing status as a key determinant of colitis severity. FLNA editing was highest in healthy colons and reduced during acute murine and human colitis. Mice that exclusively express edited FLNAR and do not downregulate editing upon challenge were highly resistant to DSS-induced colitis, whereas fully unedited FLNAQ animals developed severe inflammation. While the genetic induction of FLNA editing influenced transcriptional states of structural cells and the microbiome composition, we found that FLNAR exerts protection specifically via its influence on myeloid cells, which are not edited under physiological conditions. Introducing fixed, fully edited FLNAR did not hamper normal cell migration but reduced macrophage inflammation and rendered neutrophils less prone to NETosis. In conclusion, loss of FLNA editing correlates with colitis severity, and targeted FLNA editing of myeloid cells might serve as a novel therapeutic approach in intestinal inflammation. SummaryIn this study, Gawish et al. show that RNA editing of the actin cross-linker FLNA is similarly regulated in mice and humans and that the targeted induction of edited FLNAR in myeloid cells governs resistance to DSS-induced colitis, revealing its potential in IBD therapy.

molecular biology↗

bioRxiv2024

Suppression of NRF2-dependent cancer growth by a covalent allosteric molecular glue

The NRF2 transcription factor is constitutively active in cancer where it functions to maintain oxidative homeostasis and reprogram cellular metabolism. NRF2-active tumors exhibit NRF2-dependency and resistance to chemo/radiotherapy. Here we characterize VVD-065, a first-in-class NRF2 inhibitor that acts via an unprecedented allosteric molecular glue mechanism. In the absence of stress or mutation, NRF2 is rapidly degraded by the KEAP1-CUL3 ubiquitin-ligase complex. VVD-065 specifically and covalently engages C151 on KEAP1, which in turn promotes KEAP1-CUL3 complex formation, leading to enhancement of NRF2 degradation. Previously reported C151-directed compounds decrease KEAP1-CUL3 interactions and stabilize NRF2, thus establishing KEAP1_C151 as a tunable regulator of the KEAP1-CUL3 complex and NRF2 stability. VVD-065 inhibited NRF2-dependent tumor growth and sensitized cancers to chemo/radiotherapy, supporting an open Phase I clinical trial (NCT05954312).

cancer biology↗

bioRxiv2023

A Novel Amino Acid Deletion and Substitution in amrB Gene Associated with Gentamicin Susceptibility in Burkholderia pseudomallei from Malaysian Borneo

Burkholderia pseudomallei is a highly pathogenic saprophyte that is intrinsically resistant to a wide variety of antibiotics. Resistance to gentamicin is considered as an earmark of B. pseudomallei. However, rare susceptible strains have been isolated in certain regions due to gene mutations. Currently, data on the susceptible strains prevalence and the actual causal mutations are still scarce, particularly in Malaysian Borneo. A pool of B. pseudomallei isolates (n = 46) were screened for gentamicin susceptibility and phenotypically confirmed using the gradient minimum inhibitory concentration method. Three isolates were gentamicin-susceptible strains and were identified as having originated from Bintulu, Sarawak, Malaysian Borneo. The amrB gene mutation in these mutant strains was analysed, and the effect of amino acid substitution on the stability of the amrB protein was determined by using in silico analysis. The mutagenesis analysis identified a polymorphism-associated mutation, g.1056T>G, and two susceptible-associated mutations identified as novel in-frame amino acid deletion p.Val412del and amino acid substitution p.Thr368Arg that compromised gentamicin resistance. In silico analysis using amrB homology-modelled and AlphaFold-solved structures proposed the role of p.Thr368Arg amino acid substitution in conferring GEN susceptibility by other mechanisms than destabilising the structure of amrB protein, which is most probably due to the mutations location in the highly conserved region. The findings have shed light on the phenotypic characteristics and mutations involved in the amrB gene of the gentamicin-susceptible B. pseudomallei.

microbiology↗

bioRxiv2022

Sinking a giant: quantitative macroevolutionary comparative methods debunk qualitative assumptions

Myhrvold et al.1 suggest that our inference of subaqueous foraging among spinosaurids2 is undermined by selective bone sampling, inadequate statistical procedures, and use of inaccurate ecological categorizations. Myhrvold et al.1 ignore major details of our analyses and results, and instead choose to portray our inferences as if they were based on qualitative interpretations of our plots, without providing additional analyses to support their claims. In this manuscript, we thoroughly discuss all the concerns exposed by Myhrvold et al.1. Additional analyses based on our original datasets2 and novel data presented by Myhrvold et al.1 do not change our original interpretations: while the spinosaurid dinosaurs Spinosaurus and Baryonyx are recovered as subaqueous foragers, Suchomimus is inferred as a non-diving animal.

paleontology↗

bioRxiv2021

Metformin in nucleus accumbens core reduces cue-induced cocaine seeking in male and female rats

This study investigated the potential therapeutic effects of the FDA-approved drug metformin on cue-induced reinstatement of cocaine seeking. Metformin (dimethyl-biguanide) is a first-line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK). Cocaine self-administration and extinction is associated with decreased levels of phosphorylated AMPK within the nucleus accumbens core (NAcore). Previously it was shown that increasing AMPK activity in the NAcore decreased cue-induced reinstatement of cocaine seeking. Decreasing AMPK activity produced the opposite effect. The goal of the present study was to determine if metformin in the NAcore reduces cue-induced cocaine seeking in adult male and female Sprague Dawley rats. Rats were trained to self-administer cocaine followed by extinction prior to cue-induced reinstatement trials. Metformin microinjected in the NAcore attenuated cue-induced reinstatement in male and female rats. Importantly, metformins effects on cocaine seeking were not due to a general depression of spontaneous locomotor activity. In female rats, metformins effects did generalize to a reduction in cue-induced reinstatement of sucrose seeking. These data support a potential role for metformin as a pharmacotherapy for cocaine use disorder, but warrant caution given the potential for metformins effects to generalize to a natural reward in female rats.

neuroscience↗

bioRxiv2021

Down-regulation of A Human Herpesvirus 1 (HHV-1) MicroRNA in Infected Cells by Goniothalamin Treatment

Goniothalamin (GTN) has been proven to cause cell cycle arrest and apoptosis in human herpesvirus 1 (HHV-1) infected cells, but interestingly our preliminary transcriptomic analysis revealed other possible modes of action. The data showed that GTN treatment of HHV-1 clinical strain infected cells induced expression of the KLHL24 gene that encodes the Kelch-like 24 protein (KLHL24), a transcriptional inhibitor of HHV-1 immediate-early and early genes. An miRNA, hsv1-miR-H27, produced by HHV-1 has also been discovered to control the expression of KLHL24. In order to understand the cause of KLHL24 up-regulation, a time point study was conducted to investigate the effect of GTN on KLHL24 and hsv1-miR-H27 expression. Through RT-qPCR analysis, we found that HHV-1 down-regulated KLHL24 significantly (p < 0.05) starting from 12 hpi, while a significant up-regulation (p < 0.05) was observed upon GTN treatment of the infected cells at 4 and 8 hpi. For protein level analysis, significant down-regulation of KLHL24 (p < 0.05) was observed at all time points in HHV-1 infected cells. Intriguingly, treatment with GTN on HHV-1 infected cells showed no significant changes in protein expression compared to cells without any treatment. In addition, the miRNA hsv1-miR-H27 was detected from 16 hpi and treatment with GTN on infected cells showed down-regulation of the miRNA. This was in congruity with the recovery of KLHL24 down-regulation in GTN treated HHV-1 infected cells, confirming that GTN caused down-regulation of hsv1-miR-H27 that governs the expression of KLHL24. This study provides insights that GTN could be a potential multifaceted antiviral. ImportanceThis study provides evidence that GTN possesses a distinct mode of antivirus against HHV-1 compared to currently available antivirals. Our findings showed that GTN caused the down-regulation of a viral miRNA, which inhibits the expression of a cellular protein known as KLHL24. This protein serves as a transcriptional inhibitor of HHV-1 immediate-early and early genes. The down-regulation of this miRNA lead to the up-regulation of KLHL24 and eventually halted HHV-1 replication. With the previously reported antiviral mechanism and the outcome of this study, GTN is a potential multifaceted anti-HHV-1 agent.

microbiology↗

bioRxiv2020

Incidence and Risk Factors of Combined-Antiretroviral Therapy-Induced Hepatotoxicity among HIV Patients at the Bali District Hospital, Cameroon.

IntroductionThe incidence of hepatotoxicity is life-threatening and can result to an end-stage liver disease in long-term patients on combined antiretroviral therapy (cART). Our study sought to evaluate the incidence and predictors of cART-induced hepatotoxicity (CIH) among long term users on cART in a rural District hospital. MethodsThis was a hospital-based cross-sectional study in the Bali District Hospital. Spectrophotometric method was use for the quantitative measurement of alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) levels. Patients with elevations of both ALT and AST were considered CIH. The Chi ({chi}2) square test, ANOVA and Kaplan Meier log-ranked/ survival analyses were used to analyse the data. ResultsOf the 350 participants enrolled [156 (44.6%) males and 194 (55.4%) females], aged 43.87 {+/-} 0.79 years (range 20 - 84 years) included in this analysis, 26 (4.4%) experienced moderate CIH. We observed 57 (16.3%), 62 (17.7%) and 238 (68%) elevated levels ALT + AST, ALT and AST respectively. Two independent predictive factors of CIH were, the male sex and alcoholism during the study period. ConclusionThe prevalence of CIH in HIV-infected patients in Bali was lower than that observed in previous studies. The duration of therapy had no influence on the frequency of CIH. Alcoholism and smoking showed significant differences in the development of CIH.

biochemistry↗

bioRxiv2020

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes

Black women of African ancestry experience more aggressive breast cancer with higher mortality rates than White women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast tumors, with RNA-seq in a subset, from indigenous African patients in Nigeria in comparison to The Cancer Genome Atlas (n=76) revealed a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations and a 10.5-year younger age at diagnosis. We also found evidence for non-coding mutations in two novel drivers (ZNF217 and SYPL1) and a novel INDEL signature strongly associated with African ancestry proportion. This comprehensive analysis of an understudied population underscores the need to incorporate diversity of genomes as a key parameter in fundamental research with potential to tailor clinical intervention and promote equity in precision oncology care.

genomics↗

bioRxiv2018

Annotation of phenotypes using ontologies: a Gold Standard for the training and evaluation of natural language processing systems

Natural language descriptions of organismal phenotypes - a principal object of study in biology, are abundant in biological literature. Expressing these phenotypes as logical statements using formal ontologies would enable large-scale analysis on phenotypic information from diverse systems. However, considerable human effort is required to make the semantics of phenotype descriptions amenable to machine reasoning by (a) recognizing appropriate on-tological terms for entities in text and (b) stringing these terms into logical statements. Most existing Natural Language Processing tools stop at entity recognition, leaving a need for tools that can assist with both aspects of the task. The recently described Semantic CharaParser aims to meet this need. We describe the first expert-curated Gold Standard corpus for ontology-based annotation of phenotypes from the systematics literature. We use it to evaluate Semantic CharaParsers annotations and explore differences in performance between humans and machine. We use four annotation accuracy metrics that can account for both semantically identical and similar matches. We found that machine-human consistency was significantly lower than inter-curator (human-human) consistency. Surprisingly, allowing curators access to external information that was not available to Semantic CharaParser did not significantly increase the similarity of their annotations to the Gold Standard nor have a significant effect on inter-curator consistency. We found that the similarity of machine annotations to the Gold Standard increased after new ontology terms relevant to the input text had been added. Evaluation by the original authors of the character descriptions indicated that the Gold Standard annotations came closer to representing their intended meaning than did either the curator or machine annotations. These findings point toward ways to better design of software to augment human curators, and the Gold Standard corpus will allow training and assessment of new tools to improve phenotype annotation accuracy at scale.

evolutionary biology↗