Glucocorticoid-cholinergic interactions in the dorsal striatum in memory consolidation of inhibitory avoidance training

Extensive evidence indicates that glucocorticoid hormones act in a variety of brain regions to enhance the consolidation of memory of emotionally motivated training experiences. We previously reported that corticosterone, the major glucocorticoid in the rat, administered into the dorsal striatum immediately after inhibitory avoidance training dose-dependently enhances memory consolidation of this training. There is also abundant evidence that the intrinsic cholinergic system of the dorsal striatum is importantly involved in memory consolidation of inhibitory avoidance training. However, it is presently unknown whether these two neuromodulatory systems interact within the dorsal striatum in the formation of long-term memory. To address this issue, we first investigated in male Wistar rats whether the muscarinic receptor agonist oxotremorine administered into the dorsal striatum immediately after inhibitory avoidance training enhances 48 h retention of the training. Subsequently, we examined whether an attenuation of glucocorticoid signaling by either a systemic administration of the corticosterone-synthesis inhibitor metyrapone or an intra-striatal infusion of the glucocorticoid receptor (GR) antagonist RU 38486 would block the memory enhancement induced by oxotremorine. Our findings indicate that oxotremorine dose-dependently enhanced 48 h retention latencies, but that the administration of either metyrapone or RU 38486 prevented the memory-enhancing effect of oxotremorine. In the last experiment, corticosterone was infused into the dorsal striatum together with the muscarinic receptor antagonist scopolamine immediately after inhibitory avoidance training. Scopolamine blocked the enhancing effect of corticosterone on 48 h retention performance. These findings indicate that there are mutual interactions between glucocorticoids and the striatal cholinergic system in enhancing the consolidation of memory of inhibitory avoidance training

Resistencia de la soya [Glycine max. (L.) Merr.] al estrés por calor en estado de plántula

El objetivo del presente estudio fue conocer la respuesta de 21 genotipos de soya a altas temperaturas en estado de plántula. Se evaluaron cuatro niveles de temperatura: θ1 = 50 ± 1 °C, θ2 = 54 ± 1 °C, θ3 = 58 ± 1 °C y θ4 = 62 ± 1 °C, los cuales fueron acumulativos. Para θ1 se calificó el grado de cierre de las hojas (GCH) y para el resto de los tratamientos el grado de marchitez (GM). Posterior al último tratamiento se aplicó un riego y se observó el grado de recuperación (GR) de las plántulas estresadas. Se utilizó un diseño completamente al azar desbalanceado para GCH y GR; en GM fue completamente al azar en arreglo factorial 21 x 3. Se observaron diferencias entre genotipos en GCH: seis fueron insensibles, mientras que H98-1240 cerró sus hojas por completo. Considerando los efectos genéricos, θ4 provocó el mayor GM y entre genotipos, 15 presentaron un bajo GM, destacando H02-1337 como el menos marchito; H98-1240 resultó el más afectado. Según los efectos específicos, H02-1337 no sufrió cambios al pasar de θ2 a θ3, considerándose el más resistente en este nivel; mientras que H02-2248 aumentó en menor proporción el GM entre θ3 y θ4. El GR posterior al riego indicó que los genotipos con mayor GM tardaron más en recuperarse, incluso algunos no lo hicieron y viceversa; sin embargo dicha variabilidad se debió probablemente a efectos aleatorios

Transverse Cervicothoracic Stabbing: Multidisciplinary Management of a Surgical Emergency

Tracheobronchial injuries are closely related to orotracheal intubations and chest traumas. Stabbing injuries are very rare and often life threatening because of the damage to vital structures such as the respiratory tract and large arterial or venous vessels. Early diagnosis and treatment of penetrating neck injuries increase survival rates. We report a case of the tracheobronchial section with a penetrating stabbing wound on the left laterocervical area associated with contralateral pneumothorax, requiring urgent surgical pulmonary repair, tracheal suture, and tracheotomy. Prompt action with a multidisciplinary approach resulted in a favorable outcome

Safety, activity, and molecular heterogeneity following neoadjuvant non-pegylated liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (Opti-HER HEART): an open-label, single-group, multicenter, phase 2 trial

Antecedents: L'assaig Opti-HER HEART tenia com a objectiu optimitzar l'activitat i minimitzar el risc cardíac combinant trastuzumab, pertuzumab i paclitaxel amb doxorubicina liposomal no pegilada en el tractament del càncer de mama precoç HER2-positiu. Mètodes: Els pacients amb càncer de mama HER2 positiu en fase II-IIIB van rebre trastuzumab neoadjuvant, pertuzumab, paclitaxel i una doxorubicina liposomal no pegilada cada tres setmanes durant sis cicles. El principal criteri final va ser la seguretat cardíaca durant la teràpia neoadjuvant. Es van avaluar els esdeveniments cardíacs tipus A (insuficiència cardíaca congestiva simptomàtica) i B (reducció asimptomàtica de la fracció d'ejecció del ventricle esquerre). Els criteris finals secundaris van incloure l'avaluació de la taxa de resposta patològica completa (pCR) i la taxa de resposta global, entre d'altres. Com a anàlisi exploratòria ad-hoc , es va mesurar l'expressió de 55 gens relacionats amb el càncer de mama, inclosos els gens PAM50 , en 58 mostres de tumors basals i 60 mostres quirúrgiques. Resultats: Es van reclutar vuitanta-tres pacients. La incidència d'esdeveniments cardíacs durant el tractament neoadjuvant va ser del 2,4%. No es va observar cap esdeveniment cardíac de tipus A. La taxa global de pCR va ser del 56,6% (interval de confiança (IC) del 95%: 45,3-67,5%). El subtipus enriquit amb HER2, que representava el 52,0% de totes les mostres basals, es va associar amb una taxa de pCR més alta en comparació amb els tumors no enriquits amb HER2 (83,3% vs. 46,3%; odds ratio 5,76; 95% CI 1,71-19,42). L'associació de subtipus amb pCR va ser independent de les variables clínicopatològiques conegudes, inclòs l'estat del receptor hormonal. En comparació amb les mostres basals, els exemplars quirúrgics van mostrar una significativa regulació descendent dels nivells relacionats amb la proliferació ( MKI67 i CCNB1 ) i ERBB2 , i una regulació ascendent significativa dels relacionats amb la llum (ESR1 i PGR ) i gens immunes ( CD8A ). Conclusions: La combinació de doble bloqueig HER2 amb trastuzumab i pertuzumab amb paclitaxel i doxorubicina liposomal no pegilada s'associa amb una baixa taxa d'esdeveniments cardíacs. El subtipus enriquit amb HER2 s'associa a una alta taxa de pCR

Control central y sintomatología psicótica

En ocasiones, nuestro organismo interpreta determinadas formas de lenguaje interno como voces procedentes del exterior. El presente trabajo tiene el objetivo de averiguar si aquellos pacientes que presentan alucinaciones auditivas difieren de otros grupos clínicos en las funciones de discriminación/atribución de la fuente estimular . Los sujetos fueron clasificados según su sintomatología (Brief Psychiatric Rating Scale). Como variable criterio se contabilizaron los errores en una prueba de control central construida a tal efecto. De este estudio, únicamente se deducen diferencias en control central bajo aquellas condiciones de generación verbal en que el sujeto ve restringida su producción. Situación ésta en la que los sujetos con alucinaciones auditivas tienden a atribuir falsamente a agentes externos sus propias producciones. Posteriores investigaciones deberían explorar con más precisión las funciones verbales y motoras (voluntariedad/ involuntariedad de la acción) que definen los procesos de control

At the beginnings of the funerary Megalithism in Iberia at Campo de Hockey necropolis

[EN] The excavations undertaken at the Campo de Hockey site in 2008 led to the identification of a major Neolithic necropolis in the former Island of San Fernando (Bay of Cadiz). This work presents the results of the latest studies, which indicate that the site stands as one of the oldest megalithic necropolises in the Iberian Peninsula. The main aim of this work is to present with precision the chronology of this necropolis through a Bayesian statistical model that confirms that the necropolis was in use from c. 4300 to 3800 cal BC. The presence of prestige grave goods in the earliest and most monumental graves suggest that the Megalithism phenomenon emerged in relation to maritime routes linked to the distribution of exotic products. We also aim to examine funerary practices in these early megalithic communities, and especially their way of life and the social reproduction system. As such, in addition to the chronological information and the Bayesian statistics, we provide the results of a comprehensive interdisciplinary study, including anthropological, archaeometric and genetic data.We wish to express our gratitude to Antonio Saez Espligares (Historical Museum of San Fernando) and Lourdes Lorenzo (Figlina, s.l.) for their support during the archaeological excavation. This research was conducted in the framework of the following research projects: "Analysis of prehistoric societies from the Middle Palaeolithic to the Late Neolithic at both sides of the Strait of Gibraltar: relations and contacts", funded by the State Research Agency (SRA) and the European Regional Development Fund (ERDF). Ref.: HAR2017-87324-P. (2018-2021). "Analisis interdisciplinar para el conocimiento del poblamiento humano de la Bahia de Cadiz durante la Prehistoria Reciente (VI-II milenios a.n.e.)", funded by 2014-2020 ERDF Operational Programme and the Department of Economy, Knowledge, Business and University of the Regional Government of Andalusia. Ref.: FEDER-UCA18-106917 (2020-2023). "Analisis de los isotopos de oxigeno en conchas y de los isotopos estables de oxigeno y carbono en huesos humanos en el poblado neolitico insular de Campo de Hockey (San Fernando, Cadiz)", authorised and funded by CEIMAR. Ref.: CEIJ-015 (2018-2019). Eduardo Molina Piernas acknowledges co-funding from European Social Fund (D1113102E3) and Junta de Andalucia

Dynamics of the Multiplicity of Cellular Infection in a Plant Virus

Recombination, complementation and competition profoundly influence virus evolution and epidemiology. Since viruses are intracellular parasites, the basic parameter determining the potential for such interactions is the multiplicity of cellular infection (cellular MOI), i.e. the number of viral genome units that effectively infect a cell. The cellular MOI values that prevail in host organisms have rarely been investigated, and whether they remain constant or change widely during host invasion is totally unknown. Here, we fill this experimental gap by presenting the first detailed analysis of the dynamics of the cellular MOI during colonization of a host plant by a virus. Our results reveal ample variations between different leaf levels during the course of infection, with values starting close to 2 and increasing up to 13 before decreasing to initial levels in the latest infection stages. By revealing wide dynamic changes throughout a single infection, we here illustrate the existence of complex scenarios where the opportunity for recombination, complementation and competition among viral genomes changes greatly at different infection phases and at different locations within a multi-cellular host

Phosphofructo-1-Kinase Deficiency Leads to a Severe Cardiac and Hematological Disorder in Addition to Skeletal Muscle Glycogenosis

Mutations in the gene for muscle phosphofructo-1-kinase (PFKM), a key regulatory enzyme of glycolysis, cause Type VII glycogen storage disease (GSDVII). Clinical manifestations of the disease span from the severe infantile form, leading to death during childhood, to the classical form, which presents mainly with exercise intolerance. PFKM deficiency is considered as a skeletal muscle glycogenosis, but the relative contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. To elucidate this issue, we have generated mice deficient for PFKM (Pfkm−/−). Here, we show that Pfkm−/− mice had high lethality around weaning and reduced lifespan, because of the metabolic alterations. In skeletal muscle, including respiratory muscles, the lack of PFK activity blocked glycolysis and resulted in considerable glycogen storage and low ATP content. Although erythrocytes of Pfkm−/− mice preserved 50% of PFK activity, they showed strong reduction of 2,3-biphosphoglycerate concentrations and hemolysis, which was associated with compensatory reticulocytosis and splenomegaly. As a consequence of these haematological alterations, and of reduced PFK activity in the heart, Pfkm−/− mice developed cardiac hypertrophy with age. Taken together, these alterations resulted in muscle hypoxia and hypervascularization, impaired oxidative metabolism, fiber necrosis, and exercise intolerance. These results indicate that, in GSDVII, marked alterations in muscle bioenergetics and erythrocyte metabolism interact to produce a complex systemic disorder. Therefore, GSDVII is not simply a muscle glycogenosis, and Pfkm−/− mice constitute a unique model of GSDVII which may be useful for the design and assessment of new therapies

Ocupaciones de la Cueva de Ardales y Sima de las Palomas de Teba por sociedades neandertales

Un equipo interdisciplinar internacional viene realizando nuevas investigaciones en Cueva de Ardales (Ardales, Málaga) y en Sima de las Palomas (Teba, Málaga), enmarcadas en un Proyecto General de Investigación autorizado por la Junta de Andalucía. Presentamos un avance de los datos obtenidos en ambas cavidades en relación a la ocupación vinculada a sociedades neandertales con tecnología de tipo Paleolítico Medio.An international interdisciplinary team is carrying out new research in Cueva de Ardales (Ardales, Málaga) and Sima de las Palomas (Teba, Málaga), framed in a General Research Project authorized by the Junta de Andalucía. We present here preliminary data of Neanderthal occupations and related Middle Palaeolithic technology from both cavities.Universidad Pablo de Olavid