A Genome-Wide Analysis of FRT-Like Sequences in the Human Genome

Efficient and precise genome manipulations can be achieved by the Flp/FRT system of site-specific DNA recombination. Applications of this system are limited, however, to cases when target sites for Flp recombinase, FRT sites, are pre-introduced into a genome locale of interest. To expand use of the Flp/FRT system in genome engineering, variants of Flp recombinase can be evolved to recognize pre-existing genomic sequences that resemble FRT and thus can serve as recombination sites. To understand the distribution and sequence properties of genomic FRT-like sites, we performed a genome-wide analysis of FRT-like sites in the human genome using the experimentally-derived parameters. Out of 642,151 identified FRT-like sequences, 581,157 sequences were unique and 12,452 sequences had at least one exact duplicate. Duplicated FRT-like sequences are located mostly within LINE1, but also within LTRs of endogenous retroviruses, Alu repeats and other repetitive DNA sequences. The unique FRT-like sequences were classified based on the number of matches to FRT within the first four proximal bases pairs of the Flp binding elements of FRT and the nature of mismatched base pairs in the same region. The data obtained will be useful for the emerging field of genome engineering

Fatores preditores de resultados no tratamento do transtorno obsessivo-compulsivo com as terapias comportamental e cognitivo-comportamental: uma revisão sistemática Outcome predictor factors in the treatment of obsessive-compulsive disorder using behavior and cognitive-behavior therapies: a systematic review

INTRODUÇÃO: As terapias comportamental e cognitivo-comportamental reduzem os sintomas do transtorno obsessivo-compulsivo em mais de 70% dos pacientes. Entretanto, cerca de 30% não obtêm nenhuma melhora. Conhecer fatores associados a esses desfechos poderia auxiliar numa melhor indicação do tratamento, incrementando sua eficácia. MÉTODO: Foram revisados trabalhos que investigaram fatores preditivos de resultados nos tratamentos do transtorno obsessivo-compulsivo, nas fontes PubMed, PsycINFO e LILACS. Termos utilizados na busca: predictive factors OR prediction AND obsessive-compulsive disorder AND exposure response prevention OR ritual prevention OR behav* therapy OR cognitive behav* therapy, resultando em 104 artigos. As referências dos artigos foram analisadas, possibilitando maior número de trabalhos revisados. Excluíram-se artigos que utilizaram apenas farmacoterapia e aqueles que não abordavam o tema, resultando em 29 artigos. DISCUSSÃO: As variáveis demográficas parecem exercer papel indireto, destacando-se sexo masculino e ausência de companheiro(a) como fatores de pior prognóstico. Maior gravidade e início precoce dos sintomas indicariam piores resultados. O transtorno esquizotípico comórbido é potencialmente negativo. Sintomas relacionados ao colecionismo e com conteúdo sexual/religioso indicam pior prognóstico. Maior nível de insight, motivação e colaboração com o tratamento são características favoráveis. Maior intensidade da melhora e a remissão completa são preditores para a não-recaída. CONCLUSÃO: A identificação de fatores preditores de resultados está longe de ser esclarecida. É possível que múltiplos fatores, cujas associações são complexas, atuem em conjunto. Os resultados podem depender de fatores não-específicos, ainda não abordados pelos estudos. A heterogeneidade do transtorno obsessivo-compulsivo e das pesquisas e o uso associado de medicamentos dificultam o estabelecimento de conclusões mais definidas.<br>INTRODUCTION: Behavioral and cognitive-behavioral therapies reduce symptoms of obsessive-compulsive disorder in over 70% of patients. However, about 30% do not show any improvement. The knowledge of factors associated with these outcomes may inform better treatment indications and improve treatment efficacy. METHOD: Review of studies that investigated predictors of obsessive-compulsive disorder treatment results in PubMed, PsychoINFO and LILACS databases. Terms used in the search were predictive factors OR prediction AND obsessive-compulsive disorder AND exposure response prevention OR ritual prevention OR behav* therapy OR cognitive behav* therapy." The search retrieved 104 studies. The references of retrieved studies were also analyzed to ensure that all relevant studies were included. Studies that used only pharmacotherapy or did not discuss the topic under analysis were excluded, and 29 studies met inclusion criteria. DISCUSSION: Demographic variables seem to play an indirect role in treatment results; male sex and not having partner are factors associated with poor prognosis. Greater severity and early symptom onset also indicate poor outcomes. Comorbid schizotypal disorder is potentially negative. Symptoms associated with hoarding and sexual/religious obsessions predict poor prognosis. Greater insight, motivation and collaboration with treatment are favorable characteristics. Greater improvement and complete remission of symptoms are predictors of no relapse. CONCLUSION: The identification of outcome predictors is still far from complete. Multiple factors may contribute to results, and their associations are complex. Results may depend on unspecific factors not yet investigated. Definite conclusions are difficult to reach because of the heterogeneity of obsessive-compulsive disorder and of the studies investigating it and the combined use of drugs

Reconstitution of the immune system after hematopoietic stem cell transplantation in humans

Hematopoietic stem cell transplantation is associated with a severe immune deficiency. As a result, the patient is at high risk of infections. Innate immunity, including epithelial barriers, monocytes, granulocytes, and NK cells recovers within weeks after transplantation. By contrast, adaptive immunity recovers much slower. B- and T-cell counts normalize during the first months after transplantation, but in particular, T-cell immunity may remain impaired for years. During the last decade, much of the underlying mechanisms have been identified. These insights may provide new therapies to accelerate recovery