Biology subjects

Mohamed, S.

Publications and source records attributed to Mohamed, S..

5 recordsLinked to original sources

bioRxiv2026

Pluripotency and Transcriptional Pausing Disrupt Circadian Rhythms to Facilitate the Enrichment of Cancer Stem Cells

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype, enriched for cancer stem cells (CSCs), which are the cause of tumor recurrence. CSCs are responsible for tumor initiation and propagation; however, the molecular mechanisms underlying their formation remain largely unclear. We show that carboplatin treated TNBC cells lose their circadian rhythms and promote the enrichment of CSCs. Notably, genetic ablation of the circadian clock by itself, without carboplatin treatment, facilitated the formation of CSCs along with their ability to generate 3D tumorspheres and mouse tumors enriched with CSCs. Mechanistically, we identified an antagonistic interplay between the circadian clock and pluripotency, whereby the core pluripotent factor OCT4 disrupts the expression of circadian timekeeping genes to disable the circadian clock. Furthermore, we uncovered a transcriptional pausing program, controlling the circadian clock, to be perturbed in carboplatin treated TNBC cells. Concordantly, based on gene expression analysis from The Cancer Genome Atlas (TCGA), we found that the uncoupling of transcriptional pausing and the circadian clock correlated with low survivability across diverse cancer types. Moreover, cancer patients with poor prognosis exhibit low expression of the core timekeeping genes Clock, Npas2, Bmal1 and Rorc. Lastly, we restored circadian rhythms in Oct4 deficient TNBC cells and impaired their ability to generate tumorspheres and decreased the number of CSCs in mouse tumors. Overall, our findings demonstrate an unprecedented mechanism for the formation of CSCs that is dependent on the loss of circadian rhythms and thereby has eminent implications for developing new cancer therapies.

cancer biology↗

bioRxiv2024

Filter bank common spatial pattern and envelope-based features in multimodal EEG-fTCD brain-computer interfaces

Brain-computer interfaces (BCIs) exploit brain activity to bypass neuromuscular control with the aim of providing alternative means of communication with the surrounding environment. Such systems can significantly improve the quality of life for patients suffering from severe motor or speech impairment. Multimodal BCIs have been introduced recently to enhance the performance of BCIs utilizing single modality. In this paper, we aim to improve the performance of multimodal BCIs combining Electroencephalography (EEG) and functional transcranial Doppler ultrasound (fTCD). The BCIs included in the study utilized two different paradigms to infer user intent including motor imagery (MI) and flickering mental rotation (MR)/word generation (WG) paradigms. Filter Bank Common Spatial Pattern (FBCSP) algorithm was used to extract features from the EEG data. Several time series features were extracted from the envelope of the fTCD signals. Wilcoxon rank sum test and linear kernel Support vector machines (SVM) were used for feature selection and classification respectively. Additionally, a probabilistic Bayesian fusion approach was used to fuse the information from EEG and fTCD modalities. Average accuracies of 94.53%, 94.9% and 96.29% were achieved for right arm MI versus baseline, left arm MI versus baseline, and right arm MI versus left arm MI respectively. Whereas average accuracies of 95.27%, 85.93% and 96.97% were achieved for MR versus baseline, WG versus baseline, and MR versus WG respectively. Our results show that EEG- fTCD BCIs with the proposed analysis techniques outperformed the multimodal EEG-fNRIS BCIs in comparison.

bioengineering↗

bioRxiv2024

Genome-Wide CRISPR-Cas9 Screening Identifies a Synergy between Hypomethylating Agents and SUMOylation Blockade in MDS/AML

Hypomethylating agents (HMAs) are frontline therapies effective at altering the natural course of Myelodysplastic Neoplasms (MDS) and Acute Myeloid Leukemia (AML). However, acquired resistance and treatment failure are hallmarks of HMA therapy. To address this clinical need, we performed a genome-wide CRISPR-Cas9 screen in a human MDS-derived cell line, MDS-L, and identified TOPORS as a highly ranked loss-of-function target that synergizes with HMAs, reducing leukemic burden and improving survival in xenograft models. We demonstrate that the depletion of TOPORS mediates sensitivity to HMAs by predisposing leukemic blasts to an impaired DNA damage response (DDR) accompanied by an accumulation of SUMOylated DNMT1 in HMA-treated TOPORS-depleted cells. Importantly, the combination of HMAs with targeting of TOPORS did not functionally impair healthy hematopoiesis. While inhibitors of TOPORS are currently unavailable, we show that inhibition of protein SUMOylation (upstream of TOPORS functions) with TAK-981 partially phenocopies HMA-sensitivity and DDR impairment. Overall, our data suggest that the combination of HMAs with the inhibition of SUMOylation or TOPORS demonstrates a favourable therapeutic index and is a rational treatment framework for High-Risk MDS (HR-MDS) or AML.

molecular biology↗

bioRxiv2023

Bait, not reward: CO2-enriched Nepenthes pitchers secrete toxic nectar

Nepenthes pitchers are leaf-evolved biological traps holding high levels of CO2 within them. Extrafloral nectar (EFN) secreted by these pitchers has long been regarded as the major reward to visiting arthropods, but its chemical constituents and their role in prey capture are least explored. Here we demonstrate Nepenthes EFN as a sugar (glucose-fructose-sucrose) mix with high C:N ratio, minimal amino acids, proteins, and vitamin C. Nepenthes khasiana peristome and lid EFNs displayed strong acetylcholinesterase (AChE) inhibition; the naphthoquinone derivative, (+)-isoshinanolone, has been identified as the AChE inhibitor. Plumbagin, the major volatile naphthoquinone in Nepenthes, also showed strong AChE inhibition. Direct EFN- and (+)-isoshinanolone-feeding bioassays demonstrated symptoms of cholinergic toxicity in ants. We testify that Nepenthes EFN is a toxic bait which hinders neuronal activity in visiting arthropods. These unique traps adopt various deceptive strategies for prey capture, and our discovery abolishes the notion that Nepenthes EFN is a reward to visiting ants and other arthropods. Moreover, our findings infer elevated CO2 within their pitchers as the key factor influencing the growth, metabolism, herbivory, and carnivory in Nepenthes. HighlightNepenthes extrafloral nectar has high content of carbohydrates and minimal nitrogenous metabolites. It is laced with (+)-isoshinanolone, an acetylcholinesterase inhibitor, and acts as a toxic bait, aiding prey capture.

plant biology↗

bioRxiv2021

First description of two immune escape indian B.1.1.420 and B.1.617.1 SARS-CoV2 variants in France

Following the outbreak of the SARS-CoV2 virus worldwide in 2019, the rapid widespread overtime of variants suggests today an undergoing positive selection of variants which could potentially provide advantageous genetic property of the virus. Numerous variants have already been described across different countries including N501Y, E484K or L452R mutations on gene coding to spike protein. Most recently, 2 new Indian variants with N440K and E484Q and L452R mutations associated with impaired antibody response and immune reactions were identified in India. The potential consequences of emerging variants are increased transmissibility, increased pathogenicity and the ability to escape natural or vaccine-induced immunity. We described for the first time in France both variants: the N440K immune escape variant within a new strain detected in France in a couple of patients who did not have any history of travel abroad and the new E484Q and L452R Indian variant from a patient travelling from Indian to Marseille to embark on a ship as a crew member. Such study of the circulating viral strains and their variants within the increasing number of infected people worldwide will provide further insights into the viral dissemination. Hence, real time close monitoring variant could help the scientific community to prevent fast-spreading and raise alarms towards potentially harmful variants.

molecular biology↗