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.     

Granule-bound starch synthase: structure, function, and phylogenetic utility

Interest in the use of low-copy nuclear genes for phylogenetic analyses of plants has grown rapidly, because highly repetitive genes such as those commonly used are limited in number. Furthermore, because low- copy genes are subject to different evolutionary processes than are plastid genes or highly repetitive nuclear markers, they provide a valuable source of independent phylogenetic evidence. The gene for granule-bound starch synthase (GBSSI or waxy) exists in a single copy in nearly all plants examined so far. Our study of GBSSI had three parts: (1) Amino acid sequences were compared across a broad taxonomic range, including grasses, four dicotyledons, and the microbial homologs of GBSSI. Inferred structural information was used to aid in the alignment of these very divergent sequences. The informed alignments highlight amino acids that are conserved across all sequences, and demonstrate that structural motifs can be highly conserved in spite of marked divergence in amino acid sequence. (2) Maximum-likelihood (ML) analyses were used to examine exon sequence evolution throughout grasses. Differences in probabilities among substitution types and marked among-site rate variation contributed to the observed pattern of variation. Of the parameters examined in our set of likelihood models, the inclusion of among-site rate variation following a gamma distribution caused the greatest improvement in likelihood score. (3) We performed cladistic parsimony analyses of GBSSI sequences throughout grasses, within tribes, and within genera to examine the phylogenetic utility of the gene. Introns provide useful information among very closely related species, but quickly become difficult to align among more divergent taxa. Exons are variable enough to provide extensive resolution within the family, but with low bootstrap support. The combined results of amino acid sequence comparisons, maximum-likelihood analyses, and phylogenetic studies underscore factors that might affect phylogenetic reconstruction. In this case, accommodation of the variable rate of evolution among sites might be the first step in maximizing the phylogenetic utility of GBSSI.      

The function of communities in protein interaction networks at multiple scales

Background  

If biology is modular then clusters, or communities, of proteins derived using only protein interaction network structure should define protein modules with similar biological roles. We investigate the link between biological modules and network communities in yeast and its relationship to the scale at which we probe the network.     

Effects of proportion and configuration of Bacillus thuringiensis cotton on pest abundance, damage, and yield

Bacillus thuringiensis (Bt) transgenic cotton, Gossypium hirsutum L., kills several economically important pests, reducing injury and increasing yields. Refuges of non-Bt cotton are currently planted with Bt cotton in different designs to slow pest resistance evolution. To compare the effects of differences in Bt/non-Bt plant heterogeneity found in different refuge designs on square (flower bud) damage, abscissions, sap-feeding herbivore densities, and yield in cotton, four types of 24-row cotton plots were planted in 2001 and 2002: 1) seed mixtures of Bt and non-Bt varieties, 2) 12-row strips of Bt and non-Bt, 3) solid Bt, and 4) solid non-Bt. For both years cotton bollworm, Helicoverpa zea (Boddie), damage was less in solid Bt plots than strips and mixtures and all were less than solid non-Bt plots. Cotton fleahopper, Pseudatomoscelis seriatus (Reuter), damage was affected by refuge, but only in 2002 when damage was greater in solid Bt plots than all other plots and greater in strips than solid non-Bt plots. Abscissions were least in solid non-Bt plots, and less in mixtures and strips than solid Bt plots. In 2001, western flower thrips, Frankliniella occidentalis (Pergande), density was greatest in mixtures, whereas sweetpotato whitefly, Bemisia tabaci (Gennadius), was greatest in solid Bt plots, and greater in mixtures than solid non-Bt plots. Yield also was affected by refuge, it was greater for solid Bt plots than for solid non-Bt plots and mixtures in 2001, but the reverse was true in 2002.     

Effects of crop rotation, tillage, and fertilizer applications on sorghum head insects

Rotations, tillage, and fertilizer treatments can affect yield, costs, and profitability in sorghum, Sorghum bicolor (L.) Moench, depending on their effects on pests. Rotation or planting different crops reduces soil erosion and pests that build up when a field is planted to the same crop each year. Minimum tillage reduces the number of trips over a field, lessening soil compaction and reducing costs. We examined the effects of fertilizer, tillage, and rotation with cotton, Gossypium hirsutum L., on sorghum head insects during three sampling periods each year from 2000 to 2003. We found that fertilizer treatments did not affect pests or predators. Also, predators were unaffected by rotation and tillage, which some years affected Helicoverpa zea (Boddie) and Oebalus pugnax (F.), both pests that feed on developing sorghum kernels, thereby reducing yield. In 2000, H. zea densities were greater in continuous sorghum, regardless of tillage practice, than in sorghum-cotton rotation. However, in 2003, H. zea densities were greater in minimum tillage plots within sorghum- cotton rotation than minimum tillage plots within continuous sorghum. In 2000, in sorghum- cotton rotation, O. pugnax densities were greater in minimum tillage than conventional tillage plots, whereas in continuous sorghum the opposite was true, O. pugnax were greater in conventional tillage. Also, O. pugnax were greater in sorghum- cotton rotation than in continuous sorghum. In 2002, O. pugnax densities were greater in conventional than minimum tillage plots. These results suggest that rotation of sorghum with cotton can sometimes reduce H. zea, but this reduction may occur with increased density of O. pugnax. Also, reducing tillage may reduce O. pugnax in some instances.     

Air trapping on chest CT is associated with worse ventilation distribution in infants with cystic fibrosis diagnosed following newborn screening

Background

In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF.

Methods

Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M₁/M₀ and M₂/M₀, respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping.

Results

Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M₂/M₀ but not LCI or M₁/M₀. There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes.

Conclusion

These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF.     

Drosophilid Assemblages at Different Urbanization Levels in the City of Porto Alegre, State of Rio Grande do Sul, Southern Brazil

The present study analyzed the drosophilid assemblages in different levels of urbanization in the city of Porto Alegre, Rio Grande do Sul, Brazil. Collections were carried out in 2008 in three different environments: a highly urbanized area????Jardim Botanico,?? a forested area with intermediary urbanization????Parque Gabriel Knijnik,?? and in a relatively well-preserved forested area, although threatened by the urban growth????Morro Santana.?? In Jardim Botanico, 36 species belonging to four genera were found, with high abundance of exotic species as Drosophila simulans Sturtevant and Zaprionus indianus (Gupta). In Parque Gabriel Knijnik, 33 species that belonged to four genera were found, with higher abundances of native species belonging to the Drosophila tripunctata species group and Drosophila willistoni species subgroup, and lower abundance of exotic species. As for Morro Santana, 32 species and three genera were found, with higher abundances of native groups, low representativeness of exotic species, and absence of Zaprionus indianus. The analysis of the Jaccard index showed higher similarity in the species composition between samples collected in summer and autumn, and between samples collected in winter and spring. On the other hand, the Morisita index differentiated Jardim Botanico from the other two studied sites. Our results show that Morro Santana is an important area of native biodiversity, reinforcing, therefore, the inclusion of this area in the project for the creation of an ecological corridor as proposed by the Ministry of the Environment of Brazil.     

Altered expression of Alzheimer's disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy

Autism and Alzheimer''s disease (AD) are, respectively, neurodevelopmental and degenerative diseases with an increasing epidemiological burden. The AD-associated amyloid-β precursor protein-α has been shown to be elevated in severe autism, leading to the ‘anabolic hypothesis'' of its etiology. Here we performed a focused microarray analysis of genes belonging to NOTCH and WNT signaling cascades, as well as genes related to AD and apoptosis pathways in cerebellar samples from autistic individuals, to provide further evidence for pathological relevance of these cascades for autism. By using the limma package from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the genes belonging to these pathways displayed significant changes in expression (corrected P-values <0.05), with mitochondria-related genes being the most downregulated. We also found upregulation of GRIN1, the channel-forming subunit of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1 (or F65) were significantly lower when compared with control samples. Based on these results, we propose a model of NMDA glutamate receptor-mediated ERK activation of α-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism. Finally, systems pharmacology analyses of the model that integrates all these genes together (NOWADA) highlighted magnesium (Mg²⁺) and rapamycin as most efficient drugs to target this network model in silico. Their potential therapeutic application, in the context of autism, is therefore discussed.