Axonal stress kinase activation and tau misbehavior induced by kinesin-1 transport defects

Many neurodegenerative diseases exhibit axonal pathology, transport defects, and aberrant phosphorylation and aggregation of the microtubule binding protein tau. While mutant tau protein in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP17) causes aberrant microtubule binding and assembly of tau into filaments, the pathways leading to tau-mediated neurotoxicity in Alzheimer's disease and other neurodegenerative disorders in which tau protein is not genetically modified remain unknown. To test the hypothesis that axonal transport defects alone can cause pathological abnormalities in tau protein and neurodegeneration in the absence of mutant tau or amyloid β deposits, we induced transport defects by deletion of the kinesin light chain 1 (KLC1) subunit of the anterograde motor kinesin-1. We found that upon aging, early selective axonal transport defects in mice lacking the KLC1 protein (KLC1-/-) led to axonopathies with cytoskeletal disorganization and abnormal cargo accumulation. In addition, increased c-jun N-terminal stress kinase activation colocalized with aberrant tau in dystrophic axons. Surprisingly, swollen dystrophic axons exhibited abnormal tau hyperphosphorylation and accumulation. Thus, directly interfering with axonal transport is sufficient to activate stress kinase pathways initiating a biochemical cascade that drives normal tau protein into a pathological state found in a variety of neurodegenerative disorders including Alzheimer's disease.Fil: Falzone, Tomas Luis. Howard Hughes Medical Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Stokin, Gorazd B.. University Psychiatric Hospital; EsloveniaFil: Lillo, Concepción. University of California at San Diego; Estados UnidosFil: Rodrigues, Elizabeth M.. Howard Hughes Medical Institute; Estados UnidosFil: Westerman, Eileen L.. Howard Hughes Medical Institute; Estados UnidosFil: Williams, David S.. University of California at San Diego; Estados UnidosFil: Goldstein, Lawrence S. B.. Howard Hughes Medical Institute; Estados Unido

Lymphocyte Populations and Antibody Production in Vaccinated and Non-vaccinated Pigs Challenged with Mycoplasma hyopneumoniae

Mycoplasma hyopneumoniae (M. hyo), the cause of enzootic pneumonia in swine, is a worldwide problem. Despite the developmental vaccines that have been commercially available for several years, M. hyo-induced pneumonia is still a major concern to swine producers. The pathologic lesions observed with enzootic pneumonia consist primarily of a lymphoid cell infiltration of the lungs. Four groups of pigs consisting of challenge control, vaccinated and challenged, vaccinated only, and nonvaccinated and non-challenged were used in this study. Lymphocytes from the peripheral blood, lung, and bronchial lymph nodes were analyzed by flow cytometry (FACs) to determine the populations of cells activated by M. hyo. No significant difference in percentages of B or T lymphocytes was found between the vaccinated and nonvaccinated groups. An ELISPOT assay was used to evaluate the isotype of antibodies secreted by B lymphocytes from the same tissues. Total secreted immunoglobulin and mycoplasmal membrane specific immunoglobulin secretion were measured. A significant increase in secretion of total IgG by lymphocytes in the lungs of pigs only challenged with M. hyo, and vaccinated/challenged was observed. No mycoplasma-specific stimulation was observed. The mycoplasmal membrane preparation induced a non-specific stimulation by IgM secreting cells in all groups. Again, no mycoplasma-specific response was observed. These results suggest that although IgGsecreting lymphocytes are stimulated to secrete antibodies in infected pigs, the lymphocyte response observed in enzootic pneumonia may not be to the M. hyo membrane antigen. At this time, it is unknown whether the immune response to M. hyo is predominately an antibody- or cellmediated immune response, and how these immune responses contribute to protection from enzootic pneumonia

Two cases of fungal keratitis caused by Metarhizium anisopliae

We present two cases of keratitis due to Metarhizium anisopliae in geographically separated areas of the United States. The isolates were microscopically similar but morphologically different and were identified by ribosomal DNA sequencing. Both isolates had low minimum inhibitory concentration (MIC) values to caspofungin and micafungin, but high MIC values to amphotericin B. The morphologic and antifungal susceptibility differences between the two isolates indicate possible polyphylogeny of the group. Keywords: Metarhizium, Fungal keratitis, Keratomycosis, Antifungal susceptibilit

Transcriptomes of parents identify parenting strategies and sexual conflict in a subsocial beetle

This work was funded by UK NERC grants to M.G.R. and A.J.M. an NERC studentship to D.J.P. the University of Georgia and a US NSF grant to A.J.M. and M.G.R.Parenting in the burying beetle Nicrophorus vespilloides is complex and, unusually, the sex and number of parents that can be present is flexible. Such flexibility is expected to involve specialized behaviour by the two sexes under biparental conditions. Here, we show that offspring fare equally well regardless of the sex or number of parents present. Comparing transcriptomes, we find a largely overlapping set of differentially expressed genes in both uniparental and biparental females and in uniparental males including vitellogenin, associated with reproduction, and takeout, influencing sex-specific mating and feeding behaviour. Gene expression in biparental males is similar to that in non-caring states. Thus, being ‘biparental’ in N. vespilloides describes the family social organization rather than the number of directly parenting individuals. There was no specialization; instead, in biparental families, direct male parental care appears to be limited with female behaviour unchanged. This should lead to strong sexual conflict.Publisher PDFPeer reviewe

The Influence of Passive Immunity on Serological Responses to Mycoplasma hyopneumoniae Vaccination

Vaccine induced serum antibody levels were significantly less in pigs with passive immunity to Mycoplasma hyopneumoniae compared to pigs without passive immunity. Age at vaccination did not influence antibody responses to vaccination. The presence of passive antibodies at the time of vaccination may provide an explanation for vaccination failure under field conditions

Book Reviews As a Tool for Assessing Publisher Reputation

This article reports on the authors’ efforts to develop a method of using book reviews to establish the reputations of publishers. The authors examined the quality of books published by de Gruyter, Greenwood, Doubleday, University of Georgia Press, and Louisiana State University Press as it is expressed in abstracts of book reviews published in the online version of Book Review Digest. The authors extracted a sample for each publisher from Book Review Digest, examined the sample, and compared each publisher sample against a control sample. Although it is true that most book reviews are positive, there are discernible variations in how reviewers express themselves about books. The study also looks at Choice as a source of book reviews, and briefly examines the relationship between price and quality. This study adds to the literature of the use of book reviews as a selection tool

Diversification under sexual selection: the relative roles of mate preference strength and the degree of divergence in mate preferences

The contribution of sexual selection to diversification remains poorly understood after decades of research. This may be in part because studies have focused predominantly on the strength of sexual selection, which offers an incomplete view of selection regimes. By contrast, students of natural selection focus on environmental differences that help compare selection regimes across populations. To ask how this disparity in focus may affect the conclusions of evolutionary research, we relate the amount of diversification in mating displays to quantitative descriptions of the strength and the amount of divergence in mate preferences across a diverse set of case studies of mate choice. We find that display diversification is better explained by preference divergence rather than preference strength; the effect of the latter is more subtle, and is best revealed as an interaction with the former. Our findings cast the action of sexual selection (and selection in general) in a novel light: the strength of selection influences the rate of evolution, and how divergent selection is determines how much diversification can occur. Adopting this view will enhance tests of the relative role of natural and sexual selection in processes such as speciation