Search PubMed⌕ Search

Biomedical subjects

G Webster

Publications and source records attributed to G Webster.

At least 19 recordsLinked to original sources
PubMed2006

Bacterial community structure, compartmentalization and activity in a microbial fuel cell.

AIMS: To characterize bacterial populations and their activities within a microbial fuel cell (MFC), using cultivation-independent and cultivation approaches. METHODS AND RESULTS: Electron microscopic observations showed that the fuel cell electrode had a microbial biofilm attached to its surface with loosely associated microbial clumps. Bacterial 16S rRNA gene libraries were constructed and analysed from each of four compartments within the fuel cell: the planktonic community; the membrane biofilm; bacterial clumps (BC) and the anode biofilm. Results showed that the bacterial community structure varied significantly between these compartments. It was observed that Gammaproteobacteria phylotypes were present at higher numbers within libraries from the BC and electrode biofilm compared with other parts of the fuel cell. Community structure of the MFC determined by analyses of bacterial 16S rRNA gene libraries and anaerobic cultivation showed excellent agreement with community profiles from denaturing gradient gel electrophoresis (DGGE) analysis. CONCLUSIONS: Members of the family Enterobacteriaceae, such as Klebsiella sp. and Enterobacter sp. and other Gammaproteobacteria with Fe(III)-reducing and electrochemical activity had a significant potential for energy generation in this system. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has shown that electrochemically active bacteria can be enriched using an electrochemical fuel cell.

Anaerobiosis↗
PubMed2004

Non-payment.

Explore the source record for details and available documents.

Dentists↗
PubMed2003

Diversity of bacteria associated with natural aphid populations.

The bacterial communities of aphids were investigated by terminal restriction fragment length polymorphism and denaturing gradient gel electrophoresis analysis of 16S rRNA gene fragments generated by PCR with general eubacterial primers. By both methods, the gamma-proteobacterium Buchnera was detected in laboratory cultures of six parthenogenetic lines of the pea aphid Acyrthosiphon pisum and one line of the black bean aphid Aphis fabae, and one or more of four previously described bacterial taxa were also detected in all aphid lines except one of A. pisum. These latter bacteria, collectively known as secondary symbionts or accessory bacteria, comprised three taxa of gamma-proteobacteria (R-type [PASS], T-type [PABS], and U-type [PAUS]) and a rickettsia (S-type [PAR]). Complementary analysis of aphids from natural populations of four aphid species (A. pisum [n = 74], Amphorophora rubi [n = 109], Aphis sarothamni [n = 42], and Microlophium carnosum [n = 101]) from a single geographical location revealed Buchnera and up to three taxa of accessory bacteria, but no other bacterial taxa, in each aphid. The prevalence of accessory bacterial taxa varied significantly among aphid species but not with the sampling month (between June and August 2000). These results indicate that the accessory bacterial taxa are distributed across multiple aphid species, although with variable prevalence, and that laboratory culture does not generally result in a shift in the bacterial community in aphids. Both the transmission patterns of the accessory bacteria between individual aphids and their impact on aphid fitness are suggested to influence the prevalence of accessory bacterial taxa in natural aphid populations.

Animals↗
PubMed2001

Crystal structure of the PDZ1 domain of human Na(+)/H(+) exchanger regulatory factor provides insights into the mechanism of carboxyl-terminal leucine recognition by class I PDZ domains.

The Na(+)/H(+) exchanger regulatory factor (NHERF; also known as EBP50) contains two PDZ domains that mediate the assembly of transmembrane and cytosolic proteins into functional signal transduction complexes. The NHERF PDZ1 domain interacts specifically with the motifs DSLL, DSFL, and DTRL present at the carboxyl termini of the beta(2) adrenergic receptor (beta(2)AR), the platelet-derived growth factor receptor (PDGFR), and the cystic fibrosis transmembrane conductance regulator (CFTR), respectively, and plays a central role in the physiological regulation of these proteins. The crystal structure of the human NHERF PDZ1 has been determined at 1.5 A resolution using multiwavelength anomalous diffraction phasing. The overall structure is similar to known PDZ structures, with notable differences in the NHERF PDZ1 carboxylate-binding loop that contains the GYGF motif, and the variable loop between the beta2 and beta3 strands. In the crystalline state, the carboxyl-terminal sequence DEQL of PDZ1 occupies the peptide-binding pocket of a neighboring PDZ1 molecule related by 2-fold crystallographic symmetry. This structure reveals the molecular mechanism of carboxyl-terminal leucine recognition by class I PDZ domains, and provides insights into the specificity of NHERF interaction with the carboxyl termini of several membrane receptors and ion channels, including the beta(2)AR, PDGFR, and CFTR.

Amino Acid Motifs↗
PubMed2001

An evolutionary computational approach to the phase problem in macromolecular X-ray crystallography.

The ab initio computation of the molecular envelopes of two proteins exclusively from their corresponding diffraction amplitudes demonstrates that an efficient and inherently parallel evolutionary search algorithm can assist in the direct phasing of macromolecules for which almost no a priori structural information is available. The applicability of this evolutionary computational approach is general and should not be limited to the examples described nor to extremes of data resolution, symmetry or structural size.

Algorithms↗
PubMed2001

Crystallographic characterization of the PDZ1 domain of the human Na+/H+ exchanger regulatory factor.

The Na(+)/H(+) exchanger regulatory factor (NHERF) contains two PDZ domains that mediate the assembly of transmembrane and cytosolic proteins into functional signal transduction complexes. The human NHERF PDZ1 domain, which spans residues 11-99, interacts specifically with carboxy-terminal residues of the beta2 adrenergic receptor and the cystic fibrosis transmembrane conductance regulator. The NHERF PDZ1 was expressed in Escherichia coli as a soluble protein, purified and crystallized in the unbound form using the vapor-diffusion method with 2 M ammonium sulfate as the precipitant. Diffraction data were collected to 1.5 A resolution using synchrotron radiation. The crystals belong to space group P3(1)21 or P3(2)21, with unit-cell parameters a = b = 51.6, c = 58.9 A, and one molecule in the asymmetric unit.

Crystallography, X-Ray↗
PubMed2001

Quantity and quality of virus-specific CD8 cell response: relevance to the design of a therapeutic vaccine for chronic HBV infection.

Chronic hepatitis B virus (HBV) infection is a major cause of morbidity and mortality worldwide, yet currently available therapies fail to provide long-term control of viral replication in most patients. Strategies to boost the weak virus-specific T-cell response typically found in patients with chronic hepatitis B have been proposed as a means of terminating persistent HBV infection. The potential problems arising from the stimulation of virus-specific immunity in a disease caused by a non-cytopathic virus, where viral control and liver injury are mediated by the immune system, are discussed. Furthermore, the concept of augmenting the HBV-specific T-cell response, which has previously been focused solely on quantitative issues, is expanded in the light of new findings of qualitative differences in the HBV-specific CD8 cell response.

CD8-Positive T-Lymphocytes↗
PubMed2000

Aspartyl tRNA-synthetase from Escherichia coli: flexibility and adaptability to the substrates.

The crystal structure of aspartyl-tRNA synthetase from Escherichia coli has been determined to a resolution of 2.7 A. The structure is compared to the same enzyme co-crystallized with tRNA(Asp) and containing aspartyl adenylate or ATP. The asymmetric unit contains three monomers of the enzyme. While most parts of the protein show no significant differences in the three monomers, a few regions cannot be superimposed. Those regions are characterized by a high B-factor, and consist mostly of loops that make contacts with the tRNA in the complexes. The flexibility of the protein is seen at a global level, by the observation of a 10 to 15 degrees rotation of the N-terminal and insertion domains upon tRNA binding, and at the level of the individual amino acid residues, by main-chain and side-chain rearrangements. In contrast to these induced-fit conformational changes, a few residues essential for the tRNA anticodon or aspartyl-adenylate recognition exist in a predefined conformation, ensured by specific interactions within the protein.

Adenosine Monophosphate↗
PubMed2000

An intermediate step in the recognition of tRNA(Asp) by aspartyl-tRNA synthetase.

The crystal structures of aspartyl-tRNA synthetase (AspRS) from Thermus thermophilus, a prokaryotic class IIb enzyme, complexed with tRNA(Asp) from either T. thermophilus or Escherichia coli reveal a potential intermediate of the recognition process. The tRNA is positioned on the enzyme such that it cannot be aminoacylated but adopts an overall conformation similar to that observed in active complexes. While the anticodon loop binds to the N-terminal domain of the enzyme in a manner similar to that of the related active complexes, its aminoacyl acceptor arm remains at the entrance of the active site, stabilized in its intermediate conformational state by non-specific interactions with the insertion and catalytic domains. The thermophilic nature of the enzyme, which manifests itself in a very low kinetic efficiency at 17 degrees C, the temperature at which the crystals were grown, is in agreement with the relative stability of this non-productive conformational state. Based on these data, a pathway for tRNA binding and recognition is proposed.

Anticodon↗
PubMed2000

HCV genotypes--role in pathogenesis of disease and response to therapy.

Hepatitis C virus (HCV) shows considerable variation in its genomic structure, allowing classification into six main genotypes. Epidemiological studies have shown marked differences in genotype distribution by geographical region, and between patient groups. Improved understanding of the rate of nucleotide sequence mutation in HCV has allowed the approximate time of divergence of major genotypes to be estimated, and the origin and spread of the present epidemic of hepatitis C to be better defined. Improved methods of genotype definition over the last few years have enabled the importance of genotype in the progression of HCV-related disease and response to anti-viral therapy to be studied. Present data strongly indicates that HCV genotype is an important determinant of response to treatment, but the effect of genotype on disease progression has been harder to clarify. This is largely due to the absence of model systems of HCV infection, the epidemiological differences in patient groups infected with the different genotypes, and the lack of good prospective longitudinal clinical data. As a result of advances in methodology, and recent results of large clinical trials of combination therapy, a knowledge of HCV genotype is now central to the clinician in the management of patients with chronic hepatitis C.

Antiviral Agents↗
PubMed2000

Combination azelaic acid therapy for acne vulgaris.

There is no topical antiacne medication that acts against all four of the major pathophysiologic features of acne: hyperkeratinization, sebum production, bacterial proliferation, and inflammation. Topical azelaic acid cream helps both to normalize keratinization and to reduce the proliferation of Propionibacterium acnes, and has proven to be effective against both noninflammatory and inflammatory lesions. The results of a recent study now demonstrate that its efficacy can be enhanced, and patient ratings of overall impression improved, when it is used in combination with other topical medications such as benzoyl peroxide 4% gel, clindamycin 1% gel, tretinoin 0.025% cream, and erythromycin 3%/benzoyl peroxide 5% gel. Furthermore, another study has shown that azelaic acid plus benzoyl peroxide achieves greater efficacy and higher patient ratings of convenience than monotherapy with erythromycin-benzoyl peroxide gel.

Acne Vulgaris↗
PubMed2000

Crystallization and structure determination of the catalytic trimer of Methanococcus jannaschii aspartate transcarbamoylase.

Aspartate transcarbamoylase (ATCase) catalyzes the first step in the pyrimidine biosynthetic pathway, the reaction between carbamoyl phosphate and L-aspartate to form N-carbamoyl-L-aspartate and phosphate. The structural analysis of the ATCase catalytic trimer from Methanococcus jannaschii, a unicellular thermophilic archaeabacterium, has been undertaken in order to gain insight into the structural features that are responsible for the thermostability of the enzyme. As a first step, the catalytic trimer was crystallized in space group R32, with unit-cell parameters a = b = 265.3, c = 195.5 A and two trimers in the asymmetric unit. Its structure was determined using molecular replacement and Patterson methods. In general, structures containing multiple copies of molecules in the asymmetric unit are difficult to determine. In this case, the two trimers in the asymmetric unit are parallel to each other and use of the Patterson function greatly simplified the structure solution.

Aspartate Carbamoyltransferase↗
PubMed1999

Long-term efficacy of treatment of chronic hepatitis C with alpha interferon or alpha interferon and ribavirin.

The major objective of treatment of chronic hepatitis C virus (HCV) infection is to prevent progression to cirrhosis, and thereby prevent complications of end-stage liver disease. The established treatment of chronic HCV is with alpha interferon. Recent results with ribavirin and alpha interferon together suggest that combination antiviral therapy will become the benchmark treatment. For both naive and relapsed patients, however, it has become important to assess the long-term outcome of treatment, in order to gauge whether treatment has indeed modified the natural history of chronic hepatitis C virus infection. It seems likely that most sustained responders (85-90%) treated with combination ribavirin and alpha interferon will continue to have a long-term biochemical and virological response, as has been demonstrated with alpha interferon alone, but further long-term follow-up of patients treated with combination therapy is required.

Antiviral Agents↗