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Left-right asymmetries in the zebrafish habenular nuclei are dependent upon the formation of the parapineal, a unilateral group of neurons that arise from the medially positioned pineal complex. In this study, we show that both the left and right habenula are competent to adopt left-type molecular character and efferent connectivity upon the presence of only a few parapineal cells. This ability to impart left-sided character is lost in parapineal cells lacking Sox1a function, despite the normal specification of the parapineal itself. Precisely timed laser ablation experiments demonstrate that the parapineal influences neurogenesis in the left habenula at early developmental stages as well as neurotransmitter phenotype and efferent connectivity during subsequent stages of habenular differentiation. These results reveal a tight coordination between the formation of the unilateral parapineal nucleus and emergence of asymmetric habenulae, ensuring that appropriate lateralised character is propagated within left and right-sided circuitry.

Osteomas are benign osteogenic tumors, and there are still no guidelines for their treatment in pediatric age. The guidelines taken into consideration are usually those of adults; however, a growing skull requires another type of care. Decisions must be made on a case‐by‐case basis.

Objective. To understand the phenomenon experienced bynursing students in their academic practices in view of deathand dying. Methodology. This was a qualitative study, based onMartin Heidegger’s existential phenomenology, undertaken at apublic University in Alagoas, Brazil, between August and October2013. Seven senior students of nursing were interviewed.Results. The phenomenological analysis yielded the followingexistential themes: Facing death and dying in academic practice;Acknowledging impotence in the face of death; Glimpsing thepossibility of solicitude; Interacting with the family in view of theloss; Experiencing spirituality in the face of dying. Conclusion.It is deduced that, during the academic education, the themeinvolving death and dying has been addressed insufficiently,without precisely attending to all the demands of the nursingstudents during care in the dying process.Key words: students; nursing; death; attitude towards death. Objetivo. Compreender o fenômeno vivenciado pelos alunos de enfermagem em suas práticas acadêmicas frente a morte e o morrer. Metodologia. Trata-se de uma pesquisa qualitativa, embasada na fenomenologia existencial de Martin Heidegger, realizada numa Universidade pública de Alagoas, Brasil, entre os meses de agosto e outubro de 2013, foram entrevistados sete alunos do último ano do curso de enfermagem. Resultados. Da análise fenomenológica, emergiram as seguintes temáticas existenciais: Enfrentando a morte e o processo de morrer nas práticas acadêmicas; Reconhecendo a impotência diante da morte; Vislumbrando a possibilidade da solicitude; Convivendo com a família diante da perda; Vivenciando a espiritualidade diante do morrer. Conclusão. Deduz-se que durante as práticas acadêmicas a temática que envolve a morte e o morrer tem sido trabalhado de forma deficiente, não atendendo com precisão todas as demandas dos alunos de enfermagem durante a assistência no processo de morrer Objetivo. Comprender el fenómeno experimentado por los estudiantes de enfermería en sus prácticas académicas hacia la muerte y el morir. Metodología. Se realizó un estudio cualitativo, basado en la fenomenología existencial de Martin Heidegger, en una Universidad pública en Alagoas, Brasil, entre agosto y octubre de 2013. Se entrevistaron 7 estudiantes del último año de enfermería. Resultados. El análisis fenomenológico arrojó los siguientes temas existenciales: Frente a la muerte y el morir en la práctica académica, reconociendo la impotencia en el rostro de la muerte, vislumbrando la posibilidad de la solicitud, la interacción con la familia por la pérdida, y experimentar la espiritualidad antes de morir. Conclusión. De lo anterior se desprende que, durante las prácticas académicas, el tema que involucra la muerte y el morir se ha estado trabajado en forma inadecuada, pues no cumple con precisión todas las demandas de los estudiantes de enfermería durante la atención en el proceso de morir

Previous studies have shown that Wnt signals, relayed through β‐catenin and T‐cell factor 4 (Tcf4), are essential for the induction and maintenance of crypts in mice. We have now generated a tcf4 ( tcf7l2 ) mutant zebrafish by reverse genetics. We first observe a phenotypic defect at 4 weeks post‐fertilization (wpf), leading to death at about 6 wpf. The phenotype comprises a loss of proliferation at the base of the intestinal folds of the middle and distal parts of the intestine. The proximal intestine represents an independent compartment, as it expresses sox2 in the epithelium and barx1 in the surrounding mesenchyme, which are early stomach markers in higher vertebrates. Zebrafish are functionally stomach‐less, but the proximal intestine might share its ontogeny with the mammalian stomach. Rare adult homozygous tcf4 −/− ‘escapers’ show proliferation defects in the gut epithelium, but have no other obvious abnormalities. This study underscores the involvement of Tcf4 in maintaining proliferative self‐renewal in the intestine throughout life.

Highly conserved recursive splice sites are identified in vertebrates, particularly within long genes encoding proteins that are involved in neuronal development; analysis of the splicing mechanism reveals that such recursive splicing sites can be used to dictate different mRNA isoforms. Recursive splicing in insects and vertebrates The mechanisms by which the very longest genes in eukaryotic genomes are accurately processed are poorly understood. It was thought that intron removal generally involved a single excisive step. Later studies showed that, in flies, some introns contain internal splice sites that cause 'recursive splicing', in which single introns are removed 'bit-by-bit' in several sequential splicing reactions. Brenton Graveley and coworkers demonstrate that the scope of this regulatory mechanism is much more extensive in flies than had been appreciated. They identify nearly 200 zero-nucleotide exons in Drosophila that are the products of recursive splicing. Jernej Ule and colleagues identify recursive splicing sites in vertebrates, particularly within long genes encoding proteins that are involved in neuronal development. Analysis of the mechanism of their splicing reveals that such splicing sites can be used to dictate different mRNA isoforms. It is generally believed that splicing removes introns as single units from precursor messenger RNA transcripts. However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing 1 , 2 . The extent to which recursive splicing occurs in other species and its mechanistic basis have not been examined. Here we identify highly conserved RS-sites in genes expressed in the mammalian brain that encode proteins functioning in neuronal development. Moreover, the RS-sites are found in some of the longest introns across vertebrates. We find that vertebrate recursive splicing requires initial definition of an ‘RS-exon’ that follows the RS-site. The RS-exon is then excluded from the dominant mRNA isoform owing to competition with a reconstituted 5′ splice site formed at the RS-site after the first splicing step. Conversely, the RS-exon is included when preceded by cryptic promoters or exons that fail to reconstitute an efficient 5′ splice site. Most RS-exons contain a premature stop codon such that their inclusion can decrease mRNA stability. Thus, by establishing a binary splicing switch, RS-sites demarcate different mRNA isoforms emerging from long genes by coupling cryptic elements with inclusion of RS-exons.

RNA modifications play a fundamental role in cellular function. Pseudouridylation, the most abundant RNA modification, is catalyzed by the H/ACA small ribonucleoprotein (snoRNP) complex that shares four core proteins, dyskerin (DKC1), NOP10, NHP2, and GAR1. Mutations in DKC1, NOP10, or NHP2 cause dyskeratosis congenita (DC), a disorder characterized by telomere attrition. Here, we report a phenotype comprising nephrotic syndrome, cataracts, sensorineural deafness, enterocolitis, and early lethality in two pedigrees: males with DKC1 p.Glu206Lys and two children with homozygous NOP10 p.Thr16Met. Females with heterozygous DKC1 p.Glu206Lys developed cataracts and sensorineural deafness, but nephrotic syndrome in only one case of skewed X-inactivation. We found telomere attrition in both pedigrees, but no mucocutaneous abnormalities suggestive of DC. Both mutations fall at the dyskerin–NOP10 binding interface in a region distinct from those implicated in DC, impair the dyskerin–NOP10 interaction, and disrupt the catalytic pseudouridylation site. Accordingly, we found reduced pseudouridine levels in the ribosomal RNA (rRNA) of the patients. Zebrafish dkc1 mutants recapitulate the human phenotype and show reduced 18S pseudouridylation, ribosomal dysregulation, and a cell-cycle defect in the absence of telomere attrition. We therefore propose that this human disorder is the consequence of defective snoRNP pseudouridylation and ribosomal dysfunction.

The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-β, the toxic driver of Alzheimer’s disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges.

  La resiliencia es un término que proviene de la física, muy discutido en varias áreas, antes de este marco, el objetivo de este estudio fue analizar la resiliencia de las mujeres mayores, participantes en las actividades en el Centro de Convivencia. Estudio exploratorio, descriptivo, transversal, con abordaje cuantitativo, caracterizado por 117 mujeres con una edad media de 70 a 80 años, viudas, católicas, jubiladas, de 1-5 años de educación escolar, con ingreso familiar de 2-3 salarios mínimos, practican actividad  física, composición familiar de 1-2 miembros en la familia, con percepción positiva para el cuidado de la salud física y mental, toman de 1-2 tipos de medicamentos al día, presentan 1-2 comorbilidades, relatan actividad sexual 1 - 4 veces al mes y con nivel de resiliencia elevado