Hipercolesterolemia familiar: artículo de revisión

La hipercolesterolemia familiar (HF) es una alteración de origen genético que clínicamente se puede manifestar desde el nacimiento y que se caracteriza por niveles plasmáticos anormalmente altos de colesterol LDL (cLDL) y por una elevada tasa de morbimortalidad cardiovascular prematura. Tiene dos formas de presentación: la HF heterocigótica (HFHe) y la HF homocigótica (HFHo); esta última más severa y de aparición clínica en los primeros años de vida. Históricamente, la prevalencia para la HFHe es de un caso en 500 personas y para la HFHo de un caso por cada millón de personas; sin embargo, los datos reales probablemente son superiores porque hay evidencia de que ambas condiciones están subdiagnosticadas. La terapia recomendada, además de los cambios en el estilo de vida, son las estatinas; sin embargo, con estos fármacos es difícil lograr en muchos casos reducciones aceptables del cLDL, por lo que se requiere asociar otras modalidades terapéuticas, algunas de ellas recientemente aprobadas. Dado que en Colombia no se ha publicado ningún documento de revisión sobre HF, la Sociedad Colombiana de Cardiología y Cirugía Cardiovascular convocó a diferentes especialidades de la medicina para elaborar un documento sobre el tema, que resumiera, de manera práctica y actualizada, aspectos clínicos, genéticos, diagnósticos y de tratamiento

Specific gene disruption in the major livestock pests cochliomyia hominivorax and lucilia cuprina using CRISPR/Cas9

Cochliomyia hominivorax and Lucilia cuprina are major pests of livestock. Their larvae infest warm-blooded vertebrates and feed on host’s tissues, resulting in severe industry losses. As they are serious pests, considerable effort has been made to develop genomic resources and functional tools aiming to improve their management and control. Here, we report a significant addition to the pool of genome manipulation tools through the establishment of efficient CRISPR/Cas9 protocols for the generation of directed and inheritable modifications in the genome of these flies. Site-directed mutations were introduced in the C. hominivorax and L. cuprina yellow genes (ChY and LcY) producing lightly pigmented adults. High rates of somatic mosaicism were induced when embryos were injected with Cas9 ribonucleoprotein complexes (RNPs) pre-assembled with guide RNAs (sgRNAs) at high concentrations. Adult flies carrying disrupted yellow alleles lacked normal pigmentation (brown body phenotype) and efficiently transmitted the mutated alleles to the subsequent generation, allowing the rapid creation of homozygous strains for reverse genetics of candidate loci. We next used our established CRISPR protocol to disrupt the C. hominivorax transformer gene (Chtra). Surviving females carrying mutations in the Chtra locus developed mosaic phenotypes of transformed ovipositors with characteristics of male genitalia while exhibiting abnormal reproductive tissues. The CRISPR protocol described here is a significant improvement on the existing toolkit of molecular methods in calliphorids. Our results also suggest that Cas9-based systems targeting Chtra and Lctra could be an effective means for controlling natural populations of these important pests9930453055FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2017/05432-7We thank Marta Vargas, Rosangela Rodrigues and Yeiny Mudarra for their technical and administrative support. To Pamela Philips and John Welch for helpful discussions during the development of this project. We also thank the COPEG directors, Francisco Pinilla and Vanessa Dellis, for supporting our study at the COPEG and USDA-ARS laboratories inside the biosecurity plant in Pacora, Panama. We are very grateful for the exhaustive laboratory assistance from Nicolas Mendoza, Domitildo Martinez, Rosaura Sanchez, Hermogenes Gonzalez and Amilcar Miranda, at the COPEG and USDA-ARS laboratories and Amy Berger and Scott Harrison at NCSU. We are also thankful to Ana Junqueira for her comments on the FAPESP grant proposal and for providing the draft assembly of the C. hominivorax genome used for sgRNA design against ChY gene, Matthew Bertone for photographs of L. cuprina strains and to the three anonymous referees for their comments and suggestions that improved the final version of our manuscript. This project was supported by a grant from the São Paulo Research Foundation (FAPESP: 2017/05432-7, given to D.F.P), USDA-ARS agreement no. 58-3094-7-015-FN, ARSCOPEG agreement no. 58-6205-4-002-F, and COPEG (grant to M.J.S). D.F.P was also supported by a STRI Short Term Fellowship (project award #4168). USDA is an equal opportunity employer and provide

Em busca de um horizonte : narrativas sobre educação, artes e resistência

"APRESENTAÇÃO - Os textos reunidos no livro Em busca de um Horizonte: narrativas sobre educação, arte e resistência foram inspirados nos debates realizados durante o evento VI Simpósio Internacional Horizontes Humanos, que aconteceu na Faculdade de Educação da Universidade de Brasília, em 2018. O livro está dividido em quatro partes: Resistências cotidianas para além da utopia, Demasiado humano: as diferentes linguagens artísticas e culturais, A educação como um horizonte, Educação ambiental e ancestralidade: para continuar caminhando. Apesar da divisão em seções (sempre arbitrária), as produções - bastante diversas nas temáticas, metodologias e referenciais teóricos adotados – compartilham um alinhamento ao adotar um posicionamento político em defesa da diversidade, dos direitos humanos, da ancestralidade, do meio ambiente, da educação com valores democráticos, dos saberes populares e das diferentes linguagens artísticas. Assim, o livro se apresenta como um convite à resistência em tempos atrozes. Os organizadores

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

International audienceSpinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signal-to-noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Search for intermediate mass black hole binaries in the first observing run of Advanced LIGO

International audienceDuring their first observational run, the two Advanced LIGO detectors attained an unprecedented sensitivity, resulting in the first direct detections of gravitational-wave signals produced by stellar-mass binary black hole systems. This paper reports on an all-sky search for gravitational waves (GWs) from merging intermediate mass black hole binaries (IMBHBs). The combined results from two independent search techniques were used in this study: the first employs a matched-filter algorithm that uses a bank of filters covering the GW signal parameter space, while the second is a generic search for GW transients (bursts). No GWs from IMBHBs were detected; therefore, we constrain the rate of several classes of IMBHB mergers. The most stringent limit is obtained for black holes of individual mass 100  M⊙, with spins aligned with the binary orbital angular momentum. For such systems, the merger rate is constrained to be less than 0.93  Gpc−3 yr−1 in comoving units at the 90% confidence level, an improvement of nearly 2 orders of magnitude over previous upper limits

First low-frequency Einstein@Home all-sky search for continuous gravitational waves in Advanced LIGO data

International audienceWe report results of a deep all-sky search for periodic gravitational waves from isolated neutron stars in data from the first Advanced LIGO observing run. This search investigates the low frequency range of Advanced LIGO data, between 20 and 100 Hz, much of which was not explored in initial LIGO. The search was made possible by the computing power provided by the volunteers of the Einstein@Home project. We find no significant signal candidate and set the most stringent upper limits to date on the amplitude of gravitational wave signals from the target population, corresponding to a sensitivity depth of 48.7  [1/Hz]. At the frequency of best strain sensitivity, near 100 Hz, we set 90% confidence upper limits of 1.8×10-25. At the low end of our frequency range, 20 Hz, we achieve upper limits of 3.9×10-24. At 55 Hz we can exclude sources with ellipticities greater than 10-5 within 100 pc of Earth with fiducial value of the principal moment of inertia of 1038  kg m2