Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein Binds and Protects a Nuclear Noncoding RNA from Cellular RNA Decay Pathways

The control of RNA stability is a key determinant in cellular gene expression. The stability of any transcript is modulated through the activity of cis- or trans-acting regulatory factors as well as cellular quality control systems that ensure the integrity of a transcript. As a result, invading viral pathogens must be able to subvert cellular RNA decay pathways capable of destroying viral transcripts. Here we report that the Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein binds to a unique KSHV polyadenylated nuclear RNA, called PAN RNA, and protects it from degradation by cellular factors. ORF57 increases PAN RNA levels and its effects are greatest on unstable alleles of PAN RNA. Kinetic analysis of transcription pulse assays shows that ORF57 protects PAN RNA from a rapid cellular RNA decay process, but ORF57 has little effect on transcription or PAN RNA localization based on chromatin immunoprecipitation and in situ hybridization experiments, respectively. Using a UV cross-linking technique, we further demonstrate that ORF57 binds PAN RNA directly in living cells and we show that binding correlates with function. In addition, we define an ORF57-responsive element (ORE) that is necessary for ORF57 binding to PAN RNA and sufficient to confer ORF57-response to a heterologous intronless β-globin mRNA, but not its spliced counterparts. We conclude that ORF57 binds to viral transcripts in the nucleus and protects them from a cellular RNA decay pathway. We propose that KSHV ORF57 protein functions to enhance the nuclear stability of intronless viral transcripts by protecting them from a cellular RNA quality control pathway

The genome landscape of indigenous African cattle

Background: The history of African indigenous cattle and their adaptation to environmental and human selection pressure is at the root of their remarkable diversity. Characterization of this diversity is an essential step towards understanding the genomic basis of productivity and adaptation to survival under African farming systems. Results: We analyze patterns of African cattle genetic variation by sequencing 48 genomes from five indigenous populations and comparing them to the genomes of 53 commercial taurine breeds. We find the highest genetic diversity among African zebu and sanga cattle. Our search for genomic regions under selection reveals signatures of selection for environmental adaptive traits. In particular, we identify signatures of selection including genes and/ or pathways controlling anemia and feeding behavior in the trypanotolerant N’Dama, coat color and horn development in Ankole, and heat tolerance and tick resistance across African cattle especially in zebu breeds. Conclusions: Our findings unravel at the genome-wide level, the unique adaptive diversity of African cattle while emphasizing the opportunities for sustainable improvement of livestock productivity on the continent

Bid Regulates the Pathogenesis of Neurotropic Reovirus

Reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS). NF-κB-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response. Although both extrinsic death-receptor signaling pathways and intrinsic pathways involving mitochondrial injury are implicated in reovirus-induced apoptosis, mechanisms by which either of these pathways are activated and their relationship to NF-κB signaling following reovirus infection are unknown. The proapoptotic Bcl-2 family member, Bid, is activated by proteolytic cleavage following reovirus infection. To understand how reovirus integrates host signaling circuits to induce apoptosis, we examined proapoptotic signaling following infection of Bid-deficient cells. Although reovirus growth was not affected by the absence of Bid, cells lacking Bid failed to undergo apoptosis. Furthermore, we found that NF-κB activation is required for Bid cleavage and subsequent proapoptotic signaling. To examine the functional significance of Bid-dependent apoptosis in reovirus disease, we monitored fatal encephalitis caused by reovirus in the presence and absence of Bid. Survival of Bid-deficient mice was significantly enhanced in comparison to wild-type mice following either peroral or intracranial inoculation of reovirus. Decreased reovirus virulence in Bid-null mice was accompanied by a reduction in viral yield. These findings define a role for NF-κB-dependent cleavage of Bid in the cell death program initiated by viral infection and link Bid to viral virulence

State-of-the-Art Microbiologic Testing for Community-Acquired Meningitis and Encephalitis

Meningitis and encephalitis are potentially life-threatening diseases with a wide array of infectious, postinfectious, and noninfectious causes. Diagnostic testing is central to determining the underlying etiology, treatment, and prognosis, but many patients remain undiagnosed due to suboptimal testing and lack of tests for all pathogens. In this article, we summarize the epidemiology, barriers to diagnosis, and current best tests for meningitis and encephalitis in developed countries. We end with a brief discussion of new test methods, such as multiplex panel-based tests and metagenomic sequencing, which are likely to alter diagnostic strategies for these conditions in the near future

Evaluation of the effects of two doses of alpha glycerylphosphorylcholine on physical and psychomotor performance

Abstract Background Recent studies have suggested that alpha glycerylphosphorylcholine (A-GPC) may be an effective ergogenic aid. The present study was designed to assess the efficacy of two doses of A-GPC in comparison to placebo and caffeine for increasing countermovement jump performance, isometric strength, and psychomotor function. Methods Forty-eight healthy, college aged males volunteered for the present study and underwent baseline assessment of countermovement jump (CMJ), isometric mid thigh pull (IMTP), upper body isometric strength test (UBIST), and psychomotor vigilance (PVT). Following this assessment participants were randomly assigned to groups consisting of 500 mg A-GPC, 250 mg A-GPC, 200 mg Caffeine or Placebo taken daily. Blood samples were collected 1 h and 2 h post initial dose to quantify serum free choline and thyroid stimulating hormone then subjects returned after 7 days of supplementation to repeat CMJ, IMTP, UBIST and PVT. Results No differences were noted between groups for IMTP, UBIST or PVT performance. Serum free choline was found to be elevated in the two A-GPC groups as compared to placebo (132% and 59% respectively). Serum TSH was found to be significantly depressed in the 500 mg A-GPC group compared to other treatments (p < 0.04). Group differences were noted for maximum velocity and maximum mechanical power on the CMJ (p < 0.05) with the 250 mg A-GPC group demonstrating the greatest improvements in result. Conclusions Based upon this evidence, and previous evidence regarding A-GPC, it should be considered as an emerging ergogenic supplement