The enterocyte proteome of gilthead seabream (Sparus Aurata) acclimated to two salinited conditions

Comunicaciones a congreso

Zinc(II), cobalt(II) and manganese(II) networks with phosphoserine ligand: Synthesis, crystal structures magnetic and conduction properties

A series of zinc(II), cobalt(II) and manganese(II) coordination networks with the phosphoserine ligand (Pser) is synthesized and characterized. Whereas in compounds 1 and 2 with the general formula [M(Pser)]n [M = Zn (1) and Co(2)], the metal(II) ion presents a tetrahedral geometry, in [Co(Pser)(H2O)2]n (3) and [Mn(Pser)(H2O)]n (4)], the metal(II) ions are in a distorted octahedral geometry. The 3D frameworks are formed by inorganic layers built up from MO4 or MO6 polyhedra and phosphate groups. These layers are linked by the carboxylate groups of the phosphoserine ligand. The presence of extended hydrogen bonding stabilizes the 3D network and favors the proton transfer leading to moderate proton conductors. The highest proton conductivity, 2.70·10−5 S cm−1 (at 80 ºC and 95% RH), is obtained for compound 3. Temperature dependent magnetic susceptibility measurements for 2−4 reveal predominant antiferromagnetic interactions between the paramagnetic metal(II) ions.Proyectos MAT2013-41836-R y MAT2016-77648-R del MINECO, y proyecto (P12-FQM-1656) de la Junta de Andalucía

Advanced fluorescence microscopy reveals disruption of dynamic CXCR4 dimerization by subpocket-specific inverse agonists

Funding: This research was funded by European Union’s Horizon2020 Marie Skłodowska-Curie Actions (MSCA) Program under Grant Agreement 641833 (ONCORNET) and European Cooperation in Science and Technology (COST) Action CA18133 European Research Network on Signal Transduction (ERNEST). A. Inoue was funded by the Leading Advanced Projects for Medical Innovation (LEAP) JP19gm0010004 from the Japan Agency for Medical Research and Development.Although class A G protein−coupled receptors (GPCRs) can function as monomers, many of them form dimers and oligomers, but the mechanisms and functional relevance of such oligomerization is ill understood. Here, we investigate this problem for the CXC chemokine receptor 4 (CXCR4), a GPCR that regulates immune and hematopoietic cell trafficking, and a major drug target in cancer therapy. We combine single-molecule microscopy and fluorescence fluctuation spectroscopy to investigate CXCR4 membrane organization in living cells at densities ranging from a few molecules to hundreds of molecules per square micrometer of the plasma membrane. We observe that CXCR4 forms dynamic, transient homodimers, and that the monomer−dimer equilibrium is governed by receptor density. CXCR4 inverse agonists that bind to the receptor minor pocket inhibit CXCR4 constitutive activity and abolish receptor dimerization. A mutation in the minor binding pocket reduced the dimer-disrupting ability of these ligands. In addition, mutating critical residues in the sixth transmembrane helix of CXCR4 markedly diminished both basal activity and dimerization, supporting the notion that CXCR4 basal activity is required for dimer formation. Together, these results link CXCR4 dimerization to its density and to its activity. They further suggest that inverse agonists binding to the minor pocket suppress both dimerization and constitutive activity and may represent a specific strategy to target CXCR4.Publisher PDFPeer reviewe

Phosphorylation-dependent differences in CXCR4-LASP1-AKT1 Interaction between breast cancer and chronic myeloid leukemia

The serine/threonine protein kinase AKT1 is a downstream target of the chemokine receptor4 (CXCR4), and both proteins play a central role in the modulation of diverse cellular processes,including proliferation and cell survival. While in chronic myeloid leukemia (CML) the CXCR4is downregulated, thereby promoting the mobilization of progenitor cells into blood, the receptoris highly expressed in breast cancer cells, favoring the migratory capacity of these cells. Recently,the LIM and SH3 domain protein 1 (LASP1) has been described as a novel CXCR4 binding partnerand as a promoter of the PI3K/AKT pathway. In this study, we uncovered a direct binding ofLASP1, phosphorylated at S146, to both CXCR4 and AKT1, as shown by immunoprecipitation assays,pull-down experiments, and immunohistochemistry data. In contrast, phosphorylation of LASP1at Y171 abrogated these interactions, suggesting that both LASP1 phospho-forms interact. Finally,findings demonstrating different phosphorylation patterns of LASP1 in breast cancer and chronicmyeloid leukemia may have implications for CXCR4 function and tyrosine kinase inhibitor treatment

Structure-based exploration and pharmacological evaluation of N-substituted piperidin-4-yl-methanamine CXCR4 chemokine receptor antagonists

Using the available structural information of the chemokine receptor CXCR4, we present hit finding and hit exploration studies that make use of virtual fragment screening, design, synthesis and structure-activity relationship (SAR) studies. Fragment 2 was identified as virtual screening hit and used as a starting point for the exploration of 31 N-substituted piperidin-4-yl-methanamine derivatives to investigate and improve the interactions with the CXCR4 binding site. Additionally, subtle structural ligand changes lead to distinct interactions with CXCR4 resulting in a full to partial displacement of CXCL12 binding and competitive and/or non-competitive antagonism. Three-dimensional quantitative structure-activity relationship (3D-QSAR) and binding model studies were used to identify important hydrophobic interactions that determine binding affinity and indicate key ligand-receptor interactions

Dental metric standards for sex estimation in archaeological populations from Iran

Sex estimation of skeletal remains is one of the major components of forensic identification of unknown individuals. Teeth are a potential source of information on sex and are often recovered in archaeological or forensic contexts due to their post-mortem longevity. Currently there is limited data on dental sexual dimorphism of archaeological populations from Iran. This dissertation represents the first study to provide a dental sex estimation method for Iron Age populations. The current study was conducted on the skeletal remains of 143 adults from two Iron Age populations in close temporal and geographic proximity in the Solduz Valley (West Azerbaijan Province of Iran). 2D and 3D cervical mesiodistal and buccolingual and root volume measurements of maxillary and mandibular teeth were used to investigate the degree of sexual dimorphism in permanent dentition and to assess their applicability in sex estimation. In total 1327, 457, and 480 anterior and posterior teeth were used to collect 2D cervical, 3D cervical, and root volume measurements respectively. 2D cervical measurements were taken using Hillson-Fitzgerald dental calliper and 3D measurements were collected using CT images provided by Open Research Scan Archive (ORSA) - Penn Museum. 3D models of the teeth were created using manual segmentation in the Amira 6.01 software package. Since tooth density largely differs from crown to apex, root segmentation required two threshold levels: the segmentation of the root from the jaw and the segmentation of the crown from the root. Thresholds used for root segmentation were calculated using the half maximum height protocol of Spoor et al. (1993) for each skull, and thresholds used for crown segmentation were set visually for each tooth separately. Data was analysed using discriminant function analysis and posterior probabilities were calculated for all produced formulae where sex was previously assessed from morphological features of pelvis and skull. Bootstrapping was used to account for small sample sizes in the analysis. Statistical analysis was carried out using SPSS 23. The percentage of sexual dimorphism was also used to quantify the amount of sexual dimorphism in the sample. The results showed that incisors and canines were the most sexually dimorphic teeth, providing percentages of correct sex classification between 80% and 100% depending on the measurement used. Root volume measurement was shown to be the most sexually dimorphic variable providing an accuracy of over 90% in all functions. The present study provided the first dental metric standards for sex estimation using odontometric data in Iranian archaeological populations. Dental measurements, particularly root volume measurements, were found to be of value for sex assessment and the method presented here could be a useful tool for establishing accurate demographic data from skeletal remains of the Iron Age from Iran

Identification of a delta5-like fatty acyl desaturase from the cephalopod Octopus vulgaris (Cuvier 1797) involved in the biosynthesis of essential fatty acids

Long-chain polyunsaturated fatty acids (LC-PUFA) have been identified as essential compounds for common octopus (Octopus vulgaris), but precise dietary requirements have not been determined due in part to the inherent difficulties of performing feeding trials on paralarvae. Our objective is to establish the essential fatty acid (EFA) requirements for paralarval stages of the common octopus through characterisation of the enzymes of endogenous LC-PUFA biosynthetic pathways. In this study we isolated a cDNA with high homology to fatty acyl desaturases (Fad). Functional characterisation in recombinant yeast showed the octopus Fad exhibited ∆5 desaturation activity towards saturated and polyunsaturated fatty acyl substrates. Thus, it efficiently converted the yeast’s endogenous 16:0 and 18:0 to 16:1n-11 and 18:1n-13, respectively, and desaturated exogenously added PUFA substrates, 20:4n-3 and 20:3n-6, to 20:5n-3 (EPA) and 20:4n-6 (ARA), respectively. Although the ∆5 Fad enables common octopus to produce EPA and ARA, the low availability of its adequate substrates 20:4n-3 and 20:3n-6, either in the diet or by limited endogenous synthesis from C18 PUFA, might indicate that EPA and ARA are indeed EFA for this species. Interestingly, the octopus ∆5 Fad can also participate in the biosynthesis of non-methylene interrupted FA, PUFA that are generally uncommon in vertebrates but that have been found previously in marine invertebrates including molluscs, and now also confirmed to be present in specific tissues of common octopus