Architect genes of the brain : a look at brain evolution through genoarchitecture

The brain of modern humans is the result of the evolution of a building plan (Bauplan) that began its design 500 hundred millions years ago. The process began in basal chordates (sea animals that were living immersed in the sand) and gave rise to the first building plan of the central nervous system; this was progressively modified and shared by all vertebrates. Behind the story are gene networks, key actors in the process to give identity to the different brain regions. This evolutionary scenario provides the basis for studies that seek to understand what is «conserved» and what is «new» between different vertebrates, as well as the underlying mechanisms involved in this process. This article explores the role of genoarchitectonic studies in this human scientific endeavor

Hypothalamic Pomc expression restricted to GABAergic neurons suppresses Npy overexpression and restores food intake in obese mice

Objective: Hypothalamic arcuate proopiomelanocortin (Arc-POMC) neurons are involved in different physiological processes such as the regulation of energy balance, glucose homeostasis, and stress-induced analgesia. Since these neurons heterogeneously express different biological markers and project to many hypothalamic and extrahypothalamic areas, it is proposed that Arc-POMC neurons could be classified into different subpopulations having diverse physiological roles. The aim of the present study was to characterize the contribution of the subpopulation of Arc-POMC neurons cosecreting gamma-aminobutyric acid (GABA) neurotransmitter in the control of energy balance. Methods: Arc-Pomc expression restricted to GABAergic-POMC neurons was achieved by crossing a reversible Pomc-deficient mouse line (arcPomc−) with a tamoxifen-inducible Gad2-CreER transgenic line. Pomc expression was rescued in the compound arcPomc−/−:Gad2-CreER female and male mice by tamoxifen treatment at postnatal days 25 (P25) or 60 (P60), and body weight, daily food intake, fasting glycemia, and fasting-induced hyperphagia were measured. POMC recovery was quantified by immunohistochemistry and semiquantitative RT-PCR. Neuropeptide Y (NPY) and GABAergic neurons were identified by in situ hybridization. Arc-POMC neurons projecting to the dorsomedial hypothalamic nucleus (DMH) were studied by stereotactic intracerebral injection of fluorescent retrobeads into the DMH. Results: Tamoxifen treatment of arcPomc−/−:Gad2-CreER mice at P60 resulted in Pomc expression in ∼23–25% of Arc-POMC neurons and ∼15–23% of Pomc mRNA levels, compared to Gad2-CreER control mice. Pomc rescue in GABAergic-POMC neurons at P60 normalized food intake, glycemia, and fasting-induced hyperphagia, while significantly reducing body weight. Energy balance was also improved in arcPomc−/−:Gad2-CreER mice treated with tamoxifen at P25. Distribution analysis of rescued POMC immunoreactive fibers revealed that the DMH is a major target site of GABAergic-POMC neurons. Further, the expression of the orexigenic neuropeptide Y (NPY) in the DMH was increased in arcPomc−/− obese mice but was completely restored after Pomc rescue in arcPomc−/−:Gad2-CreER mice. Finally, we found that ∼75% of Arc-POMC neurons projecting to the DMH are GABAergic. Conclusions: In the present study, we show that the expression of Pomc in the subpopulation of Arc-GABAergic-POMC neurons is sufficient to maintain normal food intake. In addition, we found that DMH-NPY expression is negatively correlated with Pomc expression in GABAergic-POMC neurons, suggesting that food intake may be regulated by an Arc-GABAergic-POMC → DMH-NPY pathway.Fil: Trotta, Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Bello, Estefanía Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Alsina, Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Tavella, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Ferrán, José Luis. Universidad de Murcia; EspañaFil: Rubinstein, Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bumaschny, Viviana Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Regionalized differentiation of crh, trh and ghrh peptidergic neurons in the mouse hypothalamus

According to the updated prosomeric model, the hypothalamus is subdivided rostrocaudally into terminal and peduncular parts, and dorsoventrally into alar, basal, and floor longitudinal zones. In this context, we examined the ontogeny of peptidergic cell populations expressing Crh, Trh, and Ghrh mRNAs in the mouse hypothalamus, comparing their distribution relative to the major progenitor domains characterized by molecular markers such as Otp, Sim1, Dlx5, Arx, Gsh1, and Nkx2.1. All three neuronal types originate mainly in the peduncular paraventricular domain and less importantly at the terminal paraventricular domain; both are characteristic alar Otp/ Sim1-positive areas. Trh and Ghrh cells appeared specifically at the ventral subdomain of the cited areas after E10.5. Additional Ghrh cells emerged separately at the tuberal arcuate area, characterized by Nkx2.1 expression. Crh-positive cells emerged instead in the central part of the peduncular paraventricular domain at E13.5 and remained there. In contrast, as development progresses (E13.5? E18.5) many alar Ghrh and Trh cells translocate into the alar subparaventricular area, and often also into underlying basal neighborhoods expressing Nkx2.1 and/or Dlx5, such as the tuberal and retrotuberal areas, becoming partly or totally depleted at the original birth sites. Our data correlate a topologic map of molecularly defined hypothalamic progenitor areas with three types of specific neurons, each with restricted spatial origins and differential migratory behavior during prenatal hypothalamic development. The study may be useful for detailed causal analysis of the respective differential specification mechanisms. The postulated migrations also contribute to our understanding of adult hypothalamic complexity

A New Algorithm for Multivariate Genome Wide Association Studies Based on Differential Evolution and Extreme Learning Machines

Genome-wide association studies (GWAS) are observational studies of a large set of genetic variants, whose aim is to find those that are linked to a certain trait or illness. Due to the multivariate nature of these kinds of studies, machine learning methodologies have been already applied in them, showing good performance. This work presents a new methodology for GWAS that makes use of extreme learning machines and differential evolution. The proposed methodology was tested with the help of the genetic information (370,750 single-nucleotide polymorphisms) of 2049 individuals, 1076 of whom suffer from colorectal cancer. The possible relationship of 10 different pathways with this illness was tested. The results achieved showed that the proposed methodology is suitable for detecting relevant pathways for the trait under analysis with a lower computational cost than other machine learning methodologies previously proposed

R-adaptación de la asignatura de métodos econométricos en economía y finanzas del Grado de Estadística Aplicada

El objetivo fundamental de este proyecto es el de adaptar todo el contenido práctico de la asignatura de Métodos Econométricos de Economía y Finanzas de cuarto curso del Grado de Estadística Aplicada de la Facultad de Estudios Estadísticos al software libre R (dejando de usar el software comercial Eviews). Para ello se han preparado una serie de materiales y recursos didácticos que se han puesto a disposición de los alumnos en el Campus Virtual. También hemos integrado en el curso el uso de la plataforma de autoaprendizaje de R "DataCamp for classroom", y se ha preparado diverso material específico de autoevaluación en el aula mediante las plataforma “Kahood”

Resultados del retrasplante cardiaco: subanálisis del Registro Español de Trasplante Cardiaco

[Abstract] Introduction and objectives: Heart retransplantation (ReHT) is controversial in the current era. The aim of this study was to describe and analyze the results of ReHT in Spain. Methods: We performed a retrospective cohort analysis from the Spanish Heart Transplant Registry from 1984 to 2018. Data were collected on donors, recipients, surgical procedure characteristics, immunosuppression, and survival. The main outcome was posttransplant all-cause mortality or need for ReHT. We studied differences in survival according to indication for ReHT, the time interval between transplants and era of ReHT. Results: A total of 7592 heart transplants (HT) and 173 (2.3%) ReHT were studied (median age, 52.0 and 55.0 years, respectively). Cardiac allograft vasculopathy was the most frequent indication for ReHT (42.2%) and 59 patients (80.8%) received ReHT >5 years after the initial transplant. Acute rejection and primary graft failure decreased as indications over the study period. Renal dysfunction, hypertension, need for mechanical ventilation or intra-aortic balloon pump and longer cold ischemia time were more frequent in ReHT. Median follow-up for ReHT was 5.8 years. ReHT had worse survival than HT (weighted HR, 1.43; 95%CI, 1.17-1.44; P<.001). The indication of acute rejection (HR, 2.49; 95%CI, 1.45-4.27; P<.001) was related to the worst outcome. ReHT beyond 5 years after initial HT portended similar results as primary HT (weighted HR, 1.14; 95%CI, 0.86-1.50; P<.001). Conclusions: ReHT was associated with higher mortality than HT, especially when indicated for acute rejection. ReHT beyond 5 years had a similar prognosis to primary HT.[Resumen] Introducción y objetivos. El retrasplante cardiaco (ReTC) representa un tema controvertido actualmente. Nuestro objetivo es describir y analizar los resultados del ReTC en España. Métodos. Análisis retrospectivo del Registro Español de Trasplante Cardiaco de 1984 a 2018. Se recogieron datos sobre donante, receptor, cirugía, inmunosupresión y supervivencia. La mortalidad por todas las causas o la necesidad de ReTC postrasplante fueron el objetivo principal. Se estudiaron diferencias en supervivencia según indicación, tiempo entre trasplantes y época del ReTC. Resultados. Se estudiaron en total 7.592 trasplantes cardiacos (TxC) y 173 (2,3%) ReTC (mediana de edad, 52,0 y 55,0 años respectivamente). La enfermedad vascular del injerto fue la indicación de ReTC más frecuente (42,2%) y 59 pacientes (80,8%) recibieron el ReTC más de 5 años después del trasplante inicial. El rechazo agudo y el fallo primario del injerto disminuyeron como indicaciones durante el periodo estudiado. La insuficiencia renal, la hipertensión, la necesidad de ventilación mecánica o balón intraaórtico y la mayor duración de la isquemia fría fueron más frecuentes en el ReTC. La mediana de seguimiento del ReTC fue 5,8 años. El ReTC tuvo peor supervivencia que el TxC (HR ponderado = 1,43; IC95%, 1,17-1,44; p < 0,001). El rechazo agudo (HR = 2,49; IC95%, 1,45-4,27; p < 0,001) se relacionó con el peor resultado. El ReTC más allá de 5 años del trasplante inicial presagia resultados similares a los del TxC primario (HR ponderado = 1,14; IC95%, 0,86-1,50; p < 0,001). Conclusiones. El ReTC se asoció con mayor mortalidad que el TxC, especialmente por rechazo agudo. El pronóstico del ReTC realizado más de 5 años después es similar al del TxC primario

Phase II randomized trial of capecitabine with bevacizumab and external beam radiation therapy as preoperative treatment for patients with resectable locally advanced rectal adenocarcinoma: long term results

Background: Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The “Tratamiento de Tumores Digestivos” group (TTD) previously reported in a randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response). We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years. Methods: Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks). Results: In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%). Conclusions: the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term

Submarine canyons and related features in the Alboran Sea: continental margins and major isolated reliefs

The analysis of a data set of multibeam bathymetry plus high resolution seismic and parametric profiles allow us to characterize the geomorphologic units on the Alboran Sea-floor as well as the evolution of morpho-sedimentary systems along the Pliocene and Quaternary, later than the main erosive Messinian event. Since the opening of the Gibraltar Straits, the sedimentary evolution of this basin has been controlled by the interchange of water masses between the Atlantic Ocean and the Mediterranean Sea. Basin physiography is also a consequence of the Pliocene-Quaternary compression which has progressively uplifted the sourrounding reliefs and deforms the interior and the margins of the basin. On this scenario, several submarine canyons and gullies have been developed in this basin which traverse especially the northern margin and the flanks of the Northern Alboran Ridge, without affecting the African margins. This fact must be related to the action of bottom contour currents which constitute the main morpho-sedimentary process. The influence of water masses distributed the sedimentary input carried by rivers and coming from the erosion of surrounding ranges. In the southern margin of this basin this influence is stronger and inhibits the development of transversal submarine canyons

Orogenias paleozoicas en los Andes de Argentina y Chile y en la Península Antártica

Congreso Geológico Argentino (20º. 2017. San Miguel de Tucumán, Argentina). Simposio de Téctonica pre-andinaDurante el Neoproterozoico y Paleozoico, los Andes de Argentina y Chile, y desde fines del Paleozoico también la Península Antártica, formaron parte del margen SO de Gondwana. Durante este tiempo se acrecionaron a dicho margen varios fragmentos continentales de tamaño y aloctonía variable; denominados de N a S: Antofalla, Chi-Cu, Patagonia Occidental y Antártida Occidental. Estos fragmentos formaban parte de placas litosféricas, en ocasiones divididas en subplacas. La colisión de dichos fragmentos continentales con Gondwana y una última subducción bajo dicho margen, dieron lugar a 6 orogenias de extensión temporal y espacial limitada.Instituto Geológico y Minero de España, EspañaDepartamento de Geología, Universidad de Oviedo, EspañaUniversidad de Río Negro, ArgentinaServicio Geológico y Minero Argentino, ArgentinaInstituto De Bio y Geociencias Del NOA, Consejo Nacional de Investigaciones Científicas y Técnicas, ArgentinaInstituto De Bio y Geociencias Del NOA, Universidad Nacional de Salta, ArgentinaDepartamento de Geodinámica, Universidad del País Vasco, EspañaFacultad de Geología, Universidad de Barcelona, EspañaDepartamento de Geología, Universidad de Chile, ChileUniversidad Andrés Bello, ChileUnidad de Tectónica, Consejo Nacional de Investigaciones Científicas y Técnicas, ArgentinaFacultad de Geología, Universidad de Buenos Aires, ArgentinaÁrea de Geología, Universidad Rey Juan Carlos, EspañaUniversidad de Salta, ArgentinaInstituto de Investigación en Paleobiología y Geología, Universidad de Río Negro, ArgentinaInstituto de Investigación en Paleobiología y Geología, Consejo Nacional de Investigaciones Científicas y Técnicas, ArgentinaCentro de Investigaciones Geológicas, Universidad de La Plata, ArgentinaUniversidad de San Juan, ArgentinaPeer reviewe