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Mansour, H.

Publications and source records attributed to Mansour, H..

6 recordsLinked to original sources

Phenotypic and genomic changes associated with the evolutionary loss of heterostyly in primroses

Trait loss has been documented across broad phylogenetic scales and dissected genetically within species, but how the genetic basis of loss varies among lineages and over evolutionary time remains poorly understood. Heterostyly, a floral polymorphism, represents an ideal case study, as it has been lost repeatedly across angiosperms. In Primula, heterostyly is controlled by the S-locus supergene, and loss-of-function mutations in CYP cause transitions to homostyly. We investigated the critically endangered Primula boveana, whose floral morphology is debated, in the diploid, self-compatible P. sect. Sphondylia. We quantified herkogamy dynamics during anthesis, performed controlled pollination experiments, assembled a chromosome-scale genome, compared S-locus structure and gene expression with heterostylous relatives, and reconstructed phylogenetic relationships within the section. Our results revealed that P. boveana is homostylous, with a disrupted CYP. Herkogamy declines during anthesis, resulting in early anther-stigma contact, autonomous selfing, and reproductive assurance. Thus, unlike other homostylous Primula species, these developmental changes do not represent a delayed selfing strategy. These findings link developmental changes in herkogamy with autonomous selfing and support CYP inactivation as the genetic basis of long homostyly in P. boveana. The extensive degeneration of CYP suggests that prolonged relaxed selection promotes progressive degeneration of non-functional S-genes following heterostyly loss.

evolutionary biology↗

Multiomic characterization, early detection, and therapeutic targeting of myeloid sarcoma

Myeloid sarcoma, an aggressive extramedullary subtype of acute myeloid leukemia (AML), occurs in [~]10% of patients, and has not yet been included in large-scale genomic studies. The critical biological changes that drive tumor evolution are unknown, its detection in asymptomatic patients remains a clinical challenge, and treatment options are limited as patients are often excluded from clinical trials, rendering it a neglected disease entity. Based on comprehensive multi-omic profiling, we demonstrate that myeloid sarcoma evolves from medullary AML with distinct sitespecific clonal evolution patterns. Additionally, we show that circulating tumor DNA sequencing can serve as a non-invasive method for molecular profiling of myeloid sarcoma, offering a novel avenue in molecular diagnostics. We characterize unique transcriptional profiles of myeloid sarcoma, reflecting immune evasion and adaptation to an extramedullary microenvironment. We provide evidence for a key role of RAS pathway activation and demonstrate in murine models of myeloid sarcoma that RAS inhibition effectively reduces tumor burden. Overall, our data highlight key differences between medullary AML and myeloid sarcoma including universal molecular evolution and RAS pathway activation as hallmarks of the disease and nominate RAS inhibition as a promising therapeutic strategy for patients with myeloid sarcoma.

cancer biology↗

A common cross-species atlas of cortical gray matter

Translational neuroscience requires consistent anatomical frameworks to compare brain organization across species despite differences in size and specialization. Existing atlases are species-specific, limiting cross-species analyses. Here we developed a hierarchical common atlas delineating homologous cortical and subcortical gray matter regions across mouse, rat, marmoset, rhesus macaque, and human, built upon population-averaged minimal deformation templates and uniform tissue segmentation. The atlas was validated through cross-atlas Dice similarity against established human parcellations, cross-scale containment against species-specific atlases, cross-species geometric consistency of regional positioning, and comparison of independent mouse and marmoset invasive tracer connectivity, with a per-region homology confidence index quantifying the strength of each regional assignment. Cross-species tracer comparison revealed a structured gradient of correspondence, with sensorimotor connections showing strong conservation and association connections showing progressive divergence. This freely available atlas provides a unified coordinate system for comparative neuroscience, enabling quantitative evaluation of where cross-species correspondence holds and where species-specific divergence emerges.

neuroscience↗

An Open Resource: MR and light sheet microscopy stereotaxic atlas of the mouse brain

We have combined MR histology and light sheet microscopy (LSM) of five postmortem C57BL/6J mouse brains in a stereotaxic space based on micro-CT yielding a multimodal 3D atlas with the highest spatial and contrast resolution yet reported. Brains were imaged in situ with multi gradient echo (mGRE) and diffusion tensor imaging (DTI) at 15 m resolution ([~] 2.4 million times that of clinical MRI). Scalar images derived from the average DTI and mGRE provide unprecedented contrast in 14 complementary 3D volumes, each highlighting distinct histologic features. The same tissues scanned with LSM and registered into the stereotaxic space provide 17 different molecular cell type stains. The common coordinate framework labels (CCFv3) complete the multimodal atlas. The atlas has been used to correct distortions in the Allen Brain Atlas and harmonize it with Franklin Paxinos. It provides a unique resource for stereotaxic labeling of mouse brain images from many sources.

neuroscience↗

Characterization of GEXP15 as a potential regulator of Protein Phosphatase 1 and partner of ribosomal complex in Plasmodium falciparum.

The Protein Phosphatase type 1 catalytic subunit (PP1c) (PF3D7_1414400) operates in combination with various regulatory proteins to specifically direct and control its phosphatase activity. However, little is known about this phosphatase and its regulators in the human malaria parasite, Plasmodium falciparum. To address this gap, we conducted a comprehensive investigation into structural and functional characteristics of a conserved Plasmodium-specific regulator called Gametocyte EXported Protein 15, GEXP15 (PF3D7_1031600). Through in silico analysis, we identified three significant regions of interest in GEXP15: an N-terminal region housing a PP1-interacting RVxF motif, a conserved domain whose function is unknown and a GYF-like motif that potentially facilitates specific protein-protein interactions. To further elucidate the role of GEXP15, we conducted in vitro interaction studies, which demonstrated a direct interaction between GEXP15 and PP1 via the RVxF binding motif. This interaction was found to enhance phosphatase activity of PP1. Additionally, utilizing a transgenic GEXP15-tagged line and live microscopy, we observed high expression of GEXP15 in late asexual stages of the parasite, with localization predominantly in the parasite nucleus. Immunoprecipitation assays followed by mass spectrometry analyses revealed GEXP15s interaction with ribosomal and RNA binding proteins. Furthermore, through pulldown analyses of recombinant functional domains of GEXP15 tagged with a His-tag, we confirmed its binding to the ribosomal complex via the GYF domain. Collectively, our study sheds light on the PfGEXP15-PP1-ribosome interaction, which plays a crucial role in protein translation. These findings suggest that PfGEXP15 could serve as a potential target for the development of malaria drugs.

microbiology↗

A Universal Proximity CRISPR Cas12a Assay for Ultrasensitive Detection of Nucleic Acids and Proteins

Herein, we describe a proximity CRISPR Cas12a assay that harnesses \"collateral\" single-stranded DNase activity of Cas12a as a universal amplifier for the ultrasensitive detection of nucleic acids and proteins. The target recognition is achieved through proximity binding rather than recognition by CRISPR RNA (crRNA), which allows the flexible assay design and expansion to proteins. A binding-induced primer extension reaction is then used to generate a predesigned CRISPR-targetable sequence as a barcode for signal amplification. We demonstrate that our assay is highly sensitive and universal. As low as 1 fM nucleic acid target could be detected isothermally in a homogeneous solution via the integration with nicking cleavage. Weve also successfully adapted the assay for the sensitive and wash-free detection of antibodies in both buffer and diluted human serum samples.

synthetic biology↗