380 research outputs found
Aging and Immortality in a Cell Proliferation Model
We investigate a model of cell division in which the length of telomeres
within the cell regulate their proliferative potential. At each cell division
the ends of linear chromosomes change and a cell becomes senescent when one or
more of its telomeres become shorter than a critical length. In addition to
this systematic shortening, exchange of telomere DNA between the two daughter
cells can occur at each cell division. We map this telomere dynamics onto a
biased branching diffusion process with an absorbing boundary condition
whenever any telomere reaches the critical length. As the relative effects of
telomere shortening and cell division are varied, there is a phase transition
between finite lifetime and infinite proliferation of the cell population.
Using simple first-passage ideas, we quantify the nature of this transition.Comment: 6 pages, 1 figure, 2-column revtex4 format; version 2: final
published form; contains various improvements in response to referee comment
Time evolution of the Partridge-Barton Model
The time evolution of the Partridge-Barton model in the presence of the
pleiotropic constraint and deleterious somatic mutations is exactly solved for
arbitrary fecundity in the context of a matricial formalism. Analytical
expressions for the time dependence of the mean survival probabilities are
derived. Using the fact that the asymptotic behavior for large time is
controlled by the largest matrix eigenvalue, we obtain the steady state values
for the mean survival probabilities and the Malthusian growth exponent. The
mean age of the population exhibits a power law decayment. Some Monte
Carlo simulations were also performed and they corroborated our theoretical
results.Comment: 10 pages, Latex, 1 postscript figure, published in Phys. Rev. E 61,
5664 (2000
Control of telomere length by a trimming mechanism that involves generation of t-circles
Telomere lengths are maintained in many cancer cells by the ribonucleoprotein enzyme telomerase but can be further elongated by increasing telomerase activity through the overexpression of telomerase components. We report here that increased telomerase activity results in increased telomere length that eventually reaches a plateau, accompanied by the generation of telomere length heterogeneity and the accumulation of extrachromosomal telomeric repeat DNA, principally in the form of telomeric circles (t-circles). Telomeric DNA was observed in promyelocytic leukemia bodies, but no intertelomeric copying or telomere exchange events were identified, and there was no increase in telomere dysfunction-induced foci. These data indicate that human cells possess a mechanism to negatively regulate telomere length by trimming telomeric DNA from the chromosome ends, most likely by t-loop resolution to form t-circles. Additionally, these results indicate that some phenotypic characteristics attributed to alternative lengthening of telomeres (ALT) result from increased mean telomere length, rather than from the ALT mechanism itself
Exact Solution of an Evolutionary Model without Ageing
We introduce an age-structured asexual population model containing all the
relevant features of evolutionary ageing theories. Beneficial as well as
deleterious mutations, heredity and arbitrary fecundity are present and managed
by natural selection. An exact solution without ageing is found. We show that
fertility is associated with generalized forms of the Fibonacci sequence, while
mutations and natural selection are merged into an integral equation which is
solved by Fourier series. Average survival probabilities and Malthusian growth
exponents are calculated indicating that the system may exhibit mutational
meltdown. The relevance of the model in the context of fissile reproduction
groups as many protozoa and coelenterates is discussed.Comment: LaTeX file, 15 pages, 2 ps figures, to appear in Phys. Rev.
Cluster analyses from the real-world NOVELTY study : six clusters across the asthma COPD spectrum
Funding The NOVELTY study is funded by AstraZeneca. ACKNOWLEDGMENTS The authors would like to thank the patients who participated in this study and the NOVELTY Scientific Community and the NOVELTY study investigators who are listed in full in Tables E7 and E8 in the Online Repository. Medical writing support, under the direction of the authors, was provided by Richard Knight, PhD, CMC Connect, a division of IPG Health Medical Communications, funded by AstraZeneca in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med. 2022;175[9]:1298-1304). J. Vestbo is supported by the NIHR Manchester Biomedical Research Centre and the NIHR Manchester Clinical Research FacilityPeer reviewedPublisher PD
Deepening democracy within Ireland's social partnership
Ireland's social partnership process, now under attack from a number of quarters, has repeatedly been charged with being 'undemocratic' in that it undermines the sovereign position of elected political representatives, with key policy formulation and decision-making taking place in fora outside the institutions of representative democracy. These critiques echo those against new forms of networked governance more globally. A key question therefore is how (and if) democracy may be deepened within social partnership or its potential successor(s). This article addresses this question by employing a post-liberal democratic framework to examine social partnership in practice, and by drawing lessons from another partnership process, Malawi's PRSP. Drawing from Malawi's experience, it is argued that democracy can be deepened within social partnership when governance deliberations and negotiations are conducted under conditions of vibrant public debate and genuine perspective-based representation, and when the communicative and discursive norms are widened to allow for such representation
Cloning and characterization of a novel gene, striamin, that interacts with the tumor suppressor protein p53
Expression analysis of a novel cDNA isolated from immortal murine fibroblasts revealed a single transcript of 3.0 kilobase pairs that was highly expressed in mouse and human striated muscle and in mouse heart. The gene has therefore been named striamin. Its expression was confined to skeletal muscle types with a fast glycolytic (2B) contractile phenotype. It was also detected in C2C12 mouse myoblasts and was down-regulated during in vitro myogenesis. The cDNA has a single open reading frame encoding a predicted 16.8-kDa protein of 149 amino acids with no homology to known proteins. Microinjection and transfection of green fluorescence protein-tagged striamin demonstrated that it localizes to the nucleus. Coimmunoprecipitations revealed that it can interact with p53 (a positive marker for myoblast differentiation) in vivo and in vitro. Furthermore, it repressed p53 activity in p53-mediated reporter assays. Fluorescence in situ hybridization with a mouse P1 genomic clone localized the gene to chromosome 12C3, which is syntenic to human chromosome 14q21-22
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