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Abdo, M.

Publications and source records attributed to Abdo, M..

3 recordsLinked to original sources

Multiple adaptive trajectories shape antimalarial resistance evolution in Ethiopian Plasmodium falciparum

Plasmodium falciparum malaria continues to impose a substantial public health burden across sub-Saharan Africa, with Ethiopia experiencing a recent resurgence in malaria cases. We analysed whole genome data from 120 P. falciparum isolates collected in 2024 across five ecologically and epidemiologically diverse transmission settings in Ethiopia and placed these in the context of 1,220 publicly available genomes. Parasite populations were highly structured within Ethiopia, while Horn of Africa isolates formed a genetically distinct regional cluster relative to East and West African populations. We identified evidence of recent positive selection surrounding the artemisinin resistance associated PfK13 R622I variant and detected co-occurrence with Pfcrt mutations together with recurrent selection signals at genes within the PfK13-associated haemoglobin endocytosis pathway, including Pfmca2, Pfkic7, Pfkic8 and Pfkic9. We further observed the emergence of the PfPX1 D384A-PIN haplotype, with shared identity-by-descent linking Ethiopian and Ugandan carriers, supporting a recent introduction followed by local selection. Widespread Pfhrp2/3 deletions occurred on diverse genetic backgrounds. Together, these findings reveal a complex adaptive landscape shaped by antimalarial and diagnostic selection pressures and suggest that parasite evolution in the Horn of Africa proceeds through multiple adaptive trajectories, rather than through the spread of a single dominant lineage.

microbiology↗

Fragmented gut-airway microbial networks and airway Moraxella clusters in preschool wheeze

Early-life wheezing in children has been associated with microbial alterations along the gut-airway axis, yet studies simultaneously investigating bacterial communities in both compartments remain scarce. The aim of this cross-sectional exploratory pilot study (n=25) was to characterize and compare nasal and stool bacterial communities in preschool children aged 1-4 years with recurrent wheezing and healthy controls using 16S rRNA gene metabarcoding. Across participants, nasal and stool bacteriomes were highly individualized and taxonomically diverse. Overall richness, evenness, and community composition did not differ significantly between healthy children and wheezers in either compartment. However, wheezers displayed markedly higher within-group variability, particularly in nasal communities. Stratification based on microbiome similarity to healthy samples revealed increased Moraxella and reduced commensal genera including Prevotella spp. and Veillonella, along with lower richness and evenness (all p<0.001) in nasal samples with divergent bacterial communities. Stool alterations were more subtle but included trends toward reduced Bacteroides, Faecalibacterium, and Alistipes in wheezers more divergent from healthy controls. Community assembly in both compartments was largely governed by stochastic processes but accompanied by less complex and more fragmented bacterial interaction networks in wheezing children. Cross-compartment correlations were also altered, most prominently involving stool Lactococcus showing stronger and more numerous correlations with nasal taxa in wheezers than in healthy controls. Divergent wheezers exhibited distinct modular network structure and cross-compartment profiles, consistent with a differentiated microbial organization. Together, these findings suggest compartment-specific differences in microbial interaction patterns across the gut-airway axis in early-life wheezing, despite limited differences in overall community diversity. Take home messagePreschool wheezers showed fragmented gut-airway microbial networks and Moraxella-associated airway community stratification despite limited differences in overall diversity.

microbiology↗

Red blood cell-tumour cell interactions promote tumour cell progression

One critical step in the metastatic cascade is the survival of circulating tumour cells (CTCs) within the bloodstream. While numerous interactions between CTCs and various hematopoietic cells have been described, the role of red blood cells (RBCs) in this process remains underexplored. This study investigates the interactions between tumour cells and RBCs from breast and lung cancer patients, revealing significant phenotypic and functional changes in the tumour cells, unlike when the contact is with RBCs from healthy donors. In vitro co-culture of cancer cell lines with RBCs from metastatic cancer patients resulted in increased tumour cell attachment accompanied by morphological changes. Additionally, RBCs-primed tumour cells showed increased adhesion and disruption of the endothelial barrier in vitro and increased invasiveness both in vitro and in vivo. Transcriptomic analysis showed that RBCs from metastatic breast cancer patients induce significant gene expression changes, notably upregulating PAK4, which enhances migration and epithelial-mesenchymal transition. PAK4 inhibition reduced these effects. Proteomic studies revealed substantial remodelling, including actin-related changes and the accumulation of VASP at cell edges, promoting directional migration. Clinically, higher RBC distribution width (RDW) in metastatic breast cancer patients is associated with increased CTC counts and worse outcome. This study highlights the previously unrecognized role of RBCs in promoting metastatic behaviours in cancer cells and suggests potential therapeutic targets, such as PAK4, to counteract these effects. Further exploration of RBCs-tumour cell interactions could provide new insights into metastatic mechanisms and improve cancer prognosis and treatment strategies. Key PointsO_LIThis study reveals the previously unknown role of RBCs in enhancing tumour cell invasiveness and metastatic potential. C_LIO_LITumour cells undergo significant phenotypic and functional changes after contact with RBCs from cancer patients. C_LI

cancer biology↗