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Rosales, C.

Publications and source records attributed to Rosales, C..

2 recordsLinked to original sources

Total immunoglobulin G variation through the phenological cycle of migrant and resident Long-nosed bats (Leptonycteris yerbabuenae) in the drylands of Mexico and its relationship with bacterial-killing ability of plasma.

Immunological variations of bats throughout their life cycle represent an underexplored and controversial topic that has great potential for understanding their immunology. This gap is particularly large regarding the state of immunity during early life and migration, and how different immune components interact with each other. In this study, the partial migratory long-nosed bat (Leptonycteris yerbabuenae) was used as a model to assess the state of acquired humoral immunity (total IgG concentration, tIgG) during early life, during the reproductive cycle and at the extremes of the migratory range of females. We also determined the relationship of tIgG with plasma bactericidal activity against Escherichia coli. The concentration of tIgG was stable throughout the reproductive cycle of adults, and no significant changes were detected at the extremes of the migratory range of females. However, tIgG concentration was reduced during early life (2 to 3 months of age) and in non-reproductive males in March-May 2019 relative to non-reproductive males in March 2020. The tIgG concentration had a positive relationship with plasma bactericidal ability in non-reproductive females, but no relationship was observed in non-reproductive males and reproductive females. These results suggests that tIgG concentration is resilient to physiological and ecological changes experienced by adults throughout their reproductive and migratory cycle. The reduction of tIgG during early life suggests that young individuals have not developed an IgG pool comparable to that of adults. Finally, the positive relationship observed between tIgG and BKA in non-reproductive females suggests that E. coli clearance is enhanced by the presence of antibodies that facilitate the elimination of this bacteria.

ecology↗

Carvedilol suppresses ryanodine receptor-dependent Ca2+ bursts in human neurons bearing PSEN1 variants found in early onset Alzheimer's disease

Seizures are increasingly being recognized as the hallmark of Alzheimers disease (AD). Neuronal hyperactivity can be a consequence of neuronal damage caused by abnormal amyloid {beta} (A{beta}) depositions. However, it can also be a cell-autonomous phenomenon causing AD by A{beta}-independent mechanisms. Indeed, various studies using animal models showed that Ca2+ releases from the endoplasmic reticulum (ER) via type 1 inositol triphosphate receptors (InsP3R1s) and ryanodine receptors (RyRs). To investigate which is the main pathophysiological mechanism in human neurons, we measured Ca2+ signaling in neural cells derived from three early-onset AD patients harboring variants of Presenilin-1 (PSEN1 p.A246E, p.L286V, and p.M146L). Of these, it has been reported that PSEN1 p.A246E and p.L286V did not produce a significant amount of abnormal A{beta}. We found that all PSEN1-mutant neurons, but not wild-type, caused abnormal Ca2+-bursts in a manner dependent on the calcium channel, Ryanodine Receptor 2 (RyR2). Indeed, carvedilol, anRyR2 inhibitor, and VK-II-86, an analog of carvedilol without the {beta}-blocking effects, sufficiently eliminated the abnormal Ca2+ bursts. In contrast, Dantrolene, a RyR1 inhibitor, and Xestospongin c, an IP3R inhibitor, did not attenuate the Ca2+-bursts. The RNA-Seq data revealed that ER-stress responsive genes were increased, and mitochondrial Ca2+-transporter genes were decreased in PSEN1A246E cells compared to the WT neurons. Thus, we propose that aberrant Ca2+ signaling is a key link between human pathogenic PSEN1 variants and cell-intrinsic hyperactivity prior to deposition of abnormal A{beta}, offering prospects for the development of targeted prevention strategies for at-risk individuals. One Sentence SummaryAberrant Ca2+-signaling causes PSEN1-related early onset Alzheimers disease.

neuroscience↗