438 research outputs found
On dynamic network entropy in cancer
The cellular phenotype is described by a complex network of molecular
interactions. Elucidating network properties that distinguish disease from the
healthy cellular state is therefore of critical importance for gaining
systems-level insights into disease mechanisms and ultimately for developing
improved therapies. By integrating gene expression data with a protein
interaction network to induce a stochastic dynamics on the network, we here
demonstrate that cancer cells are characterised by an increase in the dynamic
network entropy, compared to cells of normal physiology. Using a fundamental
relation between the macroscopic resilience of a dynamical system and the
uncertainty (entropy) in the underlying microscopic processes, we argue that
cancer cells will be more robust to random gene perturbations. In addition, we
formally demonstrate that gene expression differences between normal and cancer
tissue are anticorrelated with local dynamic entropy changes, thus providing a
systemic link between gene expression changes at the nodes and their local
network dynamics. In particular, we also find that genes which drive
cell-proliferation in cancer cells and which often encode oncogenes are
associated with reductions in the dynamic network entropy. In summary, our
results support the view that the observed increased robustness of cancer cells
to perturbation and therapy may be due to an increase in the dynamic network
entropy that allows cells to adapt to the new cellular stresses. Conversely,
genes that exhibit local flux entropy decreases in cancer may render cancer
cells more susceptible to targeted intervention and may therefore represent
promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte
X-Ray Spectroscopy of Stars
(abridged) Non-degenerate stars of essentially all spectral classes are soft
X-ray sources. Low-mass stars on the cooler part of the main sequence and their
pre-main sequence predecessors define the dominant stellar population in the
galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense,
of X-ray spectra from the solar corona. X-ray emission from cool stars is
indeed ascribed to magnetically trapped hot gas analogous to the solar coronal
plasma. Coronal structure, its thermal stratification and geometric extent can
be interpreted based on various spectral diagnostics. New features have been
identified in pre-main sequence stars; some of these may be related to
accretion shocks on the stellar surface, fluorescence on circumstellar disks
due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot
stars clearly dominate the interaction with the galactic interstellar medium:
they are the main sources of ionizing radiation, mechanical energy and chemical
enrichment in galaxies. High-energy emission permits to probe some of the most
important processes at work in these stars, and put constraints on their most
peculiar feature: the stellar wind. Here, we review recent advances in our
understanding of cool and hot stars through the study of X-ray spectra, in
particular high-resolution spectra now available from XMM-Newton and Chandra.
We address issues related to coronal structure, flares, the composition of
coronal plasma, X-ray production in accretion streams and outflows, X-rays from
single OB-type stars, massive binaries, magnetic hot objects and evolved WR
stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures
(partly multiple); some corrections made after proof stag
Search for Charged Higgs Bosons in e+e- Collisions at \sqrt{s} = 189 GeV
A search for pair-produced charged Higgs bosons is performed with the L3
detector at LEP using data collected at a centre-of-mass energy of 188.6 GeV,
corresponding to an integrated luminosity of 176.4 pb^-1. Higgs decays into a
charm and a strange quark or into a tau lepton and its associated neutrino are
considered. The observed events are consistent with the expectations from
Standard Model background processes. A lower limit of 65.5 GeV on the charged
Higgs mass is derived at 95 % confidence level, independent of the decay
branching ratio Br(H^{+/-} -> tau nu)
Polychlorinated biphenyls, cytochrome P450 1A1 (CYP1A1) polymorphisms, and breast cancer risk among African American women and white women in North Carolina: a population-based case-control study
INTRODUCTION: Epidemiologic studies have not shown a strong relationship between blood levels of polychlorinated biphenyls (PCBs) and breast cancer risk. However, two recent studies showed a stronger association among postmenopausal white women with the inducible M2 polymorphism in the cytochrome P450 1A1 (CYP1A1) gene. METHODS: In a population-based case-control study, we evaluated breast cancer risk in relation to PCBs and the CYP1A1 polymorphisms M1 (also known as CYP1A1*2A), M2 (CYP1A1*2C), M3 (CYP1A1*3), and M4 (CYP1A1*4). The study population consisted of 612 patients (242 African American, 370 white) and 599 controls (242 African American, 357 white). RESULTS: There was no evidence of strong joint effects between CYP1A1 M1-containing genotypes and total PCBs in African American or white women. Statistically significant multiplicative interactions were observed between CYP1A1 M2-containing genotypes and elevated plasma total PCBs among white women (P value for likelihood ratio test = 0.02). Multiplicative interactions were also observed between CYP1A1 M3-containing genotypes and elevated total PCBs among African American women (P value for likelihood ratio test = 0.10). CONCLUSIONS: Our results confirm previous reports that CYP1A1 M2-containing genotypes modify the association between PCB exposure and risk of breast cancer. We present additional evidence suggesting that CYP1A1 M3-containing genotypes modify the effects of PCB exposure among African American women. Additional studies are warranted, and meta-analyses combining results across studies will be needed to generate more precise estimates of the joint effects of PCBs and CYP1A1 genotypes
A gender perspective on factors that influence outdoor recreational physical activity among the elderly
<p>Abstract</p> <p>Background</p> <p>Physical activity (PA) is part of a healthy lifestyle and prevents many chronic health problems, in addition to promoting mental health. PA performed outdoors has been found particularly good for promoting one's well-being. The aim of this study was to investigate the extent to which outdoor recreational PA was carried out during 1 year, and the factors influencing such activities from a gender perspective among persons ≥ 60 years of age.</p> <p>Methods</p> <p>This study included 999 individuals 60-96 years of age living in the south eastern part of Sweden. Data collection was carried out during the years of 2001-2003. We measured the amount of regular light and/or intense outdoor recreational PA performed during the last year and determined the probability of performing PA as a function of 10 variables covering individual and socioeconomic factors.</p> <p>Results</p> <p>Our results suggest that being independent physically and healthy enough to manage one's personal hygiene and having access to areas for country walks were the most important factors associated with the probability of engaging in outdoor recreational PA for both men and women. Despite the level of performance being almost equal for the sexes as two-thirds of both had performed outdoor recreational PA during the preceding year more factors, i.e., living alone, being unable to cover an unexpected cost, fear of being violated, and fear of falling, were associated with the possibilities of engaging in outdoor recreational PA among women. Also increasing age seems to affect activities among women negatively to a higher extent than men.</p> <p>Conclusion</p> <p>Men and women seem to have different opportunities and needs with respect to performing PA. These considerations do not seem to be sufficiently taken into account today and improvements could be made concerning e.g., health-promoting activities suggested to the elderly by healthcare personnel and spatial planning within society. Promoting outdoor recreational PA that has restorative effects on well-being needs to focus on activities which are attractive and affordable for the majority of both men and women.</p
Transcriptome-wide association study reveals candidate causal genes for lung cancer.
We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large-scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome-wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never- and ever-smokers). We performed replication analysis using lung data from the Genotype-Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever-smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E-99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E-6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3-adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E-5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk
Exploiting solar visible-range observations by inversion techniques: from flows in the solar subsurface to a flaring atmosphere
Observations of the Sun in the visible spectral range belong to standard
measurements obtained by instruments both on the ground and in the space.
Nowadays, both nearly continuous full-disc observations with medium resolution
and dedicated campaigns of high spatial, spectral and/or temporal resolution
constitute a holy grail for studies that can capture (both) the long- and
short-term changes in the dynamics and energetics of the solar atmosphere.
Observations of photospheric spectral lines allow us to estimate not only the
intensity at small regions, but also various derived data products, such as the
Doppler velocity and/or the components of the magnetic field vector. We show
that these measurements contain not only direct information about the dynamics
of solar plasmas at the surface of the Sun but also imprints of regions below
and above it. Here, we discuss two examples: First, the local time-distance
helioseismology as a tool for plasma dynamic diagnostics in the near subsurface
and second, the determination of the solar atmosphere structure during flares.
The methodology in both cases involves the technique of inverse modelling.Comment: 29 pages, 15 figures. Accepted for publication in the book "Reviews
in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds
Kabath, Jones and Skarka; publisher Springer Nature) funded by the European
Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul"
2017-1-CZ01-KA203-03556
Mechanisms and role of microRNA deregulation in cancer onset and progression
MicroRNAs are key regulators of various fundamental biological processes and, although representing only a small portion of the genome, they regulate a much larger population of target genes. Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20–23 nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis and invasion. MicroRNA targeting is mostly achieved through specific base-pairing interactions between the 5′ end (‘seed’ region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3′ UTR diminish mRNA stability. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. Calin and Croce were the first to demonstrate a connection between microRNAs and increased risk of developing cancer, and meanwhile the role of microRNAs in carcinogenesis has definitively been evidenced. It needs to be considered that the complex mechanism of gene regulation by microRNAs is profoundly influenced by variation in gene sequence (polymorphisms) of the target sites. Thus, individual variability could cause patients to present differential risks regarding several diseases. Aiming to provide a critical overview of miRNA dysregulation in cancer, this article reviews the growing number of studies that have shown the importance of these small molecules and how these microRNAs can affect or be affected by genetic and epigenetic mechanisms
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