Biology subjects

Ali, K. M.

Publications and source records attributed to Ali, K. M..

3 recordsLinked to original sources

bioRxiv2025

Coaxially Electrospun Myocardial dECM-based Nanofibrous Scaffolds Demonstrate Enhanced Cardiomyocyte Adhesion and Function

Abstract textLimited regenerative capability of mature cardiomyocytes (CMs) makes myocardial repair more challenging, requiring effective and viable alternatives to conventional heart transplants. Cardiac tissue engineering is a substitutionary approach combining cells, scaffolds, and growth factors to develop functional heart tissues in vitro. Induced pluripotent stem cells (iPSCs) represent a significant advancement in cardiac regenerative medicine, offering a continuous supply of CMs, however, the limited understanding of their microenvironment hinders translational research. Decellularized extracellular matrix (dECM) derived from myocardium is a highly promising natural scaffold for CTE, given its tissue-specific composition, mechanical properties, and biochemical cues that promote cellular regeneration. This study investigates myocardial dECM-based fibrous scaffolds for iPSC-derived CM use. Coaxially electrospun nanofibers comprising a polyurethane core and a blend of polycaprolactone and myocardial dECM as the sheath were optimized. Morphological analysis confirms the resemblance of the nanofibers to fibrillar collagen in the native dECM. ATR-FTIR and immunostaining results confirm the presence of dECM which enhanced their hydrophilicity and enzymatic degradation. Biocompatibility results show higher phenotypic retention of iPSC-CMs due to microenvironments enriched with native proteins. On the contrary, the scaffolds without myocardial proteins exhibit higher dedifferentiation of iPSC-CMs, proving that ECM proteins provide a suitable microenvironment for iPSC-CMs. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/673432v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@31a497org.highwire.dtl.DTLVardef@12cee05org.highwire.dtl.DTLVardef@beca77org.highwire.dtl.DTLVardef@1de5337_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Speed Matters: Accelerated Pharmacokinetics Reduce Persisters in Escherichia coli

Persister cells are bacterial cells that form small subpopulations and are refractory to antimicrobials. Importantly, those cells can cause the relapse of an infection and also provide a starting point for antimicrobial resistance evolution. By now, several mechanisms of persister formation have been studied. For example, it has been shown that a short exposure to sublethal concentrations of antimicrobials can induce persister formation. Given this, we hypothesised that the pharmacokinetics, the temporal changes of drug concentrations under treatment, could impact persister formation. We predicted that the longer bacteria spend under sublethal drug concentrations, the more persisters would form. Using a set-up with small chemostats and the antimicrobial peptide Pexiganan, we indeed found that faster pharmacokinetics resulted in lower persister numbers compared to slower pharmacokinetics. This finding provides a proof of principle that pharmacokinetics, which can be influenced by treatment procedures, has consequences for persister formation. Our results suggest that faster pharmacokinetics could be useful to minimize persister numbers and hence to lower the risks of relapse or resistance evolution.

evolutionary biology↗

bioRxiv2017

The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space

Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of the DNA methylation dynamics in matched primary and recurring glioblastoma tumors, based on a national population registry and a comprehensively annotated clinical cohort. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected formalin-fixed paraffin-embedded (FFPE) samples, and we validate bisulfite sequencing as a multi-purpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional tumor characteristics. Based on these data, we identified characteristic differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study provides a resource for dissecting DNA methylation heterogeneity in genetically diverse and heterogeneous tumors, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology in a representative national cohort, leveraging samples and data collected as part of routine clinical practice.

cancer biology↗