When the Tides Come, Where Will We Go?

For coastal urban areas, an increase in flooding is one of the clearest climate change threats. The research presented in this paper demonstrates how a land use-transport model can be used to forecast the short-and longer-Term impacts of a potential 4-ft sea level rise in greater Boston, Massachusetts, by 2030. The short-Term scenario represents the immediate transport system response to inundation, which provides a measure of resiliency in the case of an extreme event, such as a storm surge. In the short run, the results reveal that transit captive users will suffer more. Transit, in general, displays less resiliency, at least in part because of the center city's vulnerability and Boston's radial transit system. Trip distances would modestly decrease, and average travel speeds would go down by more than 50%. Rail transit ridership would be decimated, and overall transit usage would go down by 66%. The longer-Term scenario predicts how households and firms would prefer to relocate in the so-called new equilibrium when more than 10 mi2 of land disappears and the transport network inundations become permanent. Assuming no supply constraints, new residential growth centers would emerge on the peripheries of the inundated zones, primarily in the inner-core suburbs. Some regional urban centers and traditional industrial towns would boom. Firms would be hit harder, because of their heavy concentration in the inner core; firm relocation would largely follow households. Transit usage would again be decimated, but walking trips would increase. Results, however, should be viewed as cautious speculation

Lung tumorspheres as a drug screening platform against cancer stem cells

Treatment resistance and metastasis are linked to cancer stem cells (CSCs). This population represents a promising target, but remains unexplored in lung cancer. The main objective of this study was to characterize lung CSCs and discover new therapeutic strategies

CASA-Mot technology: how results are affected by the frame rate and counting chamber

For over 30 years, CASA-Mot technology has been used for kinematic analysis of sperm motility in different mammalian species, but insufficient attention has been paid to the technical limitations of commercial computer-aided sperm analysis (CASA) systems. Counting chamber type and frame rate are two of the most important aspects to be taken into account. Counting chambers can be disposable or reusable, with different depths. In human semen analysis, reusable chambers with a depth of 10 mm are the most frequently used, whereas for most farm animal species it is more common to use disposable chambers with a depth of 20 mm. The frame rate was previously limited by the hardware, although changes in the number of images collected could lead to significant variations in some kinematic parameters, mainly in curvilinear velocity (VCL). A frame rate of 60 frames s(-1) is widely considered to be the minimum necessary for satisfactory results. However, the frame rate is species specific and must be defined in each experimental condition. In conclusion, we show that the optimal combination of frame rate and counting chamber type and depth should be defined for each species and experimental condition in order to obtain reliable results

G protein-coupled receptor kinase 2 (GRK2) as a potential therapeutic target in cardiovascular and metabolic diseases

G protein-coupled receptor kinase 2 (GRK2) is a central signaling node involved in the modulation of many G protein-coupled receptors (GPCRs) and also displaying regulatory functions in other cell signaling routes. GRK2 levels and activity have been reported to be enhanced in patients or in preclinical models of several relevant pathological situations, such as heart failure, cardiac hypertrophy, hypertension, obesity and insulin resistance conditions, or non-alcoholic fatty liver disease (NAFLD), and to contribute to disease progression by a variety of mechanisms related to its multifunctional roles. Therefore, targeting GRK2 by different strategies emerges as a potentially relevant approach to treat cardiovascular disease, obesity, type 2 diabetes, or NAFLD, pathological conditions which are frequently interconnected and present as co-morbidities.Our laboratories are supported by Ministerio de Economía; Industria y Competitividad (MINECO) of Spain (grant SAF2017- 84125-R to FM and CM and SAF2016-80305-P to MS and AMB), CIBERCV-Instituto de Salud Carlos III, Spain (grants CB16/11/00278 and CB16/11/00286 to FM and MS, respectively, co-funded with European FEDER contribution), and Programa de Actividades en Biomedicina de la Comunidad de Madrid (grants B2017/BMD-3671-INFLAMUNE to FM and B2017/ BMD-3676-AORTASANA to MS)

Imágenes urológicas ITU por cuerpo extraño vesical

Three patients aged (a) 52 years, (b) 60 years and (c) 42 years intervened 5 years, 3 years and 2 years ago, respectively, for stress urinary incontinence using the Burch procedure via the abdominal route.Tres pacientes de (a) 52 años, (b) 60 años y (c) 42 años de edad intervenidos hace 5 años, 3 años y 2 años respectivamente de incontinencia urinaria de esfuerzo mediante la intervención de Burch vía abdominal

GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo

© The Author(s).[Background]: Insulin secretion from the pancreatic β-cell is finely modulated by different signals to allow an adequate control of glucose homeostasis. Incretin hormones such as glucagon-like peptide-1 (GLP-1) act as key physiological potentiators of insulin release through binding to the G protein-coupled receptor GLP-1R. Another key regulator of insulin signaling is the Ser/Thr kinase G protein-coupled receptor kinase 2 (GRK2). However, whether GRK2 affects insulin secretion or if GRK2 can control incretin actions in vivo remains to be analyzed. [Results]: Using GRK2 hemizygous mice, isolated pancreatic islets, and model β-cell lines, we have uncovered a relevant physiological role for GRK2 as a regulator of incretin-mediated insulin secretion in vivo. Feeding, oral glucose gavage, or administration of GLP-1R agonists in animals with reduced GRK2 levels (GRK2+/− mice) resulted in enhanced early phase insulin release without affecting late phase secretion. In contrast, intraperitoneal glucose-induced insulin release was not affected. This effect was recapitulated in isolated islets and correlated with the increased size or priming efficacy of the readily releasable pool (RRP) of insulin granules that was observed in GRK2+/− mice. Using nanoBRET in β-cell lines, we found that stimulation of GLP-1R promoted GRK2 association to this receptor and that GRK2 protein and kinase activity were required for subsequent β-arrestin recruitment. [Conclusions]: Overall, our data suggest that GRK2 is an important negative modulator of GLP-1R-mediated insulin secretion and that GRK2-interfering strategies may favor β-cell insulin secretion specifically during the early phase, an effect that may carry interesting therapeutic applications.We acknowledge support by Ministerio de Economía y Competitividad (MINECO/FEDER), Spain (grant SAF2017-84125-R to FM and CM and BFU2017-89336-R to MV); CIBER de Enfermedades Cardiovasculares (CIBERCV). Instituto de Salud Carlos III, Spain (grant CB16/11/00278 to F.M., co-funded with European FEDER contribution); CIBER de Diabetes y Enfermedades Metabólicas Asociadas (Ciberdem), Instituto de Salud Carlos III (CB07/08/0029 to MV); and Programa de Actividades en Biomedicina de la Comunidad de Madrid-B2017/BMD-3671-INFLAMUNE to FM; Medical Research Council to AT and BJ

Prevalencia de Eimeria sp y estudio morfométrico de ooquistes hallados en canes domésticos de Perú

La eimeriosis es una enfermedad causada por un protozoario del género Eimeria que afecta a todos los animales silvestres y domésticos. Dado que en Perú no existen reportes previos y en otras regiones de Latinoamérica la prevalencia es nula o baja en perros domésticos, el objetivo del presente trabajo fue determinar la prevalencia de Eimeria sp en canes de la ciudad de Cajamarca mediante un análisis coproparasitológico, utilizando el método de Faust y efectuando el estudio morfométrico de los ooquistes. Se obtuvieron aleatoriamente 206 muestras fecales en la zona Este de Cajamarca, las cuales fueron inmediatamente procesadas en el Laboratorio de Parasitología Veterinaria de la Universidad Nacional de Cajamarca, Perú. La prevalencia de Eimeria sp fue de 10,68% en canes domésticos. En el estudio morfométrico de los ooquistes, se determinaron medidas de largo y ancho, que presentaron promedios de 21,73 pm de largo y 17,77 pm de ancho para la forma ovoide; 16,40 pm de largo y 15,31 pm de ancho para la forma esférica, y finalmente 25,54 y 18,51 pm respectivamente para la forma elipsoidal. Estos resultados prueban la presencia e infección leve por Eimeria sp en perros domésticos en la serranía norte del Perú, sugiriendo además, futuros estudios del protozoario para evitar riesgos o afecciones a la salud pública

Expression and quantification of RORγt and interleukin-17 in intestinal mucosa of newborn alpaca (Vicugna pacos)

El objetivo del estudio fue determinar los niveles relativos de expresión de ARN mensajeros de RORγt e IL-17 en mucosa intestinal de crías de alpacas clínicamente sanas. Se formaron tres grupos etarios conformados por alpacas de 2 a 7 días (grupo 1, n=5), 8 a 20 días (grupo 2, n=6) y 26 a 47 días (grupo 3, n=6), sin distinción de sexo o raza. Se tomaron muestras del segmento medio del yeyuno, se extrajo el ARN total y se empleó la técnica RT-PCR con cebadores. La expresión relativa de ARNm de RORγt e IL-17 fue determinada por el método 2-∆∆Ct usando como calibradores dos crías neonatas y empleándose como control endógeno a GAPDH. La cinética de expresión de RORγt mostró una tendencia constante durante la primera y tercera semana de vida, alcanzando su máxima expresión en los animales de 2 a 7 días de edad, a diferencia de IL-17 cuya expresión fue progresiva con la edad, evidenciándose una elevada estimulación y expresión desde los primeros días de edad.The aim of the study was to determine the relative levels of expression of messenger RNAs of RORγt and IL-17 in intestinal mucosa of clinically healthy newborn alpacas. Three age groups were formed: 2 to 7 days (group 1, n=5), 8 to 20 days (group 2, n=6) and 26 to 47 days (group 3, n=6), regardless sex or breed. Samples were taken from the middle segment of the jejunum. The total RNA was extracted, and the RT-PCR technique was used with specific primers. The relative expression of mRNA of RORγt and IL-17 was determined by the 2-ΔΔCt method using two neonatal pups as calibrators and using GAPDH as an endogenous control. The kinetics of expression of RORγt showed a constant trend during the first and third week of life, reaching its maximum expression in animals from 2 to 7 days of age, unlike IL-17 whose expression was progressive with age, evidencing a high stimulation and expression from the first days of age

G Protein-Coupled Receptor Kinase 2 (GRK2) as a Potential Therapeutic Target in Cardiovascular and Metabolic Diseases

G protein-coupled receptor kinase 2 (GRK2) is a central signaling node involved in the modulation of many G protein-coupled receptors (GPCRs) and also displaying regulatory functions in other cell signaling routes. GRK2 levels and activity have been reported to be enhanced in patients or in preclinical models of several relevant pathological situations, such as heart failure, cardiac hypertrophy, hypertension, obesity and insulin resistance conditions, or non-alcoholic fatty liver disease (NAFLD), and to contribute to disease progression by a variety of mechanisms related to its multifunctional roles. Therefore, targeting GRK2 by different strategies emerges as a potentially relevant approach to treat cardiovascular disease, obesity, type 2 diabetes, or NAFLD, pathological conditions which are frequently interconnected and present as co-morbidities

Impaired DNA replication within progenitor cell pools promotes leukemogenesis.

Impaired cell cycle progression can be paradoxically associated with increased rates of malignancies. Using retroviral transduction of bone marrow progenitors followed by transplantation into mice, we demonstrate that inhibition of hematopoietic progenitor cell proliferation impairs competition, promoting the expansion of progenitors that acquire oncogenic mutations which restore cell cycle progression. Conditions that impair DNA replication dramatically enhance the proliferative advantage provided by the expression of Bcr-Abl or mutant p53, which provide no apparent competitive advantage under conditions of healthy replication. Furthermore, for the Bcr-Abl oncogene the competitive advantage in contexts of impaired DNA replication dramatically increases leukemogenesis. Impaired replication within hematopoietic progenitor cell pools can select for oncogenic events and thereby promote leukemia, demonstrating the importance of replicative competence in the prevention of tumorigenesis. The demonstration that replication-impaired, poorly competitive progenitor cell pools can promote tumorigenesis provides a new rationale for links between tumorigenesis and common human conditions of impaired DNA replication such as dietary folate deficiency, chemotherapeutics targeting dNTP synthesis, and polymorphisms in genes important for DNA metabolism