GOSLING: a rule-based protein annotator using BLAST and GO

GOSLING is a web-based protein function annotator that uses a decision tree-derived rule set to quickly predict Gene Ontology terms for a protein. A score is assigned to each term prediction that is indicative of the accuracy of the prediction. Due to its speed and accuracy GOSLING is ideally suited for high-throughput annotation tasks. AVAILABILITY: https://www.sapac.edu.au/gosling     

Preliminary results on Ochratoxin A concentrations in blood of patients with various kidney diseases in Germany

Ochratoxin A (OTA) is supposed to induce renal diseases in man and animals and a correlation between renal diseases and OTA concentration in blood is suspected. Therefore, we measured OTA concentrations in blood of subjects suffering from various renal diseases as e.g. interstitial nephritis or mesangial proliferating glomerular nephritis (GN) and compared them with the blood concentration of healthy individuals. We found OTA in 87% of all samples. There was no significant difference between OTA concentrations of healthy individuals and patients but some renal diseases (e.g. chronic glomerular nephritis) showed increased numbers of samples containing more than 1.5 nmol/l OTA in sera. In contrast, in samples from patients suffering from membranous or focal-sclerotic glomerular nephritis no concentrations above 1.5 nmol/l were found. Our preliminary results show that OTA is abundant in nearly all serum samples but some renal diseases show increased numbers of samples with high (>1.5 nmol/l) OTA concentrations.     

Evolutionary Dynamics of the Cellulose Synthase Gene Superfamily in Grasses

Phylogenetic analyses of cellulose synthase (CesA) and cellulose synthase-like (Csl) families from the cellulose synthase gene superfamily were used to reconstruct their evolutionary origins and selection histories. Counterintuitively, genes encoding primary cell wall CesAs have undergone extensive expansion and diversification following an ancestral duplication from a secondary cell wall-associated CesA. Selection pressure across entire CesA and Csl clades appears to be low, but this conceals considerable variation within individual clades. Genes in the CslF clade are of particular interest because some mediate the synthesis of (1,3;1,4)-β-glucan, a polysaccharide characteristic of the evolutionarily successful grasses that is not widely distributed elsewhere in the plant kingdom. The phylogeny suggests that duplication of either CslF6 and/or CslF7 produced the ancestor of a highly conserved cluster of CslF genes that remain located in syntenic regions of all the grass genomes examined. A CslF6-specific insert encoding approximately 55 amino acid residues has subsequently been incorporated into the gene, or possibly lost from other CslFs, and the CslF7 clade has undergone a significant long-term shift in selection pressure. Homology modeling and molecular dynamics of the CslF6 protein were used to define the three-dimensional dispositions of individual amino acids that are subject to strong ongoing selection, together with the position of the conserved 55-amino acid insert that is known to influence the amounts and fine structures of (1,3;1,4)-β-glucans synthesized. These wall polysaccharides are attracting renewed interest because of their central roles as sources of dietary fiber in human health and for the generation of renewable liquid biofuels.Recent attempts to better understand the chemistry and biology of plant cell walls have been driven by the importance of these walls as biomass sources for biofuel production systems, as sources of dietary fiber that is increasingly recognized as being highly beneficial for human health, and as key components of livestock forage and fodder. Plant cell walls consist predominantly of polysaccharides and lignin. In addition to cellulose, walls contain a wide array of complex noncellulosic polysaccharides that vary across the plant kingdom (Carpita, 1996; Popper and Fry, 2003; Niklas, 2004; Popper and Tuohy, 2010). In the dicotyledons, pectic polysaccharides and xyloglucans predominate, although smaller amounts of heteroxylans and heteromannans are also found. In evolutionary terms, a major change in noncellulosic wall composition is observed with the emergence of the Poaceae family, which contains the grasses and important cereal species. In contrast to dicots, walls of the Poaceae have relatively low levels of pectic polysaccharides and xyloglucans and correspondingly higher levels of heteroxylans, which appear to constitute the core noncellulosic wall polysaccharides in this family. In addition, walls of the Poaceae often contain (1,3;1,4)-β-glucans, which are not widely distributed in dicotyledons or other monocotyledons (Carpita, 1996; Fincher, 2009).Following the identification of the genes that encode cellulose synthases, which were designated CesA genes (Pear et al., 1996; Arioli et al., 1998), analyses of EST databases quickly revealed that the CesA group of cellulose synthase genes was in fact just one clade of a much larger superfamily that contained up to about 50 genes in most land plants (Richmond and Somerville, 2000; Hazen et al., 2002). The other members of the large gene family were designated cellulose synthase-like genes (Csl), which represent several clades in the overall phylogeny of the superfamily (Supplemental Fig. S1). The plant CesA genes were shown to have both conserved and hypervariable regions (Delmer, 1999; Doblin et al., 2002) and, together with the related Csl genes, were predicted to be integral membrane proteins and to have conserved, active-site D,D,D,QxxRW amino acid sequences. The CesA and Csl genes are members of the GT2 family of glycosyltransferases (Cantarel et al., 2009; http://www.cazy.org/).Several of the Csl genes have now been implicated in the biosynthesis of noncellulosic wall polysaccharides. Certain CslA genes mediate mannan and glucomannan synthesis (Dhugga et al., 2004; Liepman et al., 2005). Genes in the CslC clade are believed to be involved in xyloglucan biosynthesis (Cocuron et al., 2007), while genes from both the CslF and CslH clades mediate (1,3;1,4)-β-glucan synthesis in the Poaceae (Burton et al., 2006; Doblin et al., 2009). The CslJ group of enzymes is also believed to be involved in (1,3;1,4)-β-glucan synthesis (Farrokhi et al., 2006; Fincher, 2009), but the phylogeny of this group of genes remains unresolved (Yin et al., 2009). The fact that the CslF group does not form a clade with the CslH and CslJ groups on the phylogenetic tree (Supplemental Fig. S1) led to the suggestion that the genes mediating (1,3;1,4)-β-glucan synthesis have evolved independently on more than one occasion (Doblin et al., 2009; Fincher, 2009).Against this background and considering the sequence similarities between genes in the cellulose synthase gene superfamily, we have used Bayesian phylogenetic analyses of these genes from seven fully sequenced taxa to reconstruct the evolutionary origins of the CesA and Csl families in the grasses and, in particular, to investigate the evolution of the CslF, CslH, and CslJ genes. The distributions of the genes across genomes were compared, CslF gene clusters were analyzed, and the rates of synonymous and nonsynonymous nucleotide substitution were estimated to assess and compare selection histories of individual members of clades within the gene superfamily. Finally, we have constructed a refined model of the barley CslF6 enzyme to observe how selection on specific residues and regions of the enzyme has operated in a structural and functional context.     

Creatine kinase isoenzyme activity during and after an ultra-distance (200 km) run

It is commonly assumed that creatine kinase (CK) activity in plasma is related to the state of an inflammatory response at 24-48 h, and also it has shown biphasic patterns after a marathon run. No information is available on CK isoenzymes after an ultra-marathon run. The purpose of the present study is to examine the CK isoenzymes after a 200 km ultra-marathon run and during the subsequent recovery. Blood samples were obtained during registration 1 2 h before the 200-km race and during the race at 100 km, 150 km and at the end of 200 km, as well as after a 24 h period of recovery. Thirty-two male ultra-distance runners participated in the study. Serum CPK showed a marked increase throughout the race and 24 h recovery period (p < 0.001). Serum CK during the race occurs mostly in the CK-MM isoform and only minutely in the CK-MB isoform and is unchanged in the CK-BB isoform. High-sensitivity C-reactive protein (hs-CRP), oestradiol, AST and ALT increased significantly from the pre-race value at 100 km and a further increase took place by the end of the 200 km run. The results of our study demonstrate a different release pattern of creatine kinase after an ultra-distance (200 km) run compared to the studies of marathon running and intense eccentric exercise, and changes in several biomarkers, indicative of muscle damage during the race, were much more pronounced during the latter half (100–200 km) of the race. However, the increases in plasma concentration of muscle enzymes may reflect not only structural damage, but also their rate of clearance.     

Motif kernel generated by genetic programming improves remote homology and fold detection

Background  

Protein remote homology detection is a central problem in computational biology. Most recent methods train support vector machines to discriminate between related and unrelated sequences and these studies have introduced several types of kernels. One successful approach is to base a kernel on shared occurrences of discrete sequence motifs. Still, many protein sequences fail to be classified correctly for a lack of a suitable set of motifs for these sequences.     

Molecular docking analysis of bioactive compounds from Plectranthus amboinicus with glucokinase

Natural remedies from medicinal plants are known to be effective and reliable appropriate medicine for illnesses. The current research examined Plectranthus amboinicus'' anti diabetic property by docking the bioactive compounds of certain target proteins. We document the molecular docking analysis of bioactive compounds from Plectranthus amboinicus with protein Glucokinase. Molecular docking experiments were carried out in PyRx software. Results of these docking experiments showed that most of the compounds showed very strong interaction with the target protein Glucokinase. Based on the scoring parameters we have selected best four compounds (Rutin, Salvianolic acid, Luteolin and Salvigenin) which showed very good docking score and hydrogen bond interaction for diabetics.     

Rituximab treatment in rheumatoid arthritis: how does it work?

Treatment with the chimerical monoclonal antibody rituximab results in CD20-directed B cell depletion. Although this depletion is almost complete in the peripheral blood of nearly all patients with rheumatoid arthritis, a proportion of patients does not exhibit a clinical response. The paper by Nakou and colleagues suggests that a decrease in CD19+CD27+ memory B cells in both peripheral blood and bone marrow precedes the clinical response to rituximab. This finding adds to the emerging evidence that lack of response to rituximab is associated with persistence of B lineage cells in specific body compartments.     

Molecular docking of alkaloid compounds with the matrix metalloproteinase 2

Matrix metalloproteinase protein-2 (MMP-2) is linked to the human oral squamous cell carcinoma. Therefore, it is of interest to design new inhibitors for MMP-2 to combat the disease. Thus, we document the molecular docking features of Aristolochic acid, Cryptopleurine, Epipodophyllotoxin, and Fagaronine with MMP-2 for further consideration.