Potential Relevance of α1-Adrenergic Receptor Autoantibodies in Refractory Hypertension

-AAB might have a mechanistic role and could represent a therapeutic target. in cardiomyocytes and induce mesentery artery segment contraction.-AAB in hypertensive patients, and the notion of immunity as a possible cause of hypertension

Efficient and accurate modeling of electron photoemission in nanostructures with TDDFT

We derive and extend the time-dependent surface-flux method introduced in [L. Tao, A. Scrinzi, New J. Phys. 14, 013021 (2012)] within a time-dependent density-functional theory (TDDFT) formalism and use it to calculate photoelectron spectra and angular distributions of atoms and molecules when excited by laser pulses. We present other, existing computational TDDFT methods that are suitable for the calculation of electron emission in compact spatial regions, and compare their results. We illustrate the performance of the new method by simulating strong-field ionization of C60 fullerene and discuss final state effects in the orbital reconstruction of planar organic molecules

TILLING - a shortcut in functional genomics

Recent advances in large-scale genome sequencing projects have opened up new possibilities for the application of conventional mutation techniques in not only forward but also reverse genetics strategies. TILLING (Targeting Induced Local Lesions IN Genomes) was developed a decade ago as an alternative to insertional mutagenesis. It takes advantage of classical mutagenesis, sequence availability and high-throughput screening for nucleotide polymorphisms in a targeted sequence. The main advantage of TILLING as a reverse genetics strategy is that it can be applied to any species, regardless of its genome size and ploidy level. The TILLING protocol provides a high frequency of point mutations distributed randomly in the genome. The great mutagenic potential of chemical agents to generate a high rate of nucleotide substitutions has been proven by the high density of mutations reported for TILLING populations in various plant species. For most of them, the analysis of several genes revealed 1 mutation/200–500 kb screened and much higher densities were observed for polyploid species, such as wheat. High-throughput TILLING permits the rapid and low-cost discovery of new alleles that are induced in plants. Several research centres have established a TILLING public service for various plant species. The recent trends in TILLING procedures rely on the diversification of bioinformatic tools, new methods of mutation detection, including mismatch-specific and sensitive endonucleases, but also various alternatives for LI-COR screening and single nucleotide polymorphism (SNP) discovery using next-generation sequencing technologies. The TILLING strategy has found numerous applications in functional genomics. Additionally, wide applications of this throughput method in basic and applied research have already been implemented through modifications of the original TILLING strategy, such as Ecotilling or Deletion TILLING

Rural Australian community pharmacists' views on complementary and alternative medicine: a pilot study

<p>Abstract</p> <p>Background</p> <p>Complementary and alternative medicines (CAMs) are being used increasingly across the world. In Australia, community pharmacists are a major supplier of these products but knowledge of the products and interactions with other medicines is poor. Information regarding the use of CAMs by metropolitan pharmacists has been documented by the National Prescribing Service (NPS) in Australia but the views of rural/regional community pharmacists have not been explored. The aim of this pilot study was to explore the knowledge, attitudes and information seeking of a cohort of rural community pharmacists towards CAMs and to compare the findings to the larger NPS study.</p> <p>Methods</p> <p>A cross sectional self-administered postal questionnaire was mailed to all community pharmacists in one rural/regional area of Australia. Using a range of scales, data was collected regarding attitudes, knowledge, information seeking behaviour and demographics.</p> <p>Results</p> <p>Eighty eligible questionnaires were returned. Most pharmacists reported knowing that they should regularly ask consumers if they are using CAMs but many lacked the confidence to do so. Pharmacists surveyed for this study were more knowledgeable in regards to side effects and interactions of CAMs than those in the NPS survey. Over three quarters of pharmacists surveyed reported sourcing CAM information at least several times a month. The most frequently sought information was drug interactions, dose, contraindications and adverse effects. A variety of resources were used to source information, the most popular source was the internet but the most useful resource was CAM text books.</p> <p>Conclusions</p> <p>Pharmacists have varied opinions on the use of CAMs and many lack awareness of or access to good quality CAMs information. Therefore, there is a need to provide pharmacists with opportunities for further education. The data is valuable in assisting interested stakeholders with the development of initiatives to address the gaps in attitudes, knowledge and to improve effectiveness of information seeking behaviour.</p

Inhibitors of trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease.

Chagas disease remains one of the most neglected diseases in the world despite being the most important parasitic disease in Latin America. The characteristic chronic manifestation of chagasic cardiomyopathy is the region's leading cause of heart-related illness, causing significant mortality and morbidity. Due to the limited available therapeutic options, new drugs are urgently needed to control the disease. Sirtuins, also called Silent information regulator 2 (Sir2) proteins have long been suggested as interesting targets to treat different diseases, including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have hinted at the possibility to exploit these enzymes as a possible drug targets. In the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1) is genetically validated as a drug target and biochemically characterized for its NAD+-dependent deacetylase activity and its inhibition by the classic sirtuin inhibitor nicotinamide, as well as by bisnaphthalimidopropyl (BNIP) derivatives, a class of parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti-parasitic activity against T. cruzi amastigotes in vitro were investigated. The compound BNIP Spermidine (BNIPSpd) (9), was found to be the most potent inhibitor of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity similar to the reference drug benznidazole against the medically important amastigotes, while having the highest selectivity index amongst the compounds tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease, possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of the compound, as well as alternative formulations may improve activity and pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in complex with p53 peptide substrate was obtained from low resolution X-ray data (3.5 Å) to gain insight into the potential specificity of the interaction with the BNIP compounds. In conclusion, the search for TcSir2rp1 specific inhibitors may represent a valuable strategy for drug discovery against T. cruzi

Searching for eV-scale sterile neutrinos with eight years of atmospheric neutrinos at the IceCube Neutrino Telescope

We report in detail on searches for eV-scale sterile neutrinos, in the context of a 3+1 model, using eight years of data from the IceCube Neutrino Telescope. By analyzing the reconstructed energies and zenith angles of 305,735 atmospheric νμ and ¯νμ events we construct confidence intervals in two analysis spaces: sin2(2θ$_{24}$) vs Δm2¦41 under the conservative assumption θ$_{34}$=0; and sin$^{2}$ (2θ$_{24}$) vs sin$^{2}$ (2θ$_{34}$) given sufficiently large Δm2¦41 that fast oscillation features are unresolvable. Detailed discussions of the event selection, systematic uncertainties, and fitting procedures are presented. No strong evidence for sterile neutrinos is found, and the best-fit likelihood is consistent with the no sterile neutrino hypothesis with a p value of 8% in the first analysis space and 19% in the second

Searching for eV-scale sterile neutrinos with eight years of atmospheric neutrinos at the IceCube neutrino telescope

We report in detail on searches for eV-scale sterile neutrinos, in the context of a 3+1 model, using eight years of data from the IceCube neutrino telescope. By analyzing the reconstructed energies and zenith angles of 305,735 atmospheric $\nu_\mu$ and $\bar{\nu}_\mu$ events we construct confidence intervals in two analysis spaces: $\sin^2 (2\theta_{24})$ vs. $\Delta m^2_{41}$ under the conservative assumption $\theta_{34}=0$; and $\sin^2(2\theta_{24})$ vs. $\sin^2 (2\theta_{34})$ given sufficiently large $\Delta m^2_{41}$ that fast oscillation features are unresolvable. Detailed discussions of the event selection, systematic uncertainties, and fitting procedures are presented. No strong evidence for sterile neutrinos is found, and the best-fit likelihood is consistent with the no sterile neutrino hypothesis with a p-value of 8\% in the first analysis space and 19\% in the second.Comment: This long-form paper is a companion to the letter "An eV-scale sterile neutrino search using eight years of atmospheric muon neutrino data from the IceCube Neutrino Observatory". v2: update other experiments contours on results plo