5,251 research outputs found
Homo- and Heteroleptic Copper(I) Complexes with Diazabutadiene Ligands: Synthesis, Solution- and Solid-State Structural Studies
The preparation of novel copper(I) complexes of diazabutadiene (DAB) ligands with aliphatic backbones is reported. [Cu(DABR)2](BF4), [Cu(DABR)(NCMe)2](BF4) and [CuCl(DABR)] are easily synthesised and air-stable. These complexes, which remain scarce in the literature, have been fully characterised, and their behaviour both in the solid state as well as in solution has been studied by means of X-ray crystallography, NMR and UV/Vis spectroscopy
A system of three transiting super-Earths in a cool dwarf star
We present the detection of three super-Earths transiting the cool star
LP415-17, monitored by K2 mission in its 13th campaign. High resolution spectra
obtained with HARPS-N/TNG showed that the star is a mid-late K dwarf. Using
spectral synthesis models we infer its effective temperature, surface gravity
and metallicity and subse- quently determined from evolutionary models a
stellar radius of 0.58 R Sun. The planets have radii of 1.8, 2.6 and 1.9 R
Earth and orbital periods of 6.34, 13.85 and 40.72 days. High resolution images
discard any significant contamination by an intervening star in the line of
sight. The orbit of the furthest planet has radius of 0.18 AU, close to the
inner edge of the habitable zone. The system is suitable to improve our
understanding of formation and dynamical evolution of super-Earth systems in
the rocky - gaseous threshold, their atmospheres, internal structure,
composition and interactions with host stars.Comment: Accepted for publication in MNRAS Letter
The highly prevalent BRCA2 mutation c.2808_2811del (3036delACAA) is located in a mutational hotspot and has multiple origins
BRCA2-c.2808_2811del (3036delACAA) is one of the most reported
germ line mutations in non-Ashkenazi breast cancer patients. We
investigated its genetic origin in 51 Spanish carrier families that
were genotyped with 11 13q polymorphic markers. Three independent
associated haplotypes were clearly distinguished accounting for
23 [west Castilla y León (WCL)], 20 [east Castilla y León (ECL)]
and 6 (South of Spain) families. Mutation age was estimated with
the Disequilibrium Mapping using Likelihood Estimation software
in a range of 45–68 and 45–71 generations for WCL and ECL haplotypes,
respectively. The most prevalent variants, c.2808_2811del
and c.2803G > A, were located in a double-hairpin loop structure
(c.2794–c.2825) predicted by Quikfold that was proposed as a mutational
hotspot. To check this hypothesis, random mutagenesis was
performed over a 923 bp fragment of BRCA2, and 86 DNA variants
were characterized. Interestingly, three mutations reported in the
mutation databases (c.2680G > A, c.2944del and c.2957dup) were
replicated and 20 affected the same position with different nucleotide
changes. Moreover, five variants were placed in the same hairpin loop
of c.2808_2811del, and one affected the same position (c.2808A > G).
In conclusion, our results support that at least three different mutational
events occurred to generate c.2808_2811del. Other highly
prevalent DNA variants, such as BRCA1-c.68_69delAG, BRCA2-
c.5946delT and c.8537delAG, are concentrated in hairpin loops, suggesting
that these structures may represent mutational hotspots
HIFI observations of warm gas in DR21: Shock versus radiative heating
The molecular gas in the DR21 massive star formation region is known to be
affected by the strong UV field from the central star cluster and by a fast
outflow creating a bright shock. The relative contribution of both heating
mechanisms is the matter of a long debate. By better sampling the excitation
ladder of various tracers we provide a quantitative distinction between the
different heating mechanisms. HIFI observations of mid-J transitions of CO and
HCO+ isotopes allow us to bridge the gap in excitation energies between
observations from the ground, characterizing the cooler gas, and existing ISO
LWS spectra, constraining the properties of the hot gas. Comparing the detailed
line profiles allows to identify the physical structure of the different
components. In spite of the known shock-excitation of H2 and the clearly
visible strong outflow, we find that the emission of all lines up to > 2 THz
can be explained by purely radiative heating of the material. However, the new
Herschel/HIFI observations reveal two types of excitation conditions. We find
hot and dense clumps close to the central cluster, probably dynamically
affected by the outflow, and a more widespread distribution of cooler, but
nevertheless dense, molecular clumps.Comment: Accepted for publication by A&
Circulating biomarkers predicting longitudinal changes in left ventricular structure and function in a general population
Background
Serial imaging studies in the general population remain important to evaluate the usefulness of pathophysiologically relevant biomarkers in predicting progression of left ventricular (LV) remodeling and dysfunction. Here, we assessed in a general population whether these circulating biomarkers at baseline predict longitudinal changes in LV structure and function.
Methods and Results
In 592 participants (mean age, 50.8 years; 51.4% women; 40.5% hypertensive), we derived echocardiographic indexes reflecting LV structure and function at baseline and after 4.7 years. At baseline, we measured alkaline phosphatase, markers of collagen turnover (procollagen type I, C‐terminal telopeptide, matrix metalloproteinase‐1) and high‐sensitivity cardiac troponin T. We regressed longitudinal changes in LV indexes on baseline biomarker levels and reported standardized effect sizes as a fraction of the standard deviation of LV change. After full adjustment, a decline in LV longitudinal strain (−14.2%) and increase in E/e′ ratio over time (+18.9%; P≤0.019) was associated with higher alkaline phosphatase activity at baseline. Furthermore, longitudinal strain decreased with higher levels of collagen I production and degradation at baseline (procollagen type I, −14.2%; C‐terminal telopeptide, −16.4%; P≤0.029). An increase in E/e′ ratio over time was borderline associated with lower matrix metalloproteinase‐1 (+9.8%) and lower matrix metalloproteinase‐1/tissue inhibitor of metalloproteinase‐1 ratio (+11.9%; P≤0.041). Higher high‐sensitivity cardiac troponin T levels at baseline correlated significantly with an increase in relative wall thickness (+23.1%) and LV mass index (+18.3%) during follow‐up (P≤0.035).
Conclusions
We identified a set of biomarkers predicting adverse changes in LV structure and function over time. Circulating biomarkers reflecting LV stiffness, injury, and collagen composition might improve the identification of subjects at risk for subclinical cardiac maladaptation
Possible mechanisms of host resistance to Haemonchus contortus infection in sheep breeds native to the Canary Islands
Haemonchus contortus appears to be the most economically important helminth parasite for small ruminant production in many regions of the world. The two sheep breeds native to the Canary Islands display distinctly different resistant phenotypes under both natural and experimental infections. Canaria Hair Breed (CHB) tends to have significantly lower worm burden and delayed and reduced egg production than the susceptible Canaria Sheep (CS). To understand molecular mechanisms underlying host resistance, we compared the abomasal mucosal transcriptome of the two breeds in response to Haemonchus infection using RNAseq technology. The transcript abundance of 711 and 50 genes were significantly impacted by infection in CHB and CS, respectively (false discovery rate <0.05) while 27 of these genes were significantly affected in both breeds. Likewise, 477 and 16 Gene Ontology (GO) terms were significantly enriched in CHB and CS, respectively (P < 1.0 × 10(−4)). A broad range of mechanisms have evolved in resistant CHB to provide protection against the parasite. Our findings suggest that readily inducible acute inflammatory responses, complement activation, accelerated cell proliferation and subsequent tissue repair, and immunity directed against parasite fecundity all contributed to the development of host resistance to parasitic infection in the resistant breed
Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients
Background: Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert
an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and
independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional
antioxidant capacity of paricalcitol in a clinical setting.
Methods: The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was
obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following
oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups,
indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and
C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase,
reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.
Results: Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased
after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly
increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were
significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.
Conclusions: In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress
and inflammation, two well known factors leading to cardiovascular damageBackground: Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting.
Methods: The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase,
reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.
Results: Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.
Conclusions: In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage
Associations of education with 30 year life course blood pressure trajectories: Framingham Offspring Study
Background: Education is inversely associated with cardiovascular disease incidence in developed countries. Blood pressure may be an explanatory biological mechanism. However few studies have investigated educational gradients in longitudinal blood pressure trajectories, particularly over substantial proportions of the life course. Study objectives were to determine whether low education was associated with increased blood pressure from multiple longitudinal assessments over 30 years. Furthermore, we aimed to separate antecedent effects of education, and other related factors, that might have caused baseline differences in blood pressure, from potential long-term effects of education on post-baseline blood pressure changes. Methods: The study examined 3890 participants of the Framingham Offspring Study (mean age 36.7 years, 52.0% females at baseline) from 1971 through 2001 at up to 7 separate examinations using multivariable mixed linear models. Results: Mixed linear models demonstrated that mean systolic blood pressure (SBP) over 30 years was higher for participants with ≤12 vs. ≥17 years education after adjusting for age (3.26 mmHg, 95% CI: 1.46, 5.05 in females, 2.26 mmHg, 95% CI: 0.87, 3.66 in males). Further adjustment for conventional covariates (antihypertensive medication, smoking, body mass index and alcohol) reduced differences in females and males (2.86, 95% CI: 1.13, 4.59, and 1.25, 95% CI: -0.16, 2.66 mmHg, respectively). Additional analyses adjusted for baseline SBP, to evaluate if there may be educational contributions to post-baseline SBP. In analyses adjusted for age and baseline SBP, females with ≤12 years education had 2.69 (95% CI: 1.09, 4.30) mmHg higher SBP over follow-up compared with ≥17 years education. Further adjustment for aforementioned covariates slightly reduced effect strength (2.53 mmHg, 95% CI: 0.93, 4.14). Associations were weaker in males, where those with ≤12 years education had 1.20 (95% CI: -0.07, 2.46) mmHg higher SBP over follow-up compared to males with ≥17 years of education, after adjustment for age and baseline blood pressure; effects were substantially reduced after adjusting for aforementioned covariates (0.34 mmHg, 95% CI: -0.90, 1.68). Sex-by-education interaction was marginally significant (p = 0.046). Conclusion: Education was inversely associated with higher systolic blood pressure throughout a 30-year life course span, and associations may be stronger in females than males.Eric B Loucks, Michal Abrahamowicz, Yongling Xiao, John W Lync
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