RESUMO
There is a growing research interest in quantifying blood flow distribution for the entire cerebral circulation to sharpen diagnosis and improve treatment options for cerebrovascular disease of individual patients. We present a methodology to reconstruct subject-specific cerebral blood flow patterns in accordance with physiological and fluid mechanical principles and optimally informed by in vivo neuroimage data of cerebrovascular anatomy and arterial blood flow rates. We propose an inverse problem to infer blood flow distribution across the visible portion of the arterial network that best matches subject-specific anatomy and a given set of volumetric flow measurements. The optimization technique also mitigates the effect of uncertainties by reconciling incomplete flow data and by dissipating unavoidable acquisition errors associated with medical imaging data.
Assuntos
Artérias Cerebrais/fisiologia , Circulação Cerebrovascular/fisiologia , Artérias Cerebrais/anatomia & histologia , Círculo Arterial do Cérebro/fisiologia , Humanos , Pressão , Fluxo Sanguíneo Regional/fisiologia , Fatores de TempoRESUMO
BACKGROUND: Two stages of genome activation have been identified in the mouse embryo. Specifically, minor transcriptional activation is evident at the one-cell stage and a second major episode of activation occurs at the two-cell stage. Nuclear translocation of RNA polymerase II and phosphorylation of the C-terminal domain (CTD) of the largest enzyme subunit are major determinants of embryonic genome activation. P-TEFb, the Pol II CTD kinase, regulates transcriptional elongation via phosphorylation of the serine 2 residues of the CTD. RESULTS: Here, we show that the CDK9 and cyclin T1 subunits of P-TEFb are present in mouse oocytes and preimplantation embryos. Both proteins translocate to pronuclei at the late one-cell stage and are predominantly localized in nuclei at the two-cell stage. We additionally examine the effects of the CDK9-specific inhibitor, flavopiridol, on mouse preimplantation development. Our data show that treatment with the drug results in mislocalization of CDK9, cyclin T1, and phosphorylated Pol II, as well as developmental arrest at the two-cell stage. CONCLUSIONS: A change in CDK9 localization from the cytoplasm to the pronucleus occurs at the time of minor embryonic genome activation, and CDK9 accumulation at the two-cell stage is evident, concomitant with major transcriptional activation of the embryonic genome. Moreover, CDK9 inhibition triggers a developmental block at the two-cell stage. Our findings clearly indicate that CDK9 is essential for embryonic genome activation in the mouse.
Assuntos
Blastocisto/fisiologia , Ciclina T/metabolismo , Quinase 9 Dependente de Ciclina/metabolismo , Oócitos/fisiologia , Fator B de Elongação Transcricional Positiva/metabolismo , Subunidades Proteicas/metabolismo , Ativação Transcricional , Animais , Blastocisto/citologia , Blastocisto/efeitos dos fármacos , Ciclina T/química , Ciclina T/genética , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Quinase 9 Dependente de Ciclina/química , Quinase 9 Dependente de Ciclina/genética , Feminino , Flavonoides/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Isoenzimas/genética , Isoenzimas/metabolismo , Camundongos , Oócitos/citologia , Piperidinas/farmacologia , Fator B de Elongação Transcricional Positiva/química , Fator B de Elongação Transcricional Positiva/genética , Gravidez , Inibidores de Proteínas Quinases/farmacologia , Subunidades Proteicas/química , Subunidades Proteicas/genética , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Ativação Transcricional/efeitos dos fármacosRESUMO
The present report describes an extrathoracic bronchogenic cyst in a 30-day-old female calf. Histologically, the cyst wall was lined by a layer of ciliated pseudostratified columnar epithelium with peripheral arrangement of cartilage, glands, and smooth muscle fascicles. The mass was successfully removed by simple surgical excision.
