Geocronología de la Terraza Compleja de Arganda en el valle del río Jarama (Madrid, España)

La Terraza Compleja de Arganda (TCA), situada en el tramo bajo del río Jarama (Madrid), está formada por sucesivos apilamientos de secuencias fluviales denominados de abajo a arriba Arganda I, II, III y IV, en los que se han encontrado importantes yacimientos arqueológicos y paleontológicos del Pleistoceno (Áridos 1 y 2, Valdocarros o HAT), y numerosos conjuntos de industria lítica del Paleolítico inferior y medio. Hasta ahora, la única referencia cronológica disponible para la TCA era la proporcionada por el estadio evolutivo de los micromamíferos de los yacimientos Áridos 1 en Arganda I y Valdocarros en Arganda II. En este trabajo, se propone la equivalencia de las distintas unidades de la TCA con terrazas escalonadas y se establece un marco cronológico numérico, obtenido mediante dataciones de termoluminiscencia, luminiscencia ópticamente estimulada y racemización de aminoácidos. Arganda I (≈ T+30-32 m) se situaría hacia el final del MIS 11 o en el inicio del MIS 9, Arganda II (≈T+23-24 m) se correspondería con el inicio del MIS 7, Arganda III (≈T+18-20 m) se situaría entre el MIS 7 y el MIS 5, y Arganda IV comenzaría su deposición en el MIS 5 finalizando su sedimentación en el MIS 1 al sur de Arganda del Rey (Madrid)

Programming of Dopaminergic Neurons by Early Exposure to Sex Hormones: Effects on Morphine-Induced Accumbens Dopamine Release, Reward, and Locomotor Behavior in Male and Female Rats

Neonatal programming with sex hormones produces long-term functional changes in various tissues, including the brain. Previously, we demonstrated a higher content of dopamine and an increase in potassium-induced dopamine release in the nucleus accumbens of adult rats exposed to estradiol valerate. On the other hand, sex hormones also affect the opioid system increasing the expression of the μ opioid receptor and β-endorphins. Here, we investigated if neonatal programming with sex hormones alters the response to morphine during adulthood in rats and predispose them to neurochemical, rewarding and behavioral activating effects. We examined the effects of neonatal exposure to a single dose of estradiol valerate or testosterone propionate on morphine-induced (5 mg/kg, i.v.) dopamine release in the nucleus accumbens and morphine-induced (3 mg/kg, s.c.) locomotor activity and conditioned place preference when these rats were adults. Our results showed a significant increase in morphine-induced dopamine release in the nucleus accumbens of rats that were exposed neonatally to estradiol compared with control rats. This effect was correlated with higher place preference and locomotor activity induced by morphine in adult rats neonatally exposed to estradiol valerate. However, the effect of morphine on dopamine release and behaviors was similar in rats treated with testosterone compared to control rats. Additionally, the expression of mu (μ) opioid receptor, dopamine receptor type 1 (D1) and dopamine receptor type 2 (D2) in the nucleus accumbens of adult rats was not different after treatment with sex hormones. Taken together, our results demonstrated an enhancement of pharmacological effects produced by morphine in rats neonatally programmed with estradiol valerate, suggesting that early exposure to sex hormones could represent a vulnerability factor in the development of addiction to opioid drugs such as morphine and heroin in adulthood

Germinal matrix hemorrhage: can be detected effectively

La hemorragia de la matriz germinal corresponde a un evento cerebrovascular originado en sus vasos sanguíneos, es prevalente en los prematuros y es la primera causa de mortalidad infantil en Ecuador; su inadecuado diagnóstico tiene un importante impacto en el neurodesarrollo de los prematuros y puede generar secuelas graves que pueden ser mayores conforme al grado de prematuridad, especialmente en prematuros con un peso de 500 a 750 g al nacimiento. Una de las principales herramientas para diagnosticar la hemorragia de la matriz es el ultrasonido transfontanelar que es fundamental en la detección y manejo temprano la situación, se debe considerar que requiere de un radiólogo experimentado para identificar e interpretar los hallazgos. Los factores de riesgo asociados son: la edad gestacional, el peso bajo al nacer, la puntuación baja del test de Apgar, la acidosis y la asfixia neonatal. Los factores que están implicados en la hemorragia pueden ser: intravasculares, vasculares y extravasculares. Los grados pueden ir del Grado I (masa hiperecogénica por la presencia de coágulos, el plexo coroideo luce engrosado en la región del trígono), Grado II (en el que la hemorragia se extiende hacia la cisterna magna lo que incrementa el riesgo de hidrocefalia), Grado III en el que el coágulo se volverá más anecoico con el tiempo, la presencia de sangre en el LCR puede producir una ventriculitis química) y Grado IV (con hipercogenecidad paraventricular con afectación de lóbulos frontales y parietales). El ultrasonido transfontanelar puede detectar varias lesiones cerebrales en el recién nacido prematuro entre estas la hemorragia de la matriz germinal y la leucomalacia periventricular. La causa principal de la leucomalacia son los eventos hipóxicos-isquémicos, por lo que las lesiones predominan en la sustancia blanca periventricular. Se recomienda el uso de esta técnica para el diagnóstico oportuno de la hemorragia en los recién nacidos que presenten factores de riesgo.The germinal matrix hemorrhage corresponds to a cerebrovascular event originated in its blood vessels, it is prevalent in premature babies and is the first cause of infant mortality in Ecuador; Its inadequate diagnosis has an important impact on the neurodevelopment of premature infants and can generate serious sequelae that may be greater depending on the degree of prematurity, especially in premature infants weighing 500 to 750 g at birth. One of the main tools to diagnose womb bleeding is transfontanelar ultrasound, which is fundamental in the detection and early management of the situation. It should be considered that it requires an experienced radiologist to identify and interpret the findings. Some associated risk factors are: gestational age, low birth weight, low Apgar score, acidosis, and neonatal asphyxia. The factors that are involved in bleeding can be: intravascular, vascular and extravascular. The degrees can range from Grade I (hyperechogenic mass due to the presence of clots, the choroid plexus looks thickened in the trigone region), Grade II (in which the hemorrhage extends to the cisterna magna, which increases the risk of hydrocephalus) , Grade III in which the clot will become more anechoic over time, the presence of blood in the CSF can cause chemical ventriculitis) and Grade IV (with paraventricular hypercogenecity with involvement of the frontal and parietal lobes). Transfontanelar ultrasound can detect various brain lesions in the premature newborn, including bleeding from the germ matrix and periventricular leukomalacia. The main cause of leukomalacia is hypoxic-ischemic events, so that the lesions predominate in the periventricular white matter. The use of this technique is recommended for the timely diagnosis of bleeding in newborns with risk factors

Strategies against β-amyloid protein as therapeutics in Alzheimer's disease

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/12071

In-depth blood immune profiling of Good syndrome patients

[Introduction]: Good syndrome (GS) is a rare adult-onset immunodeficiency first described in 1954. It is characterized by the coexistence of a thymoma and hypogammaglobulinemia, associated with an increased susceptibility to infections and autoimmunity. The classification and management of GS has been long hampered by the lack of data about the underlying immune alterations, a controversy existing on whether it is a unique diagnostic entity vs. a subtype of Common Variable Immune Deficiency (CVID).[Methods]: Here, we used high-sensitive flow cytometry to investigate the distribution of up to 70 different immune cell populations in blood of GS patients (n=9) compared to age-matched CVID patients (n=55) and healthy donors (n=61).[Results]: All 9 GS patients displayed reduced B-cell counts -down to undetectable levels (<0.1 cells/μL) in 8/9 cases-, together with decreased numbers of total CD4+ T-cells, NK-cells, neutrophils, and basophils vs. age-matched healthy donors. In contrast, they showed expanded TCRγδ+ T-cells (p ≤ 0.05). Except for a deeper B-cell defect, the pattern of immune cell alteration in blood was similar in GS and (age-matched) CVID patients. In depth analysis of CD4+ T-cells revealed significantly decreased blood counts of naïve, central memory (CM) and transitional memory (TM) TCD4+ cells and their functional compartments of T follicular helper (TFH), regulatory T cells (Tregs), T helper (Th)2, Th17, Th22, Th1/Th17 and Th1/Th2 cells. In addition, GS patients also showed decreased NK-cell, neutrophil, basophil, classical monocyte and of both CD1c+ and CD141+ myeloid dendritic cell counts in blood, in parallel to an expansion of total and terminal effector TCRγδ+ T-cells. Interestingly, those GS patients who developed hypogammaglobulinemia several years after the thymoma presented with an immunological and clinical phenotype which more closely resembled a combined immune humoral and cellular defect, with poorer response to immunoglobulin replacement therapy, as compared to those in whom the thymoma and hypogammaglobulinemia were simultaneously detected.[Discussion]: Our findings provide a more accurate definition of the immune cell defects of GS patients and contribute to a better discrimination among GS patients between those with a pure B-cell defect vs. those suffering from a combined immunodeficiency with important consequences on the diagnosis and management of the disease.AT-V is supported by a grant from the Junta de Castilla y León (Fondo Social Europeo, Orden EDU/601/2020, Valladolid, Spain). This study has been founded by the Instituto de Salud Carlos III (ISCIII) through the project “PI20/01712” and co-founded by the European Union.Peer reviewe

Trajectories of alcohol consumption during life and the risk of developing breast cancer

Background: Whether there are lifetime points of greater sensitivity to the deleterious effects of alcohol intake on the breasts remains inconclusive. Objective: To compare the influence of distinctive trajectories of alcohol consumption throughout a woman’s life on development of breast cancer (BC). Methods: 1278 confirmed invasive BC cases and matched (by age and residence) controls from the Epi-GEICAM study (Spain) were used. The novel group-based trajectory modelling was used to identify different alcohol consumption trajectories throughout women’s lifetime. Results: Four alcohol trajectories were identified. The first comprised women (45%) with low alcohol consumption (<5 g/day) throughout their life. The second included those (33%) who gradually moved from a low alcohol consumption in adolescence to a moderate in adulthood (5 to <15 g/day), never having a high consumption; and oppositely, women in the third trajectory (16%) moved from moderate consumption in adolescence, to a lower consumption in adulthood. Women in the fourth (6%) moved from a moderate alcohol consumption in adolescence to the highest consumption in adulthood (=15 g/day), never having a low alcohol consumption. Comparing with the first trajectory, the fourth doubled BC risk (OR 2.19; 95% CI 1.27, 3.77), followed by the third (OR 1.44; 0.96, 2.16) and ultimately by the second trajectory (OR 1.17; 0.86, 1.58). The magnitude of BC risk was greater in postmenopausal women, especially in those with underweight or normal weight. When alcohol consumption was independently examined at each life stage, =15 g/day of alcohol consumption in adolescence was strongly associated with BC risk followed by consumption in adulthood. Conclusions: The greater the alcohol consumption accumulated throughout life, the greater the risk of BC, especially in postmenopausal women. Alcohol consumption during adolescence may particularly influence BC risk. © 2021, The Author(s)

Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population

Germ-line mutations in BRCA1 breast cancer susceptibility gene account for a large proportion of hereditary breast cancer families and show considerable ethnic and geographical variations. The contribution of BRCA1 mutations to hereditary breast cancer has not yet been thoroughly investigated in Middle Eastern and North African populations. In this study, 16 Tunisian high-risk breast cancer families were screened for germline mutations in the entire BRCA1 coding region and exon–intron boundaries using direct sequencing. Six families were found to carry BRCA1 mutations with a prevalence of 37.5%. Four different deleterious mutations were detected. Three truncating mutations were previously described: c.798_799delTT (916 delTT), c.3331_3334delCAAG (3450 delCAAG), c.5266dupC (5382 insC) and one splice site mutation which seems to be specific to the Tunisian population: c.212 + 2insG (IVS5 + 2insG). We also identified 15 variants of unknown clinical significance. The c.798_799delTT mutation occurred at an 18% frequency and was shared by three apparently unrelated families. Analyzing five microsatellite markers in and flanking the BRCA1 locus showed a common haplotype associated with this mutation. This suggests that the c.798_799delTT mutation is a Tunisian founder mutation. Our findings indicate that the Tunisian population has a spectrum of prevalent BRCA1 mutations, some of which appear as recurrent and founding mutations

The search for high altitude sites in South America for the SWGO detector

The Southern Wide-field Gamma-ray Observatory (SWGO) is a project for a new generation of extensive air shower front detectors, based primarily on the water Cherenkov technique, to be located in the Southern Hemisphere, where no other instrument of that kind is currently operating in the TeV gamma-ray energy range. The reference configuration of SWGO foresees an array of about 6, 000 water Cherenkov tanks deployed over a circle of 320 m diameter, about 80, 000 m2 area. In order to reach a sensitivity at energies around and below 1 TeV competitive with current and future detectors, SWGO will be placed at altitude above 4, 400 m a.s.l. Preliminary site searches have found several candidate sites in Argentina, Bolivia, Chile and Peru. The major challenge will be the water provision, considering that at least 105 m3 of water will be required. This poster will present the challenges and status of the SWGO site search in South America

The Southern Wide-field Gamma-ray Observatory reach for Primordial Black Hole evaporation

The Southern Wide-field Gamma-ray Observatory (SWGO) is a proposed ground-based gamma-ray detector that will be located in the Southern Hemisphere and is currently in its design phase. In this contribution, we will outline the prospects for Galactic science with this Observatory. Particular focus will be given to the detectability of extended sources, such as gamma-ray halos around pulsars; optimisation of the angular resolution to mitigate source confusion between known TeV sources; and studies of the energy resolution and sensitivity required to study the spectral features of PeVatrons at the highest energies. Such a facility will ideally complement contemporaneous observatories in studies of high energy astrophysical processes in our Galaxy

Benchmarking the Science for the Southern Wide-Field Gamma-ray Observatory (SWGO)

The Southern Wide-field Gamma-ray Observatory (SWGO) is the project to build a new extensive air shower particle detector for the observation of very-high-energy gamma-rays in South America. SWGO is currently planned for installation in the Southern Hemisphere, which grants it a unique science potential among ground-based gamma-ray detectors. It will complement the capabilities of CTA, working as a wide-field instrument for the monitoring of transient and variable phenomena, and will expand the sky coverage of Northern Hemisphere facilities like HAWC and LHAASO, thus granting access to the entire Galactic Plane and the Galactic Center. SWGO aims to achieve excellent sensitivity over a very large target energy range from about 100 GeV to the PeV, and improve on the performance of current sampling array instruments in all observational parameters, including energy and angular resolution, background rejection, and single-muon detection capabilities. The directives for the final observatory design will be given by a number of key science goals which are being defined over the course of the Project’s R&amp;D phase. In this contribution we will present the core science topics and target performance goals that serve as benchmarks to guide SWGO’s design configuration