The evolution and appearance of c3 duplications in fish originate an exclusive teleost c3 gene form with anti- inflammatory activity

12 páginas, 6 figuras, 3 tablas.-- This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe complement system acts as a first line of defense and promotes organism homeostasis by modulating the fates of diverse physiological processes. Multiple copies of component genes have been previously identified in fish, suggesting a key role for this system in aquatic organisms. Herein, we confirm the presence of three different previously reported complement c3 genes (c3.1, c3.2, c3.3) and identify five additional c3 genes (c3.4, c3.5, c3.6, c3.7, c3.8) in the zebrafish genome. Additionally, we evaluate the mRNA expression levels of the different c3 genes during ontogeny and in different tissues under steady-state and inflammatory conditions. Furthermore, while reconciling the phylogenetic tree with the fish species tree, we uncovered an event of c3 duplication common to all teleost fishes that gave rise to an exclusive c3 paralog (c3.7 and c3.8). These paralogs showed a distinct ability to regulate neutrophil migration in response to injury compared with the other c3 genes and may play a role in maintaining the balance between inflammatory and homeostatic processes in zebrafishThis work has been funded by the project CSD2007-00002 “Aquagenomics” from the Spanish Ministerio de Ciencia e Innovación, the ITN 289209 “FISHFORPHARMA” (EU) and project 201230E057 from the Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC).Peer reviewe

Estimation of PM10-bound As, Cd, Ni and Pb levels by means of statistical modelling: PLSR and ANN approaches

Air quality assessment regarding metals and metalloids using experimental measurements is expensive and time consuming due to the cost and time required for the analytical determination of the levels of these pollutants. According to the European Union (EU) Air Quality Framework Directive (Directive 2008/50/EC), other alternatives, such as objective estimation techniques, can be considered for ambient air quality assessment in zones and agglomerations where the level of pollutants is below a certain concentration value known as the lower assessment threshold. These conditions occur in urban areas in Cantabria (northern Spain). This work aims to estimate the levels of As, Cd, Ni and Pb in airborne PM10 at two urban sites in the Cantabria region (Castro Urdiales and Reinosa) using statistical models as objective estimation techniques. These models were developed based on three different approaches: partial least squares regression (PLSR), artificial neural networks (ANNs) and an alternative approach consisting of principal component analysis (PCA) coupled with ANNs (PCA-ANN). Additionally, these models were externally validated using previously unseen data. The results show that the models developed in this work based on PLSR and ANNs fulfil the EU uncertainty requirements for objective estimation techniques and provide an acceptable estimation of the mean values. As a consequence, they could be considered as an alternative to experimental measurements for air quality assessment regarding the aforementioned pollutants in the study areas while saving time and resources.The authors gratefully acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness through the Project CMT2010-16068. The authors also thank the Regional Environment Ministry of the Cantabria Government for providing the PM10 samples at the Castro Urdiales and Reinosa sites

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as “thymic hormones,” are produced by this gland. Although the majority of them have not been proven to be thymus-speciWc, thymic peptides comprise an eVective group of regulators, mediating important immune functions. Thymosin fraction Wve (TFV) was the Wrst thymic extract shown to stimulate lymphocyte proliferation and diVerentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin (proT) and thymosin 1 (T1) showed that they are of clinical signiWcance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeWciencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their eVect are yet not fully elucidated proT and T1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proT, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of T1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proT into the clinical setting

Genomic view of the evolution of the complement system

The recent accumulation of genomic information of many representative animals has made it possible to trace the evolution of the complement system based on the presence or absence of each complement gene in the analyzed genomes. Genome information from a few mammals, chicken, clawed frog, a few bony fish, sea squirt, fruit fly, nematoda and sea anemone indicate that bony fish and higher vertebrates share practically the same set of complement genes. This suggests that most of the gene duplications that played an essential role in establishing the mammalian complement system had occurred by the time of the teleost/mammalian divergence around 500 million years ago (MYA). Members of most complement gene families are also present in ascidians, although they do not show a one-to-one correspondence to their counterparts in higher vertebrates, indicating that the gene duplications of each gene family occurred independently in vertebrates and ascidians. The C3 and factor B genes, but probably not the other complement genes, are present in the genome of the cnidaria and some protostomes, indicating that the origin of the central part of the complement system was established more than 1,000 MYA

Standard Model Physics at the HL-LHC and HE-LHC

The successful operation of the Large Hadron Collider (LHC) and the excellent performance of the ATLAS, CMS, LHCb and ALICE detectors in Run-1 and Run-2 with $pp$ collisions at center-of-mass energies of 7, 8 and 13 TeV as well as the giant leap in precision calculations and modeling of fundamental interactions at hadron colliders have allowed an extraordinary breadth of physics studies including precision measurements of a variety physics processes. The LHC results have so far confirmed the validity of the Standard Model of particle physics up to unprecedented energy scales and with great precision in the sectors of strong and electroweak interactions as well as flavour physics, for instance in top quark physics. The upgrade of the LHC to a High Luminosity phase (HL-LHC) at 14 TeV center-of-mass energy with 3 ab$^{-1}$ of integrated luminosity will probe the Standard Model with even greater precision and will extend the sensitivity to possible anomalies in the Standard Model, thanks to a ten-fold larger data set, upgraded detectors and expected improvements in the theoretical understanding. This document summarises the physics reach of the HL-LHC in the realm of strong and electroweak interactions and top quark physics, and provides a glimpse of the potential of a possible further upgrade of the LHC to a 27 TeV $pp$ collider, the High-Energy LHC (HE-LHC), assumed to accumulate an integrated luminosity of 15 ab$^{-1}$