Study on the cyclization tendency of backbone cyclic tetrapeptides.

The cyclization kinetics of five backbone-cyclic tetrapeptides was investigated both experimentally and computationally. The aim was to both accurately measure the cyclization rates in solution and develop a method that efficiently estimates the relative cyclization tendencies computationally. Progression of the cyclization reaction was monitored directly, yielding the kinetics of changes in the amounts of the linear precursor and the products. These measurements were used to calculate the reaction rates; the results were consistent with a first-order reaction kinetics. In order to predict the cyclization rates computationally, the conformation space of the linear precursors was mapped and used to construct an approximate partition function. We assumed that the cyclization tendency was correlated with the relative probability of being found in a cyclization-prone conformation of the backbone, this probability was estimated from the partition function. The results supported this assumption and demonstrated that, within reasonable accuracy, we are able to predict the relative cyclization tendencies of the peptides measured.     

Markerless Roentgen Stereophotogrammetric Analysis for in vivo implant migration measurement using three dimensional surface models to represent bone

Recent studies have shown that model-based RSA using implant surface models to detect in vivo migration is as accurate as the classical marker-based RSA method. Use of bone surface models would be a further advancement of the model-based method by decreasing complications arising from marker insertion. The aim of this pilot investigation was to assess the feasibility of a "completely markerless" model-based RSA in detecting migration of an implant using bone surface models instead of bone markers. A total knee arthroplasty (TKA) was performed on a human cadaver knee, which was subsequently investigated by repeated RSA measurements performed by one observer. The cadaver knee was CT scanned prior to implantation of the TKA. Tibia-fibular surface models were created using two different commercially available software packages to investigate the effect of segmentation software on the accuracy of repeated migration measures of zero displacement by one observer. Reverse engineered surface models of the TKA tibial component were created. The analysis of the RSA images was repeated 10 times by one individual observer. For the markerless method, the greatest apparent migration observed about the three anatomical axes investigated was between -2.08 and 1.35 mm (SD ≤ 0.88) for z-axis translation, and -4.57° to 7.86° (SD ≤ 3.17) for R(y)-axis rotation, which were well beyond out of the range of what is typically considered adequate for clinically relevant RSA measurements. Use of tibia-fibular surface models of the bone instead of markers could provide practical advantages in evaluating implant migration. However, we found the accuracy and precision of the markerless approach to be lower than that of marker-based RSA, to a degree which precludes the use of this method for measuring implant migration in its present form.     

Polarized Growth of Fungal Hyphae Is Defined by an Alkaline pH Gradient

Robson, G. D., Prebble, E., Rickers, A., Hosking, S., Denning, D. W., Trinci, A. P. J., and Robertson, W. 1996. Polarized growth of fungal hyphae is defined by an alkaline pH gradient. Fungal Genetics and Biology 20, 289-298. Polarized cell growth is exhibited by a diverse range of eukaryotic and prokaryotic cells. The events which are responsible for this growth are poorly understood. However, the existence of ion gradients may play an important role in establishing and driving cell polarity. Using a pH-sensitive, ratiometric fluorescent dye to monitor intracellular pH in growing fungal hyphae, we report a gradient at the extending hyphal tip that is up to 1.4 pH units more alkaline than more distal regions. Both the magnitude and the length of the pH gradient were strongly correlated with the rate of hyphal extension and eradication of the gradient-arrested growth. These results suggest that alkaline pH gradients may be integral to hyphal extension in fungi.     

The canine olfactory subgenome

We identified 971 olfactory receptor (OR) genes in the dog genome, estimated to constitute approximately 80% of the canine OR repertoire. This was achieved by directed genomic DNA cloning of olfactory sequence tags as well as by mining the Celera canine genome sequences. The dog OR subgenome is estimated to have 12% pseudogenes, suggesting a functional repertoire similar to that of mouse and considerably larger than for humans. No novel OR families were discovered, but as many as 34 gene subfamilies were unique to the dog. "Fish-like" Class I ancient ORs constituted 18% of the repertoire, significantly more than in human and mouse. A set of 122 dog-human-mouse ortholog triplets was identified, with a relatively high fraction of Class I ORs. The elucidation of a large portion of the canine olfactory receptor gene superfamily, with some dog-specific attributes, may help us understand the unique chemosensory capacities of this species.     

An RNA folding method capable of identifying pseudoknots and base triples

MOTIVATION: Recently, we described a Maximum Weighted Matching (MWM) method for RNA structure prediction. The MWM method is capable of detecting pseudoknots and other tertiary base-pairing interactions in a computationally efficient manner (Cary and Stormo, Proceedings of the Third International Conference on Intelligent Systems for Molecular Biology, pp. 75-80, 1995). Here we report on the results of our efforts to improve the MWM method's predictive accuracy, and show how the method can be extended to detect base interactions formerly inaccessible to automated RNA modeling techniques. RESULTS: Improved performance in MWM structure prediction was achieved in two ways. First, new ways of calculating base pair likelihoods have been developed. These allow experimental data and combined statistical and thermodynamic information to be used by the program. Second, accuracy was improved by developing techniques for filtering out spurious base pairs predicted by the MWM program. We also demonstrate here a means by which the MWM folding method may be used to detect the presence of base triples in RNAs. AVAILABILITY: http://www.cshl.org/mzhanglab/tabaska/j axpage. html CONTACT: tabaska@cshl.org      

Ancient genomic architecture for mammalian olfactory receptor clusters

Background  

Mammalian olfactory receptor (OR) genes reside in numerous genomic clusters of up to several dozen genes. Whole-genome sequence alignment nets of five mammals allow their comprehensive comparison, aimed at reconstructing the ancestral olfactory subgenome.     

Knowledge and opinions about tissue donation and transplantation among Polish students and physicians

The idea of transplantation seems to be commonly identified by lay and professional people only with transplantation of vascularized organs like kidney or heart. The question arises whether there is any awareness of tissue transplantation among the public. A survey was therefore undertaken to assess awareness of and approaches to tissue donation and transplantation among selected social groups. A questionnaire on donation and transplantation issues was administered to respondents from the following groups: secondary school students, non-medical university students, medical university students, physicians. On the whole, 441 non-randomly sampled respondents were surveyed. The awareness of tissue transplantation is narrower than the awareness of organ transplantation. The support for tissue transplantation is weaker than for organ transplantation. This study shows that there is an acute need for education in the legal aspects of transplantation and that ways of motivating healthcare professionals to promote transplantation should be developed.     

A Not-So-Gentle Refutation of the Defence of Homeopathy

In a recent paper, Levy, Gadd, Kerridge, and Komesaroff attempt to defend the ethicality of homeopathy by attacking the utilitarian ethical framework as a basis for medical ethics and by introducing a distinction between evidence-based medicine and modern science. This paper demonstrates that their argumentation is not only insufficient to achieve that goal but also incorrect. Utilitarianism is not required to show that homeopathic practice is unethical; indeed, any normative basis of medical ethics will make it unethical, as a defence of homeopathic practice requires the rejection of modern natural sciences, which are an integral part of medical ethics systems. This paper also points out that evidence-based medicine lies at the very core of modern science. Particular arguments made by Levy et al. within the principlist medical ethics normative system are also shown to be wrong.