PAPC and the Wnt5a/Ror2 pathway control the invagination of the otic placode in Xenopus

<p>Abstract</p> <p>Background</p> <p>Paraxial protocadherin (PAPC) plays a crucial role in morphogenetic movements during gastrulation and somitogenesis in mouse, zebrafish and Xenopus. PAPC influences cell-cell adhesion mediated by C-Cadherin. A putative direct adhesion activity of PAPC is discussed. PAPC also promotes cell elongation, tissue separation and coordinates cell mass movements. In these processes the signaling function of PAPC in activating RhoA/JNK and supporting Wnt-11/PCP by binding to frizzled 7 (fz7) is important.</p> <p>Results</p> <p>Here we demonstrate by loss of function experiments in Xenopus embryos that PAPC regulates another type of morphogenetic movement, the invagination of the ear placode. Knockdown of PAPC by antisense morpholinos results in deformation of the otic vesicle without altering otocyst marker expression. Depletion of PAPC could be rescued by full-length PAPC, constitutive active RhoA and by the closely related PCNS but not by classical cadherins. Also the cytoplasmic deletion mutant M-PAPC, which influences cell adhesion, does not rescue the PAPC knockdown. Interestingly, depletion of Wnt5a or Ror2 which are also expressed in the otocyst phenocopies the PAPC morphant phenotype.</p> <p>Conclusions</p> <p>PAPC signaling via RhoA and Wnt5a/Ror2 activity are required to keep cells aligned in apical-basal orientation during invagination of the ear placode. Since neither the cytoplasmic deletion mutant M-PAPC nor a classical cadherin is able to rescue loss of PAPC we suggest that the signaling function of the protocadherin rather than its role as modulator of cell-cell adhesion is required during invagination of the ear placode.</p

A cautionary note: Toxicity of polyethylene glycol 200 injected intraperitoneally into mice

The parenteral administration of hydrophobic substances in vivo requires the use of organic solvents to ensure sufficient solubility and avoid precipitation. Dimethyl sulfoxide is commonly used for this purpose. Based on the common assumption that polyethylene glycol (PEG) is non-toxic, our local regulatory authorities recently recommended the use of PEG instead. However, mice injected intraperitoneally (i.p.) with PEG 200 at a dose of 8 mL/kg (i.e. 9 g/kg) did not tolerate PEG 200 well, and half of the animals had to be euthanized. Our results demonstrate that although PEG 200 is generally considered to be harmless, it can be toxic when injected i.p. and is painful for the recipient mice. Nevertheless, it can be used as a solvent for repeated i.p. injections in mice at a dose of 2 mL/kg (i.e. 2.25 g/kg) without obvious signs of systemic toxicity

Impairment of trophic interactions between zebrafish ( Danio rerio ) and midge larvae ( Chironomus riparius ) by chlorpyrifos

The effects of chemicals on biotic interactions, such as competition and predation, have rarely been investigated in aquatic ecotoxicology. This study presents a new approach for the investigation of predator-prey interactions between zebrafish (Danio rerio) and midge larvae (Chironomus riparius) impaired by chlorpyrifos (CHP), a neurotoxic insecticide. With a simple experimental design including four different treatments: (1) control, (2) predator exposed, (3) prey exposed and (4) both, predator and prey, exposed, we were able to detect by visual observation an increase in the feeding rate of zebrafish preying on exposed chironomids after acute (2h) exposure to 6μg/l CHP. Previously, a decrease in the burrowing behaviour of exposed chironomid larvae was observed. However, when pre-exposing simultaneously both predators and prey, no significant differences in the feeding rate of zebrafish were observed. This suggests an impairment in prey recognition of the exposed zebrafish. At a lower CHP concentration (1μg/l), no differences in feeding rate of zebrafish were observed. We therefore propose the use of trophic interactions as parameters in higher tier studies for chemical testing and evaluation of ecotoxicological risk assessmen

Comparison of wall thickening and ejection fraction by cardiovascular magnetic resonance and echocardiography in acute myocardial infarction

<p>Abstract</p> <p>Objectives</p> <p>The purpose of this study was to compare cardiovascular magnetic resonance (CMR) and echocardiography (echo) in patients treated with primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) with emphasis on the analysis of left ventricular function and left ventricular wall motion characteristics.</p> <p>Methods</p> <p>We performed CMR and echo in 52 patients with first AMI shortly after primary angioplasty and four months thereafter. CMR included cine-MR and T1-weighted first-pass and late-gadolinium enhancement (LGE) sequences. Global ejection fraction (EF_CMR, %) and regional left ventricular function (systolic wall thickening %, [SWT]) were determined from cine-MR images. In echo the global left ventricular function (EF_echo, %) and regional wall motion abnormalities were determined. A segment in echo was scored as "infarcted" if it was visually > 50% hypokinetic.</p> <p>Results</p> <p>EF_echorevealed a poor significant agreement with EF_CMRat baseline (r: 0.326; p < 0.01) but higher correlation at follow-up (r: 0.479; p < 0.001). The number of infarcted segments in echocardiography correlated best with the number of segments which showed systolic wall thickening < 30% (r: 0.498; p < 0.001) at baseline and (r: 0.474; p < 0.001) at follow-up. Improvement of EF was detected in both CMR and echocardiography increasing from 44.2 ± 11.6% to 49.2 ± 11% (p < 0.001) by CMR and from 51.2 ± 8.1% to 54.5 ± 8.3% (p < 0.001) by echocardiography.</p> <p>Conclusion</p> <p>Wall motion and EF by CMR and echocardiography correlate poorly in the acute stage of myocardial infarction. Correlation improves after four months. Systolic wall thickening by CMR < 30% indicates an infarcted segment with influence on the left ventricular function.</p

Integrated toxicity evaluation of a pulp deposit using organisms of different trophic levels

Purpose: In order to assess possible adverse effects originating from pulp deposits in a Swiss lake, a sediment quality triad approach was applied with chemical, ecotoxicological and ecological assessment methods. Materials and methods: To obtain an integrative picture of the potential ecotoxicological effects on organisms of different trophic levels, four test procedures were applied. The acute effects of pulp deposit pore water on a decomposer, the amphipod Gammarus fossarum, were monitored. Chronic toxicity of the pore water was evaluated on primary producers via a growth inhibition test with unicellular green algae (Pseudokirchneriella subcapitata) and on secondary consumers in a reproduction test with the water flea Ceriodaphnia dubia. To evaluate the effects of the pulp deposit on sediment inhabitants, a whole-life-cycle test with the non-biting midge Chironomus riparius was undertaken. Chemical assessment included dissolved organic carbon, extractable organic halogenic compounds, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and heavy metals. The composition of the macrozoobenthos community was analysed in order to assess the ecological effects. Results and discussion: G. fossarum displayed increased locomotor activity at 12.5% but not at 25% sample concentration during a short-time exposure of 20h. Chronic effects compromised the reproduction and growth of C. dubia (lowest observed effect concentration, 12.5% sample concentration) with zero population growth in 100% pulp deposit pore water. In 100% pulp deposit, C. riparius exhibited increased mortality at 10 and 17days after oviposition. Pulp deposits of 50% and 100% concentration caused a significantly lower emergence compared with the reference treatments (lake sediment and quartz sand). Additionally, the locomotor activity of chironomids decreased significantly in 25-100% pulp deposit. No chronic effects of pulp deposit pore water on algae photosynthesis and growth could be detected. The bioassay results were in accordance with an elevated content of PAHs, PCBs and metals in the pulp deposit. Significantly more organisms known to be tolerant to organic pollution were present within the macrozoobenthos community. Conclusions: In general, for sediment inhabitants such as chironomids, the pulp deposit has to be classified toxic. In the present test setup, the toxicity of the pulp deposit was reflected better by the chronic test systems applied than by the acute ones. The applied testing framework could be a suitable tool to assess the risk of contaminated sites, and this information will help decide whether risk mitigation measures should be taken. In addition, with a similar approach, the success of any mitigation measures taken can be assesse