Browsing by Author "Ahmed, Sadia"

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    Early influences of microbiota on white matter development in germ-free piglets
    Ahmed, Sadia; Travis, Sierrah; Díaz-Bahamonde, Francisca; Porter, Demisha; Henry, Sara; Ravipati, Aditya; Booker, Aryn; Ding, Hanzhang; Ju, Jing; Ramesh, Ashwin; Pickrell, Alicia M.; Wang, Maosen; LaConte, Stephen M.; Howell, Brittany R.; Yuan, Lijuan; Morton, Paul D. (Frontiers, 2021-12-27)
    Abnormalities in the prefrontal cortex (PFC), as well as the underlying white matter (WM) tracts, lie at the intersection of many neurodevelopmental disorders. The influence of microorganisms on brain development has recently been brought into the clinical and research spotlight as alterations in commensal microbiota are implicated in such disorders, including autism spectrum disorders, schizophrenia, depression, and anxiety via the gut-brain axis. In addition, gut dysbiosis is common in preterm birth patients who often display diffuse WM injury and delayed WM maturation in critical tracts including those within the PFC and corpus callosum. Microbial colonization of the gut aligns with ongoing postnatal processes of oligodendrogenesis and the peak of brain myelination in humans; however, the influence of microbiota on gyral WM development remains elusive. Here, we develop and validate a neonatal germ-free swine model to address these issues, as piglets share key similarities in WM volume, developmental trajectories, and distribution to humans. We find significant region-specific reductions, and sexually dimorphic trends, in WM volume, oligodendrogenesis, and mature oligodendrocyte numbers in germ-free piglets during a key postnatal epoch of myelination. Our findings indicate that microbiota plays a critical role in promoting WM development during early life when the brain is vulnerable to environmental insults that can result in an array of disabilities manifesting later in life.
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    Investigation of in-situ nanoimprinting of cell surface receptors: potential of a novel technique in biomarker research
    Ahmed, Sadia (Virginia Tech, 2019-01-22)
    Biomarkers are biological characteristics that can be observed or measured during disease conditions, and compared to the healthy state. Biomarkers have been used in medical history to study disease progression, to develop drugs, or to predict drug efficacy. However, in complex diseases such as in cancer, biomarkers vary tremendously among patients and disease stages. Cell surface receptors, proteins that are located at the cell surface and deliver external signals into the cell, are a significant group of easily-detectable biomarkers. Along with the detection of particular biomarkers related to a disease, extensive characterization of expression patterns is necessary to optimize their application. Therefore, we designed a technique to imprint or capture the expression pattern of these receptors on silver nanoparticles. We incorporated branched molecules that can simultaneously bind to the target receptors and the nanoparticle surface. To develop the technique, we used melanocortin receptor 1 (MC1R), a receptor present at high levels on the surface of melanoma cells, as a test system. We determined optimum binding of this molecule in an established melanoma cell line, WM-266-4. We also synthesized a labeled molecule that was used to estimate the number of MC1R proteins on these cells. These studies indicate that this might be a promising approach for developing sensitive and cost-effective tools to characterize cell surface receptors in studying complex diseases and cell mechanisms.
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    Neuroblast migration along cellular substrates in the developing porcine brain
    Porter, Demisha D. L.; Henry, Sara N.; Ahmed, Sadia; Rizzo, Amy L.; Makhlouf, Rita; Gregg, Collin; Morton, Paul D. (Cell Press, 2022-09)
    In the past decade it has become evident that neuroblasts continue to supply the human cortex with interneurons via unique migratory streams shortly following birth. Owing to the size of the human brain, these newborn neurons must migrate long distances through complex cellular landscapes to reach their final locations. This process is poorly understood, largely because of technical difficulties in acquiring and studying neurotypical postmortem human samples along with diverging developmental features of well-studied mouse models. We reasoned that migratory streams of neuroblasts utilize cellular substrates, such as blood vessels, to guide their trek from the subventricular zone to distant cortical targets. Here, we evaluate the association between young interneuronal migratory streams and their preferred cellular substrates in gyrencephalic piglets during the developmental equivalent of human birth, infancy, and toddlerhood.