Resonant Structures in the Low-Energy Electron Continuum for Single Ionization of Atoms in the Tunneling Regime

We present results of high-resolution experiments on single ionization of He, Ne and Ar by ultra-short (25 fs, 6 fs) 795 nm laser pulses at intensities 0.15-2.0x10^15 W/cm^2. We show that the ATI-like pattern can survive deep in the tunneling regime and that the atomic structure plays an important role in the formation of the low-energy photoelectron spectra even at high intensities. The absence of ponderomotive shifts, the splitting of the peaks and their degeneration for few-cycle pulses indicate that the observed structures originate from a resonant process.Comment: 11 pages, 3 figure

Identification of a Small Molecule that Increases Hemoglobin Oxygen Affinity and Reduces SS Erythrocyte Sickling

Small molecules that increase the oxygen affinity of human hemoglobin may reduce sickling of red blood cells in patients with sickle cell disease. We screened 38 700 compounds using small molecule microarrays and identified 427 molecules that bind to hemoglobin. We developed a high-throughput assay for evaluating the ability of the 427 small molecules to modulate the oxygen affinity of hemoglobin. We identified a novel allosteric effector of hemoglobin, di(5-(2,3-dihydro-1,4-benzodioxin-2-yl)-4H-1,2,4-triazol-3-yl)disulfide (TD-1). TD-1 induced a greater increase in oxygen affinity of human hemoglobin in solution and in red blood cells than did 5-hydroxymethyl-2-furfural (5-HMF), N-ethylmaleimide (NEM), or diformamidine disulfide. The three-dimensional structure of hemoglobin complexed with TD-1 revealed that monomeric units of TD-1 bound covalently to β-Cys93 and β-Cys112, as well as noncovalently to the central water cavity of the hemoglobin tetramer. The binding of TD-1 to hemoglobin stabilized the relaxed state (R3-state) of hemoglobin. TD-1 increased the oxygen affinity of sickle hemoglobin and inhibited in vitro hypoxia-induced sickling of red blood cells in patients with sickle cell disease without causing hemolysis. Our study indicates that TD-1 represents a novel lead molecule for the treatment of patients with sickle cell disease

Unexpected high seroprevalence of hepatitis e virus in patients with alcohol-related cirrhosis

Introduction: Little is known about hepatitis E virus (HEV) infection in patients with cirrhosis. The aim of the present study was to describe the frequency of HEV infection and associated risk factors in patients with cirrhosis from Argentina. Materials and methods: We evaluated HEV seroprevalence (IgG anti-HEV) and acute infections (IgM and RNA) in patients with cirrhosis (n = 140) vs. healthy controls (n = 300). Additionally, we compared the same outcomes in individuals with alcohol-related cirrhosis (n = 43) vs. patients with alcohol use disorder (without cirrhosis, n = 72). Results: The overall HEV seroprevalence in the cohort of subjects with cirrhosis was 25% (35/140), compared to 4% in the healthy control group [12/300; OR = 8; (95% CI = 4-15.99); p<0.05]. HEV seropositivity was significantly higher in alcohol-related cirrhosis compared to other causes of cirrhosis [39.5% vs. 12.4%; OR = 4.71; (95% CI = 1.9-11.6); p<0.05] and to healthy controls [OR = 15.7; (95% CI = 6.8-36.4); p = 0.0001]. The HEV seroprevalence in alcoholic-related cirrhosis vs. with alcohol use disorder was 39.5% vs. 12.5% [OR = 4.58; (95% CI = 1.81-11.58); p<0.001]. Conclusion: We found a high seroprevalence of HEV in patients with cirrhosis and in individuals with alcohol use disorder. The simultaneous presence of both factors (cirrhosis + alcohol) showed more association to HEV infection. Larger studies with prospective follow up are needed to further clarify this interaction.Fil: Fantilli, Anabella Clara. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Trinks, Julieta. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Marciano, Sebastian. Hospital Italiano; ArgentinaFil: Zárate, Raúl Fabián. Hospital Córdoba; ArgentinaFil: Balderramo, Domingo. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Martínez Wassaf, Maribel G.. LACE Laboratorios; ArgentinaFil: Haddad, Leila. Hospital Italiano; ArgentinaFil: Gadano, Adrián. Hospital Italiano; ArgentinaFil: Debes, José D.. University of Minnesota; Estados UnidosFil: Pisano, María Belén. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Ré, Viviana Elizabeth. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Hepatitis E virus infection in patients on dialysis and in solid organ transplant recipients in Argentina: exploring associated risk factors

Infection with hepatitis E virus (HEV) leads to acute hepatitis infection in immunocompetent hosts. HEV genotype 3 can present with high frequency and lead to chronic infection in individuals with a compromised immune system. The risk factors related to increased seroprevalence or chronicity in this population are not entirely understood. Moreover, most studies addressing risk factors for HEV in non-endemic areas come from developed areas such as North America and Europe. In this study we evaluated seroprevalence, chronicity and risk factors for HEV in 120 transplant recipients and 88 patients on dialysis in Argentina. We found a significantly higher seroprevalence of HEV IgG in those undergoing dialysis compared with healthy controls (10.2% and 4.3% respectively, p = 0.03). No difference in HEV seroprevalence was observed between healthy controls and transplant recipients (5.8%). We found no association between previously identified risk factors for HEV, such as pork consumption or use of tacrolimus, and HEV seroprevalence. In univariate and multivariate analyses, consumption of fish was associated with higher seroprevalence of HEV (OR = 9.33; 95% CI: 2.07–42.2; p = 0.04). None of the samples showed HEV RNA amplification, indicating that chronicity does not seem to be an issue in these cohorts. Our results show increased seroprevalence of HEV in individuals undergoing dialysis but not in transplant recipients. We also found that fish consumption can be a potential risk factor for acquiring HEV.Fil: Pisano, María Belén. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Balderramo, Domingo. Hospital Privado Centro Médico de Córdoba; ArgentinaFil: Martinez Wassaf, Maribel Graciela. LACE Laboratories; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Lotto, Martín Miguel. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Carlino, Yanina. Hospital Privado Centro Médico de Córdoba; ArgentinaFil: Ré, Viviana Elizabeth. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; ArgentinaFil: Debes, José D.. University of Minnesota; Estados Unido

Identification of a Small Molecule that Increases Hemoglobin Oxygen Affinity and Reduces SS Erythrocyte Sickling

Small molecules that increase the oxygen affinity of human hemoglobin may reduce sickling of red blood cells in patients with sickle cell disease. We screened 38 700 compounds using small molecule microarrays and identified 427 molecules that bind to hemoglobin. We developed a high-throughput assay for evaluating the ability of the 427 small molecules to modulate the oxygen affinity of hemoglobin. We identified a novel allosteric effector of hemoglobin, di(5-(2,3-dihydro-1,4-benzodioxin-2-yl)- 4H-1,2,4-triazol-3-yl)disulfide (TD-1). TD-1 induced a greater increase in oxygen affinity of human hemoglobin in solution and in red blood cells than did 5-hydroxymethyl-2-furfural (5-HMF), N-ethylmaleimide (NEM), or diformamidine disulfide. The three-dimensional structure of hemoglobin complexed with TD-1 revealed that monomeric units of TD-1 bound covalently to β-Cys93 and β-Cys112, as well as noncovalently to the central water cavity of the hemoglobin tetramer. The binding of TD-1 to hemoglobin stabilized the relaxed state (R3-state) of hemoglobin. TD-1 increased the oxygen affinity of sickle hemoglobin and inhibited in vitro hypoxia-induced sickling of red blood cells in patients with sickle cell disease without causing hemolysis. Our study indicates that TD-1 represents a novel lead molecule for the treatment of patients with sickle cell disease

Hepatitis E virus infection in hemodialysis patients: A prospective analysis

This study highlights variations in HEV serological status inpatients with ESRD undergoing HD.To assess the dynamics of HEV infection in thispopulation, we prospectively evaluated individuals with end-stagerenal disease (ESRD) undergoing HD at a private hospital in Cordoba, Argentina, between November 2014 and November 2017.Fil: Pisano, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Virología; ArgentinaFil: Leathers, James. Vanderbilt University School Of Medicine; Estados UnidosFil: Balderramo, Domingo. Hospital Privado Centro Médico de Córdoba; ArgentinaFil: Diehl, Fernando. Hospital Privado Centro Médico de Córdoba; ArgentinaFil: Bolomo, Andrea. Hospital Privado Centro Médico de Córdoba; ArgentinaFil: Fernández, Pehuen. Hospital Privado Centro Médico de Córdoba; ArgentinaFil: Martínez Wassaf, Maribel. Laboratorios Clínicos Especializados- Lace; ArgentinaFil: Cristani, Carla. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; ArgentinaFil: Di Cola Bucciarelli, Guadalupe. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Virología; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; ArgentinaFil: De la Fuente, Jorge. Hospital Privado Centro Médico de Córdoba; ArgentinaFil: Debes, José D.. Universidad de Minnesota; Estados UnidosFil: Ré, Viviana Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Virología; Argentin

Surface Plasmon Resonance Imaging-Mass Spectrometry Coupling on Antibody Array Biochip: Multiplex Monitoring of Biomolecular Interactions and On-Chip Identification of Captured Antigen

International audienceThe coupling of surface plasmon resonance imaging (SPRi) with mass spectrometry (MS) offers a very promising multidimensional analysis. This system takes advantage of the two well-established techniques: SPR, which allows for the analysis of biomolecular interactions through the determination of kinetic and thermodynamic constants, and MS, which can characterize biological structures from mass measurements and fragmentation experiments. Here, a protocol for the coupling of SPRi with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is described using a biochip grafted by antibodies in an array format. Interaction between β-lactoglobulin antibodies and the protein antigen is detected and analyzed by SPRi. Then, the arrayed biochip which fitted a commercially MALDI target was inserted in a MALDI source, and mass spectra were recorded directly from the biochip surface from each antibody spot, showing protein ions attributed to the corresponding specific protein antigens