Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Avanços recentes em nutrição de larvas de peixes

Os requisitos nutricionais de larvas de peixes são ainda mal compreendidos, o que leva a altas mortalidades e problemas de qualidade no seu cultivo. Este trabalho pretende fazer uma revisão de novas metodologias de investigação, tais como estudos com marcadores, genómica populacional, programação nutricional, génomica e proteómica funcionais, e fornecer ainda alguns exemplos das utilizações presentes e perspectivas futuras em estudos de nutrição de larvas de peixes

Eliminating pond differences with cross-over designs

Large variability between ponds in aquaculture experiments often leads to imprecise estimates of treatment effects. One solution would be to increase the number of experimental ponds but the availability of ponds is usually limited. A cross-over trial makes comparisons directly within the same pond, instead of across ponds, thus taking account of individual pond effects and potentially removing much of the variability. A cross-over trial was initiated to test the feasibility of using such designs in pond aquaculture research. When compared to a completely randomized design, the cross-over trial was more efficient for comparing the fish growth for each of the two treatments, and, on average, a considerable reduction in the standard error of the treatment estimate was achieved. Thus, under certain circumstances, the cross-over design has great potential to improve the precision of pond aquaculture experimentation