Biology subjects

Magana, A. A.

Publications and source records attributed to Magana, A. A..

7 recordsLinked to original sources

bioRxiv2026

Cardiomyocyte pyruvate dehydrogenase kinase 1 knockout activates Rho-mediated remodeling and decreases fatty acyl availability in female mice

Pyruvate dehydrogenase kinase 1 (PDK1) inhibits pyruvate dehydrogenase (PDH) and therefore may regulate the balance between glucose and fatty acid oxidation in cardiomyocytes. We assessed metabolism and function in tamoxifen-inducible, cardiomyocyte-specific Pdk1 knockout (Pdk1cKO) mice, including both males and females fed a high fat diet, to resolve the role of PDK1 in the heart. Female, but not male, Pdk1cKO hearts showed the expected increase in cardiac PDH activity. Though cardiac function was largely preserved, female Pdk1cKO hearts had smaller left ventricles. Proteomics and phosphoproteomics revealed no change in classical hypertrophic markers but downregulated aerobic respiration alongside upregulated Ca2+ handling and Rho signalling, suggesting metabolic remodeling with altered cardiomyocyte contractility and cytoarchitecture in Pdk1cKO hearts. Concordantly, lipidomics revealed membrane remodeling marked by elevated saturated phosphatidylcholine in female Pdk1cKO hearts and decreased triacylglycerols, free fatty acids and fatty acid uptake proteins (CD36, FABP3). These findings reveal novel, female-predominant cardiometabolic roles for PDK1.

molecular biology↗

bioRxiv2025

Virus infection of honey bee queens alters lipid profiles and indirectly suppresses a retinue pheromone component via reducing ovary mass

Virus infections reduce honey bee (Apis mellifera) ovary mass (in part due to resource-allocation trade-offs with immunity) and are linked to the presence of supersedure cells in colonies, indicating that workers are attempting to replace their queen. Pheromones, lipids, and lipid transport proteins could mediate relationships among virus infection, ovary mass, and supersedure. When we infected honey bee queens in the laboratory and profiled their queen retinue pheromone (QRP) components from head extracts, we found that virus infections specifically reduced the QRP component methyl oleate. Data from an observational field study were consistent with this pattern. Lipidomics analysis of the same extracts suggests that virus infection decreases triacylglycerol abundances (major sources of stored energy). Reducing ovary mass via laying restriction was sufficient to lower methyl oleate abundance [-] suggesting that virus infection reduces methyl oleate indirectly via ovary effects [-] but was insufficient to reduce abundance of most triacylglycerols or stimulate immune effector expression. Abundance of circulating apolipophorin-III, a lipid transporter and putative potentiator of immune effectors, was lower in queens with restricted laying, suggesting that its expression may be controlled by nutrient availability while its immune-stimulating capacity is governed by other mechanisms. Prior research has shown that queen pheromone blends lacking methyl oleate are less attractive to workers; therefore, diminishing methyl oleate could result in a less desirable pheromone bouquet and possibly stimulate supersedure. The mechanism of methyl oleate reduction is yet to be determined, but is clearly tied to ovary size and possibly resource availability or mobilization.

physiology↗

bioRxiv2024

Honey bee egg composition changes seasonally and after acute maternal virus infection

Honey bee (Apis mellifera) colonies depend on the reproductive output of their queens, which in turn is contingent on the care provided by worker bees. Viral infections in queens can compromise reproductive output, while worker infections can inhibit the successful functioning of a colony and its ability to care for the queen. Transgenerational immune priming (TGIP) occurs when queens transfer immune-related compounds or immune elicitors to their offspring, enhancing the ability of subsequent generations to resist infections. These maternal effects on offspring could positively impact colony health and resilience to viral infections, but little is currently known about TGIP for viruses. In this study, we investigate how viral infections affect the proteomic composition of eggs laid by virus-challenged queens (injected with a mixture of black queen cell virus and deformed wing virus B), both in controlled experimental settings and natural field conditions. Our results showed that virus-challenged queens upregulated immune effectors in their eggs and ovaries. In contrast, naturally infected queens from field surveys did not; there were no significant differences in egg protein, lipid, or metabolite composition related to maternal viral load or ovary size. However, egg collection date strongly influenced egg composition, likely reflecting seasonal variations in pollen resources. These findings highlight that while viral infections can induce transgenerational effects on egg proteomes under short-term experimental conditions, such effects are less apparent in natural settings and can be overshadowed by seasonal and other ecological factors.

zoology↗

bioRxiv2024

Parallel pheromone, metabolite, and lipid analyses reveal patterns associated with early life transitions and ovary activation in honey bee (Apis mellifera) queens

Eusocial insects exist in a state of reproductive conflict in which workers forgo reproduction in favor of helping relatives, typically queens, rear offspring. The honest signal hypothesis posits that queens emit pheromonal signals that convey information about their fecundity, which workers use to make decisions around investing in direct vs. indirect fitness and queen acceptance. We evaluated this idea using liquid chromatography-tandem mass spectrometry to measure honey bee queen retinue pheromone (QRP) components in relation to queen age, laying status, and likelihood of acceptance using a protocol that enables QRP to be measured concurrently with metabolomic and lipidomic analyses. We found that older mated queens (>1 month) were more readily accepted by colonies than younger queens (10-12 d), regardless of the queens prior laying status. This is despite non-laying queens having significantly smaller ovaries at the time of introduction. Older queens produced higher levels of the QRP components 9(R)-HDA, LEA, and HVA compared to younger queens, with HVA also positively correlating with ovary mass. However, these data suggest that ovary mass is not an influential fertility metric for worker decision-making; therefore, the relationship between HVA and ovary mass is merely an honest signal of a non-influential metric. Metabolomic and lipidomic analyses showed that samples cluster strongly according to queen age and mating status, but not ovary mass. These data also reveal some of the first hints of the importance of prostanoids in queen maturation, along with many other physiological changes that occur in the first month of a queens life. Significance statementInsect pheromones have historically been evaluated using gas chromatography-mass spectrometry, a technique that is incompatible with parallel lipidomics and metabolomics inquests. Here, we repurposed an established two-phase extraction protocol and optimized a liquid chromatography-tandem mass spectrometry method to acquire pheromone, metabolite, and lipid data concurrently from a single sample. We applied this technique to interrogate the honest signal hypothesis, which relates queen pheromone profiles to reproductive quality, but the approach is broadly applicable to any question in which simultaneous determination of complex pheromone profiles and lipidomics or metabolomics data is asset. Such applications may help uncover new pheromones and reveal relationships between pheromones, hormones, and physiology in diverse biological systems.

molecular biology↗

bioRxiv2024

Glutathione metabolism impacts fungal virulence by modulating the redox environment

Pathogens must overcome the hostile conditions of their hosts to survive, proliferate and cause disease. The fungal pathogen Cryptococcus neoformans is particularly adept at mitigating challenges in the host environment and has developed an arsenal of defense mechanisms to evade oxidative and nitrosative agents released by phagocytic cells during infection. Among these mechanisms, melanin production is crucially linked to both fungal virulence and defense against harmful free radicals that facilitate host innate immunity and clearance of invading pathogens. Here, we employed comparative global metabolomics to demonstrate that metabolism of the antioxidant glutathione (GSH) is inextricably linked to redox-active processes that facilitate melanin production, and that genetic perturbations in GSH biosynthesis affect fungal growth and virulence in a murine model of cryptococcosis. Furthermore, we show that disruption of GSH biosynthesis leads to overaccumulation of reducing and acidic compounds in the extracellular environment of mutant cells. These changes not only impacted melanin formation but also influenced titan cell and urease production as well as survival in macrophages. Overall, these findings highlight the importance of redox homeostasis and metabolic compensation in pathogen adaptation to the host environment and suggest new avenues for antifungal drug development.

microbiology↗

bioRxiv2024

Amelioration of age-related cognitive decline and anxiety in mice by Centella asiatica extract varies by sex, dose and mode of administration.

We have previously reported that a water extract (CAW) of the Ayurvedic plant Centella asiatica administered in drinking water can improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here we compared the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice. Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.2, 0.5 or 1% w/w) to provide 0, 200 mg/kg/d, 500 mg/kg/d or 1000 mg/kg/d for a total of 5 weeks. An additional group of eighteen-month-old mice were treated with CAW (10 mg/mL) in their drinking water for a total of five weeks to deliver the same exposure of CAW as the highest dietary dose (1000 mg/kg/d). CAW doses delivered were calculated based on food and water consumption measured in previous experiments. In the fourth and fifth weeks, mice underwent behavioral testing of cognition, anxiety and depression (n=12 of each sex per treatment group in each test). Aged mice of both sexes showed cognitive deficits relative to young mice while only female aged mice showed increased anxiety compared to the young female mice and no differences in depression were observed between the different ages. CAW (1000 mg/kg/d) in the drinking water improved deficits in aged mice in learning, executive function and recognition memory in both sexes and attenuated the increased measures of anxiety observed in the aged female mice. However, CAW in the diet only improved executive function in aged mice at the highest dose (1000 mg/kg/d) in both sexes and did so less robustly than when given in the water. There were no effects of CAW on depression-like behavior in aged animals regardless of whether it was administered in the diet or the water. These results suggest that CAW can ameliorate age-related changes in measures of anxiety and cognition and that the mode of administration is important for the effects of CAW on resilience to these age-related changes.

animal behavior and cognition↗

bioRxiv2022

Reversing gut microbiome-driven adipose tissue inflammation alleviates metabolic syndrome

The gut microbiota contributes to macrophage-mediated inflammation in adipose tissue with consumption of an obesogenic diet, thus driving the development of metabolic syndrome. There is a need to identify and develop interventions that abrogate this condition. The hops-derived prenylated flavonoid xanthohumol (XN) and its semi-synthetic derivative tetrahydroxanthohumol (TXN) attenuate high-fat diet-induced obesity, hepatosteatosis and metabolic syndrome in C57Bl/6J mice. This coincides with a decrease in pro-inflammatory gene expression in the gut and adipose tissue, together with alterations in the gut microbiota and bile acid composition. In this study, we integrated and interrogated multi-omics data from different organs with fecal 16S sequences and systemic metabolic phenotypic data using a transkingdom network analysis. By incorporating cell type information from single cell RNA-seq data, we discovered TXN attenuates macrophage inflammatory processes in adipose tissue. TXN treatment also reversed levels of inflammation-inducing microbes, such as Oscillibacter valericigenes, that lead to adverse metabolic phenotypes. Furthermore, in vitro validation in macrophage cell lines and in vivo mouse supplementation showed addition of O. valericigenes supernatant induced the expression of metabolic macrophage signature genes that are downregulated by TXN in vivo. Our findings establish an important mechanism by which TXN mitigates adverse phenotypic outcomes from diet-induced obesity and metabolic syndrome. It primarily reduces the abundance of pro-inflammatory gut microbes that can otherwise promote macrophage-associated inflammation in adipose tissue.

systems biology↗