We carried out a comprehensive genomic analysis of porcine copy number variants (CNVs) based on whole‐genome SNP genotyping data and provided new measures of genomic diversity (number, length and ...distribution of CNV events) for a highly inbred strain (the Guadyerbas strain). This strain represents one of the most ancient surviving populations of the Iberian breed, and it is currently in serious danger of extinction. CNV detection was conducted on the complete Guadyerbas population, adjusted for genomic waves, and used strict quality criteria, pedigree information and the latest porcine genome annotation. The analysis led to the detection of 65 CNV regions (CNVRs). These regions cover 0.33% of the autosomal genome of this particular strain. Twenty‐nine of these CNVRs were identified here for the first time. The relatively low number of detected CNVRs is in line with the low variability and high inbreeding estimated previously for this Iberian strain using pedigree, microsatellite or SNP data. A comparison across different porcine studies has revealed that more than half of these regions overlap with previously identified CNVRs or multicopy regions. Also, a preliminary analysis of CNV detection using whole‐genome sequence data for four Guadyerbas pigs showed overlapping for 16 of the CNVRs, supporting their reliability. Some of the identified CNVRs contain relevant functional genes (e.g., the SCD and USP15 genes), which are worth being further investigated because of their importance in determining the quality of Iberian pig products. The CNVR data generated could be useful for improving the porcine genome annotation.
Background
Controversy exists regarding the way alcohol use is associated with vascular structure and arterial stiffness parameters. The purpose of this study is to evaluate the association between ...alcohol consumption with vascular structure and arterial stiffness in an adult population.
Methods
We conducted a cross‐sectional study. Five hundred and one participants were recruited by random sampling from an urban population of 43,946 individuals aged 35 to 75 years, assigned from 5 healthcare centers located in Salamanca, Spain. This was a subanalysis of the EVA study. Arterial stiffness was assessed by measuring cardio‐ankle vascular index (CAVI) and brachial‐ankle pulse wave velocity (ba‐PWV) with the VaSera VS‐1500® device, and carotid‐femoral pulse wave velocity (cf‐PWV) with the Sphygmocor®. Vascular structure was evaluated by measuring the carotid intima–media thickness (c‐IMT) with a Sonosite Micromax® ultrasound. Alcohol consumption was calculated using a standardized questionnaire and quantified in g/wk.
Results
In the multiple regression analysis adjusted for sex, age, smoking status, and systolic blood pressure, the c‐IMT and cf‐PWV values of individuals drinking > 70 g/wk were higher than those of the reference group (nondrinkers) by 0.02 mm (p = 0.030) and 0.42 m/s (p = 0.021), respectively. The association between alcohol consumption with vascular structure and arterial stiffness only attains statistical significance for cf‐PWV (p = 0.039) and c‐IMT (p = 0.019), showing an association which suggests a J‐shaped association. This association was not statistically significant for ba‐PWV and CAVI (p = 0.446 and p = 0.141, respectively), although a similar trend was observed with ba‐PWV.
Conclusions
The results of this study suggest that heavy alcohol consumption (>70 g/wk) is associated with increased c‐IMT and cf‐PWV. Moreover, we found a J‐shaped association between alcohol consumption and c‐IMT and cf‐PWV values as markers of vascular structure and arterial stiffness, with no association with ba‐PWV and CAVI being observed.
The results of this study address a topical issue, the association that chronic alcohol use can have on the development of cardiovascular disease and specifically on intermediate markers in the development of atherosclerosis. Moderate alcohol consumption (≤ 30 g/week) is associated with better values of vascular structure (carotid intima‐media thickness) and arterial stiffness (carotid‐femoral pulse wave velocity).
The Gulf of California (GC) is a unique large marine ecosystem characterized by its rich biodiversity, high biological productivity and endemism of marine life, which are the basis of Mexico's most ...important fisheries. However, as many other large ecosystems worldwide, it is subject to diverse anthropogenic pressures (overfishing, losses of biodiversity and habitats, pollution, climate variability and climate change (CC)). We reviewed over 180 studies dealing with the impacts of CC and climate variability in the GC region. Main issues on the impact of ENSO events, acidification, sea level rise, and water availability are discussed for the GC in a global context. Impacts of ENSO events on the GC are geographically heterogeneous, upwelling tends to be suppressed, and this in turn influences the distribution and abundance of marine mammals, fishes, shrimps, benthic species, seaweeds and phytoplankton. ENSO events strongly impact small pelagic fishes, key components of the GC ecosystem, thus affecting fisheries in general as well as non-harvested species such as marine mammals and sea birds. Probably the most well-known phenomenon associated to ENSO impact in the GC is coral bleaching, a process by which corals expel most of their microalgal endosymbionts to become pale or white (bleached). Beside shifts in the distributional limits of benthic organisms, invasions of alien species are also occuring. Harmful algal blooms (HABs) are common and recurrent in the GC. Fourteen HAB-forming species have been recorded, with Gymnodinium catenatum being the most frequent. HABs are inhibited by El Niño and promoted by La Niña. During El Niño events the size and biomass of macroalgal blooms tend to decrease. Finally, several aspects that require further research are proposed.
This paper presents an analysis using molecular simulation of the phase equilibrium of methane hydrates under the oceanic crust conditions. Although there is a number of works dealing with ...computational simulation of gas hydrates, obtaining their phase diagrams using different techniques, simulations under realistic conditions and environments are not available yet. As the first step in this direction, we have added Na+ and Cl− ions to the water liquid phase in a model of the hydrate (S)–water (L)–methane (G) three-phase system, with the aim to simulate the system behaviour using classical Molecular Dynamics with the direct coexistence technique. The results are in good agreement with other simulations and experimental measurements reported in literature. Coexistence curves are well defined including a proper shift between water with and without NaCl. Additionally, water solvation of ions was found to interfere with crystallization process, slowing it down and preventing the incorporation of all liquid molecules to the hydrate phase.
•Methane hydrates were simulated in conditions of real oceanic deposit occurrence.•The shift in the triphasic equilibrium curve due to NaCl presence has been estimated.•This subtle shift is quantitatively captured by Molecular Dynamics simulations.•The suitability of the simulation setup used to approach oceanic hydrates is shown.
•EGFR overexpression is associated with reduced OS in women with early breast cancer.•EGFR overexpression is associated with reduced DFS in women with early breast cancer.•The worst effect appears to ...be greatest in women with triple negative tumors.
The epidermal growth factor receptor (EGFR) is a member of the ErbB family of membrane tyrosine-kinase receptors. Studies exploring the prognostic role of EGFR-overexpression in early breast cancer have shown variable results, and the true prognostic value of EGFR is unknown.
A systematic review of identified publications exploring the association between EGFR-overexpression (as defined from different techniques and cut-offs) and outcomes disease-free (DFS) and, overall survival (OS) in women with early breast cancer. The hazard ratios (HR) for DFS and OS were weighted and pooled in a meta-analysis using generic inverse variance and random effects modeling.
Fifty-three studies comprising 21,418 women were included. EGFR-overexpression was found in 27% of the patients. Primary analysis included studies reporting HRs from multivariable analyses (10 studies including 4857 patients with HRs for OS and 17 studies comprising 8747 patients with HRs for DFS), EGFR-overexpression was associated with worse OS (HR 1.98, 95% CI: 1.59–2.47, p < .001) and DFS (HR 1.59, 95% CI 1.30–1.95, p < .001). The influence of EGFR overexpression on DFS was greater in women with triple negative tumors compared to women with non-triple negative tumors (HR 2.35 versus HR 1.45, respectively; p = .01). Analysis looking at odd ratios for both 5-year and 10-year for DFS and OS showed similar results.
EGFR-overexpression appears to be associated with reduced OS and DFS in women with early breast cancer. Patients with triple negative and EGFR-overexpression have poorer OS and DFS than those with triple negative tumors and normal EGFR expression.
The cross-coupling reaction of aryl bromides and iodides with aliphatic and aromatic thiols catalyzed by palladium complexes of the bisphosphine ligand CyPF-tBu (1) is reported. Reactions occur in ...excellent yields, broad scope, high tolerance of functional groups, and with turnover numbers that exceed those of previous catalysts by 2 or 3 orders of magnitude. These couplings of bromo- and iodoarenes are more efficient than the corresponding reactions of chloroarenes and could be conducted with less catalyst loading and/or milder reaction conditions. Consequently, limitations regarding scope and functional group tolerance previously reported in the coupling of aryl chlorides are now overcome.
In this work, we report the synthesis and characterization of unsupported Pt-CeO2 (1:1 wt. % Pt:CeO2 ratio) and Pt-Pd (1:1 wt. % Pt:Pd ratio) electrocatalysts as candidate cathodes for alkaline ...direct methanol fuel cells (A-DMFCs). The catalytic activity of the cathodes for the oxygen reduction reaction (ORR) in the absence and presence of methanol, in KOH as electrolyte, was evaluated at room temperature. The materials were prepared by chemical reduction with NaBH4, and pyrolysis at 300 and 600 °C under a H2/N2 atmosphere. The XRD results indicated the formation of polycrystalline materials with particle sizes ranging from 9 to 19 nm. Analysis by HRTEM showed the formation of nanostructures with lattice fringes corresponding to Pt, Pd (i.e., the Pt-Pd cathode), or CeO2 (i.e., the Pt-CeO2 material). The electrochemical characterization in 0.1 mol L−1 KOH showed that the Pt-Pd is highly active for the ORR in alkaline medium, delivering higher onset potential and mass activity than Pt-alone. Meanwhile, the Pt-CeO2 material showed slightly lower ORR mass activity than Pt. However, in the presence of methanol, the Pt-CeO2 nanocatalyst demonstrated significantly higher selectivity and tolerance capability to the alcohol than Pt and Pt-Pd.
► Pt-Pd and Pt-CeO2 synthesized by chemical reduction and pyrolysis. ► Higher catalytic activity of Pt-Pd for the ORR in alkaline medium related to Pt. ► The Pt-CeO2 nanostructures showed high selectivity and tolerance to methanol in KOH.
Arterial spin labeling (ASL) can be implemented by combining different labeling schemes and readout sequences. In this study, the performance of 2D and 3D single-shot pulsed-continuous ASL (pCASL) ...sequences was assessed in a group of young healthy volunteers undergoing a baseline perfusion and a functional study with a sensory-motor activation paradigm. The evaluated sequences were 2D echo-planar imaging (2D EPI), 3D single-shot fast spin-echo with in-plane spiral readout (3D FSE spiral), and 3D single-shot gradient-and-spin-echo (3D GRASE). The 3D sequences were implemented with and without the addition of an optimized background suppression (BS) scheme. Labeling efficiency, signal-to-noise ratio (SNR), and gray matter (GM) to white matter (WM) contrast ratio were assessed in baseline perfusion measurements. 3D acquisitions without BS yielded 2-fold increments in spatial SNR, but no change in temporal SNR. The addition of BS to the 3D sequences yielded a 3-fold temporal SNR increase compared to the unsuppressed sequences. 2D EPI provided better GM-to-WM contrast ratio than the 3D sequences. The analysis of functional data at the subject level showed a 3-fold increase in statistical power for the BS 3D sequences, although the improvement was attenuated at the group level. 3D without BS did not increase the maximum t-values, however, it yielded larger activation clusters than 2D. These results demonstrate that BS 3D single-shot imaging sequences improve the performance of pCASL in baseline and activation studies, particularly for individual subject analyses where the improvement in temporal SNR translates into markedly enhanced power for task activation detection.
► 3D pCASL sequences increased perfusion spatial SNR by a factor of 2. ► The addition of BS to 3D readouts increased perfusion temporal SNR by a factor of 3. ► 2D EPI showed higher GM-to-WM CBF contrast ratio. ► Statistical power to detect functional activation was higher in 3D BS sequences. ► 3D BS single-shot sequences appear as the preferable readout choice in pCASL fMRI.
In adult epithelial stem cell lineages, the precise differentiation of daughter cells is critical to maintain tissue homeostasis. Notch signaling controls the choice between absorptive and ...entero-endocrine cell differentiation in both the mammalian small intestine and the Drosophila midgut, yet how Notch promotes lineage restriction remains unclear. Here, we describe a role for the transcription factor Klumpfuss (Klu) in restricting the fate of enteroblasts (EBs) in the Drosophila intestine. Klu is induced in Notch-positive EBs and its activity restricts cell fate towards the enterocyte (EC) lineage. Transcriptomics and DamID profiling show that Klu suppresses enteroendocrine (EE) fate by repressing the action of the proneural gene Scute, which is essential for EE differentiation. Loss of Klu results in differentiation of EBs into EE cells. Our findings provide mechanistic insight into how lineage commitment in progenitor cell differentiation can be ensured downstream of initial specification cues.
Can you dig it? An asymmetric synthesis of functionalized 1H‐indenes from easily available ortho‐(alkynyl)styrene derivatives under mild reaction conditions has been achieved. The reactions proceed ...through an unprecedented and selective 5‐endo‐dig gold(I)‐catalyzed cycloisomerization or alkoxycyclization, if water or an alcohol is present (see scheme).
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