Herculin, a Fourth Member of the MyoD Family of Myogenic Regulatory Genes

We have identified and cloned herculin, a fourth mouse muscle regulatory gene. Comparison of its DNA and deduced amino acid sequences with those of the three known myogenic genes (MyoD, myogenin, and Myf-5) reveals scattered short spans with similarity to one or more of these genes and a long span with strong similarity to all three. This long span includes a sequence motif that is also present in proteins of the myc, achaete-scute, and immunoglobulin enhancer-binding families. The herculin gene is physically linked to the Myf-5 gene on the chromosome; only 8.5 kilobases separate their translational start sites. A putative 27-kDa protein is encoded by three exons contained within a 1.7-kilobase fragment of the herculin gene. When expressed under the control of the simian virus 40 early promoter, transfected herculin renders murine NIH 3T3 and C3H/10T1/2 fibroblasts myogenic. In doing so, it also activates expression of myogenin, MyoD, and endogenous herculin in NIH 3T3 recipients. In adult mice, herculin is expressed in skeletal muscle but is absent from smooth muscle, cardiac muscle, and all nonmuscle tissues assayed. Direct comparison of the four known myogenic regulators in adult muscle showed that herculin is expressed at a significantly higher level than is any of the others. This quantitative dominance suggests an important role in the establishment or maintenance of adult skeletal muscle

Isolated sequences from the linked Myf-5 and MRF4 genes drive distinct patterns of muscle-specific expression in transgenic mice

In developing mouse embryos, MyoD family regulatory genes are expressed specifically in muscle precursors and mature myofibers. This pattern, taken together with the well-established ability of MyoD family members to convert a variety of cell types to skeletal muscle, suggests a significant role for these genes in regulating skeletal myogenesis. The possibility that expression of these genes may be causally associated with segregation of the myogenic lineage from other mesodermal derivatives, or with the subsequent maintenance of muscle phenotypes at later times, raises the issue of how MyoD family genes are themselves regulated during development. In this work, we have initiated studies to identify DNA sequences that govern Myf-5 and MRF4 (herculin, myf-6) transcription. Myf-5 is the first of the MyoD family to be expressed in the developing mouse embryo, while MRF4 is the most abundantly expressed myogenic factor in postnatal animals. In spite of their strikingly divergent patterns of expression, Myf-5 and MRF4 are tightly linked in the mouse genome; their translational start codons are only 8.5 kilobases apart. Here, the 5' flanking regions of the mouse Myf-5 and MRF4 genes were separately linked to a bacterial β-galactosidase (lacZ) gene, and these constructs were each used to produce several lines of transgenic mice. Transgene expression was monitored by X-gal staining of whole embryos and by in situ hybridization of embryo sections. For the Myf-5/lacZ lines, the most intense transgene expression was in the visceral arches and their craniofacial muscle derivatives, beginning at day 8.75 post coitum (p.c.). This correlates with endogenous Myf-5 expression in visceral arches. However, while Myf-5 is also expressed in somites starting at day 8 p.c., transgene expression in the trunk is not observed until day 12 p.c. Thus, the Myf-5/lacZ construct responds to early Myf-5 activators in the visceral arches but not in the somites, suggesting that myogenic determination in the nonsomitic head mesoderm may be under separate control from that of the somitic trunk mesoderm. MRF4/lacZ lines displayed an entirely different pattern from Myf-5. Transgene expression appeared in muscles starting at day 16.5 p.c. and became increasingly prominent at later times. However, an early wave of myotomal expression that is characteristic of the endogenous MRF4 was not recapitulated by the transgene

Systems Analysis by Partial Least Squares

This Collaborative Paper is one of a series embodying the outcome of a workshop and conference on Economic Structural Change: Analytical Issues, held at IIASA in July and August 1983. The conference and workshop formed part of the continuing IIASA program on Patterns of Economic Structural Change and Industrial Adjustment. Structural change was interpreted very broadly: the topics covered included the nature and causes of changes in different sectors of the world economy, the relationship between international markets and national economies, and issues of organization and incentives in large economic systems. There is a general consensus that important economic structural changes are occurring in the world economy. There are, however, several alternative approaches to measuring these changes, to modeling the process, and to devising appropriate responses in terms of policy measures and institutional redesign. Other interesting questions concern the role of the international economic system in transmitting such changes, and the merits of alternative modes of economic organization in responding to structural change. All of these issues were addressed by participants in the workshop and conference, and will be the focus of the continuation of the research program's work

Disruption of the mouse MRF4 gene identifies multiple waves of myogenesis in the myotome

MRF4 (herculin/Myf-6) is one of the four member MyoD family of transcription factors identified by their ability to enforce skeletal muscle differentiation upon a wide variety of nonmuscle cell types. In this study the mouse germline MRF4 gene was disrupted by targeted recombination. Animals homozygous for the MRF4bh1 allele, a deletion of the functionally essential bHLH domain, displayed defective axial myogenesis and rib pattern formation, and they died at birth. Differences in somitogenesis between homozygous MRF4bh1 embryos and their wild-type littermates provided evidence for three distinct myogenic regulatory programs (My1-My3) in the somite, which correlate temporally and spatially with three waves of cellular recruitment to the expanding myotome. The first program (My1), marked initially by Myf-5 expression and followed by myogenin, began on schedule in the MRF4bh1/bh1 embryos at day 8 post coitum (E8). A second program (My2) was highly deficient in homozygous mutant MRF4 embryos, and normal expansion of the myotome failed. Moreover, expression of downstream muscle-specific genes, including FGF-6, which is a candidate regulator of inductive interactions, did not occur normally. The onset of MyoD expression around E10.5 in wild-type embryos marks a third myotomal program (My3), the execution of which was somewhat delayed in MRF4 mutant embryos but ultimately led to extensive myogenesis in the trunk. By E15 it appeared to have largely compensated for the defective My2 program in MRF4 mutants. Homozygous MRF4bh1 animals also showed improper rib pattern formation perhaps due to the absence of signals from cells expressing the My2 program. Finally, a later and relatively mild phenotype was detected in intercostal muscles of newborn animals

Changes from 1986 to 2006 in reasons for liking leisure-time physical activity among adolescents

Reasons for participating in physical activity (PA) may have changed in accordance with the general modernization of society. The aim is to examine changes in self-reported reasons for liking leisure-time physical activity (LTPA) and their association with self-reported LTPA over a 20-year period. Data were collected among nationally representative samples of 13-year-olds in Finland, Norway, and Wales in 1986 and 2006 (N = 9252) as part of the WHO cross-national Health Behaviour in School-aged Children (HBSC) study. Univariate ANOVAs to establish differences according to gender, year, and country were conducted. In all countries, 13-year-olds in 2006 tended to report higher importance in terms of achievement and social reasons than their counterparts in 1986, while changes in health reasons were minor. These reasons were associated with LTPA in a similar way at both time points. Health reasons for liking LTPA were considered most important, and were the strongest predictor of LTPA. The findings seem robust as they were consistent across countries and genders. Health education constitutes the most viable strategy for promoting adolescents' motivation for PA, and interventions and educational efforts could be improved by an increased focus on LTPA and sport as a social activity

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

Skeletal muscle phenotypes initiated by ectopic MyoD in transgenic mouse heart

Forced expression of the myogenic regulatory gene MyoD in many types of cultured cells initiates their conversion into skeletal muscle. It is not known, however, if MyoD expression serves to activate all or part of the skeletal muscle program in vivo during animal development, nor is it known how limiting the influences of cellular environment may be on the regulatory effects of MyoD. To begin to address these issues, we have produced transgenic mice which express MyoD in developing heart, where neither MyoD nor its three close relatives—myogenin, Myf-5, and MRF4/herculin/Myf-6—are normally expressed. The resulting gross phenotype in offspring from multiple, independent transgenic founders includes abnormal heart morphology and ultimately leads to death. At the molecular level, affected hearts exhibit activation of skeletal muscle-specific regulatory as well as structural genes. We conclude that MyoD is able to initiate the program that leads to skeletal muscle differentiation during mouse development, even in the presence of the ongoing cardiac differentiation program. Thus, targeted misexpression of this tissue-specific regulator during mammalian embryogenesis can activate, either directly or indirectly, a diverse set of genes normally restricted to a different cell lineage and a different cellular environment

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

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

Evolution of trace gases and particles emitted by a chaparral fire in California

Biomass burning (BB) is a major global source of trace gases and particles. Accurately representing the production and evolution of these emissions is an important goal for atmospheric chemical transport models. We measured a suite of gases and aerosols emitted from an 81 hectare prescribed fire in chaparral fuels on the central coast of California, US on 17 November 2009. We also measured physical and chemical changes that occurred in the isolated downwind plume in the first ~4 h after emission. The measurements were carried out onboard a Twin Otter aircraft outfitted with an airborne Fourier transform infrared spectrometer (AFTIR), aerosol mass spectrometer (AMS), single particle soot photometer (SP2), nephelometer, LiCor CO_2 analyzer, a chemiluminescence ozone instrument, and a wing-mounted meteorological probe. Our measurements included: CO_2; CO; NO_x; NH_3; non-methane organic compounds; organic aerosol (OA); inorganic aerosol (nitrate, ammonium, sulfate, and chloride); aerosol light scattering; refractory black carbon (rBC); and ambient temperature, relative humidity, barometric pressure, and three-dimensional wind velocity. The molar ratio of excess O_3 to excess CO in the plume (ΔO_3/ΔCO) increased from −5.13 (±1.13) × 10^(−3) to 10.2 (±2.16) × 10^(−2) in ~4.5 h following smoke emission. Excess acetic and formic acid (normalized to excess CO) increased by factors of 1.73 ± 0.43 and 7.34 ± 3.03 (respectively) over the same time since emission. Based on the rapid decay of C_2H_4 we infer an in-plume average OH concentration of 5.27 (±0.97) × 10^6 molec cm^(−3), consistent with previous studies showing elevated OH concentrations in biomass burning plumes. Ammonium, nitrate, and sulfate all increased over the course of 4 h. The observed ammonium increase was a factor of 3.90 ± 2.93 in about 4 h, but accounted for just ~36% of the gaseous ammonia lost on a molar basis. Some of the gas phase NH_3 loss may have been due to condensation on, or formation of, particles below the AMS detection range. NO_x was converted to PAN and particle nitrate with PAN production being about two times greater than production of observable nitrate in the first ~4 h following emission. The excess aerosol light scattering in the plume (normalized to excess CO_2) increased by a factor of 2.50 ± 0.74 over 4 h. The increase in light scattering was similar to that observed in an earlier study of a biomass burning plume in Mexico where significant secondary formation of OA closely tracked the increase in scattering. In the California plume, however, ΔOA/ΔCO_2 decreased sharply for the first hour and then increased slowly with a net decrease of ~20% over 4 h. The fraction of thickly coated rBC particles increased up to ~85% over the 4 h aging period. Decreasing OA accompanied by increased scattering/particle coating in initial aging may be due to a combination of particle coagulation and evaporation processes. Recondensation of species initially evaporated from the particles may have contributed to the subsequent slow rise in OA. We compare our results to observations from other plume aging studies and suggest that differences in environmental factors such as smoke concentration, oxidant concentration, actinic flux, and RH contribute significantly to the variation in plume evolution observations