Key Command: Ulysses S. Grant\u27s District of Cairo

Grant\u27s Strategic Command The General as Administrator Cairo, Illinois, is the southernmost northern city of the Civil War. It is farther south than Richmond in a state that extends farther north than Cape Cod. The city\u27s location at the confluence of the Mississippi and Ohio r...

NUDT2 initiates viral RNA degradation by removal of 5′-phosphates.

While viral replication processes are largely understood, comparably little is known on cellular mechanisms degrading viral RNA. Some viral RNAs bear a 5 '-triphosphate (PPP-) group that impairs degradation by the canonical 5 '-3 ' degradation pathway. Here we show that the Nudix hydrolase 2 (NUDT2) trims viral PPP-RNA into monophosphorylated (P)-RNA, which serves as a substrate for the 5 '-3 ' exonuclease XRN1. NUDT2 removes 5 '-phosphates from PPP-RNA in an RNA sequence- and overhang-independent manner and its ablation in cells increases growth of PPP-RNA viruses, suggesting an involvement in antiviral immunity. NUDT2 is highly homologous to bacterial RNA pyrophosphatase H (RppH), a protein involved in the metabolism of bacterial mRNA, which is 5 '-tri- or diphosphorylated. Our results show a conserved function between bacterial RppH and mammalian NUDT2, indicating that the function may have adapted from a protein responsible for RNA turnover in bacteria into a protein involved in the immune defense in mammals. RNA of some viruses is protected from degradation by a 5 ' triphosphate group. Here the authors identify nudix hydrolase 2 (NUDT2) as novel antiviral defense protein that dephosphorylates viral RNA and thereby enables its degradation.We thank the core facility of the MPI of biochemistry for support

Computational cluster validation for microarray data analysis: experimental assessment of Clest, Consensus Clustering, Figure of Merit, Gap Statistics and Model Explorer

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

An international trial of quantitative PCR for monitoring Legionella in artificial water systems

To perform an international trial to derive alert and action levels for the use of quantitative PCR (qPCR) in the monitoring of Legionella to determine the effectiveness of control measures against legionellae. Laboratories (7) participated from six countries. Legionellae were determined by culture and qPCR methods with comparable detection limits. Systems were monitored over ≥10 weeks. For cooling towers (232 samples), there was a significant difference between the log mean difference between qPCR (GU l −1) and culture (CFU l −1) for Legionella pneumophila (0·71) and for Legionella spp. (2·03). In hot and cold water (506 samples), the differences were less, 0·62 for Leg. pneumophila and 1·05 for Legionella spp. Results for individual systems depended on the nature of the system and its treatment. In cooling towers, Legionella spp. GU l −1 always exceeded CFU l −1, and usually Legionella spp. were detected by qPCR when absent by culture. The pattern of results by qPCR for Leg. pneumophila followed the culture trend. In hot and cold water, culture and qPCR gave similar results, particularly for Leg. pneumophila. There were some marked exceptions with temperatures ≥50°C, or in the presence of supplementary biocides. Action and alert levels for qPCR were derived that gave results comparable to the application of the European Guidelines based on culture. Algorithms are proposed for the use of qPCR for routine monitoring. Action and alert levels for qPCR can be adjusted to ensure public health is protected with the benefit that remedial actions can be validated earlier with only a small increase in the frequency of action being required. This study confirms it is possible to derive guidelines on the use of qPCR for monitoring the control of legionellae with consequent improvement to response and public health protection

Plasma Dynamics

Contains research objectives and summary of research on nineteen research projects split into five sections.National Science Foundation (Grant ENG75-06242-A01)U.S. Energy Research and Development Administration (Contract E(11-1)-2766)U.S. Air Force - Office of Scientific Research (Grant AFOSR-77-3143)U.S. Energy Research and Development Administration (Contract EY-76-C2-02-3070.*000

Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases

The metastasis of breast cancer to the brain and central nervous system (CNS) is a problem of increasing importance. As improving treatments continue to extend patient survival, the incidence of CNS metastases from breast cancer is on the rise. New treatments are needed, as current treatments are limited by deleterious side effects and are generally palliative. We have previously described an oncolytic herpes simplex virus (HSV), designated M002, which lacks both copies of the γ134.5 neurovirulence gene and carries a murine interleukin 12 (IL-12) expression cassette, and have validated its antitumor efficacy in a variety of preclinical models of primary brain tumors. However, M002 has not been yet evaluated for use against metastatic brain tumors. Here, we demonstrate the following: both human breast cancer and murine mammary carcinoma cells support viral replication and IL-12 expression from M002; M002 replicates in and destroys breast cancer cells from a variety of histological subtypes, including “triple-negative” and HER2 overexpressing; M002 improves survival in an immunocompetent model more effectively than does a non-cytokine control virus. Thus, we conclude from this proof-of-principle study that a γ134.5-deleted IL-12 expressing oncolytic HSV may be a potential new therapy for breast cancer brain metastases

ER-shaping atlastin proteins act as central hubs to promote flavivirus replication and virion assembly

Flaviviruses, including dengue virus and Zika virus, extensively remodel the cellular endomembrane network to generate replication organelles that promote viral genome replication and virus production. However, it remains unclear how these membranes and associated cellular proteins act during the virus cycle. Here, we show that atlastins (ATLs), a subset of ER resident proteins involved in neurodegenerative diseases, have dichotomous effects on flaviviruses—with ATL2 depletion leading to replication organelle defects, and ATL3 depletion to changes in virus production pathways. We characterized non-conserved functional domains in ATL paralogues and show that the ATL interactome is profoundly reprogrammed following dengue virus infection. Screen analysis confirmed non-redundant ATL functions and identified a specific role for ATL3, and its interactor ARF4, in vesicle trafficking and virion maturation. Our data identify ATLs as central hubs targeted by flaviviruses to establish their replication organelle and to achieve efficient virion maturation and secretion