Effects of localized bending on DNA supercoiling.

The DNA double helix is straight only in the idealized case. In reality, it bends, twists and stretches in response to local base sequence and to specific interactions with proteins and other bound ligands. Naturally occurring bends appear to promote the assembly of nucleosomes, and in some cases can effectively replace regulatory DNA-binding proteins in vivo. Recently, a computational method known as 'finite element analysis', which is used routinely by engineers to analyse the stability of buildings and bridges, has been applied to the quantitative assessment of natural curvature in supercoiled DNA structures, providing new insight into the relationship between local, sequence-dependent features and the overall topology of these chains.

Flexing and folding double helical DNA.

DNA base sequence, once thought to be interesting only as a carrier of the genetic blueprint, is now recognized as playing a structural role in modulating the biological activity of genes. Primary sequences of nucleic acid bases describe real three-dimensional structures with properties reflecting those structures. Moreover, the structures are base sequence dependent with individual residues adopting characteristic spatial forms. As a consequence, the double helix can fold into tertiary arrangements, although the deformation is much more gradual and spread over a larger molecular scale than in proteins. As part of an effort to understand how local structural irregularities are translated at the macromolecular level in DNA and recognized by proteins, a series of calculations probing the structure and properties of the double helix have been performed. By combining several computational techniques, complementary information as well as a series of built-in checks and balances for assessing the significance of the findings are obtained. The known sequence dependent bending, twisting, and translation of simple dimeric fragments have been incorporated into computer models of long open DNAs of varying length and chemical composition as well as in closed double helical circles and loops. The extent to which the double helix can be forced to bend and twist is monitored with newly parameterized base sequence dependent elastic energy potentials based on the observed configurations of adjacent base pairs in the B-DNA crystallographic literature.

A survey of job satisfaction, sources of stress and psychological symptoms among New Zealand health professionals.

AIM: To assess job satisfaction, job-related stress and psychological morbidity among New Zealand physicians, surgeons and community pharmacists and provide a comparison with New Zealand general practitioners (GPs). METHODS: 411 physicians, 330 surgeons and 400 randomly sampled community pharmacists, were surveyed. Psychological morbidity was assessed by the General Health Questionnaire (GHQ-12) and job satisfaction by the Warr Cook Wall scale. RESULTS: Response rates were 70.5% for physicians, 69% for surgeons and 76% for community pharmacists. Job satisfaction scores for surgeons were similar to scores for GPs. Pharmacist and physicians scores were lower. Job satisfaction varied according to gender, the relative amount of time spent in public practice and the perceived ill effects of work on health. Pharmacists had the highest number of cases with significant scores on the GHQ-12 scale, with physicians and surgeons scoring similar to GPs. In each of these health professional groups approximately 10% described a level of symptoms that is associated with more severe psychological disturbance. CONCLUSIONS: All three groups were generally satisfied with their jobs. Pharmacists were significantly less so. Physicians and surgeons reported similar levels of psychological morbidity to GPs, which have been previously reported as a cause for concern.

Several variables of importance in the use of the cold pressor as a noxious stimulus in behavioral research.

To examine the effects of subject's sex, hand dominance, and spatial summation on cold pressor tolerance and discomfort, 80 subjects were randomly assigned to one of eight conditions using a 2 x 2 x 2 design. Analysis showed that females immersing the hand tolerated the stimulus significantly less time than males immersing the hand, females immersing the finger, or males immersing the finger. Female subjects reported significantly more pain than males, and subjects who immersed the hand reported significantly more pain than subjects who immersed the finger only. Implications are discussed.

Implant-supported facial prostheses provided by a maxillofacial unit in a U.K. regional hospital: longevity and patient opinions.

PURPOSE: The aim of this study was to acquire information on the types and longevity of implant-retained facial prostheses and the opinions of patients on several factors related to their prostheses. MATERIALS AND METHODS: A survey of 75 maxillofacial prosthetic patients currently under treatment and review at the Maxillofacial Unit, Morriston Regional Hospital was conducted through a 23-question postal questionnaire. These patients were selected as representative of a group of individuals receiving treatment or under review for the fabrication of maxillofacial prostheses. RESULTS: Of the prosthetic replacements, 83% were ear prostheses, 8% nose, 6% eye, and 2% combination prostheses. Of the 47 respondents, 8 (17%) reported that they were currently wearing their original prostheses. The remaining 39 (83%) respondents had all been provided with at least 1 replacement prosthesis. The mean lifetime of the prostheses was found to be 14 months (range: 4-36 months). The majority of replacement prostheses in this study were provided as a result of color fade or wear of the silicone material of the previous prosthesis. Individuals with no previous experience wearing a prosthesis had an unrealistic expectation of their prosthesis longevity, with a mean value of 17.8 months. In comparison, individuals with previous experience had reduced expectations, with a mean of 14.4 months. In terms of the patients' opinions of the overall quality of their prostheses, the results demonstrated that a large number of patients were satisfied. Thirty-five patients rated their prostheses as excellent and 9 as good. At 7-12 months, 4 patients rated their prostheses as excellent and 8 as good. At 13 months, 4 patients rated their prostheses as excellent and 5 as good. CONCLUSIONS: It is important that advice be given to patients on the expected average longevity of their prostheses, together with information on factors affecting the longevity (i.e., environmental staining, cosmetics, and cleaning regimes). In this study, 26% of the replacement prostheses were provided due to color fading of the original prosthesis. This highlights the need for continuing research in the development of materials used for the construction of facial prostheses with improved properties, and in particular, improved color stability.

On higher buckling transitions in supercoiled DNA.

A combination of detailed energy minimization and molecular dynamics studies of closed circular DNA offers here new information that may be relevant to the dynamics of short DNA chains and/or low superhelical densities. We find a complex dependence of supercoiled DNA energies and geometries on the linking number difference delta Lk as physiological superhelical densities (magnitude of sigma approximately 0.06) are approached. The energy minimization results confirm and extend predictions of classical elasticity theory for the equilibria of elastic rods. The molecular dynamics results suggest how these findings may affect the dynamics of supercoiled DNA. The minimization reveals sudden higher order configurational transitions in addition to the well-known catastrophic buckling from the circle to the figure-8. The competition among the bending, twisting, and self-contact forces leads to different families of supercoiled forms. Some of those families begin with configurations of near-zero twist. This offers the intriguing possibility that nicked DNA may relax to low-twist forms other than the circle, as generally assumed. Furthermore, for certain values of delta Lk, more than one interwound DNA minimum exists. The writhing number as a function of delta Lk is discontinuous in some ranges; it exhibits pronounced jumps as delta Lk is increased from zero, and it appears to level off to a characteristic slope only at higher values of delta Lk. These findings suggest that supercoiled DNA may undergo systematic rapid interconversions between different minima that are both close in energy and geometry. Our molecular dynamics simulations reveal such transitional behavior. We observe the macroscopic bending and twisting fluctuations of interwound forms about the global helix axis as well as the end-over-end tumbling of the DNA as a rigid body. The overall mobility can be related to magnitude of sigma and to the bending, twisting, and van der Waals energy fluctuations. The general character of molecular motions is thus determined by the types of energy minima found at a given delta Lk. Different time scales may be attributed to each type of motion: The overall chain folding occurs on a time scale almost an order of magnitude faster than the end-over-end tumbling. The local bending and twisting of individual chain residues occur at an even faster rate, which in turn correspond to several cycles of local variations for each large-scale bending and straightening motion of the DNA.