Identifying common prognostic factors in genomic cancer studies: A novel index for censored outcomes

Background  

With the growing number of public repositories for high-throughput genomic data, it is of great interest to combine the results produced by independent research groups. Such a combination allows the identification of common genomic factors across multiple cancer types and provides new insights into the disease process. In the framework of the proportional hazards model, classical procedures, which consist of ranking genes according to the estimated hazard ratio or the p-value obtained from a test statistic of no association between survival and gene expression level, are not suitable for gene selection across multiple genomic datasets with different sample sizes. We propose a novel index for identifying genes with a common effect across heterogeneous genomic studies designed to remain stable whatever the sample size and which has a straightforward interpretation in terms of the percentage of separability between patients according to their survival times and gene expression measurements.     

Molecular recognition of anions by synthetic receptors

Over the past year, several significant developments have been made in the field of anion binding. The fundamental principles of molecular recognition are increasingly being better understood, and of particular interest are reports of several synthetic anion receptors able to perform their task in complex natural media. Additionally, macroscopic devices such as anion specific electrodes and membranes based on a molecular recognition approach are now being made.     

New skeletal tuberculosis cases in past populations from Western Hungary (Transdanubia)

The distribution, antiquity and epidemiology of tuberculosis (TB) have previously been studied in osteoarchaeological material in the eastern part of Hungary, mainly on the Great Plain. The purpose of this study is to map the occurrence of skeletal TB in different centuries in the western part of Hungary, Transdanubia, and to present new cases we have found. Palaeopathological analysis was carried out using macroscopic observation supported by radiographic and molecular methods. A large human osteoarchaeological sample (n = 5684) from Transdanubian archaeological sites ranging from the 2nd to the 18th centuries served as a source of material. Spinal TB was observed in seven individuals (in three specimens with Pott's disease two of which also had cold abscess) and hip TB was assumed in one case. The results of DNA for Mycobacterium tuberculosis were positive in seven of the eight cases identified by paleopathology, and negative in the assumed case of hip TB. However, the molecular results are consistent with highly fragmented DNA, which limited further analysis. Based on the present study and previously published cases, osteotuberculosis was found in Transdanubia mainly during the 9th-13th centuries. However, there are no signs of TB in many other 9th-13th century sites, even in those that lie geographically close to those where osteotuberculous cases were found. This may be due to a true absence of TB caused by the different living conditions, way of life, or origin of these populations. An alternative explanation is that TB was present in some individuals with no typical paleopathology, but that death occurred before skeletal morphological features could develop.     

Oxalate pretreatment and use of a physical developer render the Kossa method selective and sensitive for calcium

Based on experiments on agarose gels and tissue, a procedure has been developed which greatly improves the sensitivity and the specifity of the Kossa method for demonstrating calcium in tissue. Tissue calcium is immobilized by acetonic oxalic acid, which simultaneously removes the other sorts of anions capable of precipitating silver ions (e.g. phosphate, carbonate). The resulting submicroscopic grains of calcium oxalate are converted first into silver oxalate then into metallic silver by a treatment with silver nitrate followed by an ultra-violet irradiation (Kossa reaction). These submicroscopic metallic silver grains are enlarged up to microscopic visibility by means of physical development, which makes the staining highly sensitive. Co-staining of the argyrophil sites in the tissue is totally suppressed by various tricks, which render the silver staining selective for calcium.     

Heat exchanges in wet suits

Flow of water under foam neoprene wet suits could halve insulation that the suits provided, even at rest in cold water. On the trunk conductance of this flow was approximately 6.6 at rest and 11.4 W . m-2 . C-1 exercising; on the limbs, it was only 3.4 at rest and 5.8 W . m-2 . degrees C-1 exercising; but during vasoconstriction in the cold, skin temperatures on distal parts of limbs were lower than were those of the trunk, allowing adequate metabolic responses. In warm water, minor postural changes and movement made flow under suits much higher, approximately 60 on trunk and 30 W . m-2 . degrees C-1 on limbs, both at rest and at work. These changes in flow allowed for a wide range of water temperatures at which people could stabilize body temperature in any given suit, neither overheating when exercising nor cooling below 35 degrees C when still. Even thin people with 4- or 7- mm suits covering the whole body could stabilize their body temperatures in water near 10 degrees C in spite of cold vasodilatation. Equations to predict limits of water temperature for stability with various suits and fat thicknesses are given.     

Tubulin subunit carboxyl termini determine polymerization efficiency

Cleavage of tubulin by subtilisin removes a small (Mr less than 2000) fragment from the C-terminal end of both alpha and beta subunits. The resulting protein is much reduced in negative charge. The cleaved, less acidic protein retains its competence to polymerize in a GTP-dependent and cold-, GDP-, and podophyllotoxin-sensitive manner and assembles into sheets or bundles of twisted filaments. The critical concentration for polymerization of the cleaved protein is about 50-fold lower than that for intact tubulin. It is proposed that the C termini of the subunits normally impede polymerization.     

Conserved DNA Motifs,Including the CENP-B Box-like,Are Possible Promoters of Satellite DNA Array Rearrangements in Nematodes

Tandemly arrayed non-coding sequences or satellite DNAs (satDNAs) are rapidly evolving segments of eukaryotic genomes, including the centromere, and may raise a genetic barrier that leads to speciation. However, determinants and mechanisms of satDNA sequence dynamics are only partially understood. Sequence analyses of a library of five satDNAs common to the root-knot nematodes Meloidogyne chitwoodi and M. fallax together with a satDNA, which is specific for M. chitwoodi only revealed low sequence identity (32–64%) among them. However, despite sequence differences, two conserved motifs were recovered. One of them turned out to be highly similar to the CENP-B box of human alpha satDNA, identical in 10–12 out of 17 nucleotides. In addition, organization of nematode satDNAs was comparable to that found in alpha satDNA of human and primates, characterized by monomers concurrently arranged in simple and higher-order repeat (HOR) arrays. In contrast to alpha satDNA, phylogenetic clustering of nematode satDNA monomers extracted either from simple or from HOR array indicated frequent shuffling between these two organizational forms. Comparison of homogeneous simple arrays and complex HORs composed of different satDNAs, enabled, for the first time, the identification of conserved motifs as obligatory components of monomer junctions. This observation highlights the role of short motifs in rearrangements, even among highly divergent sequences. Two mechanisms are proposed to be involved in this process, i.e., putative transposition-related cut-and-paste insertions and/or illegitimate recombination. Possibility for involvement of the nematode CENP-B box-like sequence in the transposition-related mechanism and together with previously established similarity of the human CENP-B protein and pogo-like transposases implicate a novel role of the CENP-B box and related sequence motifs in addition to the known function in centromere protein binding.