Biology subjects

Chachoua, I.

Publications and source records attributed to Chachoua, I..

4 recordsLinked to original sources

bioRxiv2026

A comprehensive analysis of calreticulin mutants reveals distinct biophysicochemical proprieties with a potential for refined targeted therapies

Calreticulin mutations in myeloproliferative neoplasms result in the replacement of the C-terminus acidic sequence with a positively charged tail that causes pathological activation of the thrombopoietin. The two canonical variants are Type-1 and Type-2. The remaining are mainly classified as Type-1 or Type-2 like based on the wild type sequence retained. Here, we performed in silico biophysicochemical analyses of 76 CALR exon 9 frameshift variants by their sequence and predicted biophysical properties, complemented by structural modeling of the mutant homodimers. Beyond confirming the Type-1 versus Type-2 distinction, we found that the Type 1-like variants form a continuum of charge architecture along which two reproducible subgroups can be identified, rather than sharply separated classes. This work refines the conventional mechanism-based classification into a charge-resolved framework and provides testable hypotheses linking novel-tail chemistry to receptor activation in CALR-mutant neoplasms and paves the way for improved targeted therapies based on individual mutants characteristics

bioinformatics↗

bioRxiv2026

A distal CTCF-binding site drives MYC expression plasticity in a negative feed-forward loop

Oncogene expression heterogeneity systemically diversifies cancer cell phenotypes, enabling selection and cancer evolution. Here we document that the level of MYC expression variation is coordinated by a negative feed-forward loop involving the non-coding CCAT1 eRNA and the MYC gating process. While CCAT1 eRNA indirectly antagonizes MYC gating by promoting MYC transcriptional initiation and elongation, the MYC protein promotes gated MYC expression in a feedback loop by inhibiting both MYC transcription and CCAT1 expression. This entire process is coordinated by a CTCF binding site positioned within CCAT1 at a distal, oncogenic super-enhancer, which functions as a master switch by coordinating both CCAT1 and gated MYC expression to diversify cells toward both low and high MYC levels, as determined by heterogeneity metrics. As hallmarks of this principle are frequent in breast cancer and colorectal tumors, the dynamics of this new principle may underlie transitions between therapy-resistant low-MYC, and proliferative high-MYC tumor cells. Highlights- Transcriptional rate regulates MYC gating frequency - CCAT1 expression indirectly inhibits MYC gating by promoting MYC transcription - High MYC protein levels promote gated expression by inhibiting both MYC transcription and CCAT1 expression - These features are controlled by a single CTCF binding in the distant super-enhancer to drive expression plasticity in colorectal cancer cells

cancer biology↗

bioRxiv2025

Extracellular ssDNA from P. tobira Exerts Strong Insecticidal Activity on C. hesperidum

Beyond its function as a carrier of hereditary information, recent research has uncovered novel properties of extracellular DNA, including its role in the adaptation to the environment when released from plants. The secreted DNA has been shown to exert insecticidal effects against insect pests, which play an adaptive role in plant-insect interactions, particularly in regulating populations of economically important sap-feeding insects. The molecular mechanisms underlying this insecticidal effect are underinvestigated and remain largely unknown. Therefore, there is a need for more efforts to uncover these mechanisms to better understand the plant-pest interactions, which would provide new insights into natural pest control strategies and inspire biotechnological applications. In the current study, we show that Pittosporum tobira (P. tobira) secretes single-stranded DNA (ssDNA) that exerts an insecticidal effect on Coccus hesperidum (C. hesperidum). We collected extracellular DNA from P. tobira leaves and tested its potential insecticidal effect by applying it to C. hesperidum, which is a well-known pest that causes damage to P. tobira. Our results revealed that the outermost layer of the leaf cuticle of P. tobira predominantly contains ssDNA of approximately 100 nt in length, originating from both chloroplast and nuclear genomes. This DNA exhibited pronounced insecticidal activity against C. hesperidum, with chloroplast-derived sequences significantly enriched compared to the total DNA in intact plant cells. These findings suggest that the microevolution of the P. tobira nucleome and plastome contributed to the formation of extracellular DNA with insecticidal properties (eci-DNA), which is part of its defence strategy against insect pests. Moreover, in this article for the first time we show that antisense DNA (oli-gonucleotide insecticide Coccus-11) is capable of activating insect retrotransposons and upregulating their RT-RNase H, a crucial enzyme for the DNA containment mechanism and successful action of oligonucleotide insecticides. Notably, the laboratory-developed ssDNA-based genetic zipper technology, designed for sustainable pest management, possesses characteristics similar to eci-DNA found in nature, highlighting a potential natural parallel to this biotechnological approach for sustainable pest management. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=96 SRC="FIGDIR/small/689116v4_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1552668org.highwire.dtl.DTLVardef@14c84e3org.highwire.dtl.DTLVardef@a87493org.highwire.dtl.DTLVardef@17d624f_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Single-Cell Microwave Cytometry for Drug Resistance Detection in Cancer

Monitoring biophysical changes in single cells induced by drugs is crucial for advancing cancer therapies, especially for highly heterogeneous tumours. Emerging methods for single-cell drug sensitivity testing have largely relied on phenomenological analyses. Here, we present a novel electronic cytometry platform integrating microwave resonators with impedance cytometry, enabling simultaneous, label-free measurements of cell volume and dielectric permittivity at microwave frequencies. This approach uniquely captures intracellular differential responses indicative of drug-induced biophysical states, thus providing deeper insights beyond traditional phenomenological analyses. We first validated the platform using varying salt concentrations. We then demonstrated that the sensor platform could differentiate between drug resistant versus sensitive phenotypes in multiple isogenic cancer cell lines treated with cytostatic, cytotoxic and mixed-effect drugs. Notably, we showed that the technique performs successfully in patient-derived tumor organoids, a model system highlighting its immediate clinical relevance. Our findings underscore the potential of electronic measurements at the single cell level to provide informative and actionable biophysical signals relating to cellular drug response. The implementation of this platform could significantly advance cancer treatment by identifying the resistant cell populations in heterogenous tumours and optimizing selection of drugs for each patient, paving the way towards precision medicine.

bioengineering↗