Biology subjects

Farhan, M.

Publications and source records attributed to Farhan, M..

4 recordsLinked to original sources

bioRxiv2026

The pyruvate branch point controls lymphoid cancer cell dissemination

Cancer cell dissemination critically determines clinical prognosis, yet metabolic dependencies and corresponding therapeutic targets during spread of lymphoid malignancies remain poorly understood. Here we show that the pyruvate branch point operates as a metabolic checkpoint for lymphoid cancer cell migration and disease dissemination through mitochondrial ROS (mROS)/HIF-1a signaling. Isolation of highly migratory mROShi cells led us to identify selective metabolic requirements of malignant lymphocyte migration and disease dissemination. Highly migratory cells show a reprogrammed metabolic profile characterized by increased glucose uptake and reduced glucose-carbon entry into the TCA cycle. Reprogramming of the TCA cycle with downregulation of citrate synthase provide the mechanistic basis for decreased pyruvate oxidation leading to increased migration and disease dissemination through mROS/HIF-1a signaling. Our findings connect central carbon metabolism and migratory capacity of lymphoid cancer cells and identify the pyruvate branch point as a metabolic switch and potential therapeutic target in lymphoid cancer cell dissemination.

cancer biology↗

bioRxiv2024

Characterization of Autophagy Cargo Profiles during Starvation and Exercise with a Novel Autophagosome Isolation Method

Autophagy is a cellular process to clear unwanted and dysfunctional cellular cargoes, which are sequestered in autophagosomes before their delivery to lysosomes for degradation. Autophagy cargo selection, mediated by cargo receptors, varies across cell types and conditions. Understanding the cargo features is essential for elucidating autophagys function in specific physiological or pathological contexts. Here we present a simple and rapid method for isolating LC3B-positive autophagosomes from the tissues of GFP-LC3 transgenic mice, a widely used autophagy reporter model, without relying on the complex ultracentrifugation steps required by traditional methods. When combined with quantitative proteomics, this approach enables efficient in vivo characterization of autophagy cargoes. We applied this method to establish autophagy cargo profiles in skeletal muscle during starvation and exercise, two physiological conditions that activate autophagy, and identified distinct cargo selection patterns, with significantly higher levels of ER-phagy and ribophagy observed during starvation. We further revealed the ER-phagy receptors TEX264 and RETREG1/FAM134B as potential mediators of the elevated ER-phagy under starvation. In summary, we report an efficient workflow for in vivo autophagy cargo characterization and provide detailed analysis and comparison of cargo profiles under starvation and exercise conditions.

cell biology↗

bioRxiv2024

Phosphate starvation stops bacteria digesting algal fucan that sequesters carbon

Algae provide a solar powered pathway to capture and sequester carbon by injecting stable fucan made from carbon dioxide into the ocean 1-4. Stability of the pathway is at odds with the presence of marine bacteria with genes of enzymes that can digest fucan and release the carbon dioxide 5. Biochemical explanations for stable fucan remain hypothetical 6. We assembled a biological carbon cycle model and found phosphate limitation enhanced fucan synthesis by algae, stopped digestion by bacteria and thereby stabilized the fucan carbon sequestration pathway. Marine microalgae Glossomastix sp. PLY432 increased synthesis of fucan, a part of its extracellular matrix, under nutrient-growth limiting conditions. Rate and extent of fucan digestion by a marine, isolated bacterium of the Akkermansiaceae family decreased with decreasing phosphate concentration. Phosphate starvation restricted bacterial growth rate, biomass yield and in turn increased the amount of stable fucan. Phosphate is universally required for growth but rare relative to glycan carbon in photosynthesis-derived ecosystems. The fact that phosphate is required for replication, transcription and translation explains why bacteria can digest gigatons of laminarin with a few enzymes, but not fucan during nutrient limited algal blooms. We conclude phosphate starvation constrains the ability of bacteria to digest fucan, which evolves to maintain stability around algal cells and consequentially also to keep carbon dioxide in the ocean.

microbiology↗

bioRxiv2019

Control and simulation impact on nonlinear Hepatitis-B model by using Pade-approximation based Differential Evolution

Hepatitis B is the main public health problem of the whole world. In epidemiology, mathematical models perform a key role in understanding the dynamics of infectious diseases. This paper proposes Pade approximation (Pa) with Differential Evolution (DE) for obtaining solution of Hepatitis-B model which is nonlinear numerically. The proposed strategy transforms the nonlinear model into optimization problem by using Pade approximation. Initial conditions are converted into problem constraints and constraint problem become unconstraint by using penalty function. DE is obtained numerical solution of Hepatitis-B model by solving the established problem of optimization. There is no need to choose step lengths in proposed Pade-approximation based Differential Evolution (PaDE) technique and also PaDE converges to true steady state points. Finally, a convergence and error analysis evidence that the convergence speed of PaDE is greater than Non-Standard Finite Difference (NSFD) method for different time steps.

developmental biology↗