Multiple structure alignment with msTALI

ABSTRACT: BACKGROUND: Multiple structure alignments have received increasing attention in recent years as an alternative to multiple sequence alignments. Although multiple structure alignment algorithms can potentially be applied to a number of problems, they have primarily been used for protein core identification. A method that is capable of solving a variety of problems using structure comparison is still absent. Here we introduce a program msTALI for aligning multiple protein structures. Our algorithm uses several informative features to guide its alignments: torsion angles, backbone Calpha atom positions, secondary structure, residue type, surface accessibility, and properties of nearby atoms. The algorithm allows the user to weight the types of information used to generate the alignment, which expands its utility to a wide variety of problems. RESULTS: msTALI exhibits competitive results on 824 families from the Homstrad and SABmark databases when compared to Matt and Mustang. We also demonstrate success at building a database of protein cores using 341 randomly selected CATH domains and highlight the contribution of msTALI compared to the CATH classifications. Finally, we present an example applying msTALI to the problem of detecting hinges in a protein undergoing rigid-body motion. CONCLUSIONS: msTALI is an effective algorithm for multiple structure alignment. In addition to its performance on standard comparison databases, it utilizes clear, informative features, allowing further customization for domain-specific applications. The C++ source code for msTALI is available for Linux on the web at http://ifestos.cse.sc.edu/mstali.     

Application of an independent dose calculation software for estimating the impact of inter-fractional setup shifts in Helical Tomotherapy treatments

The purpose of this study is to validate the capability of in-house independent point dose calculation software to be used as a second check for Helical Tomotherapy treatment plans. The software performed its calculations in homogenous conditions (using the Cheese phantom, which is a cylindrical phantom with radius 15 cm and length 18 cm) using a factor-based algorithm. Fifty patients, who were treated for pelvic (10), prostate (14), lung (10), head & neck (12) and brain (4) cancers, were used. Based on the individual patient kVCT images and the pretreatment MVCT images for each treatment fraction, the corresponding daily patient setup shifts in the IEC-X, IEC-Y, and IEC-Z directions were registered. For each patient, the registered fractional setup shifts were grouped into systematic and random shifts. The average systematic dosimetric variations showed small dose deviation for the different cancer types (1.0%–3.0%) compared to the planned dose. Of the fifty patients, only three had percent differences larger than 5%. The average random dosimetric variations showed relatively small dose deviations (0.2%–1.1%) compared to the planned dose. None of the patients had percent differences larger than 5%. By examining the individual fractions of each patient, it is observed that only in 31 out of 1358 fractions the percent differences exceeded the border of 5%. These results indicate that the overall dosimetric impact from systematic and random variations is small and that the software is a capable platform for independent point dose validation for the Helical Tomotherapy modality.     

Trichopsomyia ochrozona (Stackelberg, 1952) (Diptera: Syrphidae) recorded from Iran for the first time with a key to the West Palaearctic Trichopsomyia Williston, 1888 species

The hoverfly Trichopsomyia ochrozona (Stackelberg, 1952) (Diptera: Syrphidae) is recorded for the first time from Iran. An illustrated key to the West Palaearctic species of Trichopsomyia is presented. Illustrations of the puparium of Trichopsomyia joratensis Goeldin, 1997 and the larva and puparium of T. ochrozona are given and their larval and adult habitats are described. A short discussion is given on the known larval habitat of other West Palaearctic Trichopsomyia species. Some of the synonyms have been evaluated and Pipiza melancholica Meigen, 1822 is withdrawn from synonymy of Trichopsomyia flavitarsis (Meigen, 1822) and is considered as a junior synonym of Musca viduata Linnaeus, 1758 syn. nov.     

Human papillomavirus infection. Frequency and association with cervical neoplasia in a young population

One million, six hundred thirty-two thousand, eight hundred forty-seven women from two independent populations in the United States received cytologic screening during a two-year period. Condylomatous lesions (human papillomavirus [HPV] infections) were the most frequent cytologic abnormality in women in both the Planned Parenthood and private sector groups (prevalence rates of 18.6 to 19.0 in women between ages 15 to 19). The prevalence rates of mild-to-moderate dysplasia were also similar in both populations, with the highest frequencies being between ages 25 to 29. Severe dysplasia and carcinoma in situ were most frequent between ages 35 to 39. In both populations, women with condylomatous changes coexisting with dysplastic changes were about ten years younger, grade-for-grade of severity of the lesion, than women without evidence of HPV infection. Since HPV infection is believed to represent the soil from which neoplasm develops, both the frequency of condyloma and the occurrence of dysplasia and cancer in young women suggest that women should begin regular screening programs while in their teens or after they become sexually active.     

The origin of multicellularity in cyanobacteria

Background  

Cyanobacteria are one of the oldest and morphologically most diverse prokaryotic phyla on our planet. The early development of an oxygen-containing atmosphere approximately 2.45 - 2.22 billion years ago is attributed to the photosynthetic activity of cyanobacteria. Furthermore, they are one of the few prokaryotic phyla where multicellularity has evolved. Understanding when and how multicellularity evolved in these ancient organisms would provide fundamental information on the early history of life and further our knowledge of complex life forms.     

Transgenerational Propagation and Quantitative Maintenance of Paternal Centromeres Depends on Cid/Cenp-A Presence in Drosophila Sperm

In Drosophila melanogaster, as in many animal and plant species, centromere identity is specified epigenetically. In proliferating cells, a centromere-specific histone H3 variant (CenH3), named Cid in Drosophila and Cenp-A in humans, is a crucial component of the epigenetic centromere mark. Hence, maintenance of the amount and chromosomal location of CenH3 during mitotic proliferation is important. Interestingly, CenH3 may have different roles during meiosis and the onset of embryogenesis. In gametes of Caenorhabditis elegans, and possibly in plants, centromere marking is independent of CenH3. Moreover, male gamete differentiation in animals often includes global nucleosome for protamine exchange that potentially could remove CenH3 nucleosomes. Here we demonstrate that the control of Cid loading during male meiosis is distinct from the regulation observed during the mitotic cycles of early embryogenesis. But Cid is present in mature sperm. After strong Cid depletion in sperm, paternal centromeres fail to integrate into the gonomeric spindle of the first mitosis, resulting in gynogenetic haploid embryos. Furthermore, after moderate depletion, paternal centromeres are unable to re-acquire normal Cid levels in the next generation. We conclude that Cid in sperm is an essential component of the epigenetic centromere mark on paternal chromosomes and it exerts quantitative control over centromeric Cid levels throughout development. Hence, the amount of Cid that is loaded during each cell cycle appears to be determined primarily by the preexisting centromeric Cid, with little flexibility for compensation of accidental losses.     

A Segmental Semi Markov Model for protein secondary structure prediction

Hidden Markov Models (HMMs) are practical tools which provide probabilistic base for protein secondary structure prediction. In these models, usually, only the information of the left hand side of an amino acid is considered. Accordingly, these models seem to be inefficient with respect to long range correlations. In this work we discuss a Segmental Semi Markov Model (SSMM) in which the information of both sides of amino acids are considered. It is assumed and seemed reasonable that the information on both sides of an amino acid can provide a suitable tool for measuring dependencies. We consider these dependencies by dividing them into shorter dependencies. Each of these dependency models can be applied for estimating the probability of segments in structural classes. Several conditional probabilities concerning dependency of an amino acid to the residues appeared on its both sides are considered. Based on these conditional probabilities a weighted model is obtained to calculate the probability of each segment in a structure. This results in 2.27% increase in prediction accuracy in comparison with the ordinary Segmental Semi Markov Models, SSMMs. We also compare the performance of our model with that of the Segmental Semi Markov Model introduced by Schmidler et al. [C.S. Schmidler, J.S. Liu, D.L. Brutlag, Bayesian segmentation of protein secondary structure, J. Comp. Biol. 7(1/2) (2000) 233-248]. The calculations show that the overall prediction accuracy of our model is higher than the SSMM introduced by Schmidler.