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

Histological evaluation of bone healing induced by demineralized bovine bone, in bicortical defects of rat mandibles, with or without calcic collagen membranes

O emprego do osso desmineralizado (OD), sobretudo de origem bovina, tem sido extensivamente avaliado em modelos experimentais; no entanto, há dúvidas se a quantidade de proteínas ósseas morfogenéticas (BMP) seria suficiente para induzir à reparação óssea. A associação com membranas, além de evitar o encapsulamento das partículas de OD, também poderia prevenir a dissolução precoce das poucas BMPs presentes no OD. O objetivo deste trabalho foi realizar uma avaliação histológica da reparação óssea induzida por OD em defeitos criados na mandíbula de ratos, e o efeito da utilização de membranas reabsorvíveis de colágeno impregnadas com sais de cálcio. O estudo envolveu 25 ratos Wistar, nos quais discos de OD foram utilizados no preenchimento de defeitos bicorticais na região de ângulo de mandíbula; no lado esquerdo, a face lingual e vestibular foi recoberta com membranas. Os animais foram divididos em grupos de cinco indivíduos cada e, então sacrificados depois de três, 10, 20, 30 e 60 dias pós-operatórios. A análise histológica revelou que nos primeiros 20 dias, houve intensa proliferação óssea nas duas extremidades, tanto na face vestibular quanto lingual, sendo provável também que a proliferação tenha ocorrido em toda margem do defeito circular. No entanto, aos 30 dias, houve uma inversão do quadro histopatológico: a resposta inflamatória até então moderada, cedeu lugar para um intenso infiltrado inflamatório envolvendo o OD, com ausência total da membrana, reduzindo a intensidade no grupo de 60 dias, que apresentou remanescentes de reação de corpo estranho em torno do OD, sem ocorrer preenchimento do defeito por osso neoformado. Pelos resultados observados, pode-se concluir que há presença de BMPs, responsável pela grande proliferação inicial, mas em quantidade insuficiente para conduzir à reparação total do defeito ósseo; a apresentação física em lâmina do OD, a partir do qual os discos foram preparados, parece ter dificultado a reabsorção da matriz óssea remanescente, provocando uma reação de corpo estranho. Por fim, a membrana de colágeno cálcica teve pouco efeito na proliferação óssea, gerando infiltrado inflamatório moderado ao seu redor.The use of demineralized bone (DB), in special from bovine source, has been evaluated extensively in experimental models; however, doubts exist if there is sufficient quantity of bone morphogenetic proteins (BMP) to induce the bone repairing. The combination of membranes avoids the encapsulating of DB particles and also it could prevent the early dissolution of the few BMPs present in the DB. The aim of this study was to carry out a histological evaluation of the bone repairing induced by DB on defects created in the rat mandibles, and the effect of using resorbable collagen membranes impregnated with calcium salts. The study involves 25 Wistar rats, in which DB discs were employed to fill bicortical defects in the region of mandibular angle; at the left side, membranes recovered the lingual and buccal side. The animals were divided into groups of five individuals each one and then killed after three, 10, 20, 30 and 60 postoperative days. Within first 20 days, the histological analysis revealed intense bone proliferation in the two bone ends, buccal as much lingual, and it is also probable the proliferation has occurred all around of the circular margin defect. However, from 30 days, there was an inversion in the histological findings: the inflammatory reaction until then moderate became na intense inflammatory infiltrate that was involving the DB, with total absence of the membrane, and then reducing the intensity at 60-days group, which presented remnants of foreign body reaction enveloping the DB, without new bone filling of the defect. From these results, it can conclude by the presence of BMPs, responsible by the great initial bone proliferation; the physical form of DB in sheets, of which discs were prepared, seemed to have prevented resorption of the remnant bone matrix and raised foreign body reaction. Finally, the calcium-collagen membrane had little effect in the bone proliferation, raising moderate inflammatory infiltrate around it

Histological evaluation of bone repair in through-in-through defects of mandibular angle of the spontaneously hypertensive rats and controls Wistar-Kyoto

A presença da hipertensão arterial pode comprometer a qualidade da reparação óssea, pois a doença é caracterizada por alterações fisiopatológicas vasculares e do metabolismo mineral. Com o objetivo de avaliar a neoformação e o remodelamento ósseo, este trabalho investigou o processo da reparação óssea em ratos geneticamente hipertensos (SHR) e de seus controles Wistar-Kyoto (WKY). Defeitos bicorticais de 2mm de diâmetro no lado direito e de 5mm no lado esquerdo, foram realizados com trefinas na região do ângulo de mandíbula. Os animais, divididos em grupos de cinco indivíduos cada, foram sacrificados após 2, 3, 5, 10, 15, 30, 60 e 90 dias pós-operatórios; as mandíbulas foram removidas, fixadas em formol a 10%, descalcificadas em ácido fórmico a 20%, incluídas em parafina e as secções histológicas, de 7m de espessura, coradas com hematoxilina e eosina. As imagens foram capturadas com aumento de 40x e a área do defeito mensurada pelo programa de histometria digital Image J versão 1.4. A análise estatística revelou que não houve diferença significante na comparação entre as linhagens WKY e SHR (p = 0,884), independente dos períodos ou lados avaliados; entre períodos, nas linhagens WKY (p = 0,101) e SHR (p = 0,479), independente dos lados avaliados; entre períodos por linhagens no lado direito; e entre linhagens por lados, esquerdo com p = 0,466 e direito com p = 0,689, independente do fator período. Houve diferença estatisticamente significante entre o lado esquerdo e o direito (p < 0,001), independente das linhagens e períodos avaliados; entre os lados por linhagens, WKY e SHR, ambas com p < 0,001; entre períodos por linhagens no lado esquerdo, no qual o grupo WKY de 15 dias apresentou área menor que o grupo WKY de 60 dias e o grupo SHR de 10 dias, e o grupo WKY de 60 dias apresentou área maior que o grupo SHR de 30 dias e SHR de 60 dias. Apesar das alterações encontradas no lado esquerdo, que podem ser atribuídas à remodelação funcional do osso da mandíbula, não houve diferenças significantes na reparação do defeito de 5mm e de 2mm entre ratos espontaneamente hipertensos e de seus controles Wistar-Kyoto.Arterial hypertension may affect the quality of bone repair because this disease is characterized by physiopathological vascular and bone metabolism changes. With the objective of evaluating the bone neoformation and remodeling, this study investigated the process of bone repair in spontaneously hypertensive rats (SHR) and their match controls Wistar-Kyoto (WKY). Through-in-through defects were done with trephine burs in the mandibular angle area, of 2mm diameter on the right side and 5mm diameter on the left side. The animals were divided into groups of five individuals each one and killed after 2, 3, 5, 10, 15, 30, 60 and 90 postoperative days; the mandibles were removed, fixed in 10% formalin solution, decalcified with 20% formic acid, and embedded in paraffin; the histological sections of 7m thickness were stained with hematoxylin and eosin. The images were captured with 40x magnification and the defect area was measured by the image processing program Image J version 1.4. The statistical analysis showed that there is no significant difference in the comparison of WKY and SHR strains (p = 0,884), independent of periods or sides; among periods, in the WKY strain (p = 0,101) and SHR one (p = 0,479), independent of sides; among periods by strains on the right side; and among strains by sides, left side with p = 0,466 and right side with p = 0,689, independent of periods. There is a significant difference between left and right side (p < 0,001), independent of strains and periods; between sides by strains, WKY and SHR, both with p < 0,001; among periods by strains on the left side, which WKY 15 days group showed an area smaller than WKY 60 days and SHR 10 days groups, and WKY 60 days group showed an area bigger than SHR 30 days and SHR 60 days groups. Despite the changes founded on the left side that could be attributed to the functional remodeling of the mandibular bone, there were no differences in the bone repair of 5mm and 2mm diameter defects between spontaneously hypertensive rats and their match controls Wistar-Kyoto

Bone healing of mandibular critical-size defects in spontaneously hypertensive rats

Few articles have shown changes in bone metabolism caused by hypertension. The objective of this study was to investigate the relationship between hypertension and bone healing. Circular critical-size defects 5 mm and 2 mm in diameter were created, respectively, on the left and right side of the mandible in 40 spontaneously hypertensive and 40 control Wistar-Kyoto rats. Five animals from each strain were killed 2, 3, 5, 10, 15, 30, 60 and 90 days after surgery. The macroscopic evaluation showed great mandibular angle deformation on the left side and non-healed defects on both sides and groups. Histological evaluation revealed similar bone healing on both sides, with initial necrosis in the central area, and fibrosis and angiogenesis within the first 5 days. From the 10th postoperative day on, the newly formed bone displayed progressive thickening until the 90th postoperative day, when the defect margins presented a compact bone structure. Furthermore, the statistical analysis of the histometric data did not reveal any significant hypertension effect on bone healing in the defect area. These results suggest that bone healing was not different between spontaneously hypertensive rats and control rats