169 research outputs found
Large phenotype jumps in biomolecular evolution
By defining the phenotype of a biopolymer by its active three-dimensional
shape, and its genotype by its primary sequence, we propose a model that
predicts and characterizes the statistical distribution of a population of
biopolymers with a specific phenotype, that originated from a given genotypic
sequence by a single mutational event. Depending on the ratio g0 that
characterizes the spread of potential energies of the mutated population with
respect to temperature, three different statistical regimes have been
identified. We suggest that biopolymers found in nature are in a critical
regime with g0 in the range 1-6, corresponding to a broad, but not too broad,
phenotypic distribution resembling a truncated Levy flight. Thus the biopolymer
phenotype can be considerably modified in just a few mutations. The proposed
model is in good agreement with the experimental distribution of activities
determined for a population of single mutants of a group I ribozyme.Comment: to appear in Phys. Rev. E; 7 pages, 6 figures; longer discussion in
VII, new fig.
Funnel landscape and mutational robustness as a result of evolution under thermal noise
In biological systems, expression dynamics to shape a fitted phenotype for
function has evolved through mutations to genes, as observed in the evolution
of funnel landscape in protein. We study this evolutionary process with a
statistical-mechanical model of interacting spins, where the fitted phenotype
is represented by a configuration of a given set of "target spins" and
interaction matrix J among spins is genotype evolving over generations. The
expression dynamics is given by stochastic process with temperature T_S to
decrease energy for a given set of J. The evolution of J is also stochastic
with temperature T_J, following mutation in J and selection based on a fitness
given by configurations of the target spins. Below a certain temperature
T_S^{c2}, the highly adapted J evolves, whereasanother phase transition
characterised by frustration occurs at T_S^{c1}<T_S^{c2}. At temperature lower
than T_S^{c1}, the Hamiltonian exhibits a spin-glass like phase, where the
dynamics requires long time steps to produce the fitted phenotype, and the
fitness often decreases drastically by single mutation. In contrast, in the
intermediate temperature phase between T_S^{c1} and T_S^{c2}, the evolved
genotypes, that have no frustration around the target spins (we call "local
Mattis state"), give a funnel-like rapid expression dynamics and are robust to
mutation. These results imply that evolution under thermal noise beyond a
certain level leads to funnel dynamics and mutational robustness. We will
explain its mechanism with the statistical-mechanical method.Comment: 4pages, 4figure
A new method to analyse the pace of child development: Cox regression validated by a bootstrap resampling procedure
<p>Abstract</p> <p>Background</p> <p>Various perinatal factors influencing neuromotor development are known from cross sectional studies. Factors influencing the age at which distinct abilities are acquired are uncertain. We hypothesized that the Cox regression model might identify these factors.</p> <p>Methods</p> <p>Neonates treated at Aachen University Hospital in 2000/2001 were identified retrospectively (n = 796). Outcome data, based on a structured interview, were available from 466 children, as were perinatal data. Factors possibly related to outcome were identified by bootstrap selection and then included into a multivariate Cox regression model. To evaluate if the parental assessment might change with the time elapsed since birth we studied five age cohorts of 163 normally developed children.</p> <p>Results</p> <p>Birth weight, gestational age, congenital cardiac disease and periventricular leukomalacia were related to outcome in the multivariate analysis (p < 0.05). Analysis of the control cohorts revealed that the parents' assessment of the ability of bladder control is modified by the time elapsed since birth.</p> <p>Conclusions</p> <p>Combined application of the bootstrap resampling procedure and multivariate Cox regression analysis effectively identifies perinatal factors influencing the age at which distinct abilities are acquired. These were similar as known from previous cross sectional studies. Retrospective data acquistion may lead to a bias because the parental memories change with time. This recommends applying this statistical approach in larger prospective trials.</p
The Ascent of the Abundant: How Mutational Networks Constrain Evolution
Evolution by natural selection is fundamentally shaped by the fitness landscapes in which it occurs. Yet fitness landscapes are vast and complex, and thus we know relatively little about the long-range constraints they impose on evolutionary dynamics. Here, we exhaustively survey the structural landscapes of RNA molecules of lengths 12 to 18 nucleotides, and develop a network model to describe the relationship between sequence and structure. We find that phenotype abundance—the number of genotypes producing a particular phenotype—varies in a predictable manner and critically influences evolutionary dynamics. A study of naturally occurring functional RNA molecules using a new structural statistic suggests that these molecules are biased toward abundant phenotypes. This supports an “ascent of the abundant” hypothesis, in which evolution yields abundant phenotypes even when they are not the most fit
Does unemployment in family affect pregnancy outcome in conditions of high quality maternity care?
BACKGROUND: The influence of unemployment in the family on pregnancy outcome is controversial. Only a few studies have involved investigation of the effect of unemployment of the father on pregnancy. The objective of this study was to assess the effects of unemployment of one or both parents on obstetric outcome in conditions of free antenatal care attended by the entire pregnant population. METHODS: The data of 24 939 pregnancies included maternal risk factors, pregnancy characteristics and outcome, and was based on a self administered questionnaire at 20 weeks of pregnancy and on clinical records. RESULTS: Unemployment was associated with adolescent maternal age, unmarried status and overweight, anemia, smoking, alcohol consumption and prior pregnancy terminations. Multivariate logistic regression analysis indicated that after controlling for these maternal risk factors small differences only were found in pregnancy outcomes between unemployed and employed families. Unemployed women had significantly more often small-for-gestational-age (SGA) infants, at an OR of 1.26 (95% CI: 1.12 – 1.42) whereas, in families where both parents were unemployed, the risk of SGA was even higher at an OR of 1.43 (95% CI: 1.18 – 1.73). Otherwise, pregnancy outcome was comparable in the groups studied. CONCLUSION: Free antenatal care was unable to fully overcome the adverse pregnancy outcomes associated with unemployment, SGA risk being highest when both parents are unemployed
Nonheritable Cellular Variability Accelerates the Evolutionary Processes of Cancer
Heritable genetic or epigenetic changes in cells are thought to drive tumor development, metastasis, and drug resistance. This essay discusses the possibility that nonheritable phenotypic variability contributes to the evolution of cancer, suggesting new approaches to treatment
Persistent left superior vena cava: Review of the literature, clinical implications, and relevance of alterations in thoracic central venous anatomy as pertaining to the general principles of central venous access device placement and venography in cancer patients
Persistent left superior vena cava (PLSVC) represents the most common congenital venous anomaly of the thoracic systemic venous return, occurring in 0.3% to 0.5% of individuals in the general population, and in up to 12% of individuals with other documented congential heart abnormalities. In this regard, there is very little in the literature that specifically addresses the potential importance of the incidental finding of PLSVC to surgeons, interventional radiologists, and other physicians actively involved in central venous access device placement in cancer patients. In the current review, we have attempted to comprehensively evaluate the available literature regarding PLSVC. Additionally, we have discussed the clinical implications and relevance of such congenital aberrancies, as well as of treatment-induced or disease-induced alterations in the anatomy of the thoracic central venous system, as they pertain to the general principles of successful placement of central venous access devices in cancer patients. Specifically regarding PLSVC, it is critical to recognize its presence during attempted central venous access device placement and to fully characterize the pattern of cardiac venous return (i.e., to the right atrium or to the left atrium) in any patient suspected of PLSVC prior to initiation of use of their central venous access device
Signalling and the Evolution of Cooperative Foraging in Dynamic Environments
Understanding cooperation in animal social groups remains a significant challenge for evolutionary theory. Observed behaviours that benefit others but incur some cost appear incompatible with classical notions of natural selection; however, these behaviours may be explained by concepts such as inclusive fitness, reciprocity, intra-specific mutualism or manipulation. In this work, we examine a seemingly altruistic behaviour, the active recruitment of conspecifics to a food resource through signalling. Here collective, cooperative behaviour may provide highly nonlinear benefits to individuals, since group functionality has the potential to be far greater than the sum of the component parts, for example by enabling the effective tracking of a dynamic resource. We show that due to this effect, signalling to others is an evolutionarily stable strategy under certain environmental conditions, even when there is a cost associated to this behaviour. While exploitation is possible, in the limiting case of a sparse, ephemeral but locally abundant nutrient source, a given environmental profile will support a fixed number of signalling individuals. Through a quantitative analysis, this effective carrying capacity for cooperation is related to the characteristic length and time scales of the resource field
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Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the US
This article contains supporting information online at http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2113561119/-/DCSupplemental.Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multi-model ensemble forecast that combined predictions from dozens of different research groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-week horizon 3-5 times larger than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.Integrative Biolog
Cis-regulatory evolution spotlights species differences in the adaptive potential of gene expression plasticity
Plasticity allows organisms to respond to environmental change. Here the authors compare the distribution of cis-regulatory variants in the transcriptomes of Arabidopsis lyrata and A. halleriafter exposure to stress, to trace the role of polygenic selection in the evolution of gene expression plasticity
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