Loss of CDK5RAP2 affects neural but not non-neural mESC differentiation into cardiomyocytes

Biallelic mutations in the gene encoding centrosomal CDK5RAP2 lead to autosomal recessive primary microcephaly (MCPH), a disorder characterized by pronounced reduction in volume of otherwise architectonical normal brains and intellectual deficit. The current model for the microcephaly phenotype in MCPH invokes a premature shift from symmetric to asymmetric neural progenitor-cell divisions with a subsequent depletion of the progenitor pool. The isolated neural phenotype, despite the ubiquitous expression of CDK5RAP2, and reports of progressive microcephaly in individual MCPH cases prompted us to investigate neural and non-neural differentiation of Cdk5rap2-depleted and control murine embryonic stem cells (mESC). We demonstrate an accumulating proliferation defect of neurally differentiating Cdk5rap2-depleted mESC and cell death of proliferative and early postmitotic cells. A similar effect does not occur in non-neural differentiation into beating cardiomyocytes, which is in line with the lack of non-central nervous system features in MCPH patients. Our data suggest that MCPH is not only caused by premature differentiation of progenitors, but also by reduced propagation and survival of neural progenitors.     

An experimentally induced host shift in a seed beetle

Many insects use a fairly well-defined set of host plants, but are occasionally observed on an atypical host. The seed beetle Callosobruchus maculatus (F.) (Coleoptera: Chrysomelidae: Bruchinae) has rarely been reported to attack lentil, which is distantly related to its usual legume hosts. An initial assay of an Asian beetle population revealed that none of the 100 larvae entering lentil seeds survived to adult emergence. Nevertheless, three attempts at mass selection, in which more than 2 000 adults were added to lentil seeds, eventually yielded self-sustaining populations. In each case, a severe bottleneck was followed by a rapid increase in survival, which exceeded 65% after only five generations and surpassed 85% in <20 generations. Subsequent large-scale experiments indicated that survival in lentil is initially <2% and that most larvae die before they have completely entered a seed. The only potential trade-off associated with rapid adaptation to lentil was a modest increase in the time required to develop in the ancestral host, mung bean. Reciprocal crosses between a lentil-adapted line (F10) and a mung-bean line produced offspring with intermediate survival, very long development times, and small size. Although the Asian population has been kept under uniform laboratory conditions for more than 200 generations, it appears to maintain rare alleles that permit the colonization of an extremely poor host. Such standing genetic variation can account for the sporadic appearance of unusual 'biotypes' among herbivorous insects.     

Monitoring of residues of ochratoxin A in blood and kidney of chicken using HPLC-FLD

Detoxification of ochratoxin A can be achieved by chemical or enzymatic hydrolyzation, the products of such reactions are ochratoxin α and phenylalanine. Ochratoxin α like ochratoxin A, is a fluorescing molecule, therefore sensitive analysis is possible at very low concentration levels. Methods have been established that make it possible to look for residues of ochratoxin A and its main metabolite ochratoxin α in blood and tissues at very low concentration levels. Plasma is extracted by the use of small amounts of chloroform; the extract is cleaned with water and afterwards evaporated to dryness]. The residue is re-dissolved and analysed by HPLC-FLD. Using this method a limit of detection of 0.5μg/l for both ochratoxin A and ochratoxin α can be reached.     

Prospective cohort studies on risk factors for cardiovascular events in systemic lupus erythematosus: a major challenge

Cardiovascular disease (CVD) has been identified as a major contributor to morbidity and mortality in patients with systemic lupus erythematosus (SLE). The etiology of premature CVD in SLE is supposed to have many factors, including traditional coronary artery disease (CAD) risk factors, antiphospholipid antibodies, and metabolic and inflammatory factors. Despite the overwhelming interest in CVD in SLE research, prospective studies evaluating risk factors for hard endpoints (that is, cardiovascular events) are relatively scarce. The article by Gustafsson and colleagues suggests that prothrombotic factors play an important role in SLE-related CVD and that the influence of traditional CAD risk factors might be limited.