Biology subjects

Reis, T.

Publications and source records attributed to Reis, T..

5 recordsLinked to original sources

bioRxiv2026

Opportunistic pathogenicity in fungi can transcend species boundaries

Multiple fungal lineages have independently evolved the ability to opportunistically infect humans, imposing a major burden on public health. Opportunistic pathogenicity requires the confluence of pre-existing fungal traits that facilitate host colonization (e.g., the ability to grow at 37{degrees}C) and host immune filters that permit the survival of some colonizers (e.g., inborn errors of immunity). Numerous studies have shown that fungal pathogens can exhibit extensive strain-to-strain variation in the ability to cause disease. Moreover, it is also well established that non-pathogenic fungi can occasionally cause severe infections. Together, these observations raise the question: What differentiates opportunistic fungal pathogens from non-pathogens? To address this empirically, we compared phenotypic, metabolomic, and genomic variation between Aspergillus fumigatus, an organism responsible for more than 300,000 infections per year, and Aspergillus fischeri, a close relative that is not considered clinically relevant. By examining 26 phenotypic traits across 16 representative strains of A. fumigatus and 16 of A. fischeri, we found that infection-relevant traits measured under in vitro monoculture conditions showed species-specific distributions, whereas traits measured under in vitro coculture with murine macrophages overlapped. Strikingly, strains of the two species also overlapped in their virulence profiles in an immunocompromised murine model of pulmonary aspergillosis; three strains of A. fischeri exhibited lethality rates of >50% while two A. fumigatus strains were among the least virulent of all 32 strains tested. Consistent with this overlap, we could not associate virulence variation with the presence of specific genomic elements, phenotypic traits, or secondary metabolites. Our results raise the hypothesis that opportunistic pathogenicity can extend beyond the boundaries of individual species. We propose a conceptual model in which the opportunistic pathogenic potential of any fungal strain is the product of complex interactions among numerous genomic, ecological, and host immunity factors.

evolutionary biology↗

bioRxiv2026

Drosophila Arc1 is required for metabolic resilience and developmental timing during dietary challenges

Energy homeostasis at the organismal level requires balancing energy storage and mobilization to provide sufficient fuel for energy-intensive processes like development without depleting or accumulating excess stores. Fluctuations in the nutritional content of the diet present a challenge to the pathways that maintain energy balance. We previously identified the Drosophila melanogaster counterpart of human ARC (activity-regulated cytoskeleton-associated protein) as a brain-expressed protein that regulates energy storage in the major fat storage tissue of the fly, the fat body. Here we show that Arc1 expression in the brain responds to changes in diet and insulin-like peptide levels. Mutating Arc1 perturbs the ability of larvae to maintain normal body fat and rates of development upon dietary changes: mutants develop slower or faster than wild-type on nutrient-poor or nutrient-rich diets, respectively. Excess fat storage in Arc1 mutants becomes an advantage upon starvation, prolonging survival relative to the wild type. In addition to metabolic and neuronal genes, transcriptomic analysis revealed changes in key developmental drivers of development, in both diet-dependent and - independent manners. This study supports a model in which nutrient regulation of Arc1 via insulin-like peptide signaling couples dietary changes to changes in metabolism -- to maintain energy homeostasis -- and production of hormone signals, to support timely development. In this role, Arc1 is a central player in a buffering mechanism that coordinates nutrient availability, organismal metabolism, and developmental rate.

genetics↗

bioRxiv2025

Circadian Rhythms are Disrupted in Patients and Preclinical Models of Machado-Joseph Disease

Machado-Joseph disease (MJD) is caused by an abnormal CAG repeat expansion in the ATXN3 gene, leading to the expression of a mutant ataxin-3 (mutATXN3) protein. MJD patients exhibit a wide range of clinical symptoms, including motor incoordination. Emerging evidence highlights circadian rhythm disruptions as early indicators and potential risk factors for the progression of neurodegenerative conditions. Circadian rhythms are regulated by internal clocks, with the suprachiasmatic nucleus (SCN) acting as the master pacemaker to synchronize timing across the bodys behavioural and physiological functions. While sleep disturbances have been observed in MJD, the role of clock regulation in its pathophysiology remains largely unexplored in spinocerebellar ataxias. This study aimed to investigate circadian rhythms, characterize associated disruptions, and uncover the mechanisms underlying clock dysregulation in patients and preclinical models of MJD. Circadian activity in MJD patients was assessed over two weeks using actigraphy, while in a YAC-MJD transgenic mouse model, circadian rhythms were examined through: (a) wheel-running experiments; (b) telemetry-based monitoring of core body temperature; (c) immunohistochemical analysis of the neuropeptides arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) in the SCN and paraventricular nucleus (PVN); and (d) RT-qPCR evaluation of clock gene expression in the cerebellum. The impact of mutATXN3 on clock mechanisms was further investigated using Bmal1/Per2-luciferase reporters. MJD patients exhibited a progressive decline in robustness of behavioural rhythms, demonstrated by negative correlations between the circadian function index, rest-activity fragmentation, and sleep efficiency with MJD clinical scales. YAC-MJD mice exhibited reduced activity levels, increased behavioural fragmentation, and required three additional days to re-entrain after a jet lag protocol, compared to controls. Disrupted core body temperature rhythms were observed, including a phase advance and elevated temperature ([~]1 {degrees}C) at the onset of the active period. Furthermore, transgenic mice showed reduced levels of VIP and AVP in the SCN and PVN, and decreased clock gene expression in the cerebellum. Lastly, we found new mechanistic evidence that WT ATXN3 activates the promoters of Bmal1 and Per2, whereas mutATXN3 loses the capacity to drive Per2 upon polyglutamine expansion. Overall, our findings indicate that central clock dysfunction in MJD is associated with impaired clock gene expression and disruptions in activity and temperature rhythms. This study provides the first robust evidence of circadian rhythm dysregulation and underlying mechanisms in MJD, paving the way for the identification of new biomarkers and the development of novel circadian-based interventions to tackle MJD and possibly other spinocerebellar ataxias. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/631212v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@25078dorg.highwire.dtl.DTLVardef@112e523org.highwire.dtl.DTLVardef@1818356org.highwire.dtl.DTLVardef@1d5a6c0_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Spenito-dependent metabolic sexual dimorphism intrinsic to fat storage cells

Metabolism in males and females is distinct. Differences are usually linked to sexual reproduction, with circulating signals (e.g. hormones) playing major roles. By contrast, sex differences prior to sexual maturity and intrinsic to individual metabolic tissues are less understood. We analyzed Drosophila melanogaster larvae and find that males store more fat than females, the opposite of the sexual dimorphism in adults. We show that metabolic differences are intrinsic to the major fat storage tissue, including many differences in the expression of metabolic genes. Our previous work identified fat storage roles for Spenito (Nito), a conserved RNA-binding protein and regulator of sex determination. Nito knockdown specifically in the fat storage tissue abolished fat differences between males and females. We further show that Nito is required for sex-specific expression of the master regulator of sex determination, Sex-lethal (Sxl). "Feminization" of fat storage cells via tissue-specific overexpression of a Sxl target gene made larvae lean, reduced the fat differences between males and females, and induced female-like metabolic gene expression. Altogether, this study supports a model in which Nito autonomously controls sexual dimorphisms and differential expression of metabolic genes in fat cells in part through its regulation of the sex determination pathway.

genetics↗

bioRxiv2019

Gene-diet interactions: dietary rescue of metabolic defects in spen-depleted Drosophila

Obesity and its co-morbidities are a growing health epidemic. Interactions between genetic background and the environment and behavior (i.e. diet) greatly influence organismal energy balance. Previously, we described obesogenic mutations in the gene Split ends (Spen) in Drosophila melanogaster, and roles for Spen in fat storage and metabolic state. In Spen-deficient storage cells lipid catabolism is impaired, accompanied by a compensatory increase in glycolytic flux and protein catabolism. Here we investigate gene-diet interactions to determine if diets supplemented with specific macronutrients can rescue metabolic dysfunction in Spen-depleted animals. We show that a high-yeast diet partially rescues adiposity and developmental defects. High sugar partially improves developmental timing as well as adult longevity. Gene-diet interactions were heavily influenced by developmental-stage-specific organismal needs: extra yeast provides benefits early in development (larval stages) but becomes detrimental in adulthood. High sugar confers benefits at both larval and adult stages, with the caveat of increased adiposity. A high-fat diet is detrimental according to all tested criteria, regardless of genotype. Whereas Spen depletion influenced phenotypic responses to supplemented diets, diet was the dominant factor in directing the whole-organism steady-state metabolome. Obesity is a complex disease of genetic, environmental, and behavioral inputs. Our results show that diet customization can ameloriate metabolic dysfunction underpinned by a genetic factor.

genetics↗