Argentinean agid test for diagnosis of equine infectious anemia: six years of history

Equine infectious anemia (EIA) is a disease of high economic impact on the equine industry worldwide. Since horses are frequent travelers, EIA falls under strict regulatory control programs in many countries. In Argentina the national animal health authority (SENASA) states that all horses imported, moving within the country, or congregating at public assemblies must have a negative EIA report conducted within the previous 2 months. The agent causing EIA is a RNA virus from the Retroviridae family and its major capsid protein named p26 is the most immunogenic protein in the viral particle. Thus, the detection of specific antibodies directed to p26 is the aim of most diagnosis tests available in the world. The agar gel immunodifusion (AGID) is the officially accepted method to certify the diagnosis of EIA in Argentina. Since 2009 IncuINTA was working on the scaling up and production of the KIT AIE IDGA RP26, an Argentinean AGID test entirely developed in the laboratory containing a recombinant p26 protein to detect EIA antibodies in horses’ serum. Until 2015 IncuINTA produced two pilot batches and six commercial batches (one per year) containing from 24000 determinations in 2011 to 39600 determinations in 2015. Since the product was launched in 2011, the sales were increased 109%. Up to date we have placed on the market 170640 determinations. As expected, the number of laboratories buying the KIT AIE IDGA RP26 was also increasing through time being 26 in 2011 and 36 in 2015. This number of clients represents 17% of the 207 laboratories authorized by SENASA to diagnose EIA in Argentina. These laboratories are located mostly in Buenos Aires, Santa Fe, Entre Ríos, Formosa, La Pampa, Rio Negro, Cordoba, Corrientes, Salta and Tucum an provinces. Until 2009 there was no Argentinean EIA test available in our market being the imported ones very expensive. IncuINTA, which is a R&D laboratory, could scale up, produce and sell the KIT AIE IDGA RP26 during six consecutive years. After this success, IncuINTA perspective is to increase the number of batches each year to be able to attend the demand of most diagnosis laboratories in the country.Fil: Bok, Marina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Asenzo, G.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Vena, M. M.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Parreño, V.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Wigdorovitz, A.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina10th International Equine Infectious Diseases ConferenceBuenos AiresArgentinaUniversity of Kentuck

SMIT (Sodium-Myo-Inositol Transporter) 1 Regulates Arterial Contractility Through the Modulation of Vascular Kv7 Channels

Objective: The SMIT1 (sodium:myo-inositol transporter 1) regulates myo-inositol movement into cells and responses to hypertonic stimuli. Alteration of myo-inositol levels has been associated with several diseases, including hypertension, but there is no evidence of a functional role of SMIT1 in the vasculature. Recent evidence showed that in the nervous system SMIT1 interacted and modulated the function of members of the Kv7 family of voltage-gated potassium channels, which are also expressed in the vasculature where they regulate arterial contractility. Therefore, in this study, we evaluated whether SMIT1 was functionally relevant in arterial smooth muscle. Approach and Results: Immunofluorescence and polymerase chain reaction experiments revealed that SMIT1 was expressed in rat renal and mesenteric vascular smooth muscle cells. Isometric tension recordings showed that incubation of renal arteries with raffinose and myo-inositol (which increases SMIT1 expression) reduced the contractile responses to methoxamine, an effect that was abolished by preincubation with the pan-Kv7 blocker linopirdine and by molecular knockdown of Kv7.4 and Kv7.5. Knockdown of SMIT1 increased the contraction of renal arteries induced by methoxamine, impaired the response to the Kv7.2–Kv7.5 activator ML213 but did not interfere with the relaxant responses induced by openers of other potassium channels. Proximity ligation assay showed that SMIT1 interacted with heteromeric channels formed by Kv7.4 and Kv7.5 channels in both renal and mesenteric vascular smooth muscle cells. Patch-clamp experiments showed that incubation with raffinose plus myo-inositol increased Kv7 currents in vascular smooth muscle cells. Conclusions: SMIT1 protein is expressed in vascular smooth muscle cells where it modulates arterial contractility through an association with Kv7.4/Kv7.5 heteromers

Spin observables in the pn→pΛpn \to p \Lambda reaction

The T matrix of the LambdaN-> NN reaction, which is a strangeness changing weak process, is derived. The explicit formulas of the spin observables are given for s-wave p-Lambda final states which kinematically corresponds to inverse reaction of the weak nonmesonic decay of Lambda hypernuclei. One can study interferences between amplitudes of parity- conserving and violating, spin- singlet and triplet and isospin- singlet and triplet. Most of them are not available in the study of the nonmesonic decay. They clarify structure of the reaction and constrain strongly theoretical models for weak hyperon nucleon interaction.Comment: 7pages,ReVTeX,no figure

Delayed clusters accompanying nonmesonic weak decay of the Λ\Lambda-hypernuclei: a clue to nonleptonic processes

The nonmesonic decay of $\Lambda$-hypernuclei provides access to the nonleptonic weak decay process $\Lambda N \to NN$, which is achievable only through the observation of hypernuclear ground-state decays. We continue the discussion of some specific cases which make it possible to detect a few exclusive transitions, namely, the stripping of nucleon from the ground state results in a resonance state decaying via emission of two clusters. Delayed clusters accompanying weak decay of light hypernuclei give a unique information on spin dependence of the weak decay matrix elements.Comment: Presented at International Bogolyubov Conference "Problems of Theoretical and Mathematical Physics" (dedicated to the 100th anniversary of the birth of N.N.~Bogolyubov) Dubna, Russia, August 21 - 27, 200

The weak strangeness production reaction pn→pΛpn \to p\Lambda in a one-boson-exchange model

The weak production of Lambdas in nucleon-nucleon scattering is studied in a meson-exchange framework. The weak transition operator for the $NN \to N \Lambda$ reaction is identical to a previously developed weak strangeness-changing transition potential $\Lambda N \to NN$ that describes the nonmesonic decay of hypernuclei. The initial $NN$ and final $YN$ state interaction has been included by using realistic baryon-baryon forces that describe the available elastic scattering data. The total and differential cross sections as well as the parity-violating asymmetry are studied for the reaction $pn \to p\Lambda$. These observables are found to be sensitive to the choice of the strong interaction potential and the structure of the weak transition potential.Comment: 25 pages, 8 postscript figures. Submitted to Phys. Rev.

Variational study of two-nucleon systems with lattice QCD

The low-energy spectrum and scattering of two-nucleon systems are studied with lattice quantum chromodynamics using a variational approach. A wide range of interpolating operators are used: dibaryon operators built from products of plane-wave nucleons, hexaquark operators built from six localized quarks, and quasilocal operators inspired by two-nucleon bound-state wave functions in low-energy effective theories. Sparsening techniques are used to compute the timeslice-to-all quark propagators required to form correlation-function matrices using products of these operators. Projection of these matrices onto irreducible representations of the cubic group, including spin-orbit coupling, is detailed. Variational methods are applied to constrain the low-energy spectra of two-nucleon systems in a single finite volume with quark masses corresponding to a pion mass of 806 MeV. Results for S- and D-wave phase shifts in the isospin singlet and triplet channels are obtained under the assumption that partial-wave mixing is negligible. Tests of interpolating-operator dependence are used to investigate the reliability of the energy spectra obtained and highlight both the strengths and weaknesses of variational methods. These studies and comparisons to previous studies using the same gauge-field ensemble demonstrate that interpolating-operator dependence can lead to significant effects on the two-nucleon energy spectra obtained using both variational and nonvariational methods, including missing energy levels and other discrepancies. While this study is inconclusive regarding the presence of two-nucleon bound states at this quark mass, it provides robust upper bounds on two-nucleon energy levels that can be improved in future calculations using additional interpolating operators and is therefore a step toward reliable nuclear spectroscopy from the underlying Standard Model of particle physics

The nonmesonic weak decay of the hypertriton

The nonmesonic decay of the hypertriton is calculated based on a hypertriton wavefunction and 3N scattering states, which are rigorous solutions of 3-body Faddeev equations using realistic NN and hyperon-nucleon interactions. The pion-exchange together with heavier meson exchanges for the $\Lambda N \to N N$ transition is considered. The total nonmesonic decay rate is found to be 0.5% of the free $\Lambda$ decay rate. Integrated as well as differential decay rates are given. The p- and n- induced decays are discussed thoroughly and it is shown that the corresponding total rates cannot be measured individually.Comment: 27 pages, 20 figures, revtex, submitted to Phys. Rev.

What Does Free Space Lambda-Lambda Interaction Predict for Lambda-Lambda Hypernuclei?

Data on Lambda-Lambda hypernuclei provide a unique method to learn details on the strangeness S =-2 sector of the baryon-baryon interaction. From the free space Bonn-Julich potentials, determined from data on baryon-baryon scattering in the S=0,-1 channels, we construct an interaction in the S =-2 sector to describe the experimentally known Lambda-Lambda hypernuclei. After including short--range (Jastrow) and RPA correlations, we find masses for these Lambda-Lambda hypernuclei in a reasonable agreement with data, taking into account theoretical and experimental uncertainties. Thus, we provide a natural extension, at low energies, of the Bonn-Julich OBE potentials to the S =-2 channel.Comment: 4 pages, 2 figures, revtex4 style. Minor changes in conclusions. References updated. Accepted in Phys. Rev. Let

A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity

Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new antigenic profiles and altered specificity for histo-blood group antigens (HBGA), the determinants of cell attachment and susceptibility, hampering the development of immunotherapeutics. Here, we show that a llama-derived nanobody M4 neutralizes multiple GII.4 variants with high potency in human intestinal enteroids. The crystal structure of M4 complexed with the protruding domain of the GII.4 capsid protein VP1 revealed a conserved epitope, away from the HBGA binding site, fully accessible only when VP1 transitions to a “raised” conformation in the capsid. Together with dynamic light scattering and electron microscopy of the GII.4 VLPs, our studies suggest a mechanism in which M4 accesses the epitope by altering the conformational dynamics of the capsid and triggering its disassembly to neutralize GII.4 infection.Instituto de VirologíaFil: Salmen, Wilhelm. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Hu, Liya. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Bok, Marina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnologicas; ArgentinaFil: Bok, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chaimongkol, Natthawan. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Ettayebi, Khalil. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Sosnovtsev, Stanislav V. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Soni, Kaundal. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Ayyar, B. Vijayalakshmi. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Shanker, Sreejesh. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Neill, Frederick H. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Sankaran, Banumathi. Berkeley Center for Structural Biology. Molecular Biophysics and Integrated Bioimaging. Lawrence Berkeley Laboratory; Estados UnidosFil: Atmar, Robert L. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Atmar, Robert L. Baylor College of Medicine. Department of Medicine; Estados UnidosFil: Estes, Mary K. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Estes, Mary K. Baylor College of Medicine. Department of Medicine; Estados UnidosFil: Green, Kim Y. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virologia e Innovaciones Tecnologicas (IVIT); ArgentinaFil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Prasad, B. V. Venkataram. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Prasad, B. V. Venkataram. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados Unido

Strangeness nuclear physics: a critical review on selected topics

Selected topics in strangeness nuclear physics are critically reviewed. This includes production, structure and weak decay of $\Lambda$--Hypernuclei, the $\bar K$ nuclear interaction and the possible existence of $\bar K$ bound states in nuclei. Perspectives for future studies on these issues are also outlined.Comment: 63 pages, 51 figures, accepted for publication on European Physical Journal