Epstein–Barr Virus MicroRNAs Are Evolutionarily Conserved and Differentially Expressed

The pathogenic lymphocryptovirus Epstein–Barr virus (EBV) is shown to express at least 17 distinct microRNAs (miRNAs) in latently infected cells. These are arranged in two clusters: 14 miRNAs are located in the introns of the viral BART gene while three are located adjacent to BHRF1. The BART miRNAs are expressed at high levels in latently infected epithelial cells and at lower, albeit detectable, levels in B cells. In contrast to the tissue-specific expression pattern of the BART miRNAs, the BHRF1 miRNAs are found at high levels in B cells undergoing stage III latency but are essentially undetectable in B cells or epithelial cells undergoing stage I or II latency. Induction of lytic EBV replication was found to enhance the expression of many, but not all, of these viral miRNAs. Rhesus lymphocryptovirus, which is separated from EBV by ≥13 million years of evolution, expresses at least 16 distinct miRNAs, seven of which are closely related to EBV miRNAs. Thus, lymphocryptovirus miRNAs are under positive selection and are likely to play important roles in the viral life cycle. Moreover, the differential regulation of EBV miRNA expression implies distinct roles during infection of different human tissues

Early Regeneration of Thymic Progenitors in Rhesus Macaques Infected with Simian Immunodeficiency Virus

The thymus plays a critical role in the maturation and production of T lymphocytes and is a target of infection by human immunodeficiency virus (HIV) and the related simian immunodeficiency virus (SIV). Using the SIV/macaque model of AIDS, we examined the early effects of SIV on the thymus. We found that thymic infection by SIV resulted in increased apoptosis 7–14 d after infection, followed by depletion of thymocyte progenitors by day 21. A marked rebound in thymocyte progenitors occurred by day 50 and was accompanied by increased levels of cell proliferation in the thymus. Our results demonstrate a marked increase in thymic progenitor activity very early in the course of SIV infection, long before marked declines in peripheral CD4+ T cell counts

Vaccine protection against simian immunodeficiency virus in monkeys using recombinant gamma-2 herpesvirus

Recombinant strains of replication-competent rhesus monkey rhadinovirus (RRV) were constructed in which strong promoter/enhancer elements were used to drive expression of simian immunodeficiency virus (SIV) Env or Gag or a Rev-Tat-Nef fusion protein. Cultured rhesus monkey fibroblasts infected with each recombinant strain were shown to express the expected protein. Three RRV-negative and two RRV-positive rhesus monkeys were inoculated intravenously with a mixture of these three recombinant RRVs. Expression of SIV Gag was readily detected in lymph node biopsy specimens taken at 3 weeks postimmunization. Impressive anti-SIV cellular immune responses were elicited on the basis of major histocompatibility complex (MHC) tetramer staining and gamma interferon enzyme-linked immunospot (ELISPOT) assays. Responses were much greater in magnitude in the monkeys that were initially RRV negative but were still readily detected in the two monkeys that were naturally infected with RRV at the time of immunization. By 3 weeks postimmunization, responses measured by MHC tetramer staining in the two Mamu-A*01(+) RRV-negative monkeys reached 9.3% and 13.1% of all CD8(+) T cells in peripheral blood to the Gag CM9 epitope and 2.3% and 7.3% of all CD8(+) T cells in peripheral blood to the Tat SL8 epitope. Virus-specific CD8(+) T cell responses persisted at high levels up to the time of challenge at 18 weeks postimmunization, and responding cells maintained an effector memory phenotype. Despite the ability of the RRVenv recombinant to express high levels of Env in cultured cells, and despite the appearance of strong anti-RRV antibody responses in immunized monkeys, anti-Env antibody responses were below our ability to detect them. Immunized monkeys, together with three unimmunized controls, were challenged intravenously with 10 monkey infectious doses of SIVmac239. All five immunized monkeys and all three controls became infected with SIV, but peak viral loads were 1.2 to 3.0 log(10) units lower and chronic-phase viral loads were 1.0 to 3.0 log(10) units lower in immunized animals than the geometric mean of unimmunized controls. These differences were statistically significant. Anti-Env antibody responses following challenge indicated an anamnestic response in the vaccinated monkeys. These findings further demonstrate the potential of recombinant herpesviruses as preventive vaccines for AIDS. We hypothesize that this live, replication-competent, persistent herpesvirus vector could match, or come close to matching, live attenuated strains of SIV in the degree of protection if the difficulty with elicitation of anti-Env antibody responses can be overcome

Nitrides as ammonia synthesis catalysts and as potential nitrogen transfer reagents

In this article, an overview of the application of selected metal nitrides as ammonia synthesis catalysts is presented. The potential development of some systems into nitrogen transfer reagents is also described

Modelling the economic efficiency of using different strategies to control Porcine Reproductive & Respiratory Syndrome at herd level

PRRS is among the diseases with the highest economic impact in pig production worldwide. Different strategies have been developed and applied to combat PRRS at farm level. The broad variety of available intervention strategies makes it difficult to decide on the most cost-efficient strategy for a given farm situation, as it depends on many farm-individual factors like disease severity, prices or farm structure. Aim of this study was to create a simulation tool to estimate the cost-efficiency of different control strategies at individual farm level. Baseline is a model that estimates the costs of PRRS, based on changes in health and productivity, in a specific farm setting (e.g. farm type, herd size, type of batch farrowing). The model evaluates different intervention scenarios: depopulation/repopulation (D/R), close & roll-over (C&R), mass vaccination of sows (MS), mass vaccination of sows and vaccination of piglets (MS + piglets), improvements in internal biosecurity (BSM), and combinations of vaccinations with BSM. Data on improvement in health and productivity parameters for each intervention were obtained through literature review and from expert opinions. The economic efficiency of the different strategies was assessed over 5 years through investment appraisals: the resulting expected value (EV) indicated the most cost-effective strategy. Calculations were performed for 5 example scenarios with varying farm type (farrow-to-finish – breeding herd), disease severity (slightly – moderately – severely affected) and PRRSV detection (yes – no). The assumed herd size was 1000 sows with farm and price structure as commonly found in Germany. In a moderately affected (moderate deviations in health and productivity parameters from what could be expected in an average negative herd), unstable farrow-to-finish herd, the most cost-efficient strategies according to their median EV were C&R (€1′126′807) and MS + piglets (€ 1′114′649). In a slightly affected farrow-to-finish herd, no virus detected, the highest median EV was for MS + piglets (€ 721′745) and MS (€ 664′111). Results indicate that the expected benefits of interventions and the most efficient strategy depend on the individual farm situation, e.g. disease severity. The model provides new insights regarding the cost-efficiency of various PRRSV intervention strategies at farm level. It is a valuable tool for farmers and veterinarians to estimate expected economic consequences of an intervention for a specific farm setting and thus enables a better informed decision

Two-dimensional superstrings and the supersymmetric matrix model

We present evidence that the supersymmetric matrix model of Marinari and Parisi represents the world-line theory of N unstable D-particles in type II superstring theory in two dimensions. This identification suggests that the matrix model gives a holographic description of superstrings in a two-dimensional black hole geometry.Comment: 22 pages, 2 figures; v2: corrected eqn 4.6; v3: corrected appendices and discussion of vacua, added ref

ADCC Develops Over Time during Persistent Infection with Live-Attenuated SIV and Is Associated with Complete Protection against SIV(mac)251 Challenge

Live-attenuated strains of simian immunodeficiency virus (SIV) routinely confer apparent sterilizing immunity against pathogenic SIV challenge in rhesus macaques. Understanding the mechanisms of protection by live-attenuated SIV may provide important insights into the immune responses needed for protection against HIV-1. Here we investigated the development of antibodies that are functional against neutralization-resistant SIV challenge strains, and tested the hypothesis that these antibodies are associated with protection. In the absence of detectable neutralizing antibodies, Env-specific antibody-dependent cell-mediated cytotoxicity (ADCC) emerged by three weeks after inoculation with SIVDeltanef, increased progressively over time, and was proportional to SIVDeltanef replication. Persistent infection with SIVDeltanef elicited significantly higher ADCC titers than immunization with a non-persistent SIV strain that is limited to a single cycle of infection. ADCC titers were higher against viruses matched to the vaccine strain in Env, but were measurable against viruses expressing heterologous Env proteins. In two separate experiments, which took advantage of either the strain-specificity or the time-dependent maturation of immunity to overcome complete protection against SIV(mac)251 challenge, measures of ADCC activity were higher among the SIVDeltanef-inoculated macaques that remained uninfected than among those that became infected. These observations show that features of the antibody response elicited by SIVDeltanef are consistent with hallmarks of protection by live-attenuated SIV, and reveal an association between Env-specific antibodies that direct ADCC and apparent sterilizing protection by SIVDeltanef

Equivalence of the super Lax and local Dunkl operators for Calogero-like models

Following Shastry and Sutherland I construct the super Lax operators for the Calogero model in the oscillator potential. These operators can be used for the derivation of the eigenfunctions and integrals of motion of the Calogero model and its supersymmetric version. They allow to infer several relations involving the Lax matrices for this model in a fast way. It is shown that the super Lax operators for the Calogero and Sutherland models can be expressed in terms of the supercharges and so called local Dunkl operators constructed in our recent paper with M. Ioffe. Several important relations involving Lax matrices and Hamiltonians of the Calogero and Sutherland models are easily derived from the properties of Dunkl operators.Comment: 25 pages, Latex, no figures. Accepted for publication in: Jounal of Physics A: Mathematical and Genera

Non-intersecting squared Bessel paths and multiple orthogonal polynomials for modified Bessel weights

We study a model of $n$ non-intersecting squared Bessel processes in the confluent case: all paths start at time $t = 0$ at the same positive value $x = a$, remain positive, and are conditioned to end at time $t = T$ at $x = 0$. In the limit $n \to \infty$, after appropriate rescaling, the paths fill out a region in the $tx$-plane that we describe explicitly. In particular, the paths initially stay away from the hard edge at $x = 0$, but at a certain critical time $t^*$ the smallest paths hit the hard edge and from then on are stuck to it. For $t \neq t^*$ we obtain the usual scaling limits from random matrix theory, namely the sine, Airy, and Bessel kernels. A key fact is that the positions of the paths at any time $t$ constitute a multiple orthogonal polynomial ensemble, corresponding to a system of two modified Bessel-type weights. As a consequence, there is a $3 \times 3$ matrix valued Riemann-Hilbert problem characterizing this model, that we analyze in the large $n$ limit using the Deift-Zhou steepest descent method. There are some novel ingredients in the Riemann-Hilbert analysis that are of independent interest.Comment: 59 pages, 11 figure