scholarly journals The “friend and foe” of deterministic and stochastic cell-cell variations

Author(s):  
Søren Vedel ◽  
Andrej Košmrlj ◽  
Harry Nunns ◽  
Ala Trusina

Abstract By diversifying, cells in a clonal population can together overcome the limits of individuals. Diversity in single-cell growth rates allows the population to survive environmental stresses, such as antibiotics, and grow faster than undiversified population. These functional cell-cell variations can arise stochastically, from noise in biochemical reactions, or deterministically, by asymmetrically distributing damaged components. While each of the mechanism is well understood, the effect of the combined mechanisms is unclear. To evaluate the contribution of the deterministic component we mapped the growing population to the Ising model. Model results, confirmed by simulations and experimental data, show that cell-cell variations increase near-linearly with stress. As a consequence, we predict that the entropic gain — the gain in population doubling time compared to an “average” cell — is primarily stochastic at low stress but crosses over to deterministic at higher stresses. Furthermore, we find that while the deterministic component minimizes population damage, stochastic variations antagonize this effect. Together our results may help identifying stress-tolerant pathogenic cells and thus inspire novel antibiotic strategies.

2019 ◽  
Author(s):  
Reinaldo García-García ◽  
Arthur Genthon ◽  
David Lacoste

Using a population dynamics inspired by an ensemble of growing cells, a set of fluctuation theorems linking observables measured at the lineage and population levels are derived. One of these relations implies inequalities comparing the population doubling time with the mean generation time at the lineage or population levels. We argue that testing these inequalities provides useful insights into the underlying mechanism controlling the division rate in such branching processes.


1990 ◽  
Vol 258 (2) ◽  
pp. E368-E376 ◽  
Author(s):  
G. Shillabeer ◽  
J. M. Forden ◽  
J. C. Russell ◽  
D. C. Lau

We have investigated the in vitro rate of replication and differentiation of preadipocytes derived from lean (+/+) and obese (cp/cp) male JCR:LA-corpulent (cp) rats in an attempt to identify mechanisms that regulate adipose tissue growth. Cp/cp rats were twofold heavier than age-matched lean rats by 9-10 mo. Cp/cp-derived preadipocytes demonstrated an inherently slower rate of replication than +/+ preadipocytes (population doubling time: cp/cp 52.3 +/- 9.6 h vs. +/+ 19.7 +/- 1.6 h), although the preadipocyte pool in the cp/cp was significantly greater. Cp/cp preadipocytes were resistant to hormonally induced differentiation (19.9 +/- 9.4% of cells accumulated lipid) but differentiated when cocultured with mature adipocytes to the same extent as preadipocytes derived from Sprague-Dawley (SD) rats (cp/cp 48.4 +/- 15.2% vs. SD 52.2 +/- 11.9%). In contrast, SD preadipocytes did not differentiate in response to mature adipocytes from +/+ rats (13.8 +/- 5.2%). Our observations suggest that preadipocyte replication and maturation may not be controlled in a coordinated manner.


2019 ◽  
Vol 19 (5) ◽  
pp. 1363-1370
Author(s):  
Xiao-Bao Nie ◽  
Yu-Qing Wu ◽  
Yuan-Nan Long ◽  
Chang-Bo Jiang ◽  
Li Kong

Abstract Aquatic macro-organisms, such as naidids, propagate excessively in biological activated carbon (BAC) filters. This has become a troublesome problem for drinking water plants. For successful control of naidid contamination risk, it is necessary to determine the population dynamics under different environmental conditions within drinking water plants, with special emphasis on BAC filters. In this study, field studies of naidid distribution in a drinking water plant were conducted, and the effects of temperature and dissolved oxygen (DO) on naidid population dynamics were investigated using the life table method. The results indicated that naidid pollution in the water plant occurred seasonally and was induced by the excessive propagation of naidids in the BAC filters. Increased temperature and DO increased the naidid intrinsic rate of natural increase and decreased the naidid population doubling time. The life table method was also used to acquire the reproductive parameters of naidids in BAC filters based on simulative experiments. These results indicated that naidids can reproduce asexually in BAC filters, and the population doubling time was 12.60 days.


1993 ◽  
Vol 265 (2) ◽  
pp. C571-C576 ◽  
Author(s):  
H. L. Kirschenlohr ◽  
J. C. Metcalfe ◽  
P. L. Weissberg ◽  
D. J. Grainger

Vascular smooth muscle cells (VSMC) from adult human aortas proliferated in culture in response to fetal calf serum (FCS) with a population doubling time of 70-85 h compared with 35 +/- 5 h for VSMC derived from adult rat aortas. Medium conditioned on cultures prepared from aortas from three different donors and mixed 1:1 with fresh Dulbecco's modified Eagle's medium plus 20% FCS [human conditioned medium (HCM)] reduced the rate of proliferation of rat VSMC by 46 +/- 6% (n = 3) after 48 h compared with cells in fresh medium. HCM did not reduce the proportion (> 65%) of rat VSMC that entered DNA synthesis but delayed entry into mitosis by at least 18 h. This effect was similar to previous observations of the action of transforming growth factor-beta (TGF-beta) on rat VSMC (G. K. Owens, A. A. Geisterfer, Y. W. Yang, and A. Komoriya. J. Cell Biol. 107: 771-780, 1988). A TGF-beta assay using DNA synthesis in mink lung epithelial cells confirmed that human, but not rat, VSMC in culture secrete active TGF-beta. Addition of a neutralizing antibody to TGF-beta to human VSMC in the presence of 20% FCS decreased the population doubling time from 74 +/- 3 to 46 +/- 6 h (n = 3). These observations demonstrate that the long population doubling time of human VSMC is due to the production of active TGF-beta and to an inhibitory autocrine loop.


The Auk ◽  
2006 ◽  
Vol 123 (2) ◽  
pp. 393-404 ◽  
Author(s):  
Bryan D. Watts ◽  
A. Catherine Markham ◽  
Mitchell A. Byrd

Abstract We evaluated the relationship between salinity and Bald Eagle (Haliaeetus leucocephalus) population parameters using 26 years of survey data for the lower Chesapeake Bay. Tidal tributaries within the study area were stratified according to the Chesapeake Bay Program's segmentation scheme, and segments with the same salinity classification were considered spatial replicates. Salinity categories included tidal fresh, oligohaline, mesohaline, and polyhaline. Four parameters— colonization rate, nesting density, projected carrying capacity, and productivity— were derived from nesting data within each shoreline segment and compared across the salinity gradient. The study-wide Bald Eagle population is exhibiting exponential growth, with an average doubling time of 7.9 years. All population parameters showed significant directional variation with salinity. Average population doubling time for tidal fresh reaches was <6 years, compared with >16 years for polyhaline areas. Current Bald Eagle nesting density is negatively related to salinity and varies by a factor of 4 across the gradient. Comparison of current densities with projected carrying capacity suggests that these differences will be stable or increasing as the geographic areas approach equilibrium densities. We suggest that fisheries within lower saline reaches, including spring spawning runs of anadromous Clupeidae (shad and herring), are the most likely explanation for salinity effects. Observed distribution patterns suggest that lands along low-salinity waters are the core of the Bald Eagle nesting population within the lower Chesapeake Bay and should be the focus of long-term programs designed to benefit nesting eagles. Salinidad y Parámetros Poblacionales de Haliaeetus leucocephalus en la Bahia de Chesapeake


2019 ◽  
Vol 20 (6) ◽  
pp. 1485 ◽  
Author(s):  
Xiao-Shu Zhan ◽  
Saeed El-Ashram ◽  
Dong-Zhang Luo ◽  
Hui-Na Luo ◽  
Bing-Yun Wang ◽  
...  

Mesenchymal stem cells (MSCs) are the most promising seed cells for cell therapy. Comparing the biological and transcriptome gene characteristics of MSCs from different sources provides an important basis for the screening of clinically used cells. The main purpose of this experiment was to establish methods for the isolation and culture of MSCs from five different canine sources, including adipose tissue, bone marrow, umbilical cord, amniotic membrane, and placenta, and compare biological and transcriptome characteristics of MSCs, in order to provide a basis for the clinical application of canine MSCs. MSCs were isolated from Chinese pastoral dogs, and the following experiments were performed: (1) the third, sixth, and ninth generations of cells were counted, respectively, and a growth curve was plotted to calculate the MSC population doubling time; (2) the expression of CD34 and CD44 surface markers was studied by immunofluorescence; (3) the third generation of cells were used for osteogenetic and adipogenic differentiation experiments; and (4) MSC transcriptome profiles were performed using RNA sequencing. All of the five types of MSCs showed fibroblast-like adherent growth. The cell surface expressed CD44 instead of CD34; the third-generation MSCs had the highest proliferative activity. The average population doubling time of adipose mesenchymal stem cells (AD-MSCs), placenta mesenchymal stem cells (P-MSCs), bone marrow mesenchymal stem cells (BM-MSCs), umbilical cord mesenchymal stem cells (UC-MSCs), and amniotic mesenchymal stem cells (AM-MSCs) were 15.8 h, 21.2 h, 26.2 h, 35 h, and 41.9 h, respectively. All five types of MSCs could be induced to differentiate into adipocytes and osteoblasts in vitro, with lipid droplets appearing after 8 days and bone formation occurring 5 days after AD-MSC induction. However, the multilineage differentiation for the remaining of MSCs was longer compared to that of the AD-MSCs. The MSC transcriptome profiles showed that AD-MSC and BM-MSCs had the highest homology, while P-MSCs were significantly different compared to the other four types of MSCs. All the isolated MSCs had the main biological characteristics of MSCs. AD-MSCs had the shortest time for proliferation, adipogenesis, and osteogenic differentiation.


2008 ◽  
Vol 68 (2) ◽  
pp. 379-383 ◽  
Author(s):  
FC. Massaro ◽  
O. Rocha

Hydras, the most representative freshwater Cnidaria, are of common occurrence in bodies of water in every continent except Antarctica. This study was planned with the aim of maintaining a population of Hydra viridissima in laboratory culture to enable the determination of the individual and population growth-rates of this species, as well as its population doubling time and generation time, with a view to employing these common animals as test-organisms in ecotoxicological assays. The organisms were maintained in reconstituted water at 20 ± 2 °C, illuminated at 800 lux with a photoperiod of 12 hours light: 12 hours dark, and were fed on neonates of the cladoceran Ceriodaphnia silvestrii (3 or 4 neonates per hydra, 3 times a week). The individual growth-rate (k) of the species was 0.43, the maximum length of the column 2.53 mm and the generation time 6.6 ± 1.5 days on average. The hydra population showed an intrinsic growth-rate (r) of 0.0468, according to the fitted curve, and a doubling time of 14.8 ± 2.63 days. Hydra viridissima is easy to grow in the laboratory and performs well in the conditions used in this study. It is thus a promising candidate test-organism for ecotoxicological studies.


2003 ◽  
Vol 23 (22) ◽  
pp. 8363-8376 ◽  
Author(s):  
Girdhar G. Sharma ◽  
Kyu-kye Hwang ◽  
Raj K. Pandita ◽  
Arun Gupta ◽  
Sonu Dhar ◽  
...  

ABSTRACT Telomeres are associated with the nuclear matrix and are thought to be heterochromatic. We show here that in human cells the overexpression of green fluorescent protein-tagged heterochromatin protein 1 (GFP-HP1) or nontagged HP1 isoforms HP1Hsα or HP1Hsβ, but not HP1Hsγ, results in decreased association of a catalytic unit of telomerase (hTERT) with telomeres. However, reduction of the G overhangs and overall telomere sizes was found in cells overexpressing any of these three proteins. Cells overexpressing HP1Hsα or HP1Hsβ also display a higher frequency of chromosome end-to-end associations and spontaneous chromosomal damage than the parental cells. None of these effects were observed in cells expressing mutants of GFP-ΔHP1Hsα, GFP-ΔHP1Hsβ, or GFP-ΔHP1Hsγ that had their chromodomains deleted. An increase in the cell population doubling time and higher sensitivity to cell killing by ionizing radiation (IR) treatment was also observed for cells overexpressing HP1Hsα or HP1Hsβ. In contrast, cells expressing mutant GFP-ΔHP1Hsα or GFP-ΔHP1Hsβ showed a decrease in population doubling time and decreased sensitivity to IR compared to the parental cells. The effects on cell doubling times were paralleled by effects on tumorigenicity in mice: overexpression of HP1Hsα or HP1Hsβ suppressed tumorigenicity, whereas expression of mutant HP1Hsα or HP1Hsβ did not. Collectively, the results show that human cells are exquisitely sensitive to the amount of HP1Hsα or HP1Hsβ present, as their overexpression influences telomere stability, population doubling time, radioresistance, and tumorigenicity in a mouse xenograft model. In addition, the isoform-specific effects on telomeres reinforce the notion that telomeres are in a heterochromatinized state.


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