Genetic analysis of the two zebrafish patched homologues identifies novel roles for the hedgehog signaling pathway

Background  

Aberrant activation of the Hedgehog (Hh) signaling pathway in different organisms has shown the importance of this family of morphogens during development. Genetic screens in zebrafish have assigned specific roles for Hh in proliferation, differentiation and patterning, but mainly as a result of a loss of its activity. We attempted to fully activate the Hh pathway by removing both receptors for the Hh proteins, called Patched1 and 2, which are functioning as negative regulators in this pathway.     

A realistic meteorological assessment of perennial biofuel crop deployment: a Southern Great Plains perspective

Utility of perennial bioenergy crops (e.g., switchgrass and miscanthus) offers unique opportunities to transition toward a more sustainable energy pathway due to their reduced carbon footprint, averted competition with food crops, and ability to grow on abandoned and degraded farmlands. Studies that have examined biogeophysical impacts of these crops noted a positive feedback between near‐surface cooling and enhanced evapotranspiration (ET), but also potential unintended consequences of soil moisture and groundwater depletion. To better understand hydrometeorological effects of perennial bioenergy crop expansion, this study conducted high‐resolution (2‐km grid spacing) simulations with a state‐of‐the‐art atmospheric model (Weather Research and Forecasting system) dynamically coupled to a land surface model. We applied the modeling system over the Southern Plains of the United States during a normal precipitation year (2007) and a drought year (2011). By focusing the deployment of bioenergy cropping systems on marginal and abandoned farmland areas (to reduce the potential conflict with food systems), the research presented here is the first realistic examination of hydrometeorological impacts associated with perennial bioenergy crop expansion. Our results illustrate that the deployment of perennial bioenergy crops leads to widespread cooling (1–2 °C) that is largely driven by an enhanced reflection of shortwave radiation and, secondarily, due to an enhanced ET. Bioenergy crop deployment was shown to reduce the impacts of drought through simultaneous moistening and cooling of the near‐surface environment. However, simulated impacts on near‐surface cooling and ET were reduced during the drought relative to a normal precipitation year, revealing differential effects based on background environmental conditions. This study serves as a key step toward the assessment of hydroclimatic sustainability associated with perennial bioenergy crop expansion under diverse hydrometeorological conditions by highlighting the driving mechanisms and processes associated with this energy pathway.     

Production of ribonucleotides by autolysis of Pichia anomala mutant and some physiological activities

Various mutants of Pichia anomala were isolated by ethyl methanesulfonate (EMS) treatment and UV irradiation through cycloheximide resistance and KCl sensitivity. The selected mutant HA-2 accumulated a higher content of RNA and grew faster than the wild-type strain in yeast extract-malt (YM) broth. Autolysis of the HA-2 mutant at 60 degrees C and pH 7.0 for 6 h was the best condition to obtain maximum yields of 5'-ribonucleotides, inosinic monophosphate (IMP) (6.2 mg/g biomass) and guanylic monophosphate (GMP) (35.5 mg/g biomass). The yield of adenylic monophosphate (AMP) (7.8 mg/g biomass) was optimal at 60 degrees C at pH 6.5 for 6 h. The inhibitory activity of the angiotensin-converting enzyme and the nitrite-scavenging activity for autolysates of the HA-2 mutant were about 13.0% and 47.0% higher than those of native strain, respectively.     

Structural characterization of genomes by large scale sequence-structure threading: application of reliability analysis in structural genomics

Background  

We establish that the occurrence of protein folds among genomes can be accurately described with a Weibull function. Systems which exhibit Weibull character can be interpreted with reliability theory commonly used in engineering analysis. For instance, Weibull distributions are widely used in reliability, maintainability and safety work to model time-to-failure of mechanical devices, mechanisms, building constructions and equipment.     

A knowledge discovery object model API for Java

Background  

Biological data resources have become heterogeneous and derive from multiple sources. This introduces challenges in the management and utilization of this data in software development. Although efforts are underway to create a standard format for the transmission and storage of biological data, this objective has yet to be fully realized.     

Production of pediocin PA-1 in the methylotrophic yeast Pichia pastoris reveals unexpected inhibition of its biological activity due to the presence of collagen-like material

Expression of the pedA gene from Pediococcus acidilactici, coding for mature bacteriocin Pediocin PA-1, was investigated using the yeast Pichia pastoris to obtain larger quantities of pediocin to support additional studies, including structure-function research. Following various cloning strategies, a KM71H (Mut(s)) strain was selected. A significant concentration (74 microg/ml) of extracellular recombinant pediocin was obtained but the pediocin showed no biological activity. Supernatant fluids from P. pastoris cultures, harboring or not pedA, inhibited the biological activity of natural pediocin PA-1. The recombinant pediocin appeared as a mixture of three main fractions (7-8, 11, 20 kDa vs. 4.6 kDa for natural pediocin PA-1). The recombinant pediocin was also less hydrophobic and behaved differently when subjected to isoelectric focusing. Strong evidence indicated that some "collagen-like" material was tightly associated, most probably via covalent binding, to the recombinant pediocin. The "collagen-like" material was most probably responsible for the lack of biological activity of the recombinant pediocin and for the differences observed regarding some of the physico-chemical properties. Both the recombinant pediocin and natural pediocin were sensitive to collagenase, suggesting that pediocin PA-1 may possess a somewhat "collagen-like" nature. Interestingly, recombinant pediocin preparations showed the ability to assemble into fibrils.     

Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells

Background

Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells.

Methods

We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro.

Results

We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus.

Conclusion

The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.