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Biomedical subjects

N L Williams

Publications and source records attributed to N L Williams.

12 recordsLinked to original sources
PubMed2001

Locking the ATP-operated clamp of DNA gyrase: probing the mechanism of strand passage.

DNA gyrase catalyses DNA supercoiling by passing one segment of DNA (the T segment) through another (the G segment) in a reaction coupled to the binding and hydrolysis of ATP. The N-terminal domains of the gyrase B dimer constitute an ATP-operated clamp that is proposed to capture the T segment during the DNA supercoiling reaction. We have locked this clamp in the closed conformation using the non-hydrolysable ATP analogue ADPNP (5'-adenylyl beta,gamma-imidodiphosphate). The clamp-locked enzyme is able to bind and cleave DNA, albeit at a reduced level. Although the locked enzyme is not capable of carrying out DNA supercoiling, it can catalyse limited DNA relaxation, consistent with the ability to complete one strand passage event per enzyme molecule via entry of the T segment through the exit gate of the enzyme. The DNA-protein complex of the clamp-locked enzyme has a conformation that differs from the normal positively wrapped conformation of the gyrase-DNA complex. These experiments confirm the role of the ATP-operated clamp in the strand-passage reactions of gyrase and suggest a model for the interaction of DNA with gyrase in which a conformation with the T segment in equilibrium across the DNA gate can be achieved via T-segment entry through the ATP-operated clamp or through the exit gate.

Adenosine Triphosphate↗
PubMed2000

The looming maladaptive style: anxiety, danger, and schematic processing.

The importance of cognitive styles as psychological antecedents of psychopathology has gained increasing acceptance over the past 2 decades. Although ample research has explored cognitive styles that confer vulnerability to depression, cognitive styles that confer vulnerability to anxiety have received considerably less attention. In the present investigation, we examined the looming maladaptive style (LMS) as a cognitive style that functions as a danger schema to produce specific vulnerability to anxiety, but not to depression. In 4 studies, we examined the psychometric properties of a revised measure of the LMS, its predictive utility, and its effects on threat-related schematic processing. Results provided evidence for the validity of the LMS and indicated that it predicts anxiety and schematic processing of threat over and above the effects of other cognitive appraisals of threat, even in individuals who are currently nonanxious.

Adaptation, Psychological↗
PubMed2000

Temperature-sensitive suppressor mutations of the Escherichia coli DNA gyrase B protein.

Escherichia coli strain LE316 contains a mutation in gyrB that results in the substitution of Val164 to Gly and confers both chlorobiocin resistance and temperature sensitivity. Selection for suppressors of the ts phenotype yielded second-site mutations in GyrB at His38 and Thr157. The properties of proteins bearing these mutations have been characterized, and a mechanism of suppression is proposed based upon structural considerations.

Antibiotics, Antineoplastic↗
PubMed1999

Locking the DNA gate of DNA gyrase: investigating the effects on DNA cleavage and ATP hydrolysis.

Supercoiling by DNA gyrase involves the passage of one segment of double-stranded DNA through another. This requires a DNA duplex to be cleaved and the broken ends separated by at least 20 A. This is accomplished by the opening of a dimer interface, termed the DNA gate, which is covalently attached to the broken ends of the DNA. After strand passage, the DNA gate closes allowing the reunion of the broken ends. We have cross-linked the DNA gate of gyrase using cysteine cross-linking to block gate opening. We show that this locked gate mutant can bind quinolone drugs and perform DNA cleavage. However, locking the DNA gate prevents strand passage and the ability of DNA to stimulate ATP hydrolysis. We discuss the mechanistic implications of these results.

Adenosine Triphosphate↗
PubMed1999

Probing the two-gate mechanism of DNA gyrase using cysteine cross-linking.

Cross-linking a pair of novel cysteine residues on either side of the bottom dimer interface of DNA gyrase blocks catalytic supercoiling. Limited strand passage is allowed, but release of the transported DNA segment (T segment) via opening of the bottom dimer interface is prevented. In contrast, ATP-independent relaxation of negatively supercoiled DNA is completely abolished, suggesting that T-segment entry via the bottom gate is blocked. These findings support a two-gate model for supercoiling by DNA gyrase and suggest that relaxation by gyrase is the reverse of supercoiling. Cross-linking a truncated version of gyrase (A64(2)B2), which lacks the DNA wrapping domains, does not block ATP-dependent relaxation. This indicates that passage of DNA through the bottom dimer interface is not essential for this reaction. The mechanistic implications of these results are discussed.

Adenosine Triphosphate↗
PubMed1981

Treatment of stress urinary incontinence due to paravaginal fascial defect.

This study supports the thesis that the physical findings of pelvic relaxation, such as cystourethrocele, are the results of isolated defects in the pelvic fascia rather than the results of generalized stretching or attenuation of the supporting structures. The most frequently encountered defect resulting in cystourethrocele with stress urinary incontinence was a paravaginal break in the pubocervical segment of the endopelvic fascia between the lateral edge of the vagina and the pelvic sidewall. The operative approach to this paravaginal defect is described. The overall results in 233 procedures performed by 2 separate groups are analyzed. Functionally satisfactory results were obtained in over 95% of patients with 2 to 8 years of follow-up. The use of an indwelling urethral catheter was found to be unnecessary, and all patients experienced a rapid return of normal bladder function. The average length of the postoperative hospital stay was 5 days.

Fascia↗
PubMed1976

A new look at pelvic relaxation.

The concept is presented that most cystoceles and/or urethroceles result from insolated defects in the connective tissue supports of the anterior quadrant of the pelvis. Four areas in which defects have been found to occur are identified. Sixty patients are presented who were found to have isolated defects in the endopelvic fascia at the lateral sidewall of the pelvis with significant cystourethroceles and stress urinary incontinence. The surgical treatment consisted only of a direct approach to and closure of the isolated defect. The operative results at 3 to 48 months were excellent in 91.7 per cent, improved in 5 per cent, and failed in 3.3 per cent. Discussion is offered of the possibility of the study of the pelvic floor from the viewpoint of a mechanical engineer.

Female↗
PubMed1976

Decreasing postpartum sexual abstinence time.

Postpartum sexual abstinence time can be safely shortened for most patients when episiotomy repair is done meticulously with fine PGA suture on small needles. The time preferred by patients for resumption of intercourse seems to be between the second and third postpartum week. We have seen no ill effects from this, and we feel that sexual intercourse at these early dates does not influence the healing of the episiotomy in any way.

Episiotomy↗