Biology subjects

Ghasemi, M.

Publications and source records attributed to Ghasemi, M..

5 recordsLinked to original sources

bioRxiv2026

Bottom-up engineering of EV-mimetic vesicles reveals selective protein loading and modulates cellular uptake and biodistribution

Biological systems such as extracellular vesicles (EVs) are highly sophisticated and functionally diverse. Despite growing recognition of EVs' roles in health and disease through mediating intercellular communication, their inherent heterogeneity and challenges in purity and yield hinder their mechanistic research and clinical translation. To address this gap, we sought to translate essential EV properties into a controllable and simplified platform by engineering biomimetic synthetic vesicles (SVs) incorporating defined proteins and lipids. Using microfluidics, we generated SVs loaded with bulk membrane and cytosolic proteins from cancer cells, as well as individual organotropism-associated integrins. Bulk membrane protein incorporation into SVs reduced surface charge, modified lipid profiles, and enhanced cellular uptake, while integrin incorporation altered biodistribution. To investigate protein loading, we profiled input materials and SVs by mass spectrometry, identifying features linked to high incorporation, such as low molecular weight, positive charge, high isoelectric point, and predicted stability, globularity, lipidation, and amphipathic helices. This work presents a synthetic platform for dissecting the roles of EV-associated features and cargo, while providing insights into protein properties relevant to the optimization of delivery systems.

bioengineering↗

bioRxiv2024

deadtrees.earth - An Open-Access and Interactive Database for Centimeter-Scale Aerial Imagery to Uncover Global Tree Mortality Dynamics

Excessive tree mortality is a global concern and remains poorly understood as it is a complex phenomenon. We lack global and temporally continuous coverage on tree mortality data. Ground-based observations on tree mortality, e.g., derived from national inventories, are very sparse, not standardized and not spatially explicit. Earth observation data, combined with supervised machine learning, offer a promising approach to map tree mortality over time. However, global-scale machine learning requires broad training data covering a wide range of environmental settings and forest types. Drones provide a cost-effective source of training data by capturing high-resolution orthophotos of tree mortality events at sub-centimeter resolution. Here, we introduce deadtrees.earth, an open-access platform hosting more than a thousand centimeter-resolution orthophotos, covering already more than 300,000 ha, of which more than 58,000 ha are fully annotated. This community-sourced and rigorously curated dataset shall serve as a foundation for a global initiative to gather comprehensive reference data. In concert with Earth observation data and machine learning it will serve to uncover tree mortality patterns from local to global scales. This will provide the foundation to attribute tree mortality patterns to environmental changes or project tree mortality dynamics to the future. Thus, the open and interactive nature of deadtrees.earth together with the collective effort of the community is meant to continuously increase our capacity to uncover and understand tree mortality patterns.

ecology↗

bioRxiv2024

Fatty acids are not a significant contributor to the TCA cycle in cancer cell lines: evidence of incomplete fatty acid oxidation.

Upregulated fatty acid oxidation (FAO) is a hallmark of many aggressive cancers and is widely presumed to fuel the tricarboxylic acid (TCA) cycle for ATP production. However, the quantitative relationship between FAO capacity and its contribution to mitochondrial metabolism relative to other fuels remains unclear. Here, we combined parallel stable-isotope tracing with metabolic phenotyping across a diverse panel of 27 cancer cell lines to reveal a fundamental capacity-contribution paradox. Despite exhibiting FAO rates that varied over eight-fold, exogenous long-chain fatty acids consistently contributed minimally (<10%) to TCA cycle intermediates in all cancer cell lines. We demonstrated that FAO functions as a compensatory source of acetyl-CoA in cells with limited glucose-derived acetyl-CoA synthesis, rather than acting as a primary fuel source. In this context, high FAO rates do not primarily result from FAO-mediated suppression of glucose oxidation, but instead reflect the recruitment of fatty acid- and glutamine-derived carbons via a malic enzyme-dependent shunt to sustain the mitochondrial acetyl-CoA pool while preserving glucose-derived anaplerotic flux. These findings challenge the prevailing view that FAO serves as a primary bioenergetic fuel in cancer, instead identifying it as a compensatory rheostat that supplements acetyl-CoA supply in glucose-limited settings by working together with glutamine-driven, malic enzyme-dependent anaplerosis, providing a mechanistic framework to reinterpret the efficacy of FAO inhibitors beyond simple caloric starvation.

cancer biology↗

bioRxiv2022

Inverse Material Parameter Estimation of Patient Specific Finite Element Models at the Carotid Bifurcation: The Impact of Excluding the Zero Pressure Configuration and Residual Stress

Abstract SummaryThe carotid bifurcation experiences a complex loading environment due to its anatomical structure. Previous in-vivo material parameter estimation methods often use simplified model geometries, isotropic hyperelastic constitutive equations or neglect key aspects of the vessel, such as the zero-pressure configuration or residual stress. These factors have independently been shown to alter the stress environment of the vessel wall. Characterising the location of high stress in the vessel wall has often been proposed as a potential indicator of structural weakness. However, excluding the afore-mentioned zero-pressure configuration, residual stress and patient specific material parameters can lead to an incorrect estimation of the true stress values observed, meaning stress alone as a risk indicator of rupture is insufficient. In this study, we investigate how the estimated material parameters and overall stress distributions in geometries of carotid bifurcations, extracted from in-vivo MR images, alter with the inclusion of the zero-pressure configuration and residual stress. This approach consists of the following steps: (1) geometry segmentation and hexahedral meshing from in-vivo MRI images at two known phases; (2) computation of the zero-pressure configuration and the associated residual stresses; (3) minimisation of an objective function built on the difference between the stress states of an " almost true" stress field at two known phases and a "deformed" stress field by altering the input material parameters to determine patient specific material properties; and (4) comparison of the stress distributions throughout these carotid bifurcations for all cases with estimated material parameters. This numerical approach provides insights into the need for estimation of both the zero-pressure configuration and residual stress for accurate material property estimation and stress analysis for the carotid bifurcation, establishing the reliability of stress as a rupture risk metric. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=56 SRC="FIGDIR/small/487823v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@a63f0forg.highwire.dtl.DTLVardef@7612f1org.highwire.dtl.DTLVardef@1d5beb7org.highwire.dtl.DTLVardef@1dbfbfd_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2019

Genetic and physical interaction of Drosophila Ino80 with Polycomb Responsive Element

The chromatin remodeling protein, dIno80 (Drosophila Ino80) regulates homeotic genes. We show that Ino80, along with Trx and ETP (Enhancer of Trithorax and Polycomb) proteins, interacts with two Polycomb/Trithorax Responsive Elements (PRE/TRE), iab-7 and bxd PRE in flies and the larval imaginal discs. In S2 cells, dIno80 localizes to the endogenous iab-7 and bxd-PREs. The localization of Ino80 and Pleiohomeotic (Pho) at the PRE is sensitive to the cellular abundance of each other; when levels of Ino80 are limiting, there is increased Pho enrichment, and Pho knock-down leads to increased enrichment of Ino80. We demonstrate that over-expression of dIno80 rescues the pupal lethality in pleiohomeotic (pho) deficient flies, which suggests that dIno80 has a role in cellular memory. The apparent competition between Pho and Ino80 for binding at the PRE indicates that Ino80 may act as a potential recruiter of the regulatory complex in addition to being a chromatin remodeler.\n\nAuthor SummaryThe null mutants of Pho and dIno80 show lethality at different stages of development in the fly, implying that they may function independent of each other. The observation that Pho-lethality can be rescued by overexpression of dIno80 with significant penetrance and that Ino80 has its own DNA binding domain, led us to predict that Ino80 may have Pho-independent functions, perhaps through non-canonical complexes. In the current study, we show that dIno80 interacts with bxd and iab-7 PRE in cooperation with Polycomb and Trithorax proteins and regulate the homeotic genes. The effect of knock-down or mutation of dIno80 results in altered phenotype in adult flies and rescue of Lac-Z expression in imaginal discs, in parallel with similar effect of Pho mutation or knock-down. We provide evidence of direct interaction of dIno80 with iab7- and bxd-PRE using chromatin immunoprecipitation. The dIno80 localization in and around the PRE sequence was enhanced in the absence of Pho, indicating competition between Pho and dIno80 for binding at the PRE.

developmental biology↗