Predicting coexistence and predominance patterns between the introduced Manila clam (Ruditapes philippinarum) and the European native clam (Ruditapes decussatus)

In several European estuaries, the introduced Manila clam (Ruditapes philippinarum) has become a widespread and predominating species supplanting the native carpet shell clam (Ruditapes decussatus) whereas in other estuaries such as the Bay of Santander (Gulf of Biscay) this pattern has not been detected. Using this estuary as a case study, the potential coexistence/predominance patterns between these two species were explored with the objective of providing insight into the capacity of expansion of R. philippinarum. Firstly, the Ecological Niche Factor Analysis (ENFA) was applied to determine the niches of both species, using seven contemporary environmental variables, i.e. salinity, water depth, current velocity, and sediment sand, gravel, silt and organic matter content. Secondly, ENFA-derived habitat-suitability (HS) maps were simultaneously treated, using geospatial techniques and following HS index-based criteria, to determine the potential distribution patterns. Both species models performed well according to the cross-validation evaluation method. The environmental variables that most determined the presence of both clams were depth, current velocity and salinity. ENFA factors showed that R. philippinarum habitat differs more from the mean environmental conditions over the estuary (i.e. higher marginality) and has less narrow requirements (i.e. lower specialization). R. philippinarum dominated areas, determined by relatively lower current velocities and percentages of sand, higher organic matter contents and slightly shallower depths, were very reduced (i.e. 2.0% of the bay surface) compared to coexistence (47%) and R. decussatus predominance areas (7.4%). These results suggest that HS may regulate the expansion of R. philippinarum. ENFA, together with geospatial analysis of HS index, seems to be a valuable approach to explore the expansion potential of estuarine invasive or introduced species and thus support conservation decisions regarding native species

LARVAHS: Predicting clam larval dispersal and recruitment using habitat suitability-based particle tracking model

We herein explore the potential larval dispersal and recruitment patterns of Ruditapes decussatus and Ruditapes philippinarum clams, influenced by larval behavior and hydrodynamics, by means of a particle-tracking model coupled to a hydrodynamic model. The main contribution of this study is that a habitat suitability-based (ENFA, Environmental Niche Factor Analysis) settlement–recruitment submodel was incorporated into the larval dispersal model to simulate settlement behavior and post-settlement mortality. For this purpose, a specific study was carried out in the Bay of Santander (Northern Spain), a well-mixed shallow water estuary where shellfishery of both species is carried out. The model was fed with observed winds, freshwater flows and astronomical tides to obtain predictions during the clams spawning period. Dispersion of larvae from seven spawning zones was tracked, subjected to three-dimensional advection, vertical turbulent diffusion and imposed vertical migration behavior parameterized from existing literature. Three simulation periods (Spring, Summer and Autumn) and two initial releases (spring/neap tide) were combined in six different modeling scenarios. The LARVAHS model proved to be a powerful approach to estimating recruitment success, highlighting the role of habitat suitability, larval swimming behavior, planktonic duration, season (i.e. predominating winds) and spawning ground location on recruitment success together with the effect of the tidal phase at spawning. Moreover, it has proven to be a valuable tool for determining major spawning and nursery grounds and to explore the connectivity between them, having important implications for restoration strategies and shellfisheries as well as aquaculture management

Deficiency of Parkinson’s Related Protein DJ-1 Alters Cdk5 Signalling and Induces Neuronal Death by Aberrant Cell Cycle Re-entry

DJ-1 is a multifunctional protein involved in Parkinson disease (PD) that can act as antioxidant, molecular chaperone, protease, glyoxalase, and transcriptional regulator. However, the exact mechanism by which DJ-1 dysfunction contributes to development of Parkinson’s disease remains elusive. Here, using a comparative proteomic analysis between wild-type cortical neurons and neurons lacking DJ-1 (data available via ProteomeXchange, identifier PXD029351), we show that this protein is involved in cell cycle checkpoints disruption. We detect increased amount of p-tau and α-synuclein proteins, altered phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signalling pathways, and deregulation of cyclin-dependent kinase 5 (Cdk5). Cdk5 is normally involved in dendritic growth, axon formation, and the establishment of synapses, but can also contribute to cell cycle progression in pathological conditions. In addition, we observed a decrease in proteasomal activity, probably due to tau phosphorylation that can also lead to activation of mitogenic signalling pathways. Taken together, our findings indicate, for the first time, that aborted cell cycle re-entry could be at the onset of DJ-1-associated PD. Therefore, new approaches targeting cell cycle re-entry can be envisaged to improve current therapeutic strategies

New clues to metabolic regulation through changes in the thiol redox proteome

Comunicaciones a congreso

Thioredoxin Downregulation Enhances Sorafenib Effects in Hepatocarcinoma Cells

Sorafenib is the first-line recommended therapy for patients with advanced hepatocarcinoma (HCC) in de-differentiation stage (presenting epithelial–mesenchymal transition, EMT). We studied the role of the thioredoxin system (Trx1/TrxR1) in the sensitivity or resistance of HCC cells to the treatment with Sorafenib. As a model, we used a set of three established HCC cell lines with different degrees of de-differentiation as occurs in metastasis. By quantitative proteomics, we found that the expression levels of Trx1 and TrxR1 followed the same trend as canonical EMT markers in these cell lines. Treatment with Sorafenib induced thiol redox reductive changes in critical elements of oncogenic pathways in all three cell lines but induced drastic proteome reprograming only in HCC cell lines of intermediate stage. Trx1 downregulation counteracted the thiol reductive effect of Sorafenib on Signal Transducer and Activator of Transcription 3 (STAT3) but not on Mitogen-Activated Protein Kinase (MAPK) or Protein Kinase B (Akt) and transformed advanced HCC cells into Sorafenib-sensitive cells. Ten targets of the combined Sorafenib–siRNATrx1 treatment were identified that showed a gradually changing expression trend in parallel to changes in the expression of canonical EMT markers, likely as a result of the activation of Hippo signaling. These findings support the idea that a combination of Sorafenib with thioredoxin inhibitors should be taken into account in the design of therapies against advanced HCC.Ministerio de Economía y Competitividad BFU2016-80006-PInstituto de Salud Carlos III (ISCIII) PI13/00021 y PI16/00090Junta de Andalucía Consejería de Economía, Innovación, Ciencia y Empleo BIO-0216 y CTS-6264Junta de Andalucía Consejería de Igualdad, Salud y Políticas Sociales PI-00025-2013 y PI-0198-201

Application of iTRAQ reagent to relatively quantify the reversible redox state of cysteines

Comunicaciones a congreso

Loss of PRDX6 aborts proliferative and migratory signaling in hepatocarcinoma cell lines

Peroxiredoxin 6 (PRDX6), the only mammalian 1-Cys member of the peroxiredoxin family, has peroxidase, phospholipase A2 (PLA2), and lysophosphatidylcholine (LPC) acyltransferase (LPCAT) activities. It has been associated with tumor progression and cancer metastasis, but the mechanisms involved are not clear. We constructed an SNU475 hepatocarcinoma cell line knockout for PRDX6 to study the processes of migration and invasiveness in these mesenchymal cells. They showed lipid peroxidation but inhibition of the NRF2 transcriptional regulator, mitochondrial dysfunction, metabolic reprogramming, an altered cytoskeleton, down-regulation of PCNA, and a diminished growth rate. LPC regulatory action was inhibited, indicating that loss of both the peroxidase and PLA2 activities of PRDX6 are involved. Upstream regulators MYC, ATF4, HNF4A, and HNF4G were activated. Despite AKT activation and GSK3β inhibition, the prosurvival pathway and the SNAI1-induced EMT program were aborted in the absence of PRDX6, as indicated by diminished migration and invasiveness, down-regulation of bottom-line markers of the EMT program, MMP2, cytoskeletal proteins, and triggering of the “cadherin switch”. These changes point to a role for PRDX6 in tumor development and metastasis, so it can be considered a candidate for antitumoral therapies

Identification of new immunoprotective surface protein vaccine candidates against streptococcus suis infection by proteomics

Comunicaciones a congreso

Differential distribution pattern of native Ruditapes decussatus and introduced Ruditapes philippinarum clam populations in the Bay of Santander

The aim of the present study is to provide a first characterization of the grooved carpet shell clam Ruditapes decussatus (native) and the Manila clam Ruditapes phillippinarum (nonindigenous) populations in the Bay of Santander in order to improve the management of these commercially exploited resources. For this purpose a field survey was carried out in different fishing areas where samples were taken on transects, following artisanal shellfisher exploitation techniques. Biometric relationships, size frequency distributions, densities and stocks were evaluated for different fishing zones. In addition, a hydrodynamic model was applied in order to understand larval transport and recruitment patterns associated to the tidal currents and water flow. Within this context, the first evaluation of the clam populations in the Bay of Santander showed: (a) that fishing activity is performed on individuals under the minimum legal size (40 mm) and in closed areas, (b) a significant differences on density by zone (c) a distribution pattern with areas where both species coexist and areas where one of them dominates, (d) R. decussatus occurs at relatively low density in stations near the culture parks and (e) a limited recruitment in the inner parts of Cubas tidal fresh for R. phillippinarum and in the southern zones for R. decussatus. Based on this study, some managing guidelines are presented mainly focused on avoiding the overfishing of the native clam R. decussatus.The work described in this paper was partially supported by the Department of Livestock, Agriculture and Fisheries from the Regional Government of Cantabria, through the Regional Fisheries and Food Administration and by the VI National Plan (2008–2011) for Research in Science & Technological Innovation of the Spanish Government (Project CGL2009-10620)

External validation of a prognostic model based on total tumor load of sentinel lymph node for early breast cancer patients

Background: A prognostic model based on the results of molecular analysis of sentinel lymph nodes (SLN) is needed to replace the information that staging the entire axilla provided. The aim of the study is to conduct an external validation of a previously developed model for the prediction of 5-year DFS in a group of breast cancer patients that had undergone SLN biopsy assessed by the One Step Nucleic Acid Amplification (OSNA) method. Methods: We collected retrospective data of 889 patients with breast cancer, who had not received systemic treatment before surgery, and who underwent SLN biopsy and evaluation of all SLN by OSNA. The discrimination ability of the model was assessed by the area under the ROC curve (AUC ROC), and its calibration by comparing 5-years DFS Kaplan–Meier estimates in quartile groups of model predicted probabilities (MPP). Results: The AUC ROC ranged from 0.78 (at 2 years) to 0.73 (at 5 years) in the training set, and from 0.78 to 0.71, respectively, in the validation set. The MPP allowed to distinguish four groups of patients with heterogeneous DFS (log-rank test p < 0.0001). In the highest risk group, the HR were 6.04 [95% CI 2.70, 13.48] in the training set and 4.79 [2.310, 9.93] in the validation set. Conclusions: The model for the prediction of 5-year DFS was successfully validated using the most stringent form of validation, in centers different from those involved in the development of the model. The external validation of the model confirms its utility for the prediction of 5-year DFS and the usefulness of the TTL value as a prognostic variable.This study was supported by Sysmex España S.L