The c-fos serum response element responds to protein kinase C-dependent and -independent signals but not to cyclic AMP

Transcription of the c-fos proto-oncogene is rapidly induced by serum growth factors. A short c-fos DNA element, the serum response element (SRE), is required for this response to serum. However, serum activates a series of distinct intracellular signaling pathways, and it is not known to which of these pathways the SRE responds. To address this question, mutations have been introduced into the SRE of an otherwise intact c-fos promoter/enhancer. These mutations strongly reduce the binding of a nuclear factor to this site. Plasmids carrying either a wild-type or mutant c-fos SRE were transfected into fibroblasts and tested for their response to whole serum, purified recombinant c-sis protein, the protein kinase C activator phorbol myristate acetate, and activators of the cyclic AMP (cAMP) second messenger system. Assays were carried out under normal conditions and after chronic phorbol ester-treatment to deplete phorbol ester activatable protein kinase C activity from transfected cells. The results show that the SRE is necessary and sufficient for response to both protein kinase C-dependent and -independent intracellular signaling pathways but not for response to the cAMP pathway

DNA bending and orientation-dependent function of YY1 in the c-fos promoter

The assembly of multicomponent complexes at promoters, enhancers, and silencers likely entails perturbations in the path of the DNA helix. We present evidence that YY1, a ubiquitously expressed DNA-binding protein, regulates the activity of the c-fos promoter primarily through an effect on DNA structure. YY1 binds to and induces a phased DNA bend at three sites in this promoter. By use of a truncated c-fos promoter activity containing a single functional YY1 site, we show that YY1 represses promoter activity but that repression does not appear to be an intrinsic property of the protein in this context. Moreover, when the orientation of the YY1 site is reversed, YY1 activates the same promoter. Repression by YY1 is also alleviated by changing the relative phasing of factor-binding sites on either side of YY1. We conclude that the principal function of YY1 in this promoter is to bend DNA to regulate contact between other proteins. Thus, YY1 represents a new class of transcription factors that influences promoter function by affecting promoter structure rather than by directly contacting the transcriptional machinery. We provide evidence that the product of the male sex determination gene SRY may also belong to this class of structural factors

Growth-regulated expression of D-type cyclin genes in human diploid fibroblasts

The human CCND1 cyclin D1/PRAD1 gene was previously identified by a genetic screen for G1 cyclin function in Saccharomyces cerevisiae and also was identified as the putative BCL1 oncogene. However, its role in human cell proliferation is not known. To determine if expression of human D-type cyclin genes correlates with the state of cell growth, we examined the level of mRNAs for CCND1 and a related gene, CCND3, in normal human diploid fibroblasts (HDF). The levels of both mRNAs decrease upon serum depletion or at high cell densities. Following stimulation of quiescent fibroblasts with serum, the mRNA levels increase gradually to a peak at about 12 hr, prior to the onset of S phase. Induction of cyclin gene expression by serum is reduced concomitantly with the decline in FOS induction in aging HDFs, suggesting a possible relationship to the decrease in the proliferative response to mitogens during cellular senescence. Cycloheximide partially blocks the induction of CCND1 and CCND3 gene expression by serum, suggesting that both de novo protein synthesis-dependent and -independent pathways contribute to induction. Treatment of HDFs with defined growth factors suggests a correlation between CCND mRNA induction and DNA synthesis. However, induction of these genes is not sufficient for the transition from quiescence through G1 into S phase

Transition between nuclear and quark-gluon descriptions of hadrons and light nuclei

We provide a perspective on studies aimed at observing the transition between hadronic and quark-gluonic descriptions of reactions involving light nuclei. We begin by summarizing the results for relatively simple reactions such as the pion form factor and the neutral pion transition form factor as well as that for the nucleon and end with exclusive photoreactions in our simplest nuclei. A particular focus will be on reactions involving the deuteron. It is noted that a firm understanding of these issues is essential for unraveling important structure information from processes such as deeply virtual Compton scattering as well as deeply virtual meson production. The connection to exotic phenomena such as color transparency will be discussed. A number of outstanding challenges will require new experiments at modern facilities on the horizon as well as further theoretical developments.Comment: 37 pages, 17 figures, submitted to Reports on Progress in Physic

Charged Scalar Particles and τ\tau Leptonic Decay

Charged scalar particles introduced in some extensions of the standard model can induce $\tau$ leptonic decay at tree level. We find that with some charged SU(2)-singlet scalar particles, like ones introduced in Zee-type models, $\tau$ leptonic decay width is always smaller than what is predicted by the standard model, therefore they may offer a natural solution to $\tau$ decay puzzle. To be more specific, we examine some Zee-type models in detail to see if at the same time they are acceptable in particle physics, cosmology and astrophysics. It is shown that $\tau$ decay data do put some constrains on these models.Comment: ICTP Report No. IC/93/31, 12 pages, Latex, one figure is not included, it is available upon deman

A Multi-disciplinary Overview of Chagas in Periurban Peru

There are between 8 and 11 million cases of America Human Trypanosomiasis, commonly known as Chagas disease, in Latin America. Chagas is endemic in southern Peru, especially the Arequipa region, where it has expanded from poor, rural areas to periurban communities. This paper summarizes the findings of four studies in periurban Arequipa: on determinants of disease-vector infestation; on prevalence, spatial patterns, and risk factors of Chagas; on links between migration, settlement patterns, and disease-vector infestation; and on the relationship between discordant test results and spatially clustered transmission hotspots. These studies identified two risk factors associated with the disease: population dynamics and the urbanization of poverty. Understanding the disease within this new urban context will allow for improved public health prevention efforts and policy initiatives. Discovered in 1909 by Brazilian physician Carlos Chagas, American Human Trypanosomiasis is a chronic and potentially life-threatening illness found throughout Latin America (Moncayo, 2003). Indeed, it is estimated that there are between 8 and 11 million cases in Mexico and Central and South America (Centers for Disease Control [CDC], 2009). Chagas disease, as it is most commonly known, is endemic in southern Peru, especially in the region of Arequipa. Once thought to be limited to poor, rural areas, the disease is now appearing in the periurban communities that surround Arequipa City, the capital of the region (Cornejo del Carpio, 2003). Understanding the urbanization of Chagas disease will allow public health and medical professionals to better combat the further transmission of the disease. After providing an overview of Chagas and introducing the scope of the disease in Latin America, this paper will summarize the findings of four recent studies conducted in periurban districts in Arequipa. Ultimately, this paper seeks to identify the risk factors associated with Chagas infection in Arequipa’s periurban communities

Experimental determination of the evolution of the Bjorken integral at low Q^2

We extract the Bjorken integral Gamma^{p-n}_1 in the range 0.17 < Q^2 < 1.10 GeV^2 from inclusive scattering of polarized electrons by polarized protons, deuterons and 3He, for the region in which the integral is dominated by nucleon resonances. These data bridge the domains of the hadronic and partonic descriptions of the nucleon. In combination with earlier measurements at higher Q^2, we extract the non-singlet twist-4 matrix element f_2.Comment: Quoted world data updated. Minor change in some results, Minor rephrasin

A Common Explanation for the Atmospheric, Solar-Neutrino and Double Beta Decay Anomalies

We make a number of small changes, including correcting an error in our heavy-neutrino decay rate. None of our analysis is changed, either in substance or detail.Comment: 25 pages, 6 Figures, McGill-93/1

Constraints on a Massive Dirac Neutrino Model

We examine constraints on a simple neutrino model in which there are three massless and three massive Dirac neutrinos and in which the left handed neutrinos are linear combinations of doublet and singlet neutrinos. We examine constraints from direct decays into heavy neutrinos, indirect effects on electroweak parameters, and flavor changing processes. We combine these constraints to examine the allowed mass range for the heavy neutrinos of each of the three generations.Comment: latex, 29 pages, 7 figures (not included), MIT-CTP-221