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Development of regular cellular spacing in the retina: theoretical models.

During development of the nervous system, neurons should be appropriately positioned to enable them to make the right functional contacts. Neurons do not immediately migrate to their correct location, but instead regular arrangements gradually emerge from randomly arranged cell populations. This phenomenon has been studied often in the retina, due to its relatively simple layered organisation. In this review, I highlight the principal mechanisms that are thought to be involved, and how mathematical modelling has helped to further our understanding of the role of these processes upon mosaic formation. Three developmental mechanisms are studied in detail, namely, lateral migration, cell fate and cell death. As a case study, I then consider which mechanisms might be involved in the formation of retinal ganglion cell mosaics.

Algorithms↗

A theoretical model of restriction endonuclease NlaIV in complex with DNA, predicted by fold recognition and validated by site-directed mutagenesis and circular dichroism spectroscopy.

Restriction enzymes (REases) are commercial reagents commonly used in DNA manipulations and mapping. They are regarded as very attractive models for studying protein-DNA interactions and valuable targets for protein engineering. Their amino acid sequences usually show no similarities to other proteins, with rare exceptions of other REases that recognize identical or very similar sequences. Hence, they are extremely hard targets for structure prediction and modeling. NlaIV is a Type II REase, which recognizes the interrupted palindromic sequence GGNNCC (where N indicates any base) and cleaves it in the middle, leaving blunt ends. NlaIV shows no sequence similarity to other proteins and virtually nothing is known about its sequence-structure-function relationships. Using protein fold recognition, we identified a remote relationship between NlaIV and EcoRV, an extensively studied REase, which recognizes the GATATC sequence and whose crystal structure has been determined. Using the 'FRankenstein's monster' approach we constructed a comparative model of NlaIV based on the EcoRV template and used it to predict the catalytic and DNA-binding residues. The model was validated by site-directed mutagenesis and analysis of the activity of the mutants in vivo and in vitro as well as structural characterization of the wild-type enzyme and two mutants by circular dichroism spectroscopy. The structural model of the NlaIV-DNA complex suggests regions of the protein sequence that may interact with the 'non-specific' bases of the target and thus it provides insight into the evolution of sequence specificity in restriction enzymes and may help engineer REases with novel specificities. Before this analysis was carried out, neither the three-dimensional fold of NlaIV, its evolutionary relationships or its catalytic or DNA-binding residues were known. Hence our analysis may be regarded as a paradigm for studies aiming at reducing 'white spaces' on the evolutionary landscape of sequence-function relationships by combining bioinformatics with simple experimental assays.

Amino Acid Sequence↗

Reevaluating the theoretical model underlying the neurodevelopmental theory. A literature review.

The purpose of this paper is to evaluate the foundations of prevalent physical therapy technique based on the current research on motor control. The conceptual framework of the neurodevelopmental theory, as described in the writings of the Bobaths, is presented. Their explanations of central nervous system disorders and recommendations for intervention are based upon a unidirectional model of the nervous system in which postural and voluntary motion become two separate and distinct entities. Systems theory is an alternative model of nervous system structure. In systems theory, the organism is a circular network of interacting yet autonomous subsystems, rather than a vertical structure of descending controls. Relevant research that supports the systems viewpoint is discussed and applied to the theories in the neurodevelopmental approach. Thus, another model is offered for understanding the functioning of the central nervous system when it is intact and when it is in a pathological state.

Animals↗

Theoretical modelling of experimental diagnostic procedures employed during pre-dose dosimetry of quartz.

The pre-dose technique in thermoluminescence (TL) is used for dating archaeological ceramics and for accident dosimetry. During routine applications of this technique, the sensitisation of the quartz samples is measured as a function of the annealing temperature, yielding the so-called thermal activation characteristic (TAC). The measurement of multiple TACs and the study of the effect of UV-radiation on the TL sensitivity of quartz are important analytical and diagnostic tools. In this paper, it is shown that a modified Zimmerman model for quartz can successfully model the experimental steps undertaken during a measurement of multiple TACs.

Algorithms↗

Nursing home care quality: a multidimensional theoretical model.

This exploratory study was undertaken to discover the defining dimensions of nursing home care quality and to propose a conceptual model to guide nursing home quality research and the development of instruments to measure nursing home care quality. Three focus groups were conducted in three central Missouri communities. A naturalistic inductive analysis of the transcribed content was completed. Two core variables (interaction and odor) and several related concepts emerged from the data. Using the core variables, related concepts, and detailed descriptions from participants, three models of nursing home care quality emerged from the analysis: (1) a model of a nursing home with good quality care; (2) a model of a nursing home with poor quality care; and (3) a multidimensional model of nursing home care quality. The seven dimensions of the multidimensional model of nursing home care quality are: central focus, interaction, milieu, environment, individualized care, staff, and safety. To pursue quality, the many dimensions must be of primary concern to nursing homes. We are testing an instrument based on the model to observe and score the dimensions of nursing home care quality.

Attitude to Health↗

The antiretroviral rollout and drug-resistant HIV in Africa: insights from empirical data and theoretical models.

The U.S. Government has pledged to spend $15 billion in Africa and the Caribbean on AIDS. A central focus of this plan is to provide antiretroviral treatment (ART) to millions. Here, we evaluate whether the plan to rollout ART in Africa is likely to generate an epidemic of drug-resistant strains of HIV. We review what has occurred as a result of high usage of ART in developed countries in terms of changes in risky behavior, and the emergence and transmission of drug-resistant HIV. We also review how mathematical models have been used to predict the evolution of drug-resistant HIV epidemics. We then show how models can be used to predict the likely impact of the ART rollout on the evolution of drug-resistant HIV in Africa. At currently planned levels of treatment coverage, we predict that (over the next decade) in Africa: (i) the impact of ART on reducing HIV transmission (and prevalence) is likely to be undetectable (unless accompanied by substantial changes in behavior), (ii) the transmission rate of drug-resistant HIV will be below the WHO surveillance threshold of 5%, and (ii) the majority of cases of drug-resistant HIV that will occur will be due to acquired (and not transmitted) resistance. For the next decade, large-scale surveillance for detecting transmitted resistance in Africa is unnecessary. Instead, we recommend that patients should be closely monitored for acquired resistance, and sentinel surveillance (in a few urban centers) should be used to monitor transmitted resistance.

Africa↗

Cerebral arteriovenous malformation feeding artery aneurysms: a theoretical model of intravascular pressure changes after treatment.

OBJECTIVE: A quantitative model may be used to estimate the magnitude of expected pressure changes along the vascular tree with shunt ablation and may provide information to assess the hemodynamic risk of arteriovenous malformation (AVM) treatment. METHODS: A computer model of the cerebral circulation was applied to estimate the changes in intravascular pressure, velocity, biomechanical stress, and shear stress that might be expected from either endovascular or surgical ablation of AVMs. Two AVM sizes and two feeding artery constellations were simulated. The effect of different shunt flows on vascular pressure was modeled. In each simulation, AVMs were occluded in a stepwise fashion. The effects of systemic hypertension and hypotension in various vascular zones were also simulated. RESULTS: As large (1000 ml/min) AVMs were occluded, the mean feeding arterial pressure increased from 18 to 68 mm Hg; the percent-occlusion at half-maximal pressure increase was 92%. For medium (500 ml/min) AVMs, feeding arterial pressure increased from 37 to 66 mm Hg; the percent-occlusion at half-maximal pressure increase was 71%. During manipulation of systemic pressure, hemodynamic changes in the circulation close to the nidus were proportionally less than changes in systemic pressure; the degree of proportionality depended on the magnitude of AVM shunt flow. CONCLUSION: In this simulation, shunt obliteration increased pressure in the nidus and feeding arteries with little effect on the proximal circulation. The shunt provided a "buffering" effect, i.e., higher flow fistulas were exposed to smaller variations in intravascular pressure in feeding artery and nidal pressures during manipulation of systemic pressure.

Adult↗

A theoretical model of the determinants of mortality.

Outcome research in nursing has been criticized for being atheoretical. Although there has been research investigating patient mortality as an outcome, there has been little discussion about models or theories of nursing-related determinants of mortality for hospitalized patients. Yet, unnecessary patient mortality is an important patient safety outcome. This article describes development of beginning theory of determinants of patient mortality culminating with a revised mortality model. Conclusions are made related to plans for further testing and refinement of the revised mortality model. Further, the utility of the proposed model in practice is discussed.

Acute Disease↗

Microbial diversity, producer-decomposer interactions and ecosystem processes: a theoretical model.

Interactions between the diversity of primary producers and that of decomposers--the two key functional groups that form the basis of all ecosystems--might have major consequences on the functioning of depauperate ecosystems. I present a simple ecosystem model in which primary producers (plants) and decomposers (microbes) are linked through material cycling. The model considers a diversity of plant organic compounds and a diversity of microbial species. Nutrient recycling efficiency from organic compounds to decomposers is then the key parameter that controls ecosystem processes (primary productivity, secondary productivity, producer biomass and decomposer biomass). The model predicts that microbial diversity has a positive effect on nutrient recycling efficiency and ecosystem processes through either greater intensity of microbial exploitation of organic compounds or functional niche complementarity, much like in plants. Microbial niche breadth and overlap should not affect ecosystem processes unless they increase the number of organic compounds that are decomposed. In contrast, the model predicts that plant organic compound diversity can only have a negative effect or, at best, no effect on ecosystem processes, at least in a constant environment. This creates a tension between the effects of plant diversity and microbial diversity on ecosystem functioning, which may explain some recent experimental results.

Bacteria↗

Fitness and evolutionary stability in game theoretic models of finite populations.

We investigate two methods of measuring fitness in evolutionary games played among members of a finite population. Classical notions of stability account for the action of selection only, and use immediate reproductive gains as a measure of fitness. This classical interpretation of fitness is what we call reproductive fitness (RF), and is found in the early studies of evolutionary stability in finite populations. More recent work has incorporated the influence of random genetic drift by applying fixation probability (FP) as a measure of fitness. When defined in this way, fitness represents a measure of ultimate evolutionary success. Our main result describes an equivalence between candidate evolutionarily stable strategies under both the RF and FP interpretations of fitness. We apply this result to matrix games in which the use of mixed strategies is permitted, and find here an equivalence between the RF and FP conditions for evolutionary stability.

Biological Evolution↗