bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.05.27.596085

Thermal variation influences the transcriptome of the major malaria vector Anopheles stephensi.

Abstract

The abundance and distribution of ectotherms is being shaped at unprecedented scales by human-induced climate change. Unraveling molecular adaptations to thermal variation is prescient. Vector-borne diseases are of particular concern and although mosquitoes are responsible for most of the 621 million cases annually, their response to temperature is not well characterized. We describe the transcriptome of the major vector for human malaria, Anopheles stephensi maintained under a diurnal temperature regime (DTR) totaling 9{degrees}C and daily means of 20{degrees}C, 24{degrees}C and 28{degrees}C respectively. Gene expression profiles were examined in the midguts and carcasses of adult mosquitoes from one to 19 days post-blood meal. Differences in temporal expression profiles at each temperature revealed a total of 3,106 and 3,590 genes in the carcasses and midguts respectively and analyzed further to make three inferences. First, we identified genes with shared temporal expression profiles across all three temperatures, suggesting their indispensability to mosquito life history. Second, tolerance to 20 DTR 9{degrees}C and 28 DTR 9{degrees}C was associated with a larger and more diverse repertoire of gene products compared to 24 DTR 9{degrees}C; assuming physiological costs scale accordingly, this finding could explain the fitness trade-offs underlying the unimodal effect of temperature. Third, the long duration of our study revealed two general trends in gene expression, representative of a coordinated, tissue- and temperature-specific response to blood meal digestion, managing oxidative stress, and reproduction. Our results suggest how temperature could regulate the mosquitos capacity to transmit Plasmodium parasites and offer a reference point for understanding ectotherm adaptation.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Pathak, A. K., Quek, S., Sharma, R., Shiau, J. C., Thomas, M. B., Hughes, G. L., Murdock, C. C.. 2024-05-28. Thermal variation influences the transcriptome of the major malaria vector Anopheles stephensi.. https://doi.org/10.1101/2024.05.27.596085

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Trans-branching of polyubiquitin chains orchestrates the DNA replication stress response

Polyubiquitin chain geometry dictates functional consequences of ubiquitylation. Although branched polyubiquitin chains are abundant in cells, little is known about their functions. Here we show that branching on the DNA replication factor PCNA, mediated by the ubiquitin-conjugating enzyme UBE2K and involving lysines 63 and 48 of ubiquitin, orchestrates the sequence of events in response to replication stress. By inducing VCP-dependent extraction of PCNA from chromatin, branching promotes re-priming of stalled forks and necessitates a BRCA1-dependent pathway of daughter-strand gap repair. Our study identifies hyper-accumulation of daughter-strand gaps as the mechanistic basis underlying the toxicity of inhibitors of the PCNA-specific isopeptidase, USP1, in BRCA1-deficient cells. Moreover, an unexpected preference of UBE2K to operate in trans suggests a general timing mechanism to organize hierarchies amongst ubiquitin signals.

molecular biology↗

Impaired proteostasis is an early feature of the diabetic heart in humans and mice

Diabetes and obesity increase cardiac lipid levels leading to cardiomyopathy and heart failure. We hypothesized that intermittent fasting would reduce cardiac lipid levels. Surprisingly, intermittent fasting increased myocardial triglyceride content, but rescued mortality and attenuated cardiomyopathy in mice overexpressing cardiomyocyte acyl-CoA synthetase 1 (MHC-ACSL1). Lipid overload caused cardiomyocyte accumulation of polyubiquitinated protein aggregates containing desmin, a scaffolding intermediate filament protein, which intermittent fasting prevented. Furthermore, intermittent fasting reversed elevated myocardial C16:0 ceramide content, and knockdown of ceramide synthase CerS5 and CerS6 reduced palmitate-induced protein aggregation, highlighting a role for C16:0 ceramides in this pathology. Conversely, impairing aggrephagy with cardiomyocyte-specific p62 ablation induced heart failure in mice fed a high-fat diet, with paradoxically reduced cardiac lipid content. Crucially, non-failing diabetic human hearts also exhibited protein aggregate pathology. Taken together, these results demonstrate that impaired proteostasis characterizes cardiomyopathy from cardiac lipid overload and identify a promising new therapeutic target for this condition.

molecular biology↗

Spatial profiling and neurovascular communication in the developing and adolescent cortex following prenatal alcohol exposure

Fetal alcohol spectrum disorders (FASD) constitute a wide range of developmental, cognitive, and behavioral impairments caused by prenatal alcohol exposure (PAE). Although neuronal and vascular consequences of PAE have been studied, how alcohol affects the cerebrovasculature within the framework of the neurovascular unit (NVU) across development remains poorly understood. At minimum, the NVU comprises neurons, astrocyte endfeet, and endothelial cells (ECs), which coordinate to maintain brain homeostasis. Here, we used the NanoString Digital Spatial Profiling platform to characterize spatial transcriptomic data from neurons, astrocytes, and ECs from PAE and saccharin (SAC) control cortices at embryonic day 18 (E18) and postnatal day 28 (P28). Differentially expressed genes were then used for Ingenuity Pathway Analysis (IPA) to identify altered biological pathways and perform comparison analyses across developmental time points, while CellChat was used to infer cell cell communication networks. We uncovered thousands of differentially expressed genes and numerous altered pathways and biological processes in PAE cortices across development. Both IPA and CellChat analyses implicated dysregulation of vascular and extracellular matrix (ECM) remodeling, cell adhesion, and neuroinflammatory signaling. CellChat further predicted the loss of several key bidirectional relationships and altered ligand-receptor interactions among neurovascular cell types at E18 and P28. Overall, these findings identify PAE associated alterations in neurovascular gene expression and intercellular signaling across development, providing potential mechanisms by which PAE may disrupt neurodevelopment.

molecular biology↗