BRAF and TERT mutations in papillary thyroid cancer patients of Latino ancestry.

Papillary thyroid cancer (PTC) is the second most commonly diagnosed malignancy in U.S. Latinas and in Colombian women. Studies in non-Latinos indicate that BRAF and TERT mutations are PTC prognostic markers. This study aimed to determine the prevalence and clinical associations of BRAF and TERT mutations in PTC Latino patients from Colombia. We analyzed mutations of BRAF (V600E) and TERT promoter (C228T, C250T) in tumor DNA from 141 patients (75 with classical variant PTC, CVPTC; 66 with follicular variant PTC, FVPTC) recruited through a multi-center study. Associations between mutations and clinical variables were evaluated with Fisher exact tests. Survival was evaluated with Kaplan-Meier plots. Double-mutant tumors (BRAF+/TERT+, n = 14 patients) were more common in CVPTC (P = 0.02). Relative to patients without mutations (n = 48), double mutations were more common in patients with large tumors (P = 0.03), lymph node metastasis (P = 0.01), extra-thyroid extension (P = 0.03), and advanced stage (P = 6.0 × 10-5). In older patients, TERT mutations were more frequent (mean age 51 years vs 45 years for wild type TERT, P = 0.04) and survival was lower (HR = 1.20; P = 0.017); however, given the small sample size, the decrease in survival was not statically significant between genotypes. Comparisons with published data in US whites revealed that Colombian patients had a higher prevalence of severe pathological features and of double-mutant tumors (10 vs 6%, P = 0.001). Mutations in both oncogenes show prognostic associations in Latinos from Colombia. Our study is important to advance Latino PTC precision medicine and replicates previous prognostic associations between BRAF and TERT in this population

The HABP2 G534E polymorphism does not increase nonmedullary thyroid cancer risk in Hispanics.

Familial nonmedullary thyroid cancer (NMTC) has not been clearly linked to causal germline variants, despite the large role that genetic factors play in risk. Recently, HABP2 G534E (rs7080536A) has been implicated as a causal variant in NMTC. We have previously shown that the HABP2 G534E variant is not associated with TC risk in patients from the British Isles. Hispanics are the largest and the youngest minority in the United States and NMTC is now the second most common malignancy in women from this population. In order to determine if the HABP2 G534E variant played a role in NMTC risk among Hispanic populations, we analyzed 281 cases and 1105 population-matched controls from a multicenter study in Colombia, evaluating the association through logistic regression. We found that the HABP2 G534E variant was not significantly associated with NMTC risk (P=0.843) in this Hispanic group. We also stratified available clinical data by multiple available clinicopathological variables and further analyzed the effect of HABP2 on NMTC presentation. However, we failed to detect associations between HABP2 G534E and NMTC risk, regardless of disease presentation (P≥0.273 for all cases). Therefore, without any significant associations between the HABP2 G534E variant and NMTC risk, we conclude that the variant is not causal of NMTC in this Hispanic population

Colloidal nanomaterials for water quality improvement and monitoring

Water is the most important resource for all kind forms of live. It is a vital resource distributed unequally across different regions of the globe, with populations already living with water scarcity, a situation that is spreading due to the impact of climate change. The reversal of this tendency and the mitigation of its disastrous consequences is a global challenge posed to Humanity, with the scientific community assuming a major obligation for providing solutions based on scientific knowledge. This article reviews literature concerning the development of nanomaterials for water purification technologies, including collaborative scientific research carried out in our laboratory (nanoLAB@UA) framed by the general activities carried out at the CICECO-Aveiro Institute of Materials. Our research carried out in this specific context has been mainly focused on the synthesis and surface chemical modification of nanomaterials, typically of a colloidal nature, as well as on the evaluation of the relevant properties that arise from the envisaged applications of the materials. As such, the research reviewed here has been guided along three thematic lines: 1) magnetic nanosorbents for water treatment technologies, namely by using biocomposites and graphite-like nanoplatelets; 2) nanocomposites for photocatalysis (e.g., TiO2/Fe3O4 and POM supported graphene oxide photocatalysts; photoactive membranes) and 3) nanostructured substrates for contaminant detection using surface enhanced Raman scattering (SERS), namely polymers loaded with Ag/Au colloids and magneto-plasmonic nanostructures. This research is motivated by the firm believe that these nanomaterials have potential for contributing to the solution of environmental problems and, conversely, will not be part of the problem. Therefore, assessment of the impact of nanoengineered materials on eco-systems is important and research in this area has also been developed by collaborative projects involving experts in nanotoxicity. The above topics are reviewed here by presenting a brief conceptual framework together with illustrative case studies, in some cases with original research results, mainly focusing on the chemistry of the nanomaterials investigated for target applications. Finally, near-future developments in this research area are put in perspective, forecasting realistic solutions for the application of colloidal nanoparticles in water cleaning technologies.publishe

Multifunctional silver-coated transparent TiO2 thin films for photocatalytic and antimicrobial applications

Transparent TiO2 thin films coated with Ag NPs were synthesized using two industrially applicable techniques, pulsed laser ablation (PLAL) and spray pyrolysis without using high vacuum. These transparent thin films were deposited on glass in order to generate glass materials with photocatalytic and antimicrobial properties and a minimum loss of transparency. The structural, morphological and optical properties of the thin films were examined using Grazing incidence X-ray diffraction (GIXRD), Raman spectroscopy, Scanning electron microscopy (SEM) and ultraviolet–visible spectroscopy. Transmission electron microscopy (TEM) was used to identify the NPs on the TiO2 surface. The transmittance value for the thin films was greater than 80%.The thin films thus synthesized were then assessed to determine their photocatalytic capacity by monitoring the degradation of Rhodamine B (RhB) under UV light irradiation. Ag NPs on the TiO2 surface ensures an improvement in the photocatalytic properties, with a 99% degradation of RhB in 210 min under UV light. In addition, these transparent thin films showed high antimicrobial activity on Gram-negative bacteria when irradiated by UV light for 4 h, killing 93% of these bacteria.Funding for open access charge: CRUE-Universitat Jaume

New flavonoid \u2013 N,N-dibenzyl(N-methyl)amine hybrids: Multi-target-directed agents for Alzheimer\ub4s disease endowed with neurogenic properties

The design of multi-target directed ligands (MTDLs) is a valid approach for obtaining effective drugs for complex pathologies. MTDLs that combine neuro-repair properties and block the first steps of neurotoxic cascades could be the so long wanted remedies to treat neurodegenerative diseases (NDs). By linking two privileged scaffolds with well-known activities in ND-targets, the flavonoid and the N,N-dibenzyl(N-methyl)amine (DBMA) fragments, new CNS-permeable flavonoid \u2013 DBMA hybrids (1\u201313) were obtained. They were subjected to biological evaluation in a battery of targets involved in Alzheimer\u2019s disease (AD) and other NDs, namely human cholinesterases (hAChE/hBuChE), \u3b2-secretase (hBACE-1), monoamine oxidases (hMAO-A/B), lipoxygenase-5 (hLOX-5) and sigma receptors (\u3c31R/\u3c32R). After a funnel-type screening, 6,7-dimethoxychromone \u2013 DBMA (6) was highlighted due to its neurogenic properties and an interesting MTD-profile in hAChE, hLOX-5, hBACE-1 and \u3c31R. Molecular dynamic simulations showed the most relevant drug-protein interactions of hybrid 6, which could synergistically contribute to neuronal regeneration and block neurodegeneration

Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling

Neuroinflammation is characterized by activation of microglial cells, followed by production of nitric oxide (NO), which may have different outcomes on neurogenesis, favoring or inhibiting this process. In the present study, we investigated how the inflammatory mediator NO can affect proliferation of neural stem cells (NSCs), and explored possible mechanisms underlying this effect. We investigated which mechanisms are involved in the regulation of NSC proliferation following treatment with an inflammatory stimulus (lipopolysaccharide plus IFN-gamma), using a culture system of subventricular zone (SVZ)-derived NSCs mixed with microglia cells obtained from wild-type mice (iNOS(+/+)) or from iNOS knockout mice (iNOS(-/-)). We found an impairment of NSC cell proliferation in iNOS(+/+) mixed cultures, which was not observed in iNOS(-/-) mixed cultures. Furthermore, the increased release of NO by activated iNOS(+/+) microglial cells decreased the activation of the ERK/MAPK signaling pathway, which was concomitant with an enhanced nitration of the EGF receptor. Preventing nitrogen reactive species formation with MnTBAP, a scavenger of peroxynitrite (ONOO-), or using the ONOO- degradation catalyst FeTMPyP cell proliferation and ERK signaling were restored to basal levels in iNOS(+/+) mixed cultures. Moreover, exposure to the NO donor NOC-18 (100 mu M), for 48 h, inhibited SVZ-derived NSC proliferation. Regarding the antiproliferative effect of NO, we found that NOC-18 caused the impairment of signaling through the ERK/MAPK pathway, which may be related to increased nitration of the EGF receptor in NSC. Using MnTBAP nitration was prevented, maintaining ERK signaling, rescuing NSC proliferation. We show that NO from inflammatory origin leads to a decreased function of the EGF receptor, which compromised proliferation of NSC. We also demonstrated that NO-mediated nitration of the EGF receptor caused a decrease in its phosphorylation, thus preventing regular proliferation signaling through the ERK/MAPK pathway.Foundation for Science and Technology, (FCT, Portugal); COMPETE; FEDER [PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014, PTDC/SAU-NEU/102612/2008, PTDC/NEU-OSD/0473/2012]; FCT, Portugal [SERH/BPD/78901/2011, SERH/BD/38127/2007, SFRH/BD/77903/2011, SFRH/BD/79308/2011]info:eu-repo/semantics/publishedVersio

Coccolithophore calcification is independent of carbonate chemistry in the tropical ocean

Marañón, Emilio ... et al.-- 13 pages, 7 figures, 1 table, supporting information https://dx.doi.org/10.1002/lno.10295Short-term experiments indicate that seawater acidification can cause a decrease in the rate of calcification by coccolithophores, but the relationship between carbonate chemistry and coccolithophore calcification rate in natural assemblages is still unclear. During the Malaspina 2010 circumnavigation, we measured primary production, calcification, coccolithophore abundance, particulate inorganic carbon (PIC) concentration, and the parameters of the carbonate system, along basin-scale transects in the tropical Atlantic, Indian and Pacific oceans. Euphotic layer-integrated calcification and mean cell-specific calcification in the euphotic layer ranged between 2–10 mgC m−2 d−1 and 5–20 pgC cell−1 d−1, respectively. We found a significant relationship between primary production and calcification, such that the calcification to primary production (CP/PP) ratio was relatively invariant among ocean basins, with an overall mean value of 0.05 ± 0.04. Extrapolating this value to the entire ocean would result in a global pelagic calcification rate of 2.4 PtC yr−1. The mean PIC concentration in surface waters was 1.8 ± 1.6 mgC m−3 and its turnover time averaged 20 d. We combined our data of calcification, primary production, and carbonate chemistry from Malaspina 2010 with those obtained during two previous cruises in the northern Arabian Sea. Both the CP/PP ratio and cell-specific calcification were largely constant across a wide range of calcite saturation state (1.5–6.5), [ inline image]/[H+] (0.08–0.24; mol: μmol), and pH (7.6–8.1), which indicates that calcification by natural coccolithophore assemblages was independent of carbonate chemistry. Our results suggest that coccolithophore calcification, at least in tropical regions, may not be decreasing in the currently acidifying oceanFunding for this study was provided by the Spanish Ministry of Science and Innovation through research projects Malaspina 2010 (grant no. CSD2008-00077), PERSEO (CTM2007-28925-E/MAR), MANIFEST (CTM2012-32017) and TERRIFIC (CTM2014-53582-R). Funding for W.M.B. came from the NSF (OCE-0961660; OCE1220068), NASA (NNX11AO72G; NNX11AL93G; NNX14AQ41G; NNX14AQ43A; NNX14AL92G; NNX14AM77G) and NOAA (NA11OAR4310055).Peer Reviewe

Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia

BACKGROUND: The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. METHODS: BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. RESULTS: The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. CONCLUSIONS: Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening

Phytoplankton across Tropical and Subtropical Regions of the Atlantic, Indian and Pacific Oceans

Postprint4,411

Evaluación del impacto social de la Licenciatura en Educación Especial en dos subregiones de Antioquia, Colombia

This research paper presents the results of the evaluation of the social impact of the Special Education undergraduate program, of the University of Antioquia’s Education Faculty, in the East and Southwest subregions of the Antioquia department (Colombia). The main objective was to evaluate the impact of the Program among the graduates and other audiences. The methodology was carried out under a qualitative design, in the evaluative research modality, Social Programs impact type of evaluation. The results of the research were structured under the following categories: Assessment of the quality of the Program, the role of the Special Educator, significant experiences and their impact, and location and working conditions of the graduates. Finally, it poses recommendations to various academic units of the University.Keywords: special education, evaluation, social impact, graduates, occupational performance, assessment.En el presente artículo se dan a conocer los resultados de la evaluación del impacto social del programa de Licenciatura en Educación Especial, Facultad de Educación de la Universidad de Antioquia, en las subregiones de Oriente y Suroeste del departamento de Antioquia (Colombia), cuyo objetivo principal fue evaluar el impacto del Programa desde los egresados y otras audiencias. La metodología se llevó a cabo bajo un diseño cualitativo, modalidad de investigación evaluativa, tipo de evaluación de impacto de programas sociales. Los resultados se estructuraron bajo las categorías: valoración de la calidad del Programa, rol del educador especial, experiencias significativas y su impacto, y ubicación y condiciones laborales de los egresados y egresadas. Finalmente, se plantean recomendaciones a diferentes unidades académicas de la Universidad