A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation

Autosomal dominant polycystic liver disease results from mutations in PRKCSH or SEC63. The respective gene products, glucosidase IIβ and SEC63p, function in protein translocation and quality control pathways in the endoplasmic reticulum. Here we show that glucosidase IIβ and Sec63p are required in mice for adequate expression of a functional complex of the polycystic kidney disease gene products, polycystin-1 and polycystin-2. We find that polycystin-1 is the rate-limiting component of this complex and that there is a dose-response relationship between cystic dilation and levels of functional polycystin-1 following mutation of Prkcsh or Sec63. Reduced expression of polycystin-1 also serves to sensitize the kidney to cyst formation resulting from mutations in Pkhd1, the recessive polycystic kidney disease gene. Finally, we show that proteasome inhibition increases steady-state levels of polycystin-1 in cells lacking glucosidase IIβ and that treatment with a proteasome inhibitor reduces cystic disease in orthologous gene models of human autosomal dominant polycystic liver disease.     

Characterization and Preparation of Bimetallic Nanoparticles

1 Results Bimetallic particles in the nanometer size range are of substantial interest due to their vast applications in catalysis[1].The synthesis of bimetallic nanoparticles with definite size with a well-control over their nanostructure remains a challenging problem.Thus there exists a great demand for both synthesis and atomic level characterization of nanostructure of bimetallic nanoparticles (NPs).With the recent advent of high-intensity tunable sources of X-rays,now available at synchrotron radia...     

Analysts’ Dynamic Decisions: Timeliness versus Accuracy

For analysts there is a tradeoff between the accuracy and the timeliness of their forecasts. Prior literature heavily investigates analyst forecast accuracy. Few papers investigate the importance of timeliness. To our best knowledge, there are no empirical papers to date to investigate the dynamic interplay between these key characteristics. We show that if analysts experience a period of high accuracy relative to their peers, they subsequently focus more on the timeliness of their forecasts in the subsequent period and thus issue their forecasts earlier than they did in the prior period. Copyright © 2016 John Wiley & Sons, Ltd.     

Tree size and understory phytomass production in a western juniper woodland

Understory phytomass production in a western juniper ( Juniperus occidentalis ) woodland was examined relative to tree size in central Oregon in 1983 and 1984. Vegetation was sampled in two zones, the canopy zone (beneath the canopy) and the intercanopy zone (the space between canopies), on two adjacent sites—a lower slope site with shallow soil and an upper slope site with deeper soil. Sampling was stratified into three tree size classes. Individual species production was significantly affected by tree size and location relative to tree canopy. Production of bottlebrush squirreltail, bluebunch wheatgrass, cheatgrass, miscellaneous annual grasses, perennial forbs, and annual forbs increased with increasing tree size. Sandberg bluegrass production was greater in the intercanopy than the canopy zone, while production of bottlebrush squirreltail, bluebunch wheatgrass, miscellaneous annual grasses, and both perennial and annual forbs was greater in the canopy zone. Production of cheatgrass was determined by the interaction of tree size and zone. Phytomass relationships were expressed to a greater degree on the upper slope site, where total production exceeded that of the lower slope site by approximately 50% the second year of the study. Individual trees appear to exert a great influence on associated vegetation as western juniper woodlands progress from the seedling (tree establishment) phase to closed stands of mature trees. Original community dominants appear to be spatially segregated beneath tree canopies and associated with large trees, while formerly less common species, such as cheatgrass, come to dominate the entire site.     

New use of BCG for recombinant vaccines

BCG, a live attenuated tubercle bacillus, is the most widely used vaccine in the world and is also a useful vaccine vehicle for delivering protective antigens of multiple pathogens. Extrachromosomal and integrative expression vectors carrying the regulatory sequences for major BCG heat-shock proteins have been developed to allow expression of foreign antigens in BCG. These recombinant BCG strains can elicit long-lasting humoral and cellular immune responses to foreign antigens in mice.     

HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.