19,731 research outputs found
Circadian rhythm and cell population growth
Molecular circadian clocks, that are found in all nucleated cells of mammals,
are known to dictate rhythms of approximately 24 hours (circa diem) to many
physiological processes. This includes metabolism (e.g., temperature, hormonal
blood levels) and cell proliferation. It has been observed in tumor-bearing
laboratory rodents that a severe disruption of these physiological rhythms
results in accelerated tumor growth. The question of accurately representing
the control exerted by circadian clocks on healthy and tumour tissue
proliferation to explain this phenomenon has given rise to mathematical
developments, which we review. The main goal of these previous works was to
examine the influence of a periodic control on the cell division cycle in
physiologically structured cell populations, comparing the effects of periodic
control with no control, and of different periodic controls between them. We
state here a general convexity result that may give a theoretical justification
to the concept of cancer chronotherapeutics. Our result also leads us to
hypothesize that the above mentioned effect of disruption of circadian rhythms
on tumor growth enhancement is indirect, that, is this enhancement is likely to
result from the weakening of healthy tissue that are at work fighting tumor
growth
Circadian rhythms and hormonal homeostasis: Pathophysiological implications
Over recent years, a deeper comprehension of the molecular mechanisms that control biological clocks and circadian rhythms has been achieved. In fact, many studies have contributed to unravelling the importance of the molecular clock for the regulation of our physiology, including hormonal and metabolic homeostasis. Here we will review the structure, organisation and molecular machinery that make our circadian clock work, and its relevance for the proper functioning of physiological processes. We will also describe the interconnections between circadian rhythms and endocrine homeostasis, as well as the underlying consequences that circadian dysregulations might have in the development of several pathologic affections. Finally, we will discuss how a better knowledge of such relationships might prove helpful in designing new therapeutic approaches for endocrine and metabolic diseases
Circadian rhythms of proliferation events in two mouse carcinomas
We studied the index of DNA synthesis (DNAs) of two cellular carcinomas: the hepatocellular ES12a and the mammary TN60 of mice, throughout one circadian cycle. In the results, we observed that both tumors have circadian rhythms (CRs), but the peaks of DNAs vary. Besides, the mean of DNAs along 24 h shows significative differences, the TN60 has higher values than the ES12a. These observed CR in the DNAs index in both carcinomas mean that, at least in partly, the proliferation of cancer cells can be regulated by endocrine factor as it normally occurs in ordinary cells. The big problem we can find for the chronopharmacology is that it is impossible to know in advance the rate of proliferation of each tumor.Fil: Garcia, Marcela. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Andrini, Laura Beatríz. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Martinez, Marina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Inda, Ana. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Palma, Maria Belen. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miriuka, Santiago Gabriel. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Errecalde, Ana Lia. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentin
Analysis of DNA-Damage Response to ionizing radiation in serum-shock synchronized human fibroblasts.
Many aspects of cellular physiology, including cellular response to genotoxic stress, are related to the circadian rhythmicity induced by the molecular clock. The current study investigated if the cellular response to DNA damage is in relation to endogenous expression levels of the PER2 protein, a key component of the molecular regulatory system that confers rhythmicity in mammalian cells. Human normal fibroblasts (CCD-34Lu) were subjected to serum shock to induce circadian oscillations of the PER2 protein and then irradiated with \u3b3- rays at times corresponding to the trough and peak expression of the PER2 protein. To better examine cellular response to DNA damage, the experiments performed in this study were carried out in non-proliferating CCD-34Lu fibroblasts in order to maintain the cell and circadian cycles separated while they were being exposed to genotoxic stress. Study results demonstrated that clonogenic cell survival, double-strand break repair kinetics, and TP53 protein levels were affected in the cells irradiated at the trough than in those irradiated at peak expression of the PER2 protein
The influence of biological rhythms on host–parasite interactions
Biological rhythms, from circadian control of cellular processes to annual cycles in life history, are a main structural element of biology. Biological rhythms are considered adaptive because they enable organisms to partition activities to cope with, and take advantage of, predictable fluctuations in environmental conditions. A flourishing area of immunology is uncovering rhythms in the immune system of animals, including humans. Given the temporal structure of immunity, and rhythms in parasite activity and disease incidence, we propose that the intersection of chronobiology, disease ecology, and evolutionary biology holds the key to understanding host–parasite interactions. Here, we review host–parasite interactions while explicitly considering biological rhythms, and propose that rhythms: influence within-host infection dynamics and transmission between hosts, might account for diel and annual periodicity in host–parasite systems, and can lead to a host–parasite arms race in the temporal domain
Comparison of Perron and Floquet eigenvalues in age structured cell division cycle models
We study the growth rate of a cell population that follows an age-structured
PDE with time-periodic coefficients. Our motivation comes from the comparison
between experimental tumor growth curves in mice endowed with intact or
disrupted circadian clocks, known to exert their influence on the cell division
cycle. We compare the growth rate of the model controlled by a time-periodic
control on its coefficients with the growth rate of stationary models of the
same nature, but with averaged coefficients. We firstly derive a delay
differential equation which allows us to prove several inequalities and
equalities on the growth rates. We also discuss about the necessity to take
into account the structure of the cell division cycle for chronotherapy
modeling. Numerical simulations illustrate the results.Comment: 26 page
An inequality for the Perron and Floquet eigenvalues of monotone differential systems and age structured equations
For monotone linear differential systems with periodic coefficients, the
(first) Floquet eigenvalue measures the growth rate of the system. We define an
appropriate arithmetico-geometric time average of the coefficients for which we
can prove that the Perron eigenvalue is smaller than the Floquet eigenvalue. We
apply this method to Partial Differential Equations, and we use it for an
age-structured systems of equations for the cell cycle. This opposition between
Floquet and Perron eigenvalues models the loss of circadian rhythms by cancer
cells.Comment: 7 pages, in English, with an abridged French versio
Quantitative analysis of regulatory flexibility under changing environmental conditions
The circadian clock controls 24-h rhythms in many biological processes, allowing appropriate timing of biological rhythms relative to dawn and dusk. Known clock circuits include multiple, interlocked feedback loops. Theory suggested that multiple loops contribute the flexibility for molecular rhythms to track multiple phases of the external cycle. Clear dawn- and dusk-tracking rhythms illustrate the flexibility of timing in Ipomoea nil. Molecular clock components in Arabidopsis thaliana showed complex, photoperiod-dependent regulation, which was analysed by comparison with three contrasting models. A simple, quantitative measure, Dusk Sensitivity, was introduced to compare the behaviour of clock models with varying loop complexity. Evening-expressed clock genes showed photoperiod-dependent dusk sensitivity, as predicted by the three-loop model, whereas the one- and two-loop models tracked dawn and dusk, respectively. Output genes for starch degradation achieved dusk-tracking expression through light regulation, rather than a dusk-tracking rhythm. Model analysis predicted which biochemical processes could be manipulated to extend dusk tracking. Our results reveal how an operating principle of biological regulators applies specifically to the plant circadian clock
Organellar carbon metabolism is co-ordinated with distinct developmental phases of secondary xylem
Subcellular compartmentation of plant biosynthetic pathways in the mitochondria and plastids requires coordinated regulation of nuclear encoded genes, and the role of these genes has been largely ignored by wood researchers. In this study, we constructed a targeted systems genetics coexpression network of xylogenesis in Eucalyptus using plastid and mitochondrial carbon metabolic genes and compared the resulting clusters to the aspen xylem developmental series. The constructed network clusters reveal the organization of transcriptional modules regulating subcellular metabolic functions in plastids and mitochondria. Overlapping genes between the plastid and mitochondrial networks implicate the common transcriptional regulation of carbon metabolism during xylem secondary growth. We show that the central processes of organellar carbon metabolism are distinctly coordinated across the developmental stages of wood formation and are specifically associated with primary growth and secondary cell wall deposition. We also demonstrate that, during xylogenesis, plastid-targeted carbon metabolism is partially regulated by the central clock for carbon allocation towards primary and secondary xylem growth, and we discuss these networks in the context of previously established associations with wood-related complex traits. This study provides a new resolution into the integration and transcriptional regulation of plastid- and mitochondrial-localized carbon metabolism during xylogenesis
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