The importance of assessing parameter sensitivity when using biophysical models: a case study using plethodontid salamanders

Landscapes are continually changing due to numerous assaults, including habitat alteration, anthropogenic disturbances, and climate change. Understanding how species will respond to these changes is of critical importance for conservation and management. Mechanistic models, such as biophysical models (BPMs), are an increasingly popular tool to predict how local population dynamics or species’ distributions may be altered in response to environmental and climate changes. By mechanistically modeling relationships between environmental conditions, physiology and behavior, it is possible to make accurate predictions about how species may respond. However, BPMs are often difficult to implement due to lack of appropriate, species-specific data that is biologically realistic or relevant. In this study, we present a BPM for the salamander Plethodon jordani and assess how adding more biological realism has potential to alter model predictions about annual energy budgets. Additionally, we conducted local and global sensitivity analyses to evaluate the importance of accurately specifying model parameter values and functional relationships. We found that the addition of biological realism resulted in greater model complexity as well as substantially different estimates of energy balance. Correct parameterization of biophysical models is also critical, as small changes in parameter values can result in disproportionately large changes in downstream model estimates. Our model highlights the overall importance of using ecologically relevant and specific data for input parameters, as well as careful assessment of parameter sensitivity. We encourage researchers to be aware of the data they are using to parameterize BPMs, and urge the collection of system-specific data that is relevant in spatial and temporal scale. We also recommend greater and more transparent use of sensitivity analyses to provide a better understanding of the model, as well as greater confidence in model predictions.     

Determination of antibiotic chemicals using microbiological tests: evaluation of the limits of sensitivity]

Sensitivity of Bacillus subtilis BGA and Bacillus stearothermophilus var. calidolactis disc assays to 53 chemio-antibiotics was tested. Test-microorganisms were sown in two different mediums: PM Indicator Agar, Difco U.S.A., and Standard II Nutrient Agar, Merck Germany, modified according to Nouws. The mediums were used with or without addition of Trimethoprim (at a concentration of 0.12 or 0.024 mcg/ml of medium for B. subtilis and for B. stearothermophilus respectively). B. stearothermophilus did not grow in Standard II. However, the B. subtilis assay gave the best results with Standard II, apart for aminoglycosides. The B. stearothermophilus disc assay was the most sensitive to penicillins (Minimum Inhibiting Concentration in mcg/ml, MIC, between 0.001 and 0.004), cephalosporins (MIC between 0.003 and 0.09, apart from Ceftazidime, 0.3) and aminoglycosides (MIC between 0.03 and 0.6). The B.subtilis disc assay showed better sensitivity to quinolines (MIC between 0.05 and 4) and to some tetracyclines (oxytetracycline and chlortetracycline, MIC 0.03). Trimethoprim, where added, determined a higher sensitivity to sulfonamides (MIC between 0.025 and 0.25).     

A comparative study on neoplastic transformation of human and Syrian hamster cells

Three approaches have been taken to study simultaneously Syrian hamster cells and human cells in order to develop an extrapolation from the more established hamster system to human cells. On the Characterization of normal cells in comparison to tumor cells, human tumor cells and hamster tumor cells showed similarity in displaying anchorage independence, growth in suspension as micro tumor spheroids, and xenotumorigenicity in contrast to their respective normal cells; in addition, these tumor cells exhibited shorter population doubling time, higher saturation density, higher cloning efficiency, and higher fibrinolytic activity relative to their respective normal cell types. Other differences including ploidy change, contact inhibition on growth, serum requirement, and morphological transformation were also noted between human and hamster cells. On the application of microcarrier culture for a xenotumorigenicity test, the microcarrier technique seemed to have enhanced the sensitivity by reducing the number of inoculated tumor cells required for tumor formation. On the in vitro transformation of normal human and hamster cells, the highest efficiency of morphological transformation of hamster cells has been observed in the group treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by griseofulvin which was employed to enhance the transformation by disturbing the chromosome apparatus. However, no evidence of transformation was observed in the treated human cells thus far.     

土壤有机质分解的温度敏感性:培养与测定模式

土壤有机质分解的温度敏感性(Q_(10))不仅是生态学和土壤学研究的核心科学问题之一,也是全球变化生态学研究的热点领域。国内外学者对Q_(10)的影响因素或机制开展了大量卓有成效的研究工作,并有不少相关的综述或展望;然而,迄今为止有关培养与测定模式的探讨却非常少。鉴于培养和测定模式对研究结果的重要性,在简要描述Q_(10)定义、基本理论和计算方法的基础上,重点比较了当前Q_(10)研究的不同培养和测定模式及其优缺点。结合最新研究进展,重点介绍了新发展的连续变温培养+连续自动测试模式,并简要阐述了新模式的应用前景。通过探讨,希望能为国内从事Q_(10)研究的学者提供一定的经验与借鉴;同时,希望能引起青年科研人员重视研究方法、技术和仪器的研发,更好更快地推动原创性研究。     

Temperature sensitivity of planktic foraminifera and its influence on the oxygen isotope record

We used oxygen isotope measurements from Holocene surface sediments to infer optimum temperature and temperature sensitivity of the planktic foraminiferal species Globigerinoides ruber (pink) and Globigerinoides sacculifer. The (isotopic) optimum temperature of G. ruber (pink) is close to 27°C. G. sacculifer seems to have optimum vital conditions around 22°C and is less temperature sensitive than G. ruber (pink). Our estimations of optimum temperature and temperature sensitivity are in good accordance with laboratory and field investigations. Two simple experiments show that the temperature sensitivity of planktic foraminifera, determined from oxygen isotopes, can influence phase and amplitude of oxygen isotope records, if the temperature distribution at the sea surface changes through time. To use this distortion for paleoceanography, we suggest to derive an ‘isotopic transfer function’ which allows the calculation of average temperature, temperature variability and the isotopic composition of seawater if the oxygen-isotope differences between at least three species are known.     

Temperature sensitivity of catecholamine secretion and ion fluxes in bovine adrenal chromaffin cells

The effects of temperature on ion fluxes and catecholamine secretion that are mediated by nicotinic acetylcholine receptors (nAChRs), voltage-sensitive calcium channels (VSCCs), and voltage-sensitive sodium channels (VSSCs) were investigated using bovine adrenal chromaffin cells. When the chromaffin cells were stimulated with DMPP, a nicotinic cholinergic agonist, or 50 mM K+, the intracellular calcium ([Ca2+]i) elevation reached a peak and decreased more slowly at lower temperatures. The DMPP-induced responses were more sensitive to temperature changes compared to high K+-induced ones. In the measurement of intracellular sodium concentrations ([Na+]i), it was found that nicotinic stimulation required a longer time to attain the maximal level of [Na+]i at lower temperatures. In addition, the VSSCs-mediated [Na+]i increase evoked by veratridine was also reduced as the temperature decreased. The measurement of [3H]norepinephrine (NE) secretion showed that the secretion within the first 3 min evoked by DMPP or high K+ was greatest at 37 degrees C. However, at 25 degrees C, the secretion evoked by DMPP, but not that by the 50 mM K+, was greater after 10 min of stimulation. This data suggest that temperature differentially affects the activity of nAChRs, VSCCs, and VSSCs, resulting in differential [Na+]i and [Ca2+]i elevation, and in the [3H]NE secretion by adrenal chromaffin cells.     

A pilot study: microbiological conditions of the oral cavity in minipigs for peri-implantitis models

As peri-implantitis is an emerging problem, the development of validated animal models is mandatory. The aim of this pilot study was to provide a first step in describing the normal oral flora of minipigs. In five minipigs, samples of the oral flora were collected with sterile cotton swabs from the buccal gingiva of the lower jaw. Two swabs per animal were collected, followed by bacterial isolation under both aerobe and anaerobe conditions. Microbiological analyses included biochemical tests, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rDNA gene sequence analysis. A total of 61 taxa were detected, 14-21 different bacterial taxa from each minipig. Among the Gram-positive cocci, mainly staphylococcal and streptococcal species were identified. Different Actinomyces species were the most abundant taxa in the group of Gram-positive rods. Among the anaerobic bacteria, the Gram-negative genera Fusobacterium, Bacteroides and Prevotella were the most often observed taxa. This is the first study which begins to describe the normal oral flora in minipigs in cultures to allow for the detection of a broad spectrum. Several bacterial species identified are different from human ones. No specific species for peri-implantitis could be detected in that healthy sample.     

Change in the sensitivity to methotrexate of neoplastic cells cultivated in the presence of folic acid]

Cultivation of tumour L-cells in the presence of increasing folic acid concentrations led to the rise in the resistance of these cells population to metotrexate. With the subsequent cultivation, when the folic acid concentration was not increased the population of such cells became more sensitive to metotrexate even in comparison with the initial L-cells.     

Applications of omics approaches to the development of microbiological risk assessment using RNA virus dose–response models as a case study

T e in the amount of ‘omics’ data available and in our ability to interpret those data. The aim of this paper was to consider how omics techniques can be used to improve and refine microbiological risk assessment, using dose–response models for RNA viruses, with particular reference to norovirus through the oral route as the case study. The dose–response model for initial infection in the gastrointestinal tract is broken down into the component steps at the molecular level and the feasibility of assigning probabilities to each step assessed. The molecular mechanisms are not sufficiently well understood at present to enable quantitative estimation of probabilities on the basis of omics data. At present, the great strength of gene sequence data appears to be in giving information on the distribution and proportion of susceptible genotypes (for example due to the presence of the appropriate pathogen‐binding receptor) in the host population rather than in predicting specificities from the amino acid sequences concurrently obtained. The nature of the mutant spectrum in RNA viruses greatly complicates the application of omics approaches to the development of mechanistic dose–response models and prevents prediction of risks of disease progression (given infection has occurred) at the level of the individual host. However, molecular markers in the host and virus may enable more broad predictions to be made about the consequences of exposure in a population. In an alternative approach, comparing the results of deep sequencing of RNA viruses in the faeces/vomitus from donor humans with those from their infected recipients may enable direct estimates of the average probability of infection per virion to be made.     

Temperature sensitivity of DNA synthesis in mouse testicular germ cells in vitro

The effect of temperature on testicular DNA synthesis in mice was studied in vitro. By using cultures of cryptorchid testis, DNA synthesis of differentiated germ cells, such as intermediate and type B spermatogonia and resting primary spermatocytes, was shown to be temperature-sensitive, while that of undifferentiated type A spermatogonia was not. DNA synthesis of non-germ cells was not temperature-sensitive. This temperature sensitivity of germ cells in DNA synthesis may be one cause of the thermal inhibition of germ cell differentiation.     

Temperature sensitivity on proliferation and morphologic alteration of human esophageal carcinoma cells in culture

Summary As basic studies of hyperthermia and hypothermia on malignant tumor, the kinetics of proliferative activity, the morphologic changes in the two cell lines, SGF-3 and SGF-5, established in our department after the change of culture temperature were examined. The results obtained were: a) A significant difference was found in the sensitivity to temperatures between the two cell lines originated from human esophageal squamous cell carcinoma. The temperature range allowing cultured cell to proliferate were from 31° to 39° C in SGF-3 and from 29° to 41° C in SGF-5. b) Minor difference occurred in the results between the two cell lines examined during the recovery of proliferative activity, but no proliferative activity was discovered after the cells were exposed to 42° C for 72 h. Two cell lines resumed their proliferation after having been exposed to 27° or 28° C for 72 h. c) Morphologic changes of the cell lines cultured at high temperature were cytoplasmic vacuolation and cell aggregation by phase contrast microscope and the increase of heterochromatin, the decrease of granular formation in nucleoli, and nucleolar vacuolation by transmission electron microscopy (TEM). At low temperatures the changes observed included cytoplasmic ballooning and circumnuclear halo formation by phase contrast microscope, and the increase of heterochromatin, nucleolar segregation, swelling of mitochondria, and dilatation of rough endoplasmic reticulum (rER) by TEM.