A DNA-structured mathematical model of cell-cycle progression in cyclic hypoxia

New experimental data have shown how the periodic exposure of cells to low oxygen levels (i.e., cyclic hypoxia) impacts their progress through the cell-cycle. Cyclic hypoxia has been detected in tumours and linked to poor prognosis and treatment failure. While fluctuating oxygen environments can be reproduced in vitro, the range of oxygen cycles that can be tested is limited. By contrast, mathematical models can be used to predict the response to a wide range of cyclic dynamics. Accordingly, in this paper we develop a mechanistic model of the cell-cycle that can be combined with in vitro experiments, to better understand the link between cyclic hypoxia and cell-cycle dysregulation. A distinguishing feature of our model is the inclusion of impaired DNA synthesis and cell-cycle arrest due to periodic exposure to severely low oxygen levels. Our model decomposes the cell population into four compartments and a time-dependent delay accounts for the variability in the duration of the S phase which increases in severe hypoxia due to reduced rates of DNA synthesis. We calibrate our model against experimental data and show that it recapitulates the observed cell-cycle dynamics. We use the calibrated model to investigate the response of cells to oxygen cycles not yet tested experimentally. When the re-oxygenation phase is sufficiently long, our model predicts that cyclic hypoxia simply slows cell proliferation since cells spend more time in the S phase. On the contrary, cycles with short periods of re-oxygenation are predicted to lead to inhibition of proliferation, with cells arresting from the cell-cycle when they exit the S phase. While model predictions on short time scales (about a day) are fairly accurate (i.e, confidence intervals are small), the predictions become more uncertain over longer periods. Hence, we use our model to inform experimental design that can lead to improved model parameter estimates and validate model predictions.

Molecular evolutionary dynamics of energy limited microorganisms

Microorganisms have the unique ability to survive extended periods of time in environments with extremely low levels of exploitable energy. To determine the extent that energy limitation affects microbial evolution, we examined the molecular evolutionary dynamics of a phylogenetically diverse set of taxa over the course of 1,000-days. We found that periodic exposure to energy limitation affected the rate of molecular evolution, the accumulation of genetic diversity, and the rate of extinction. We then determined the degree that energy limitation affected the spectrum of mutations as well as the direction of evolution at the gene level. Our results suggest that the initial depletion of energy altered the direction and rate of molecular evolution within each taxon, though after the initial depletion the rate and direction did not substantially change. However, this consistent pattern became diminished when comparisons were performed across phylogenetically distant taxa, suggesting that while the dynamics of molecular evolution under energy limitation are highly generalizable across the microbial tree of life, the targets of adaptation are specific to a given taxon.

Effect of Nano-Filled Protective Coating and Different pH Enviroment on Wear Resistance of New Glass Hybrid Restorative Material

The purpose of the study was to determine the wear rate of Equia Forte HT Fil with Equia Forte Coat or without coating and compare it with Fuji IX GP high-viscosity glass ionomer cement (GIC) in conditions with acid load or at neutral pH. The samples were stored for 7 days: (1) in artificial saliva, (2) in artificial saliva and cyclically exposed to low pH, and (3) in distilled water and cyclically exposed to low pH. Wear was determined by measuring the difference in mass before and after brushing in an abrasion testing device. The wear of Fuji IX GP was significantly higher than that of Equia Forte HT Fil with or without coating (p = 0.000). The difference between Equia Forte HT Fil with and without Coat was not statistically significant (p < 0.803). The differences in wear resistance between samples stored in saliva and in distilled water were not significant (p = 0.588). Periodic exposure to the low pH solution significantly affected the wear resistance of all materials (p = 0.000). Equia Forte HT Fil was more resistant to wear than Fuji IX GP in all storage conditions. A resinous coat did not significantly increase wear resistance.

Estimasi Emisi Kendaraan Bermotor dan Tampakan Lumut Kerak untuk Memprediksi Paparan Traffic-Related Air Pollution pada Sekolah Dasar di Kota Kendari

Increasing the number of vehicles in Kendari could has the potential to increase TRAP exposure in elementary schools located on the side of the highway. The purpose of this study was to describe the emission load of vehicles, the appearance of lichens and to predict exposure to TRAP in Sekolah Dasar Negeri (SDN) on the side of the highway in Kendari City. This study uses a quantitative approach, survey methods with sampling techniques in three different locations. The results showed that the emission burden of vehicles at SDN 6 Kendari and SDN 25 Kendari was higher, the percentage of lichens present was lower and the appearance was duller than SDN 92 Kendari. This condition can be predicted as an initial indication of a decline in air quality at that location due to periodic exposure to TRAP.

Gill and Muscles abrasion associated with exposure to malathion in fresh water fish

Malathion has a long range of application in agriculture, which leads its accumulation in animal tissues and may influence biochemical balance of aquatic organisms. Present study on fish gills and muscles has remarkable potential in understanding the adverse effect of selected toxicant on the biochemical and structural integrity of tissues. Twelve fingerlings were exposed to LC50 (406 ìg/L) concentration of malathion over a period of 96hrs. Periodic exposure of malathion at 24th, 48th, 72th and 96th hr, resulted in the form of reduction in gills protein content (-13.99%), (-18.56%), (-33.90%) and (48.14%) respectively. On other hand, in muscles similar reductive pattern of protein content was recorded as (-8.25 %), (-26.37%), (25.82%) and (-43.58%). Such negative protein alterations may be used as potential biomarker for pesticide toxicity in fresh water ecosystem.

Photochemical effects of white light on the Briggs-Rauscher self-oscillatory reaction

For the Briggs-Rauscher reaction, the synchronization effect for concentration self-oscillations of the system components under exposure to external periodic white light was investigated. The high sensitivity of the self-oscillatory mode of the reaction to periodic exposure to the light is demonstrated. The sync band dependence on the light power has been revealed. The power limits of external light exposure for which self-oscillations are not going on, have been established. The maximal oscillation synchronization range under external light exposure (from 0.04 up to 0.10 Hz) has been determined. “Frequency pulling” effect was observed for exposure to light with frequencies from 0.029 up to 0.039 Hz and from 0.10 up to 0.14 Hz. Under the influence of light from a lamp with a power of more than 500 W, the reaction was “turned off”, which is probably due to an increase in the rate of formation of intermediate components of the system and an increase in their concentrations at which it exited from a state of self-oscillation to a stationary state. In addition, the periodic exposure to white light led to "adaptation" of concentration oscillations of the BR reaction to the external action into the phase that is characterized by the blue color of the solution (the formation of clathrate "iodine-starch"), which can be explained by a sharp decrease in the concentration of hydrogen peroxide in the system and, consequently, oxygen. The sensitivity of the Briggs-Rauscher reaction to the spectral composition of the initial source indicates the expediency of its further studies.

Identification of a dynamic middle ear microbiome in healthy adults

Background The entrenched dogma of a sterile middle ear in health is incongruent with its periodic exposure to exhaled air when the tympanic (Eustachian) tube opens while swallowing, yawning or inhaling deeply. Tubal patency is brief but frequent to provide adequate aeration, equalize pressure across the eardrum and drain mucus down the sides of the oropharynx. It also provides a mechanism for aerial dispersal of microorganisms from the aerodigestive tract. Method We designed a pilot study and received institutional approval to collect otic secretions that naturally drain on the sides of the oropharynx, behind the palatopharyngeal arch. This protocol bypassed the need to surgically access the middle ear through or around the eardrum, allowed us to collect samples from individuals with no underlying otic conditions, and prevented sample cross-contamination. As controls, we also collected samples from the center of the oropharynx and buccal mucosae seeded by saliva, which may serve as sources of microbial dispersal into the middle ear. Results We sequenced 16S rRNA-V4 amplicons from otic, oropharyngeal and buccal samples collected from a cohort of 19 healthy young adults. The survey identified in the otic samples a diverse bacterial community with many oropharyngeal and buccal keystone taxa and most of the functional traits of the neighboring oral microbiomes. Neutral community models predicted a large contribution of oral dispersal to the composition of the otic microbiome as well as several taxa responsive to positive selection. This was further supported by the enrichment in the otic communities of obligate anaerobes of Bacteroidetes and Fusobacteria over facultative anaerobic Proteobacteria and Firmicutes. Furthermore, the prevalence of the anaerobic members decreased with the more frequent otic aeration predicted from the equalization training of scuba divers recruited to the study. Conclusions These results challenge the long held view of a sterile middle ear and suggest instead that frequent seeding with oral microbes supports the establishment of a rich and robust otic community dynamically adapted to the episodic ventilation of the tympanic space.

Directed cultivation of Chlorella sorokiniana for the increase in carotenoids’ synthesis

The metabolism of Chlorella sorokiniana is subjected to changes caused by various cultivation conditions. If dosed ultraviolet radiation is used, there is a possibility of a compensatory increase in the synthesis of carotenoids which prevent oxidative stress. Strain 211-8k was cultured under various lighting conditions: control sample was subjected to fluorescent light; sample 1 was subjected to dosed periodic ultraviolet irradiation for 15 minutes every day and fluorescent lighting; sample 2 was subjected to ultraviolet irradiation for 30 minutes in the stabilization phase. Periodic UV exposure negatively affects the population growth of C. sorokiniana which was possible to detect only on the ninth day and the biomass yield significantly decreased. A single UV exposure for 30 minutes lead to a slight decrease in the yield of air-dry biomass which with a further population growth may be compensated. Periodic exposure to UV radiation stimulates carotenoids synthesis, the yield in terms of dry biomass exceeded the control sample on average by 30%. A single ultraviolet irradiation for 30 minutes in the stabilization phase lead to a decrease in the biomass content of both chlorophyll and carotenoids. Microscopy of microalgae showed that ultraviolet radiation leads to the formation of cells with signs of apoptosis.