Interactions between 2,4-bis-pteridine-1,5-benzodiazepine and group 12 dihalides: synthesis, spectral and XRD structural studies and theoretical calculations

2,4-Bis(1,3,7-trimethyl-pteridine-2,4(1H,3H)-dione-6-yl)-2,3-dihydro-2-methyl-1H-1,5-benzodiazepine (DLMBZD) has been prepared and its molecular and crystal structures have been determined from spectral and XRD data. The benzodiazepine ligand was reacted with zinc(II), cadmium(II) and mercury(II) chloride, bromide and iodide to give complexes with general formula [M(DLMBZD)X2]. The complexes have been synthesized and characterized by IR, NMR and elemental analysis. The structure of seven complexes has been obtained by single crystal X-ray diffraction. In all the cases, the metal is (2 + 2 + 1)-five-coordinated by two halide ligands, two nitrogen atoms from pyrazine and diazepine rings and a carbonyl oxygen from a pteridine ring. The coordinated-metal environment is a square-based pyramid, with increasing trigonality from Hg(II) to Zn(II) complexes. To coordinate the metals, the ligand folds itself, establishing four intramolecular σ–π interactions with the pyrimidine and pyrazine rings. A topological analysis of the electron density using the Quantum Theory of Atoms in Molecules and the complexes stability has been performed.Supported by the University of Jaén (Plan de Apoyo a la Investigación, al Desarrollo Tecnológico y a la Innovación), Junta de Andalucía (PAIDI groups FQM195, FQM273 and FQM337) and the State Secretariat for Research, Development and Innovation of Spanish Ministry of Economy and Competitivity (Project “Red de Excelencia MetalBio”, CTQ2015-71211-REDT)

Functionalization of reduced graphene oxide with polysulfone brushes enhance antibacterial properties and reduce human cytotoxicity

The present study reports two routes to modify reduced graphene oxide (rGO) nanosheets with polysulfone (PSU) brushes via nitrene chemistry. The PSU polymer is bonded to rGO at the extremity (rGO-PSU end) and at the middle of the PSU chain (rGO-PSU mid). The resulting rGO-PSU synthetic products are carefully characterized by Raman and FTIR spectroscopy, XPS, TEM, and thermogravimetric analysis, evidencing the successful grafting of PSU onto rGO surfaces. The long-term stability of these nanosheets is also determined in common solvents. The antibacterial properties of polymer-functionalized rGO against the planktonic Bacilus subtilis and Escherichia coli are also investigated. It is established that the antimicrobial properties of these nanocomposites are due to the production of reactive oxygen species. The results also demonstrate that rGO-PSU mid presents better antimicrobial properties due to shorter polymer chains, which improves the contact of the microorganisms with the graphene surface.This work was financially supported by the Spanish Ministry of Economy and Competitiveness (MAT2014-57557-R), and partially supported by the U.S. National Science Foundation Career Award (NSF Award #104093). R.O. would like acknowledge support from U.S. National Science Foundation (CMMI-1538730 and DUE-CMMI-1538730/1003574). Janire Peña wants to acknowledge mobility grant from Carlos III University and Instituto Tecnológico de Química y Materiales “Alonso Barba”. Authors acknowledge Dr. A. Esteban-Arranz for giving access to ATR equipment

Twenty years of ground-based NDACC FTIR spectrometry at Izaña Observatory - overview and long-term comparison to other techniques

High-resolution Fourier transform infrared (FTIR) solar observations are particularly relevant for climate studies, as they allow atmospheric gaseous composition and multiple climate processes to be monitored in detail. In this context, the present paper provides an overview of 20 years of FTIR measurements taken in the framework of the NDACC (Network for the Detection of Atmospheric Composition Change) from 1999 to 2018 at the subtropical Izaña Observatory (IZO, Spain). Firstly, long-term instrumental performance is comprehensively assessed, corroborating the temporal stability and reliable instrumental characterization of the two FTIR spectrometers installed at IZO since 1999. Then, the time series of all trace gases contributing to NDACC at IZO are presented (i.e. C2H6, CH4, ClONO2, CO, HCl, HCN, H2CO, HF, HNO3, N2O, NO2, NO, O3, carbonyl sulfide (OCS), and water vapour isotopologues H162O, H182O, and HD16O), reviewing the major accomplishments drawn from these observations. In order to examine the quality and long-term consistency of the IZO FTIR observations, a comparison of those NDACC products for which other high-quality measurement techniques are available at IZO has been performed (i.e. CH4, CO, H2O, NO2, N2O, and O3). This quality assessment was carried out on different timescales to examine what temporal signals are captured by the FTIR records, and to what extent. After 20 years of operation, the IZO NDACC FTIR observations have been found to be very consistent and reliable over time, demonstrating great potential for climate research. Long-term NDACC FTIR data sets, such as IZO, are indispensable tools for the investigation of atmospheric composition trends, multi-year phenomena, and complex climate feedback processes, as well as for the validation of past and present space-based missions and chemistry climate models.The Izaña FTIR station has been supported by the German Bundesministerium für Wirtschaft und Energie (BMWi) via DLRunder grants 50EE1711A and by the Helmholtz Society via the research program ATMO. In addition, this research was funded by the European Research Council under FP7/(2007-2013)/ERC Grant agreement nº 256961 (project MUSICA), by the Deutsche Forschungsgemeinschaft for the project MOTIV (GeschaFTIRzeichen SCHN 1126/2-1), by the Ministerio de Economía y Competitividad from Spain through the projects CGL2012-37505 (project NOVIA) and CGL2016-80688-P (project INMENSE), and by EUMETSAT under its Fellowship Programme (project VALIASI)

New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease without a well-defined genetic alteration responsible for the onset of the disease. Several lines of evidence coincide in identifying stimulatory and growth signals delivered by B-cell receptor (BCR), and co-receptors together with NFkB pathway, as being the driving force in B-cell survival in CLL. However, the molecular mechanism responsible for this activation has not been identified. Based on the hypothesis that BCR activation may depend on somatic mutations of the BCR and related pathways we have performed a complete mutational screening of 301 selected genes associated with BCR signaling and related pathways using massive parallel sequencing technology in 10 CLL cases. Four mutated genes in coding regions (KRAS, SMARCA2, NFKBIE and PRKD3) have been confirmed by capillary sequencing. In conclusion, this study identifies new genes mutated in CLL, all of them in cases with progressive disease, and demonstrates that next-generation sequencing technologies applied to selected genes or pathways of interest are powerful tools for identifying novel mutational changes

The Expanded mtDNA Phylogeny of the Franco-Cantabrian Region Upholds the Pre-Neolithic Genetic Substrate of Basques

The European genetic landscape has been shaped by several human migrations occurred since Paleolithic times. The accumulation of archaeological records and the concordance of different lines of genetic evidence during the last two decades have triggered an interesting debate concerning the role of ancient settlers from the Franco-Cantabrian region in the postglacial resettlement of Europe. Among the Franco-Cantabrian populations, Basques are regarded as one of the oldest and more intriguing human groups of Europe. Recent data on complete mitochondrial DNA genomes focused on macrohaplogroup R0 revealed that Basques harbor some autochthonous lineages, suggesting a genetic continuity since pre-Neolithic times. However, excluding haplogroup H, the most representative lineage of macrohaplogroup R0, the majority of maternal lineages of this area remains virtually unexplored, so that further refinement of the mtDNA phylogeny based on analyses at the highest level of resolution is crucial for a better understanding of the European prehistory. We thus explored the maternal ancestry of 548 autochthonous individuals from various Franco-Cantabrian populations and sequenced 76 mitogenomes of the most representative lineages. Interestingly, we identified three mtDNA haplogroups, U5b1f, J1c5c1 and V22, that proved to be representative of Franco-Cantabria, notably of the Basque population. The seclusion and diversity of these female genetic lineages support a local origin in the Franco-Cantabrian area during the Mesolithic of southwestern Europe, ∼10,000 years before present (YBP), with signals of expansions at ∼3,500 YBP. These findings provide robust evidence of a partial genetic continuity between contemporary autochthonous populations from the Franco-Cantabrian region, specifically the Basques, and Paleolithic/Mesolithic hunter-gatherer groups. Furthermore, our results raise the current proportion (≈15%) of the Franco-Cantabrian maternal gene pool with a putative pre-Neolithic origin to ≈35%, further supporting the notion of a predominant Paleolithic genetic substrate in extant European populations

Validation of the Spanish Version of the ICECAP-O for Nursing Home Residents with Dementia

Background Measurement of health-related quality of life (HRQoL) is important for a chronic disease, such as dementia, which impairs the quality of life of affected patients in addition to their length of life. This is important in the context of economic evaluations when interventions do not (only) affect HRQoL and these other factors also affect overall quality of life. Objective To validate the Spanish translation of the ICECAP-O's capability to measure Health-related quality of life in elderly with dementia who live in nursing homes. Method Cross-sectional study. For 217 residents living in 8 Spanish nursing homes, questionnaires were completed by nursing professionals serving as proxy respondents. We analyzed the internal consistency and other psychometric properties. We investigated the convergent validity of the ICECAP-O with other HRQoL instruments, the EQ-5D extended with a cognitive dimension (EQ-5D+C), the Alzheimer's Disease Related Quality of Life (ADRQL) measures, and the Barthel Index measure of activities of daily living (ADL). Results The ICECAP-O presents satisfactory internal consistency (alpha 0.820). The factorial analysis indicated a structure of five principal dimensions that explain 66.57% of the total variance. Convergent validity between the ICECAP-O, EQ-5D+C, ADRQL, and Barthel Index scores was moderate to good (with correlations of 0.62, 0.61, and 0.68, respectively), but differed between dimensions of the instruments. Discriminant validity was confirmed by finding differences in ICECAP-O scores between subgroups based on ADL scores (0.70 low, 0.59 medium, and 0.39 high level care), dementia severity (0.72 mild, 0.63 medium, and 0.50 severe), and ages (0.59 below 75 years and 0.84 above 75 years). Conclusions This study presented the first use of a Spanish version of the ICECAP-O. The results indicate that the ICECAP-O appears to be a reliable Health-related quality of life measurement instrument showing good convergent and discriminant validity for people with dementia

Self-Reported Health Status in Primary Health Care: The Influence of Immigration and Other Associated Factors

OBJECTIVE: The aims of this study are to compare self-reported health status between Spanish-born and Latin American-born Spanish residents, adjusted by length of residence in the host country; and additionally, to analyse sociodemographic and psychosocial variables associated with a better health status. DESIGN: This is a cross-sectional population based study of Latin American-born (n = 691) and Spanish-born (n = 903) in 15 urban primary health care centres in Madrid (Spain), carried out between 2007 and 2009. The participants provided information, through an interview, about self-reported health status, socioeconomic characteristics, psychosocial factors and migration conditions. Descriptive and multiple logistic regression analyses were conducted. RESULTS: The Spanish-born participants reported a better health status than the Latin America-born participants (79.8% versus 69.3%, p<0.001). Different patterns of self-reported health status were observed depending on the length of residence in the host country. The proportion of immigrants with a better health status is greater in those who have been in Spain for less than five years compared to those who have stayed longer. Better health status is significantly associated with being men, under 34 years old, being Spanish-born, having a monthly incomes of over 1000 euros, and having considerable social support and low stress. CONCLUSIONS: Better self-reported health status is associated with being Spanish-born, men, under 34 years old, having an uppermiddle-socioeconomic status, adequate social support, and low stress. Additionally, length of residence in the host country is seen as a related factor in the self-reported health status of immigrants

Genome-Wide Association Study of Multiple Sclerosis Confirms a Novel Locus at 5p13.1

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80–0.89; p = 1.36×10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS