STING Millennium Suite: integrated software for extensive analyses of 3d structures of proteins and their complexes

Background  

The integration of many aspects of protein/DNA structure analysis is an important requirement for software products in general area of structural bioinformatics. In fact, there are too few software packages on the internet which can be described as successful in this respect. We might say that what is still missing is publicly available, web based software for interactive analysis of the sequence/structure/function of proteins and their complexes with DNA and ligands. Some of existing software packages do have certain level of integration and do offer analysis of several structure related parameters, however not to the extent generally demanded by a user.     

Genome-scale metabolic reconstruction and <Emphasis Type="Italic">in silico</Emphasis> analysis of methylotrophic yeast <Emphasis Type="Italic">Pichia pastoris</Emphasis> for strain improvement

Background  

Pichia pastoris has been recognized as an effective host for recombinant protein production. A number of studies have been reported for improving this expression system. However, its physiology and cellular metabolism still remained largely uncharacterized. Thus, it is highly desirable to establish a systems biotechnological framework, in which a comprehensive in silico model of P. pastoris can be employed together with high throughput experimental data analysis, for better understanding of the methylotrophic yeast's metabolism.     

Defective trafficking and localization of mutated transferrin receptor 2: implications for type 3 hereditary hemochromatosis

Transferrin receptor 2 (TfR2), a homologue of transferrin receptor 1 (TfR1), is a key molecule involved in the regulation of iron homeostasis. Mutations in TfR2 result in iron overload with similar features to HFE-associated hereditary hemochromatosis. The precise role of TfR2 in iron metabolism and the functional consequences of disease-causing mutations have not been fully determined. We have expressed wild-type and various mutant forms of TfR2 that are associated with human disease in a mouse liver cell line. Intracellular and surface analysis shows that all the TfR2 mutations analyzed cause the intracellular retention of the protein in the endoplasmic reticulum, whereas the wild-type protein is expressed in endocytic structures and at the cell surface. Our results indicate that the majority of mutations that cause type 3 hereditary hemochromatosis are a consequence of the defective localization of the protein.     

Determinants of lepidopteran community composition and species diversity in eastern deciduous forests: roles of season, eco-region and patch size

Ecologists have long recognized that factors operating at both local and regional scales influence whether a given species occurs in an ecological community. The relative roles of variables manifested at local and regional scales on community structure, however, remain an unexplored issue for many faunas. To address this question, we compared the community composition and species diversity of forest Lepidoptera between (i) large forest tracts in historically glaciated and unglaciated regions of the eastern deciduous forest in North America, and (ii) large and small forest patches within a highly fragmented forest landscape. Specifically, we used seasonally stratified sampling to test whether regional and local differences in moth communities were related to variation in stand structure and floristic composition. At the local scale, we tested three alternative hypotheses describing the effects of patch size on moth species richness: species impoverishment, species replacement, or species supplementation. Cluster analysis revealed significant compositional differences in moth communities sampled between (i) early and late seasons, (ii) glaciated and unglaciated forest eco‐regions, and (iii) large and small forest patches. Canonical correspondence analysis suggested that floristic variation at regional scales had a greater role in determining moth community composition than local vegetation or patch‐size effects. Species richness was higher in the glaciated North Central Tillplain, and was attributable to a more diverse herbaceous feeding moth assemblage. Finally, we found evidence that both species impoverishment and species replacement processes structure the moth fauna of small woodlots; the richness of moths with larvae that feed on woody plants decreased with patch area, but herbaceous feeding species increased in diversity in smaller patches. Thus, our results suggest that local and regional differences in moth community structure are mediated by differences in host‐plant resources attributable to regional biogeographic history and local differences in patch size. Because community composition appeared to be more sensitive to environmental variation than species richness, we suggest that monitoring lepidopteran species diversity in forests will not detect significant changes in species composition due to environmental change.     

Restoring Lepidopteran Communities to Oak Savannas: Contrasting Influences of Habitat Quantity and Quality

Ecological restoration is deemed important for the long‐term conservation of biodiversity, but ecologists still lack an understanding of how habitat availability and habitat quality in a restored system interact to determine species diversity. This problem seems particularly apparent in Tallgrass Prairie and savanna ecoregions, where restored management units represent the majority of extant habitat. In this study, we tested three principal hypotheses, each stating that the diversity of Lepidoptera would be greater in (1) patches of savanna habitat that were larger; (2) patches that were of higher habitat quality; and (3) patches that had greater connectivity to management units of similar physiognomy. Lepidoptera were sampled in 2003 from 13 unmanaged woodland remnants within Neal Smith National Wildlife Refuge, a 2,292‐ha prairie and savanna reconstruction project. We also measured 11 environmental variables within each site to assess variation in habitat quantity and quality. Principal components analysis (PCA) was used to identify major gradients of environmental variation among the 13 sites. Our PCA differentiated among woodlands along three environmental gradients, defined by (1) stand size, shape, topography, and oak dominance; (2) degree of disturbance; and (3) isolation. Total lepidopteran species richness, however, was only predicted by variation in the first principal component. Species richness of Lepidoptera known to be oak specialists was significantly affected by variation along all three PCA gradients. Surprisingly, more isolated woodland remnants contained a greater richness of oak feeders. Our results suggest that approaches to restoring oak savannas should emphasize aspects of both habitat quantity and quality. Beyond making individual management units larger, priority sites for restoration should possess a low importance of trees that are indicative of past habitat disturbance (e.g., Honey locust, White mulberry) even if canopy closure is substantial. Connectivity among restored habitats may benefit savanna moth communities only when habitat linkages contain a flora similar in composition to focal patches.     

Polymer optoelectronic structures for retinal prosthesis

This commentary highlights the effectiveness of optoelectronic properties of polymer semiconductors based on recent results emerging from our laboratory, where these materials are explored as artificial receptors for interfacing with the visual systems. Organic semiconductors based polymer layers in contact with physiological media exhibit interesting photophysical features, which mimic certain natural photoreceptors, including those in the retina. The availability of such optoelectronic materials opens up a gateway to utilize these structures as neuronal interfaces for stimulating retinal ganglion cells. In a recently reported work entitled “A polymer optoelectronic interface provides visual cues to a blind retina,” we utilized a specific configuration of a polymer semiconductor device structure to elicit neuronal activity in a blind retina upon photoexcitation. The elicited neuronal signals were found to have several features that followed the optoelectronic response of the polymer film. More importantly, the polymer-induced retinal response resembled the natural response of the retina to photoexcitation. These observations open up a promising material alternative for artificial retina applications.     

Apoptosis,cytokine and chemokine induction by non-structural 1 (NS1) proteins encoded by different influenza subtypes

Background

Influenza pandemic remains a serious threat to human health. Viruses of avian origin, H5N1, H7N7 and H9N2, have repeatedly crossed the species barrier to infect humans. Recently, a novel strain originated from swine has evolved to a pandemic. This study aims at improving our understanding on the pathogenic mechanism of influenza viruses, in particular the role of non-structural (NS1) protein in inducing pro-inflammatory and apoptotic responses.

Methods

Human lung epithelial cells (NCI-H292) was used as an in-vitro model to study cytokine/chemokine production and apoptosis induced by transfection of NS1 mRNA encoded by seven infleunza subtypes (seasonal and pandemic H1, H2, H3, H5, H7, and H9), respectively.

Results

The results showed that CXCL-10/IP10 was most prominently induced (> 1000 folds) and IL-6 was slightly induced (< 10 folds) by all subtypes. A subtype-dependent pattern was observed for CCL-2/MCP-1, CCL3/MIP-1α, CCL-5/RANTES and CXCL-9/MIG; where induction by H5N1 was much higher than all other subtypes examined. All subtypes induced a similar temporal profile of apoptosis following transfection. The level of apoptosis induced by H5N1 was remarkably higher than all others. The cytokine/chemokine and apoptosis inducing ability of the 2009 pandemic H1N1 was similar to previous seasonal strains.

Conclusions

In conclusion, the NS1 protein encoded by H5N1 carries a remarkably different property as compared to other avian and human subtypes, and is one of the keys to its high pathogenicity. NCI-H292 cells system proves to be a good in-vitro model to delineate the property of NS1 proteins.

     

Short-Term Temporal Effects on Community Structure of Lepidoptera in Restored and Remnant Tallgrass Prairies

Understanding the degree to which species assemblages naturally vary over time will be critically important when assessing whether direct management effects or contingency is responsible for species gain or loss. In this study, we tested three predictions related to short‐term variation in prairie moth communities: (1) communities would only exhibit significant temporal variation in newly restored sites (1–3 years old); (2) prairie size and age would positively influence community reassembly, with larger, older restorations sampling a greater proportion of the regional species pool; and (3) older restorations (7–10 years old) would have yet to converge on the community composition of prairie remnants. Moths were sampled from 13 Tallgrass prairie restorations and remnants in central Iowa in 2004–2005. Repeated measures analysis of variance revealed significant effects of sampling year on moth species richness and abundance as well as on the richness of two functional groups, but difference among prairie types was only observed in 2005. Rarefaction analysis revealed that older restorations and prairie remnants supported higher species richness compared to recently planted sites, and nonmetric, multidimensional scaling ordination indicated that restorations older than 7 years were clearly converging on the species composition of remnants. These results suggest that moth communities in restorations and remnants are highly variable in time but that as restorations age, they appear to reaccumulate moth species found in prairie remnants. The long‐term persistence of a particular species assemblage within a given site, however, might be a difficult endpoint to attain in central Iowa prairies because of significant annual variation in species occurrence.