Abdi, A. A. | Search bioRxiv

bioRxiv2026

Evidence of Anopheles stephensi involvement in the transmission of Plasmodium vivax in Djibouti, 2024

PurposeAnopheles stephensi is a malaria mosquito vector that has been raising international concern due to its invasive nature in Africa, including the nation of Djibouti. Since its initial detection in Djibouti in 2012, malaria morbidity and mortality have increased exponentially in the county. While there is an observed association increase in human malaria cases since the arrival of An. stephensi, high-quality evidence of An. stephensi carrying infective sporozoites is essential to determine the role of the invasive vector in malaria dynamics in Djibouti. This study seeks to confirm the link between An. stephensi and malaria transmission in Djibouti and examine genetic relatedness between Djiboutian An. stephensi populations and populations across the Horn of Africa. Such information regarding the An. stephensi populations and the Plasmodium species they transmit is necessary to devise appropriate control strategies and limit malaria transmission within and beyond the country. MethodsOne hundred and ninety-six adult An. stephensi mosquitoes from Djibouti were collected, molecularly confirmed, analyzed for a portion of the cytochrome c oxidase subunit 1 (COI), and tested for infective sporozoites using a highly sensitive and specific multiplex circumsporozoite enzyme linked immunosorbent assay (csELISA) bead assay. The COI sequences of one hundred and fourteen samples were further used to characterize the population genetic structure of the sampled An. stephensi and its genetic relatedness to other An. stephensi populations across the Horn of Africa. ResultsAll 196 samples were morphologically and molecularly confirmed to be An. stephensi. Plasmodium vivax210 sporozoites were detected with a positivity rate of 1.02%. An analysis of the COI region showed that the infected An. stephensi have the most prevalent COI haplotypes of invasive An. stephensi circulating in the Horn of Africa. ConclusionsThe findings from this study confirm the involvement of An. stephensi in P. vivax transmission in Djibouti and describe the genetic relatedness of Djiboutian An. stephensi populations to other populations across the Horn of Africa. This highlights the threat of An. stephensi invasion and supports a rapid and comprehensive response to mitigate the harm that An. stephensi populations cause, particularly through surveillance and control of adult populations. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/707780v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@19f762corg.highwire.dtl.DTLVardef@7624forg.highwire.dtl.DTLVardef@c7492borg.highwire.dtl.DTLVardef@194c11f_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2022

Alterations in neural stem cell quiescence and activation in the 3xTG-AD model of Alzheimers Disease

Alzheimers Disease (AD) is the most common form of dementia with progressive cognitive deficits and mood disorders (Knopman et al., 2021). Recent studies have associated AD pathology with the impairment of adult neurogenesis, as indicated by impaired neural stem cell (NSCs) homeostasis (Bond et al., 2015). Recent work has further associated AD progression with a decline in the number and maturation of adult-born neurons in the SGZ, distinct from typical age-related decline (Moreno-Jimenez et al., 2019). In 3xTG-AD mice, a well-established mouse model of AD, our and other groups have demonstrated impairments to NSC pool and neural progenitor proliferation, as well as adult-born neurons, before the onset of A{beta} plaques and NFTs (Hamilton et al., 2010, 2015; Rodriguez et al., 2008, 2009). However, the regulatory mechanisms underlying the functional impairment of adult NSCs remain to be resolved. Here, we employ single-cell RNA-Seq to establish population-specific defects in the 3xTG-AD mouse model during adult SGZ neurogenesis. Relative to control mice, we observe a dramatic AD-induced decrease in the primed and activated NSC population, which results in a progressive loss of cells committed to neurogenesis. Transcriptome measurements suggest that 3xTG-AD NSCs and their progeny represent enhanced ribosomal and mitochondrial biogenesis, and disturbed Notch signaling pathway. RNA velocity analysis reveals reduced NSC activation as evidenced by a large fraction of Ascl1-postive cells, instead of entering cell cycle, returning to the primed and quiescent state. This is further supported by reduced numbers of Lpar1-expressing cells, a marker of neural progenitor cells, in the SGZ. Our work explores, at a stage-specific resolution, changes in the regulatory networks guiding adult neurogenesis, and identifies niche disturbances in the regulation of NSC quiescence and activation. These NSC deficits underlying impaired neurogenesis identified in AD mice, may be key contributors underlying the compromised hippocampal function in AD.

neuroscience↗