1,392 research outputs found
Trends in U.S. Public Awareness of Racial and Ethnic Health Disparities (1999-2010): Study Brief
None provided
Robust LHC Higgs Search in Weak Boson Fusion
We demonstrate that an LHC Higgs search in weak boson fusion production with
subsequent decay to weak boson pairs is robust against extensions of the
Standard Model or MSSM involving a large number of Higgs doublets. We also show
that the transverse mass distribution provides unambiguous discrimination of a
continuum Higgs signal from the Standard Model.Comment: 12p, 2 figs., additional comments on backgrounds, version to appear
in PR
Validación de una metodología analítica para la cuantificación de polifenoles totales, en procesos de extracción asistida por microondas sobre frutos de la especie colombiana Vaccinium meridionale
En este trabajo se muestra el desarrollo y la validación de un método analítico para la cuantificación de polifenoles totales con el reactivo de Folin-Ciocalteu (F–C),en procesos de extracción asistida por microondas (MAE), sobre frutos de la especie colombiana Vaccinium meridionale. Los resultados obtenidos en los parámetros selectividad, linealidad, repetibilidad y exactitud muestran que la metodología propuesta es confiable para evaluar el efecto de las condiciones de extracción sobre la cantidad de polifenoles removidos.The in vitro pharmacological model of P. falciparum culture is crucial in the initial screening for substances or plant extracts with possible antiplasmodial activity. The parasite density can be determined by varied methods, however have been described numerous advantages and disadvantages associated with each of them.The incubation time required for staining and the use of synchronous or asynchronous cultures were assessed for optimal settings; showing optimal time of 2 h, and lower limits of detection and quantification in asynchronous cultures. Employing the FCB2 and FCR3 strains, was evidenced a background noise of 12% and 38% respectively; linearity showed a good correlation, r2 of 0.9644 (FCR3) and 0.9841 (FCB2) and a slope of 1761.8 and 852.4, respectively. It was evidenced agreement between the methods, fluorometric with SYBR Green I (SYBRG I) and microscopic with Giemsa, the mean difference was 0.00002% and 0.09109% respectively for FCR3 and FCB2, The limits of detection and quantification were 0.5% and 1.5% of parasitaemia. The Z factor was 0.376 with FCB2, whereas with FCR3 reached 0.702. The inhibitory concentration 50 (IC50) against P. falciparum FCR3, generated by chloroquine (CQ), was 0.37 mcg/mL by microscopy and 0.35 mcg/mL by fluorometry.Our findings suggest that the SYBRG I fluorescence based assay, by using fluorometers commonly available in many laboratories, is precise, robust, fast and accurate; for the in vitro evaluation of substances or extracts with possible antiplasmodial activity
Planeamiento estratégico del sector de operación y mantenimiento en petróleo y gas
La producción de petróleo y gas ha estado consolidándose en el mundo. A 2014
Europa depende de Rusia, Alemania, y los Países Árabes para su desarrollo energético e
industrial; y en América, EE.UU., Brasil, México, y Venezuela generan la mayor producción
de crudo. Para el Sector de Operación y Mantenimiento en Petróleo y Gas, esta
consolidación constituye una oportunidad de focalizar sus esfuerzos para abarcar un mercado
que cada vez se hace más exigente en términos de eficiencia operacional. La reciente
reducción de los precios de petróleo establece como prioridad la necesidad de optimizar los
costos y por ello elementos como la tecnología, la investigación, y desarrollo se hacen
cruciales para mantener la eficiencia operativa del Sector.
Conscientes de esta necesidad, se desarrolla el plan estratégico para el Sector de
Operación y Mantenimiento en Petróleo y Gas con la finalidad de: (a) fortalecerlo, (b)
ampliar mercado a otros países de América, (c) generar un nivel técnico y tecnológico a partir
de procesos de investigación y desarrollo que le permita ser más competitivo, (d) lograr el
liderazgo del mercado latinoamericano, y (e) generar impactos positivos en las comunidades
que seguirá siendo un aspecto de especial atención en el desarrollo del Sector.
En este sentido las estrategias van dirigidas a cumplir con estos propósitos y por ello
estas tratan de: (a) incrementar el mercado a través de alianzas y cubrimiento de nuevos
países, (b) mejorar las condiciones de trabajo con el mejoramiento de los procesos
incorporando tecnología y vinculando a la empresa privada en proyectos de investigación y
desarrollo, y (c) crear esquemas de sustentabilidad de las operaciones trabajando con la
comunidad para mejorar sus condiciones de vida. Con estas propuestas se espera contribuir
en el posicionamiento de Colombia como protagonista competitivo en el Sector de Operación
y Mantenimiento en Petróleo y Gas puesto que se incrementaría la productividad y por ende
la rentabilidad de las compañías de producción de petróleo y gas.The production of oil and gas has been consolidating in the world. In 2014, Europe
depended on Russia, Germany, and the Arabian Countries for its energy and industrial
development; and in America, USA, Brazil, Mexico, and Venezuela generated the largest oil
production. For the Operation and Maintenance in Oil and Gas Industry, this consolidation is
an opportunity to focus their efforts to cover a market that is becoming more demanding in
terms of operational efficiency. The recent decline in oil prices prioritizes the need to
optimize costs and thus elements such as technology, research and development become
crucial to maintain operational efficiency of the Industry.
Recognizing this need, the strategic plan for the Operation and Maintenance in Oil
and Gas Industry in order to develop is: (a) strengthen, (b) expand market to other countries
in America, (c) generating a technical and technological level from processes of research and
development to enable you to be more competitive, (d) achieve leadership in the Latin
American market, and (e) generate positive impacts on communities will remain an area of
particular focus in the development of this Industry.
For this reason, strategies are directed to accomplish these objectives and these
strategies are: (a) increase the market through partnerships and developing new countries, (b)
improve working conditions with process improvement incorporating technology and linking
private enterprise in research and development, and (c) creating operation’s sustainability
schemes working with the community to improve their living conditions.
These proposals are expected will contribute to the positioning of Colombia as a
competitive player in the Operation and Maintenance in Oil and Gas Industry because
productivity would increase and thus the profitability of companies producing oil and gas.Tesi
Drivers of variability in blue carbon stocks and burial rates across europeanestuarine habitats
The implementation of climate change mitigation strategies based on the conservation and restoration of Blue Carbon ecosystems requires a deep understanding of themagnitude and variability in organic carbon (Corg) storage across and within these ecosystems. This study explored the variability in soil Corg stocks and burial rates across and within intertidal estuarine habitats of the Atlantic European coast and its relation to biotic and abiotic drivers. A total of 136 soil cores were collected across saltmarshes located at different tidal zones (high marsh, N = 45; low marsh, N = 30), seagrass meadows (N=17) and tidal flats (N=44), and from the inner to the outer sections of five estuaries characterized by different basin land uses. Soil Corg stocks were higher in high-marsh communities (65±3 Mg ha-1) than in low-marsh communities (38 ±3 Mg ha-1), seagrass meadows (40 ± 5 Mg ha-1) and unvegetated tidal flats (46± 3Mg ha-1) whereas Corg burial rates also tended to be higher in highmarshes (62±13 g m-2 y-1) compared to low marshes (43 ± 15 g m-2 y-1) and tidal flats (35 ± 9 g m-2 y-1). Soil Corg stocks and burial rates decreased from inner to outer estuarine sections in most estuaries reflecting the decrease in the river influence towards the estuary mouth. Higher soil Corg stocks were related to higher content of silt and clay and higher proportion of forest and natural land within the river basin, pointing at new opportunities for protecting coastal natural carbon sinks based on the conservation and restoration of upland ecosystems. Our study contributes to the global inventory of Blue Carbon by adding data from unexplored regions and habitats in Europe, and by identifying drivers of variability across and within estuaries.The authors acknowledge the financial support fromthe Government of Cantabria through the “Fénix Programme”. IM was supported by a Juan de la Cierva Incorporación postdoctoral fellowship of the Spanish Ministry of Science, Innovation and Universities (JC2020-045917-I).OS was supported by I+D+i projects RYC2019-027073-I and PIE HOLOCENO 20213AT014 funded by the Spanish Ministry of Science, Innovation and Universities (MCIN/AEI/10.13039/501100011033) and FEDER. The IAEA is grateful for the support provided to its Marine Environment Laboratories by the Government of the Principality of Monaco. PM was supported by the
Australian Research Council. J.G.O. acknowledges the financial support of the Spanish Ministry of Science, Innovation and Universities, through the “Maria de Maeztu” program for Units of Excellence (CEX2019-000940-M)
and the Generalitat de Catalunya (MERS; 2017 SGR–1588). This research was carried out with the contribution of the LIFE Programme of the European Union to the Project ADAPTA BLUES (ref. LIFE18 CCA/ES/001160). This document reflects only the authors' view and the Agency/Commission is not responsible for any use that may be made of the information it contains
The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity
The RNA polymerase II-associated protein 1 (RPAP1) is conserved across metazoa and required for stem cell differentiation in plants; however, very little is known about its mechanism of action or its role in mammalian cells. Here, we report that RPAP1 is essential for the expression of cell identity genes and for cell viability. Depletion of RPAP1 triggers cell de-differentiation, facilitates reprogramming toward pluripotency, and impairs differentiation. Mechanistically, we show that RPAP1 is essential for the interaction between RNA polymerase II (RNA Pol II) and Mediator, as well as for the recruitment of important regulators, such as the Mediator-specific RNA Pol II factor Gdown1 and the C-terminal domain (CTD) phosphatase RPAP2. In agreement, depletion of RPAP1 diminishes the loading of total and Ser5-phosphorylated RNA Pol II on many genes, with super-enhancer-driven genes among the most significantly downregulated. We conclude that Mediator/RPAP1/RNA Pol II is an ancient module, conserved from plants to mammals, critical for establishing and maintaining cell identity.We
are
grateful
to
Elisa
Varela
for
assistance
with
morula
and
blastocyst
fixa-
tion.
Work
in
the
laboratory
of
M.S.
is
funded
by
the
CNIO
and
the
IRB
and
by
grants
from
the
Spanish
Ministry
of
Economy
co-funded
by
the
European
Regional
Development
Fund
(ERDF)
(SAF2013-48256-R),
the
European
Research
Co
uncil
(ERC-2014-AdG/66
9622),
the
Region
al
Government
of
Ma-
drid
co-funded
by
the
Euro
pean
Social
Fund
(ReCaRe
project),
the
Euro
pean
Union
(RISK-IR
project),
the
Botin
Foundation
and
Banco
Santander
(Santander
Universities
Glo
bal
Division),
the
Ramon
Areces
Found ation,
and
the
AXA
Foundation.
S.R.
was
funded
by
a
contract
from
the
Ramon
y
Cajal
Program(RYC-2011-09242)
and
by
the
Spanish
Ministry
of
Economy
co-
funded
by
the
ERDF
(SAF2013-49147-
P
and
SAF2016-80874-PS
Beneficial effect of ursodeoxycholic acid in patients with acyl-CoA oxidase 2 (ACOX2) deficiency-associated hypertransaminasemia
Background and aims: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly 3?,7?,12?-trihydroxy-5?-cholestanoic acid (THCA). We aimed to investigate the prevalence of ACOX2 deficiency-associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration.
Methods and results: Among 33 patients with unexplained hypertransaminasemia from 11 hospitals and 13 of their relatives, seven individuals with abnormally high C27-BA levels (>50% of total BAs) were identified by high-performance liquid chromatography-mass spectrometry. The p.Arg225Trp variant was found in homozygosity (exon amplification/sequencing) in two patients and three family members. Two additional nonrelated patients were heterozygous carriers of different alleles: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). In patients with ADAH, impaired liver expression of ACOX2, but not ACOX3, was found (immunohistochemistry). Treatment with UDCA normalized aminotransferase levels. Incubation of HuH-7 hepatoma cells with THCA, which was efficiently taken up, but not through BA transporters, increased reactive oxygen species production (flow cytometry), endoplasmic reticulum stress biomarkers (GRP78, CHOP, and XBP1-S/XBP1-U ratio), and BAX? expression (reverse transcription followed by quantitative polymerase chain reaction and immunoblot), whereas cell viability was decreased (tetrazolium salt-based cell viability test). THCA-induced cell toxicity was higher than that of major C24-BAs and was not prevented by UDCA. Fourteen predicted ACOX2 variants were generated (site-directed mutagenesis) and expressed in HuH-7 cells. Functional tests to determine their ability to metabolize THCA identified six with the potential to cause ADAH.
Conclusions: Dysfunctional ACOX2 has been found in several patients with unexplained hypertransaminasemia. This condition can be accurately identified by a noninvasive diagnostic strategy based on plasma BA profiling and ACOX2 sequencing. Moreover, UDCA treatment can efficiently attenuate liver damage in these patients.Funding information: This study was supported by the following grants: CIBERehd (EHD15PI05/2016); Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI19/00819 and PI20/00189), co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”; “Junta de Castilla y León” (SA074P20); Fundació Marato TV3 (201916–31); AECC Scientific Foundation (2017/2020), Spain; and “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from grants PID2019-111669RBI-100, PID2020-115055RB-I00 from Plan Nacional de I+D funded by the “Agencia Estatal de Investigación” (AEI) and the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA/NIH, as well as support from AGAUR of the “Generalitat de Catalunya” SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network. Marta Alonso-Peña was the recipient of a predoctoral fellowship from “Ministerio de Educación, Cultura y Deporte” (BOE-A-2015-9456; FPU-14/00214) and a Mobility Grant for Short Stays from “Ministerio de Ciencia, Innovación y Universidades” (EST17/00186). Ricardo Espinosa-Escudero is the recipient of a predoctoral fellowship from “Junta de Castilla y León” and “Fondo Social Europeo” (EDU/574/2018). The funding sources were not involved in the research design or preparation of the article
ATP5H/KCTD2 locus is associated with Alzheimer's disease risk
To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10-6 were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10 -7 in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10 -9). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation
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