Endogenous Excitatory Amino Acid Neurotransmission Regulates Thyroid-Stimulating Hormone and Thyroid Hormone Secretion in Conscious Freely Moving Male Rats

The role of neurotransmission of endogenous excitatory amino acid (EAA) on serum thyroid hormones and thyroid-stimulating hormone (TSH) levels was examined in conscious and freely moving adult male SpragueDawley rats. The rats were cannulated at the third ventricle 2 d before the experiments. Several glutamate receptor agonists, such as kainic acid and domoic acid, and antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and dizocilpine (MK-801) were administered into the third ventricle. Serum TSH levels were assesed by radioimmunoassay, and serum thyroid hormone levels were assessed by enzyme immunoassay. The results showed that the administration of CNQX and MK-801 produced a decrease in serum levels of TSH and thyroid hormones. The administration of kainic acid and domoic acid increased TSH concentrations, whereas CNQX completely blocked the release of TSH induced by kainic acid and domoic acid. These results suggest the importance of endogenous EAA in the regulation of hormone secretion from the pituitary-thyroid axis, as well as the role of the N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the stimulatory effect of EAAs on the pituitary-thyroid axis

Tracing Water Sources and Fluxes in a Dynamic Tropical Environment: From Observations to Modeling

Código de proyecto: Isotope Network for Tropical Ecosystem Studies (ISONet). Producción relacionada con el Observatorio del Agua y Cambio Global (OACG).Tropical regions cover approximately 36% of the Earth’s landmass. These regions are home to 40% of the world’s population, which is projected to increase to over 50% by 2030 under a remarkable climate variability scenario often exacerbated by El Niño Southern Oscillation (ENSO) and other climate teleconnections. In the tropics, ecohydrological conditions are typically under the influence of complex land-ocean-atmosphere interactions that produce a dynamic cycling of mass and energy reflected in a clear partition of water fluxes. Here, we present a review of 7 years of a concerted and continuous water stable isotope monitoring across Costa Rica, including key insights learned, main methodological advances and limitations (both in experimental designs and data analysis), potential data gaps, and future research opportunities with a humid tropical perspective. The uniqueness of the geographic location of Costa Rica within the mountainous Central America Isthmus, receiving moisture inputs from the Caribbean Sea (windward) and the Pacific Ocean (complex leeward topography), and experiencing strong ENSO events, poses a clear advantage for the use of isotopic variations to underpin key drivers in ecohydrological responses. In a sequential approach, isotopic variations are analyzed from moisture transport, rainfall generation, and groundwater/surface connectivity to Bayesian and rainfall-runoff modeling. The overarching goal of this review is to provide a robust humid tropical example with a progressive escalation from common water isotope observations to more complex modeling outputs and applications to enhance water resource management in the tropics.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de FísicaUCR::Vicerrectoría de Docencia::Ciencias Sociales::Facultad de Ciencias Sociales::Escuela de Geografí

A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients' experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.This work was partially supported by the Fundacion Espanola para la Ciencia y la Tecnologia (UCA PR214), the Asociacion Pablo Ugarte (APU, Spain), Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000154), Ministry of Science and Technology, Spain (PID2019110895RB-I00), and Inversion Territorial Integrada de la Provincia de Cadiz (ITI-0038-2019)

Síntesis de ésteres metílicos de ácidos grasos por catálisis heterogénea con zeolita natural modificada químicamente

El trabajo describe la síntesis de ésteres metílicos de ácidos grasos utilizando como catalizador zeolita natural del yacimiento de Palmarito, modificada en forma ácida. Esta zeolita contiene un 85 % de mordenita, cuya estructura cristalina, por el diámetro de sus poros y canales, particularmente cuando es modificada en forma ácida, hace posible acometer la obtención de diversos productos. La esterificación de los ácidos grasos con alcoholes menores, como el metanol, reviste gran importancia en algunos procesos industriales. Esto se ha llevado a cabo normalmente con catalizadores ácidos, minerales u orgánicos y con resinas ácidas

Experiencia práctica de tipo interdisciplinar para manejo de dispositivos de potencia, instrumentación electrónica, sistemas microprocesadores e identificación paramétrica de sistemas dinámicos

El cambio en el entorno y en las dimensiones internas de las instituciones de educación superior provoca la necesidad de revisar el modelo educativo. Actualmente asistimos a la transformación de la Universidad provocada en gran medida por la revolución del conocimiento y las nuevas tecnologías de la información, que generan cambios tanto en el entorno como en los recursos internos disponibles en las universidades. El reto imperativo durante la próxima década es el cambio que debe producirse tanto en los productos que la Universidad ofrece (titulaciones, programas de postgrado, investigación, difusión, etc.) como en la forma en la que ofrece estos produ ctos, resultando necesario revisar los procesos docentes y haciéndose imperativa la introducción de la formación multidisciplinar. En este trabajo se presenta una experiencia práctica de tipo multidisciplinar, que aúna conceptos relacionados c on el manejo de herramientas de simulación basadas en Matlab y Simulink para el estudio de sistemas electrónicos digitales, analógicos y de potencia, así como el procesamiento de la señal y la identificación paramétrica de sistemas dinámicos. Se describirá el sistema con el que se trabajará (una máquina de inducción de 5 fases gobernada por un convertidor de potencia de 2 nivel es), para posteriormente definir su modelado empleando Matlab y Simulink y plantear los objetivos del trabajo de si mulación a realizar por los alumnos

Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial

Background: Several studies show the importance of accurately quantifying not only KRAS and other low-abundant mutations because benefits of anti-EGFR therapies may depend on certain sensitivity thresholds. We assessed whether ultra-selection of patients using a high-sensitive digital PCR (dPCR) to determine KRAS, NRAS, BRAF and PIK3CA status can improve clinical outcomes of panitumumab plus FOLFIRI. Patients and methods: This was a single-arm phase II trial that analysed 38 KRAS, NRAS, BRAF and PIK3CA hotspots in tumour tissues of irinotecan-resistant metastatic colorectal cancer patients who received panitumumab plus FOLFIRI until disease progression or early withdrawal. Mutation profiles were identified by nanofluidic dPCR and correlated with clinical outcomes (ORR, overall response rate; PFS, progression-free survival; OS, overall survival) using cut-offs from 0% to 5%. A quantitative PCR (qPCR) analysis was also performed. Results: Seventy-two evaluable patients were enrolled. RAS (KRAS/NRAS) mutations were detected in 23 (32%) patients and RAS/BRAF mutations in 25 (35%) by dPCR, while they were detected in 7 (10%) and 11 (15%) patients, respectively, by qPCR. PIK3CA mutations were not considered in the analyses as they were only detected in 2 (3%) patients by dPCR and in 1 (1%) patient by qPCR. The use of different dPCR cut-offs for RAS (KRAS/NRAS) and RAS/BRAF analyses translated into differential clinical outcomes. The highest ORR, PFS and OS in wild-type patients with their lowest values in patients with mutations were achieved with a 5% cut-off. We observed similar outcomes in RAS/BRAF wild-type and mutant patients defined by qPCR. Conclusions: High-sensitive dPCR accurately identified patients with KRAS, NRAS, BRAF and PIK3CA mutations. The optimal RAS/BRAF mutational cut-off for outcome prediction is 5%, which explains that the predictive performance of qPCR was not improved by dPCR. The biological and clinical implications of low-frequent mutated alleles warrant further investigations

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Primer trasplante de islotes realizado en Colombia, experiencia fundación Valle del Lili

Introducción De acuerdo con las estadísticas suministradas en el 2014 por la Federación Internacional de Diabetes, la prevalencia de pacientes con diabetes está en aumento a nivel mundial, actualmente alrededor de 382 millones de personas sufren de esta patología. En relación con la diabetes tipo 1 se estima que corresponde al 5% de todos los casos diagnosticados de diabetes en adultos. Para el caso de Colombia, la incidencia de diabetes tipo 1 es de 3-4 por 100.000 niños menores de 15 años y la prevalencia se estima en 0,07%. Para el municipio de Santiago de Cali, según datos de la oficina de estadística de la Secretaría de Salud Pública, la diabetes (tipo 1 y 2) se encuentra entre las diez primeras causas de muerte en la ciudad, ocupando el octavo lugar en el grupo de hombres y el séptimo entre las mujeres. Cabe resaltar que la prevalencia de diabetes para Cali es del 6,76%, seguida del 5,4% para el departamento del Valle del Cauca, cifra mucho más alta cuando se compara con la prevalencia nacional que es de 2%. Específicamente, cuando nos referimos a la diabetes tipo 1, es una patología autoinmune crónica, que se presenta con una predisposición genética específica y en un 0,4% aparece sin antecedentes familiares. Su presentación se hace de forma inesperada, a causa de la destrucción rápidamente progresiva de las células beta pancreáticas, por esta razón requiere la suplencia total de insulina exógena de forma crónica. Lo anterior ocasiona que la enfermedad esté ligada a una carga económica alta para los pacientes, sus familias y el sistema de salud. A nivel global se estima que más del 10% de la inversión en salud se destina a gastos relacionados directamente con diabetes. En cuanto al tratamiento médico de la diabetes tipo 1, la recomendación actual está basada en la terapia intensiva con insulina exógena, sin embargo, este tratamiento se caracteriza por ser de difícil adherencia, costoso, y por conllevar a un incremento considerable de los eventos de hipoglicemia severa. Estos eventos aumentan en alto grado el riesgo de sufrir deterioro cardiovascular y cognitivo. Por lo tanto, existe una gran necesidad de encontrar mejores alternativas de tratamiento para estos pacientes, que impliquen menores riesgos biológicos y ofrezcan mejor calidad de vida

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat