Impact of Host Genetics and Biological Response Modifiers on Respiratory Tract Infections

Biological response modifiers; Immunogenetics; Inborn errorsModificadors de la resposta biològica; Immunogenètica; Errors congènitsModificadores de la respuesta biológica; Inmunogenética; Errores congénitosHost susceptibility to respiratory tract infections (RTI) is dependent on both genetic and acquired risk factors. Repeated bacterial and viral RTI, such as pneumonia from encapsulated microorganisms, respiratory tract infections related to respiratory syncytial virus or influenza, and even the development of bronchiectasis and asthma, are often reported as the first symptom of primary immunodeficiencies. In the same way, neutropenia is a well-known risk factor for invasive aspergillosis, as well as lymphopenia for Pneumocystis, and mycobacterial infections. However, in the last decades a better knowledge of immune signaling networks and the introduction of next generation sequencing have increased the number and diversity of known inborn errors of immunity. On the other hand, the use of monoclonal antibodies targeting cytokines, such as tumor necrosis factor alpha has revealed new risk groups for infections, such as tuberculosis. The use of biological response modifiers has spread to almost all medical specialties, including inflammatory diseases and neoplasia, and are being used to target different signaling networks that may mirror some of the known immune deficiencies. From a clinical perspective, the individual contribution of genetics, and/or targeted treatments, to immune dysregulation is difficult to assess. The aim of this article is to review the known and newly described mechanisms of impaired immune signaling that predispose to RTI, including new insights into host genetics and the impact of biological response modifiers, and to summarize clinical recommendations regarding vaccines and prophylactic treatments in order to prevent infections

Análisis de los sistemas agropecuarios del departamento de Santander.

Se describen y analizan las características ambientales, sociales y económicas del sector agropecuario del departamento de Santander y los componentes de los sistemas agropecuarios, con base en características de los agroecosistemas, relativas al clima, relieve, provincias de humedad, cobertura vegetal y nivel de tecnología empleada. Como resultado se obtuvieron 20 sistemas productivos entre agrícolas, agropecuarios, pecuarios y agroforestales, con lo cual se busca facilitar la planificación de la investigación y transferencia de tecnología de CORPOICA en el departamento. La información se procesó a partir de la configuración de una base de datos, mediante el Sistema de Información Georeferenciada SIG-ILWI

Ecological, genetic and evolutionary drivers of regional genetic differentiation in Arabidopsis thaliana

Background: Disentangling the drivers of genetic differentiation is one of the cornerstones in evolution. This is because genetic diversity, and the way in which it is partitioned within and among populations across space, is an important asset for the ability of populations to adapt and persist in changing environments. We tested three major hypotheses accounting for genetic differentiation—isolation-by-distance (IBD), isolation-by-environment (IBE) and isolation-by-resistance (IBR)—in the annual plant Arabidopsis thaliana across the Iberian Peninsula, the region with the largest genomic diversity. To that end, we sampled, genotyped with genome-wide SNPs, and analyzed 1772 individuals from 278 populations distributed across the Iberian Peninsula. Results: IBD, and to a lesser extent IBE, were the most important drivers of genetic differentiation in A. thaliana. In other words, dispersal limitation, genetic drift, and to a lesser extent local adaptation to environmental gradients, accounted for the within- and among-population distribution of genetic diversity. Analyses applied to the four Iberian genetic clusters, which represent the joint outcome of the long demographic and adaptive history of the species in the region, showed similar results except for one cluster, in which IBR (a function of landscape heterogeneity) was the most important driver of genetic differentiation. Using spatial hierarchical Bayesian models, we found that precipitation seasonality and topsoil pH chiefly accounted for the geographic distribution of genetic diversity in Iberian A. thaliana. Conclusions: Overall, the interplay between the influence of precipitation seasonality on genetic diversity and the effect of restricted dispersal and genetic drift on genetic differentiation emerges as the major forces underlying the evolutionary trajectory of Iberian A. thaliana

Revisiting the Taxonomy of the Genus Arcobacter: Getting Order From the Chaos

Since the description of the genus Arcobacter in 1991, a total of 27 species have been described, although some species have shown 16S rRNA similarities below 95%, which is the cut-off that usually separates species that belong to different genera. The objective of the present study was to reassess the taxonomy of the genus Arcobacter using information derived from the core genome (286 genes), a Multilocus Sequence Analysis (MLSA) with 13 housekeeping genes, as well as different genomic indexes like Average Nucleotide Identity (ANI), in silico DNA–DNA hybridization (isDDH), Average Amino-acid Identity (AAI), Percentage of Conserved Proteins (POCPs), and Relative Synonymous Codon Usage (RSCU). The study included a total of 39 strains that represent all the 27 species included in the genus Arcobacter together with 13 strains that are potentially new species, and the analysis of 57 genomes. The different phylogenetic analyses showed that the Arcobacter species grouped into four clusters. In addition, A. lekithochrous and the candidatus species ‘A. aquaticus’ appeared, as did A. nitrofigilis, the type species of the genus, in separate branches. Furthermore, the genomic indices ANI and isDDH not only confirmed that all the species were well-defined, but also the coherence of the clusters. The AAI and POCP values showed intra-cluster ranges above the respective cut-off values of 60% and 50% described for species belonging to the same genus. Phenotypic analysis showed that certain test combinations could allow the differentiation of the four clusters and the three orphan species established by the phylogenetic and genomic analyses. The origin of the strains showed that each of the clusters embraced species recovered from a common or related environment. The results obtained enable the division of the current genus Arcobacter in at least seven different genera, for which the names Arcobacter, Aliiarcobacter gen. nov., Pseudoarcobacter gen. nov., Haloarcobacter gen. nov., Malacobacter gen. nov., Poseidonibacter gen. nov., and Candidate ‘Arcomarinus’ gen. nov. are proposedThis work was supported in part by Grants JPIW2013-69095-C03-03 from the Ministerio de Economía y Competitividad (MINECO), AQUAVALENS of the Seventh Framework Program (FP7/2007-2013) grant agreement 311846 from the European Union and AGL2013-42628-R and AGL2016-77539-R (AEI/FEDER UE) from the Agencia Estatal de Investigación (Spain)S

Understanding the indirect DNA read-out specificity of I-CreI Meganuclease

The high DNA specificity of homing endonucleases makes them a powerful protein scaffold to engineer enzymes for genome manipulation. Understanding their molecular recognition of DNA is an important prerequisite to generate engineered enzymes able to cleave DNA in specific desired genome sites. Protein-DNA recognition studies have been mostly focused on specific direct contacts between amino acid side chains and bases to redesign the binding interface. However, the important role of indirect readout in the central region of the target DNA of the homing endonuclease I-CreI suggested that indirect readout may play a key role in the redesign of protein-DNA interactions. The sequences of the I-CreI central substrate region, 2NN, along with the adjacent 5NNN, are key for substrate cleavage. Here, we analyse the mechanism of target discrimination at the 5NNN region by the I-CreI protein, revealing its critical role in the location and occupancy of the catalytic metal ions, which is crucial for cleavage. Our data highlight the importance of indirect readout for target DNA cleavage, thus aiding I-CreI engineering when targeting new DNA sequences.e thank the Swiss Light Source (SLS) and ALBA beamline staff for their support. This work was supported by the Spanish MINECO (JCI-2011-09308 to R.M and CTQ2017-83810-R to F.J.B.), the Severo Ochoa Excellence Accreditation (SEV-2016-0644) and the Novo Nordisk Foundation (Grant NNF14CC0001 to G.M.),S

Applications of Direct Injection Soft Chemical Ionisation-Mass Spectrometry for the Detection of Pre-blast Smokeless Powder Organic Additives

Analysis of smokeless powders is of interest from forensics and security perspectives. This article reports the detection of smokeless powder organic additives (in their pre-detonation condition), namely the stabiliser diphenylamine and its derivatives 2-nitrodiphenylamine and 4-nitrodiphenylamine, and the additives (used both as stabilisers and plasticisers) methyl centralite and ethyl centralite, by means of swab sampling followed by thermal desorption and direct injection soft chemical ionisation-mass spectrometry. Investigations on the product ions resulting from the reactions of the reagent ions H3O+ and O2+ with additives as a function of reduced electric field are reported. The method was comprehensively evaluated in terms of linearity, sensitivity and precision. For H3O+, the limits of detection (LoD) are in the range of 41-88 pg of additive, for which the accuracy varied between 1.5 and 3.2%, precision varied between 3.7 and 7.3% and linearity showed R20.9991. For O2+, LoD are in the range of 72 to 1.4 ng, with an accuracy of between 2.8 and 4.9% and a precision between 4.5 and 8.6% and R20.9914. The validated methodology was applied to the analysis of commercial pre-blast gun powders from different manufacturers.(VLID)4826148Accepted versio

Variations in the cellular proliferation of prolactin cells from late pregnancy to lactation in rats

[EN]Lactation is a physiological process associated with hyperactivity of hypophyseal prolactin-producing cells. It is known that the percentage of these cells is increased during lactation, although there are discrepancies in the reports regarding the mechanisms responsible for increasing the number of prolactin cells. In order to analyse whether this increase is a result of previous proliferation, variations in the proliferation rate of prolactinpositive cells were determined from late pregnancy to lactation in adult female rats by means of observation of the immunohistochemical expression of PCNA as a marker of cellular proliferation. During late pregnancy, a very significant increase in the percentage of proliferating prolactin cells was observed in comparison to non-pregnant females in the proestrus phase (p < 0.01). Although the percentage of prolactin-positive cells after one week of lactation was higher than in non-lactating or in pregnant females (p < 0.01), the proliferation rate was lower than in the other groups studied. In sum, our results suggest that late pregnancy constitutes a preliminary proliferative phase preparatory to the ensuing lactation phase and that endocrine changes in late pregnancy involve the cellular proliferation of hypophyseal prolactin cells in order to prepare the gland for later demands and to prevent proliferative changes from occurring during lactation

Ordered vacancy network induced by the growth of epitaxial graphene on Pt(111)

We have studied large areas of (v3×v3)R30° graphene commensurate with a Pt(111) substrate. A combination of experimental techniques with ab initio density functional theory indicates that this structure is related to a reconstruction at the Pt surface, consisting of an ordered vacancy network formed in the outermost Pt layer and a graphene layer covalently bound to the Pt substrate. The formation of this reconstruction is enhanced if low temperatures and polycyclic aromatic hydrocarbons are used as molecular precursors for epitaxial growth of the graphene layers

Impact of Host Genetics and Biological Response Modifiers on Respiratory Tract Infections

Host susceptibility to respiratory tract infections (RTI) is dependent on both genetic and acquired risk factors. Repeated bacterial and viral RTI, such as pneumonia from encapsulated microorganisms, respiratory tract infections related to respiratory syncytial virus or influenza, and even the development of bronchiectasis and asthma, are often reported as the first symptom of primary immunodeficiencies. In the same way, neutropenia is a well-known risk factor for invasive aspergillosis, as well as lymphopenia for Pneumocystis, and mycobacterial infections. However, in the last decades a better knowledge of immune signaling networks and the introduction of next generation sequencing have increased the number and diversity of known inborn errors of immunity. On the other hand, the use of monoclonal antibodies targeting cytokines, such as tumor necrosis factor alpha has revealed new risk groups for infections, such as tuberculosis. The use of biological response modifiers has spread to almost all medical specialties, including inflammatory diseases and neoplasia, and are being used to target different signaling networks that may mirror some of the known immune deficiencies. From a clinical perspective, the individual contribution of genetics, and/or targeted treatments, to immune dysregulation is difficult to assess. The aim of this article is to review the known and newly described mechanisms of impaired immune signaling that predispose to RTI, including new insights into host genetics and the impact of biological response modifiers, and to summarize clinical recommendations regarding vaccines and prophylactic treatments in order to prevent infections