Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus

The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent virus (MVvac), and C-deficient virus grows poorly relative to the parental virus. Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKR^kd cells), we demonstrated that a reduction in PKR partially rescued the growth defect of C knockout (C^ko) virus but had no effect on the growth of either wild-type (WT) or V knockout (V^ko) virus. Increased growth of the C^ko virus in PKR^kd cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased phosphorylation of PKR and the α subunit of eukaryotic initiation factor 2. Furthermore, infection with WT, V^ko, or especially C^ko virus caused significantly less apoptosis in PKR^kd cells than in PKR-sufficient cells. Although apoptosis induced by C^ko virus infection in PKR-sufficient cells was blocked by a caspase antagonist, the growth of C^ko virus was not restored to the WT level by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection but that the virus growth restriction by PKR is not dependent upon the induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the proapoptotic and antiviral activities of PKR.     

Patterns of Sleeping Site and Sleeping Tree Selection by Black-and-Gold Howler Monkeys (Alouatta caraya) in Northern Argentina

International Journal of Primatology - The selection of sleeping sites and sleeping trees in nonhuman primates is related to social and ecological factors. We investigate the role of body...     

Plasma Biomarkers Discriminate Clinical Forms of Multiple Sclerosis

Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients.     

The Evolution of Exploitation in Humans: ‘Surrounded by Strangers I Thought Were My Friends’1

Early humans were obligately social, living in nested kin groups or close associations of related individuals. Theoretical and empirical research has demonstrated that group life is characterized by both costs (e.g. increased likelihood of disease transmission) and benefits (e.g. enhanced predator defense). This paper addresses the evolution of exploitation in humans (e.g. slavery, infanticide) as a response to within‐group competition for limiting resources (e.g. food, mates), a potential cost of living in groups. Exploitation is defined as one individual's use of another for selfish ends, in particular, the acquisition and/or use of another's resources for the optimization of inclusive fitness. It is argued that exploitation is most likely to occur in relationships characterized by asymmetries such as dependence, intimacy, and/or differential access to resources. A simple mathematical treatment assesses exploitation as a facultative response to local competition among relatives, providing insights into the conditions favorable and adverse to exploitation of conspecifics. Possible applications of the formulations are discussed, including the conditions under which intraspecific exploitation may be beneficial to both actor and recipient(s). Constraints on the evolution of exploitation in humans are identified, and suggestions are made for testing hypotheses related to the differential costs and benefits of exploitation to conspecifics. Future studies may promote the mitigation of exploitation's deleterious effects in Homo sapiens, a body of research which may apply, as well, to other social mammals.     

Industrial yeast strain improvement: construction of strains having the killer character and capable of utilizing starch

Summary A hybrid of Saccharomyces cerevisiae with the ability to utilize starch and to produce the killer toxin was constructed by the protoplast fusion technique. The hybrid was obtained in two steps. In the first, a wild killer strain was fused with a laboratory strain (S. cerevisiae STA2). A fusion product which carried the killer factor and the ability to grow on starch was selected. In the second step, this hybrid was fused with a baker's yeast.     

Fish infected with Sphaerospora spp. Thélohan (Myxosporea) from waters enzootic for proliferative kidney disease of salmonids

Sphaerospores were found among three species of fish examined from waters known to be enzootic for proliferative kidney disease (PKD) of salmonids. They were detected in the renal tubules of both hatchery-reared rainbow trout (Salmo gairdneri) exposed to the infectious stage of PKD and in chubs (Gila bicolor) in the headwaters of a hatchery where PKD is enzootic. Sticklebacks (Gasterosteus aculeatus) collected near net pens where Pacific salmon had experienced a PKD epizootic were also found to harbor sphaerospores in the lumen of the kidney tubules. The latter two host species contained developmental stages of a myxosporidan in the blood and in the lumen of the kidney tubules which are similar to those of PKX, the causative agent of PKD in salmonid fish. The sphaerospores observed in the rainbow trout are the first to be observed in this species. The similarity to previously observed developmental stages, rarity, and presence of these sphaerospores in salmonid fish from a hatchery where PKD is enzootic suggest that they are the most mature stage of the PKX myxosporidan yet observed.     

Trypsin-sensitive neutralization site on VP1 of Theiler''s murine encephalomyelitis viruses.

We generated Theiler's murine encephalomyelitis virus mutants resistant to several neutralizing monoclonal antibodies (MAbs) having their epitopes near a trypsin cleavage site of VP1. Neutralization and Western blot (immunoblot) studies suggest that two of the MAbs have identical epitopes that partly overlap the epitope of a third MAb. Sequencing of RNA of the mutants localized the epitopes to a site near the carboxyl end of VP1. The limited diversity of nucleotide changes seen in the mutants and the immunodominance of the site suggest that the carboxyl end of VP1 may have an important function.