libcov: A C++ bioinformatic library to manipulate protein structures, sequence alignments and phylogeny

BACKGROUND: An increasing number of bioinformatics methods are considering the phylogenetic relationships between biological sequences. Implementing new methodologies using the maximum likelihood phylogenetic framework can be a time consuming task. RESULTS: The bioinformatics library libcov is a collection of C++ classes that provides a high and low-level interface to maximum likelihood phylogenetics, sequence analysis and a data structure for structural biological methods. libcov can be used to compute likelihoods, search tree topologies, estimate site rates, cluster sequences, manipulate tree structures and compare phylogenies for a broad selection of applications. CONCLUSION: Using this library, it is possible to rapidly prototype applications that use the sophistication of phylogenetic likelihoods without getting involved in a major software engineering project. libcov is thus a potentially valuable building block to develop in-house methodologies in the field of protein phylogenetics

Expression and activity of 20α-hydroxysteroid dehydrogenase (AKR1C1) in abdominal subcutaneous and omental adipose tissue in women

We have examined the expression and activity of 20a-hydroxysteroid dehydrogenase (20a-HSD) in abdominal adipose tissue in women. This recently-characterized enzyme from the aldoketoreductase 1C family (AKR1C1) is responsible for the conversion of progesterone into 20a-hydroxyprogesterone. Abdominal subcutaneous (SC) and omental (OM) adipose tissue biopsies were obtained from a sample of 32 women aged 47.7+-5.9 years (BMI: 27.6+-5.0 kg/m2 ) undergoing abdominal hysterectomies. Body composition and body fat distribution measurements were performed before the surgery by dual energy x-ray absorptiometry and computed tomography respectively. The expression of 20a-HSD was determined by real-time RT-PCR, and its activity was measured in whole tissue homogenates. Messenger RNA and activity of the enzyme were detected in both the SC and OM fat depots, the two measures being significantly higher in the SC compartment. Women characterized by a visceral adipose tissue area greater than or equal to 100 cm2 had an increased 20a-HSD conversion rate in their omental adipose tissue compared to women without visceral obesity (13.99+-2.07 vs. 7.92+-0.83 fmol/ug protein/24h, p<0.05). Accordingly, a positive correlation was found between omental adipose tissue 20a-HSD activity and computed tomography-measured visceral adipose tissue area (r=0.36, p<0.05). Significant positive correlations were also found between omental 20a-HSD activity and omental adipocyte diameter (r=0.49, p<0.05) and omental adipose tissue LPL activity (r=0.36, p=0.06). In conclusion, 20a-HSD activity and mRNA were detected in SC and OM adipose tissue in women, and omental 20a-hydroxylation of progesterone was highest in women with visceral obesity. Further studies are required to establish whether local conversion of progesterone may impact on the metabolism and function of adipocytes located within the abdominal cavity

Nondestructive Structure Characterization by Laser-Ultrasonics

Peer reviewed: YesNRC publication: Ye

Applications of Laser-Ultrasonics and Laser Tapping to Aerospace Composite Structures

Peer reviewed: YesNRC publication: Ye

Detection of Skin Disbond in Honeycombs and Coating Detachment by Laser Tapping Technique

Peer reviewed: YesNRC publication: Ye

Laser-ultrasonic and laser-tapping techniques for probing aerospace composite structures

Peer reviewed: YesNRC publication: Ye

Genetic diversity of Anaplasma species major surface proteins and implications for anaplasmosis serodiagnosis and vaccine development

The genus Anaplasma (Rickettsiales: Anaplasmataceae) includes several pathogens of veterinary and human medical importance. An understanding of the diversity of Anaplasma major surface proteins (MSPs), including those MSPs that modulate infection, development of persistent infections, and transmission of pathogens by ticks, is derived in part, by characterization and phylogenetic analyses of geographic strains. Information concerning the genetic diversity of Anaplasma spp. MSPs will likely influence the development of serodiagnostic assays and vaccine strategies for the control of anaplasmosi

Secondary structure is required for 3′ splice site recognition in yeast

Higher order RNA structures can mask splicing signals, loop out exons, or constitute riboswitches all of which contributes to the complexity of splicing regulation. We identified a G to A substitution between branch point (BP) and 3′ splice site (3′ss) of Saccharomyces cerevisiae COF1 intron, which dramatically impaired its splicing. RNA structure prediction and in-line probing showed that this mutation disrupted a stem in the BP-3′ss region. Analyses of various COF1 intron modifications revealed that the secondary structure brought about the reduction of BP to 3′ss distance and masked potential 3′ss. We demonstrated the same structural requisite for the splicing of UBC13 intron. Moreover, RNAfold predicted stable structures for almost all distant BP introns in S. cerevisiae and for selected examples in several other Saccharomycotina species. The employment of intramolecular structure to localize 3′ss for the second splicing step suggests the existence of pre-mRNA structure-based mechanism of 3′ss recognition

Insertions and the emergence of novel protein structure: a structure-based phylogenetic study of insertions

<p>Abstract</p> <p>Background</p> <p>In protein evolution, the mechanism of the emergence of novel protein domain is still an open question. The incremental growth of protein variable regions, which was produced by stochastic insertions, has the potential to generate large and complex sub-structures. In this study, a deterministic methodology is proposed to reconstruct phylogenies from protein structures, and to infer insertion events in protein evolution. The analysis was performed on a broad range of SCOP domain families.</p> <p>Results</p> <p>Phylogenies were reconstructed from protein 3D structural data. The phylogenetic trees were used to infer ancestral structures with a consensus method. From these ancestral reconstructions, 42.7% of the observed insertions are nested insertions, which locate in previous insert regions. The average size of inserts tends to increase with the insert rank or total number of insertions in the variable regions. We found that the structures of some nested inserts show complex or even domain-like fold patterns with helices, strands and loops. Furthermore, a basal level of structural innovation was found in inserts which displayed a significant structural similarity exclusively to themselves. The β-Lactamase/D-ala carboxypeptidase domain family is provided as an example to illustrate the inference of insertion events, and how the incremental growth of a variable region is capable to generate novel structural patterns.</p> <p>Conclusion</p> <p>Using 3D data, we proposed a method to reconstruct phylogenies. We applied the method to reconstruct the sequences of insertion events leading to the emergence of potentially novel structural elements within existing protein domains. The results suggest that structural innovation is possible via the stochastic process of insertions and rapid evolution within variable regions where inserts tend to be nested. We also demonstrate that the structure-based phylogeny enables the study of new questions relating to the evolution of protein domain and biological function.</p

Reproducing the manual annotation of multiple sequence alignments using a SVM classifier

Motivation: Aligning protein sequences with the best possible accuracy requires sophisticated algorithms. Since the optimal alignment is not guaranteed to be the correct one, it is expected that even the best alignment will contain sites that do not respect the assumption of positional homology. Because formulating rules to identify these sites is difficult, it is common practice to manually remove them. Although considered necessary in some cases, manual editing is time consuming and not reproducible. We present here an automated editing method based on the classification of ‘valid’ and ‘invalid’ sites