1,466 research outputs found
Multifractal characterisation of length sequences of coding and noncoding segments in a complete genome
The coding and noncoding length sequences constructed from a complete genome
are characterised by multifractal analysis. The dimension spectrum and
its derivative, the 'analogous' specific heat , are calculated for the
coding and noncoding length sequences of bacteria, where is the moment
order of the partition sum of the sequences. From the shape of the
and curves, it is seen that there exists a clear difference between the
coding/noncoding length sequences of all organisms considered and a completely
random sequence. The complexity of noncoding length sequences is higher than
that of coding length sequences for bacteria. Almost all curves for
coding length sequences are flat, so their multifractality is small whereas
almost all curves for noncoding length sequences are multifractal-like.
We propose to characterise the bacteria according to the types of the
curves of their noncoding length sequences.Comment: 15 pages with 5 figures, Latex, Accepted for publication in Physica
Network Physiology reveals relations between network topology and physiological function
The human organism is an integrated network where complex physiologic
systems, each with its own regulatory mechanisms, continuously interact, and
where failure of one system can trigger a breakdown of the entire network.
Identifying and quantifying dynamical networks of diverse systems with
different types of interactions is a challenge. Here, we develop a framework to
probe interactions among diverse systems, and we identify a physiologic
network. We find that each physiologic state is characterized by a specific
network structure, demonstrating a robust interplay between network topology
and function. Across physiologic states the network undergoes topological
transitions associated with fast reorganization of physiologic interactions on
time scales of a few minutes, indicating high network flexibility in response
to perturbations. The proposed system-wide integrative approach may facilitate
the development of a new field, Network Physiology.Comment: 12 pages, 9 figure
Measure representation and multifractal analysis of complete genomes
This paper introduces the notion of measure representation of DNA sequences.
Spectral analysis and multifractal analysis are then performed on the measure
representations of a large number of complete genomes. The main aim of this
paper is to discuss the multifractal property of the measure representation and
the classification of bacteria. From the measure representations and the values
of the spectra and related curves, it is concluded that these
complete genomes are not random sequences. In fact, spectral analyses performed
indicate that these measure representations considered as time series, exhibit
strong long-range correlation. For substrings with length K=8, the
spectra of all organisms studied are multifractal-like and sufficiently smooth
for the curves to be meaningful. The curves of all bacteria
resemble a classical phase transition at a critical point. But the 'analogous'
phase transitions of chromosomes of non-bacteria organisms are different. Apart
from Chromosome 1 of {\it C. elegans}, they exhibit the shape of double-peaked
specific heat function.Comment: 12 pages with 9 figures and 1 tabl
Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models
The distances over which biological molecules and their complexes can
function range from a few nanometres, in the case of folded structures, to
millimetres, for example during chromosome organization. Describing phenomena
that cover such diverse length, and also time scales, requires models that
capture the underlying physics for the particular length scale of interest.
Theoretical ideas, in particular, concepts from polymer physics, have guided
the development of coarse-grained models to study folding of DNA, RNA, and
proteins. More recently, such models and their variants have been applied to
the functions of biological nanomachines. Simulations using coarse-grained
models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure
Yeast thioredoxin reductase Trr1p controls TORC1-regulated processes
The thioredoxin system plays a predominant role in the control of cellular redox status. Thioredoxin reductase fuels the system with reducing power in the form of NADPH. The TORC1 complex promotes growth and protein synthesis when nutrients, particularly amino acids, are abundant. It also represses catabolic processes, like autophagy, which are activated during starvation. We analyzed the impact of yeast cytosolic thioredoxin reductase TRR1 deletion under different environmental conditions. It shortens chronological life span and reduces growth in grape juice fermentation. TRR1 deletion has a global impact on metabolism during fermentation. As expected, it reduces oxidative stress tolerance, but a compensatory response is triggered, with catalase and glutathione increasing. Unexpectedly, TRR1 deletion causes sensitivity to the inhibitors of the TORC1 pathway, such as rapamycin. This correlates with low Tor2p kinase levels and indicates a direct role of Trr1p in its stability. Markers of TORC1 activity, however, suggest increased TORC1 activity. The autophagy caused by nitrogen starvation is reduced in the trr1Δ mutant. Ribosomal protein Rsp6p is dephosphorylated in the presence of rapamycin. This dephosphorylation diminishes in the TRR1 deletion strain. These results show a complex network of interactions between thioredoxin reductase Trr1p and the processes controlled by TOR
Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors
Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects
An assessment of existing models for individualized breast cancer risk estimation in a screening program in Spain
Background: The aim of this study was to evaluate the calibration and discriminatory power of three predictive
models of breast cancer risk.
Methods: We included 13,760 women who were first-time participants in the Sabadell-Cerdanyola Breast Cancer
Screening Program, in Catalonia, Spain. Projections of risk were obtained at three and five years for invasive cancer
using the Gail, Chen and Barlow models. Incidence and mortality data were obtained from the Catalan registries.
The calibration and discrimination of the models were assessed using the Hosmer-Lemeshow C statistic, the area
under the receiver operating characteristic curve (AUC) and the Harrell’s C statistic.
Results: The Gail and Chen models showed good calibration while the Barlow model overestimated the number of
cases: the ratio between estimated and observed values at 5 years ranged from 0.86 to 1.55 for the first two models
and from 1.82 to 3.44 for the Barlow model. The 5-year projection for the Chen and Barlow models had the highest
discrimination, with an AUC around 0.58. The Harrell’s C statistic showed very similar values in the 5-year projection
for each of the models. Although they passed the calibration test, the Gail and Chen models overestimated the
number of cases in some breast density categories.
Conclusions: These models cannot be used as a measure of individual risk in early detection programs to
customize screening strategies. The inclusion of longitudinal measures of breast density or other risk factors in joint
models of survival and longitudinal data may be a step towards personalized early detection of BC.This study was funded by grant PS09/01340 and The Spanish Network on Chronic Diseases REDISSEC (RD12/0001/0007) from the Health Research Fund (Fondo de Investigación Sanitaria) of the Spanish Ministry of Health
Phenotypic Variation and Bistable Switching in Bacteria
Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.
Magnetism, FeS colloids, and Origins of Life
A number of features of living systems: reversible interactions and weak
bonds underlying motor-dynamics; gel-sol transitions; cellular connected
fractal organization; asymmetry in interactions and organization; quantum
coherent phenomena; to name some, can have a natural accounting via
interactions, which we therefore seek to incorporate by expanding the horizons
of `chemistry-only' approaches to the origins of life. It is suggested that the
magnetic 'face' of the minerals from the inorganic world, recognized to have
played a pivotal role in initiating Life, may throw light on some of these
issues. A magnetic environment in the form of rocks in the Hadean Ocean could
have enabled the accretion and therefore an ordered confinement of
super-paramagnetic colloids within a structured phase. A moderate H-field can
help magnetic nano-particles to not only overcome thermal fluctuations but also
harness them. Such controlled dynamics brings in the possibility of accessing
quantum effects, which together with frustrations in magnetic ordering and
hysteresis (a natural mechanism for a primitive memory) could throw light on
the birth of biological information which, as Abel argues, requires a
combination of order and complexity. This scenario gains strength from
observations of scale-free framboidal forms of the greigite mineral, with a
magnetic basis of assembly. And greigite's metabolic potential plays a key role
in the mound scenario of Russell and coworkers-an expansion of which is
suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed
Krishnaswami Alladi, Springer 201
TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells
TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4+CD8+ double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in an uncontrolled expansion that was dependent on the nonclassical major histocompatibility complex (MHC) protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR)
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