Molecular models of the intercellular lipid lamellae from epidermal stratum corneum

The purpose of the present study was to test the hypothesis that the 13 nm trilamellar repeat units within the intercellular spaces of epidermal stratum corneum are composed of lamellae with alternating 5-3-5 nm dimensions as presented in previous models [J. Invest. Dermatol. 92 (1989) 251, P.W. Wertz, Integral lipids in hair and stratum corneum, in: P. Jolles, H. Zahn, H. Hocker (Eds.), Hair: Biology And Structure, Birkhauser Verlag, Basel, 1996, pp. 227-238, Acta Derm.-Venereol., Suppl. 208 (2000) 23]. Electron density profiles were measured from transmission electron micrographs of porcine stratum corneum prepared using ruthenium tetroxide [J. Invest. Dermatol. 92 (1989) 251]. Center-to-center distances of adjacent electron-dense bands as well as adjacent lucent bands were measured. Dense band center-to-center measurements were consistent with a 5-3-5 nm arrangement. However, lucent band center-to-center measurements revealed uniform lamellar thickness. It is suggested that linoleate chains in the central lamella reduce more ruthenium than the predominantly saturated chains in the outer lamellae and that this additional reduced ruthenium accumulates under the polar head group regions. A similar phenomenon involving the sphingosine moieties of the covalently bound omega-hydroxyceramide molecules accounts for the three-band pattern seen between the ends of adjacent corneocytes. It is concluded that the component lamellae of the several types of 13 nm trilamellar units of the stratum corneum are all of equal thickness.     

A new method for choosing sample size for confidence interval-based inferences

Scientists often need to test hypotheses and construct corresponding confidence intervals. In designing a study to test a particular null hypothesis, traditional methods lead to a sample size large enough to provide sufficient statistical power. In contrast, traditional methods based on constructing a confidence interval lead to a sample size likely to control the width of the interval. With either approach, a sample size so large as to waste resources or introduce ethical concerns is undesirable. This work was motivated by the concern that existing sample size methods often make it difficult for scientists to achieve their actual goals. We focus on situations which involve a fixed, unknown scalar parameter representing the true state of nature. The width of the confidence interval is defined as the difference between the (random) upper and lower bounds. An event width is said to occur if the observed confidence interval width is less than a fixed constant chosen a priori. An event validity is said to occur if the parameter of interest is contained between the observed upper and lower confidence interval bounds. An event rejection is said to occur if the confidence interval excludes the null value of the parameter. In our opinion, scientists often implicitly seek to have all three occur: width, validity, and rejection. New results illustrate that neglecting rejection or width (and less so validity) often provides a sample size with a low probability of the simultaneous occurrence of all three events. We recommend considering all three events simultaneously when choosing a criterion for determining a sample size. We provide new theoretical results for any scalar (mean) parameter in a general linear model with Gaussian errors and fixed predictors. Convenient computational forms are included, as well as numerical examples to illustrate our methods.     

Investigating semantic similarity measures across the Gene Ontology: the relationship between sequence and annotation

MOTIVATION: Many bioinformatics data resources not only hold data in the form of sequences, but also as annotation. In the majority of cases, annotation is written as scientific natural language: this is suitable for humans, but not particularly useful for machine processing. Ontologies offer a mechanism by which knowledge can be represented in a form capable of such processing. In this paper we investigate the use of ontological annotation to measure the similarities in knowledge content or 'semantic similarity' between entries in a data resource. These allow a bioinformatician to perform a similarity measure over annotation in an analogous manner to those performed over sequences. A measure of semantic similarity for the knowledge component of bioinformatics resources should afford a biologist a new tool in their repertoire of analyses. RESULTS: We present the results from experiments that investigate the validity of using semantic similarity by comparison with sequence similarity. We show a simple extension that enables a semantic search of the knowledge held within sequence databases. AVAILABILITY: Software available from http://www.russet.org.uk.     

Humans deceived by predatory stealth strategy camouflaging motion

Motion camouflage is a stealth strategy that allows a predator to conceal its apparent motion as it approaches a moving prey. Although male hoverflies have been observed to move in a manner consistent with motion camouflage to track females, the successful application of the technique has not previously been demonstrated. This article describes the implementation and results of a psychophysical experiment suggesting that humans are susceptible to motion camouflage. The experiment masqueraded as a computer-game competition. The basis of the competition was a game designed to test the comparative success of different predatory-approach strategies. The experiment showed that predators were able to approach closer to their prey (the player of the game) before being detected when using motion camouflage than when using other approach strategies tested. For an autonomous predator, the calculation of a motion-camouflage approach is a non-trivial problem. It was, therefore, of particular interest that in the game the players were deceived by motion-camouflage predators controlled by artificial neural systems operating using realistic levels of input information. It is suggested that these results are especially of interest to biologists, visual psychophysicists, military engineers and computer-games designers.     

Comparative NMR studies of diffusional water permeability of red blood cells from different species: XIV. Little Penguin, Eudyptula minor

As part of a programme of comparative measurements of diffusional water permeability (Pd) the red blood cells (RBC) from Little Penguin (Eudyptula minor) were studied. The cell dimensions were measured with light and electron microscopy, and by a newly described non-invasive technique, NMR q-space analysis. In view of its relative novelty for cell biologists, an overview of this technique is presented. The RBC revealed an ellipsoidal shape that is characteristic of avian RBC, with axis lengths ("diameters") estimated to be: a=16.0 microm; b=9.6 microm; c=5.0 microm. The values of P(d)were: 2.0 x 10(-3)cm s(-1)at 5 degrees C, 3.3 x 10(-3)cm s(-1)at 10 degrees C, 4.6 x 10(-3)cm s(-1)at 15 degrees C and approximately 5.4 x 10(-3)cm s(-1)at 20, 25, 30, 37 and 42 degrees C.There was a lack of inhibition of water permeability by p-chloromercuribenzensulfonate (PCMBS), the well-known inhibitor of RBC aquaporin. It was notable that in the temperature range 5-20 degrees C the NMR parameters, and hence the permeability, varied linearly as is found for other species, but at temperatures higher than 20 degrees C there was no temperature-dependence of Pd. Consequently, there was an obvious break at approximately 20 degrees C in the Arrhenius plot, of the mean residence life time of water inside the cells, 1/Te, versus temperature. For temperatures less than 20 degrees C the activation energy E(a,d) was 45.6 +/- 6.6 kJ/mol. For temperatures higher than 25 degrees C E(a,d) was zero. The lack of inhibition of water permeability by PCMBS and the very high value of E(a,d) for diffusive water exchange suggests that the water permeation occurs primarily via the membrane bilayer per se, i.e., there is no aquaporin in Little Penguin RBC. The discontinuity at approximately 20 degrees C in the Arrhenius plot is an interesting finding, not seen before in other species, and we suggest that it reflects a phase transition in the membrane lipids.     

Absence of poly(ADP-ribose)polymerase-1 alters nuclear factor-kappa B activation and gene expression of apoptosis regulators after reperfusion injury

Poly(ADP-ribose) polymerase-1 (PARP-1) is activated in response to DNA injury in eukaryotic cells and has been implicated in cell dysfunction in reperfusion injury. In this study we investigated the role of PARP-1 on apoptosis in early myocardial reperfusion injury. Mice genetically deficient of PARP-1 (PARP-1-/-) and wild-type littermates were subjected to myocardial ischemia and reperfusion. Myocardial injury was assessed by measuring the serum levels of creatine phosphokinase and oligonucleosomal DNA fragments in the infarcted area. Expression of the anti-apoptotic protein, Bcl-2, and the pro-apoptotic protein, Bax, was analyzed by Western blot. Activation of caspases, important executioners of apoptosis, and activation of the nuclear factor kappa B (NF-kappa B) pathway were evaluated. Gene expression profiles for apoptotic regulators between PARP-1-/- and wild-type mice also were compared. Myocardial damage in PARP-1-/- mice was reduced significantly, as indicated by lower serum creatine phosphokinase levels and reduction of apoptosis, as compared with wild-type mice. Western blot analyses showed increased expression of Bcl-2, which was associated with reduction of caspase-1 and caspase-3 activation. This cardioprotection was associated with significant reduction of the activation of I kappa B kinase complex and NF-kappa B DNA binding. Microarray analysis demonstrated that the expression of 29 known genes of apoptotic regulators was significantly altered in PARP-1-/- mice compared with wild-type mice, whereas 6 known genes were similarly expressed in both genotypes. The data indicate that during reperfusion absence of PARP-1 leads to reduction of myocardial apoptosis, which is associated with reduced NF-kappa B activation and altered gene expression profiles.