Tissue-specific expression from a compound TATA-dependent and TATA-independent promoter

We have found that the mouse metallothionein-I (MT-I) gene promoter functions in an unusual, compound manner. It directs both TATA-dependent and TATA-independent modes of transcription in vivo. The TATA-dependent message is initiated at the previously characterized +1 transcription start site and is the predominant species in most tissues. In many cell types it is metal inducible. The TATA-independent initiation sites are distributed over the 160 bp upstream of the previously characterized +1 start site, and the RNA products are present in all tissues examined. Only in testis, however, do the TATA-independent transcripts predominate, accumulating to highest levels in pachytene-stage meiotic cells and early spermatids. Unlike the TATA-dependent +1 transcript, these RNAs are not induced by metal, even in cultured cells in which the +1 species is induced. Transfection studies of site-directed mutants show that destruction of the TATA element drastically alters the ratio of the two RNA classes in cells in which the +1 transcripts normally dominates. In TATA-minus mutants, the TATA-independent RNAs become the most prevalent, although they remain refractory to metal induction. Thus, the MT-I promoter utilizes two different types of core promoter function within a single cell population. The two different types of core promoter respond very differently to environmental stimuli, and the choice between them appears to be regulated in a tissue-specific fashion

Ubiquinol Reduces Muscle Wasting but Not Fatigue in Tumor-Bearing Mice

Purpose: Fatigue is the most common and distressing symptom reported by cancer patients during and after treatment. Tumor growth increases oxidative stress and cytokine production, which causes skeletal muscle wasting and cardiac dysfunction. The purpose of this study was to determine whether treatment with the antioxidant ubiquinol improves muscle mass, cardiac function, and behavioral measures of fatigue in tumor-bearing mice. Method: Adult female mice were inoculated with colon26 tumor cells. Half the control and tumor-bearing mice were administered ubiquinol (500 mg/kg/day) in their drinking water. Voluntary wheel running (i.e., voluntary running activity [VRA]) and grip strength were measured at Days 0, 8, 14, and 17 of tumor growth. Cardiac function was measured using echocardiography on Day 18 or 19. Biomarkers of inflammation, protein degradation, and oxidative stress were measured in serum and heart and gastrocnemius tissue. Results: VRA and grip strength progressively declined in tumor-bearing mice. Muscle mass and myocardial diastolic function were decreased, and expression of proinflammatory cytokines was increased in serum and muscle and heart tissue on Day 19 of tumor growth. Oxidative stress was present only in the heart, while biomarkers of protein degradation were increased only in the gastrocnemius muscle. Ubiquinol increased muscle mass in the tumor-bearing and control animals but had no effect on the expression of biomarkers of inflammation, protein degradation, or oxidative stress or on behavioral measures of fatigue

Using FRITIOF to Model Nucleus-Nucleus Interactions in a Cosmic Ray Detector

Ascintillating optical fiber calorimeter (SOFCAL) isbeing developed by NASA/Marshall Space Flight Center for use in experiments to study the spectrum of high-energy cosmic rays and gamma rays from 100 GeV to 1,000 TeV. SOFCAL willnot saturate for long exposures and this calorimeter inthese balloon-borne emulsion chambers willbe helpful for the study of the composition of primary cosmic-ray nuclei. For primary nuclei with energies much greater than 1014 eV, nucleus-nucleus interactions are likely to exhibit characteristics of a quark-gluon plasma (QGP). Aparticle event generator was used tomodel the collision of a cosmic-ray nucleus with a target nucleus inan emulsion chamber. FRITIOF withLUCIAE was chosen tomodel collisions of primary cosmic rays inan emulsion chamber with SOFCAL. Pseudo-rapidity distributions were computed for protons on lead at 200 GeV/c and compared with experimental data. Pseudo-rapidity distributions were computed for protons or iron incident on a carbon or silver nucleus. For gamma-rays from nucleus-nucleus interactions, the total energy of the electromagnetic component Z£y was computed. The partial coefficient ofinelasticity kr defined by L£ y = kY E0 ,was computed from the primary energy Eo of the cosmic rays. The f(ky )-distributions were computed and compared with existing calorimeter data. Funding was provided by the NASA/University Joint Venture (JOVE) Program

Quasar 3C 298: a test-case for meteoritic nanodiamond 3.5 µm emission

Aims. We calculate the dust emission expected at 3.43 and 3.53 µm if meteoritic (i.e. hydrogenated) nanodiamonds are responsible for most of the far-UV break observed in quasars. Methods. We integrate the UV flux that hydrogenated nanodiamonds must absorb to reproduce the far-UV break. Based on laboratory spectra of H-terminated diamond surfaces, we analyse the radiative energy budget and derive theoretically the IR emission profiles expected for possible C-H surface stretch modes of the diamonds. Results. Using as test case a spectrum of 3C 298 provided by the Spitzer Observatory, we do not find evidence of these emission bands. Conclusions. While diamonds without surface adsorbates remain a viable candidate for explaining the far-UV break observed in quasars, hydrogenated nanodiamonds appear to be ruled out, as they would give rise to IR emission bands, which have not been observed so far

Evaporites and the salinity of the ocean during the Phanerozoic: Implications for climate, ocean circulation and life

A compilation of data on volumes and masses of evaporite deposits is used as the basis for reconstruction of the salinity of the ocean in the past. Chloride is tracked as the only ion essentially restricted to the ocean, and past salinities are calculated from reconstructed chlorine content of the ocean. Models for ocean salinity through the Phanerozoic are developed using maximal and minimal estimates of the volumes of existing evaporite deposits, and using constant and declining volumes of ocean water through the Phanerozoic. We conclude that there have been significant changes in the mean salinity of the ocean accompanying a general decline throughout the Phanerozoic. The greatest changes are related to major extractions of salt into the young ocean basins which developed during the Mesozoic as Pangaea broke apart. Unfortunately, the sizes of these salt deposits are also the least well known. The last major extractions of salt from the ocean occurred during the Miocene, shortly after the large scale extraction of water from the ocean to form the ice cap of Antarctica. However, these two modifications of the masses of H2O and salt in the ocean followed in sequence and did not cancel each other out. Accordingly, salinities during the Early Miocene were between 37‰ and 39‰. The Mesozoic was a time of generally declining salinity associated with the deep sea salt extractions of the North Atlantic and Gulf of Mexico (Middle to Late Jurassic) and South Atlantic (Early Cretaceous). The earliest of the major extractions of the Phanerozoic occurred during the Permian. There were few large extractions of salt during the earlier Palaeozoic. The models suggest that this was a time of relatively stable but slowly increasing salinities ranging through the upper 40‰'s into the lower 50‰'s. Higher salinities for the world ocean have profound consequences for the thermohaline circulation of the ocean in the past. In the modern ocean, with an average salinity of about 34.7‰, the density of water is only very slightly affected by cooling as it approaches the freezing point. Consequently, salinization through sea-ice formation or evaporation is usually required to make water dense enough to sink into the ocean interior. At salinities above about 40‰ water continues to become more dense as it approaches the freezing point, and salinization is not required. The energy-consuming phase changes involved in sea-ice formation and evaporation would not be required for vertical circulation in the ocean. The hypothesized major declines in salinity correspond closely to the evolution of both planktonic foraminifera and calcareous nannoplankton. Both groups were restricted to shelf regions in the Jurassic and early Cretaceous, but spread into the open ocean in the mid-Cretaceous. Their availability to inhabit the open ocean may be directly related to the decline in salinity. The Permian extraction may have created stress for marine organisms and may have been a factor contributing to the end-Permian extinction. The modeling also suggests that there was a major salinity decline from the Late Precambrian to the Cambrian, and it is tempting to speculate that this may have been a factor in the Cambrian explosion of life

Multigenome DNA sequence conservation identifies Hox cis-regulatory elements

To learn how well ungapped sequence comparisons of multiple species can predict cis-regulatory elements in Caenorhabditis elegans, we made such predictions across the large, complex ceh-13/lin-39 locus and tested them transgenically. We also examined how prediction quality varied with different genomes and parameters in our comparisons. Specifically, we sequenced ∼0.5% of the C. brenneri and C. sp. 3 PS1010 genomes, and compared five Caenorhabditis genomes (C. elegans, C. briggsae, C. brenneri, C. remanei, and C. sp. 3 PS1010) to find regulatory elements in 22.8 kb of noncoding sequence from the ceh-13/lin-39 Hox subcluster. We developed the MUSSA program to find ungapped DNA sequences with N-way transitive conservation, applied it to the ceh-13/lin-39 locus, and transgenically assayed 21 regions with both high and low degrees of conservation. This identified 10 functional regulatory elements whose activities matched known ceh-13/lin-39 expression, with 100% specificity and a 77% recovery rate. One element was so well conserved that a similar mouse Hox cluster sequence recapitulated the native nematode expression pattern when tested in worms. Our findings suggest that ungapped sequence comparisons can predict regulatory elements genome-wide

Bandt-Pompe symbolization dynamics for time series with tied values: A data-driven approach

In 2002, Bandt and Pompe [Phys. Rev. Lett. 88, 174102 (2002)] introduced a successfully symbolic encoding scheme based on the ordinal relation between the amplitude of neighboring values of a given data sequence, from which the permutation entropy can be evaluated. Equalities in the analyzed sequence, for example, repeated equal values, deserve special attention and treatment as was shown recently by Zunino and co-workers [Phys. Lett. A 381, 1883 (2017)]. A significant number of equal values can give rise to false conclusions regarding the underlying temporal structures in practical contexts. In the present contribution, we review the different existing methodologies for treating time series with tied values by classifying them according to their different strategies. In addition, a novel data-driven imputation is presented that proves to outperform the existing methodologies and avoid the false conclusions pointed by Zunino and co-workers.Fil: Traversaro Varela, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Lanús; ArgentinaFil: Redelico, Francisco Oscar. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Risk, Marcelo. Hospital Italiano; Argentina. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Frery, Alejandro César. Universidade Federal de Alagoas; BrasilFil: Rosso, Osvaldo Aníbal. Hospital Italiano; Argentina. Universidade Federal de Alagoas; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Los Andes; Chil

XMM-Newton Surveys of the Canada-France Redshift Survey Fields - III: The Environments of X-ray Selected AGN at 0.4<z<0.6

The environmental properties of a sample of 31 hard X-ray selected AGN are investigated, from scales of 500 kpc down to 30 kpc, and are compared to a control sample of inactive galaxies. The AGN all lie in the redshift range 0.4<z<0.6. The accretion luminosity-density of the Universe peaks close to this redshift range, and the AGN in the sample have X-ray luminosities close to the knee in the hard X-ray luminosity function, making them representative of the population which dominated this important phase of energy conversion. Using both the spatial clustering amplitude and near neighbour counts it is found that the AGN have environments that are indistinguishable from normal, inactive galaxies over the same redshift range and with similar optical properties. Typically, the environments are of sub-cluster richness, in contrast to similar studies of high-z quasars, which are often found in clusters with comparable richness to the Abell R>=0 clusters. It is suggested that minor mergers with low mass companions is a likely candidate for the mechanism by which these modest luminosity AGN are fuelled.Comment: 12 pages, 6 figures, accepted by MNRA

Globally sparse PLS regression

Volume 56 ; Print ISBN : 978-1-4614-8282-6Partial least squares (PLS) regression combines dimensionality reduction and prediction using a latent variable model. It provides better predictive ability than principle component analysis by taking into account both the independent and re- sponse variables in the dimension reduction procedure. However, PLS suffers from over-fitting problems for few samples but many variables. We formulate a new criterion for sparse PLS by adding a structured sparsity constraint to the global SIMPLS optimization. The constraint is a sparsity-inducing norm, which is useful for selecting the important variables shared among all the components. The optimization is solved by an augmented Lagrangian method to obtain the PLS components and to perform variable selection simultaneously. We propose a novel greedy algorithm to overcome the computation difficulties. Experiments demonstrate that our approach to PLS regression attains better performance with fewer selected predictor