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1.
Complex linear appearing structures and networks (e.g. blood vessels, leaf veins, nerves) are formed reproducibly during the development of nearly every organism, but the molecular mechanism leading to such patterns is still unknown. A model is proposed in which a few simple coupled biochemical reactions are able to generate such structures. Among undifferentiated cells, a local peak of differentiation-inducing substance (activator) is formed by autocatalysis and lateral inhibition. The activator peak triggers the differentiation of the cell at that location. Due to changes in metabolism, the differentiated cell repels the activator peak and drives it to a neighbouring cell which then also differentiates. The repulsion between the activator peak and the already differentiated cells forces the activator peak to move ahead of the tip of the extending filament. Long filaments of differentiated cells may be formed, which can split, branch laterally, reconnect with each other and grow towards specific target cells. Partial differential equations describing the mutual interaction of the substances involved were presented and solved with a computer. The resulting patterns show self-regulating properties and other features found in the leaf vascular system, the pattern of tracheae in insect epidermis, and other biological networks.  相似文献   

2.
The first model in marine ecology was that of the biocoenosis by Moebius (1883), conceived as a self-contained box limited by a finite food resource. This box was almost immediately broken bown by Dean (1893) and demonstrated to be a bit of a muddle, but the concept and the general term has persisted. Today, the construction of elaborate diagrams and mystico-mathematical representations of assumed relationships powered by selected values is a favorite pastime of many ecologists and environmental engineers. When taken with a grain of salt (preferably benzoate of soda), such models may stimulate further thought. Fisheries biologists have had some success with single species or paucispecific models, but complex models require simplification and selection of data unrepresentative of nature. A model which is simply an elaborate mathematical summary of a textbook does not tell us much more than we allready know, and its formulation involves a questionable diversion of funds.  相似文献   

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6.
Requirements on models of the active transport of ions in biomembranes have been formulated. The basic requirements include an explicit dependence of the resting potential and intracellular concentrations of ions on the difference of ATP-ADP chemical potentials, a consideration of the reversibility of the ionic pump operation, a correlation between theoretical and experimental data on the resting potential and intracellular concentrations of ions for different types of cells, the pump efficiency approaching 100%, and a tendency of the resting potential to the Donnan potential if the active transport is blocked. A model satisfying the aforementioned requirements has been proposed by the authors as an example.  相似文献   

7.
Osteoarthritis (OA) is a multidimensional health problem and a common chronic disease. It has a substantial impact on patient quality of life and is a common cause of pain and mobility issues in older adults. The functional limitations, lack of curative treatments, and cost to society all demonstrate the need for translational and clinical research. The use of OA models in mice is important for achieving a better understanding of the disease. Models with clinical relevance are needed to achieve 2 main goals: to assess the impact of the OA disease (pain and function) and to study the efficacy of potential treatments. However, few OA models include practical strategies for functional assessment of the mice. OA signs in mice incorporate complex interrelations between pain and dysfunction. The current review provides a comprehensive compilation of mouse models of OA and animal evaluations that include static and dynamic clinical assessment of the mice, merging evaluation of pain and function by using automatic and noninvasive techniques. These new techniques allow simultaneous recording of spontaneous activity from thousands of home cages and also monitor environment conditions. Technologies such as videography and computational approaches can also be used to improve pain assessment in rodents but these new tools must first be validated experimentally. An example of a new tool is the digital ventilated cage, which is an automated home-cage monitor that records spontaneous activity in the cages.

Osteoarthritis (OA) is a multidimensional health problem and a common chronic disease.36 Functional limitations, the absence of curative treatments, and the considerable cost to society result in a substantial impact on quality of life.76 Historically, OA has been described as whole joint and whole peri-articular diseases and as a systemic comorbidity.9,111 OA consists of a disruption of articular joint cartilage homeostasis leading to a catabolic pathway characterized by chondrocyte degeneration and destruction of the extracellular matrix (ECM). Low-grade chronic systemic inflammation is also actively involved in the process.42,92 In clinical practice, mechanical pain, often accompanied by a functional decline, is the main reason for consultations. Recommendations to patients provide guidance for OA management.22, 33,49,86 Evidence-based consensus has led to a variety of pharmacologic and nonpharmacologic modalities that are intended to guide health care providers in managing symptomatic patients. Animal-based research is of tremendous importance for the study of early diagnosis and treatment, which are crucial to prevent the disease progression and provide better care to patients.The purpose of animal-based OA research is 2-fold: to assess the impact of the OA disease (pain and function) and to study the efficacy of a potential treatment.18,67 OA model species include large animals such as the horse, goat, sheep, and dog, whose size and anatomy are expected to better reflect human joint conditions. However, small animals such as guinea pig, rabbit, mouse, and rat represent 77% of the species used.1,87 In recent years, mice have become the most commonly used model for studying OA. Mice have several advantageous characteristics: a short development and life span, easy and low-cost breeding and maintenance, easy handling, small joints that allow histologic analysis of the whole joint,32 and the availability of genetically modified lines.108 Standardized housing, genetically defined strains and SPF animals reduce the genetic and interindividual acquired variability. Mice are considered the best vertebrate model in terms of monitoring and controlling environmental conditions.7,14,15,87 Mouse skeletal maturation is reached at 10 wk, which theoretically constitutes the minimal age at which mice should be entered into an OA study.64,87,102 However, many studies violate this limit by testing mice at 8 wk of age.Available models for OA include the following (32,111 physical activity and exercise induced OA; noninvasive mechanical loading (repetitive mild loading and single-impact injury); and surgically induced (meniscectomy models or anterior cruciate ligament transection). The specific model used would be based on the goal of the study.7 For example, OA pathophysiology, OA progression, and OA therapies studies could use spontaneous, genetic, surgical, or noninvasive models. In addition, pain studies could use chemical models. Lastly, post-traumatic studies would use surgical or noninvasive models; the most frequently used method is currently destabilization of the medial meniscus,32 which involves transection of the medial meniscotibial ligament, thereby destabilizing the joint and causing instability-driven OA. An important caveat for mouse models is that the mouse and human knee differ in terms of joint size, joint biomechanics, and histologic characteristics (layers, cellularity),32,64 and joint differences could confound clinical translation.10 Table 1. Mouse models of osteoarthritis.
ModelsProsCons
SpontaneousWild type mice7,9,59,67,68,70,72,74,80,85,87,115,118,119,120- Model of aging phenotype
- The less invasive model
- Physiological relevance: mimics human pathogenesis
- No need for technical expertise
- No need for specific equipment
- Variability in incidence
- Large number of animals at baseline
- Long-term study: Time consuming (time of onset: 4 -15 mo)
- Expensive (husbandry)
Genetically modified mice2,7,25,40,50,52,67,72,79,80, 89,120- High incidence
- Earlier time of onset: 18 wk
- No need for specific equipment
- Combination with other models
- Time consuming for the strain development
- Expensive
Chemical- inducedMono-iodoacetate injection7,11,46,47,60,66,90,91,101,128- Model of pain-like phenotype
- To study mechanism of pain and antalgic drugs
- Short-term study: Rapid progression (2-7 wk)
- Reproducible
- Low cost
- Need for technical expertise
- Need for specific equipment
- Systemic injection is lethal
- Destructive effect: does not allow to study the early phase of pathogenesis
Papain injection66,67,120- Short-term study: rapid progression
- Low cost
- Need for technical expertise
- Need for specific equipment
- Does not mimic natural pathogenesis
Collagenase injection7,65,67,98- Short-term study: rapid progression (3 wk)
- Low cost
- Need for technical expertise
- Need for specific equipment
- Does not mimic natural pathogenesis
Non-invasiveHigh-fat diet (Alimentary induced obesity model)5,8,43,45,57,96,124Model of metabolic phenotype
No need for technical expertise
No need for specific equipment
Reproducible
Long-term study: Time consuming (8 wk–9 mo delay)
Expensive
Physical activity and exercise model45,73Model of post traumatic phenotype
No need for technical expertise
Long-term study: time consuming (18 mo delay)
Expensive
Disparity of results
Mechanical loading models Repetitive mild loading models Single-impact injury model7,16,23,24, 32,35,104,105,106Model of post traumatic phenotype
Allow to study OA development
Time of onset: 8-10 wk post injury
Noninvasive
Need for technical expertise
Need for specific equipment
Heterogeneity in protocol practices
Repetitive anesthesia required or ethical issues
SurgicalOvariectomy114Contested.
Meniscectomy model7,32,63,67,87 Model of post traumatic phenotype
High incidence
Short-term study: early time of onset (4 wk from surgery)
To study therapies
Need for technical expertise
Need for specific equipment
Surgical risks
Rapid progression compared to human
Anterior cruciate ligament transection (ACLT)7,39,40,61,48,67,70,87,126Model of posttraumatic phenotype
High incidence
Short-term study: early time of onset (3-10 wk from surgery)
Reproducible
To study therapies
Need for technical expertise
Need for specific equipment
Surgical risks
Rapid progression compared to human
Destabilization of medial meniscus (DMM)7,32,39,40Model of post traumatic phenotype
High incidence
Short-term study: early time of onset (4 wk from surgery)
To study therapies
The most frequently used method
Need for technical expertise
Need for specific equipment
Surgical risks
Rapid progression compared to human
Open in a separate windowSince all animal models have strengths and weaknesses, it is often best to plan using a number of models and techniques together to combine the results.In humans, the lack of correlation between OA imaging assessment and clinical signs highlights the need to consider the functional data and the quality of life to personalize OA management. Clinical outcomes are needed to achieve 2 main goals: to assess the impact of the OA in terms of pain and function and to study the efficacy of treatments.65 Recent reviews offer few practical approaches to mouse functional assessment and novel approaches to OA models in mice.7,32,67,75,79,83,87, 100,120 This review will focus on static and dynamic clinical assessment of OA using automatic and noninvasive emerging techniques (
Test nameTechniquesKind of assessmentOutputSpecific equipment required
Static measurement
Von Frey filament testingCalibrated nylon filaments of various thickness (and applied force) are pressed against the skin of the plantar surface of the paw in ascending order of forceStimulus- evoked pain-like behavior
Mechanical stimuli - Tactile allodynia
The most commonly used test
Latency to paw withdrawal
and
Force exerted are recorded
Yes
Knee extension testApply a knee extension on both the intact and affected knee
or
Passive extension range of the operated knee joint under anesthesia
Stimulus-evoked pain-like behaviorNumber of vocalizations evoked in 5 extensionsNone
HotplateMouse placed on hotplate. A cutoff latency has been determined to avoid lesionsStimulus-evoked pain-like behavior
Heat stimuli- thermal sensitivity
Latency of paw withdrawalYes
Righting abilityMouse placed on its backNeuromuscular screeningLatency to regain its footingNone
Cotton swab testBringing a cotton swab into contact with eyelashes, pinna, and whiskersStimulus-evoked pain-like behavior
Neuromuscular screening
Withdrawal or twitching responseNone
Spontaneous activity
Spontaneous cage activityOne by one the cages must be laid out in a specific platformSpontaneous pain behavior
Nonstimulus evoked pain
Activity
Vibrations evoked by animal movementsYes
Open field analysisExperiment is performed in a clear chamber and mice can freely exploreSpontaneous pain behavior
Nonstimulus evoked pain
Locomotor analysis
Paw print assessment
Distance traveled, average walking speed, rest time, rearing
Yes
Gait analysisMouse is placed in a specific cage equipped with a fluorescent tube and a glass plate allowing an automated quantitative gait analysisNonstimulus evoked pain
Gait analysis
Indirect nociception
Intensity of the paw contact area, velocity, stride frequency, length, symmetry, step widthYes
Dynamic weight bearing systemMouse placed is a specific cage. This method is a computerized capacitance meter (similar to gait analysis)Nonstimulus evoked pain
Weight-bearing deficits
Indirect nociception
Body weight redistribution to a portion of the paw surfaceYes
Voluntary wheel runningMouse placed is a specific cage with free access to stainless steel activity wheels. The wheel is connected to a computer that automatically record dataNonstimulus evoked pain
Activity
Distance traveled in the wheelYes
Burrowing analysisMouse placed is a specific cage equipped with steel tubes (32 cm in length and 10 cm in diameter) and quartz sand in Plexiglas cages (600 · 340x200 mm)Nonstimulus evoked pain
Activity
Amount of sand burrowedYes
Digital video recordingsMouse placed is a specific cage according to the toolNonstimulus evoked pain
Or
Evoked pain
Scale of pain or specific outcomeYes
Digital ventilated cage systemNondisrupting capacitive-based technique: records spontaneous activity 24/7, during both light and dark phases directly from the home cage rackSpontaneous pain behavior
Nonstimulus evoked pain
Activity-behavior
Distance walked, average speed, occupation front, occupation rear, activation density.
Animal locomotion index, animal tracking distance, animal tracking speed, animal running wheel distance and speed or rotation
Yes
Challenged activity
Rotarod testGradual and continued acceleration of a rotating rod onto which mice are placedMotor coordination
Indirect nociception
Rotarod latency: riding time and speed with a maximum cut off.Yes
Hind limb and fore grip strengthMouse placed over a base plate in front of a connected grasping toolMuscle strength of limbsPeak force, time resistanceYes
Wire hang analysisSuspension of the mouse on the wire and start the timeMuscle strength of limbs: muscle function and coordinationLatency to fall grippingNone
(self -constructed)
Open in a separate windowPain cannot be directly measured in rodents, so methods have been developed to quantify “pain-like” behaviors. The clinical assessment of mice should be tested both before and after the intervention (induced-OA ± administration of treatment) to take into account the habituation and establish a baseline to compare against.  相似文献   

8.
Multinomial Distribution and Ascertainment Models     
A. K. Gupta  S. G. Lindle 《Biometrical journal. Biometrische Zeitschrift》1985,27(6):691-695
In this paper general ascertainment models are studied relaxing the strong assumption of complete dominance. Probabilitis of ascertaiment for both the complete and incomplete models depending on family size and register size for two types of affected individuals are derived.  相似文献   

9.
新生血管生成模型及应用     
魏仙  姚于勤  杨金亮 《生物技术通讯》2015,(3):421-425
新生血管生成包括血管发生和微血管生成。微血管生成也称血管新生,在胚胎发育、正常生理和病理生理过程中均发挥重要作用。近年来研究发现,肿瘤、糖尿病视网膜病变和风湿性关节炎等疾病的发生发展均与新生血管生成有关,而抑制血管生成已成为治疗这些疾病的有效策略。建立新生血管生成模型对研究该类疾病的分子机制和研发相关的治疗药物有极其重要的价值。为此,我们简要综述近年来新生血管生成模型及其应用进展。  相似文献   

10.
Models of race and cline     
A M Brues 《American journal of physical anthropology》1972,37(3):389-399
Computer models have been constructed to depict in the form of two-dimensional maps the effect of local selection on gene frequencies, particularly where partial barriers to gene flow are present at some points in an area. It was found that small amounts of uniform gene flow between foci of contrasting selection tend to produce evenly spaced isogenes, giving a “clinal” pattern. The interposition of partial barriers causes isogenes to become closer together in the region of the barriers and to become parallel to the barriers. A corollary result is that in the region of the barriers the isogene systems for different genes tend to become parallel to one another even though the exact foci of active selection for the genes do not coincide. This resembles a “racial” rather than “clinal” trait distribution. It was further observed that if a focus of active selection was peripheral in position (i.e., far from a genetic barrier) a clinal pattern extended across the area it affected between it and the barrier. If such a focus lies close to the barrier, the area it affects becomes rather uniform in gene frequency, with the “hinterland” approximating the gene frequency of the focus of active selection. On the basis of these models interpretation of the distribution of cold-adapted Mongoloid traits, and of the distribution of skin color across Europe and Africa, are suggested.  相似文献   

11.
Models for cytogenetics and embryology   总被引:1,自引:0,他引:1  
K Benirschke 《Federation proceedings》1969,28(1):170-178
  相似文献   

12.
Spatial Uncertainty and Ecological Models     
Jager  Henriette I.  King  Anthony W. 《Ecosystems》2004,7(8):841-847
Applied ecological models that are used to understand and manage natural systems often rely on spatial data as input. Spatial uncertainty in these data can propagate into model predictions. Uncertainty analysis, sensitivity analysis, error analysis, error budget analysis, spatial decision analysis, and hypothesis testing using neutral models are all techniques designed to explore the relationship between variation in model inputs and variation in model predictions. Although similar methods can be used to answer them, these approaches address different questions. These approaches differ in (a) whether the focus is forward or backward (forward to evaluate the magnitude of variation in model predictions propagated or backward to rank input parameters by their influence); (b) whether the question involves model robustness to large variations in spatial pattern or to small deviations from a reference map; and (c) whether processes that generate input uncertainty (for example, cartographic error) are of interest. In this commentary, we propose a taxonomy of approaches, all of which clarify the relationship between spatial uncertainty and the predictions of ecological models. We describe existing techniques and indicate a few areas where research is needed.  相似文献   

13.
Which Models Are Appropriate for Six Subtropical Forests: Species-Area and Species-Abundance Models     
Shi Guang Wei  Lin Li  Zhen Cheng Chen  Ju Yu Lian  Guo Jun Lin  Zhong Liang Huang  Zuo Yun Yin 《PloS one》2014,9(4)
The species-area relationship is one of the most important topic in the study of species diversity, conservation biology and landscape ecology. The species-area relationship curves describe the increase of species number with increasing area, and have been modeled by various equations. In this paper, we used detailed data from six 1-ha subtropical forest communities to fit three species-area relationship models. The coefficient of determination and F ratio of ANOVA showed all the three models fitted well to the species-area relationship data in the subtropical communities, with the logarithm model performing better than the other two models. We also used the three species-abundance distributions, namely the lognormal, logcauchy and logseries model, to fit them to the species-abundance data of six communities. In this case, the logcauchy model had the better fit based on the coefficient of determination. Our research reveals that the rare species always exist in the six communities, corroborating the neutral theory of Hubbell. Furthermore, we explained why all species-abundance figures appeared to be left-side truncated. This was due to subtropical forests have high diversity, and their large species number includes many rare species.  相似文献   

14.
Mass Action Stoichiometric Simulation Models: Incorporating Kinetics and Regulation into Stoichiometric Models     
Neema Jamshidi 《Biophysical journal》2010,98(2):175-185
  相似文献   

15.
眼镜蛇伤模型造模探讨及多项指标的动态观察   总被引:5,自引:1,他引:4  
唐荣德  李景新  蒋三员  刘社炎  王理德 《蛇志》2003,15(2):25-28
目的 探讨眼镜蛇伤模型的造模方法并观察模型多项指标的动态变化。方法 用中华眼镜蛇毒于家兔左小腿作皮下注射制作眼镜蛇伤模型,并分别于注蛇毒前1天,注蛇毒后6h,24h和7天从家兔耳缘静脉采血作血液和生化等多项指标的检查。结果 与生理盐水组相比,眼镜蛇毒组的家兔在注毒后数小时至24h可出现炎症反应和急性弥漫性血管内凝血(DIC),心功能及水盐代谢亦受到一些影响。结论 利用家兔可制作出眼镜蛇伤模型。  相似文献   

16.
Models and experiments? An exploration     
William C. Wimsatt 《Biology & philosophy》2015,30(2):293-298
  相似文献   

17.
Hidden Markov Models and Animal Behaviour     
Iain L. Macdonald  David Raubenheimer 《Biometrical journal. Biometrische Zeitschrift》1995,37(6):701-712
This paper proposes the use of hidden Markov time series models for the analysis of the behaviour sequences of one or more animals under observation. These models have advantages over the Markov chain models commonly used for behaviour sequences, as they can allow for time-trend or expansion to several subjects without sacrificing parsimony. Furthermore, they provide an alternative to higher-order Markov chain models if a first-order Markov chain is unsatisfactory as a model. To illustrate the use of such models, we fit multivariate and univariate hidden Markov models allowing for time-trend to data from an experiment investigating the effects of feeding on the locomotory behaviour of locusts (Locusta migratoria).  相似文献   

18.
Models of immunologic diseases and disorders   总被引:2,自引:0,他引:2  
R A Good  J Finstad  W A Cain  A Fish  D Y Perey  R A Gatti 《Federation proceedings》1969,28(1):191-205
  相似文献   

19.
度量误差模型及其应用   总被引:1,自引:0,他引:1  
唐守正  张淑梅 《生物数学学报》1998,13(2):161-166
本文介绍度量误差模型的基本概念和参数估计的基本结果以及与通常回归之间的关系.并讨论了这个模型在生物学中应用的可能性.  相似文献   

20.
Hans Ussing, Experiments and Models     
Lindemann B 《The Journal of membrane biology》2001,184(3):203-210
The article describes work and impact of Hans H. Ussing, a founder of epithelial physiology. Emphasis is on Ussing's model of epithelial transport, which showed early how a complex function can arise from a few basic principles. The KJU-model was developed 1958 for the amphibian epidermis and later applied and adapted to many epithelia, but especially to those that express amiloride-sensitive sodium channels in their apical membrane. Some of the subsequent research dealing with such channels and their cellular environment is briefly reviewed. The ideas of Hans Ussing were and are an inspiration to many of us, who continue to work in the way Ussing has taught us.  相似文献   

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