Bmp suppression in mangrove killifish embryos causes a split in the body axis

This is the final version of the article. Available from Public Library of Science via the DOI in this record.Bone morphogenetic proteins (Bmp) are major players in the formation of the vertebrate body plan due to their crucial role in patterning of the dorsal-ventral (DV) axis. Despite the highly conserved nature of Bmp signalling in vertebrates, the consequences of changing this pathway can be species-specific. Here, we report that Bmp plays an important role in epiboly, yolk syncytial layer (YSL) movements, and anterior-posterior (AP) axis formation in embryos of the self-fertilizing mangrove killifish, Kryptolebias marmoratus. Stage and dose specific exposures of embryos to the Bmp inhibitor dorsomorphin (DM) produced three distinctive morphologies, with the most extreme condition creating the splitbody phenotype, characterised by an extremely short AP axis where the neural tube, somites, and notochord were bilaterally split. In addition, parts of caudal neural tissues were separated from the main body and formed cell islands in the posterior region of the embryo. This splitbody phenotype, which has not been reported in other animals, shows that modification of Bmp may lead to significantly different consequences during development in other vertebrate species.SM was funded by a PhD studentship from the Natural and Environmental Research Council (NERC) in the U

Propagation of regional seismic phases (Lg and Sn) and Pn velocity structure along the Africa-Iberia plate boundary zone

An edited version of this paper was published by Blackwell Publishing. Copyright 2000, Blackwell Publishing. See also: http://www.blackwell-synergy.com/doi/abs/10.1046/j.1365-246x.2000.00160.x; http://atlas.geo.cornell.edu/morocco/publications/calvert2000GJI.htmWe used over 1000 regional waveforms recorded by 60 seismic stations located in northwest Africa and Iberia to map the efficiency of L g and Sn wave propagation beneath the Gulf of Cadiz, Alboran Sea and bounding Betic, Rif and Atlas mountain belts. Crustal attenuation is inferred from the tomographic inversion of L g/Pg amplitude ratios. Upper mantle attenuation is inferred from maps of Sn propagation efficiency derived by inversion of well-defined qualitative efficiency assignments based on waveform characteristics. Regions of L g attenuation correlate well with areas of thinned continental or oceanic crust, significant sedimentary basins, and lateral crustal variations. Comparison of the Sn efficiency results with velocities obtained from an anisotropic Pn traveltime inversion shows a fairly good correlation between regions of poor Sn efficiency and low Pn velocity. A low Pn velocity (7.6?7.8 km s-1) and significant Sn attenuation in the uppermost mantle is imaged beneath the Betics in southern Spain, in sharp contrast to the relatively normal Pn velocity (8.0?8.1 km s-1) and efficient Sn imaged beneath the Alboran Sea. Slow Pn velocity anomalies are also imaged beneath the Rif and Middle Atlas in Morocco. We do not identify any conclusive evidence of lithospheric-scale upper mantle attenuation beneath the Rif, although the crust in the Gibraltar region appears highly attenuating, making observations at stations in this region ambiguous. Paths crossing the Gulf of Cadiz, eastern Atlantic and the Moroccan and Iberian mesetas show very efficient Sn propagation and are imaged with high Pn velocities (8.1?8.2 km s-1). The spatial distribution of attenuation and velocity anomalies lead us to conclude that some recovery of the mantle lid beneath the Alboran Sea must have occurred since the early Miocene episode of extension and volcanism. We interpret the low velocity and attenuating regions beneath the Betics and possibly the Rif as indicating the presence of partial melt in the uppermost mantle which may be underlain by faster less attenuating mantle. In the light of observations from other geophysical and geological studies, the presence of melt at the base of the Betic crust may be an indication that delamination of continental lithosphere has played a role in the Neogene evolution of the Alboran Sea region

Geodynamic evolution of the lithosphere and upper mantle beneath the Alboran region of the western Mediterranean: Constraints from travel time tomography

An edited version of this paper was published by the American Geophysical Union. Copyright 2000, AGU. See also: http://www.agu.org/pubs/crossref/2000/2000JB900024.shtml; http://atlas.geo.cornell.edu/morocco/publications/calvert2000.htmA number of different geodynamic models have been proposed to explain the extension that occurred during the Miocene in the Alboran Sea region of the western Mediterranean despite the continued convergence and shortening of northern Africa and southern Iberia. In an effort to provide additional geophysical constraints on these models, we performed a local, regional, and teleseismic tomographic travel time inversion for the lithospheric and upper mantle velocity structure and earthquake locations beneath the Alboran region in an area of 800 x 800 km^2. We picked P and S arrival times from digital and analog seismograms recorded by 96 seismic stations in Morocco and Spain between 1989 and 1996 and combined them with arrivals carefully selected from local and global catalogs (1964-1998) to generate a starting data set containing over 100,000 arrival times. Our results indicate that a N-S line of intermediate depth earthquakes extending from crustal depths significantly inland from the southern Iberian coat to depths of over 100 km beneath the center of the Alboran Sea coincided with a W to E transition from high to low velocities imaged in the uppermost mantle. A high-velocity body, striking approximately NE-SW, is imaged to dip southeastwards from lithospheric depths beneath the low-velocity region to depths of ~350 km. Between 350 and 500 km the imaged velocity anomalies become more diffuse. However, pronounced high-velocity anomalies are again imaged at 600 km near an isolated cluster of deep earthquakes. In addition to standard tomographic methods of error assessment, the effects of systematic and random errors were assessed using block shifting and bootstrap resampling techniques, respectively. We interpret the upper mantle high-velocity anomalies as regions of colder mantle that originate from lithospheric depths. These observations, when combined with results from other studies, suggest that delamination of a continental lithosphere played an important role in the Neogene and Quaternary evolution of the region

New insights into organ-specific oxidative stress mechanisms using a novel biosensor zebrafish

This is the final version. Available from Elsevier via the DOI in this record. Background: Reactive oxygen species (ROS) arise as a result from, and are essential in, numerous cellular processes. ROS, however, are highly reactive and if left unneutralised by endogenous antioxidant systems, can result in extensive cellular damage and/or pathogenesis. In addition, exposure to a wide range of environmental stressors can also result in surplus ROS production leading to oxidative stress (OS) and downstream tissue toxicity. Objectives: Our aim was to produce a stable transgenic zebrafish line, unrestricted by tissue-specific gene regulation, which was capable of providing a whole organismal, real-time read-out of tissue-specific OS following exposure to a wide range of OS-inducing environmental contaminants and conditions. This model could, therefore, serve as a sensitive and specific mechanistic in vivo biomarker for all environmental conditions that result in OS. Methods: To achieve this aim, we exploited the pivotal role of the electrophile response element (EpRE) as a globally-acting master regulator of the cellular response to OS. To test tissue specificity and quantitative capacity, we selected a range of chemical contaminants known to induce OS in specific organs or tissues, and assessed dose-responsiveness in each using microscopic measures of mCherry fluorescence intensity. Results: We produced the first stable transgenic zebrafish line Tg (3EpRE:hsp70:mCherry) with high sensitivity for the detection of cellular RedOx imbalances, in vivo in near-real time. We applied this new model to quantify OS after exposure to a range of environmental conditions with high resolution and provided quantification both of compound- and tissue-specific ROS-induced toxicity. Discussion: Our model has an extremely diverse range of potential applications not only for biomonitoring of toxicants in aqueous environments, but also in biomedicine for identifying ROS-mediated mechanisms involved in the progression of a number of important human diseases, including cancer.Natural Environmental Research CouncilEuropean Unio

Seismic risk in the city of Al Hoceima (north of Morocco) using the vulnerability index method, applied in Risk-UE project

The final publication is available at Springer via http://dx.doi.org/10.1007/s11069-016-2566-8Al Hoceima is one of the most seismic active regions in north of Morocco. It is demonstrated by the large seismic episodes reported in seismic catalogs and research studies. However, seismic risk is relatively high due to vulnerable buildings that are either old or don’t respect seismic standards. Our aim is to present a study about seismic risk and seismic scenarios for the city of Al Hoceima. The seismic vulnerability of the existing residential buildings was evaluated using the vulnerability index method (Risk-UE). It was chosen to be adapted and applied to the Moroccan constructions for its practicality and simple methodology. A visual inspection of 1102 buildings was carried out to assess the vulnerability factors. As for seismic hazard, it was evaluated in terms of macroseismic intensity for two scenarios (a deterministic and probabilistic scenario). The maps of seismic risk are represented by direct damage on buildings, damage to population and economic cost. According to the results, the main vulnerability index of the city is equal to 0.49 and the seismic risk is estimated as Slight (main damage grade equal to 0.9 for the deterministic scenario and 0.7 for the probabilistic scenario). However, Moderate to heavy damage is expected in areas located in the newer extensions, in both the east and west of the city. Important economic losses and damage to the population are expected in these areas as well. The maps elaborated can be a potential guide to the decision making in the field of seismic risk prevention and mitigation strategies in Al Hoceima.Peer ReviewedPostprint (author's final draft

Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish

 This is the author accepted manuscript. The final version is available on open access from American Chemical Society via the DOI in this record The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but direct causal links are unclear in humans and animal models. Here we simulated measured (1×) and predicted worst-case (10×) maximum foetal exposures for BPA, or equivalent concentrations of its metabolite MBP, using fluorescent reporter embryo-larval zebrafish capable of quantifying Estrogen Response Element (ERE) activation throughout the body. Heart valves were primary sites for ERE activation by BPA and MBP, and transcriptomic analysis of micro-dissected heart tissues showed that both chemicals perturbed similar downstream molecular pathways and biological processes, including down-regulation of cartilage morphogenesis and filamentous protein synthesis. Collagen/keratin deficiency and impact on heart valve structural integrity were confirmed by histopathology for high-level MBP exposure, and structural defects (abnormal curvature) of the atrio-ventricular valves corresponded with impaired cardiovascular function (reduced ventricular beat rate and blood flow). Our results are the first to demonstrate plausible mechanistic links between ERE activation in the heart valves by BPA’s reactive metabolite MBP and the development of valvular- cardiovascular disease states.Biotechnology & Biological Sciences Research Council (BBSRC)Natural Environment Research Council (NERC

The Drosophila GIPC Homologue Can Modulate Myosin Based Processes and Planar Cell Polarity but Is Not Essential for Development

Epithelia often show, in addition to the ubiquitous apico-basal (A/B) axis, a polarization within the plane of the epithelium, perpendicular to the A/B axis. Such planar cell polarity (PCP) is for example evident in the regular arrangement of the stereocilia in the cochlea of the mammalian inner ear or in (almost) all Drosophila adult external structures. GIPCs (GAIP interacting protein, C terminus) were first identified in mammals and bind to the Gαi GTPase activating protein RGS-GAIP. They have been proposed to act in a G-protein coupled complex controlling vesicular trafficking. Although GIPCs have been found to bind to numerous proteins including Frizzled receptors, which participate in PCP establishment, there is little in vivo evidence for the functional role(s) of GIPCs. We show here that overexpressed Drosophila dGIPC alters PCP generation in the wing. We were however unable to find any binding between dGIPC and the Drosophila receptors Fz1 and Fz2. The effect of overexpressed dGIPC is likely due to an effect on the actin cytoskeleton via myosins, since it is almost entirely suppressed by removing a genomic copy of the Myosin VI/jaguar gene. Surprisingly, although dGIPC can interfere with PCP generation and myosin based processes, the complete loss-of-function of dGIPC gives viable adults with no PCP or other detectable defects arguing for a non-essential role of dGIPC in viability and normal Drosophila development

Integrin α5β1 Function Is Regulated by XGIPC/kermit2 Mediated Endocytosis during Xenopus laevis Gastrulation

During Xenopus gastrulation α5β1 integrin function is modulated in a temporally and spatially restricted manner, however, the regulatory mechanisms behind this regulation remain uncharacterized. Here we report that XGIPC/kermit2 binds to the cytoplasmic domain of the α5 subunit and regulates the activity of α5β1 integrin. The interaction of kermit2 with α5β1 is essential for fibronectin (FN) matrix assembly during the early stages of gastrulation. We further demonstrate that kermit2 regulates α5β1 integrin endocytosis downstream of activin signaling. Inhibition of kermit2 function impairs cell migration but not adhesion to FN substrates indicating that integrin recycling is essential for mesoderm cell migration. Furthermore, we find that the α5β1 integrin is colocalized with kermit2 and Rab 21 in embryonic and XTC cells. These data support a model where region specific mesoderm induction acts through kermit2 to regulate the temporally and spatially restricted changes in adhesive properties of the α5β1 integrin through receptor endocytosis