BlaSTorage: a fast package to parse, manage and store BLAST results

Background

Large-scale sequence studies requiring BLAST-based analysis produce huge amounts of data to be parsed. BLAST parsers are available, but they are often missing some important features, such as keeping all information from the raw BLAST output, allowing direct access to single results, and performing logical operations over them.

Findings

We implemented BlaSTorage, a Python package that parses multi BLAST results and returns them in a purpose-built object-database format. Unlike other BLAST parsers, BlaSTorage retains and stores all parts of BLAST results, including alignments, without loss of information; a complete API allows access to all the data components.

Conclusions

BlaSTorage shows comparable speed of more basic parser written in compiled languages as C++ and can be easily integrated into web applications or software pipelines.     

Kidins220/ARMS interacts with Pdzrn3, a protein containing multiple binding domains

We report the identification of a novel partner of Kidins220/ARMS (Kinase D-interacting substrate of 220 kDa/Ankyrin Repeat-rich Membrane Spanning) an adaptor of neurotrophin receptors playing crucial roles during neurogenesis. Screening a phage display library of brain cDNA products we found that D. rerio Pdzrn3, a protein containing RING-finger and PDZ-domains, interacts with Kidins220/ARMS through its first PDZ-domain. Both zebrafish proteins share high homology with the corresponding mammalian proteins and both genes are developmentally expressed in neural districts where early neurogenesis occurs. The interaction was also confirmed by biochemical assays and by co-localization at the tips of growing neurites of PC12 cells induced with nerve growth factor.     

6-aryl-2,4-dioxo-5-hexenoic acids, novel integrase inhibitors active against HIV-1 multiplication in cell-based assays

A series of 6-aryl-2,4-dioxo-5-hexenoic acids, were synthesized and tested against HIV-1 in cell-based assays and against recombinant HIV-1 integrase (rIN) in enzyme assays. Compound 8a showed potent antiretroviral activity (EC(50)=1.5 microM) and significant inhibition against rIN (strand transfer: IC(50)=7.9 microM; 3'-processing: IC(50)=7.0 microM). A preliminary molecular modeling study was carried out to compare the spatial conformation of 8a with those of L-731988 (4) and 5CITEP (7) in the IN core.     

Mechanical testing of cancellous bone from the femoral head: experimental errors due to off-axis measurements

The aim of this study was to verify whether a misalignment between the testing direction and the trabecular main direction has a significant effect on the compressive behaviour of cancellous bone. Ten cylindrical specimens were extracted from femoral heads with a misalignment to the trabecular main direction of approximately 20 degrees. Each specimen was paired with a specimen extracted aligned with the main direction of the trabeculae on the basis of the closest bone volume fraction, obtaining two groups, one 'aligned' and one 'misaligned'. The average off-axis angle was 6.1 degrees and 21.6 degrees for the 'aligned' and 'misaligned' group, respectively. The specimens underwent micro-tomographic analysis, compressive testing, micro-indentation testing and ashing. No significant differences were found in histomorphometric parameters, hardness and ash density between the two groups, whereas significant differences were found in Young's modulus and ultimate stress: both parameters, measured for the 'misaligned' group, were about 40% lower than those measured for the 'aligned' group. These results demonstrate a great effect of the angle between the testing direction and the main direction of the trabecular structure on the compressive behaviour of cancellous bone. This angle should be reduced as much as possible (in the present work the average value was 6.6+/-3.3 degrees), in any case measured, and always reported together with the mechanical parameters of cancellous bone.     

Antiinflammatory Effect of Phytosterols in Experimental Murine Colitis Model: Prevention,Induction, Remission Study

Phytosterols, besides hypocholesterolemic effect, present anti-inflammatory properties. Little information is available about their efficacy in Inflammatory Bowel Disease (IBD). Therefore, we have evaluated the effect of a mixture of phytosterols on prevention/induction/remission in a murine experimental model of colitis. Phytosterols were administered x os before, during and after colitis induction with Dextran Sodium Sulfate (DSS) in mice. Disease Activity Index (DAI), colon length, histopathology score, ¹⁸F-FDG microPET, oxidative stress in the intestinal tissue (ileum and colon) and gallbladder ileum and colon spontaneous and carbachol (CCh) induced motility, plasma lipids and plasma, liver and biliary bile acids (BA) were evaluated. A similar longitudinal study was performed in a DSS colitis control group. Mice treated with DSS developed severe colitis as shown by DAI, colon length, histopathology score, ¹⁸F-FDG microPET, oxidative stress. Both spontaneous and induced ileal and colonic motility were severely disturbed. The same was observed with gallbladder. DSS colitis resulted in an increase in plasma cholesterol, and a modification of the BA pattern. Phytosterols feeding did not prevent colitis onset but significantly reduced the severity of the disease and improved clinical and histological remission. It had strong antioxidant effects, almost restored colon, ileal and gallbladder motility. Plasmatic levels of cholesterol were also reduced. DSS induced a modification in the BA pattern consistent with an increase in the intestinal BA deconjugating bacteria, prevented by phytosterols. Phytosterols seem a potential nutraceutical tool for gastrointestinal inflammatory diseases, combining metabolic systematic and local anti-inflammatory effects.     

Meiotic behavior and pollen morphology variation in Centaurium pulchellum (Gentianaceae)

Centaurium pulchellum is an annual herb native to Europe, but introduced in South America, where it is widely used in the preparation of digestive infusions and bitter drinks. In this species, a wide variation in the aperture pattern of pollen grains was reported and has been attributed to environmental factors or irregularities at meiosis. For this reason, cytological and palynological studies have been undertaken on two different populations. The pollen grain analysis showed that some types are more frequent within each population, but the most common forms were the typical 3-colporate and 4-colporate. The cytological analysis revealed that the analyzed populations of C. pulchellum have chromosome number 2n = 36. The presence of tetravalents at meiosis strongly suggests that these populations are autotetraploid based on x = 9. The meiotic behavior showed a significant percentage of irregularities in different phases: off-plate bivalents, precocious segregation, laggard chromosomes, bridges, and cytomixis. However these irregularities are not related to the variation in the aperture pattern of pollen grains. The heteromorphism in the pollen grains observed in C. pulchellum could be a normal condition to which the species is well adapted.     

Regional Distribution and Evolution of Gray Matter Damage in Different Populations of Multiple Sclerosis Patients

Background

Both gray-matter (GM) atrophy and lesions occur from the earliest stages of Multiple Sclerosis (MS) and are one of the major determinants of long-term clinical outcomes. Nevertheless, the relationship between focal and diffuse GM damage has not been clarified yet. Here we investigate the regional distribution and temporal evolution of cortical thinning and how it is influenced by the local appearance of new GM lesions at different stages of the disease in different populations of MS patients.

Methods

We studied twenty MS patients with clinically isolated syndrome (CIS), 27 with early relapsing-remitting MS (RRMS, disease duration <5 years), 29 with late RRMS (disease duration ≥ 5 years) and 20 with secondary-progressive MS (SPMS). The distribution and evolution of regional cortical thickness and GM lesions were assessed during 5-year follow-up.

Results

The results showed that new lesions appeared more frequently in hippocampus and parahippocampal gyri (9.1%), insula (8.9%), cingulate cortex (8.3%), superior frontal gyrus (8.1%), and cerebellum (6.5%). The aforementioned regions showed the greatest reduction in thickness/volume, although (several) differences were observed across subgroups. The correlation between the appearance of new cortical lesions and cortical thinning was stronger in CIS (r² = 50.0, p<0.001) and in early RRMS (r² = 52.3, p<0.001), compared to late RRMS (r² = 25.5, p<0.001) and SPMS (r² = 6.3, p = 0.133).

Conclusions

We conclude that GM atrophy and lesions appear to be different signatures of cortical disease in MS having in common overlapping spatio-temporal distribution patterns. However, the correlation between focal and diffuse damage is only moderate and more evident in the early phase of the disease.