Removing Cancer when it is Correlated with other Causes of Death

This paper presents an identifiability theorem in the theory of dependent competing risks and it applies the result by examining the effect of removing cancer from the United States population when cancer is correlated with the other causes of death. The paper shows how dependence can be modeled with copula functions and it shows that calculating the survival probabilities after cancer is removed is equivalent to solving a system of nonlinear differential equations.     

Culture conditions differentially affect the translation of individual Escherichia coli mRNAs.

Our aim is to investigate whether changes in growth conditions can differentially affect the initiation of translation from individual Escherichia coli mRNAs that are not subjected to specific translational control. As a model system, we have constructed a series of point-mutated lacZ genes which differ in their Shine-Dalgarno (SD) sequence, their initiator codon, or the secondary structure around these elements. Alterations in growth conditions produced large (up to 8-fold) changes in the relative expression from these genes, which, we argue, stem from changes in their relative efficiencies of translation initiation. In particular, compared to genes bearing mutations outside the SD or initiator codon, genes mutated in these elements experience a significant decrease in their expression when cells are grown in minimal rather than rich medium; at 42 degrees C rather than 37 degrees C; or under amino acid starvation. We discuss the mechanisms underlying these effects, and evocate their possible generality.     

Interaction of the Two Structural Domains of Calmodulin with Mature and Immature Rat Brain Microtubules

The inhibitory effect of calmodulin on the assembly of mature and immature rat brain microtubules was compared with that of the two major structural domains of this protein, the COOH-terminal fragment (amino acids 78-148) and the NH2-terminal fragment (amino acids 1-77), to determine the calmodulin structural domain responsible for the inhibitory effect on microtubule assembly. Microtubules prepared during the early stages of brain development, i.e., during intensive neurite outgrowth, are more sensitive to inhibition by the Ca2(+)-calmodulin complex than those obtained from adult brain. Significant inhibition of immature microtubule assembly was observed with both fragments in the absence of Ca2+, but the effects were more important when Ca2+ was present. With adult brain microtubules, the two fragments remained without effect on assembly in the absence of Ca2+, whereas some inhibition was seen in its presence but only with the COOH-terminal polypeptide. Under all these conditions, the COOH-terminal fragment was always more active than the NH2-terminal fragment on microtubule polymerization, albeit to a lesser extent than native calmodulin.     

Sequential Exercise in Triathletes: Variations in GH and Water Loss

Growth hormone (GH) may stimulate water loss during exercise by activating sweating. This study investigated GH secretion and water loss during sequential cycling and running, taking postural changes into account. The two exercise segments had similar durations and were performed at the same relative intensity to determine their respective contributions to water loss and the plasma volume variation noted in such trials. Eight elite triathletes first performed an incremental cycle test to assess maximal oxygen consumption. Then, the triathletes performed one of two trials in randomized order: constant submaximal cycling followed by treadmill running (C₁-R₂) or an inversed succession of running followed by cycling (R₁-C₂). Each segment of both trials was performed for 20 minutes at ∼75% of maximal oxygen consumption. The second trial, reversing the segment order of the first trial, took place two weeks later. During cycling, the triathletes used their own bicycles equipped with a profiled handlebar. Blood sampling (for GH concentrations, plasma viscosity and plasma volume variation) was conducted at rest and after each segment while water loss was estimated from the post- and pre-measures. GH increases were significantly lower in R₂ than C₂ (72.2±50.1 vs. 164.0±157 ng.ml⁻¹.min⁻¹, respectively; P<0.05). Water loss was significantly lower after C₁-R₂ than R₁-C₂ (1105±163 and 1235±153 ml, respectively; P<0.05). Plasma volume variation was significantly negative in C₁ and R₁ (−6.15±2.0 and −3.16±5.0%, respectively; P<0.05), not significant in C₂, and significantly positive for seven subjects in R₂ (4.05±3.1%). We concluded that the lower GH increases in R₂ may have contributed to the smaller reduction in plasma volume by reducing sweating. Moreover, this lower GH response could be explained by the postural change during the transition from cycling to running. We recommend to pay particular attention to their hydration status during R₁ which could limit a potential dehydration during C₂.     

pGIAK1, a Heavy Metal Resistant Plasmid from an Obligate Alkaliphilic and Halotolerant Bacterium Isolated from the Antarctic Concordia Station Confined Environment

pGIAK1 is a 38-kb plasmid originating from the obligate alkaliphilic and halotolerant Bacillaceae strain JMAK1. The strain was originally isolated from the confined environments of the Antarctic Concordia station. Analysis of the pGIAK1 38,362-bp sequence revealed that, in addition to its replication region, this plasmid contains the genetic determinants for cadmium and arsenic resistances, putative methyltransferase, tyrosine recombinase, spore coat protein and potassium transport protein, as well as several hypothetical proteins. Cloning the pGIAK1 cad operon in Bacillus cereus H3081.97 and its ars operon in Bacillus subtilis 1A280 conferred to these hosts cadmium and arsenic resistances, respectively, therefore confirming their bona fide activities. The pGIAK1 replicon region was also shown to be functional in Bacillus thuringiensis, Bacillus subtilis and Staphylococcus aureus, but was only stably maintained in B. subtilis. Finally, using an Escherichia coli - B. thuringiensis shuttle BAC vector, pGIAK1 was shown to display conjugative properties since it was able to transfer the BAC plasmid among B. thuringiensis strains.     

Binding of Net-Fla,a Netropsin-Flavin Hybrid Molecule,to DNA: Molecular Mechanics and Dynamics Studies in vacuo and in Water Solution

Abstract

We have studied the binding of the hybrid netropsin-flavin (Net-Fla) molecule onto four sequences containing four A.T base pairs. Molecular mechanics minimizations in vacuo show numerous minimal conformations separated by one base pair. 400 ps molecular dynamics simulations in vacuo have been performed using the lowest minima as the starting conformations. During these simulations, the flavin moiety of the drug makes two hydrogen bonds with an amino group of a neighboring guanine. A 200 ps molecular dynamics simulation in explicit water solution suggests that the binding of Net-Fla upon the DNA substrate is enhanced by water bridges. A water molecule bridging the amidinium of Net-Fla to the N3 atom of an adenine seems to be stuck in the dmg-DNA complex during the whole simulation. The fluctuations of the DNA helical parameters and of the torsion angles of the sugar-phosphate backbone are very similar in the simulations in vacuo and in water. The time auto-correlation functions for the DNA helical parameters decrease rapidly in the picosecond range in vacuo. The same functions computed from the water solution molecular dynamics simulations seem to have two modes: the rapid mode is similar to the behavior in vacuo, and is followed by a slower mode in the 10 ps range.     

Comparaisons des séquences d'ADN hautement répétées chez l'homme et diverses espèces de primates

Highly repeated DNA sequences from man, five other primate species and rat were compared using five restriction endonucleases. Calculations of a similarity index based on the mobility of various bands indicate that man, chimpanzee and baboons are very similar. The sequences of the genomes studied have apparently been reorganized during primate evolution.     

Interfacial Susceptibilities in Nanoplasmonics via Inversion of Fresnel Coefficients

The reflection coefficients of a nanoparticle film are driven to a large extent by perpendicular and parallel interfacial susceptibilities that have the meaning of “dielectric thicknesses” which combine the actual geometry of the film and its dielectric properties. The direct determination of these parameters faces the long-standing issue of the derivation of complex optical constants from Fresnel coefficients via a unique spectroscopic measurement. The present work sets up an iterative algorithm based on inversion of the reflection coefficients recorded in the UV–visible range for two polarization states s and p and Kramers–Kronig (KK) analysis. To calculate the KK integrals over a limited energy window, the strategy was to complement measurements by spectra calculated in the framework of the spheroidal dipole approximation. The algorithm has been successfully tested on synthetic data of differential reflectivity for supported truncated spheres. These were chosen to span different dielectric behaviors, involving (a) for the particles, metals whose optical response is dominated by plasmonic excitations with a noticeable Drude behavior (Ag and Au) and (b) for the substrate, either nonabsorbing wide bandgap (alumina) or semiconducting (zincite and titania) oxides. Unlike the thin plate model, the approach was proven to apply to “dielectric thicknesses” of several tens of nanometres in cases in which, even for geometric sizes of the order of the nanometer, the classical long-wavelength dielectric approximation fails because of strong plasmon resonances. Therefore, the disentanglement of dielectric behaviors along the parallel and perpendicular directions simplifies the understanding on the interface polarization process by removing substrate contribution. The present work that deals with plasmonics in nanoparticles can be easily generalized to different morphologies as well as to other combinations of Fresnel coefficients.     

Expression Patterns and Potential Biological Roles of Dip2a

Disconnected (disco)-interacting protein 2 homolog A is a member of the DIP2 protein family encoded by Dip2a gene. Dip2a expression pattern has never been systematically studied. Functions of Dip2a in embryonic development and adult are not known. To investigate Dip2a gene expression and function in embryo and adult, a Dip2a-LacZ mouse model was generated by insertion of β-Gal cDNA after Dip2a promoter using CRISPR/Cas9 technology. Dip2a-LacZ mouse was designed to be a lacZ reporter mouse as well as a Dip2a knockout mouse. Heterozygous mice were used to study endogenous Dip2a expression and homozygotes to study DIP2A-associated structure and function. LacZ staining indicated that Dip2a is broadly expressed in neuronal, reproductive and vascular tissues, as well as in heart, kidney, liver and lung. Results demonstrate that Dip2a is expressed in ectoderm-derived tissues in developing embryos. Adult tissues showed rich staining in neurons, mesenchymal, endothelial, smooth muscle cells and cardiomyocytes by cell types. The expression pattern highly overlaps with FSTL1 and supports previous report that DIP2A to be potential receptor of FSTL1 and its protective roles of cardiomyocytes. Broad and intense embryonic and adult expression of Dip2a has implied their multiple structural and physiological roles.