Tensile fatigue behaviour of articular cartilage

Although fatigue has been implicated in cartilage failure there are only two studies by the same author, and in both of which cartilage was tested in the direction parallel to the collagen orientation in the surface layer. In the present work articular cartilage was tested also along the perpendicular direction, being the direction in which cartilage possesses lower tensile strength.Specimens were tested under cyclic tensile load. Number of cycles at failure was recorded as well as elongation of the specimen. To date 72 specimens have been tested all from one knee joint.The number of cycles to failure ranged between two and 1.5 million. The surface and deep layers have better fatigue properties whether tested in the parallel or the perpendicular direction, while the middle layer was far weaker. Better fatigue behaviour was observed with specimens tested in parallel than in perpendicular direction to the fibres.     

Mechanisms controlling the integrity of replicating chromosomes in budding yeast

Cells are continually challenged by genomic insults that originate from chemical and physical agents diffused in the environment, but also normal cellular metabolism produces genotoxic effects. Moreover, DNA replication and recombination generate intermediates potentially dangerous for genome stability. Growing evidence show that many genetic disorders are characterized by high levels of chromosome alterations due to genomic instability, which is also a hallmark of cancer cells. Recent work shed some light on the molecular events that maintain the integrity of chromosomes during unperturbed S phase and in the face of odds.     

Anorexia nervosa and refusal of naso-gastric treatment: a response to Heather Draper

Imposing artificial feeding on people with anorexia nervosa may be unethical. This seems to be Heather Draper's suggestion in her article, 'Anorexia Nervosa and Respecting a Refusal of Life-Prolonging Therapy: A Limited Justification.' Although this is an important point, I shall show that the arguments supporting this point are flawed. Draper should have made a brave claim: she should have claimed that people with anorexia nervosa, who competently decide not to be artificially fed, should be respected because everybody is entitled to exercise their autonomy, not only 'in the middle' of their life, but also at the end of it, or when their own life is at stake, because autonomy also extends to the most difficult moments of our life, and, ultimately, 'stretches [.*T*.*T*.] far out into the distance' at the end of it. I explain why Draper should have made the brave claim, and why she has not made it. I conclude that a defence of people's entitlement to competently refuse artificial feeding cannot rest upon the arguments developed by Draper. Whether or not we should respect competent refusal of artificial feeding depends on the normative strength that we are ready to ascribe to the principle of autonomy, to the moral relevance that we ascribe to the circumstances in which a person's autonomy is exercised, and, perhaps, eventually, on our sense of compassion.     

γ-Ray footprinting and fluorescence polarization anisotropy of a 30-mer synthetic DNA fragment with one 2′-deoxy-7-hydro-8- oxoguanosine lesion

The influence of the oxidative lesion 2'-deoxy-7-hydro-8-oxoguanosine (8-oxodG) on some conformational properties of DNA has been studied. Four 30-mer duplexes of the form [5'-GATCCTCTAGAGTC[G(*) or G]ACCTGCAGGCATGCA-3']:[3'-CTAGGAGATCTCAG[C or A]TGGACGTCCGTACGT-5'], in which G(*) is the 8-oxodG lesion, were synthesized in order to compare the effect of the GA mismatch and of the damaged G(*)C and G(*)A forms with the normal GC. Spectroscopic measurements performed by means of UV denaturation and circular dichroism experiments do not show gross changes of stability and overall structure in the damaged and mismatched samples. The control DNA and the samples containing GA mismatch show very similar gamma-rays cutting patterns, indicating that the introduction of the GA mismatch does not perturb the phosphate backbone geometry. In the samples containing the 8-oxodG there are some variations of the cleavage pattern near G(*) which are extended for almost one helical turn. Some differences are observed between G(*)C and G(*)A duplexes. In particular, in the G(*)C sample the reduced accessibility to OH radicals at the G15 site, observed in the control, spreads on the intrastrand adjacent bases and in the G(*)A sample a shift of the minimum is observed. The hydrodynamic radius R(h) derived by fluorescence polarization anisotropy decay exhibits a constant value of 11.4 +/- 0.2 A between 5 and 40 degrees C, in all the samples. The torsional constant alpha of each oligomer decreases when the temperature is raised and the alpha values of the damaged samples are higher than those of the normal ones.     

International conference on basic and clinical aspects of cell-cycle control

Scientists of numerous medical and life science disciplines met in Siena, Italy to discuss the latest proceedings in basic and clinical research. General models of interconnected linear and back-feeding cell-cycle control pathways provide a basis for applied molecular research. Cell-cycle determining factors essential for the control of cellular homeostasis either become markers to determine characteristics of a disease and/or become therapeutic targets. Apart from animal and tissue culture models, molecular theories finally have to stand proof in clinical application and evaluation. Therefore, the clinical feedback to the basic scientist's bench is essential for necessary adjustments of their models to improve future approaches to research challenges. A select group of speakers provided the audience with such an interdisciplinary dialogue at the first International Conference on Basic and Clinical Aspects of Cell-Cycle Control from May 29 to 31, 2000 in Siena, Italy.     

New dimensions in cancer biology and therapy

The most successful and productive approach to defeat cancer relies on highly integrated and interchanging cooperation between basic research, diagnosis, and therapeutic innovation. Nevertheless, much remains to be done to achieve a consistent and continuous flow of theoretical and practical information among scientists actively involved in these equally relevant fields. The major objective of the International Conferences, "New Dimensions in Cancer Biology and Therapy," has been identified in gathering together basic scientists and clinicians who represent scientific leaders in their field, whose working efforts are focused on specific human malignancies. Thus, in pursuit of this well-defined goal, the third edition of the Conference has focused on human immunodeficiency virus (HIV) and cancer, cutaneous melanoma, and colorectal carcinoma, which are ideal clinical examples for innovative diagnostic and therapeutic intervention, as well as optimal models to unveil new mechanisms of tumor pathogenesis.     

Novel growth characteristics and high rates of nitrate reduction of an Escherichia coli strain, LCB2048, that expresses only a periplasmic nitrate reductase

Escherichia coli strain LCB2048 is a double mutant defective in the synthesis of the two membrane-associated nitrate reductases A and Z. This strain can grow anaerobically on a non-fermentable carbon source, glycerol, in the presence of nitrate even in media supplemented with high concentrations of tungstate. This growth was totally dependent upon a highly active, periplasmic nitrate reductase (Nap). Due to the presence of a previously unreported narL mutation, synthesis of the periplasmic nitrate reductase by this strain was induced during anaerobic growth by nitrate. We have also demonstrated that methyl viologen is an ineffective electron donor to Nap: its use leads to an underestimation of the contribution of Nap activity to the rate of nitrate reduction in vivo.     

Icetexane and abietane diterpenoids from Salvia gilliessi

One icetexane and two abietane diterpenes were isolated from the aerial parts of Salvia gilliesii, and characterized as 5-epi-icetexone; 12-hydroxy-11,14-diketo-6,8,12-abietatrien-19,20-olide and 6 alpha,12,19-trihydroxy-11,14-diketo-8,12-abietadien-20,7 beta-olide, respectively. The structures were established by analysis of their 1H and 13C NMR spectra with the aid of 2D experiments. The triterpene oleanolic acid was isolated from the same source.