Behavioural and cognitive changes in a patient with leukoencephalopathy due to lymphomatosis cerebri

A 59 years old female with a prior history of facial hemangioma, with a three-month progressive cognitive impairment (MoCA score 15/30) combined with abulia, unmotivated crying,  non-fluent language, limb paratonia, bilateral Hoffman and palmomental reflex; and apraxic gait.  Presentamos el caso de una mujer de 59 años con antecedente de hemangioma facial, con deterioro cognitivo progresivo de tres meses de evolucón (puntuación MoCA 15/30) combinado con abulia, llanto desmotivado, lenguaje no fluido, paratonia de extremidades, Hoffman bilateral y reflejo palmomental; y marcha apráxica.Se realizó resonancia magnética cerebral al ingreso, que reveló una lesión extensa que involucraba la sustancia blanca periventricular, subcortical y profunda. La espectroscopia multivoxel mostró un aumento en la colina y la disminución de NAA.En la evaluación: un laboratorio específico para infecciones virales, sífilis, VIH, LDH y CEA fue normal. Además, el LCR fue normal y la citología del LCR y la citometría de flujo fueron negativas. La angiografía cerebral descartó la presencia de fístula arteriovenosa o anastomosis anormal. Una biopsia determinó que la lesión era un linfoma no Hodgkin de células B (CD20 +). Debido a su extensión, se realizó el diagnóstico definitivo de linfomatosis cerebral. No se encontró lesión primaria. &nbsp

Noninfectious retrovirus particles drive the APOBEC3/Rfv3 dependent neutralizing antibody response.

Members of the APOBEC3 family of deoxycytidine deaminases counteract a broad range of retroviruses in vitro through an indirect mechanism that requires virion incorporation and inhibition of reverse transcription and/or hypermutation of minus strand transcripts in the next target cell. The selective advantage to the host of this indirect restriction mechanism remains unclear, but valuable insights may be gained by studying APOBEC3 function in vivo. Apobec3 was previously shown to encode Rfv3, a classical resistance gene that controls the recovery of mice from pathogenic Friend retrovirus (FV) infection by promoting a more potent neutralizing antibody (NAb) response. The underlying mechanism does not involve a direct effect of Apobec3 on B cell function. Here we show that while Apobec3 decreased titers of infectious virus during acute FV infection, plasma viral RNA loads were maintained, indicating substantial release of noninfectious particles in vivo. The lack of plasma virion infectivity was associated with a significant post-entry block during early reverse transcription rather than G-to-A hypermutation. The Apobec3-dependent NAb response correlated with IgG binding titers against native, but not detergent-lysed virions. These findings indicate that innate Apobec3 restriction promotes NAb responses by maintaining high concentrations of virions with native B cell epitopes, but in the context of low virion infectivity. Finally, Apobec3 restriction was found to be saturable in vivo, since increasing FV inoculum doses resulted in decreased Apobec3 inhibition. By analogy, maximizing the release of noninfectious particles by modulating APOBEC3 expression may improve humoral immunity against pathogenic human retroviral infections

Breakdown transients in high-k multilayered MOS stacks: Role of the oxide-oxide thermal boundary resistance

In this work, breakdown transients of multilayered gate oxide stacks were analyzed to study the impact of the interfaces between oxides on the heat dissipation considering an electromigration-based progressive breakdown model. Using two distinct measurement setups on four different sets of samples, featuring two layers and three layers of Al 2 O 3 and HfO 2 interspersed, the breakdown transients were captured and characterized in terms of the degradation rate. Experimental results show that the number of oxide-oxide interfaces present in the multilayered stack has no visible impact on the breakdown growth rate among our samples. This strongly supports the interpretation of the bulk materials dominating the heat transfer to the surroundings of a fully formed conductive filament that shows no electrical differences between our various multilayered stack configurations.Fil: Boyeras Baldomá, Santiago. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires. Unidad de Investigación y Desarrollo de las Ingenierías; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pazos, Sebastián Matías. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires. Unidad de Investigación y Desarrollo de las Ingenierías; ArgentinaFil: Aguirre, F. L.. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires. Unidad de Investigación y Desarrollo de las Ingenierías; ArgentinaFil: Palumbo, Felix Roberto Mario. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires. Unidad de Investigación y Desarrollo de las Ingenierías; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Serendipitous discovery of RR Lyrae stars in the Leo V ultra-faint galaxy

During the analysis of RR Lyrae stars discovered in the High cadence Transient Survey (HiTS) taken with the Dark Energy Camera at the 4-m telescope at Cerro Tololo Inter-American Observatory, we found a group of three very distant, fundamental mode pulsator RR Lyrae (type ab). The location of these stars agrees with them belonging to the Leo V ultra-faint satellite galaxy, for which no variable stars have been reported to date. The heliocentric distance derived for Leo V based on these stars is 173 +/- 5 kpc. The pulsational properties (amplitudes and periods) of these stars locate them within the locus of the Oosterhoff II group, similar to most other ultra-faint galaxies with known RR Lyrae stars. This serendipitous discovery shows that distant RR Lyrae stars may be used to search for unknown faint stellar systems in the outskirts of the Milky Way.Comment: Accepted in ApJ Letter

Cellular HIV-1 inhibition by truncated old world primate APOBEC3A proteins lacking a complete deaminase domain

AbstractThe APOBEC3 (A3) deaminases are retrovirus restriction factors that were proposed as inhibitory components of HIV-1 gene therapy vectors. However, A3 mutational activity may induce undesired genomic damage and enable HIV-1 to evade drugs and immune responses. Here, we show that A3A protein from Colobus guereza (colA3A) can restrict HIV-1 replication in producer cells in a deaminase-independent manner without inducing DNA damage. Neither HIV-1 reverse transcription nor integration were significantly affected by colA3A, but capsid protein synthesis was inhibited. The determinants for colA3A restriction mapped to the N-terminal region. These properties extend to A3A from mandrills and De Brazza׳s monkeys. Surprisingly, truncated colA3A proteins expressing only the N-terminal 100 amino acids effectively exclude critical catalytic regions but retained potent cellular restriction activity. These highlight a unique mechanism of cellular HIV-1 restriction by several Old World monkey A3A proteins that may be exploited for functional HIV-1 cure strategies

A Single Nucleotide Polymorphism in Tetherin Promotes Retrovirus Restriction In Vivo

Tetherin is a membrane protein of unusual topology expressed from rodents to humans that accumulates enveloped virus particles on the surface of infected cells. However, whether this ‘tethering’ activity promotes or restricts retroviral spread during acute retrovirus infection in vivo is controversial. We report here the identification of a single nucleotide polymorphism in the Tetherin gene of NZW/LacJ (NZW) mice that mutated the canonical ATG start site to GTG. Translation of NZW Tetherin from downstream ATGs deleted a conserved dual-tyrosine endosomal sorting motif, resulting in higher cell surface expression and more potent inhibition of Friend retrovirus release compared to C57BL/6 (B6) Tetherin in vitro. Analysis of (B6×NZW)F1 hybrid mice revealed that increased Tetherin cell surface expression in NZW mice is a recessive trait in vivo. Using a classical genetic backcrossing approach, NZW Tetherin expression strongly correlated with decreased Friend retrovirus replication and pathogenesis. However, the protective effect of NZW Tetherin was not observed in the context of B6 Apobec3/Rfv3 resistance. These findings identify the first functional Tetherin polymorphism within a mammalian host, demonstrate that Tetherin cell surface expression is a key parameter for retroviral restriction, and suggest the existence of a restriction factor hierarchy to counteract pathogenic retrovirus infections in vivo

Differential virus restriction patterns of rhesus macaque and human APOBEC3A: Implications for lentivirus evolution

AbstractThe human apolipoprotein B mRNA editing enzyme catalytic peptide-like 3 (APOBEC3; A3) family of proteins (A3A-H) are known to restrict various retroviruses and retroelements, but the full complement of rhesus macaque A3 proteins remains unclear. We report the isolation and characterization of the hA3A homologue from rhesus macaques (rhA3A) and show that the rhesus macaque and human A3 genes are orthologous. RhA3A is expressed at high levels in activated CD4+ T cells, is widely expressed in macaque tissues, and is degraded in the presence of the human immunodeficiency virus (HIV-1) and simian–human immunodeficiency virus (SHIV) genomes. Our results indicate that rhA3A is a potent inhibitor of SHIVΔvif and to a lesser extent HIV-1Δvif. Unlike hA3A, rhA3A did not inhibit adeno-associated virus 2 (AAV-2) replication and L1 retrotransposition. These data suggest an evolutionary switch in primate A3A virus specificity and provide the first evidence that a primate A3A can inhibit lentivirus replication

Implementación banco de pruebas GRID

La computación Grid permite a grupos de recursos distribuidos y heterogéneos trabajar en forma coordinada para solucionar problemas complejos, que seria costoso o imposible de solucionar con las máquinas disponibles en forma aislada. En este trabajo desarrollaremos el proyecto de extensión presentado en la Universidad Nacional del Comahue junto con el CRIBABB para la interconexión y puesta en marcha de laboratorios para la investigación.Eje: OtrosRed de Universidades con Carreras en Informática (RedUNCI