The ecogenetic link between demography and evolution: can we bridge the gap between theory and data?

Calls to understand the links between ecology and evolution have been common for decades. Population dynamics, i.e. the demographic changes in populations, arise from life history decisions of individuals and thus are a product of selection, and selection, on the contrary, can be modified by such dynamical properties of the population as density and stability. It follows that generating predictions and testing them correctly requires considering this ecogenetic feedback loop whenever traits have demographic consequences, mediated via density dependence (or frequency dependence). This is not an easy challenge, and arguably theory has advanced at a greater pace than empirical research. However, theory would benefit from more interaction between related fields, as is evident in the many near-synonymous names that the ecogenetic loop has attracted. We also list encouraging examples where empiricists have shown feasible ways of addressing the question, ranging from advanced data analysis to experiments and comparative analyses of phylogenetic data.     

Mitochondrial stress: a bridge between mitochondrial dysfunction and metabolic diseases?

Under pathophysiological conditions such as obesity, excessive oxidation of nutrients may induce mitochondrial stress, leading to mitochondrial unfolded protein response (UPR^mt) and initiation of a retrograde stress signaling pathway. Defects in the UPR^mt and the retrograde signaling pathways may disrupt the integrity and homeostasis of the mitochondria, resulting in endoplasmic reticulum stress and insulin resistance. Improving the capacity of mitochondria to reduce stress may be an effective approach to improve mitochondria function and to suppress obesity-induced metabolic disorders such as insulin resistance and type 2 diabetes.     

Fluctuating asymmetry as an indicator of fitness: can we bridge the gap between studies?

There is growing evidence from both experimental and non-experimental studies that fluctuating asymmetry does not consistently index stress or fitness. The widely held--yet poorly substantiated--belief that fluctuating asymmetry can act as a universal measure of developmental stability and predictor of stress-mediated changes in fitness, therefore staggers. Yet attempts to understand why the reported relationships between fluctuating asymmetry, stress and fitness are so heterogeneous--i.e. whether the associations are truly weak or non-existent or whether they become confounded during different stages of the analytical pathways remain surprisingly scarce. Hence, we attempt to disentangle these causes, by reviewing the various statistical and conceptual factors that are suspected to confound potential relationships between fluctuating asymmetry, stress and fitness. Two main categories of factors are discerned: those associated with the estimation of developmental stability through fluctuating asymmetry and those associated with the effects of genotype and environment on developmental stability. Next, we describe a series of statistical tools that have recently been developed to help reduce this noise. We argue that the current lack of a theoretical framework that predicts if and when relationships with developmental stability can be expected, urges for further theoretical and empirical research, such as on the genetic architecture of developmental stability in stressed populations. If the underlying developmental mechanisms are better understood, statistical patterns of asymmetry variation may become a biologically meaningful tool.     

Can biochemical traits bridge the gap between genomics and plant performance? A study in rice under drought

The possibility of introducing metabolic/biochemical phenotyping to complement genomics-based predictions in breeding pipelines has been considered for years. Here we examine to what extent and under what environmental conditions metabolic/biochemical traits can effectively contribute to understanding and predicting plant performance. In this study, multivariable statistical models based on flag leaf central metabolism and oxidative stress status were used to predict grain yield (GY) performance for 271 indica rice (Oryza sativa) accessions grown in the field under well-watered and reproductive stage drought conditions. The resulting models displayed significantly higher predictability than multivariable models based on genomic data for the prediction of GY under drought (Q² = 0.54–0.56 versus 0.35) and for stress-induced GY loss (Q² = 0.59–0.64 versus 0.03–0.06). Models based on the combined datasets showed predictabilities similar to metabolic/biochemical-based models alone. In contrast to genetic markers, models with enzyme activities and metabolite values also quantitatively integrated the effect of physiological differences such as plant height on GY. The models highlighted antioxidant enzymes of the ascorbate–glutathione cycle and a lipid oxidation stress marker as important predictors of rice GY stability under drought at the reproductive stage, and these stress-related variables were more predictive than leaf central metabolites. These findings provide evidence that metabolic/biochemical traits can integrate dynamic cellular and physiological responses to the environment and can help bridge the gap between the genome and the phenome of crops as predictors of GY performance under drought.

Biochemical traits outperform the explanatory power of genetic markers when used as variables in models for predicting yield performance in rice under drought stress.     

Nicotine: the link between cigarette smoking and the progression of renal injury?

Cigarette smoke (CS) is the most important source of preventable morbidity and mortality in the United States. Recent clinical studies have suggested that, in addition to being a major cardiovascular risk factor, CS promotes the progression of kidney disease. The mechanisms by which CS promotes the progression of chronic kidney disease have not been elucidated. Here we demonstrate for the first time that human mesangial cells (MCs) are endowed with the nicotinic ACh receptors (nAChRs) alpha4, alpha5, alpha7, beta2, beta3, and beta4. Studies performed in other cell types have shown that these nAChRs are ionotropic receptors that function as agonist-regulated Ca(2+) channels. Nicotine induced MC proliferation in a dose-dependent manner. At 10 (-7) M, a concentration found in the plasma of active smokers, nicotine induced MC proliferation [control, 1,328 +/- 50 vs. nicotine, 2,761 +/- 90 counts/minute (cpm); P < 0.05] and increased the synthesis of fibronectin (50%), a critical matrix component involved in the progression of chronic kidney disease. We and others have shown that, in response to PKC activation, MC synthesize reactive oxygen species (ROS) via NADPH oxidase. In the current studies we demonstrate that PKC inhibition as well as diphenyleneiodonium and apocynin, two inhibitors of NADPH oxidase, prevented the effects of nicotine on MC proliferation and fibronectin production, hence establishing ROS as second messengers of the actions of nicotine. Furthermore, nicotine increased the production of ROS as assessed by 2',7'-dichlorofluorescein diacetate fluorescence [control, 184.4 +/- 26 vs. nicotine, 281.5 +/- 26 arbitrary fluorescence units (AFU); n = 5 experiments, P < 0.05]. These studies unveil previously unrecognized mechanisms that indict nicotine, a component of CS, as an agent that may accelerate and promote the progression of kidney disease.     

Primary cilia and organogenesis: is Hedgehog the only sculptor?

The primary cilium is a small microtubule-based organelle projecting from the plasma membrane of practically all cells in the mammalian body. In the past 8 years, a flurry of papers has indicated a crucial role of this long-neglected organelle in the development of a wide variety of organs, including derivatives of all three germ layers. A common theme of these studies is the critical dependency of signal transduction of the Hedgehog pathway upon functionally intact cilia to regulate organogenesis. Another common theme is the role that the cilium plays, not necessarily in the determination of the embryonic anlagen of these organs, although this too occurs but rather in the proliferation and morphogenesis of the previously determined organ. We outline the various organ systems that are dependent upon primary cilia for their proper development and we discuss the cilia-dependent roles that Sonic and Indian Hedgehog play in these processes. In addition and most importantly for the field, we discuss the controversial involvement of another major developmental pathway, Wnt signaling, in cilia-dependent organogenesis.     

Early warning signals of regime shifts for aquatic systems: Can experiments help to bridge the gap between theory and real-world application?

Early-warning signals of a regime shift (EWS) indicate, for a wide range of systems, if a tipping-point is being approached. In ecology, EWS are well established from a theoretical perspective but are far from unequivocal when applied to field data. The gap between theory and application is caused by a set of limitations, like the lack of coherence between different EWS, data acquisition issues, and false results. Experiments assessing EWS may provide an empirical mechanistic understanding of why an EWS was observed (or failed to be observed), which often cannot be elucidated by simple computational modeling or pure environmental data. Here we focused on aquatic experiments to explore to what extent the existing EWS experiments can bridge the gap between the theory and real-world application. For that, we used the Thomson-ISI Web of Science© database to retrieve EWS experiments executed before early-2020, detailing their experimental designs and each EWS assessed. Success rates - correct anticipation of tipping points – were around 70% for the most used EWS (assessment of autocorrelation, variance, recovery, and shape of the distribution using abundance, Chlorophyll-a, Phycocyanin, and dissolved oxygen data). Yet, no EWS showed to be 100% reliable, and their use demands cautious interpretation. As a rule, we observed that experiments were not designed to tackle issues encountered in real-world situations. They lack a deep mechanistic understanding of why, when, and how an EWS was observed or not. When experiments did aim to assess issues encountered in the real world, the experimental designs were often of low ecological significance. We also investigated the relationship between sampling and the success rate of EWS, observing that the sampling regime might have to be tailor-made towards specific monitoring objectives. Moreover, experiments have taught us that the use of EWS can be more versatile than expected, going from monitoring the extinction of single populations to the anticipation of transient regime shifts. Most of the experiments presented here supported empirical proof of the existence of EWS in aquatic systems. Still, to bridge the gap between theory and application, experiments will have to move closer to real-world conditions and better support a mechanistic understanding of why EWS may succeed or fail to anticipate a regime shift. For that, we provide six elements to take into account when designing experiments that could enhance the capabilities of EWS to go beyond the stage of proof-of-concept.     

Pelmatozoan arms from the Middle Cambrian of Australia: bridging the gap between brachioles and brachials?

The early Middle Cambrian Monastery Creek Phosphorite (Beetle Creek Formation, Queensland, Australia) contains an assemblage of disarticulated echinoderm ossicles that are exquisitely preserved. Amongst this material we recognize pelmatozoan brachials, radials, basals and holomeric columnals. Although we cannot reconstruct the complete animal with precision, these elements represent the oldest known pelmatozoan with crinoid-like appendages. Key elements include isotomously to heterotomously branched uniserial appendage plates with a tripartite adoral food groove, a longitudinal central canal interpreted as housing entoneural nerve, and differentiated articulation facets. There are also epispire-bearing radials bearing one to four arm insertion-facets, each one pierced by a central neural canal. These canals run internal towards the oral area beneath the external food groove. Co-occuring material includes single truncated cone-shaped basals and holomeric columnals, both with a similar articulation pattern, and irregular, epispire-bearing thecal plates. This mosaic of crinozoan (uniserial isotomous to heterotomous arms with neural canal), blastozoan (epispire-bearing thecal plates, appendage leading to oral thecal food groove without direct connection with body cavity) and apomorphic characters (circumoral instead of basal entoneural plexus) is unexpected and demonstrates that crinoid-like pelmatozoans with uniserial, branched arms appeared significantly earlier than the Tremadocian, when the first articulated crinoid skeletons are found. It also raises questions about the polyphyletic appearance of feeding appendages among pelmatozoan echinoderms.     

Mitochondrial dysfunction: A potential link between neuroinflammation and neurodegeneration?

Dysfunctional mitochondria are thought to play a cardinal role in the pathogenesis of various neurological disorders, such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease and stroke. In addition, neuroinflammation is a common denominator of these diseases. Both mitochondrial dysfunction and neuroinflammatory processes lead to increased production of reactive oxygen species (ROS) which are detrimental to neurons. Therefore, neuroinflammation is increasingly recognized to contribute to processes underlying neurodegeneration. Here we describe the involvement of mitochondrial (dys)function in various neurological disorders and discuss the putative link between mitochondrial function and neuroinflammation.     

Multi-scale modeling in biology: how to bridge the gaps between scales?

Human physiological functions are regulated across many orders of magnitude in space and time. Integrating the information and dynamics from one scale to another is critical for the understanding of human physiology and the treatment of diseases. Multi-scale modeling, as a computational approach, has been widely adopted by researchers in computational and systems biology. A key unsolved issue is how to represent appropriately the dynamical behaviors of a high-dimensional model of a lower scale by a low-dimensional model of a higher scale, so that it can be used to investigate complex dynamical behaviors at even higher scales of integration. In the article, we first review the widely-used different modeling methodologies and their applications at different scales. We then discuss the gaps between different modeling methodologies and between scales, and discuss potential methods for bridging the gaps between scales.     

The gut microbiota-artery axis: A bridge between dietary lipids and atherosclerosis?

Atherosclerotic cardiovascular disease is one of the major leading global causes of death. Growing evidence has demonstrated that gut microbiota (GM) and its metabolites play a pivotal role in the onset and progression of atherosclerosis (AS), now known as GM-artery axis. There are interactions between dietary lipids and GM, which ultimately affect GM and its metabolites. Given these two aspects, the GM-artery axis may play a mediating role between dietary lipids and AS. Diets rich in saturated fatty acids (SFAs), omega-6 polyunsaturated fatty acids (n-6 PUFAs), industrial trans fatty acids (TFAs), and cholesterol can increase the levels of atherogenic microbes and metabolites, whereas monounsaturated fatty acids (MUFAs), ruminant TFAs, and phytosterols (PS) can increase the levels of antiatherogenic microbes and metabolites. Actually, dietary phosphatidylcholine (PC), sphingomyelin (SM), and omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been demonstrated to affect AS via the GM-artery axis. Therefore, that GM-artery axis acts as a communication bridge between dietary lipids and AS. Herein, we will describe the molecular mechanism of GM-artery axis in AS and discuss the complex interactions between dietary lipids and GM. In particular, we will highlight the evidence and potential mechanisms of dietary lipids affecting AS via GM-artery axis.