Biology subjects

Mohamed, M.

Publications and source records attributed to Mohamed, M..

13 recordsLinked to original sources

bioRxiv2026

Collagen-dependent DDR1 ectodomain shedding regulates proliferative signaling in radiation-resistant glioblastoma

Glioblastoma (GBM) is characterized by near-universal recurrence and resistance to therapy. Although tumor-intrinsic mechanisms of radiation resistance have been extensively studied, how the extracellular matrix influences signaling in radiation-resistant GBM remains poorly understood. Here, we investigated discoidin domain receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase, using matched radiation-sensitive parental and radiation-resistant patient-derived GBM models generated through serial in vivo irradiation. Within a three-dimensional collagen I matrix, radiation-resistant GBM cells exhibited distinct temporal patterns of Ki-67 positivity and ERK1/2 phosphorylation compared with parental cells. Despite increased DDR1 expression, radiation-resistant cells exhibited markedly reduced DDR1 phosphorylation and enhanced ectodomain shedding, characterized by accumulation of the membrane-associated C-terminal fragment and release of the N-terminal fragment. DDR1 depletion reduced ERK1/2 phosphorylation, supporting its contribution to ERK1/2 signaling under these conditions. ADAMTS1 was markedly upregulated in radiation-resistant cells, and its knockdown reduced DDR1 ectodomain shedding while increasing full-length DDR1 abundance, ERK1/2 and RB phosphorylation, cyclin D1 expression, and Ki-67 positivity. Together, these findings reveal a distinct DDR1 regulatory state in acquired radiation-resistant GBM, characterized by enhanced ADAMTS1-associated ectodomain shedding, reduced receptor phosphorylation, and attenuated proliferative signaling within a three-dimensional collagen I matrix.

cancer biology↗

bioRxiv2026

Spontaneous behavior predicts colony membership, individual identity, and rank in naked mole-rat societies

Animal societies are organized across scales, from moment-to-moment actions of individuals to dynamic group structure. A central challenge in sociobiology is to understand how behaviors of individuals shape group structure. Here, using machine vision to map recurrent fine-scale behavioral modules in the eusocial naked mole-rat (Heterocephalus glaber), we show that spontaneous behavior in isolation predicts group-level social organization, including colony membership and individual identity. We determined dominance relationships and found highly linear hierarchies, with ranks stable over months to years. Remarkably, fine-scale behavioral profiles in isolation correctly predicted pairwise dominance relationships, allowing reconstruction of rank order within each colony. Models trained within one colony predicted rank poorly in others, suggesting that naked mole-rats express social position through behavioral patterns specific to each colony. Together, our results connect fine-scale behavior to social structure maintained over years and show that, even when an animal is alone, its behavior carries signatures of its identity, colony, and place within that society.

animal behavior and cognition↗

bioRxiv2026

SON-mediated circular RNA suppression promotes PKR signaling and radiation resistance in glioblastoma

Glioblastoma (GBM) exhibits extensive loss of circular RNAs (circRNAs), yet the mechanisms driving this depletion and its functional consequences remain unclear. Here, we identify the splicing co-factor SON as a previously unrecognized suppressor of circRNA biogenesis in GBM. CircRNA sequencing revealed widespread increases in circRNA abundance following SON knockdown. Conversely, elevated SON expression in GBM, with further increases in radiation-resistant models, was associated with widespread circRNA loss, including reduced expression of circUSP1 and circSUCO. SON knockdown increased circRNA abundance and attenuated activation of the dsRNA-responsive kinase PKR and downstream NF{kappa}B signaling, whereas radiation-resistant GBM cells exhibited enhanced PKR/NF{kappa}B activation that was attenuated by SON depletion. Importantly, overexpression of the SON-suppressed circRNAs circUSP1 and circSUCO reduced PKR activation and selectively decreased clonogenic survival following irradiation in radiation-resistant GBM cells, with little effect on parental cells. Together, these findings identify a previously unrecognized SON/circRNA/PKR regulatory pathway linking RNA processing to acquired radiation resistance in GBM and highlight specific PKR-inhibitory circRNAs as potential therapeutic tools for resensitizing radiation-resistant GBM to radiotherapy.

cancer biology↗

bioRxiv2026

Small-RNA Profiling Links 5'-tRNA Halves to Post-therapeutic Disease Persistence and Poor Patient Survival in Glioblastoma

Glioblastoma (GBM) is a highly lethal brain cancer with limited therapeutic durability, where the majority of patients develop recurrent or persistent disease after standard chemoradiotherapy. Meanwhile, tRNA-derived fragments (tRFs) have become increasingly relevant to cancer biology; however, their clinical relevance in GBM remains undefined. Here, we report that a specific family of tRFs, 5-tRNA halves (tiR5s) dominates the small RNA landscape of GBM patient tumors and associates with worse overall survival, post-therapeutic disease persistence, and pro-invasive proteogenomic pathways across two independent GBM patient cohorts. This association between elevated tiR5 levels and therapeutic resistance re-emerges in radiation-resistant GBM xenograft models. Our findings reveal that tiR5s are an underappreciated molecular feature of highly aggressive GBM tumors, supporting further investigation into their biological roles and prognostic utility in GBM. HighlightsO_LItiR5s are the predominant tRF family in primary GBM patient tumors C_LIO_LIElevated tiR5 expression distinguishes primary GBM tumors that develop persistent disease after first-line therapy C_LIO_LIRadiation-resistant GBM PDX models show elevated tiR5 expression C_LIO_LIElevated tiR5 expression associates with poor overall patient survival and pro-invasive molecular programs in GBM patient tumors C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/738483v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@3219d5org.highwire.dtl.DTLVardef@13e09b8org.highwire.dtl.DTLVardef@1f0328borg.highwire.dtl.DTLVardef@867b09_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2026

SaVanache: indexing and visualizing pangenome variation graphs

With the rapid increase in genome sequencing and the growing availability of genomic resources, genomics is shifting toward pangenome representations that capture intra- and inter-specific diversity by integrating multiple genomes into a single entity. These pangenomes are increasingly modeled as graphs, encoding complex genomic variations in structures such as de Bruijn or variation graphs. However, while genome browsers provide standard and effective solutions for visualizing single or limited numbers of genomes, equivalent interactive tools for graph-based pangenomes remain limited, particularly for variation graph models. We developed SaVanache, a multi-resolution visualization interface designed to explore pangenome variation graphs at various depths. SaVanache enables the exploration of both global diversity and structural variations (SVs) across genomes relative to a user-defined linear pivot genome. Unlike synteny viewers, SaVanache emphasizes variations by representing SV types through a dedicated set of glyphs, facilitating intuitive one-to-many comparisons. To support smooth exploration, SaVanache preprocesses a Graphical Fragment Assembly (GFA) pangenome file into optimized index and data structures, enabling fast, real-time queries on large pangenome graphs. By combining advanced visualization techniques with efficient data handling, SaVanache provides a robust tool for scientists to analyze and visualize genetic variation within genomes and pangenomes, facilitating the identification of genetic determinants associated with phenotypes of interest and fully exploiting current genomic resources. Author summaryWe introduce SaVanache, an innovative tool that transforms the way we explore genomic resources. SaVanache allows visualization and analysis of pangenome variation graphs (PVGs), which capture genomic diversity by integrating structural variants (SV) and single nucleotide polymorphisms (SNPs) across multiple genomes. Unlike traditional genome browsers limited to a few genomes, SaVanache offers a multi-level, user-friendly interface that allows users to explore from whole pangenomes down to individual structural variants, enabling multidimensional research and development. Using a linear pivot genome as a visual reference, SaVanache simplifies complex PVG structures into intuitive comparisons. It efficiently handles large datasets and speeds up data retrieval through internal parsing. The front-end, built with modern JavaScript frameworks, provides interactive and responsive visualization, while the Python/Django backend supports real-time data updates. Users can detect and classify SVs by comparing syntenic segments between genomes, visualized through a novel glyph-based system that uses shapes and colors to represent complex rearrangements. SaVanache supports seamless zooming from chromosome-wide to nucleotide-level views, interactive diversity scatterplots, dynamic pivot genome switching, and grouping genomes by metadata to explore genotype-phenotype links. In addition, export functions bridge visualization with downstream bioinformatics. Developed with user feedback, SaVanache balances biological relevance and computational efficiency, overcoming PVG complexity to empower users with unprecedented insight into genomic diversity and SVs.

bioinformatics↗

bioRxiv2025

GraTools, an user-friendly tool for exploring and manipulating pangenome variation graphs

BackgroundPangenome variation graphs (PVGs), which represent genomic diversity through multiple genomes alignment, are powerful tools for studying genomic variations in populations. However, current tools often lack integration, efficiency, or require format conversions, to use them, hindering their usability. ResultsHere, we introduce GraTools, a member of the GraSuite [1], and a fast and user-friendly command-line tool for manipulating PVGs using the original GFA file. After a one-time graph import, GraTools enables rapid subgraph extraction, FASTA sequence retrieval, and comprehensive analyses, including core/dispensable genome ratio calculation or group-specific segment identification. The import step results in conversion in standard data formats (BAM/BED), enabling the reuse of well-optimized existing tools, allowing an efficient storage and the querying of the PVGs large complex data structures. Scalability is ensured by a modular architecture supporting parallel processing and asynchronous I/O operations. GraTools supports coordinates defined on both the primary reference as well as from alternative genomes within the graph without re-import, and its outputs can be easily visualized or manipulated using external tools. Using an Asian rice pangenome graph (13 accessions), we demonstrate its ability to easily extract subgraphs, compute depth statistics, and identify subspecies-specific segments. An intuitive command-line interface, a real-time execution feedback and a detailed logging system make this tool suitable for a wide range of applications, from population genetics to breeding and genomic medicine, for both biologists and bioinformaticians. ConclusionsThrough its unified graph manipulation interface, GraTools offers an interesting alternative to the few existing tools for manipulating PVGs, facilitating rapid, efficient and flexible downstream analyses. It is available as an open-source tool (GNU GPLv3), with its documentation available at https://gratools.readthedocs.io.

bioinformatics↗

bioRxiv2025

Phytochemical Screening, Radical Scavenging and Antimicrobial Activities of the Crude Ethanolic, Methanolic, Ethyl Acetate and Chloroform Leaf Extracts of Arayat Pitogo (Cycas riuminiana Porte ex Regel)

In the Philippines, Cycas spp. are found in Luzon Island particularly in Pampanga, Batangas, Bataan and Isabela provinces.. In this study, the bioactive potentials of the crude methanolic, ethanolic, ethyl acetate and chloroform leaf extracts of Cycas riuminiana Porte ex Regel were investigated. Based on the results of the four solvents used, the best extraction solvent for the phytochemicals is ethanol, followed by methanol, ethyl acetate and chloroform. The ethanolic and methanolic leaf extracts showed comparable antioxidant activity. The chloroform and ethyl acetate extracts also have comparable antioxidant activity but significantly lower than both methanolic and ethanolic extracts. However the greatest antimicrobial activity was exhibited by the ethyl acetate extract, followed by chloroform, methanolic and ethanolic extracts. The variation and similarity in the antioxidant and antimicrobial activities of the different extracts can be attributed to different mechanisms of interactions, namely, independent joint action, additive, synergistic, competitive or antagonistic interactions, among the bioactive compounds present in the crude extracts. Further studies are needed to elucidate the structure of the different phytochemicals present in the leaf extracts of Arayat Pitogo (C. riuminiana Porte ex Regel) and the specific mechanisms of interaction among these phytochemicals. SUMMARYThe extracts were tested for the presence (trace, moderate or abundant amounts) of flavonoids, saponins, tannins, triterpenes, alkaloids, sterols and glycosides. The ethanolic extract was positive for all phytochemicals screened with sterols, flavonoids, glycosides and tannins being abundant, alkaloids being moderate and triterpenes and saponins in trace amounts. The methanolic extract was also positive for all constituents but in trace amounts, except for flavonoids which were abundant. The ethyl acetate extract contained abundant sterols, moderate alkaloids and trace amounts of saponins, glycosides and tannins. Finally, the chloroform extract contained abundant sterols, and trace amounts of alkaloids, saponins and glycosides. The radical scavenging assay revealed that the highest percent inhibition was obtained for the ethanolic leaf extract (60.53{+/-}0.7801%), followed by methanolic extract (59.92{+/-}3.160%), chloroform extract (50.17{+/-}4.779%) and ethyl acetate extract (47.25{+/-}3.759%). In terms of antibacterial activity, the ethyl acetate extract registered the highest inhibition against the three test organisms, namely, Staphylococcus aureus, Bacillus subtilis and Escherichia coli. The chloroform extract inhibited S. aureus and B. subtilis. The methanol extract inhibited S. aureus only. Finally, the ethanolic extract failed to inhibit any of the test organisms despite its abundant phytochemicals and high antioxidant activity. In terms of antifungal activity, the different extracts inhibited Candida albicans with the ethyl acetate and chloroform extracts showing a high degree of inhibition followed by the methanolic and ethanolic extracts. However, none of the extracts showed any bioactivity against Aspergillus niger.

plant biology↗

bioRxiv2025

Human plastins are novel cytoskeletal pH sensors with a reduced F-actin bundling capacity at basic pH

Intracellular pH (pHi) is a fundamental component of cell homeostasis. Controlled elevations in pHi precede and accompany cell polarization, cytokinesis, and directional migration. pH dysregulation contributes to cancer, neurodegenerative diseases, diabetes, and other metabolic disorders. While cytoskeletal rearrangements are crucial for these processes, only a few cytoskeletal proteins, namely Cdc42, cofilin, talin, cortactin, -actinin, and AIP1 have been documented as pH sensors. Here, we report that actin-bundling proteins plastin 2 (PLS2, aka LCP1) and plastin 3 (PLS3) respond to physiological scale pH fluctuations by a reduced F-actin bundling at alkaline pH. The inhibition of PLS2 actin-bundling activity at elevated pH stems from the reduced affinity of the N-terminal actin-binding domain (ABD1) to actin. In fibroblast cells, elevated cytosolic pH caused the dissociation of ectopically expressed PLS2 from actin structures, whereas acidic conditions promoted its tighter association with focal adhesions and stress fibers. We identified His207 as one of the pH-sensing residues whose mutation to Lys and Tyr reduces pH sensitivity by enhancing and inhibiting the bundling ability, respectively. Our results suggest that weaker actin bundling by plastin isoforms at alkaline pH favors higher dynamics of the actin cytoskeleton. Therefore, like other cytoskeleton pH sensors, plastins promote disassembly and faster dynamics of cytoskeletal components during cytokinesis and cell migration. Since both plastins are implemented in cancer, their pH sensitivity may contribute to the accelerated proliferation and enhanced invasive and metastatic potentials of cancer cells at alkaline pHi. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/645573v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@18430a4org.highwire.dtl.DTLVardef@19584b1org.highwire.dtl.DTLVardef@13a8354org.highwire.dtl.DTLVardef@840dc3_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

Temporal and spatial niche partitioning in a retrotransposon community of the Drosophila genome

Transposable elements (TEs), widespread genetic parasites, pose potential threats to the stability of their host genomes. Hence, the interactions observed today between TEs and their host genomes, as well as among the different TE species coexisting in the same host, likely reflect those that did not lead to the extinction of either the host or the TEs. It is not clear to what extent the expression and integration steps of the TE replication cycles are involved in this peaceful coexistence. Here, we show that four Drosophila LTR RetroTransposable Elements (LTR-RTEs), although sharing the same overall integration mechanism, preferentially integrate into distinct open chromatin domains of the host germline. Notably, the differential expressions of the gtwin and ZAM LTR-RTEs in ovarian and embryonic somatic tissues, respectively, result in differential integration timings and targeting of accessible chromatin landscapes that differ between early and late embryonic nuclei, highlighting connections between temporal and spatial LTR-RTEs niche partitionings.

genomics↗

bioRxiv2023

A mouse model of ZTTK syndrome reveals indispensable SON functions in organ development and hematopoiesis

Rare diseases are underrepresented in biomedical research, leading to insufficient awareness. Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare disease caused by genetic alterations that result in heterozygous loss-of-function of SON. While ZTTK syndrome patients suffer from numerous symptoms, the lack of model organisms hamper our understanding of both SON and this complex syndrome. Here, we developed Son haploinsufficiency (Son+/-) mice as a model of ZTTK syndrome and identified the indispensable roles of Son in organ development and hematopoiesis. Son+/- mice recapitulated clinical symptoms of ZTTK syndrome, including growth retardation, cognitive impairment, skeletal abnormalities, and kidney agenesis. Furthermore, we identified hematopoietic abnormalities in Son+/- mice, similar to those observed in human patients. Surface marker analyses and single-cell transcriptome profiling of hematopoietic stem and progenitor cells revealed that Son haploinsufficiency inclines cell fate toward the myeloid lineage but compromises lymphoid lineage development by reducing key genes required for lymphoid and B cell lineage specification. Additionally, Son haploinsufficiency causes inappropriate activation of erythroid genes and impaired erythroid maturation. These findings highlight the importance of the full gene dosage of Son in organ development and hematopoiesis. Our model serves as an invaluable research tool for this rare disease and related disorders associated with SON dysfunction.

genetics↗

bioRxiv2023

Altered X-chromosome inactivation predisposes to autoimmune manifestations in mice

In mammals, males and females show marked differences in immune responses. Males are globally more sensitive to infectious diseases while females are more susceptible to systemic autoimmunity. X-chromosome inactivation (XCI), the epigenetic mechanism that ensures the silencing of one X in females, may participate in these sex-biases. Here, we perturbed the expression of the trigger of XCI, the non-coding RNA Xist, in female mice. This resulted in reactivation of genes on the inactive X, including members of the Toll-like receptor 7 (TLR7) signalling pathway, in monocyte/macrophages, dendritic and B cells. Consequently, female mice spontaneously developed inflammatory signs typical of lupus, including anti-nucleic acid autoantibodies, increased frequencies of age-associated and germinal centre B cells and expansion of monocyte/macrophages and dendritic cells. Mechanistically, TLR7 signalling is dysregulated in macrophages, which leads to sustained expression of target genes upon stimulation. These findings provide a direct link between maintenance of XCI and female-biased autoimmune manifestations and highlight altered XCI as a cause of autoimmunity. TeaserThe reason why autoimmunity mostly affects women is unclear. Here, we show that aberrant expression of genes on the X induces signs of lupus in female mice.

immunology↗

bioRxiv2022

TrEMOLO: Accurate transposable element allele frequency estimation using long-read sequencing data combining assembly and mapping-based approaches

Transposable Element MOnitoring with LOng-reads (TrEMOLO) is a new software that combines assembly- and mapping-based approaches to robustly detect genetic elements called transposable elements (TEs). Using high- or low-quality genome assemblies, TrEMOLO can detect most TE insertions and deletions and estimate their allele frequency in populations. Benchmarking with simulated data revealed that TrEMOLO outperforms other state-of-the-art computational tools. TE detection and frequency estimation by TrEMOLO were validated using simulated and experimental datasets. Therefore, TrEMOLO is a comprehensive and suitable tool to accurately study TE dynamics. TrEMOLO is available under GNU GPL3.0 at https://github.com/DrosophilaGenomeEvolution/TrEMOLO.

bioinformatics↗

bioRxiv2019

Comparative Anatomical, Ultrasonographical and Radiological studies of the biliary system of Rabbits and Domestic cats in Egypt

Under the prevailing overall Conditions of all veterinarians for the diagnosis of biliary diseases, application of surgical procedures and liver transplantation in Cats as carnivorous pet animal, and Rabbits as herbivorous pet animal and also as a human model in research. The present study was constructed on twelve native breeds of rabbits (Oryctolagus cuniculus) and eighteen adult domestic cats (Felis catus domesticus). We concluded that, in brief; the rabbit gall bladder was relatively small, fixed by several small hepato-cystic ducts to its fossa. The rabbit bile duct was formed commonly by the junction of the left hepatic duct and the cystic duct. The cystic duct was commonly fairly large, received the right hepatic duct that collected the right lobe in its route to enter the duodenum, the bile duct receives the branch of the caudate process of the caudate lobe. The present study revealed other four anatomic variations dealing with the shape and size of the feline native breeds gall bladder from fundic duplication, bilobed, truncated fundus and distended rounded fundus. Commonly, the bile duct was formed by the triple convergence of the left and the right hepatic ducts with the cystic duct. However, in some exceptional cases a short common hepatic duct was formed. Sonographically, the normal gall bladder in rabbit appeared small, elongated with anechoic lumen bordered by right lobe laterally and quadrate lobe medially and has no visible wall, but in cat varied in conformation, bordered by the right medial lobe laterally and the quadrate lobe medially surrounded by echogenic wall.

scientific communication and education↗