Microarray evidence for off target effects in tick RNA interference experiments, and the lack of strong correlation between DSRNA and antibody phenotypes in tick In vitro treatments for vaccine candidate screening

No abstract availabl

Is the classical Bukhvostov-Lipatov model integrable? A Painlev\'e analysis

In this work we apply the Weiss, Tabor and Carnevale integrability criterion (Painlev\'e analysis) to the classical version of the two dimensional Bukhvostov-Lipatov model. We are led to the conclusion that the model is not integrable classically, except at a trivial point where the theory can be described in terms of two uncoupled sine-Gordon models

Pathological Behavior in the Spectral Statistics of the Asymmetric Rotor Model

The aim of this work is to study the spectral statistics of the asymmetric rotor model (triaxial rigid rotator). The asymmetric top is classically integrable and, according to the Berry-Tabor theory, its spectral statistics should be Poissonian. Surprisingly, our numerical results show that the nearest neighbor spacing distribution $P(s)$ and the spectral rigidity $\Delta_3(L)$ do not follow Poisson statistics. In particular, $P(s)$ shows a sharp peak at $s=1$ while $\Delta_3(L)$ for small values of $L$ follows the Poissonian predictions and asymptotically it shows large fluctuations around its mean value. Finally, we analyze the information entropy, which shows a dissolution of quantum numbers by breaking the axial symmetry of the rigid rotator.Comment: 11 pages, 7 figures, to be published in Phys. Rev.

The role of disulfide bond replacements in analogues of the Tarantula toxin ProTx-II and their effects on inhibition of the voltage-gated sodium ion channel Nav1.7

Spider venom toxins, such as Protoxin-II (ProTx-II), have recently received much attention as selective Nav1.7 channel blockers, with potential to be developed as leads for the treatment of chronic nocioceptive pain. ProTx-II is a 30-amino acid peptide with three disulfide bonds that has been reported to adopt a well-defined inhibitory cystine knot (ICK) scaffold structure. Potential drawbacks with such peptides include poor pharmacodynamics and potential scrambling of the disulfide bonds in vivo. In order to address these issues, in the present study we report the solid-phase synthesis of lanthionine-bridged analogues of ProTx-II, in which one of the three disulfide bridges is replaced with a thioether linkage, and evaluate the biological properties of these analogues. We have also investigated the folding and disulfide bridging patterns arising from different methods of oxidation of the linear peptide precursor. Finally, we report the X-ray crystal structure of ProTx-II to atomic resolution; to our knowledge this is the first crystal structure of an ICK spider venom peptide not bound to a substrate

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine