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At least 1,081 records · Page 60Linked to original sources
PubMed2001

Disinhibitory psychopathology in male adolescents: discriminating conduct disorder from attention-deficit/hyperactivity disorder through concurrent assessment of multiple autonomic states.

T. P. Beauchaine recently proposed a model of autonomic nervous system functioning that predicts divergent patterns of psychophysiological responding across disorders of disinhibition. This model was tested by comparing groups of male adolescents with attention-deficit/hyperactivity disorder (ADHD) and attention-deficit/hyperactivity disorder plus conduct disorder (CD/ADHD) with controls while performing a repetitive motor task in which rewards were administered and removed across trials. Participants then watched a videotaped peer conflict. Electrodermal responding (EDR), cardiac pre-ejection period (PEP), and respiratory sinus arrhythmia (RSA) were monitored. Compared with controls, the ADHD and CD/ADHD participants exhibited reduced EDR. The CD/ADHD group was differentiated from the ADHD and control groups on PEP and from the control group on RSA. Findings are discussed in terms of the motivational and regulational systems indexed. Implications for understanding rates of comorbidity between CD and ADHD are considered.

Adolescent↗
PubMed2005

Ultrabithorax is required for membranous wing identity in the beetle Tribolium castaneum.

The two pairs of wings that are characteristic of ancestral pterygotes (winged insects) have often undergone evolutionary modification. In the fruitfly, Drosophila melanogaster, differences between the membranous forewings and the modified hindwings (halteres) depend on the Hox gene Ultrabithorax (Ubx). The Drosophila forewings develop without Hox input, while Ubx represses genes that are important for wing development, promoting haltere identity. However, the idea that Hox input is important to the morphologically specialized wing derivatives such as halteres, and not the more ancestral wings, requires examination in other insect orders. In beetles, such as Tribolium castaneum, it is the forewings that are modified (to form elytra), while the hindwings retain a morphologically more ancestral identity. Here we show that in this beetle Ubx 'de-specializes' the hindwings, which are transformed to elytra when the gene is knocked down. We also show evidence that elytra result from a Hox-free state, despite their diverged morphology. Ubx function in the hindwing seems necessary for a change in the expression of spalt, iroquois and achaete-scute homologues from elytron-like to more typical wing-like patterns. This counteracting effect of Ubx in beetle hindwings represents a previously unknown mode of wing diversification in insects.

Animals↗
PubMed2006

The structure of the exocyst subunit Sec6p defines a conserved architecture with diverse roles.

The exocyst is a conserved protein complex essential for trafficking secretory vesicles to the plasma membrane. The structure of the C-terminal domain of the exocyst subunit Sec6p reveals multiple helical bundles, which are structurally and topologically similar to Exo70p and the C-terminal domains of Exo84p and Sec15, despite <10% sequence identity. The helical bundles appear to be evolutionarily related molecular scaffolds that have diverged to create functionally distinct exocyst proteins.

Animals↗
PubMed2006

Genetic dissection of neuronal pathways controlling energy homeostasis.

Recent research has identified a number of genes playing critical roles in the central regulation of energy homeostasis. Subsequently, models of the neurocircuitry regulating energy balance have been suggested, although their physiological relevance remains mostly untested. Using the Cre/loxP system, we can now genetically dissect these neurocircuits and establish the specific roles of these genes in small neuronal subpopulations. Here we focus on two receptors shown to be critical in the central regulation of energy homeostasis: leptin (LepR) and melanocortin-4 receptors (MC4R). Mice and humans deficient in either leptin or melanocortin signaling are severely obese. A prominent model of leptin action places the arcuate nucleus of the hypothalamus, and in particular arcuate proopiomelanocortin (POMC) neurons, at the center stage of energy balance regulation. By deleting LepR specifically from POMC neurons in mice, we showed that LepR on POMC neurons are required but not solely responsible for leptin's regulation of body weight homeostasis. Thus, LepR on other neurons must also be critically important in leptin-mediated regulation of body weight homeostasis. Data from MC4R-deficient mice have shown that MC4Rs regulate both sides of the energy intake/energy expenditure balance. Our recent experiments used MC4R-deficient mice with restored MC4R expression only in the paraventricular hypothalamus and a subpopulation of amygdala neurons. We showed that MC4Rs in the paraventricular hypothalamus and/or amygdala are sufficient to control food intake but that MC4Rs elsewhere control energy expenditure, thereby discovering the novel concept of functional and anatomical divergence of MC4Rs.

Animals↗
PubMed2001

Properties of the C-terminal domain of 4.1 proteins.

At the C-terminus of all known 4.1 proteins is a sequence domain unique to these proteins, known as the C-terminal domain (CTD). Mammalian CTDs are associated with a growing number of protein-protein interactions, although such activities have yet to be associated with invertebrate CTDs. Mammalian CTDs are generally defined by sequence alignment as encoded by exons 18-21. Comparison of known vertebrate 4.1 proteins with invertebrate (Caenorhabditis elegans and Drosophila melanogaster) 4.1 proteins indicates that mammalian 4.1 exon 19 represents a vertebrate adaptation that extends the sequence of the CTD with a Ser/Thr-rich sequence. The CTD was first described as a 22/24-kDa domain by chymotryptic digestion of erythrocyte 4.1 (4.1R) [Leto, T.L. & Marchesi, V.T. (1984) J. Biol. Chem. 259, 4603-4608]. Here we show that in 4.1R the 22/24-kDa fragment is not stable but rapidly processed to a 15-kDa fragment by chymotrypsin. The 15-kDa fragment is extremely stable, being resistant to overnight digestion in chymotrypsin on ice. Analysis of this fragment indicates that it is derived from residues 709-858 (SwissProt accession no. P48193), and represents the CTD of 4.1R. The fragment behaves as a globular monomer in solution. Secondary-structure predictions indicate that this domain is composed of five or six beta strands with an alpha helix before the most C-terminal of these. Together these data indicate that the CTD probably represents an independent folding structure which has gained function since the divergence of vertebrates from invertebrates.

Amino Acid Sequence↗
PubMed1993

Origin of the human alcohol dehydrogenase system: implications from the structure and properties of the octopus protein.

In contrast to the multiplicity of alcohol dehydrogenase in vertebrates, a class III type of the enzyme [i.e., a glutathione-dependent formaldehyde dehydrogenase; formaldehyde; NAD+ oxidoreductase (glutathione-formylating), EC 1.2.1.1.] is the only form detectable in appreciable yield in octopus. It is enzymatically and structurally highly similar to the human class III enzyme, with limited overall residue differences (26%) and only a few conservative residue exchanges at the substrate and coenzyme pockets, reflecting "constant" characteristics of this class over wide time periods. It is distinct from the ethanol-active "variable" class I type of the enzyme (i.e., classical liver alcohol dehydrogenase; alcohol:NAD+ oxidoreductase, EC 1.1.1.1). The residue conservation of class III is also spaced differently from that of class I but is typical of that of proteins in general, emphasizing that class I, with divergence at three functional segments, is the form with deviating properties. In spite of the conservation in class III, surface charges differ considerably. The apparent absence of a class I enzyme in octopus and the constant nature of the class III enzyme support the concept of a duplicative origin of the class I line from the ancient class III form. Still more distant relationships define further enzyme lines that have subunits with other properties.

Alcohol Dehydrogenase↗
PubMed1998

Reorganization of auditory cortex in tinnitus.

Magnetic source imaging was used to determine whether tonotopy in auditory cortex of individuals with tinnitus diverges from normative functional organization. Ten tinnitus subjects and 15 healthy controls were exposed to four sets of tones while magnetoencephalographic recordings were obtained from the two cortical hemispheres in sequence. A marked shift of the cortical representation of the tinnitus frequency into an area adjacent to the expected tonotopic location was observed. The Euclidean distance of the tinnitus frequency from the trajectory of the tonotopic map was 5.3 mm (SD = 3.1) compared with a distance of 2.5 mm (SD = 1.3) of a corresponding frequency in the healthy controls (t = 3.13, P < 0.01). In addition, a strong positive correlation was found between the subjective strength of the tinnitus and the amount of cortical reorganization (r = 0.82, P < 0.01). These results demonstrate that tinnitus is related to plastic alterations in auditory cortex. Similarities between these data and the previous demonstrations that phantom limb pain is highly correlated with cortical reorganization suggest that tinnitus may be an auditory phantom phenomenon.

Acoustic Stimulation↗
PubMed2000

A conserved transcription motif suggesting functional parallels between Caenorhabditis elegans SKN-1 and Cap'n'Collar-related basic leucine zipper proteins.

In Caenorhabditis elegans, the predicted transcription factor SKN-1 is required for embryonic endodermal and mesodermal specification and for maintaining differentiated intestinal cells post-embryonically. The SKN-1 DNA-binding region is related to the Cap'n'Collar (CNC) family of basic leucine zipper proteins, but uniquely, SKN-1 binds DNA as a monomer. CNC proteins are absent in C. elegans, however; and their involvement in the endoderm and mesoderm suggests some functional parallels to SKN-1. Using a cell culture assay, we show that SKN-1 induces transcription and contains three potent activation domains. The functional core of one domain is a short motif, the DIDLID element, which is highly conserved in a subgroup of vertebrate CNC proteins. The DIDLID element is important for SKN-1-driven transcription, suggesting a likely significance in other CNC proteins. SKN-1 binds to and activates transcription through the p300/cAMP-responsive element-binding protein-binding protein (CBP) coactivator, supporting the genetic prediction that SKN-1 recruits the C. elegans p300/CBP ortholog, CBP-1. The DIDLID element appears to act independently of p300/CBP, however, suggesting a distinct conserved target. The evolutionarily preservation of the DIDLID transcriptional element supports the model that SKN-1 and some CNC proteins interact with analogous cofactors and may have preserved some similar functions despite having divergent DNA-binding domains.

Animals↗
PubMed2003

Purification of the Arabidopsis 26 S proteasome: biochemical and molecular analyses revealed the presence of multiple isoforms.

The 26 S proteasome is a multisubunit protease complex responsible for degrading a wide range of intracellular proteins in eukaryotes, especially those modified with polyubiquitin chains. It is composed of a self-compartmentalized core protease (CP) that houses the peptidase active sites appended on either or both ends by a regulatory particle (RP) that identifies appropriate substrates and translocates them into the lumen of the CP for breakdown. Here, we describe the molecular and biochemical properties of the 26 S proteasome from the plant Arabidopsis thaliana. Like the CP and the ATPase ring of the RP, the RP non-ATPase subunits are often encoded by two transcriptionally active genes with some pairs displaying sufficient sequence divergence to suggest functional differences. Most RPN subunits could functionally replace their yeast counterparts, implying that they have retained their positions and activities within the complex. A method was developed to purify the 26 S proteasome intact from whole Arabidopsis seedlings. These preparations are biochemically indistinguishable from those from yeast and mammals, including the need for ATP to maintain integrity and a strong sensitivity to the inhibitors MG115, MG132, lactacystin, and epoxomicin. Mass spectrometric analysis of the complex detected the presence of almost all CP and RP subunits. In many cases, both products of paralogous genes were detected, demonstrating that each isoform assembles into the mature particle. As with the yeast and animal 26 S proteasomes, attenuation of individual RP genes induces a coordinated up-regulation of many of the other 26 S proteasome genes, suggesting that plants contain a negative feedback mechanism to regulate the 26 S proteasome levels. The incorporation of paralogous subunits into the Arabidopsis holoprotease raises the intriguing possibility that plants synthesize multiple 26 S proteasome types with unique properties and/or target specificities.

Adenosine Triphosphatases↗
PubMed2006

The Arabidopsis thaliana PARTING DANCERS gene encoding a novel protein is required for normal meiotic homologous recombination.

Recent studies of meiotic recombination in the budding yeast and the model plant Arabidopsis thaliana indicate that meiotic crossovers (COs) occur through two genetic pathways: the interference-sensitive pathway and the interference-insensitive pathway. However, few genes have been identified in either pathway. Here, we describe the identification of the PARTING DANCERS (PTD) gene, as a gene with an elevated expression level in meiocytes. Analysis of two independently generated transferred DNA insertional lines in PTD showed that the mutants had reduced fertility. Further cytological analysis of male meiosis in the ptd mutants revealed defects in meiosis, including reduced formation of chiasmata, the cytological appearance of COs. The residual chiasmata in the mutants were distributed randomly, indicating that the ptd mutants are defective for CO formation in the interference-sensitive pathway. In addition, transmission electron microscopic analysis of the mutants detected no obvious abnormality of synaptonemal complexes and apparently normal late recombination nodules at the pachytene stage, suggesting that the mutant's defects in bivalent formation were postsynaptic. Comparison to other genes with limited sequence similarity raises the possibility that PTD may present a previously unknown function conserved in divergent eukaryotic organisms.

Amino Acid Sequence↗
PubMed1988

Recombination within a subclass of restriction fragment length polymorphisms may help link classical and molecular genetics.

Restriction fragment length polymorphisms (RFLPs) are being used to construct complete linkage maps for many eukaryotic genomes. These RFLP maps can be used to predict the inheritance of important phenotypic loci and will assist in the molecular cloning of linked gene(s) which affect phenotypes of scientific, medical and agronomic importance. However, genetic linkage implies very little about the actual physical distances between loci. An assay is described which uses genetic recombinants to measure physical distance from a DNA probe to linked phenotypic loci. We have defined the subset of all RFLPs which have polymorphic restriction sites at both ends as class II RFLPs. The frequency of class II RFLPs is computed as a function of sequence divergence and total RFLP frequency for highly divergent genomes. Useful frequencies exist between organisms which differ by more than 7% in DNA sequence. Recombination within class II RFLPs will produce fragments of novel sizes which can be assayed by pulsed field electrophoresis to estimate physical distance in kilobase pairs between linked RFLP and phenotypic loci. This proposed assay should have particular applications to crop plants where highly divergent and polymorphic species are often genetically compatible and thus, where class II RFLPs will be most frequent.

Chromosome Mapping↗
PubMed2003

Isolation of two plastid division ftsZ genes from Chlamydomonas reinhardtii and its evolutionary implication for the role of FtsZ in plastid division.

In order to elucidate the origin of the plastid division gene ftsZ in green plant lineage, and to understand the significance of this divergence for the function of FtsZ proteins in plants, two full-length cDNAs (accession numbers AF449446 and AB084236) were isolated from Chlamydomonas reinhardtii, a base species of green plant lineage. A phylogenetic analysis based on amino acid sequences of eukaryotic FtsZs reveals that an ancient duplication of the ftsZ gene occurred after the endosymbiotic event. The ancient duplication implies that two ftsZ families might play an indispensable role at the early endosymbiotic stage.

Algal Proteins↗
PubMed1986

A novel chlorophyll a/b binding (Cab) protein gene from petunia which encodes the lower molecular weight Cab precursor protein.

The 16 petunia Cab genes which have been characterized are all closely related at the nucleotide sequence level and they encode Cab precursor polypeptides which are similar in sequence and length. Here we describe a novel petunia Cab gene which encodes a unique Cab precursor protein. This protein is a member of the smallest class of Cab precursor proteins for which no gene has previously been assigned in petunia or any other species. The features of this Cab precursor protein are that it is shorter by 2-3 amino acids than the formerly characterized Cab precursors, its transit peptide sequence is unrelated, and the mature polypeptide is significantly diverged at the functionally important N terminus from other petunia Cab proteins. Gene structure also discriminates this gene which is the only intron containing Cab gene in petunia genomic DNA.

Amino Acid Sequence↗
PubMed2004

PIRSF: family classification system at the Protein Information Resource.

The Protein Information Resource (PIR) is an integrated public resource of protein informatics. To facilitate the sensible propagation and standardization of protein annotation and the systematic detection of annotation errors, PIR has extended its superfamily concept and developed the SuperFamily (PIRSF) classification system. Based on the evolutionary relationships of whole proteins, this classification system allows annotation of both specific biological and generic biochemical functions. The system adopts a network structure for protein classification from superfamily to subfamily levels. Protein family members are homologous (sharing common ancestry) and homeomorphic (sharing full-length sequence similarity with common domain architecture). The PIRSF database consists of two data sets, preliminary clusters and curated families. The curated families include family name, protein membership, parent-child relationship, domain architecture, and optional description and bibliography. PIRSF is accessible from the website at http://pir.georgetown.edu/pirsf/ for report retrieval and sequence classification. The report presents family annotation, membership statistics, cross-references to other databases, graphical display of domain architecture, and links to multiple sequence alignments and phylogenetic trees for curated families. PIRSF can be utilized to analyze phylogenetic profiles, to reveal functional convergence and divergence, and to identify interesting relationships between homeomorphic families, domains and structural classes.

Amino Acid Motifs↗
PubMed2001

Simian homologues of Epstein-Barr virus.

Gamma-herpesviruses closely related to the Epstein-Barr virus (EBV) are known to naturally infect Old World non-human primates and are classified in the same lymphocryptovirus (LCV) genera. LCV infecting humans and Old World primates share similar biology, and recent studies have demonstrated that these viruses share a similar repertoire of viral genes. Surprisingly, the latent infection genes associated with cell growth transformation demonstrate the most striking sequence divergence, but the functional mechanisms for these genes are generally well conserved. The recent discovery of LCVs naturally infecting New World primates has rewritten the old paradigm of LCV host range restriction to humans and Old World non-human primates, so that these viruses are more widespread than previously believed. However, the New World LCV genome has significant and interesting differences from EBV and other Old World LCVs despite similar biological properties. Thus, the simian homologues of EBV can provide an important animal model for studying LCV pathogenesis, and the similarities and differences that have evolved among these related viruses can provide a unique perspective towards a better understanding of EBV.

Animals↗
PubMed2004

Hypervariability, suppressed recombination and the genetics of individuality.

We define 'genetic individuality' as intraspecies variation that has substantial heritability and involves traits that are sufficiently common that they can be observed in any modest-sized sampling of individuals. We propose that genetic individuality is largely shaped by the combinatory shuffling of a modest number of genes, each of which exists as a family of functionally and structurally diverged alleles. Unequivocal examples of such allele families are found at the O-antigen-biosynthetic locus in Pseudomonas aeruginosa and the human leucocyte antigen locus in humans. We examine characteristic features of these allele families and explore the possibility that genetic loci with similar characteristics can be recognized in a whole-genome scan of human genetic variation.

Alleles↗
PubMed1980

The catabolism of arginine by Pseudomonas aeruginosa.

Mutants isolated from Pseudomonas aeruginosa strain PAO1632 (Hut-Ami) were unable to utilize L-arginine or L-ornithine as the carbon source for growth. Arginine deiminase (AD), catabolic ornithine carbamoyltransferase (cOTC) and N2-acetylornithine 5-aminotransferase (ACOAT) were present in the mutants but these enzymes were not induced to higher levels by exogenous L-arginine. One group of mutants could utilize L-ornithine but not L-arginine and in these strains L-arginine induced the synthesis of ACOAT but not AD or cOTC. The mutations of the arginine utilization-negative mutants were all in genes of the same transductional linkage group and mapped in the 45 to 50 min region of the chromosome. Revertants isolated on L-arginine or L-ornithine plates were derepressed for the synthesis of ACOAT. It is suggested that L-arginine is normally catabolized by the wild-type strain via the arginine deiminase pathway and requires a threshold level of ACOAT. The regulatory factors controlling the functioning of the divergent arginine deiminase and arginine carboxylase pathways are discussed.

Arginine↗
PubMed1998

Gene discovery by EST sequencing in Toxoplasma gondii reveals sequences restricted to the Apicomplexa.

To accelerate gene discovery and facilitate genetic mapping in the protozoan parasite Toxoplasma gondii, we have generated >7000 new ESTs from the 5' ends of randomly selected tachyzoite cDNAs. Comparison of the ESTs with the existing gene databases identified possible functions for more than 500 new T. gondii genes by virtue of sequence motifs shared with conserved protein families, including factors involved in transcription, translation, protein secretion, signal transduction, cytoskeleton organization, and metabolism. Despite this success in identifying new genes, more than 50% of the ESTs correspond to genes of unknown function, reflecting the divergent evolutionary status of this parasite. A newly recognized class of genes was identified based on its similarity to sequences known only from other members of the same phylum, therefore identifying sequences that are apparently restricted to the Apicomplexa. Such genes may underlie pathways common to this group of medically important parasites, therefore identifying potential targets for intervention.

Animals↗