University of Costa Rica

About: University of Costa Rica is a education organization based out in San José, Costa Rica. It is known for research contribution in the topics: Population & Venom. The organization has 9817 authors who have published 16781 publications receiving 238208 citations. The organization is also known as: UCR & Universidad de Costa Rica.

Large electrocaloric effects in oxide multilayer capacitors over a wide temperature range

Abstract: Heat pumps based on magnetocaloric and electrocaloric working bodies—in which entropic phase transitions are driven by changes of magnetic and electric field, respectively—use displaceable fluids to establish relatively large temperature spans between loads to be cooled and heat sinks1,2. However, the performance of prototypes is limited because practical magnetocaloric working bodies driven by permanent magnets3–5 and electrocaloric working bodies driven by voltage6–16 display temperature changes of less than 3 kelvin. Here we show that high-quality multilayer capacitors of PbSc0.5Ta0.5O3 display large electrocaloric effects over a wide range of starting temperatures when the first-order ferroelectric phase transition is driven supercritically (as verified by Landau theory) above the Curie temperature of 290 kelvin by electric fields of 29.0 volts per micrometre. Changes of temperature in the large central area of the capacitor peak at 5.5 kelvin near room temperature and exceed 3 kelvin for starting temperatures that span 176 kelvin (complete thermalization would reduce these values from 5.5 to 3.3 kelvin and from 176 to 73 kelvin). If magnetocaloric working bodies were to be replaced with multilayer capacitors of PbSc0.5Ta0.5O3, then the established design principles behind magnetocaloric heat pumps could be repurposed for better performance without bulky and expensive permanent magnets. High-quality multilayer capacitors of a perovskite oxide show that large electric-field-driven caloric effects could improve solid-state refrigeration technology and challenge today’s standard (based on magnetocaloric effects in gadolinium).

Somatic instability of the expanded CTG triplet repeat in myotonic dystrophy type 1 is a heritable quantitative trait and modifier of disease severity

Abstract: Deciphering the contribution of genetic instability in somatic cells is critical to our understanding of many human disorders. Myotonic dystrophy type 1 (DM1) is one such disorder that is caused by the expansion of a CTG repeat that shows extremely high levels of somatic instability. This somatic instability has compromised attempts to measure intergenerational repeat dynamics and infer genotype-phenotype relationships. Using single-molecule PCR, we have characterized more than 17 000 de novo somatic mutations from a large cohort of DM1 patients. These data reveal that the estimated progenitor allele length is the major modifier of age of onset. We find no evidence for a threshold above which repeat length does not contribute toward age at onset, suggesting pathogenesis is not constrained to a simple molecular switch such as nuclear retention of the DMPK transcript or haploinsufficiency for DMPK and/or SIX5. Importantly, we also show that age at onset is further modified by the level of somatic instability; patients in whom the repeat expands more rapidly, develop the symptoms earlier. These data establish a primary role for somatic instability in DM1 severity, further highlighting it as a therapeutic target. In addition, we show that the level of instability is highly heritable, implying a role for individual-specific trans-acting genetic modifiers. Identifying these trans-acting genetic modifiers will facilitate the formulation of novel therapies that curtail the accumulation of somatic expansions and may provide clues to the role these factors play in the development of cancer, aging and inherited disease in the general population.

Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and Understanding

Abstract: The historical development of discoveries and conceptual frames for understanding the hemorrhagic activity induced by viperid snake venoms and by hemorrhagic metalloproteinases (SVMPs) present in these venoms is reviewed. Histological and ultrastructural tools allowed the identification of the capillary network as the main site of action of SVMPs. After years of debate, biochemical developments demonstrated that all hemorrhagic toxins in viperid venoms are zinc-dependent metalloproteinases. Hemorrhagic SVMPs act by initially hydrolyzing key substrates at the basement membrane (BM) of capillaries. This degradation results in the weakening of the mechanical stability of the capillary wall, which becomes distended owing of the action of the hemodynamic biophysical forces operating in the circulation. As a consequence, the capillary wall is disrupted and extravasation occurs. SVMPs do not induce rapid toxicity to endothelial cells, and the pathological effects described in these cells in vivo result from the mechanical action of these hemodynamic forces. Experimental evidence suggests that degradation of type IV collagen, and perhaps also perlecan, is the key event in the onset of microvessel damage. It is necessary to study this phenomenon from a holistic, systemic perspective in which the action of other venom components is also taken into consideration.

Arguments for the sake of endophenotypes: Examining common misconceptions about the use of endophenotypes in psychiatric genetics

Abstract: Endophenotypes are measurable biomarkers that are correlated with an illness, at least in part, because of shared underlying genetic influences. Endophenotypes may improve our power to detect genes influencing risk of illness by being genetically simpler, closer to the level of gene action, and with larger genetic effect sizes or by providing added statistical power through their ability to quantitatively rank people within diagnostic categories. Furthermore, they also provide insight into the mechanisms underlying illness and will be valuable in developing biologically-based nosologies, through efforts such as RDoC, that seek to explain both the heterogeneity within current diagnostic categories and the overlapping clinical features between them. While neuroimaging, electrophysiological, and cognitive measures are currently most used in psychiatric genetic studies, researchers currently are attempting to identify candidate endophenotypes that are less genetically complex and potentially closer to the level of gene action, such as transcriptomic and proteomic phenotypes. Sifting through tens of thousands of such measures requires automated, high-throughput ways of assessing and ranking potential endophenotypes, such as the Endophenotype Ranking Value. However, despite the potential utility of endophenotypes for gene characterization and discovery, there is considerable resistance to endophenotypic approaches in psychiatry. In this review, we address and clarify some of the common issues associated with the usage of endophenotypes in the psychiatric genetics community.