Apoptosis regulates notochord development in Xenopus

AbstractThe notochord is the defining characteristic of the chordate embryo and plays critical roles as a signaling center and as the primitive skeleton. In this study we show that early notochord development in Xenopus embryos is regulated by apoptosis. We find apoptotic cells in the notochord beginning at the neural groove stage and increasing in number as the embryo develops. These dying cells are distributed in an anterior to posterior pattern that is correlated with notochord extension through vacuolization. In axial mesoderm explants, inhibition of this apoptosis causes the length of the notochord to approximately double compared to controls. In embryos, however, inhibition of apoptosis decreases the length of the notochord and it is severely kinked. This kinking also spreads from the anterior with developmental stage such that, by the tadpole stage, the notochord lacks any recognizable structure, although notochord markers are expressed in a normal temporal pattern. Extension of the somites and neural plate mirrors that of the notochord in these embryos, and the somites are severely disorganized. These data indicate that apoptosis is required for normal notochord development during the formation of the anterior–posterior axis, and its role in this process is discussed

Dignity and Equality: Law’s Reasonable Claimant and Human Dignity under Section 15

The concept of human dignity is an essential and inextricable element of equality rights. In Law v. Canada the Supreme Court united around the concept of dignity to determine section 15(1) cases. This test was abandoned in R v. Kapp, deciding that dignity was too abstract and subjective. This paper argues that the problems with the Law test did not come from the concept of dignity itself, but rather from the reasonable claimant test which focused on subjective feelings and legislative intentions. This paper presents an alternative conception of human dignity, which proposes that substantive equality should be a matter of equal concern based on two principles of human dignity: the principle of equal intrinsic value and the principle of personal responsibility. The analysis must be truly contextual, focused on the objective consequences of discrimination and the circumstances that create and foster inequality.MAS

Un historien parle aux historiens : politique et écriture de l’histoire dans le Traité de l’historien parfait du Chinois Liu Zhiji

International audienc

Demographic profile for graduate students enrolled in FiBS curriculum.

<p>Demographic profile for graduate students enrolled in FiBS curriculum.</p

Ordinal logistic regression models for improved performance in FiBS curriculum: Crude and adjusted values.

<p>Dependent variable ranked as: Fail/Pass/High performer, as previously defined. All variables included in adjusted model. Test of Parallel Lines = 0.57 for model. Significant correlations are indicated in bold.</p

Pharmacokinetic evaluation of rifabutin in combination with lopinavir-ritonavir in patients with HIV infection and active tuberculosis

Human immunodeficiency virus (HIV)-associated tuberculosis is difficult to treat, given the propensity for drug interactions between the rifamycins and the antiretroviral drugs. We examined the pharmacokinetics of rifabutin before and after the addition of lopinavir-ritonavir. We analyzed 10 patients with HIV infection and active tuberculosis in a state tuberculosis hospital. Plasma was collected for measurement of rifabutin, the microbiologically active 25-desacetyl-rifabutin, and lopinavir by validated high-performance liquid chromatography assays. Samples were collected 2-4 weeks after starting rifabutin at 300 mg thrice weekly without lopinavir-ritonavir, 2 weeks after the addition of lopinavir-ritonavir at 400 and 100 mg, respectively, twice daily to rifabutin at 150 mg thrice weekly, and (if rifabutin plasma concentrations were below the normal range) 2 weeks after an increase in rifabutin to 300 mg thrice weekly with lopinavir-ritonavir. Noncompartmental and population pharmacokinetic analyses (2-compartment open model) were performed. Rifabutin at 300 mg without lopinavir-ritonavir produced a low maximum plasma concentration (C(max)) in 5 of 10 patients. After the addition of lopinavir-ritonavir to rifabutin at 150 mg, 9 of 10 had low C(max) values. Eight patients had dose increases to 300 mg of rifabutin with lopinavir-ritonavir. Most free rifabutin (unbound to plasma protein) C(max) values were below the tuberculosis minimal inhibitory concentration. For most patients, values for the area under the plasma concentration-time curve were as low or lower than those associated with treatment failure or relapse and with acquired rifamycin resistance in Tuberculosis Trials Consortium/US Public Health Service Study 23. One of the 10 patients experienced relapse with acquired rifamycin resistance. The recommended rifabutin doses for use with lopinavir-ritonavir may be inadequate in many patients. Monitoring of plasma concentrations is recommended