Context dependent splicing functions of Bud31/Ycr063w define its role in budding and cell cycle progression

The yeast Bud31 protein, a Prp19 complex (NTC) member, aids spliceosome assembly and thus promotes efficient pre-mRNA splicing. The bud31 null cells show mild budding abnormalities at optimal growth temperatures and, at higher temperatures, have growth defects with aberrant budding. Here we have assessed cell cycle transitions which require Bud31. We find Bud31 facilitates passage through G1-S regulatory point (Start) but is not needed for G2-M transition or for exit from mitosis. To co-relate Bud31 functions in cell division with splicing, we studied the splicing status of transcripts that encode proteins involved in budding. We find Bud31 promotes efficient splicing of only some of these pre-mRNAs, for example, ARP2 and SRC1. Wild type cells have a long and a short isoform of SRC1 mRNA and protein, out of which the shorter mRNA splice variant is predominant. bud31 Delta cells show inefficient SRC1 splicing and entirely lack the shorter SRC1 spliced mRNA isoform. Yeast PRP17, another NTC sub-complex member, is also required for G1-S and G2-M cell cycle transitions. We examined genetic interactions between BUD31 and PRP17. While both factors were needed for efficient cell cycle dependent gene expression, our data indicate that distinct pre-mRNAs depend on each of these non-essential splicing factors.

Sum rules and three point functions

Sum rules constraining the R-current spectral densities are derived holographically for the case of D3-branes, M2-branes and M5-branes all at finite chemical potentials. In each of the cases the sum rule relates a certain integral of the spectral density over the frequency to terms which depend both on long distance physics, hydrodynamics and short distance physics of the theory. The terms which which depend on the short distance physics result from the presence of certain chiral primaries in the OPE of two it-currents which are turned on at finite chemical potential. Since these sum rules contain information of the OPE they provide an alternate method to obtain the structure constants of the two R-currents and the chiral primary. As a consistency check we show that the 3 point function derived from the sum rule precisely matches with that obtained using Witten diagrams.

Some questions on integral geometry on noncompact symmetric spaces of higher rank

Let be a noncompact symmetric space of higher rank. We consider two types of averages of functions: one, over level sets of the heat kernel on and the other, over geodesic spheres. We prove injectivity results for functions in which extend the results in Pati and Sitaram (Sankya Ser A 62:419-424, 2000).

Diverse functions of restriction-modification systems in addition to cellular defense

Restriction-modification (R-M) systems are ubiquitous and are often considered primitive immune systems in bacteria. Their diversity and prevalence across the prokaryotic kingdom are an indication of their success as a defense mechanism against invading genomes. However, their cellular defense function does not adequately explain the basis for their immaculate specificity in sequence recognition and nonuniform distribution, ranging from none to too many, in diverse species. The present review deals with new developments which provide insights into the roles of these enzymes in other aspects of cellular function. In this review, emphasis is placed on novel hypotheses and various findings that have not yet been dealt with in a critical review. Emerging studies indicate their role in various cellular processes other than host defense, virulence, and even controlling the rate of evolution of the organism. We also discuss how R-M systems could have successfully evolved and be involved in additional cellular portfolios, thereby increasing the relative fitness of their hosts in the population.

Bactericidal/permeability increasing protein: A multifaceted protein with functions beyond LPS neutralization

Bactericidal permeability increasing protein (BPI), a 55-60kDa protein, first reported in 1975, has gone a long way as a protein with multifunctional roles. Its classical role in neutralizing endotoxin (LPS) raised high hopes among septic shock patients. Today, BPI is not just a LPS-neutralizing protein, but a protein with diverse functions. These functions can be as varied as inhibition of endothelial cell growth and inhibition of dendritic cell maturation, or as an anti-angiogenic, chemoattractant or opsonization agent. Though the literature available is extremely limited, it is fascinating to look into how BPI is gaining major importance as a signalling molecule. In this review, we briefly summarize the recent research focused on the multiple roles of BPI and its use as a therapeutic.

Splicing Functions and Global Dependency on Fission Yeast Slu7 Reveal Diversity in Spliceosome Assembly

The multiple short introns in Schizosaccharomyces pombe genes with degenerate cis sequences and atypically positioned polypyrimidine tracts make an interesting model to investigate canonical and alternative roles for conserved splicing factors. Here we report functions and interactions of the S. pombe slu7(+) (spslu7(+)) gene product, known from Saccharomyces cerevisiae and human in vitro reactions to assemble into spliceosomes after the first catalytic reaction and to dictate 3' splice site choice during the second reaction. By using a missense mutant of this essential S. pombe factor, we detected a range of global splicing derangements that were validated in assays for the splicing status of diverse candidate introns. We ascribe widespread, intron-specific SpSlu7 functions and have deduced several features, including the branch nucleotide-to-3' splice site distance, intron length, and the impact of its A/U content at the 5' end on the intron's dependence on SpSlu7. The data imply dynamic substrate-splicing factor relationships in multiintron transcripts. Interestingly, the unexpected early splicing arrest in spslu7-2 revealed a role before catalysis. We detected a salt-stable association with U5 snRNP and observed genetic interactions with spprp1(+), a homolog of human U5-102k factor. These observations together point to an altered recruitment and dependence on SpSlu7, suggesting its role in facilitating transitions that promote catalysis, and highlight the diversity in spliceosome assembly.

REPRODUCING KERNEL FOR A CLASS OF WEIGHTED BERGMAN SPACES ON THE SYMMETRIZED POLYDISC

A natural class of weighted Bergman spaces on the symmetrized polydisc is isometrically embedded as a subspace in the corresponding weighted Bergman space on the polydisc. We find an orthonormal basis for this subspace. It enables us to compute the kernel function for the weighted Bergman spaces on the symmetrized polydisc using the explicit nature of our embedding. This family of kernel functions includes the Szego and the Bergman kernel on the symmetrized polydisc.

On the images of Sobolev spaces under the heat kernel transform on the Heisenberg group

The aim of this paper is to obtain certain characterizations for the image of a Sobolev space on the Heisenberg group under the heat kernel transform. We give three types of characterizations for the image of a Sobolev space of positive order H-m (H-n), m is an element of N-n, under the heat kernel transform on H-n, using direct sum and direct integral of Bergmann spaces and certain unitary representations of H-n which can be realized on the Hilbert space of Hilbert-Schmidt operators on L-2 (R-n). We also show that the image of Sobolev space of negative order H-s (H-n), s(> 0) is an element of R is a direct sum of two weighted Bergman spaces. Finally, we try to obtain some pointwise estimates for the functions in the image of Schwartz class on H-n under the heat kernel transform. (C) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

CFT(4) partition functions and the heat kernel on AdS(5)

We consider four-dimensional CFTs which admit a large-N expansion, and whose spectrum contains states whose conformal dimensions do not scale with N. We explicitly reorganise the partition function obtained by exponentiating the one-particle partition function of these states into a heat kernel form for the dual string spectrum on AdS(5). On very general grounds, the heat kernel answer can be expressed in terms of a convolution of the one-particle partition function of the light states in the four-dimensional CFT. (C) 2013 Elsevier B.V. All rights reserved.

Effect of choice of basis functions in neural network for capturing unknown function for dynamic inversion control

The basic requirement for an autopilot is fast response and minimum steady state error for better guidance performance. The highly nonlinear nature of the missile dynamics due to the severe kinematic and inertial coupling of the missile airframe as well as the aerodynamics has been a challenge for an autopilot that is required to have satisfactory performance for all flight conditions in probable engagements. Dynamic inversion is very popular nonlinear controller for this kind of scenario. But the drawback of this controller is that it is sensitive to parameter perturbation. To overcome this problem, neural network has been used to capture the parameter uncertainty on line. The choice of basis function plays the major role in capturing the unknown dynamics. Here in this paper, many basis function has been studied for approximation of unknown dynamics. Cosine basis function has yield the best response compared to any other basis function for capturing the unknown dynamics. Neural network with Cosine basis function has improved the autopilot performance as well as robustness compared to Dynamic inversion without Neural network.

The relationship between classification of multi-domain proteins using an alignment-free approach and their functions: a case study with immunoglobulins

Establishing functional relationships between multi-domain protein sequences is a non-trivial task. Traditionally, delineating functional assignment and relationships of proteins requires domain assignments as a prerequisite. This process is sensitive to alignment quality and domain definitions. In multi-domain proteins due to multiple reasons, the quality of alignments is poor. We report the correspondence between the classification of proteins represented as full-length gene products and their functions. Our approach differs fundamentally from traditional methods in not performing the classification at the level of domains. Our method is based on an alignment free local matching scores (LMS) computation at the amino-acid sequence level followed by hierarchical clustering. As there are no gold standards for full-length protein sequence classification, we resorted to Gene Ontology and domain-architecture based similarity measures to assess our classification. The final clusters obtained using LMS show high functional and domain architectural similarities. Comparison of the current method with alignment based approaches at both domain and full-length protein showed superiority of the LMS scores. Using this method we have recreated objective relationships among different protein kinase sub-families and also classified immunoglobulin containing proteins where sub-family definitions do not exist currently. This method can be applied to any set of protein sequences and hence will be instrumental in analysis of large numbers of full-length protein sequences.

PLIC: protein-ligand interaction clusters

Most of the biological processes are governed through specific protein-ligand interactions. Discerning different components that contribute toward a favorable protein-ligand interaction could contribute significantly toward better understanding protein function, rationalizing drug design and obtaining design principles for protein engineering. The Protein Data Bank (PDB) currently hosts the structure of similar to 68 000 protein-ligand complexes. Although several databases exist that classify proteins according to sequence and structure, a mere handful of them annotate and classify protein-ligand interactions and provide information on different attributes of molecular recognition. In this study, an exhaustive comparison of all the biologically relevant ligand-binding sites (84 846 sites) has been conducted using PocketMatch: a rapid, parallel, in-house algorithm. PocketMatch quantifies the similarity between binding sites based on structural descriptors and residue attributes. A similarity network was constructed using binding sites whose PocketMatch scores exceeded a high similarity threshold (0.80). The binding site similarity network was clustered into discrete sets of similar sites using the Markov clustering (MCL) algorithm. Furthermore, various computational tools have been used to study different attributes of interactions within the individual clusters. The attributes can be roughly divided into (i) binding site characteristics including pocket shape, nature of residues and interaction profiles with different kinds of atomic probes, (ii) atomic contacts consisting of various types of polar, hydrophobic and aromatic contacts along with binding site water molecules that could play crucial roles in protein-ligand interactions and (iii) binding energetics involved in interactions derived from scoring functions developed for docking. For each ligand-binding site in each protein in the PDB, site similarity information, clusters they belong to and description of site attributes are provided as a relational database-protein-ligand interaction clusters (PLIC).

Analytical test functions for free vibration analysis of rotating non-homogeneous Timoshenko beams

In this paper, the governing equations for free vibration of a non-homogeneous rotating Timoshenko beam, having uniform cross-section, is studied using an inverse problem approach, for both cantilever and pinned-free boundary conditions. The bending displacement and the rotation due to bending are assumed to be simple polynomials which satisfy all four boundary conditions. It is found that for certain polynomial variations of the material mass density, elastic modulus and shear modulus, along the length of the beam, the assumed polynomials serve as simple closed form solutions to the coupled second order governing differential equations with variable coefficients. It is found that there are an infinite number of analytical polynomial functions possible for material mass density, shear modulus and elastic modulus distributions, which share the same frequency and mode shape for a particular mode. The derived results are intended to serve as benchmark solutions for testing approximate or numerical methods used for the vibration analysis of rotating non-homogeneous Timoshenko beams.

The HORMA domain: an evolutionarily conserved domain discovered in chromatin-associated proteins, has unanticipated diverse functions

The HORMA domain (for Hop1p, Rev7p and MAD2) was discovered in three chromatin-associated proteins in the budding yeast Saccharomyces cerevisiae. This domain has also been found in proteins with similar functions in organisms including plants, animals and nematodes. The HORMA domain containing proteins are thought to function as adaptors for meiotic checkpoint protein signaling and in the regulation of meiotic recombination. Surprisingly, new work has disclosed completely unanticipated and diverse functions for the HORMA domain containing proteins. A. M. Villeneuve and colleagues (Schvarzstein et al., 2013) show that meiosis-specific HORMA domain containing proteins plays a vital role in preventing centriole disengagement during Caenorhabditis elegans spermatocyte meiosis. Another recent study reveals that S. cerevisiae Atg13 HORMA domain acts as a phosphorylation-dependent conformational switch in the cellular autophagic process. (C) 2014 Elsevier B.V. All rights reserved.