Property:Abstract
From Complex Time
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<p>Pairwise models are commonly used to describe many-species communities. In these models, an individual receives additive fitness effects from pairwise interactions with each species in the community ('additivity assumption'). All pairwise interactions are typically represented by a single equation where parameters reflect signs and strengths of fitness effects ('universality assumption'). Here, we show that a single equation fails to qualitatively capture diverse pairwise microbial interactions. We build mechanistic reference models for two microbial species engaging in commonly-found chemical-mediated interactions, and attempt to derive pairwise models. Different equations are appropriate depending on whether a mediator is consumable or reusable, whether an interaction is mediated by one or more mediators, and sometimes even on quantitative details of the community (e.g. relative fitness of the two species, initial conditions). Our results, combined with potential violation of the additivity assumption in many-species communities, suggest that pairwise modeling will often fail to predict microbial dynamics.</p> +
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<p>The importance of transient dynamics in ecological systems and in the models that describe them has become increasingly recognized. However, previous work has typically treated each instance of these dynamics separately. We review both empirical examples and model systems, and outline a classification of transient dynamics based on ideas and concepts from dynamical systems theory. This classification provides ways to understand the likelihood of transients for particular systems, and to guide investigations to determine the timing of sudden switches in dynamics and other characteristics of transients. Implications for both management and underlying ecological theories emerge.</p> +
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Available energy fluxes drive a transition in the diversity, stability, and functional structure of microbial communities +
A fundamental goal of microbial ecology is to understand what determines the diversity, stability, and structure of microbial ecosystems. The microbial context poses special conceptual challenges because of the strong mutual influences between the microbes and their chemical environment through the consumption and production of metabolites. By analyzing a generalized consumer resource model that explicitly includes cross-feeding, stochastic colonization, and thermodynamics, we show that complex microbial communities generically exhibit a transition as a function of available energy fluxes from a "resource-limited" regime where community structure and stability is shaped by energetic and metabolic considerations to a diverse regime where the dominant force shaping microbial communities is the overlap between species' consumption preferences. These two regimes have distinct species abundance patterns, different functional profiles, and respond differently to environmental perturbations. Our model reproduces large-scale ecological patterns observed across multiple experimental settings such as nestedness and differential beta diversity patterns along energy gradients. We discuss the experimental implications of our results and possible connections with disorder-induced phase transitions in statistical physics. +
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A number of fundamental mathematical models of the evolutionary process exhibit dynamics that can be difficult to understand analytically. Here we show that a precise mathematical analogy can be drawn between certain evolutionary and thermodynamic systems, allowing application of the powerful machinery of statistical physics to analysis of a family of evolutionary models. Analytical results that follow directly from this approach include the steady-state distribution of fixed genotypes and the load in finite populations. The analogy with statistical physics also reveals that, contrary to a basic tenet of the nearly neutral theory of molecular evolution, the frequencies of adaptive and deleterious substitutions at steady state are equal. Finally, just as the free energy function quantitatively characterizes the balance between energy and entropy, a free fitness function provides an analytical expression for the balance between natural selection and stochastic drift. +
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A sensitive, precise and accurate quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the measurement of erythromycin A (EA) and related substances in commercial samples was developed and validated. The samples were chromatographed on a reversed-phase column with a polar endcapping and analyzed by ion trap tandem mass spectrometry in the multiple reaction monitoring (MRM) mode using positive electrospray ionization. The method showed high recovery (>98.82%), high sensitivity (lower limit of quantitation of 0.25 ng/mL for EA and less than 7.3 ng/mL for the related substances) and high precision (<0.52%) as well as excellent linearity (r2 > 0.991) with a run time of only 13 min. The method was successfully applied to the determination of EA and related substances in commercial samples. Moreover, using the advanced data-dependent acquisition capability of the ion trap software two new unexpected EA related substances could be detected and possible structures for these substances were postulated. © 2006 Elsevier B.V. All rights reserved. +
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AIMS: We have previously suggested that acute ethanol consumption by normal subjects decreases the availability of circulating tryptophan (Trp) to the brain by activating liver Trp pyrrolase, the first and rate-limiting enzyme of the (major) kynurenine pathway of Trp degradation. The aim of the present study was to examine this hypothesis further by measuring plasma levels of kynurenine metabolites following alcohol consumption. METHODS: After an overnight fast and a light breakfast, each of 10 healthy subjects received one of five drinks (placebo and doses of ethanol of 0.2, 0.4, 0.6 and 0.8 g/kg body weight in tonic water) on five different occasions. Blood samples were withdrawn 2 h later and plasma was analysed for concentrations Trp, competing amino acids (CAA) and kynurenine metabolites. RESULTS: Along with the depletion of plasma Trp and the decrease in its availability to the brain, as expressed by the ratio of [Trp]/[CAA], plasma kynurenine was elevated by doses of ethanol of 0.2-0.8 g/kg body weight. The ratio% of [kynurenine]/[Trp], an index of the expression of Trp pyrrolase activity, was also increased by all doses of ethanol. CONCLUSIONS: We conclude that activation of liver Trp pyrrolase mediates the depletion of plasma Trp and the decrease in its availability to the brain induced by acute ethanol consumption. +
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Adaptation to a novel environment is altered by the presence of co-occurring species. Species in diverse communities evolved complementary resource use, which altered the functioning of the experimental ecosystems. +
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The Effects of APOE and ABCA7 on Cognitive Function and Alzheimer’s Disease Risk in African Americans: A Focused Mini Review +
African Americans have double the prevalence of Alzheimer’s disease (AD), as compared to European Americans. However, the underlying causes of this health disparity are due to a multitude of environmental, lifestyle, and genetic factors that are not yet fully understood. Here, we review the effects of the two largest genetic risk factors for AD in African Americans: Apolipoprotein E (APOE) and ABCA7. We will describe the direct effects of genetic variation on neural correlates of cognitive function and report the indirect modulating effects of genetic variation on modifiable AD risk factors, such as aerobic fitness. As a means of integrating previous findings, we present a novel schematic diagram to illustrate the many factors that contribute to AD risk and impaired cognitive function in older African Americans. Finally, we discuss areas that require further inquiry, and stress the importance of racially diverse and representative study populations. +
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Age-related alterations of the immune system affect both antibody and cell-mediated immune responses, T-cell responses being more severely affected than B-cell responses. Within the T-cell population, aging leads to replacement of virgin by memory cells and to accumulation of cells with signal transduction defects. Changes in T-cell subsets and in cytokine production profiles may produce suitable conditions for T-cell-mediated disregulation of antibody responses characterized by the production of low affinity and self-reactive antibodies. Also B-cells exhibit intrinsic defects and natural killer (NK) cell activity a profound loss in old mice. Whether age-related immune disfunctions influence life span and tumor incidence has been examined in mice genetically selected for high or low antibody responsiveness. It has been found that genetic selection of vigorous antibody responses in most cases produces mice with longer life span and lower lymphoma incidence. Moreover, the results of genetic segregation experiments indicate that antibody responsiveness and life span are polygenic traits regulated by a small number of the same or closely linked loci. Mice genetically selected for high or low mitotic responsiveness to PHA exhibit low or high tumor incidence, respectively, but no difference in life span, suggesting that T-cell activity is restricted to immune surveillance of neoplastic transformation. Studies on mice genetically selected for resistance or sensitivity to chemical carcinogenesis have uncovered loci that control both resistance to tumor induction and longevity while have no effects on immunity and disease incidence. Thus, the relative role of the immune system in conditioning the duration and the biological quality of life remains to be determined. +
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Aging leads to changes in the relative proportions of several functionally distinct T cell subsets, including increases in the proportions of memory cells in the CD4 and CD8 subsets and in the proportion of T cells expressing the multiple-drug resistance pump P-glycoprotein. To see whether individual differences in T cell subset levels predict life span, we measured the levels of five age-sensitive T cell subsets, at 8 and again at 18 months of age, in the peripheral blood of genetically heterogeneous mice bred as the progeny of CB6F1 females and C3D2F1 males. The strongest immunological predictor of life span in univariate regression analyses was the proportion of CD4 memory cells measured at 18 months of age (P=0.003). CD4 memory cell levels remained strongly correlated with life span (P<0.0003) in a multiple regression analysis after adjustment for sex. The proportion of CD4 cells expressing P-glycoprotein was also correlated with life span (P<0.01), but only in male mice. Weaker relationships were observed between life span and 8-month tests of CD8 memory and CD8 P-glycoprotein levels, for CD4 naive cells at 18 months, and for the change in CD4 naive cells between 8 and 18 months of age; these were, however, near the margin of statistical significance and could reflect chance relationships. The relationship between CD4 memory cell levels and life span was similarly strong regardless of the cause of death in mice whose death was attributable to lymphoma, fibrosarcoma, mammary carcinoma, and other forms of terminal pathology. Additional work is needed to discriminate between two hypotheses: 1) that high levels of CD4 memory cell themselves predispose to disease and early death, particularly from neoplasia; or 2) that accumulation of CD4 memory cells is a biomarker of some underlying process-perhaps accelerated aging-that itself leads to early mortality. +
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All life requires the capacity to recover from challenges that are as inevitable as they are unpredictable. Understanding this resilience is essential for managing the health of humans and their livestock. It has long been difficult to quantify resilience directly, forcing practitioners to rely on indirect static indicators of health. However, measurements from wearable electronics and other sources now allow us to analyze the dynamics of physiology and behavior with unsurpassed resolution. The resulting flood of data coincides with the emergence of novel analytical tools for estimating resilience from the pattern of microrecoveries observed in natural time series. Such dynamic indicators of resilience may be used to monitor the risk of systemic failure across systems ranging from organs to entire organisms. These tools invite a fundamental rethinking of our approach to the adaptive management of health and resilience. +
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Although accumulation of molecular damage is suggested to be an important molecular mechanism of aging, a quantitative link between the dynamics of damage accumulation and mortality of species has so far remained elusive. To address this question, we examine stability properties of a generic gene regulatory network (GRN) and demonstrate that many characteristics of aging and the associated population mortality rate emerge as inherent properties of the critical dynamics of gene regulation and metabolic levels. Based on the analysis of age-dependent changes in gene-expression and metabolic profiles in Drosophila melanogaster, we explicitly show that the underlying GRNs are nearly critical and inherently unstable. This instability manifests itself as aging in the form of distortion of gene expression and metabolic profiles with age, and causes the characteristic increase in mortality rate with age as described by a form of the Gompertz law. In addition, we explain late-life mortality deceleration observed at very late ages for large populations. We show that aging contains a stochastic component, related to accumulation of regulatory errors in transcription/translation/metabolic pathways due to imperfection of signaling cascades in the network and of responses to environmental factors. We also establish that there is a strong deterministic component, suggesting genetic control. Since mortality in humans, where it is characterized best, is strongly associated with the incidence of age-related diseases, our findings support the idea that aging is the driving force behind the development of chronic human diseases. +
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The heritability of general cognitive ability increases linearly from childhood to young adulthood +
Although common sense suggests that environmental influences increasingly account for individual differences in behavior as experiences accumulate during the course of life, this hypothesis has not previously been tested, in part because of the large sample sizes needed for an adequately powered analysis. Here we show for general cognitive ability that, to the contrary, genetic influence increases with age. The heritability of general cognitive ability increases significantly and linearly from 41% in childhood (9 years) to 55% in adolescence (12 years) and to 66% in young adulthood (17 years) in a sample of 11 000 pairs of twins from four countries, a larger sample than all previous studies combined. In addition to its far-reaching implications for neuroscience and molecular genetics, this finding suggests new ways of thinking about the interface between nature and nurture during the school years. Why, despite life's 'slings and arrows of outrageous fortune', do genetically driven differences increasingly account for differences in general cognitive ability? We suggest that the answer lies with genotype-environment correlation: as children grow up, they increasingly select, modify and even create their own experiences in part based on their genetic propensities. +
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Extended Twilight among Isogenic C. elegans Causes a Disproportionate Scaling between Lifespan and Health +
Although many genetic factors and lifestyle interventions are known to affect the mean lifespan of animal populations, the physiological variation displayed by individuals across their lifespans remains largely uncharacterized. Here, we use a custom culture apparatus to continuously monitor five aspects of aging physiology across hundreds of isolated Caenorhabditis elegans individuals kept in a constant environment from hatching until death. Aggregating these measurements into an overall estimate of senescence, we find two chief differences between longer- and shorter-lived individuals. First, though long- and short-lived individuals are physiologically equivalent in early adulthood, longer-lived individuals experience a lower rate of physiological decline throughout life. Second, and counter-intuitively, long-lived individuals have a disproportionately extended “twilight” period of low physiological function. While longer-lived individuals experience more overall days of good health, their proportion of good to bad health, and thus their average quality of life, is systematically lower than that of shorter-lived individuals. We conclude that, within a homogeneous population reared under constant conditions, the period of early-life good health is comparatively uniform, and the most plastic period in the aging process is end-of-life senescence. +
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Although species longevity is subject to a diverse range of selective forces, the mortality curves of a wide variety of organisms are rather similar. We argue that aging and its universal characteristics may have evolved by means of a gradual increase in the systemic interdependence between a large collection of biochemical or mechanical components. Modeling the organism as a dependency network which we create using a constructive evolutionary process, we age it by allowing nodes to be broken or repaired according to a probabilistic algorithm that accounts for random failures/repairs and dependencies. Our simulations show that the network slowly accumulates damage and then catastrophically collapses. We use our simulations to fit experimental data for the time dependent mortality rates of a variety of multicellular organisms and even complex machines such as automobiles. Our study suggests that aging is an emergent finite-size effect in networks with dynamical dependencies and that the qualitative and quantitative features of aging are not sensitively dependent on the details of system structure. +
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An ongoing debate in ecology concerns the impacts of ecological drift and selection on community assembly. Here, we show that there is a transition in diverse ecological communities between a selection-dominated regime (the niche phase) and a drift-dominated regime (the neutral phase). Simulations and analytic arguments show that the niche phase is favored in communities with large population sizes and relatively constant environments, whereas the neutral phase is favored in communities with small population sizes and fluctuating environments. Our results demonstrate how apparently neutral populations may arise even in communities inhabited by species with varying traits. +
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Bi-directional selective breeding for antibody (Ab) responsiveness to heterologous erythrocytes (Selection I) produced a high (H) and a low (L) responder line of mice which were also remarkably separated for Ab responses to many unrelated natural antigens (Ags) such as heterologous proteins, viruses, bacteria, parasites and haptens carried by these immunogens. The character "quantitative Ab responsiveness" is controlled by several independently segregating loci (polygenic regulation). The major genetic modification is produced at the level of macrophage activities. The Ag is slowly catabolized and persists for a long time on the macrophage membrane of the H line, whereas it is rapidly destroyed in L line macrophages. The bactericidal and bacteriostatic activity of the macrophage is also strong in the L line and weak in the H line. The opposite genetic regulation of Ab responsiveness and macrophage activity is a fundamental phenomenon for understanding natural and vaccination-induced anti-infectious immunity. The L line is more resistant than the H line against the infections due to intracellular microorganisms (Salmonellae, Yersinia, Mycobacteria, Brucellae, Leishmania) where the macrophage plays the dominant defensive barrier. The H line is more resistant than the L line to the extracellular microorganisms which are efficiently counteracted by a strong antibody response (Pneumococcus, Klebsiella, Plasmodia, Trypanosoma). The intensity of T cell-mediated immunity as measured by delayed type hypersensitivity, which is independent of the genetic regulation of antibody responsiveness, is correlated with the degree of non-specific inflammation produced at the site of the reaction by the Ag injection in non-sensitized mice. The intensity of the non-specific inflammatory reactions to an inert substrate presents a continuous phenotypic variation in inbred lines of mice. Therefore this character is subject to polygenic regulation. The inflammatory reaction constitutes one of the most important non-specific components of immunity. We have therefore initiated a selective breeding experiment to produce lines of mice endowed with maximal and minimal intensity of non-specific inflammatory reactions. This model of selective breeding is described. © 1987.
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Life-Span, tumor incidence, and natural killer cell activity in mice selected for high or low antibody responsiveness +
Biozzi mice selected for high (H) or low (L) antibody responsiveness to natural antigens have been followed for their entire life-span to examine their pathology at death. As previously found in selection I, shorter life-span and higher lymphoma incidence were observed in L responder mice than in H responder mice selected for antibody responsiveness to sheep red blood cells (selection II). In mice selected for antibody responsiveness to Salmonella flagellar antigens (selection III), similar life-span and similar lymphoma incidence were found in H and L responder mice. Natural killer (NK) cell activity, as assessed in spleen cells from young mice, was lower in L than in H responder mice of selection I but higher in L than in H responder mice of both selections II and III. All these results indicate that longevity and lymphoma incidence at death are independent of NK cell activity in mice selected for H or L antibody responsiveness to natural antigens. Furthermore, genetic selection for antibody responsiveness does not always appear to influence life-span and lymphoma incidence. +
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Body size determines key behavioral and life history traits across species, as well as interactions between individuals within and between species. Therefore, variation in sizes of immigrants, by exerting variation in trophic interaction strengths, may drive the trajectory and outcomes of community assembly. Here, I study the effects of size variation in the immigration pool on assembly dynamics and equilibrium distributions of sizes and consumer-resource size-ratios using a general mathematical model. I find that because small sizes both, improve the ability to invade and destabilize the community, invasibility and stability pull body size distributions in opposite directions, favoring an increase in both size and size-ratios during assembly, and ultimately yielding a right-skewed size and a symmetric size-ratio distribution. In many scenarios, the result at equilibrium is a systematic increase in body sizes and size-ratios with trophic level. Thus these patterns in size structure are 'signatures' of dynamically constrained, non-neutral community assembly. I also show that for empirically feasible distributions of body sizes in the immigration pool, immigration bias in body sizes cannot counteract dynamical constraints during assembly and thus signatures emerge consistently. I test the theoretical predictions using data from nine terrestrial and aquatic communities and find strong evidence that natural communities do indeed exhibit such signatures of dynamically constrained assembly. Overall, the results provide new measures to detect general, non-neutral patterns in community assembly dynamics, and show that in general, body size is dominant trait that strongly influences assembly and recovery of natural communities and ecosystems. +
Cerebral cartography can be understood in a limited, static, neuroanatomical sense. Temporal information from electrical recordings contributes information on regional interactions adding a functional dimension. Selective tagging and imaging of molecules adds biochemical contributions. Cartographic detail can also be correlated with normal or abnormal psychological or behavioural data. Modern cerebral cartography is assimilating all these elements. Cartographers continue to collect ever more precise data in the hope that general principles of organization will emerge.However, even detailed cartographic data cannot generate knowledge without a multi-scale framework making it possible to relate individual observations and discoveries. We propose that, in the next quarter century, advances in cartography will result in progressively more accurate drafts of a data-led, multi-scale model of human brain structure and function. These blueprints will result from analysis of large volumes of neuroscientific and clinical data, by a process of reconstruction, modelling and simulation. This strategy will capitalize on remarkable recent developments in informatics and computer science and on the existence of much existing, addressable data and prior, though fragmented, knowledge. Themodels will instantiate principles that govern how the brain is organized at different levels and how different spatio-temporal scales relate to each other in an organ-centred context. +
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Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some older adults show little decline in cognitive ability compared with young adults and are thus termed ‘optimally ageing’. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of the neural mechanisms underlying these two outcomes. However, interpreting the age-related changes and differences in brain structure, activation and functional connectivity that this research reveals is an ongoing challenge. Ambiguous terminology is a major source of difficulty in this venture. Three terms in particular — compensation, maintenance and reserve — have been used in a number of different ways, and researchers continue to disagree about the kinds of evidence or patterns of results that are required to interpret findings related to these concepts. As such inconsistencies can impede progress in both theoretical and empirical research, here, we aim to clarify and propose consensual definitions of these terms. +
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Consumer–resource interactions are often influenced by other species in the community. At present these ‘trophic interaction modifications’ are rarely included in ecological models despite demonstrations that they can drive system dynamics. Here, we advocate and extend an approach that has the potential to unite and represent this key group of non-trophic interactions by emphasising the change to trophic interactions induced by modifying species. We highlight the opportunities this approach brings in comparison to frameworks that coerce trophic interaction modifications into pairwise relationships. To establish common frames of reference and explore the value of the approach, we set out a range of metrics for the ‘strength’ of an interaction modification which incorporate increasing levels of contextual information about the system. Through demonstrations in three-species model systems, we establish that these metrics capture complimentary aspects of interaction modifications. We show how the approach can be used in a range of empirical contexts; we identify as specific gaps in current understanding experiments with multiple levels of modifier species and the distributions of modifications in networks. The trophic interaction modification approach we propose can motivate and unite empirical and theoretical studies of system dynamics, providing a route to confront ecological complexity. +
Contemporary niche theory is a powerful conceptual framework for understanding how organisms interact with each other and with their shared environment. Here we show that a large segment of niche theory is equivalent to a Minimum Environmental Perturbation Principle (MEPP): ecosystems self-organize into a state that minimizes the impact of organisms on their environment. Different choices of environmental dynamics naturally give rise to distinct dissimilarity measures for quantifying environmental impact. The MEPP allows for the analysis of ecosystems with large numbers of species and environmental factors and provides a new avenue for analyzing ecological invasions. The MEPP also rigorously connects ecological bistability with the existence of multiple minima in a statistical-physics inspired landscapes. We show that the presence of environmental feedbacks where organisms can produce new resources in addition to depleting them violates the global MEPP. However, even in the presence of such feedbacks, a weaker, local version of the MEPP still applies in a limited region of resource space. +
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Defined as the invariance of system structure or function following a nontrivial perturbation to one or more important system components, robustness is a characteristic property of all adaptive systems. This chapter reviews the theory of robustness in biology, the design of experiments used to assay robustness (including the functional behavior or outputs of a system), and the adaptive response of those parts or components which are compromised by a perturbation. Emphasis is given to a rigorous logic of measurements that carefully factors apart the many casual contributions to robust function. Insights from the study of robustness in biology are applied to the social and decision-making domains, and modifications of experimental design and theory are proposed to account for challenges unique to human agents. +
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Delirium occurring in patients with dementia is referred to as delirium superimposed on dementia (DSD). People who are older with dementia and who are institutionalized are at increased risk of developing delirium when hospitalized. In addition, their prior cognitive impairment makes detecting their delirium a challenge. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision are considered the standard reference for the diagnosis of delirium and include criteria of impairments in cognitive processes such as attention, additional cognitive disturbances, or altered level of arousal. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision does not provide guidance regarding specific tests for assessment of the cognitive process impaired in delirium. Importantly, the assessment or inclusion of preexisting cognitive impairment is also not addressed by these standards. The challenge of DSD gets more complex as types of dementia, particularly dementia with Lewy bodies, which has features of both delirium and dementia, are considered. The objective of this article is to critically review key elements for the diagnosis of DSD, including the challenge of neuropsychological assessment in patients with dementia and the influence of particular tests used to diagnose DSD. To address the challenges of DSD diagnosis, we present a framework for guiding the focus of future research efforts to develop a reliable reference standard to diagnose DSD. A key feature of a reliable reference standard will improve the ability to clinically diagnose DSD in facility-based patients and research studies. +
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Dietary restriction (DR) increases life-span in organisms from yeast to mammals, presumably by slowing the accumulation of aging-related damage. Here we show that in Drosophila, DR extends life-span entirely by reducing the short-term risk of death. Two days after the application of DR at any age for the first time, previously fully fed flies are no more likely to die than flies of the same age that have been subjected to long-term DR. DR of mammals may also reduce short-term risk of death, and hence DR instigated at any age could generate a full reversal of mortality. +
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Brain state stability during working memory is explained by network control theory, modulated by dopamine D1/D2 receptor function, and diminished in schizophrenia +
Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory entails brain-wide switching between activity states. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Schizophrenia patients show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations. +
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Ecology letters (2011) 14: 914–921AbstractThe Arrhenius equation has emerged as the favoured model for describing the temperature dependence of consumption in predator–prey models. To examine the relevance of this equation, we undertook a meta-analysis of published relationships between functional response parameters and temperature. We show that, when plotted in lin-log space, temperature dependence of both attack rate and maximal ingestion rate exhibits a hump-shaped relationship and not a linear one as predicted by the Arrhenius equation. The relationship remains significantly downward concave even when data from temperatures above the peak of the hump are discarded. Temperature dependence is stronger for attack rate than for maximal ingestion rate, but the thermal optima are not different. We conclude that the use of the Arrhenius equation to describe consumption in predator–prey models requires the assumption that temperatures above thermal optima are unimportant for population and community dynamics, an assumption that is untenable given the available data. +
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Empirical findings in the Cognitive Sciences on the relationship between feeling states and subjective time have led to the assumption that time perception entails emotional and interoceptive states. The perception of time would thereafter be embodied; the bodily self, the continuous input from the body is the functional anchor of phenomenal experience and the mental self. Subjective time emerges through the existence of the self across time as an enduring and embodied entity. This relation is prominently disclosed in studies on altered states of consciousness such as in meditative states, under the influence of hallucinogens as well as in many psychiatric and neurological conditions. An increased awareness of oneself coincides with an increased awareness of time. Conversely, a decreased awareness of the self is associated with diminished awareness of time. The body of empirical work within different conceptual frameworks on the intricate relationship between self and time is presented and discussed. +
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Stressor interaction networks suggest antibiotic resistance co-opted from stress responses to temperature +
Environmental factors like temperature, pressure, and pH partly shaped the evolution of life. As life progressed, new stressors (e.g., poisons and antibiotics) arose as part of an arms race among organisms. Here we ask if cells co-opted existing mechanisms to respond to new stressors, or whether new responses evolved de novo. We use a network-clustering approach based purely on phenotypic growth measurements and interactions among the effects of stressors on population growth. We apply this method to two types of stressors—temperature and antibiotics—to discover the extent to which their cellular responses overlap in Escherichia coli. Our clustering reveals that responses to low and high temperatures are clearly separated, and each is grouped with responses to antibiotics that have similar effects to cold or heat, respectively. As further support, we use a library of transcriptional fluorescent reporters to confirm heat-shock and cold-shock genes are induced by antibiotics. We also show strains evolved at high temperatures are more sensitive to antibiotics that mimic the effects of cold. Taken together, our results strongly suggest that temperature stress responses have been co-opted to deal with antibiotic stress. +
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Temperature dependence of trophic interactions are driven by asymmetry of species responses and foraging strategy +
Environmental temperature has systematic effects on rates of species interactions, primarily through its influence on organismal physiology. We present a mechanistic model for the thermal response of consumer-resource interactions. We focus on how temperature affects species interactions via key traits - body velocity, detection distance, search rate and handling time - that underlie per capita consumption rate. The model is general because it applies to all foraging strategies: active-capture (both consumer and resource body velocity are important), sit-and-wait (resource velocity dominates) and grazing (consumer velocity dominates). The model predicts that temperature influences consumer-resource interactions primarily through its effects on body velocity (either of the consumer, resource or both), which determines how often consumers and resources encounter each other, and that asymmetries in the thermal responses of interacting species can introduce qualitative, not just quantitative, changes in consumer-resource dynamics. We illustrate this by showing how asymmetries in thermal responses determine equilibrium population densities in interacting consumer-resource pairs. We test for the existence of asymmetries in consumer-resource thermal responses by analysing an extensive database on thermal response curves of ecological traits for 309 species spanning 15 orders of magnitude in body size from terrestrial, marine and freshwater habitats. We find that asymmetries in consumer-resource thermal responses are likely to be a common occurrence. Overall, our study reveals the importance of asymmetric thermal responses in consumer-resource dynamics. In particular, we identify three general types of asymmetries: (i) different levels of performance of the response, (ii) different rates of response (e.g. activation energies) and (iii) different peak or optimal temperatures. Such asymmetries should occur more frequently as the climate changes and species' geographical distributions and phenologies are altered, such that previously noninteracting species come into contact. 6. By using characteristics of trophic interactions that are often well known, such as body size, foraging strategy, thermy and environmental temperature, our framework should allow more accurate predictions about the thermal dependence of consumer-resource interactions. Ultimately, integration of our theory into models of food web and ecosystem dynamics should be useful in understanding how natural systems will respond to current and future temperature change.
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Evolution drives, and is driven by, demography. A genotype moulds its phenotype’s age patterns of mortality and fertility in an environment; these two patterns in turn determine the genotype’s fitness in that environment. Hence, to understand the evolution of ageing, age patterns of mortality and reproduction need to be compared for species across the tree of life. However, few studies have done so and only for a limited range of taxa. Here we contrast standardized patterns over age for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants and a green alga. Although it has been predicted that evolution should inevitably lead to increasing mortality and declining fertility with age after maturity, there is great variation among these species, including increasing, constant, decreasing, humped and bowed trajectories for both long- and short-lived species. This diversity challenges theoreticians to develop broader perspectives on the evolution of ageing and empiricists to study the demography of more species. +
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Explaining the strong variation in lifespan among organisms remains a major challenge in evolutionary biology. Whereas previous work has concentrated mainly on differences in selection regimes and selection pressures, we hypothesize that differences in genetic drift may explain some of this variation. We develop a model to formalize this idea and show that the strong positive relationship between lifespan and genetic diversity predicted by this model indeed exists among populations of Daphnia magna, and that ageing is accelerated in small populations. Additional results suggest that this is due to increased drift in small populations rather than adaptation to environments favoring faster life histories. First, the correlation between genetic diversity and lifespan remains significant after statistical correction for potential environmental covariates. Second, no trade-offs are observed; rather, all investigated traits show clear signs of increased genetic load in the small populations. Third, hybrid vigor with respect to lifespan is observed in crosses between small but not between large populations. Together, these results suggest that the evolution of lifespan and ageing can be strongly affected by genetic drift, especially in small populations, and that variation in lifespan and ageing may often be nonadaptive, due to a strong contribution from mutation accumulation. +
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Fisher's geometrical model and the mutational patterns of antibiotic resistance across dose gradients +
Fisher's geometrical model (FGM) has been widely used to depict the fitness effects of mutations. It is a general model with few underlying assumptions that gives a large and comprehensive view of adaptive processes. It is thus attractive in several situations, for example adaptation to antibiotics, but comes with limitations, so that more mechanistic approaches are often preferred to interpret experimental data. It might be possible however to extend FGM assumptions to better account for mutational data. This is theoretically challenging in the context of antibiotic resistance because resistance mutations are assumed to be rare. In this article, we show with Escherichia coli how the fitness effects of resistance mutations screened at different doses of nalidixic acid vary across a dose-gradient. We found experimental patterns qualitatively consistent with the basic FGM (rate of resistance across doses, gamma distributed costs) but also unexpected patterns such as a decreasing mean cost of resistance with increasing screen dose. We show how different extensions involving mutational modules and variations in trait covariance across environments, can be discriminated based on these data. Overall, simple extensions of the FGM accounted well for complex mutational effects of resistance mutations across antibiotic doses. +
C
Food webs have markedly non-random network structure. Ecologists maintain that this non-random structure is key for stability, since large random ecological networks would invariably be unstable and thus should not be observed empirically. Here we show that a simple yet overlooked feature of natural food webs, the correlation between the effects of consumers on resources and those of resources on consumers, substantially accounts for their stability. Remarkably, random food webs built by preserving just the distribution and correlation of interaction strengths have stability properties similar to those of the corresponding empirical systems. Surprisingly, we find that the effect of topological network structure on stability, which has been the focus of countless studies, is small compared to that of correlation. Hence, any study of the effects of network structure on stability must first take into account the distribution and correlation of interaction strengths. +
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In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming Cellular reprogramming by transient expression of Yamanaka factors ameliorates age-associated symptoms, prolongs lifespan in progeroid mice, and improves tissue homeostasis in older +
Graphical Abstract Highlights d Partial reprogramming erases cellular markers of aging in mouse and human cells d Induction of OSKM in progeria mice ameliorates signs of aging and extends lifespan d In vivo reprogramming improves regeneration in 12-month-old wild-type mice +
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Healthy aging has been associated with decreased specialization in brain function. This characterization has focused largely on describing age-accompanied differences in specialization at the level of neurons and brain areas. We expand this work to describe systems-level differences in specialization in a healthy adult lifespan sample (n = 210; 20-89 y). A graph-theoretic framework is used to guide analysis of functional MRI resting-state data and describe systems-level differences in connectivity of individual brain networks. Young adults' brain systems exhibit a balance of within- and between-system correlations that is characteristic of segregated and specialized organization. Increasing age is accompanied by decreasing segregation of brain systems. Compared with systems involved in the processing of sensory input and motor output, systems mediating "associative" operations exhibit a distinct pattern of reductions in segregation across the adult lifespan. Of particular importance, the magnitude of association system segregation is predictive of long-term memory function, independent of an individual's age. +
I
Inheritance of immune responsiveness, life span, and disease incidence in interline crosses of mice selected for high or low multispecific antibody production. +
High (H) and low (L) antibody responder lines of mice separated by selective breeding present a maximal interline difference in antibody (Ab) response to Ag of different specificities (general genetic regulation). The analysis of SRBC agglutinin response in H line, L line, F1 hybrids, F2, and backcross segregants demonstrates that Ab responsiveness is a polygenic trait regulated by the additive interaction of 5 to 7 independent loci, with an incomplete dominance (44% +/- 7%) of the high response character, and a 30% +/- 10% impact of the environmental factors. The life span of H, L, F1, F2, and backcross populations is correlated positively with 2-ME-resistant agglutinin response (r = 0.97, p less than 0.001) and negatively with 2-ME-sensitive agglutinin response (r = 0.95, p = 0.01) (interpopulation correlation). Similar correlations are also observed in individuals of the various populations, especially in F1 x L backcross, in which the largest phenotypic variance is found. The positive correlation between Ab responsiveness and life span was confirmed by ELISA titration for distinct IgG isotypes (intrapopulation correlation). Malignant lymphomas and chronic nephritis were the two most common diseases observed. The age-adjusted incidence of such diseases, which is largely affected by environmental factors, accounts for the longer life span of H, as compared with L, mouse populations. The longevity of the 30% or less survivors, chiefly determined by the rate of physiologic aging, is a polygenic character regulated by the cumulative interaction of 3 to 7 independent loci, with a complete dominance of the long life trait and an impact of the environmental factors of about 60%. Thus we have grounds for regarding general Ab responsiveness and life span as polygenic traits regulated by a small number of identical or closely linked gene loci, and immune responsiveness as a defense mechanism against neoplastic and inflammatory diseases. +
S
How do children and adults differ in their search for rewards? We consider three different hypotheses that attribute developmental differences to either children’s increased random sampling, more directed exploration towards uncertain options, or narrower generalization. Using a search task in which noisy rewards are spatially correlated on a grid, we compare 55 younger children (age 7-8), 55 older children (age 9-11), and 50 adults (age 19-55) in their ability to successfully generalize about unobserved outcomes and balance the exploration-exploitation dilemma. Our results show that children explore more eagerly than adults, but obtain lower rewards. Building a predictive model of search to disentangle the unique contributions of the three hypotheses of developmental differences, we find robust and recoverable parameter estimates indicating that children generalize less and rely on directed exploration more than adults. We do not, however, find reliable differences in terms of random sampling. +
How producers of public goods persist inmicrobial communities is amajor question in 8 evolutionary biology. Cooperation is evolutionarily unstable, since cheating strains can reproduce 9 quicker and take over. Spatial structure has been shown to be a robustmechanism for the 0 1 evolution of cooperation. Here we study how spatial assortmentmight emerge from native 1 1 dynamics and show that fluid flow shear promotes cooperative behavior. Social structures arise 2 1 naturally from our advection-diffusion-reactionmodel as self-reproducing Turing patterns. We 13 computationally study the effects of fluid advection on these patterns as amechanism to enable or 4 1 enhance social behavior. Our central finding is that flow shear enables and promotes social 5 1 behavior inmicrobes by increasing the group fragmentation rate and thereby limiting the spread of 6 1 cheating strains. Regions of the flow domain with higher shear admit high cooperativity and large 7 1 population density, whereas low shear regions are devoid of life due to opportunisticmutations. +
N
Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as "cortical hubs" of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six "target" hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two "control" hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury. +
T
In 1943, a Greek war veteran named Stamatis Moraitis came to the United States for treatment of a combat-mangled arm. He’d survived a gunshot wound, escaped to Turkey and eventually talked his way onto the Queen Elizabeth, then serving as a troopship, to cross the Atlantic. Moraitis settled in Port Jefferson, N.Y., an enclave of countrymen from his native island, Ikaria. He quickly landed a job doing manual labor. Later, he moved to Boynton Beach, Fla. Along the way, Moraitis married a Greek-American woman, had three children and bought a three-bedroom house and a 1951 Chevrolet.\r\n\r\nOne day in 1976, Moraitis felt short of breath. Climbing stairs was a chore; he had to quit working midday. After X-rays, his doctor concluded that Moraitis had lung cancer. As he recalls, nine other doctors confirmed the diagnosis. They gave him nine months to live. He was in his mid-60s.\r\n\r\nMoraitis considered staying in America and seeking aggressive cancer treatment at a local hospital. That way, he could also be close to his adult children. But he decided instead to return to Ikaria, where he could be buried with his ancestors in a cemetery shaded by oak trees that overlooked the Aegean Sea. He figured a funeral in the United States would cost thousands, a traditional Ikarian one only $200, leaving more of his retirement savings for his wife, Elpiniki. Moraitis and Elpiniki moved in with his elderly parents, into a tiny, whitewashed house on two acres of stepped vineyards near Evdilos, on the north side of Ikaria. At first, he spent his days in bed, as his mother and wife tended to him. He reconnected with his faith. On Sunday mornings, he hobbled up the hill to a tiny Greek Orthodox chapel where his grandfather once served as a priest. When his childhood friends discovered that he had moved back, they started showing up every afternoon. They’d talk for hours, an activity that invariably involved a bottle or two of locally produced wine. I might as well die happy, he thought.\r\n\r\nIn the ensuing months, something strange happened. He says he started to feel stronger. One day, feeling ambitious, he planted some vegetables in the garden. He didn’t expect to live to harvest them, but he enjoyed being in the sunshine, breathing the ocean air. Elpiniki could enjoy the fresh vegetables after he was gone.\r\n\r\nSix months came and went. Moraitis didn’t die. Instead, he reaped his garden and, feeling emboldened, cleaned up the family vineyard as well. Easing himself into the island routine, he woke up when he felt like it, worked in the vineyards until midafternoon, made himself lunch and then took a long nap. In the evenings, he often walked to the local tavern, where he played dominoes past midnight. The years passed. His health continued to improve. He added a couple of rooms to his parents’ home so his children could visit. He built up the vineyard until it produced 400 gallons of wine a year. Today, three and a half decades later, he’s 97 years old — according to an official document he disputes; he says he’s 102 — and cancer-free. He never went through chemotherapy, took drugs or sought therapy of any sort. All he did was move home to Ikaria.
S
In order to maintain brain function, neural activity needs to be tightly coordinated within the brain network. How this coordination is achieved and related to behavior is largely unknown. It has been previously argued that the study of the link between brain and behavior is impossible without a guiding vision. Here we propose behavioral-level concepts and mechanisms embodied as structured flows on manifold (SFM) that provide a formal description of behavior as a low-dimensional process emerging from a network's dynamics dependent on the symmetry and invariance properties of the network connectivity. Specifically, we demonstrate that the symmetry breaking of network connectivity constitutes a timescale hierarchy resulting in the emergence of an attractive functional subspace. We show that behavior emerges when appropriate conditions imposed upon the couplings are satisfied, justifying the conductance-based nature of synaptic couplings. Our concepts propose design principles for networks predicting how behavior and task rules are represented in real neural circuits and open new avenues for the analyses of neural data. +
M
In the ocean, organic particles harbour diverse bacterial communities, which collectively digest and recycle essential nutrients. Traits like motility and exo-enzyme production allow individual taxa to colonize and exploit particle resources, but it remains unclear how community dynamics emerge from these individual traits. Here we track the taxon and trait dynamics of bacteria attached to model marine particles and demonstrate that particle-attached communities undergo rapid, reproducible successions driven by ecological interactions. Motile, particle-degrading taxa are selected for during early successional stages. However, this selective pressure is later relaxed when secondary consumers invade, which are unable to use the particle resource but, instead, rely on carbon from primary degraders. This creates a trophic chain that shifts community metabolism away from the particle substrate. These results suggest that primary successions may shape particle-attached bacterial communities in the ocean and that rapid community-wide metabolic shifts could limit rates of marine particle degradation. +
B
Brain disorders? Not really: Why network structures block reductionism in psychopathology research +
In the past decades, reductionism has dominated both research directions and funding policies in clinical psychology and psychiatry. The intense search for the biological basis of mental disorders, however, has not resulted in conclusive reductionist explanations of psychopathology. Recently, network models have been proposed as an alternative framework for the analysis of mental disorders, in which mental disorders arise from the causal interplay between symptoms. In this target article, we show that this conceptualization can help explain why reductionist approaches in psychiatry and clinical psychology are on the wrong track. First, symptom networks preclude the identification of a common cause of symptomatology with a neurobiological condition; in symptom networks, there is no such common cause. Second, symptom network relations depend on the content of mental states and, as such, feature intentionality. Third, the strength of network relations is highly likely to depend partially on cultural and historical contexts as well as external mechanisms in the environment. Taken together, these properties suggest that, if mental disorders are indeed networks of causally related symptoms, reductionist accounts cannot achieve the level of success associated with reductionist disease models in modern medicine. As an alternative strategy, we propose to interpret network structures in terms of D. C. Dennett's (1987) notion of real patterns , and suggest that, instead of being reducible to a biological basis, mental disorders feature biological and psychological factors that are deeply intertwined in feedback loops. This suggests that neither psychological nor biological levels can claim causal or explanatory priority, and that a holistic research strategy is necessary for progress in the study of mental disorders. +
A
A Major Role of the Macrophage in Quantitative Genetic Regulation of Immunoresponsiveness and Antiinfectious Immunity +
It is clear today that the immune system is constituted by a coordinated network of perfectly integrated and interacting cells and molecules subject to strict cooperation to ensure the highest possible efficiency in antiinfectious immunity. A simplified scheme of the immune system in higher vertebrates is represented in this chapter. The enzyme equipment of macrophage phagosomes endows these cells with bactericidal or bacteriostatic activity on ingested microorganisms, therefore, constituting the first important mechanism in antiinfectious defense. The metabolic activity of macrophages on engulfed antigens also regulates the specific response of T and B lymphocytes through a complex process of antigen handling and antigen presentation, establishing a sort of symbiotic relationship between lymphocytes and macrophages. There are two essential components in the immune response: one is specific and the other nonspecific. The specific response involves the stereospecific selective recognition. The nonspecific aspect of the immune response includes the handling of the phagocytized antigen and the rate at which the process of multiplication and differentiation of small lymphocytes takes place. The protective effect of specific vaccination is essentially based on immunological memory. The antibody molecules, according to their isotypes, play specialized defensive roles against various types of invading microorganisms, particularly in collaboration with the complement system, inducing bactericidal or opsonizing effects. © 1984, Academic Press, Inc. All rights reserved. +
Laboratory experiments show us that the deleterious character of accumulated novel age-specific mutations is reduced and made less variable with increased age. While theories of aging predict that the frequency of deleterious mutations at mutation-selection equilibrium will increase with the mutation's age of effect, they do not account for these age-related changes in the distribution of de novo mutational effects. Furthermore, no model predicts why this dependence of mutational effects upon age exists. Because the nature of mutational distributions plays a critical role in shaping patterns of senescence, we need to develop aging theory that explains and incorporates these effects. Here we propose a model that explains the age dependency of mutational effects by extending Fisher's geometrical model of adaptation to include a temporal dimension. Using a combination of simple analytical arguments and simulations, we show that our model predicts age-specific mutational distributions that are consistent with observations from mutation-accumulation experiments. Simulations show us that these age-specific mutational effects may generate patterns of senescence at mutation-selection equilibrium that are consistent with observed demographic patterns that are otherwise difficult to explain. +
Machine Learning (ML) is one of the most exciting and dynamic areas of modern research
and application. The purpose of this review is to provide an introduction to the core
concepts and tools of machine learning in a manner easily understood and intuitive
to physicists. The review begins by covering fundamental concepts in ML and modern
statistics such as the bias-variance tradeoff, overfitting, regularization, and generalization
before moving on to more advanced topics in both supervised and unsupervised learning.
Topics covered in the review include ensemble models, deep learning and neural networks,
clustering and data visualization, energy-based models (including MaxEnt models and
Restricted Boltzmann Machines), and variational methods. Throughout, we emphasize
the many natural connections between ML and statistical physics. A notable aspect of
the review is the use of Jupyter notebooks to introduce modern ML/statistical packages
to readers using physics-inspired datasets (the Ising Model and Monte-Carlo simulations
of supersymmetric decays of proton-proton collisions). We conclude with an extended
outlook discussing possible uses of machine learning for furthering our understanding
of the physical world as well as open problems in ML where physicists maybe able to
contribute. +
F
Many bacterial species are composed of multiple lineages distinguished by extensive variation in gene content. These often co-circulate in the same habitat, but the evolutionary and ecological processes that shape these complex populations are poorly understood. Addressing these questions is particularly important for Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen, as the changes in population structure associated with the recent introduction of partial-coverage vaccines have significantly reduced pneumococcal disease. Here we show pneumococcal lineages from multiple populations each have a distinct combination of intermediate frequency genes. Functional analysis suggested these loci were likely subject to negative frequency-dependent selection (NFDS) through interactions with other bacteria, hosts, or mobile elements. Correspondingly, these genes had similar frequencies in four populations with dissimilar lineage compositions. These frequencies were maintained following substantial alterations in lineage prevalences once vaccination programmes began. Fitting a multilocus NFDS model of post-vaccine population dynamics to three genomic datasets using Approximate Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: +
E
Microbes assemble into complex, dynamic, and species-rich communities that play critical roles in human health and in the environment. The complexity of natural environments and the large number of niches present in most habitats are often invoked to explain the maintenance of microbial diversity in the presence of competitive exclusion. Here we show that soil and plant-associated microbiota, cultivated ex situ in minimal synthetic environments with a single supplied source of carbon, universally re-assemble into large and dynamically stable communities with strikingly predictable coarse-grained taxonomic and functional compositions. We find that generic, non-specific metabolic cross-feeding leads to the assembly of dense facilitation networks that enable the coexistence of multiple competitors for the supplied carbon source. The inclusion of universal and non-specific cross-feeding in ecological consumer-resource models is sufficient to explain our observations, and predicts a simple determinism in community structure, a property reflected in our experiments. +
