A shortcut to identifying small molecule signals that regulate behavior and development in Caenorhabditis elegans

Small molecule metabolites play important roles in Caenorhabditis elegans biology, but effective approaches for identifying their chemical structures are lacking. Recent studies revealed that a family of glycosides, the ascarosides, differentially regulate C. elegans development and behavior. Low concentrations of ascarosides attract males and thus appear to be part of the C. elegans sex pheromone, whereas higher concentrations induce developmental arrest at the dauer stage, an alternative, nonaging larval stage. The ascarosides act synergistically, which presented challenges for their identification via traditional activity-guided fractionation. As a result the chemical characterization of the dauer and male attracting pheromones remained incomplete. Here, we describe the identification of several additional pheromone components by using a recently developed NMR-spectroscopic approach, differential analysis by 2D NMR spectroscopy (DANS), which simplifies linking small molecule metabolites with their biological function. DANS-based comparison of wild-type C. elegans and a signaling-deficient mutant, daf-22, enabled identification of 3 known and 4 previously undescribed ascarosides, including a compound that features a p-aminobenzoic acid subunit. Biological testing of synthetic samples of these compounds revealed additional evidence for synergy and provided insights into structure–activity relationships. Using a combination of the three most active ascarosides allowed full reconstitution of the male-attracting activity of wild-type pheromone extract. Our results highlight the efficacy of DANS as a method for identifying small-molecule metabolites and placing them within a specific genetic context. This study further supports the hypothesis that ascarosides represent a structurally diverse set of nematode signaling molecules regulating major life history traits

Screening enhancement factors for laboratory CNO and rp astrophysical reactions

Cross sections of laboratory CNO and rp astrophysical reactions are enhanced due to the presence of the multi-electron cloud that surrounds the target nuclei. As a result the relevant astrophysical factors are overestimated unless corrected appropriately. This study gives both an estimate of the error committed if screening effects are not taken into account and a rough profile of the laboratory energy thresholds at which the screening effect appears. The results indicate that, for most practical purposes, screening corrections to past relevant experiments can be disregarded. Regarding future experiments, however, screening corrections to the CNO reactions will certainly be of importance as they are closely related to the solar neutrino fluxes and the rp process. Moreover, according to the present results, screening effects will have to be taken into account particularly by the current and future LUNA experiments, where screened astrophysical factors will be enhanced to a significant degree.Comment: 6 RevTex pages + 2 ps figures. (Revised version). Accepted for publication in Journal of Physics

Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression.

To analyze the clinical presentation and complications of varicella zoster virus (VZV) infection in children with rheumatic diseases treated with immunosuppressive medication such as biological disease-modifying antirheumatic drugs (bDMARDs) and/or conventional disease-modifying antirheumatic drugs (cDMARDs), and to analyze the therapeutic approach to VZV infections with respect to the concomitant immunosuppressive treatment. Retrospective multicenter study using the Swiss Pediatric Rheumatology registry. Children with rheumatic diseases followed in a Swiss center for pediatric rheumatology and treated with cDMARD and/or bDMARD with a clinical diagnosis of varicella or herpes zoster between January 2004 and December 2013 were included. Twenty-two patients were identified, of whom 20 were treated for juvenile idiopathic arthritis, 1 for a polyglandular autoimmune syndrome type III, and 1 for uveitis. Of these 22 patients, 16 had varicella and 6 had herpes zoster. Median age at VZV disease was 7.6 years (range 2 to 17 years), with 6.3 years (range 2 to 17 years) for those with varicella and 11.6 years (range 5 to 16 years) for those with herpes zoster. The median interval between start of immunosuppression and VZV disease was 14.1 months (range 1 to 63 months). Two patients had received varicella vaccine (1 dose each) prior to start of immunosuppression. Concomitant immunosuppressive therapy was methotrexate (MTX) monotherapy (n = 9) or bDMARD monotherapy (n = 2), or a combination of bDMARD with prednisone, MTX or Leflunomide (n = 11). Four patients experienced VZV related complications: cellulitis in 1 patient treated with MTX, and cellulitis, sepsis and cerebellitis in 3 patients treated with biological agents and MTX combination therapy. Six children were admitted to hospital (range of duration: 4 to 9 days) and 12 were treated with valaciclovir or aciclovir. The clinical course of varicella and herpes zoster in children under immunosuppression is variable, with 4 (18 %) of 22 children showing a complicated course. Thorough assessment of VZV disease and vaccination history and correct VZV vaccination according to national guidelines at diagnosis of a rheumatic autoimmune disease is essential to minimize VZV complications during a later immunosuppressive treatment

Isotope shift in the electron affinity of chlorine

The specific mass shift in the electron affinity between ^{35}Cl and ^{37}Cl has been determined by tunable laser photodetachment spectroscopy to be -0.51(14) GHz. The isotope shift was observed as a difference in the onset of the photodetachment process for the two isotopes. In addition, the electron affinity of Cl was found to be 29138.59(22) cm^{-1}, giving a factor of 2 improvement in the accuracy over earlier measurements. Many-body calculations including lowest-order correlation effects demonstrates the sensitivity of the specific mass shift and show that the inclusion of higher-order correlation effects would be necessary for a quantitative description.Comment: 16 pages, 6 figures, LaTeX2e, amsmat

Isotopic Scaling in Nuclear Reactions

A three parameter scaling relationship between isotopic distributions for elements with Z$\leq 8$ has been observed that allows a simple description of the dependence of such distributions on the overall isospin of the system. This scaling law (termed iso-scaling) applies for a variety of reaction mechanisms that are dominated by phase space, including evaporation, multifragmentation and deeply inelastic scattering. The origins of this scaling behavior for the various reaction mechanisms are explained. For multifragmentation processes, the systematics is influenced by the density dependence of the asymmetry term of the equation of state.Comment: 10 Pages, 2 Figure

Steering in computational science: mesoscale modelling and simulation

This paper outlines the benefits of computational steering for high performance computing applications. Lattice-Boltzmann mesoscale fluid simulations of binary and ternary amphiphilic fluids in two and three dimensions are used to illustrate the substantial improvements which computational steering offers in terms of resource efficiency and time to discover new physics. We discuss details of our current steering implementations and describe their future outlook with the advent of computational grids.Comment: 40 pages, 11 figures. Accepted for publication in Contemporary Physic

Persistent, depth-intensified mixing during the Western Mediterranean Transition's initial stages

Piñeiro, S., González-Pola, C., Fernández-Díaz, J. M., Naveira-Garabato, A. C., Sánchez-Leal, R., Puig, P., et al. (2021). Persistent, depth-intensified mixing during the Western Mediterranean Transition's initial stages. Journal of Geophysical Research: Oceans, 126, e2020JC016535. https://doi.org/10.1029/2020JC016535. © 2020. American Geophysical Union. All Rights Reserved.© 2020. American Geophysical Union. All Rights Reserved. Major deep-convection activity in the northwestern Mediterranean during winter 2005 triggered the formation of a complex anomalous deep-water structure that substantially modified the properties of the Western Mediterranean deep layers. Since then, evolution of this thermohaline structure, the so-called Western Mediterranean Transition (WMT), has been traced through a regularly sampled hydrographic deep station located on the outer continental slope of Minorca Island. A rapid erosion of the WMT's near-bottom thermohaline signal was observed during 2005–2007. The plausible interpretation of this as local bottom-intensified mixing motivates this study. Here, the evolution of the WMT structure through 2005–2007 is reproduced by means of a one-dimensional diffusion model including double-diffusive mixing that allows vertical variation of the background mixing coefficient and includes a source term to represent the lateral advection of deep-water injections from the convection area. Using an optimization algorithm, a best guess for the depth-dependent background mixing coefficient is obtained for the study period. WMT evolution during its initial stages is satisfactorily reproduced using this simple conceptual model, indicating that strong depth-intensified mixing (K ∞ (z) ≈ 22 × 10−4 m2 s−1; z ⪆ 1,400 dbar) is a valid explanation for the observations. Extensive hydrographic and current observations gathered over the continental slope of Minorca during winter 2018, the first deep-convective winter intensively sampled in the region, provide evidence of topographically localized enhanced mixing concurrent with newly formed dense waters flowing along-slope toward the Algerian sub-basin. This transport-related boundary mixing mechanism is suggested to be a plausible source of the water-mass transformations observed during the initial stages of the WMT off Minorca.CTM2014-54374-R. BES-2015-074316.Versión del editor3,17

Analysis of TACI mutations in CVID & RESPI patients who have inherited HLA B*44 or HLA*B8

<p>Abstract</p> <p>Background</p> <p>Recent reports have suggested that Common Variable Immunodeficieny (CVID) can present as an autosomal dominant trait dependent on the inheritance of a set of uncommon mutations/alleles of TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) involving exons 3 or 4. Penetrance, however, appears to be incomplete. Among our clinic population, the greatest genetic linkage for CVID is to the major histocompatibility complex (MHC) on chromosome 6. The majority of our patients have inherited HLA *DQ2, *DR7, *DR3(17), *B8, and/or *B44. Of these, HLA*B44 was present in almost half of the patients and was thus the most common susceptibility allele. HLA *B44 was also found to be over-represented among patients who presented to our clinic with adult-onset recurrent sinopulmonary infections (RESPI) and normal serum immunoglobulin levels, a cohort that included first and second degree relatives of patients with CVID. One of the two original reports of the association between TACI and CVID also reported Human Leukocyte Antigen (HLA) haplotypes. Of 13 affected subjects, nine had inherited HLA *B8 and six had inherited HLA B44. This raised the possibility that TACI mutations might synergize with MHC class I alleles to enhance susceptibility to humoral immune deficiency.</p> <p>Methods</p> <p>We identified 63 CVID patients irrespective of HLA status and 13 RESPI patients who had inherited HLA*B44. To evaluate for mutations in the gene for TACI, we PCR amplified and sequenced TACI exons 3 and 4 from these patients.</p> <p>Results</p> <p>Of the 76 patients, eleven proved heterozygous for a previously reported, silent T->G polymorphism [rs35062843] at proline 97 in exon 3. However, none of the 13 RESPI patients and only one of the 63 CVID patients inherited a TACI allele previously associated with CVID. This patient was heterozygous for the TACI A181E allele (exon 4). She did not carry *DQ2, *DR7, *DR3(17), *B8, or *B44.</p> <p>Conclusion</p> <p>These findings suggest that TACI mutations are unlikely to play a critical role in creating susceptibility to CVID among patients with previously recognized MHC class I and class II susceptibility alleles.</p> <p>Supported by NIH/USIDNET N01-AI30070, NIH R21 AI079741 and NIH M01-RR00032</p

Classical wave experiments on chaotic scattering

We review recent research on the transport properties of classical waves through chaotic systems with special emphasis on microwaves and sound waves. Inasmuch as these experiments use antennas or transducers to couple waves into or out of the systems, scattering theory has to be applied for a quantitative interpretation of the measurements. Most experiments concentrate on tests of predictions from random matrix theory and the random plane wave approximation. In all studied examples a quantitative agreement between experiment and theory is achieved. To this end it is necessary, however, to take absorption and imperfect coupling into account, concepts that were ignored in most previous theoretical investigations. Classical phase space signatures of scattering are being examined in a small number of experiments.Comment: 33 pages, 13 figures; invited review for the Special Issue of J. Phys. A: Math. Gen. on "Trends in Quantum Chaotic Scattering