Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evaluación de diferentes Niveles de Lípidos totales en la dieta sobre el Crecimiento y Supervivencia de los Juveniles de Corvina (Cilus Gilberti) en el Centro de Acuicultura Morro Sama del distrito de Sama las Yaras, provincia de Tacna, región Tacna.

TesisLa corvina (Cilus gilberti) es una especie con alto valor comercial en el mercado nacional y extranjero, con un potencial para su cultivo. Recientemente Fondepes a través de su Centro de Acuicultura Morro Sama inició la investigación del paquete tecnológico para su cultivo, por ello es de suma importancia investigar los requerimientos nutricionales y elaborar dietas específicasque actualmente no existe en el mercado peruano, para el desarrollo de esta especie. En este trabajo de investigación durante tres meses se evaluó diferentes niveles de lípidos totales en la dieta sobre el crecimiento y supervivencia de los juveniles de corvina (Cilus gilberti). Se formuló tres dietas para tres tratamientos (T1=10%, T2=15% y T3=20% de lípidos), donde en cada tratamiento se utilizó400 unidades de 39.47g y 13.78cmaproximadamente, con tres repeticiones (R1, R2 y R3). Se trabajó en total 3600 unidades distribuidas equitativamente en 9 tanques, de las cuales se tomó al azar de cada tratamiento el 10% de muestra para realizar biometrías quincenales. Los resultados finales en la evaluación de los índices de crecimiento (Tasa específica de crecimiento, incremento de peso e incremento de talla) mostraron que la mejor unidad experimental fue el tratamiento 3, seguido del tratamiento 2 y finalmente el tratamiento 1. El T3 (20% de lípidos) mostró la mayor tasa específica de crecimiento, siendo este 0.88%, seguido del T2 (15% de lípidos) con 0.83% y finalmente el T1 (10% de lípidos) con 0.82%. El mejor incremento de peso en la experimentación, lo obtuvo el T3 reportando 48.71g, a diferencia del T2 que mostró 44.7g y el T1 que tuvo un incremento de peso de 43.57g.El tratamiento con mayor incremento de talla fue el T3 con 4.59cm superando al T2 que obtuvo 4.53cm, mientras que el T1 con 4.31cm.En cuanto a la supervivencia los tres tratamientos reportaron un 99.75% de supervivencia. Estos resultados indican que de los juveniles de Cilus gilberti, requieren por lo menos un 20% de lípidos totales en la dieta, para su mayor crecimiento

Estilos de crianza y habilidades sociales en adolescentes de colegios del distrito de Cayma

TesisLa presente investigación tuvo como objetivo determinar la relación entre las variables estilos de crianza y habilidades sociales en adolescentes de colegios del distrito de Cayma. El estudio siguió el enfoque cuantitativo, es de tipo descriptivo-correlacional y de diseño no experimental transversal. Los datos se obtuvieron a través de la Escala de Estilos de Crianza de L. Steinberg adaptada por Merino (2004), y la Escala de Habilidades Sociales de E. Gismero adaptada por el Ps. César Ruiz Alva (Trujillo-2006). La muestra estuvo conformada por 186 adolescentes de ambos sexos de 4to y 5to grado de Educación Secundaria, con edades comprendidas entre los 14 a 16 años. Los resultados señalaron que no existe una relación significativa (χ2= 8.543; p= .382) entre los estilos de crianza y habilidades sociales en los adolescentes. Además, el estilo de crianza predominante encontrado en los adolescentes es el estilo de crianza autoritativo con un 39.8 %, y el nivel de habilidades sociales predominante en los adolescentes es el nivel bajo en un 51,1%

Partially redundant enhancers cooperatively maintain Mammalian Pomc expression above a critical functional threshold

Cell-specific expression of many genes is conveyed by multiple enhancers, with each individual enhancer controlling a particular expression domain. In contrast, multiple enhancers drive similar expression patterns of some genes involved in embryonic development, suggesting regulatory redundancy. Work in Drosophila has indicated that functionally overlapping enhancers canalize development by buffering gene expression against environmental and genetic disturbances. However, little is known about regulatory redundancy in vertebrates and in genes mainly expressed during adulthood. Here we study nPE1 and nPE2, two phylogenetically conserved mammalian enhancers that drive expression of the proopiomelanocortin gene (Pomc) to the same set of hypothalamic neurons. The simultaneous deletion of both enhancers abolished Pomc expression at all ages and induced a profound metabolic dysfunction including early-onset extreme obesity. Targeted inactivation of either nPE1 or nPE2 led to very low levels of Pomc expression during early embryonic development indicating that both enhancers function synergistically. In adult mice, however, Pomc expression is controlled additively by both enhancers, with nPE1 being responsible for ∼80% and nPE2 for ∼20% of Pomc transcription. Consequently, nPE1 knockout mice exhibit mild obesity whereas nPE2-deficient mice maintain a normal body weight. These results suggest that nPE2-driven Pomc expression is compensated by nPE1 at later stages of development, essentially rescuing the earlier phenotype of nPE2 deficiency. Together, these results reveal that cooperative interactions between the enhancers confer robustness of Pomc expression against gene regulatory disturbances and preclude deleterious metabolic phenotypes caused by Pomc deficiency in adulthood. Thus, our study demonstrates that enhancer redundancy can be used by genes that control adult physiology in mammals and underlines the potential significance of regulatory sequence mutations in common diseases.Fil: Lam, Daniel D.. University of Michigan. Medical School. Department of Molecular and Integrative Physiology; Estados UnidosFil: Silva Junqueira de Souza, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Nasif, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Yamashita, Miho. University of Michigan. Medical School. Department of Molecular and Integrative Physiology; Estados UnidosFil: López Leal, Rodrigo. Centro de Estudios Científicos; ChileFil: Otero Corchon, Veronica. University of Michigan. Medical School. Department of Molecular and Integrative Physiology; Estados UnidosFil: Meece, Kana. Columbia University. College of Physicians and Surgeons. Department of Medicine; Estados UnidosFil: Sampath, Harini. Oregon Health & Science University. Center for Research on Occupational and Environmental Toxicology; Estados UnidosFil: Mercer, Aaron J.. University of Michigan. Medical School. Department of Molecular and Integrative Physiology; Estados UnidosFil: Wardlaw, Sharon L.. Columbia University. College of Physicians and Surgeons. Department of Medicine; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. University of Michigan. Medical School. Department of Molecular and Integrative Physiology; Estados Unidos. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Low, Malcolm J.. University of Michigan. Medical School. Department of Molecular and Integrative Physiology; Estados Unido

<i>Pomc</i> expression in adult nPE mutant mice.

<p>(A) Representative <i>Pomc in situ</i> hybridization with a digoxigenin-labeled riboprobe in coronal sections through the hypothalamic arcuate nucleus of adult male mice (age 8 wk). 3V, third ventricle. Scale bar, 100 μm. (B) Histogram of integrated density of the cellular colorimetric <i>in situ</i> hybridization signal. Images from a minimum of 4 sections per biological replicate were thresholded for minimum object size and intensity, and automated cell counts, together with their individual integrated optical densities, were performed by the NIS Elements software (Nikon). (C-E) <i>Pomc</i> expression measured by qRT-PCR in hypothalamus (C), anterior pituitary (D), and brainstem (E) of adult male mice (age 8 wk). n = 8 per genotype. All quantitative data are presented as mean + 1 S.E.M. Genotype means were compared by two-tailed t-tests. * <i>P</i> < 0.05, *** <i>P</i> < 0.001 compared to +/+.</p

The <i>Pomc</i> neuronal enhancers nPE1 and nPE2 Share a common <i>cis</i>-regulatory code.

<p>(A) Evolutionary tree of placental mammalian lineages. The relative lengths of DNA sequences in kilobases (kb) separating nPE1 from nPE2 and nPE2 from exon 1 are illustrated by purple and green bars, respectively. (B) Alignment between an almost palindromic sequence carrying canonical homeodomain binding sites (HDBS) present in nPE1core and a remarkably similar sequence present within nPE2 region 1. (C) Scheme of nPE1core and regions 1 and 3 of nPE2 showing the relative positions of conserved HDBS. nPE1core carries a pair of inverted HDBS similar to another present in nPE2 region 1 (green boxes, full sequences depicted in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004935#pgen.1004935.g001" target="_blank">Fig. 1B</a>). Another pair of HDBS is present in region 3 of nPE2 (purple boxes). Canonical HDBS of the NKX subfamily are shown (blue boxes). Red letters indicate the mutated nucleotides. Grey boxes denote the critical enhancer regions determined previously in transgenic mice. (D) Two nearly identical transgenes were constructed to study the importance of the HDBS present in nPE1core. The control nPE1core<i>Pomc</i>-EGFP carries the wild-type (wt) enhancer sequence whereas nPE1core(mut)<i>Pomc</i>-EGFP (mut) carries six nucleotide substitutions covering all HDBS (red letters in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004935#pgen.1004935.g001" target="_blank">Fig. 1C</a>). Coronal brain sections showing EGFP expression in hypothalamic arcuate nucleus of nPE1core<i>Pomc</i>-EGFP (Left) but not in nPE1core(mut)<i>Pomc</i>-EGFP transgenic founder newborn mice (Right). (E) Two nearly identical transgenes were constructed to study the importance of the HDBS present in nPE2. The control transgene nPE2<i>Pomc</i>-EGFP carries the wild-type (wt) enhancer whereas nPE2(mut)<i>Pomc</i>-EGFP (mut) carries twelve nucleotide substitutions covering all HDBS (red letters in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004935#pgen.1004935.g001" target="_blank">Fig. 1C</a>). EGFP is expressed in the arcuate nucleus of founder transgenic mice carrying nPE2<i>Pomc</i>-EGFP (Left) but not nPE2(mut)<i>Pomc</i>-EGFP (Right). 3V, third ventricle.</p

Hypothalamic POMC-derived peptides in nPE mutant mice.

<p>(A) Representative ACTH immunohistochemistry in coronal hypothalamic sections. 3V, third ventricle. Scale bar, 200 μm. (B) Hypothalamic α-MSH and (C) β-endorphin content measured by radioimmunoassay. All data are from adult male mice (age 8 wk). n = 6–18. All quantitative data are presented as mean + 1 S.E.M. Genotype means were compared by two-tailed t-tests. *** <i>P</i> < 0.001 compared to +/+.</p

Behavioral and Neuroanatomical Abnormalities in Pleiotrophin Knockout Mice

Pleiotrophin (PTN) is an extracellular matrix-associated protein with neurotrophic and neuroprotective effects that is involved in a variety of neurodevelopmental processes. Data regarding the cognitive-behavioral and neuroanatomical phenotype of pleiotrophin knockout (KO) mice is limited. The purpose of this study was to more fully characterize this phenotype, with emphasis on the domains of learning and memory, cognitive-behavioral flexibility, exploratory behavior and anxiety, social behavior, and the neuronal and vascular microstructure of the lateral entorhinal cortex (EC). PTN KOs exhibited cognitive rigidity, heightened anxiety, behavioral reticence in novel contexts and novel social interactions suggestive of neophobia, and lamina-specific decreases in neuronal area and increases in neuronal density in the lateral EC. Initial learning of spatial and other associative tasks, as well as vascular density in the lateral EC, was normal in the KOs. These data suggest that the absence of PTN in vivo is associated with disruption of specific cognitive and affective processes, raising the possibility that further study of PTN KOs might have implications for the study of human disorders with similar features