69 research outputs found
Identification and functional characterization of cDNAs coding for hydroxybenzoate/hydroxycinnamate glucosyltransferases co-expressed with genes related to proanthocyanidin biosynthesis
Grape proanthocyanidins (PAs) play a major role in the organoleptic properties of wine. They are accumulated mainly in grape skin and seeds during the early stages of berry development. Despite the recent progress in the identification of genes involved in PA biosynthesis, the mechanisms involved in subunit condensation, galloylation, or fine regulation of the spatio-temporal composition of grape berries in PAs are still not elucidated. Two Myb transcription factors, VvMybPA1 and VvMybPA2, controlling the PA pathway have recently been identified and ectopically over-expressed in an homologous system. In addition to already known PA genes, three genes coding for glucosyltransferases were significantly differentially expressed between hairy roots over-expressing VvMybPA1 or VvMybPA2 and control lines. The involvement of these genes in PA biosynthesis metabolism is unclear. The three glucosyltransferases display high sequence similarities with other plant glucosyltransferases able to catalyse the formation of glucose esters, which are important intermediate actors for the synthesis of different phenolic compounds. Studies of the in vitro properties of these three enzymes (Km, Vmax, substrate specificity, pH sensitivity) were performed through production of recombinant proteins in E. coli and demonstrated that they are able to catalyse the formation of 1-O-acyl-Glc esters of phenolic acids but are not active on flavonoids and stilbenes. The transcripts are expressed in the early stages of grape berry development, mainly in the berry skins and seeds. The results presented here suggest that these enzymes could be involved in vivo in PA galloylation or in the synthesis of hydroxycinnamic esters
Dark Matter Searches with the ANTARES Neutrino Telescope
[EN] The MOSCAB experiment (Materia OSCura A Bolle) uses the Geyser technique for dark matter search. The results of the first 0.5 kg mass prototype detector using superheated C3F8 liquid were very encouraging, achieving a 5 keV nuclear recoil threshold with high insensitivity to gamma radiation. Additionally, the technique seems to be easily scalable to higher masses for both in terms of complexity and costs, resulting in a very competitive technique for direct dark matter search, especially for the spin dependent case. Here, we report as well in the construction and commissioning of the big detector of 40 kg at the Milano-Bicocca University. The detector, the calibration tests and the evaluation of the background will be presented. Once demonstrated the functionality of the detector, it will be operated at the Gran Sasso National Laboratory in 2015.We acknowledge the financial support of the Spanish Ministerio de Ciencia e Innovación (MICINN) and Ministerio de Economía y Competitividad (MINECO), Grants FPA2012-37528-C02-02, and Consolider MultiDark CSD2009-00064, and of the Generalitat Valenciana, Grants ACOMP/2014/153 and PrometeoII/2014/079.Ardid Ramírez, M. (2016). Dark Matter Searches with the ANTARES Neutrino Telescope. Nuclear and Particle Physics Proceedings. 273:378-382. https://doi.org/10.1016/j.nuclphysbps.2015.09.054S37838227
Sedimentation and Fouling of Optical Surfaces at the ANTARES Site
ANTARES is a project leading towards the construction and deployment of a
neutrino telescope in the deep Mediterranean Sea. The telescope will use an
array of photomultiplier tubes to detect the Cherenkov light emitted by muons
resulting from the interaction with matter of high energy neutrinos. In the
vicinity of the deployment site the ANTARES collaboration has performed a
series of in-situ measurements to study the change in light transmission
through glass surfaces during immersions of several months. The average loss of
light transmission is estimated to be only ~2% at the equator of a glass sphere
one year after deployment. It decreases with increasing zenith angle, and tends
to saturate with time. The transmission loss, therefore, is expected to remain
small for the several year lifetime of the ANTARES detector whose optical
modules are oriented downwards. The measurements were complemented by the
analysis of the ^{210}Pb activity profile in sediment cores and the study of
biofouling on glass plates. Despite a significant sedimentation rate at the
site, in the 0.02 - 0.05 cm.yr^{-1} range, the sediments adhere loosely to the
glass surfaces and can be washed off by water currents. Further, fouling by
deposits of light-absorbing particulates is only significant for surfaces
facing upwards.Comment: 18 pages, 14 figures (pdf), submitted to Astroparticle Physic
Efeito do genótipo e da idade de ovinos na reatividade medida em pista de venda
Objetivou-se avaliar o comportamento de ovinos e relacionar aspectos comportamentais com a raça e idade dos animais. Foram observados 5.971 animais divididos em 181 lotes quanto às raças – Corriedale (n = 2.731), Ideal (n = 1.574), Merino (n = 168), Texel (n = 717), Suffolk (n = 247) e 6 mestiços (n = 534) – e quanto à idade – cordeiras (1,5 ano, n = 3.021), ovelhas (acima de 1,5 ano, n = 2457) e cordeiras dente-de-leite (média de 6 meses de idade, n = 493). O comportamento médio dos lotes foi avaliado pela atribuição de escores de movimentação e resistência à condução na entrada, permanência e saída da pista de comercialização. Os animais das raças mais especializadas para produção de carne (Suffolk e Texel) e os animais jovens foram os mais agitados e apresentaram maior resistência à condução pelo homem em comparação àqueles das raças produtoras de lã e aos mais velhos. Os escores comportamentais foram positivamente relacionados entre si, o que permite a escolha de qualquer um deles para medir o comportamento dos ovinos. O comportamento de ovinos em pista de venda é influenciado pela idade e raça.The objective of this work was to evaluate behavior of sheep and to relate behavioral aspects with breed and age of animals. It was observed 5,971 animals distributed in 181 plots regarded to: breed - Corriedale (n=2,731), Ideal (n=1,574), Merino (n=168), Texel (n=717), Suffolk (n=247) and six crossbreds (n=534); age - yearlings (1.5 year, n=3,021), ewes (above 1.5 year, n =2,457) and lambs (average 6 months of age, n=493). Average behavior of plots was evaluated by attributing scores of movement and resistance to conduction at entrance, permanence and exit from the market auction. Animals from more specialized breeds for meat production (Sulfock and Texel) and young animals were the most agitated and they showed more resistance to human conduction compared to those wool producer breeds and to the older ones. Behavior scores positively correlated among each other, allowing to choose any of them to measure sheep behavior. Sheep on market auction behavior is influenced by age and breed
Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry
Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients
Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry
Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF
Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry
Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes
Expression of a Neurospora crassa metallothionein and its variants in Escherichia coli.
The Neurospora crassa metallothionein (NC) synthesis gene was cloned and expressed in Escherichia coli in two different expression vectors (pING2 and pUA7), both under the regulation of the Salmonella typhimurium arabinose operon. Upon induction with arabinose, the pING2-NC vector expressed as inclusion body-localized AraB'::NC fusion protein of 21 kilodaltons. The pUA7-NC vector expressed a 5.3-kilodalton Lpp::NC fusion protein anchored to the outer membrane of the cell. Cells expressing the NC fusion proteins accumulated Cd2+ and Cu+ (between 2.3- and 11-fold) compared with nonexpressing cells. To generate novel forms of metal-binding peptides, a set of specific mutant genes for N. crassa NC was designed in which each cysteine residue was replaced with a subset of amino acids implicated in peptide-metal coordination (Asn, Asp, His, Lys, or Tyr residues). These mutant NC sequences were cloned into the two vectors and expressed in E. coli. One of the mutant proteins (containing His residues) showed accumulation of Cd2+ and Cu+ (threefold) from a mixture of 16 heavy metals species. None of the other heavy metals present in the culture was accumulated
Canadian Cohort Expanded-Access Program of Nivolumab Plus Ipilimumab in Advanced Melanoma
Background: The combination of nivolumab and ipilimumab is approved in several jurisdictions (United States, European Union, Canada) for the first-line treatment of patients with advanced melanoma. CheckMate 218 is a North American expanded-access program (EAP) of nivolumab plus ipilimumab in patients with advanced melanoma. Here, we report safety and survival outcomes for the Canadian cohort in the eap. Methods: Eligible patients were those 18 years of age or older with unresectable stage III or IV melanoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior anti–PD-1 or anti–CTLA-4 therapy. Patients were treated with nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks for 4 cycles (induction phase); they then continued with nivolumab 3 mg/kg every 2 weeks (maintenance phase) until progression, unacceptable toxicity, or a maximum of 48 weeks, whichever occurred first. Safety and overall survival (OS) data were collected. Results: Of 194 patients enrolled, 174 were treated, and 51% continued on nivolumab maintenance. Median follow-up was 12.9 months. All-grade and grades 3–4 treatment-related adverse events were reported in 98% and 60% of patients respectively and led to treatment discontinuation in 40% and 28% of patients. Two treatment-related deaths were reported. The 12- and 18-month OS rates were 80% [95% confidence interval (CI): 73% to 86%] and 76% (95% CI: 67% to 82%) respectively. Conclusions: In this Canadian population, nivolumab plus ipilimumab demonstrated a safety profile and survival outcomes consistent with phase II and III clinical trial data
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