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Nanofibrils play a pivotal role in spider silk and are responsible for many of the impressive properties of this unique natural material. However, little is known about the internal structure of these protein fibrils. We carry out polarized Raman and polarized Fourier-transform infrared spectroscopies on native spider silk nanofibrils and determine the concentrations of six distinct protein secondary structures, including β-sheets, and two types of helical structures, for which we also determine orientation distributions. Our advancements in peak assignments are in full agreement with the published silk vibrational spectroscopy literature. We further corroborate our findings with X-ray diffraction and magic-angle spinning nuclear magnetic resonance experiments. Based on the latter and on polypeptide Raman spectra, we assess the role of key amino acids in different secondary structures. For the recluse spider we develop a highly detailed structural model, featuring seven levels of structural hierarchy. The approaches we develop are directly applicable to other proteinaceous materials. Secondary fibril structure is a key component of the mechanical properties of protein materials like silk, yet, limited information is known about the internal structure of these protein fibrils. Here, the authors report on the use of polarised Raman and FTIR spectroscopy to study silk materials and identify six distinct secondary structures.

The simultaneous use of 2-pyridyl oximes (pyridine-2 amidoxime, H2pyaox; 2-methyl pyridyl ketoxime, Hmpko) and 1,3,5-benzenetricarboxylic acid (H3btc) provided access to five new compounds, namely [Zn(H2btc)2(H2pyaox)2]•2H2O (1•2H2O), [Zn(Hbtc)(H2pyaox)2]n (2), [Cu(Hbtc)(H2pyaox)]n (3), [Cu(Hbtc)(HmpKo)]n (4) and [Cu2(Hbtc)2(Hmpko)2(H2O)2]•4H2O (5•4H2O). Among them, 3 is the first example of a metal-organic framework (MOF) containing H2pyaox. Its framework can be described as a 3-c uninodal net of hcb topology with the layers being parallel to the (1,0,1) plane. Furthermore, 3 is the third reported MOF based on a 2-pyridyl oxime in general. 2 and 4 are new members of a small family of coordination polymers containing an oximic ligand. 1–5 form 3D networks through strong intermolecular interactions. Dc magnetic susceptibility studies were carried out in a crystalline sample of 3 and revealed the presence of weak exchange interactions between the metal centres; the experimental data were fitted to a theoretical model with the fitting parameters being J = −0.16(1) cm−1 and g = 2.085(1). The isotropic g value was also confirmed by electronic paramagnetic resonance (EPR) spectroscopy. Reactivity studies were performed for 3 in the presence of metal ions; the reaction progress was studied and discussed for Fe(NO3)3 by the use of several characterization techniques, including single crystal X-ray crystallography and IR spectroscopy.

Hypertension places a major burden on individual and public health, but the genetic basis of this complex disorder is poorly understood. We conducted a genome-wide association study of systolic and diastolic blood pressure (SBP and DBP) in Amish subjects and found strong association signals with common variants in a serine/threonine kinase gene, STK39. We confirmed this association in an independent Amish and 4 non-Amish Caucasian samples including the Diabetes Genetics Initiative, Framingham Heart Study, GenNet, and Hutterites (meta-analysis combining all studies: n = 7,125, P < 10⁻⁶). The higher BP-associated alleles have frequencies > 0.09 and were associated with increases of 3.3/1.3 mm Hg in SBP/DBP, respectively, in the Amish subjects and with smaller but consistent effects across the non-Amish studies. Cell-based functional studies showed that STK39 interacts with WNK kinases and cation-chloride cotransporters, mutations in which cause monogenic forms of BP dysregulation. We demonstrate that in vivo, STK39 is expressed in the distal nephron, where it may interact with these proteins. Although none of the associated SNPs alter protein structure, we identified and experimentally confirmed a highly conserved intronic element with allele-specific in vitro transcription activity as a functional candidate for this association. Thus, variants in STK39 may influence BP by increasing STK39 expression and consequently altering renal Na⁺ excretion, thus unifying rare and common BP-regulating alleles in the same physiological pathway.

A new Schiff base complex, Cu(H2L)2 (H3L: 6,6′-((1E,1′E)-((azanediylbis(ethane-2,1-diyl))bis(azanylylidene))bis(methanylylidene))bis(2-methoxyphenol)), through the reaction of ligand H3L with Cu(NO3)2 3H2O, in the ratio of 2 : 1 in methanol solvent was prepared. The obtained ligand (H3L) was characterized by FT-IR, 13C NMR, 1H NMR and elemental analyses. Then its copper(II) complex was prepared and characterized by FT-IR spectroscopy, thermal studies, elemental analyses and single crystal X-ray diffraction. The X-ray crystallography revealed that the two H3L ligands in bidentate fashion coordinated to one copper center for producing Cu(H2L)2 complex. We used copper(II) Schiff base complex, Cu(H2L)2, for the preparation of CuO nanoparticles via solid-state thermal decomposition. The crystalline structure of the product was studied by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). XRD indicated that the new product was copper oxide. SEM image showed that the size of CuO nanoparticles was between 46 and 53 nm, and they had uniform shape. The antibacterial properties of the complex and ligand were also investigated. The results revealed that Schiff base complex showed higher biological activity than Schiff base ligand.

Background Elevated serum bilirubin has been associated with reduced risk of cardiovascular disease (CVD). However, serum bilirubin is also related with several potential confounders related to CVD, such as obesity. Mendelian randomization has been proposed as a method to address challenges to validity from confounding and reverse causality. It utilizes genotype to estimate causal relationships between a gene product and physiological outcomes. In this report, we demonstrate its use in assessing direct causal relations between serum bilirubin levels and CVD risk factors, including obesity, cholesterol, measures of vascular function and blood pressure. Methods Study subjects included 868 asymptomatic individuals. Study subjects were genotyped at the UGT1A1*28 locus, which is strongly associated with bilirubin levels. Results Serum bilirubin levels were inversely associated with levels of several cardiovascular disease risk factors, including body mass index ( p = 0.003), LDL ( p = 0.0005) and total cholesterol ( p = 0.0002). In contrast, UGT1A1*28 genotype, a known cause of elevated bilirubin levels, was not significantly associated with any of these traditional CVD risk factors. We did observe an association between genotype and brachial artery diameter ( p = 0.003) and cold pressor reactivity ( p = 0.01). Conclusions Our findings imply that the observed association of serum bilirubin levels with body mass index and cholesterol are likely due to confounding and suggest that previously established CVD benefits of increased bilirubin may in part be mediated by the early regulation of vascular structure and reactivity.

The use of 2-pyridyl oximes in metal complexes chemistry has been extensively investigated in the last few decades as a fruitful source of species with interesting magnetic properties. In this work, the initial combination of pyridine-2-amidoxime (pyaoxH2) and 2-methyl pyridyl ketoxime (mpkoH) with isonicotinic acid (HINA) and 3,5-pyrazole dicarboxylic acid (H3pdc) has provided access to three new compounds, [Ni4(INA)2(pyaox)2(pyaoxH)2(DMF)2] (1), [Co5(mpko)6(mpkoH)2(OMe)2(H2O)](ClO4)6 (2), and [Co5(OH)(Hpdc)5(H2pdc)] (3). 1 displays a square-planar metal topology, being the first example that bears simultaneously HINA and pyaoxH2 in their neutral or ionic form. The neighbouring Ni4 units in 1 are held together through strong intermolecular hydrogen bonding interactions, forming a three-dimensional supramolecular framework. 2 and 3 are mixed-valent Co4IIICoII and Co2IIICoII3 compounds with a bowtie and trigonal bipyramidal metal topology, accordingly. Direct current and alternate current magnetic susceptibility studies revealed that the exchange interactions between the NiII ions in 1 are ferromagnetic (J = 1.79(4) cm−1), while 2 exhibits weak AC signals in the presence of a magnetic field. The syntheses, crystal structures, and magnetic properties of 1–3 are discussed in detail.

Elevated serum levels of uric acid consistently correlate with hypertension, but the directionality of the association remains debated. To help define this relationship, we used a controlled setting within a homogeneous Amish community and the Mendelian randomization of a nonsynonymous coding single-nucleotide polymorphism, rs16890979 (Val253Ile), in the SLC2A9 gene. This gene expresses the GLUT9 transporter that also transports uric acid and is associated with lower serum uric acid levels. We studied the unconfounded association between genotype and blood pressure in 516 Amish adults, each placed for 6 days on standardized diets, first with high sodium, followed by low sodium, with an intervening washout period. Blood pressure, measured using 24-h ambulatory monitoring, during both diet periods was used as the primary outcome. All participants were free of diuretic or other antihypertensive medications and the relationships between GLUT9 genotype and both serum uric acid and blood pressure were assessed. Each copy of the GLUT9 minor Ile allele was found to confer a significant 0.44mg/dl reduction in serum uric acid and was associated with a significant mean decrease in the systolic blood pressure of 2.2 and 1.5mmHg on the high- and low-sodium diet, respectively. Thus, a Mendelian randomization analysis using variants in the GLUT9 gene indicates that a decrease in serum uric acid has a causal effect of lowering blood pressure.

Ischemic stroke (IS), caused by obstruction of cerebral blood flow, is one of the leading causes of death. While neurologists agree on delineation of IS into three subtypes (cardioembolic stroke (CES), large artery stroke (LAS), and small vessel stroke (SVS)), several subtyping systems exist. The most commonly used systems are TOAST (Trial of Org 10172 in Acute Stroke Treatment) and CCS (Causative Classification System for Stroke), but agreement is only moderate. We have compared two approaches to combining the existing subtyping systems for a phenotype suited for a genome-wide association study (GWAS). We used the NINDS Stroke Genetics Network dataset (SiGN, 11,477 cases with CCS and TOAST subtypes and 28,026 controls). We defined two new phenotypes: the intersect, for which an individual must be assigned the same subtype by CCS and TOAST; and the union, for which an individual must be assigned a subtype by either CCS or TOAST. The union yields the largest sample size while the intersect yields a phenotype with less potential misclassification. We performed GWAS for all subtypes, using the original subtyping systems, the intersect, and the union as phenotypes. In each subtype, heritability was higher for the intersect compared with the other phenotypes. We observed stronger effects at known IS variants with the intersect compared with the other phenotypes. With the intersect, we identify rs10029218:G>A as an associated variant with SVS. We conclude that this approach increases the likelihood to detect genetic associations in ischemic stroke.

Dietary intake and higher serum concentrations of lycopene have been associated with lower incidence of prostate cancer and other chronic diseases. Identifying determinants of serum lycopene concentrations may thus have important public health implications. Prior studies have suggested that serum lycopene concentrations are under partial genetic control. The goal of this research was to identify genetic predictors of serum lycopene concentrations using the genome-wide association study (GWAS) approach among a sample of 441 Old Order Amish adults that consumed a controlled diet. Linear regression models were utilized to evaluate associations between genetic variants and serum concentrations of lycopene. Variant rs7680948 on chromosome 4, located in the intron region of the SETD7 gene, was significantly associated with serum lycopene concentrations (p = 3.41 × 10−9). Our findings also provided nominal support for the association previously noted between SCARB1 and serum lycopene concentrations, although with a different SNP (rs11057841) in the region. This study identified a novel locus associated with serum lycopene concentrations and our results raise a number of intriguing possibilities regarding the nature of the relationship between SETD7 and lycopene, both of which have been independently associated with prostate cancer. Further investigation into this relationship might help provide greater mechanistic understanding of these associations.