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At least 685 records · Page 38Linked to original sources
PubMed2005

Suppression subtractive hybridization as a basis to assess Mycoplasma agalactiae and Mycoplasma bovis genomic diversity and species-specific sequences.

The phylogenically related Mycoplasma agalactiae and Mycoplasma bovis species are two ruminant pathogens difficult to differentiate and for which a limited amount of sequence data are available. To assess the degree of genomic diversity existing between and within these mycoplasma species, sets of DNA fragments specific for M. bovis type-strain PG45 or for M. agalactiae type-strain PG2 were isolated by suppression subtractive hybridization and used as probes on a panel of M. agalactiae and M. bovis field isolates. Results indicated that approximately 70 % of the DNA fragments specific to one or the other type strain are represented in all field isolates of the corresponding species. Only one M. bovis isolate, which was first classified as M. agalactiae, reacted with 15 % of the PG2-specific probes, while several M. agalactiae isolates reacted with 15 % of the PG45-specific probes. Sequence analyses indicated that most of the genomic diversity observed within one species is related to ORFs with (i) no homologies to proteins recorded in the databases or (ii) homologies to proteins encoded by restriction modification systems. Reminiscent of gene transfer as a means for genomic diversity, a PG45-specific DNA fragment with significant homologies to a central protein of an integrative conjugative element of Mycoplasma fermentans (ICEF) was found in most M. bovis field isolates and in a few M. agalactiae isolates. Finally, sequences encoding part of DNA polymerase III were found in both sets of M. agalactiae- and M. bovis-specific DNA fragments and were used to design a species-specific PCR assay for the identification and differentiation of M. agalactiae and M. bovis.

Animals↗
PubMed2006

Genomic instability due to V(D)J recombination-associated transposition.

The first step in assembling immunoglobulin and T-cell receptors by V(D)J recombination has similarities to transposon excision. The excised transposon-like element then integrates into DNA targets at random in vitro, but whether this activity significantly threatens the genomic integrity of its host has been unclear. Here, we recover examples where the putative transposon associated with V(D)J recombination integrated into the genome of a pre-B-cell line. Transposition accounted for a surprisingly high proportion (one-third) of integrations, while most of the remaining events had parallels to other aberrant V(D)J recombination pathways linked to oncogenic translocation. In total, transposition occurred approximately once every 50,000 V(D)J recombinations. Transposition may thus contribute significantly to genomic instability.

Animals↗
PubMed2001

Electron-phonon coupling spectrum in photodoped pentacene crystals.

The coupling between conduction charges and the vibrational modes of the molecular lattice plays a defining role in the transport characteristics of organic semiconductors. Using electron tunneling spectroscopy, we obtain the electron--optical-phonon coupling spectrum in photodoped pentacene crystals at energies <30 meV. Comparison of the tunneling spectrum to infrared absorption data on the optical phonon density of states yields the energy dependence of the electron-phonon scattering matrix element. The integrated spectral weight of the electron-phonon coupling shows that superconductivity in pentacene is likely of electron-phonon origin.

Journal Article↗
PubMed2004

Differentiate to thrive: lessons from the Legionella pneumophila life cycle.

When confronted by disparate environments, microbes routinely alter their physiology to tolerate or exploit local conditions. But some circumstances require more drastic remodelling of the bacterial cell, as sporulation by the Bacillus and Streptomyces species of soil bacteria vividly illustrates. Cellular differentiation is also crucial for pathogens, the challenge for which is to colonize one host, then be transmitted to the next. Using the Gram-negative Legionella pneumophila as a model intracellular pathogen, we describe how biogenesis of the replication vacuole is determined by the developmental state of the bacterium. Subsequently, when replicating bacteria have exhausted the nutrient supply, the pathogens couple their conversion to stationary phase physiology with expression of traits that promote transmission to a new host. The cellular differentiation of L. pneumophila is co-ordinated by a regulatory circuit that integrates several elements that are broadly conserved in the microbial world. The alarmone (p)ppGpp promotes transcription directed by the alternative sigma factors RpoS, FliA and, probably, RpoN, and also post-transcriptional control mediated by a two-component regulatory system, LetA/S (GacA/S), and an mRNA-binding protein, CsrA (RsmA). By applying knowledge of microbial differentiation in combination with tools to screen the complete genomes of pathogens, experiments can be designed to identify two distinct classes of virulence traits: factors that promote replication and those dedicated to transmission.

Amoeba↗
PubMed2005

A large, mobile pathogenicity island confers plant pathogenicity on Streptomyces species.

Potato scab is a globally important disease caused by polyphyletic plant pathogenic Streptomyces species. Streptomyces acidiscabies, Streptomyces scabies and Streptomyces turgidiscabies possess a conserved biosynthetic pathway for the nitrated dipeptide phytotoxin thaxtomin. These pathogens also possess the nec1 gene which encodes a necrogenic protein that is an independent virulence factor. In this article we describe a large (325-660 kb) pathogenicity island (PAI) conserved among these three plant pathogenic Streptomyces species. A partial DNA sequence of this PAI revealed the thaxtomin biosynthetic pathway, nec1, a putative tomatinase gene, and many mobile genetic elements. In addition, the PAI from S. turgidiscabies contains a plant fasciation (fas) operon homologous to and colinear with the fas operon in the plant pathogen Rhodococcus fascians. The PAI was mobilized during mating from S. turgidiscabies to the non-pathogens Streptomyces coelicolor and Streptomyces diastatochromogenes on a 660 kb DNA element and integrated site-specifically into a putative integral membrane lipid kinase. Acquisition of the PAI conferred a pathogenic phenotype on S. diastatochromogenes but not on S. coelicolor. This PAI is the first to be described in a Gram-positive plant pathogenic bacterium and is responsible for the emergence of new plant pathogenic Streptomyces species in agricultural systems.

Base Sequence↗
PubMed2006

Two distinct regions of the large serine recombinase TnpX are required for DNA binding and biological function.

The large serine recombinase, TnpX, from the Clostridium perfringens integrative mobilizable element Tn4451, consists of three domains and has two known DNA binding regions. In this study random and site-directed mutagenesis was used to identify other regions of TnpX that were required for biological activity. Genetic and biochemical analysis of these mutants led to the identification of important TnpX residues in the N-terminal catalytic pocket. In addition, another region of TnpX (aa 243-261), which is conserved within large serine recombinases, was shown to be essential for both excision and insertion. Mutation of charged residues within this region led to a loss of biological activity and aberrant DNA binding. This phenotype was mediated by interaction with the distal DNA binding region (aa 598-707). In these mutants, removal of residues 598-707 resulted in loss of DNA binding, despite the presence of the primary DNA binding region (aa 533-583). Analysis of mutations within the aa 243-261 region indicated that different protein conformations were involved in the insertion and the excision reactions. In summary, we have shown that TnpX is a complex protein that has multiple intra- and intermolecular interaction sites, providing insight into the structural and functional complexity of this important enzyme family.

Amino Acid Sequence↗
PubMed2005

Central coherence in typically developing preschoolers: does it cohere and does it relate to mindreading and executive control?

BACKGROUND: Frith and Happé (1994) describe central coherence (CC) as the normal tendency to integrate individual elements into a coherent whole, a cognitive style which varies in the general population. Individuals with autism are at the extreme (weak) end of the continuum of coherence. There has been debate over whether CC is independent from other psychological functions such as theory of mind and executive control. METHODS: We examined the validity of the CC construct in 76 typically developing 4- and 5-year-old children using four visuospatial coherence tasks. We also investigated the extent to which individual differences in performance on CC measures were associated with individual differences on measures of mindreading and executive functioning (EF). RESULTS: Unexpectedly, the CC variables were not highly intercorrelated and did not form a single coherence factor. Instead, the results revealed a two-factor structure, one of which corresponded to visuospatial constructional ability. Correlations between the emerging factors of coherence and mindreading ability were weak, even when developmental differences in age and verbal and nonverbal ability were taken into account. In contrast, visuospatial constructional ability was reliably related to measures of EF, whilst correlations between EF and the second CC factor were very weak. CONCLUSIONS: CC in typically developing preschoolers is not a unitary construct. Whilst there is little relationship between CC and mindreading abilities in these young children, executive control appears to be associated with one aspect of coherence: visuospatial construction.

Child Development↗
PubMed2006

Biomechanical behavior of muscle-tendon complex during dynamic human movements.

This paper reviews the research findings regarding the force and length changes of the muscle-tendon complex during dynamic human movements, especially those using ultrasonography and computer simulation. The use of ultrasonography demonstrated that the tendinous structures of the muscle-tendon complex are compliant enough to influence the biomechanical behavior (length change, shortening velocity, and so on) of fascicles substantially. It was discussed that the fascicles are a force generator rather than a work generator; the tendinous structures function not only as an energy re-distributor but also as a power amplifier, and the interaction between fascicles and tendinous structures is essential for generating higher joint power outputs during the late pushoff phase in human vertical jumping. This phenomenon could be explained based on the force-length/velocity relationships of each element (contractile and series elastic elements) in the muscle-tendon complex during movements. Through computer simulation using a Hill-type muscle-tendon complex model, the benefit of making a countermovement was examined in relation to the compliance of the muscle-tendon complex and the length ratio between the contractile and series elastic elements. Also, the integral roles of the series elastic element were simulated in a cyclic human heel-raise exercise. It was suggested that the storage and reutilization of elastic energy by the tendinous structures play an important role in enhancing work output and movement efficiency in many sorts of human movements.

Biomechanical Phenomena↗
PubMed2003

Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus.

Vancomycin is usually reserved for treatment of serious infections, including those caused by multidrug-resistant Staphylococcus aureus. A clinical isolate of S. aureus with high-level resistance to vancomycin (minimal inhibitory concentration = 1024 microg/ml) was isolated in June 2002. This isolate harbored a 57.9-kilobase multiresistance conjugative plasmid within which Tn1546 (vanA) was integrated. Additional elements on the plasmid encoded resistance to trimethoprim (dfrA), beta-lactams (blaZ), aminoglycosides (aacA-aphD), and disinfectants (qacC). Genetic analyses suggest that the long-anticipated transfer of vancomycin resistance to a methicillin-resistant S. aureus occurred in vivo by interspecies transfer of Tn1546 from a co-isolate of Enterococcus faecalis.

Anti-Bacterial Agents↗
PubMed2005

A stretchable form of single-crystal silicon for high-performance electronics on rubber substrates.

We have produced a stretchable form of silicon that consists of submicrometer single-crystal elements structured into shapes with microscale, periodic, wavelike geometries. When supported by an elastomeric substrate, this "wavy" silicon can be reversibly stretched and compressed to large levels of strain without damaging the silicon. The amplitudes and periods of the waves change to accommodate these deformations, thereby avoiding substantial strains in the silicon itself. Dielectrics, patterns of dopants, electrodes, and other elements directly integrated with the silicon yield fully formed, high-performance "wavy" metal oxide semiconductor field-effect transistors, p-n diodes, and other devices for electronic circuits that can be stretched or compressed to similarly large levels of strain.

Journal Article↗
PubMed2003

A new Bacteroides conjugative transposon that carries an ermB gene.

The erythromycin resistance gene ermB has been found in a variety of gram-positive bacteria. This gene has also been found in Bacteroides species but only in six recently isolated strains; thus, the gene seems to have entered this genus only recently. One of the six Bacteroides ermB-containing isolates, WH207, could transfer ermB to Bacteroides thetaiotaomicron strain BT4001 by conjugation. WH207 was identified as a Bacteroides uniformis strain based on the sequence of its 16S rRNA gene. Results of pulsed-field gel electrophoresis experiments demonstrated that the transferring element was normally integrated into the Bacteroides chromosome. The element was estimated from pulsed-field gel data to be about 100 kb in size. Since the element appeared to be a conjugative transposon (CTn), it was designated CTnBST. CTnBST was able to mobilize coresident plasmids and the circular form of the mobilizable transposon NBU1 to Bacteroides and Escherichia coli recipients. A 13-kb segment that contained ermB was cloned and sequenced. Most of the open reading frames in this region had little similarity at the amino acid sequence level to any proteins in the sequence databases, but a 1,723-bp DNA segment that included a 950-bp segment downstream of ermB had a DNA sequence that was virtually identical to that of a segment of DNA found previously in a Clostridium perfringens strain. This finding, together with the finding that ermB is located on a CTn, supports the hypothesis that CTnBST could have entered Bacteroides from some other genus, possibly from gram-positive bacteria. Moreover, this finding supports the hypothesis that many transmissible antibiotic resistance genes in Bacteroides are carried on CTns.

Bacteroides↗
PubMed2004

Identification of operators and promoters that control SXT conjugative transfer.

Transfer of SXT, a Vibrio cholerae-derived integrating conjugative element that encodes multiple antibiotic resistance genes, is repressed by SetR, a lambda434 cI-related repressor. Here we identify divergent promoters between s086 and setR that drive expression of the regulators of SXT transfer. One transcript encodes the activators of transfer, setC and setD. The second transcript codes for SetR and, like the cI transcript of lambda, is leaderless. SetR binds to four operators located between setR and s086; the locations and relative affinities of these sites suggest a model for regulation of SXT transfer.

Base Sequence↗
PubMed1991

Overlapping retrovirus U5 sequence elements are required for efficient integration and initiation of reverse transcription.

A secondary structure in the 5' noncoding region of avian retrovirus RNA, called the U5-leader stem, was shown previously to have a role in initiation of reverse transcription (D. Cobrinik, L. Soskey, and J. Leis, J. Virol. 62:3622-3630, 1988). We now show that an additional RNA secondary structure near the U5 terminus, called the U5-IR stem, is also important for reverse transcription. Mutations that disrupt the U5-IR stem cause a replication defect associated with both a decrease in synthesis of viral DNA in infected cells and a decrease in initiation of reverse transcription in melittin-permeabilized virions. Structure-compensating base substitutions in the U5-IR restore reverse transcription efficiency. In viral DNA, U5-IR sequences are included in the U5 terminal region that functions as a viral integration donor site. When base substitutions are introduced into these sequences, a reduced efficiency of integration in vitro and in vivo is observed. These observations indicate that U5-IR sequences have a structural role in reverse transcription of viral RNA and a sequence-specific role in the integration of viral DNA.

Avian Sarcoma Viruses↗
PubMed2002

Chromosomal integration of retinoic acid response elements prevents cooperative transcriptional activation by retinoic acid receptor and retinoid X receptor.

All-trans-retinoic acid receptors (RAR) and 9-cis-retinoic acid receptors (RXR) are nuclear receptors known to cooperatively activate transcription from retinoid-regulated promoters. By comparing the transactivating properties of RAR and RXR in P19 cells using either plasmid or chromosomal reporter genes containing the mRAR beta 2 gene promoter, we found contrasting patterns of transcriptional regulation in each setting. Cooperativity between RXR and RAR occurred at all times with transiently introduced promoters, but was restricted to a very early stage (<3 h) for chromosomal promoters. This time-dependent loss of cooperativity was specific for chromosomal templates containing two copies of a retinoid-responsive element (RARE) and was not influenced by the spacing between the two RAREs. This loss of cooperativity suggested a delayed acquisition of RAR full transcriptional competence because (i) cooperativity was maintained at RAR ligand subsaturating concentrations, (ii) overexpression of SRC-1 led to loss of cooperativity and even to strong repression of chromosomal templates activity, and (iii) loss of cooperativity was observed when additional cis-acting response elements were activated. Surprisingly, histone deacetylase inhibitors counteracted this loss of cooperativity by repressing partially RAR-mediated activation of chromosomal promoters. Loss of cooperativity was not correlated to local histone hyperacetylation or to alteration of constitutive RNA polymerase II (RNAP) loading at the promoter region. Unexpectedly, RNAP binding to transcribed regions was correlated to the RAR activation state as well as to acetylation levels of histones H3 and H4, suggesting that RAR acts at the mRAR beta promoter by triggering the switch from an RNA elongation-incompetent RNAP form towards an RNA elongation-competent RNAP.

Acetylation↗
PubMed2006

Mechanotransduction involving multimodular proteins: converting force into biochemical signals.

Cells can sense and transduce a broad range of mechanical forces into distinct sets of biochemical signals that ultimately regulate cellular processes, including adhesion, proliferation, differentiation, and apoptosis. Deciphering at the nanoscale the design principles by which sensory elements are integrated into structural protein motifs whose conformations can be switched mechanically is crucial to understand the process of transduction of force into biochemical signals that are then integrated to regulate mechanoresponsive pathways. While the major focus in the search for mechanosensory units has been on membrane proteins such as ion channels, integrins, and associated cytoplasmic complexes, a multimodular design of tandem repeats of various structural motifs is ubiquitously found among extracellular matrix proteins, as well as cell adhesion molecules, and among many intracellular players that physically link transmembrane proteins to the contractile cytoskeleton. Single-molecule studies have revealed an unexpected richness of mechanosensory motifs, including force-regulated conformational changes of loop-exposed molecular recognition sites, intermediate states in the unraveling pathway that might either expose cryptic binding or phosphorylation sites, or regions that display enzymatic activity only when unmasked by force. Insights into mechanochemical signal conversion principles will also affect various technological fields, from biotechnology to tissue engineering and drug development.

Animals↗
PubMed2004

Imbalance of glial-neuronal interaction in synapses: a possible mechanism of the pathophysiology of bipolar disorder.

There is a wave of new information suggesting that glia, especially astrocytes, are intimately involved in the active control of neuronal activity and synaptic transmission. Synaptically associated astrocytes should be viewed as integral modulatory elements of tripartite synapses consisting of the presynapse, the postsynapse, and the glial element (astrocytes). Smit and coworkers proposed a model of a cholinergic tripartite synapse based on the identification of a glial-derived binding protein (BP) that is secreted into the synapse and binds free acetylcholine (ACh), thus reducing the levels of ACh available for stimulating the postsynapse. Here the author proposes an explanatory model of the pathophysiology of bipolar disorder focusing on the possible dynamics in cholinergic tripartite synapses. The hypothesis is that an imbalance between neurotransmitters and glial BPs in the synaptic cleft is determined by glia. If glial BPs are overexpressed, synaptic transmission is suppressed because of reduced levels of bioavailable neurotransmitters. This state could cause a depression on the behavioral level. In contrast, if glial BPs are underexpressed, the excess of neurotransmitters in the cleft leads to an overbalanced state of synaptic information transmission. This state could cause manic behavior. Under certain conditions, underbalanced and overbalanced synapses at different locations in the same brain could disturb brain function in parallel causing a mixed episode of bipolar disorder. If glial BPs and mutations in genes expressing glial BPs in the various synapses of the brain are identified, this hypothesis can be experimentally tested.

Bipolar Disorder↗
PubMed2005

Nonfunctional glial proteins in tripartite synapses: a pathophysiological model of schizophrenia.

A model for the pathophysiology of schizophrenia is proposed that focuses on an unbalance of transmission in tripartite synapses. Synaptically associated astrocytes should be viewed as integral modulatory elements of tripartite synapses consisting of the presynapse, the postsynapse, and the glial element. Astrocytes may secrete glial binding protein into the synaptic cleft, thus binding free neurotransmitters and thereby reducing the levels of neurotransmitters available for stimulating the postsynapse. Astrocytes also have membrane-bound receptors for neurotransmitters, and when these bind neurotransmitters, the astrocytes upregulate the amount of binding protein secreted into the synapse, resulting in a negative feedback to the presynaptic terminal. The hypothesis presented here is that glia lose their negative feedback function due to loss of function mutations in the genes encoding the binding proteins and glial receptors. The mutations generate proteins that cannot be occupied by their cognate substances of the neuronal system, primarily neurotransmitters. Therefore, the glial-neuronal interaction in tripartite synapses affected becomes totally unbalanced, and the glia lose their inhibitory or boundary-setting function. As a result, neural flux is unconstrained by normal glial boundaries, also the flux of thought on the phenomenological level. Schizophrenia may be caused by the inability to delimit conceptual boundaries.

Animals↗