A novel N-terminal domain may dictate the glucose response of Mondo proteins.

Glucose is a fundamental energy source for both prokaryotes and eukaryotes. The balance between glucose utilization and storage is integral for proper energy homeostasis, and defects are associated with several diseases, e.g.

Brain cancer prognosis: independent validation of a clinical bioinformatics approach.

Translational and evidence based medicine can take advantage of biotechnology advances that offer a fast growing variety of high-throughput data for screening molecular activities of genomic, transcriptional, post-transcriptional and translational observations. The clinical information hidden in these data can be clarified with clinical bioinformatics approaches. We have recently proposed a method to analyze different layers of high-throughput (omic) data to preserve the emergent properties that appear in the cellular system when all molecular levels are interacting.

Phylogenetic analysis and classification of the fungal bHLH domain.

The basic Helix-Loop-Helix (bHLH) domain is an essential highly conserved DNA-binding domain found in many transcription factors in all eukaryotic organisms. The bHLH domain has been well studied in the Animal and Plant Kingdoms but has yet to be characterized within Fungi. Herein, we obtained and evaluated the phylogenetic relationship of 490 fungal-specific bHLH containing proteins from 55 whole genome projects composed of 49 Ascomycota and 6 Basidiomycota organisms.

Evolution of the Max and Mlx networks in animals.

Transcription factors (TFs) are essential for the regulation of gene expression and often form emergent complexes to perform vital roles in cellular processes. In this paper, we focus on the parallel Max and Mlx networks of TFs because of their critical involvement in cell cycle regulation, proliferation, growth, metabolism, and apoptosis. A basic-helix-loop-helix-zipper (bHLHZ) domain mediates the competitive protein dimerization and DNA binding among Max and Mlx network members to form a complex system of cell regulation.

Joint analysis of transcriptional and post- transcriptional brain tumor data: searching for emergent properties of cellular systems.

Background: Advances in biotechnology offer a fast growing variety of high-throughput data for screening molecular activities of genomic, transcriptional, post-transcriptional and translational observations. However, to date, most computational and algorithmic efforts have been directed at mining data from each of these molecular levels (genomic, transcriptional, etc.) separately.

Site-specific evolutionary rates in proteins are better modeled as non-independent and strictly relative.

Motivation: In a nucleotide or amino acid sequence, not all sites evolve at the same rate, due to differing selective constraints at each site. Currently in computational molecular evolution, models incorporating rate heterogeneity always share two assumptions. First, the rate of evolution at each site is assumed to be independent of every other site.

Biochemical and functional evidence of p53 homology is inconsistent with molecular phylogenetics for distant sequences.

The tumor suppressor p53 is mutated in approximately 50% of all human cancer cases worldwide. It is commonly assumed that the phylogenetic history of this important tumor suppressor has been thoroughly studied; however, few detailed studies of the entire extended p53 protein family have been reported, and none comprehensively and simultaneously consider functional, molecular, and phylogenetic data. Herein we examine a diverse collection of reported p53-like protein sequences, including representatives from the arthropods, nematodes, and protists, with the goal of answering several important questions.

Hepatic endopolyploidy as a cellular consequence of age-specific selection for rate of development in mice.

Endopolyploidy is the generation of polyploid cells by DNA replication without subsequent cell division and is correlated with hypertrophic growth or growth via cell size. Thus, selection that alters growth may also change onset and frequency of endopolyploidy as a correlated response. We search for endopolyploidy in the liver in response to age-specific restricted index selection for the rate of development.

Application of complex demodulation on bZIP and bHLH-PAS protein domains.

Proteins are built with molecular modular building blocks such as an alpha-helix, beta-sheet, loop region and other structures. This is an economical way of constructing complex molecules. Periodicity analysis of protein sequences has allowed us to obtain meaningful information concerning their structure, function and evolution.

Molecular architecture of the DNA-binding region and its relationship to classification of basic helix-loop-helix proteins.

Multivariate statistical analyses are used to explore the molecular architecture of the DNA-binding and dimerization regions of basic helix-loop-helix (bHLH) proteins. Alphabetic amino acid data are transformed to biologically meaningful quantitative values using a set of 5 multivariate "indices." These multivariate indices summarize variation in a large suite of amino acid physiochemical attributes and reflect variability in polarity-accessibility-hydrophobicity, propensity for secondary structure, molecular size, codon composition, and electrostatic charge.

Gaussian quadrature formulae for arbitrary positive measures.

We present computational methods and subroutines to compute Gaussian quadrature integration formulas for arbitrary positive measures. For expensive integrands that can be factored into well-known forms, Gaussian quadrature schemes allow for efficient evaluation of high-accuracy and -precision numerical integrals, especially compared to general ad hoc schemes. In addition, for certain well-known density measures (the normal, gamma, log-normal, Student's t, inverse-gamma, beta, and Fisher's F) we present exact formulae for computing the respective quadrature scheme.

Spectral analysis of sequence variability in basic-helix-loop-helix (bHLH) protein domains.

The basic helix-loop-helix (bHLH) family of transcription factors is used as a paradigm to explore structural implications of periodicity patterns in amino acid sequence variability. A Boltzmann-Shannon entropy profile represents site-by-site amino acid variation in the bHLH domain. Spectral analysis of almost 200 bHLH sequences documents the periodic nature of the bHLH sequence variation.

Networks of coevolving sites in structural and functional domains of serpin proteins.

Amino acids do not occur randomly in proteins; rather, their occurrence at any given site is strongly influenced by the amino acid composition at other sites, the structural and functional aspects of the region of the protein in which they occur, and the evolutionary history of the protein. The goal of our research study is to identify networks of coevolving sites within the serpin proteins (serine protease inhibitors) and classify them as being caused by structural-functional constraints or by evolutionary history. To address this, a matrix of pairwise normalized mutual information (NMI) values was computed among amino acid sites for the serpin proteins.

Sequence signatures and the probabilistic identification of proteins in the Myc-Max-Mad network.

Accurate identification of specific groups of proteins by their amino acid sequence is an important goal in genome research. Here we combine information theory with fuzzy logic search procedures to identify sequence signatures or predictive motifs for members of the Myc-Max-Mad transcription factor network. Myc is a well known oncoprotein, and this family is involved in cell proliferation, apoptosis, and differentiation.

Solving the protein sequence metric problem.

Biological sequences are composed of long strings of alphabetic letters rather than arrays of numerical values. Lack of a natural underlying metric for comparing such alphabetic data significantly inhibits sophisticated statistical analyses of sequences, modeling structural and functional aspects of proteins, and related problems. Herein, we use multivariate statistical analyses on almost 500 amino acid attributes to produce a small set of highly interpretable numeric patterns of amino acid variability.

Phylogenetic analysis of plant basic helix-loop-helix proteins.

The basic helix-loop-helix (bHLH) family of proteins is a group of functionally diverse transcription factors found in both plants and animals. These proteins evolved early in eukaryotic cells before the split of animals and plants, but appear to function in 'plant-specific' or 'animal-specific' processes. In animals bHLH proteins are involved in regulation of a wide variety of essential developmental processes.

QUANTITATIVE GENETIC MODELS FOR DEVELOPMENT, EPIGENETIC SELECTION, AND PHENOTYPIC EVOLUTION.

Herein we describe a general multivariate quantitative genetic model that incorporates two potentially important developmental phenomena, maternal effects and epigenetic effects. Maternal and epigenetic effects are defined as partial regression coefficients and phenotypic variances are derived in terms of age-specific genetic and environmental variances. As a starting point, the traditional quantitative genetic model of additive gene effects and random environmental effects is cast in a developmental time framework.

UTERINE EFFECTS, EPIGENETICS, AND POSTNATAL SKELETAL DEVELOPMENT IN THE MOUSE.

Reciprocal embryo transfer experiments show that skeletal dimensions in adult mice are significantly influenced by the genotype of the female providing the uterine environment in which they were raised. Embryo transfers among C3HeB/FeJ, SWR/J, and the C3SWF, hybrid strain (C3H females x SWR males) permit separation of uterine maternal genotype effects from effects arising from the progeny's own genotype. Many different aspects of adult skeletal form are significantly influenced by uterine genotype and, in some instances, the pattern of these effects correlates with events during skeletal embryology.

CORRELATED RESPONSE IN THE DEVELOPMENTAL CHOREOGRAPHIES OF THE MOUSE MANDIBLE TO SELECTION FOR BODY COMPOSITION.

The correlated response to 13 generations of selection for percent fatness and leanness is investigated in 11 mandible traits in mice. Five selection lines are examined including high fat (HF), low fat (LF), high lean (HL), low lean (LL) and a randomly selected control strain (RC. The ontogenetic patterns of growth in the RC strain serve as a model to evaluate the developmental consequences of directional selection.

HOW SIMILAR ARE GENETIC CORRELATION STRUCTURES? DATA FROM MICE AND RATS.

An integral assumption of many models of morphometric evolution is the equality of the genetic variance-covariance structure across evolutionary time. To examine this assumption, the quantitative-genetic aspects of morphometric form are examined for eight pelvic traits in laboratory rats (Rattus norvegicus) and random-bred ICR mice (Mus musculus). In both species, all traits are significantly heritable, and there are significant phenotypic and genetic correlations among traits, although environmental correlations among the eight traits are low.

DEVELOPMENTAL QUANTITATIVE GENETICS AND THE EVOLUTION OF ONTOGENIES.

A model is presented which permits integration of developmental information into genetic discussions about evolutionary change in morphology. Development of a trait is described in terms of an ontogenetic trajectory whose properties are defined by a small number of parameters. Some evolutionary aspects of development are examined from the perspective of this quantitative genetic model.