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Biology subjects

Delgado, G.

Publications and source records attributed to Delgado, G..

3 recordsLinked to original sources

Invasion history of Aedes (Stegomyia) albopictus into Mesoamerica based on mitogenomes and Wolbachia symbionts: Multiple introductions with temperate origins.

The global invasion of the Asian tiger mosquito Aedes albopictus has led to an increase in arboviral disease, including within Mesoamerica. Understanding vector invasion routes is important for public health because it directs biosecurity and identifies sources of adaptive allele spread. Panama is an important hub of global trade with opportunities for Aedes introduction through both maritime and overland routes but dispersal into the Isthmus has not yet been investigated. We therefore sought to investigate the population structure and invasion history of Ae. albopictus into Panama, targeting both its mitogenome and associated Wolbachia. Historical demographic analysis with Bayesian phylogeographic diffusion models and estimates of divergence revealed that Panamanian Ae. albopictus and its associated Wolbachia have a convergent evolutionary history resulting from multiple introductions. Both could be traced to Asian-derived lineages introduced via the Americas, with invasion primarily through the maritime trade of the Panama Canal rather than overland dispersal from neighboring Costa Rica. An investigation of the relative density of Wolbachia in Panama revealed that both the strains wAlbB and wAlbA were at a notably lower density compared to other worldwide locations. This finding has implications for arbovirus transmission and raises important questions about how Wolbachia density is impacted by the environment and impacts on population control. Overall, the Panama Canal is a key route for vector introductions into Mesoamerica.

evolutionary biology↗

The COPI coatomer influences LDL receptor activity, hepatic lipid storage, and apoB secretion

BackgroundDecreased hepatic removal of low density lipoproteins (LDL) and increased apolipoprotein B (apoB) production cause hypercholesterolemia, a major causal risk factor of atherosclerotic cardiovascular disease (ASCVD). By a genome-wide siRNA screen, we previously identified subunits of the Coat protein I (COPI) complex to limit LDL uptake into Huh-7 hepatocarcinoma cells. MethodsThese findings were validated by targeted in vitro experiments as well as genetic association studies in humans and three mouse models with mutated or disrupted COPI genes. ResultsSilencing of COPA, COPB1, COPB2, ARCN1, COPG1, and COPZ1 in Huh-7 cells resulted in decreased uptake of LDL and aberrant glycosylation and altered cell surface abundance of the LDL receptor (LDLR) as well as increased apoB secretion and cellular lipid storage. Single nucleotide polymorphisms of ARCN1 were associated with lower ARCN1 expression and higher levels of LDL-cholesterol (LDL-C). Rare variants of COPA and COPG1 were enriched among patients with LDL-C > 5 mmol/L. Patients and mice carrying other rare immunopathogenic missense variants of COPA and COPG1 did not present with elevated plasma levels of LDL-C, while hepatic knockdown of murine Copg1 increased the concentrations of non-HDL-cholesterol in plasma and triglycerides in the liver. ConclusionsThe COPI coatomer regulates LDLR activity and apoB secretion as well as lipid content of liver cells. Loss of function of some variants of COPI genes are associated with higher LDL-C levels.

cell biology↗

Complementary roles for hippocampus and anterior cingulate in composing continuous choice

Naturalistic, goal directed behavior often requires continuous actions directed at dynamically changing goals. In this context, the closest analogue to choice is a strategic reweighting of multiple goal-specific control policies in response to shifting environmental pressures. To understand the algorithmic and neural bases of choice in continuous contexts, we examined behavior and brain activity in humans performing a continuous prey-pursuit task. Using a newly developed control-theoretic decomposition of behavior, we find pursuit strategies are well described by a meta-controller dictating a mixture of lower-level controllers, each linked to specific pursuit goals. We find that hippocampal neurons encode the policy blending variable in a value-invariant manner and monitor policy switches after they occur. ACC neurons encode policy switches in a value-dependent manner, with value related modulation detectable several hundred ms before the switch, alongside a ramping increase in mean firing rate toward the switch. Meanwhile, OFC activity is consistent with an encoding of the current value structure of the task, rather than policy switching. Together these results are consistent with a tripartite functional division in which hippocampus serves as a controller over behavior, ACC serves as a meta-controller, and OFC provides a value context signal. Overall, our results shed light onto the complex processes associated with choice during naturalistic continuous interactive behavior.

neuroscience↗