Investigations of Ramachandran disallowed conformations in protein domain families

In peptide and protein structures, occurrence of (phi,psi.) angles in the disallowed region of the Ramachandran map almost always suggests local regions of error or poor accuracy. However, very rarely genuine disallowed conformations occur as noted in the current study in proteins of known structure available at ultra-high resolution (<= 1.2 (A) over circle). In the current work, extent of conservation of genuine disallowed conformations in homologous proteins of known structures has been analyzed. From a dataset of 124 protein domain families, with structure of at least one constituent member in each family available at a resolution of 1.2 (A) over circle or better, we have analyzed the conservation of 221 disallowed conformations. It is observed that the disallowed conformation is only moderately conservedin protein domain families. In the gross dataset no particular residue type adopting disallowed conformation elicit high conservation of residue type though there are alignment positions in the dataset with complete conservation of both the residue type and the disallowed conformation. Conserved disallowed conformation in protein domain families play biologically significant role in roughly 50% of the cases. The residues with the disallowed conformation or its flanking residues are often located within or around the functional site of the protein. (C) 2013 Elsevier B.V. All rights reserved.

Analysis on conservation of disulphide bonds and their structural features in homologous protein domain families

Background: Disulphide bridges are well known to play key roles in stability, folding and functions of proteins. Introduction or deletion of disulphides by site-directed mutagenesis have produced varying effects on stability and folding depending upon the protein and location of disulphide in the 3-D structure. Given the lack of complete understanding it is worthwhile to learn from an analysis of extent of conservation of disulphides in homologous proteins. We have also addressed the question of what structural interactions replaces a disulphide in a homologue in another homologue. Results: Using a dataset involving 34,752 pairwise comparisons of homologous protein domains corresponding to 300 protein domain families of known 3-D structures, we provide a comprehensive analysis of extent of conservation of disulphide bridges and their structural features. We report that only 54% of all the disulphide bonds compared between the homologous pairs are conserved, even if, a small fraction of the non-conserved disulphides do include cytoplasmic proteins. Also, only about one fourth of the distinct disulphides are conserved in all the members in protein families. We note that while conservation of disulphide is common in many families, disulphide bond mutations are quite prevalent. Interestingly, we note that there is no clear relationship between sequence identity between two homologous proteins and disulphide bond conservation. Our analysis on structural features at the sites where cysteines forming disulphide in one homologue are replaced by non-Cys residues show that the elimination of a disulphide in a homologue need not always result in stabilizing interactions between equivalent residues. Conclusion: We observe that in the homologous proteins, disulphide bonds are conserved only to a modest extent. Very interestingly, we note that extent of conservation of disulphide in homologous proteins is unrelated to the overall sequence identity between homologues. The non-conserved disulphides are often associated with variable structural features that were recruited to be associated with differentiation or specialisation of protein function.

Families of asymptotic tensile crack tip stress fields in elastic-perfectly plastic single crystals

In this work, two families of asymptotic near-tip stress fields are constructed in an elastic-ideally plastic FCC single crystal under mode I plane strain conditions. A crack is taken to lie on the (010) plane and its front is aligned along the [(1) over bar 01] direction. Finite element analysis is first used to systematically examine the stress distributions corresponding to different constraint levels. The general framework developed by Rice (Mech Mater 6:317-335, 1987) and Drugan (J Mech Phys Solids 49:2155-2176, 2001) is then adopted to generate low triaxiality solutions by introducing an elastic sector near the crack tip. The two families of stress fields are parameterized by the normalized opening stress (tau(A)(22)/tau(o)) prevailing in the plastic sector in front of the tip and by the coordinates of a point where elastic unloading commences in stress space. It is found that the angular stress variations obtained from the analytical solutions show good agreement with finite element analysis.

DNA- and chromatin-condensing properties of rat testes H1a and H1t compared to those of rat liver H1bdec: H1t is a poor condenser of chromatin

Histones H1a and H1t are two major linker histone variants present at the pachytene interval of mammalian spermatogenesis. The DNA- and chromatin-condensing properties of these two variants isolated from rat testes were studied and compared with those from rat liver. For this purpose, the histone H1 subtypes were purified from the respective tissues using bath acid and salt extraction procedures, Circular dichroism studies revealed that acid exposure during isolation affects the alpha-helical structure of both the globular domain (in the presence of 1 M NaCl) and the C-terminal lambda-tail (in the presence of 60% trifluoroethanol). The condensation of rat oligonucleosomal DNA, as measured by circular dichroism spectroscopy, by the salt-extracted histone H1 was at least 10 times more efficient than condensation by the acid-extracted histone H1. A site size of 16-20 base pairs was calculated for the salt-extracted histone H1. Among the different histone H1 subtypes, somatic histone H1bdec had the highest DNA-condensing property, followed by histone H1a and histone H1t. All the salt-extracted histones condensed rat oligonucleosomal DNA more efficiently than linear pBR-322 DNA, Histones H1bdec and H1a condensed histone H1-depleted chromatin, prepared from rat liver nuclei, with relatively equal efficiency. On the other hand, there was no condensation of histone H1-depleted chromatin with the testes specific histone H1t. A comparison of the amino acid sequences of histone H1d (rat) and histone H1t (rat) revealed several interesting differences in the occurrence of DNA-binding motifs at the C-terminus. A striking observation is the presence of a direct repeat of an octapeptide motif K(A)T(S)PKKA(S)K(T)K(A) in histone H1d that is absent in histone H1t.

DNA-condensing and chromatin-condensing properties of rat testes hla and hit compared to those of rat-liver hlbdec - hlt is a poor condenser of chromatin

Histones H1a and H1t are two major linker histone variants present at the pachytene interval of mammalian spermatogenesis. The DNA- and chromatin-condensing properties of these two variants isolated from rat testes were studied and compared with those from rat liver. For this purpose, the histone H1 subtypes were purified from the respective tissues using bath acid and salt extraction procedures, Circular dichroism studies revealed that acid exposure during isolation affects the alpha-helical structure of both the globular domain (in the presence of 1 M NaCl) and the C-terminal lambda-tail (in the presence of 60% trifluoroethanol). The condensation of rat oligonucleosomal DNA, as measured by circular dichroism spectroscopy, by the salt-extracted histone H1 was at least 10 times more efficient than condensation by the acid-extracted histone H1. A site size of 16-20 base pairs was calculated for the salt-extracted histone H1. Among the different histone H1 subtypes, somatic histone H1bdec had the highest DNA-condensing property, followed by histone H1a and histone H1t. All the salt-extracted histones condensed rat oligonucleosomal DNA more efficiently than linear pBR-322 DNA, Histones H1bdec and H1a condensed histone H1-depleted chromatin, prepared from rat liver nuclei, with relatively equal efficiency. On the other hand, there was no condensation of histone H1-depleted chromatin with the testes specific histone H1t. A comparison of the amino acid sequences of histone H1d (rat) and histone H1t (rat) revealed several interesting differences in the occurrence of DNA-binding motifs at the C-terminus. A striking observation is the presence of a direct repeat of an octapeptide motif K(A)T(S)PKKA(S)K(T)K(A) in histone H1d that is absent in histone H1t.

COMMON-Sense net:Improved water management for resource-poor farmers via sensor networks

We describe the on-going design and implementation of a sensor network for agricultural management targeted at resource-poor farmers in India. Our focus on semi-arid regions led us to concentrate on water-related issues. Throughout 2004, we carried out a survey on the information needs of the population living in a cluster of villages in our study area. The results highlighted the potential that environment-related information has for the improvement of farming strategies in the face of highly variable conditions, in particular for risk management strategies (choice of crop varieties, sowing and harvest periods, prevention of pests and diseases, efficient use of irrigation water etc.). This leads us to advocate an original use of Information and Communication Technologies (ICT). We believe our demand-driven approach for the design of appropriate ICT tools that are targeted at the resource-poor to be relatively new. In order to go beyond a pure technocratic approach, we adopted an iterative, participatory methodology.

Scheduling parallel batch processors with incompatible job families using ant colony optimization

The present work concerns with the static scheduling of jobs to parallel identical batch processors with incompatible job families for minimizing the total weighted tardiness. This scheduling problem is applicable in burn-in operations and wafer fabrication in semiconductor manufacturing. We decompose the problem into two stages: batch formation and batch scheduling, as in the literature. The Ant Colony Optimization (ACO) based algorithm called ATC-BACO algorithm is developed in which ACO is used to solve the batch scheduling problems. Our computational experimentation shows that the proposed ATC-BACO algorithm performs better than the available best traditional dispatching rule called ATC-BATC rule.

A Genetic Study of Immunoglobulin E and Atopic Disease Based on Families Ascertained through Asthmatic Children

In order to investigate the modes of inheritance of serum immunoglobulin E (IgE) levels and atopic disease, serum IgE levels and data on allergic disease were obtained from 42 families ascertained through asthmatic children visiting an allergy clinic. Although the mean IgE levels were elevated (mean 637 U/ml), the prevalence of atopic disease in this population was surprisingly low. When the data were analyzed using complex segregation analysis, no major locus could be detected. Moreover, the polygenic heritability was unexpectedly small even though the correlation between serum IgE levels and the liability to atopic disease was around 0.4. Given this unusual set of findings, it is postulated that parasitic infections in this population have (in accordance with well-established results of parasitic disease) caused both elevated levels of serum IgE and a decreased prevalence of allergic disease with the possible masking of the various genetic components of serum IgE levels and atopic disease.

Desorption from concentrated polymer solutions in good and poor solvents

The objective of the study was to investigate the effects of the nature of solvent and polymer concentration on the mass-transfer coefficients in desorption of solvents and to develop a correlation to predict them. Desorption was experimentally studied in a Lewis cell with concentrated binary solutions of polymer in good and poor solvents. The range of parameters covered are polymer weight fraction between 0.25 and 0.6, Reynolds number between 3 and 100; Schmidt number between 1.4 X lo6 and 2.5 X lo8, and Sherwood number between 3.5 X lo2 and 1.2 X lo4. Desorption from moderately concentrated solutions (polymer weight fraction -0.25) is gas-phase controlled. Studies with more concentrated solutions showed that the effects of solvent and concentration were such that corrections due to concentration-dependent diffusivity and viscosity as well as high flux had to be applied to the mass-transfer coefficients before they could be correlated.

Minimizing total completion time on a batch processing machine with job families

We consider the problem of minimizing the total completion time on a single batch processing machine. The set of jobs to be scheduled can be partitioned into a number of families, where all jobs in the same family have the same processing time. The machine can process at most B jobs simultaneously as a batch, and the processing time of a batch is equal to the processing time of the longest job in the batch. We analyze that properties of an optimal schedule and develop a dynamic programming algorithm of polynomial time complexity when the number of job families is fixed. The research is motivated by the problem of scheduling burn-in ovens in the semiconductor industry

Germline BRCA1 mutation analysis in Indian breast/ovarian cancer families

Most of the predisposition to hereditary breast and ovarian cancer has been attributed to inherited defects in two tumor suppressor genes BRCA1 and BRCA2. To explore the contribution of BRCA1 mutations to hereditary breast cancer among Indian women, we examined the coding sequence of the BRCA1 gene in 14 breast cancer patients with a positive family history of breast and/or ovarian cancer. Mutation analysis was carried out using conformation sensitive gel electrophoresis (CSGE) followed by sequencing. Three mutations (21%) in the BRCA1 gene were identified. Two of them are novel mutations of which one is a missense mutation in exon 7 near the RING finger domain, while the other is a one base pair deletion in exon 11 which results in protein truncation. The third mutation, 185delAG, has been previously described in Ashkenazi Jewish families. To our knowledge this is the first report of a study of germline BRCA1 mutation analysis in familial breast cancer in India. Our data from 14 different families suggests a lower prevalence but definite involvement of germline mutations in the BRCA1 gene among Indian women with breast cancer and a family history of breast cancer.

Structural basis for poor uracil excision from hairpin DNA

Two-dimensional NMR and molecular dynamics simulations have been used to determine the three-dimensional structures of two hairpin DNA structures: d-CTAGAG GATCCUTTTGGATCCT (abbreviated as U1-hairpin) and d-CTAGAGGATCCTTUTGGATCCT (abbreviated as U3-hairpin). The (1) H resonances of both of these hairpin structures have been assigned almost completely. NMR restrained molecular dynamics and energy minimization procedures have been used to describe the three-dimensional structures of these hairpins. This study and concurrent NMR structural studies on two other d-CTAGAGGA TCCTUTTGGATCCT (abbreviated as U2-hairpin) and d-CTAGAGGATCCTTTUGGATCCT (abbreviated as U4-hairpin) have shed light upon various interactions reported between Echerichia coli uracil DNA glycosylase (UDG) and uracil-containing DNA. The backbone torsion angles, which partially influence the local conformation of U12 and U14 in U1 and U3-hairpins, respectively, are probably locked in the trans conformation as in the case of U-13 in the U2-hairpin. Such a stretched-out backbone conformation in the vicinity of U-12 and U-14 is thought to be the reason why the K-m value is poor for U1- and U3-hairpins as it is for the U2-hairpin. Furthermore, the bases U-12 and U-14 in both U1- and U3-hairpins adopt an anti conformation, in contrast with the base conformation of U-13 in the U2-hairpin, which adopts a syn conformation. The clear discrepancy observed in the U-base orientation with respect to the sugar moieties could explain why the V-max value is 10- to 20-fold higher for the U1- and U3-hairpins compared with the U2-hairpin. Taken together, these observations support our interpretation that the unfavourable backbone results in a poor K-m value, whereas the unfavourable nucleotide conformation results in a poor V-max value. These two parameters therefore make the U1- and U3-hairpins better substrates for UDG compared with the U2-hairpin, as reported earlier [Kumar, N. V. & Varshney, U. (1997) Nucleic Acids Res. 25, 2336-2343.].

Two new families of low-correlation interleaved QAM sequence

Two families of low correlation QAM sequences are presented here. In a CDMA setting, these sequences have the ability to transport a large amount of data as well as enable variable-rate signaling on the reverse link. The first family Á2SQ - B2− is constructed by interleaving 2 selected QAM sequences. This family is defined over M 2-QAM, where M = 2 m , m ≥ 2. Over 16-QAM, the normalized maximum correlation [`(q)]maxmax is bounded above by <~1.17 ÖNUnknown control sequence '\lesssim' , where N is the period of the sequences in the family. This upper bound on [`(q)]maxmax is the lowest among all known sequence families over 16-QAM.The second family Á4SQ4 is constructed by interleaving 4 selected QAM sequences. This family is defined over M 2-QAM, where M = 2 m , m ≥ 3, i.e., 64-QAM and beyond. The [`(q)]maxmax for sequences in this family over 64-QAM is upper bounded by <~1.60 ÖNUnknown control sequence '\lesssim' . For large M, [`(q)]max <~1.64 ÖNUnknown control sequence '\lesssim' . These upper bounds on [`(q)]maxmax are the lowest among all known sequence families over M 2-QAM, M = 2 m , m ≥ 3.