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The growth hormone secretagogue receptor (GHSR), primarily known as the receptor for the hunger hormone ghrelin, potently controls food intake, yet the specific Ghsr-expressing cells mediating the orexigenic effects of this receptor remain incompletely characterized. Since Ghsr is expressed in gamma-aminobutyric acid (GABA)–producing neurons, we sought to investigate whether the selective expression of Ghsr in a subset of GABA neurons is sufficient to mediate GHSR's effects on feeding. First, we crossed mice that express a tamoxifen-dependent Cre recombinase in the subset of GABA neurons that express glutamic acid decarboxylase 2 (Gad2) enzyme (Gad2-CreER mice) with reporter mice, and found that ghrelin mainly targets a subset of Gad2-expressing neurons located in the hypothalamic arcuate nucleus (ARH) and that is predominantly segregated from Agouti-related protein (AgRP)–expressing neurons. Analysis of various single-cell RNA-sequencing datasets further corroborated that the primary subset of cells coexpressing Gad2 and Ghsr in the mouse brain are non-AgRP ARH neurons. Next, we crossed Gad2-CreER mice with reactivable GHSR-deficient mice to generate mice expressing Ghsr only in Gad2-expressing neurons (Gad2-GHSR mice). We found that ghrelin treatment induced the expression of the marker of transcriptional activation c-Fos in the ARH of Gad2-GHSR mice, yet failed to induce food intake. In contrast, food deprivation–induced refeeding was higher in Gad2-GHSR mice than in GHSR-deficient mice and similar to wild-type mice, suggesting that ghrelin-independent roles of GHSR in a subset of GABA neurons is sufficient for eliciting full compensatory hyperphagia in mice.

The tuberal hypothalamic ventral premamillary nucleus (VPM) described in mammals links olfactory and metabolic cues with mating behavior and is involved in the onset of puberty. We offer here descriptive and experimental evidence on a migratory phase in the development of this structure in mice at E12.5–E13.5. Its cells originate at the retromamillary area (RM) and then migrate tangentially rostralward, eschewing the mamillary body, and crossing the molecularly distinct perimamillary band, until they reach a definitive relatively superficial ventral tuberal location. Corroborating recent transcriptomic studies reporting a variety of adult glutamatergic cell types in the VPM, and different projections in the adult, we found that part of this population heterogeneity emerges already early in development, during tangential migration, in the form of differential gene expression properties of at least 2–3 mixed populations possibly derived from subtly different parts of the RM. These partly distribute differentially in the core and shell parts of the final VPM. Since there is a neighboring acroterminal source of Fgf8, and Fgfr2 is expressed at the early RM, we evaluated a possible influence of Fgf8 signal on VPM development using hypomorphic Fgf8neo/null embryos. These results suggested a trophic role of Fgf8 on RM and all cells migrating tangentially out of this area (VPM and the subthalamic nucleus), leading in hypomorphs to reduced cellularity after E15.5 without alteration of the migrations proper.

The interpeduncular nucleus (IPN) is a hindbrain structure formed by three main subdivisions, the prodromal (Pro) domain located at the isthmus (Ist), and the rostral and caudal interpeduncular domains (IPR, IPC) within rhombomere 1 (r1). Various cell populations can be detected in the IPN through the expression of the Nkx6.1, Otp, Otx2, Pax7, and/or Irx2 transcription factors. These cell populations follow independent dorsoventral tangential and radial migratory routes targeting the ventral paramedian region of Ist and r1. Here we set out to examine the influence of the Netrin-1/DCC pathway on these migrations, since it is known to regulate other processes of neuronal migration in the brain. To this end, we analyzed IPN development in late gestational wild-type and DCC–/– mice, using mainly in situ hybridization (ISH) to identify the cells expressing each of the aforementioned genes. We found that the migration of Nkx6.1+ and Irx2+ cells into the Pro domain was strongly disrupted by the loss of DCC, as occurred with the migration of Pax7+, Irx2+, and Otp+ cells that would normally form the IPR. In addition, there was mild impairment of the migration of the Pax7+ and Otx2+ cells that form the IPC. These results demonstrate that the Netrin-1/DCC signaling pathway is involved in the migration of most of the IPN populations, mainly affecting those of the Pro and IPR domains of this nucleus. There are psychiatric disorders that involve the medial habenula (mHb)-IPN system, so that this experimental model could provide a basis to study their neurodevelopmental etiology.

El Derecho civil común ha evolucionado a favor de una mayor autonomía del menor de edad, alineándose así con una tendencia consolidada en los ordenamientos civiles autonómicos; asimismo, se admite que los menores son titulares plenos de sus derechos fundamentales, reconocimientos que propician la preparación del tránsito a la edad adulta e independiente. En el presente trabajo se defiende la capacidad de obrar del menor de edad, graduable, o dinámica, en función de sus condiciones de madurez y a la vez limitada, en atención a las disposiciones dictadas para su protección, porque, no obstante el reconocimiento de esa esfera de válida actuación del menor que legalmente es considerado con suficiente madurez, nunca puede llegar a prevalecer sobre las normas generales tuitivas, que prevén la participación de sus representantes legales, o, en su caso, de la autoridad judicial o del defensor judicial. Además, en el estudio se propugna conceder mayor relevancia a la necesaria coordinación entre los órganos jurisdiccionales encargados de la defensa de los menores con los notarios, por estimar que la intervención de estos fedatarios públicos es imprescindible y así se dedica un apartado especial del trabajo al juicio de suficiencia notarial de la capacidad necesaria para otorgar el acto o contrato y, en su caso, juicio de suficiencia notarial de la representación. También, se analizará pormenorizadamente el tipo de ineficacia de los actos concluidos por los propios menores y de los celebrados por sus representantes legales sin la preceptiva autorización, cuestión que ha originado gran parte de los litigios en este ámbito. En fin, no se descuida la concesión de la importancia que en un estudio de esta índole corresponde al principio general del «interés superior del menor», que servirá para que cuando entre en juego deba imponerse sobre otros y frente a otras soluciones. Por lo demás, el trabajo se realiza al amparo de la últimas reformas de 2015 y de la legislación civil auto, The common civil law has evolved in favour of greater autonomy of the minor, aligning themselves with a consolidated trend on the autonomous civil systems; also is admitted that minors are fully entitled to their fundamental rights, recognition conducive to the preparation of transition to independent adult age. In this study it argues that the ability of the minor is adjustable and dynamic depending on their degree of maturity, in view of the provisions laid down for its protection, because, despite the recognition that defends sphere valid performance of the minor never prevail over the tuitiva general rules, which provide for the participation of their legal representatives, or, where appropriate, of the judicial authority or the judicial defensor. Likewise, I defend the necessary coordination between the courts and notaries. Are also analyzed the acts performed by minors and their legal representatives without authorization, an issue that has caused much litigation in this area. Finally, the granting of the importance in a study of this kind corresponds to the general principle of "superior interests of the minor” hermeneutical criterion that will serve so that when the interests of a minor comes into play be imposed on others. Moreover, work is performed under the latest reforms of 2015 and the autonomous civil law; the analysis of the issue is completed by the most representative scientific doctrine on the subject and illustrated with relevant decisions of the Constitutional Court and the Supreme Court and the doctrine of the Directorate General of Registries and Notaries

O turismo desempeña un papel cada vez máis importante na economía e, singularmente, as viaxes combinadas constitúen unha parte fundamental da actividade turística. Non cabe dúbida de que o sector dos servizos combinados se vería estimulado para alcanzar maior crecemento e produtividade adoptándose un mínimo de normas que supoñan unha serie de garantías efectivas para os consumidores e usuarios de viaxes combinadas. Dito doutro xeito, se o turismo pode ser o alicerce do progreso social e económico de calquera país, cómpre coñecer e familiarizarse con toda a normativa, a doutrina e as decisións xurisprudenciais que garanten unha axeitada protección dos consumidores e usuarios das viaxes, vacacións, circuítos combinados e do transporte aéreo. Por outra parte, coa chegada das vacacións proliferan nos medios de comunicación noticias sobre atrasos aéreos, con perdas de enlaces e de días de vacacións; extravío de equipaxes; denegacións de embarque; cancelación de voos… coas conseguintes escenas nos aeroportos dos lugares máis dispares. En efecto, os tipos de incidencia que poden ocorrer con ocasión dunha viaxe en avión son moitas e de diversa índole. Isto supuxo que, tanto no ámbito internacional, como no comunitario e interno, se adoptasen medidas tendentes a regular, por un lado, os dereitos dos pasaxeiros e, por outro, a responsabilidade dos transportistas aéreos. Partindo desas premisas, a unidade didáctica que se presenta ao alumnado como instrumento académico de traballo, ten a pretensión de afrontar as devanditas cuestións dende unha perspectiva estritamente xurídica.

As exercise while wearing protective clothing exacerbates body heat storage, compared to exercise in the heat, and as exercise alters immune responses, it appeared interesting to examine immune and stress responses while wearing protective clothing during moderate exercise. Methods: Eight subjects completed two bouts of exercise at 45% VO2 max in a thermo neutral environment: once while wearing shorts only (Control trial, CON) and again while wearing protective clothing (PRO). Venous blood samples were taken to analyze TNF-a mRNA by RT-PCR in LPS simulated blood, plasma catecholamines, and cortisol. Blood cell count was analyzed by flow cytometry. Rectal temperature (Tre) was monitored continuously., Published in Aviation, Space, and Environmental Medicine, v79 n6 p570-576, June 2008.