The past decade has seen a dramatic rise in consumer technologies able to monitor a variety of cardiovascular parameters. Such devices initially recorded markers of exercise, but now include physiological and health-care focused measurements. The public are keen to adopt these devices in the belief that they are useful to identify and monitor cardiovascular disease.
View Article and Find Full Text PDFWith limited availability of vaccines, an efficient use of the limited supply of vaccines in order to achieve herd immunity will be an important tool to combat the wide-spread prevalence of COVID-19. Here, we compare a selection of strategies for vaccine distribution, including a novel targeted vaccination approach (EHR) that provides a noticeable increase in vaccine impact on disease spread compared to age-prioritized and random selection vaccination schemes. Using high-fidelity individual-based computer simulations with Oslo, Norway as an example, we find that for a community reproductive number in a setting where the base pre-vaccination reproduction number R = 2.
View Article and Find Full Text PDFBackground: While invasive social distancing measures have proven efficient to control the spread of pandemics failing wide-scale deployment of vaccines, they carry vast societal costs. The development of a diagnostic methodology for identifying COVID-19 infection through simple testing was a reality only a few weeks after the novel virus was officially announced. Thus, we were interested in exploring the ability of regular testing of non-symptomatic people to reduce cases and thereby offer a non-pharmaceutical tool for controlling the spread of a pandemic.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
June 2021
Each animal in the Darwinian theater is exposed to a number of abiotic and biotic risk factors causing mortality. Several of these risk factors are intimately associated with the act of energy acquisition as such and with the amount of reserve the organism has available from this acquisition for overcoming temporary distress. Because a considerable fraction of an individual's lifetime energy acquisition is spent on somatic maintenance, there is a close link between energy expenditure on somatic maintenance and mortality risk.
View Article and Find Full Text PDFThe aim of this position paper is to provide a brief overview of the current status of cardiovascular modelling and of the processes required and some of the challenges to be addressed to see wider exploitation in both personal health management and clinical practice. In most branches of engineering the concept of the digital twin, informed by extensive and continuous monitoring and coupled with robust data assimilation and simulation techniques, is gaining traction: the Gartner Group listed it as one of the top ten digital trends in 2018. The cardiovascular modelling community is starting to develop a much more systematic approach to the combination of physics, mathematics, control theory, artificial intelligence, machine learning, computer science and advanced engineering methodology, as well as working more closely with the clinical community to better understand and exploit physiological measurements, and indeed to develop jointly better measurement protocols informed by model-based understanding.
View Article and Find Full Text PDFThe brain lacks lymph vessels and must rely on other mechanisms for clearance of waste products, including amyloid [Formula: see text] that may form pathological aggregates if not effectively cleared. It has been proposed that flow of interstitial fluid through the brain's interstitial space provides a mechanism for waste clearance. Here we compute the permeability and simulate pressure-mediated bulk flow through 3D electron microscope (EM) reconstructions of interstitial space.
View Article and Find Full Text PDFWe describe an emerging initiative - the 'Functional Annotation of All Salmonid Genomes' (FAASG), which will leverage the extensive trait diversity that has evolved since a whole genome duplication event in the salmonid ancestor, to develop an integrative understanding of the functional genomic basis of phenotypic variation. The outcomes of FAASG will have diverse applications, ranging from improved understanding of genome evolution, to improving the efficiency and sustainability of aquaculture production, supporting the future of fundamental and applied research in an iconic fish lineage of major societal importance.
View Article and Find Full Text PDFA major rationale for the advocacy of epigenetically mediated adaptive responses is that they facilitate faster adaptation to environmental challenges. This motivated us to develop a theoretical-experimental framework for disclosing the presence of such adaptation-speeding mechanisms in an experimental evolution setting circumventing the need for pursuing costly mutation-accumulation experiments. To this end, we exposed clonal populations of budding yeast to a whole range of stressors.
View Article and Find Full Text PDFComputational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well-established numerical techniques. Unfortunately, there have been only a few attempts to create a comprehensive public domain resource for cardiovascular researchers.
View Article and Find Full Text PDFIn many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning.
View Article and Find Full Text PDFThe capacity to map traits over large cohorts of individuals-phenomics-lags far behind the explosive development in genomics. For microbes, the estimation of growth is the key phenotype because of its link to fitness. We introduce an automated microbial phenomics framework that delivers accurate, precise, and highly resolved growth phenotypes at an unprecedented scale.
View Article and Find Full Text PDFA scientific understanding of individual variation is key to personalized medicine, integrating genotypic and phenotypic information via computational physiology. Genetic effects are often context-dependent, differing between genetic backgrounds or physiological states such as disease. Here, we analyse in silico genotype-phenotype maps (GP map) for a soft-tissue mechanics model of the passive inflation phase of the heartbeat, contrasting the effects of microstructural and other low-level parameters assumed to be genetically influenced, under normal, concentrically hypertrophic and eccentrically hypertrophic geometries.
View Article and Find Full Text PDFSingle-channel optical density measurements of population growth are the dominant large scale phenotyping methodology for bridging the gene-function gap in yeast. However, a substantial amount of the genetic variation induced by single allele, single gene or double gene knock-out technologies fail to manifest in detectable growth phenotypes under conditions readily testable in the laboratory. Thus, new high-throughput phenotyping technologies capable of providing information about molecular level consequences of genetic variation are sorely needed.
View Article and Find Full Text PDFThis year we celebrate the 150th anniversary of the law of mass action. This law is often assumed to have been "there" forever, but it has its own history, background, and a definite starting point. The law has had an impact on chemistry, biochemistry, biomathematics, and systems biology that is difficult to overestimate.
View Article and Find Full Text PDFExposing natural selection driving phenotypic and genotypic adaptive differentiation is an extraordinary challenge. Given that an organism's life stages are exposed to the same environmental variations, we reasoned that fitness components, such as the lag, rate, and efficiency of growth, directly reflecting performance in these life stages, should often be selected in concert. We therefore conjectured that correlations between fitness components over natural isolates, in a particular environmental context, would constitute a robust signal of recent selection.
View Article and Find Full Text PDFThe mouse is an important model for theoretical-experimental cardiac research, and biophysically based whole organ models of the mouse heart are now within reach. However, the passive material properties of mouse myocardium have not been much studied. We present an experimental setup and associated computational pipeline to quantify these stiffness properties.
View Article and Find Full Text PDFHypertension is one of the most common age-related chronic disorders, and by predisposing individuals for heart failure, stroke, and kidney disease, it is a major source of morbidity and mortality. Its etiology remains enigmatic despite intense research efforts over many decades. By use of empirically well-constrained computer models describing the coupled function of the baroreceptor reflex and mechanics of the circulatory system, we demonstrate quantitatively that arterial stiffening seems sufficient to explain age-related emergence of hypertension.
View Article and Find Full Text PDFIn mammals, two carotenoid cleaving oxygenases are known; beta-carotene 15,15'-monooxygenase (BCMO1) and beta-carotene 9',10'-oxygenase (BCO2). BCMO1 is a key enzyme in vitamin A synthesis by symmetrically cleaving beta-carotene into 2 molecules of all-trans-retinal, while BCO2 is responsible for asymmetric cleavage of a broader range of carotenoids. Here, we show that the Atlantic salmon beta-carotene oxygenase (bco) gene family contains 5 members, three bco2 and two bcmo1 paralogs.
View Article and Find Full Text PDFEuropean funding under Framework 7 (FP7) for the virtual physiological human (VPH) project has been in place now for 5 years. The VPH Network of Excellence (NoE) has been set up to help develop common standards, open source software, freely accessible data and model repositories, and various training and dissemination activities for the project. It is also working to coordinate the many clinically targeted projects that have been funded under the FP7 calls.
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