438 research outputs found
Androgen-induced rhox homeobox genes modulate the expression of AR-regulated genes
Rhox5, the founding member of the reproductive homeobox on the X chromosome (Rhox) gene cluster, encodes a homeodomain-containing transcription factor that is selectively
expressed in Sertoli cells, where it promotes the survival of male germ cells. To identify Rhox5-regulated genes, we generated 15P-1 Sertoli cell clones expressing physiological levels of Rhox5 from a stably transfected expression vector. Microarray analysis identified many
genes altered in expression in response to Rhox5, including those encoding proteins controlling cell cycle regulation, apoptosis, metabolism, and cell-cell interactions. Fifteen of these Rhox5-regulated genes were chosen for further analysis. Analysis of Rhox5-null male
mice indicated that at least 9 of these are Rhox5-regulated in the testes in vivo. Many of them have distinct postnatal expression patterns and are regulated by Rhox5 at different postnatal time points. Most of them are expressed in Sertoli cells, indicating that they are
candidates to be directly regulated by Rhox5. Transfection analysis with expression vectors encoding different mouse and human Rhox family members revealed that the regulatory
response of a subset of these Rhox5-regulated genes is both conserved and redundant. Given that Rhox5 depends on AR for expression in Sertoli cells, we examined whether some Rhox5-regulated genes are also regulated by androgen receptor (AR). We provide several lines of evidence that this is the case, leading us to propose that RHOX5 serves as a key intermediate transcription factor that directs some of the actions of AR in the testes
Pregnancy Reprograms the Epigenome of Mammary Epithelial Cells and Blocks the Development of Premalignant Lesions
Pregnancy causes a series of cellular and molecular changes in mammary epithelial cells (MECs) of female adults. In addition, pregnancy can also modify the predisposition of rodent and human MECs to initiate oncogenesis. Here, we investigate how pregnancy reprograms enhancer chromatin in the mammary epithelium of mice and influences the transcriptional output of the oncogenic transcription factor cMYC. We find that pregnancy induces an expansion of the active cis-regulatory landscape of MECs, which influences the activation of pregnancy-related programs during re-exposure to pregnancy hormones in vivo and in vitro. Using inducible cMYC overexpression, we demonstrate that post-pregnancy MECs are resistant to the downstream molecular programs induced by cMYC, a response that blunts carcinoma initiation, but does not perturb the normal pregnancy-induced epigenomic landscape. cMYC overexpression drives post-pregnancy MECs into a senescence-like state, and perturbations of this state increase malignant phenotypic changes. Taken together, our findings provide further insight into the cell-autonomous signals in post-pregnancy MECs that underpin the regulation of gene expression, cellular activation, and resistance to malignant development
A population Monte Carlo scheme with transformed weights and its application to stochastic kinetic models
This paper addresses the problem of Monte Carlo approximation of posterior
probability distributions. In particular, we have considered a recently
proposed technique known as population Monte Carlo (PMC), which is based on an
iterative importance sampling approach. An important drawback of this
methodology is the degeneracy of the importance weights when the dimension of
either the observations or the variables of interest is high. To alleviate this
difficulty, we propose a novel method that performs a nonlinear transformation
on the importance weights. This operation reduces the weight variation, hence
it avoids their degeneracy and increases the efficiency of the importance
sampling scheme, specially when drawing from a proposal functions which are
poorly adapted to the true posterior.
For the sake of illustration, we have applied the proposed algorithm to the
estimation of the parameters of a Gaussian mixture model. This is a very simple
problem that enables us to clearly show and discuss the main features of the
proposed technique. As a practical application, we have also considered the
popular (and challenging) problem of estimating the rate parameters of
stochastic kinetic models (SKM). SKMs are highly multivariate systems that
model molecular interactions in biological and chemical problems. We introduce
a particularization of the proposed algorithm to SKMs and present numerical
results.Comment: 35 pages, 8 figure
Atl1 Regulates Choice between Global Genome and Transcription-Coupled Repair of O6-Alkylguanines
Nucleotide excision repair (NER) has long been known to remove DNA lesions induced by chemical carcinogens, and the molecular mechanism has been partially elucidated. Here we demonstrate that in Schizosaccharomyces pombe a DNA recognition protein, alkyltransferase-like 1 (Atl1), can play a pivotal role in selecting a specific NER pathway, depending on the nature of the DNA modification. The relative ease of dissociation of Atl1 from DNA containing small O6-alkylguanines allows accurate completion of global genome repair (GGR), whereas strong Atl1 binding to bulky O6-alkylguanines blocks GGR, stalls the transcription machinery, and diverts the damage to transcription-coupled repair. Our findings redraw the initial stages of the NER process in those organisms that express an alkyltransferase-like gene and raise the question of whether or not O6-alkylguanine lesions that are poor substrates for the alkyltransferase proteins in higher eukaryotes might, by analogy, signal such lesions for repair by NER
Fly's time
The struggle between public and private efforts to sequence the fly genome is the subject of Michael Ashburner's new book, Won for All: How the Drosophila Genome Was Sequence
Classification and analyses of of coating flows
YesA classification of coating flows is presented to facilitate a fundamental approach to their study. Four categories are observed: free, metered, transfer and gravure coating flows. They are all limited by free surface(s) which make their analysis difficult. Various analytical approaches have been used and these are briefly reviewed in this paper
Observational diagnostics of gas in protoplanetary disks
Protoplanetary disks are composed primarily of gas (99% of the mass).
Nevertheless, relatively few observational constraints exist for the gas in
disks. In this review, I discuss several observational diagnostics in the UV,
optical, near-IR, mid-IR, and (sub)-mm wavelengths that have been employed to
study the gas in the disks of young stellar objects. I concentrate in
diagnostics that probe the inner 20 AU of the disk, the region where planets
are expected to form. I discuss the potential and limitations of each gas
tracer and present prospects for future research.Comment: Review written for the proceedings of the conference "Origin and
Evolution of Planets 2008", Ascona, Switzerland, June 29 - July 4, 2008. Date
manuscript: October 2008. 17 Pages, 6 graphics, 134 reference
Reach, recruitment, dose, and intervention fidelity of the GoActive school-based physical activity intervention in the UK: a mixed-methods process evaluation
School-based multi-component physical activity (PA) promotion is advocated; however, research has indicated that a multi-component approach may not always be effective at increasing adolescent PA. Evaluation of the GoActive 12-week multi-component school-based intervention showed no effect on adolescent PA. A mixed-methods process evaluation was embedded to facilitate greater understanding of the results, to elicit subgroup perceptions, and to provide insight into contextual factors influencing intervention implementation. This paper presents the reach, recruitment, dose, and fidelity of GoActive, and identifies challenges to implementation. The process evaluation employed questionnaires (1543 Year 9s), individual interviews (16 Year 9s; 7 facilitators; 9 contact teachers), focus groups (48 Year 9s; 58 mentors), alongside GoActive website analytics and researcher observations. GoActive sessions reached 39.4% of Year 9s. Intervention satisfaction was relatively high for mentors (87.3%) and facilitators (85.7%), but lower for Year 9s (59.5%) and teachers (50%). Intervention fidelity was mixed within and between schools. Mentorship was the most implemented component. Factors potentially contributing to low implementation included ambiguity of the roles subgroups played within intervention delivery, Year 9 engagement, institutional support, and further school-level constraints. Multiple challenges and varying contextual considerations hindered the implementation of GoActive in multiple school sites. Methods to overcome contextual challenges to implementation warrant in-depth consideration and innovative approaches
An Excursion-Theoretic Approach to Stability of Discrete-Time Stochastic Hybrid Systems
We address stability of a class of Markovian discrete-time stochastic hybrid
systems. This class of systems is characterized by the state-space of the
system being partitioned into a safe or target set and its exterior, and the
dynamics of the system being different in each domain. We give conditions for
-boundedness of Lyapunov functions based on certain negative drift
conditions outside the target set, together with some more minor assumptions.
We then apply our results to a wide class of randomly switched systems (or
iterated function systems), for which we give conditions for global asymptotic
stability almost surely and in . The systems need not be time-homogeneous,
and our results apply to certain systems for which functional-analytic or
martingale-based estimates are difficult or impossible to get.Comment: Revised. 17 pages. To appear in Applied Mathematics & Optimizatio
Quasielastic axial-vector mass from experiments on neutrino-nucleus scattering
We analyze available experimental data on the total and differential
charged-current cross sections for quasielastic neutrino and antineutrino
scattering off nucleons, measured with a variety of nuclear targets in the
accelerator experiments at ANL, BNL, FNAL, CERN, and IHEP, dating from the end
of sixties to the present day. The data are used to adjust the poorly known
value of the axial-vector mass of the nucleon.Comment: 27 pages, 19 figures. Typos corrected; tables, figures and references
added, discussion extended; matches published versio
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