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Two decades ago, sphingosine 1-phosphate (S1P) was discovered as a novel bioactive molecule that regulates a variety of cellular functions. The plethora of S1P-mediated effects is due to the fact that the sphingolipid not only modulates intracellular functions but also acts as a ligand of G protein-coupled receptors after secretion into the extracellular environment. In the plasma, S1P is found in high concentrations, modulating immune cell trafficking and vascular endothelial integrity. The liver is engaged in modulating the plasma S1P content, as it produces apolipoprotein M, which is a chaperone for the S1P transport. Moreover, the liver plays a substantial role in glucose and lipid homeostasis. A dysfunction of glucose and lipid metabolism is connected with the development of liver diseases such as hepatic insulin resistance, non-alcoholic fatty liver disease, or liver fibrosis. Recent studies indicate that S1P is involved in liver pathophysiology and contributes to the development of liver diseases. In this review, the current state of knowledge about S1P and its signaling in the liver is summarized with a specific focus on the dysregulation of S1P signaling in obesity-mediated liver diseases. Thus, the modulation of S1P signaling can be considered as a potential therapeutic target for the treatment of hepatic diseases.
Moving Beyond ERP Components
(2018)
Relationships between neuroimaging measures and behavior provide important clues about brain function and cognition in healthy and clinical populations. While electroencephalography (EEG) provides a portable, low cost measure of brain dynamics, it has been somewhat underrepresented in the emerging field of model-based inference. We seek to address this gap in this article by highlighting the utility of linking EEG and behavior, with an emphasis on approaches for EEG analysis that move beyond focusing on peaks or "components" derived from averaging EEG responses across trials and subjects (generating the event-related potential, ERP). First, we review methods for deriving features from EEG in order to enhance the signal within single-trials. These methods include filtering based on user-defined features (i.e., frequency decomposition, time-frequency decomposition), filtering based on data-driven properties (i.e., blind source separation, BSS), and generating more abstract representations of data (e.g., using deep learning). We then review cognitive models which extract latent variables from experimental tasks, including the drift diffusion model (DDM) and reinforcement learning (RL) approaches. Next, we discuss ways to access associations among these measures, including statistical models, data-driven joint models and cognitive joint modeling using hierarchical Bayesian models (HBMs). We think that these methodological tools are likely to contribute to theoretical advancements, and will help inform our understandings of brain dynamics that contribute to moment-to-moment cognitive function.
The article is a review of Patrick Gray's latest monograph: Shakespeare and the Fall of the Roman Republic: Selfhood, Stoicism and Civil War. Gray analyzes Shakespare's and his characters' representation of the 'self' in Julius Caesar and Antony and Cleopatra, with Coriolanus used for comparative purposes. The book induced a lively discussion of its content in academic community.
Introduction:
We aim to highlight the utility of this model in the analysis of the psycho-behavioral implications of family cancer, presenting the scientific literature that used Leventhal’s model as the theoretical framework of approach.
Material and methods:
A systematic search was performed in six databases (EBSCO, ScienceDirect, PubMed Central, ProQuest, Scopus, and Web of Science) with empirical studies published between 2006 and 2015 in English with regard to the Common Sense Model of Self-Regulation (CSMR) and familial/hereditary cancer. The key words used were: illness representations, common sense model, self regulatory model, familial/hereditary/genetic cancer, genetic cancer counseling. The selection of studies followed the PRISMA-P guidelines (Moher et al., 2009; Shamseer et al., 2015), which suggest a three-stage procedure.
Results:
Individuals create their own cognitive and emotional representation of the disease when their health is threatened, being influenced by the presence of a family history of cancer, causing them to adopt or not a salutogenetic behavior. Disease representations, particularly the cognitive ones, can be predictors of responses to health threats that determine different health behaviors. Age, family history of cancer, and worrying about the disease are factors associated with undergoing screening. No consensus has been reached as to which factors act as predictors of compliance with cancer screening programs.
Conclusions:
This model can generate interventions that are conceptually clear as well as useful in regulating the individuals’ behaviors by reducing the risk of developing the disease and by managing as favorably as possible health and/or disease.
As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue-and cell-specific actions of p53 and its downstream signaling pathways. In this review, we focus on studies reporting p53's impact on adipocyte development, function, and maintenance, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue (AT) with respect to systemic energy homeostasis. While whole body p53 knockout mice gain less weight and fat mass under a high-fat diet owing to increased energy expenditure, modifying p53 expression specifically in adipocytes yields more refined insights: (1) p53 is a negative regulator of in vitro adipogenesis; (2) p53 levels in white AT are increased in diet-induced and genetic obesity mouse models and in obese humans; (3) functionally, elevated p53 in white AT increases senescence and chronic inflammation, aggravating systemic insulin resistance; (4) p53 is not required for normal development of brown AT; and (5) when p53 is activated in brown AT in mice fed a high-fat diet, it increases brown AT temperature and brown AT marker gene expression, thereby contributing to reduced fat mass accumulation. In addition, p53 is increasingly being recognized as crucial player in nutrient sensing pathways. Hence, despite existence of contradictory findings and a varying density of evidence, several functions of p53 in adipocytes and ATs have been emerging, positioning p53 as an essential regulatory hub in ATs. Future studies need to make use of more sophisticated in vivo model systems and should identify an AT-specific set of p53 target genes and downstream pathways upon different (nutrient) challenges to identify novel therapeutic targets to curb metabolic diseases
Evaluating climate geoengineering proposals in the context of the Paris Agreement temperature goals
(2018)
Current mitigation efforts and existing future commitments are inadequate to accomplish the Paris Agreement temperature goals. In light of this, research and debate are intensifying on the possibilities of additionally employing proposed climate geoengineering technologies, either through atmospheric carbon dioxide removal or farther-reaching interventions altering the Earth’s radiative energy budget. Although research indicates that several techniques may eventually have the physical potential to contribute to limiting climate change, all are in early stages of development, involve substantial uncertainties and risks, and raise ethical and governance dilemmas. Based on present knowledge, climate geoengineering techniques cannot be relied on to significantly contribute to meeting the Paris Agreement temperature goals.
Reviews and syntheses
(2018)
The cycling of carbon (C) between the Earth surface and the atmosphere is controlled by biological and abiotic processes that regulate C storage in biogeochemical compartments and release to the atmosphere. This partitioning is quantified using various forms of C-use efficiency (CUE) - the ratio of C remaining in a system to C entering that system. Biological CUE is the fraction of C taken up allocated to biosynthesis. In soils and sediments, C storage depends also on abiotic processes, so the term C-storage efficiency (CSE) can be used. Here we first review and reconcile CUE and CSE definitions proposed for autotrophic and heterotrophic organisms and communities, food webs, whole ecosystems and watersheds, and soils and sediments using a common mathematical framework. Second, we identify general CUE patterns; for example, the actual CUE increases with improving growth conditions, and apparent CUE decreases with increasing turnover. We then synthesize > 5000CUE estimates showing that CUE decreases with increasing biological and ecological organization - from uni-cellular to multicellular organisms and from individuals to ecosystems. We conclude that CUE is an emergent property of coupled biological-abiotic systems, and it should be regarded as a flexible and scale-dependent index of the capacity of a given system to effectively retain C.
Methodological and technological advances have recently paved the way for metabolic flux profiling in higher organisms, like plants. However, in comparison with omics technologies, flux profiling has yet to provide comprehensive differential flux maps at a genome-scale and in different cell types, tissues, and organs. Here we highlight the recent advances in technologies to gather metabolic labeling patterns and flux profiling approaches. We provide an opinion of how recent local flux profiling approaches can be used in conjunction with the constraint-based modeling framework to arrive at genome-scale flux maps. In addition, we point at approaches which use metabolomics data without introduction of label to predict either non-steady state fluxes in a time-series experiment or flux changes in different experimental scenarios. The combination of these developments allows an experimentally feasible approach for flux-based large-scale systems biology studies.
The primary function of leaves is to provide an interface between plants and their environment for gas exchange, light exposure and thermoregulation. Leaves have, therefore a central contribution to plant fitness by allowing an efficient absorption of sunlight energy through photosynthesis to ensure an optimal growth. Their final geometry will result from a balance between the need to maximize energy uptake while minimizing the damage caused by environmental stresses. This intimate relationship between leaf and its surroundings has led to an enormous diversification in leaf forms. Leaf shape varies between species, populations, individuals or even within identical genotypes when those are subjected to different environmental conditions. For instance, the extent of leaf margin dissection has, for long, been found to inversely correlate with the mean annual temperature, such that Paleobotanists have used models based on leaf shape to predict the paleoclimate from fossil flora. Leaf growth is not only dependent on temperature but is also regulated by many other environmental factors such as light quality and intensity or ambient humidity. This raises the question of how the different signals can be integrated at the molecular level and converted into clear developmental decisions. Several recent studies have started to shed the light on the molecular mechanisms that connect the environmental sensing with organ-growth and patterning. In this review, we discuss the current knowledge on the influence of different environmental signals on leaf size and shape, their integration as well as their importance for plant adaptation.
The relevance for in vitro three-dimensional (3D) tissue culture of skin has been present for almost a century. From using skin biopsies in organ culture, to vascularized organotypic full-thickness reconstructed human skin equivalents, in vitro tissue regeneration of 3D skin has reached a golden era. However, the reconstruction of 3D skin still has room to grow and develop. The need for reproducible methodology, physiological structures and tissue architecture, and perfusable vasculature are only recently becoming a reality, though the addition of more complex structures such as glands and tactile corpuscles require advanced technologies. In this review, we will discuss the current methodology for biofabrication of 3D skin models and highlight the advantages and disadvantages of the existing systems as well as emphasize how new techniques can aid in the production of a truly physiologically relevant skin construct for preclinical innovation.
This work reviews the literature on an alleged global warming 'pause' in global mean surface temperature (GMST) to determine how it has been defined, what time intervals are used to characterise it, what data are used to measure it, and what methods used to assess it. We test for 'pauses', both in the normally understood meaning of the term to mean no warming trend, as well as for a 'pause' defined as a substantially slower trend in GMST. The tests are carried out with the historical versions of GMST that existed for each pause-interval tested, and with current versions of each of the GMST datasets. The tests are conducted following the common (but questionable) practice of breaking the linear fit at the start of the trend interval ('broken' trends), and also with trends that are continuous with the data bordering the trend interval. We also compare results when appropriate allowance is made for the selection bias problem. The results show that there is little or no statistical evidence for a lack of trend or slower trend in GMST using either the historical data or the current data. The perception that there was a 'pause' in GMST was bolstered by earlier biases in the data in combination with incomplete statistical testing.
Narcissists are assumed to lack the motivation and ability to share and understand the mental states of others. Prior empirical research, however, has yielded inconclusive findings and has differed with respect to the specific aspects of narcissism and socioemotional cognition that have been examined. Here, we propose a differentiated facet approach that can be applied across research traditions and that distinguishes between facets of narcissism (agentic vs. antagonistic) on the one hand, and facets of socioemotional cognition ability (SECA; self-perceived vs. actual) on the other. Using five nonclinical samples in two studies (total N = 602), we investigated the effect of facets of grandiose narcissism on aspects of socioemotional cognition across measures of affective and cognitive empathy, Theory of Mind, and emotional intelligence, while also controlling for general reasoning ability. Across both studies, agentic facets of narcissism were found to be positively related to perceived SECA, whereas antagonistic facets of narcissism were found to be negatively related to perceived SECA. However, both narcissism facets were negatively related to actual SECA. Exploratory condition-based regression analyses further showed that agentic narcissists had a higher directed discrepancy between perceived and actual SECA: They self-enhanced their socio-emotional capacities. Implications of these results for the multifaceted theoretical understanding of the narcissism-SECA link are discussed.
The protein fractions of cocoa have been implicated influencing both the bioactive potential and sensory properties of cocoa and cocoa products. The objective of the present review is to show the impact of different stages of cultivation and processing with regard to the changes induced in the protein fractions. Special focus has been laid on the major seed storage proteins throughout the different stages of processing. The study starts with classical introduction of the extraction and the characterization methods used, while addressing classification approaches of cocoa proteins evolved during the timeline. The changes in protein composition during ripening and maturation of cocoa seeds, together with the possible modifications during the post-harvest processing (fermentation, drying, and roasting), have been documented. Finally, the bioactive potential arising directly or indirectly from cocoa proteins has been elucidated. The state of the art suggests that exploration of other potentially bioactive components in cocoa needs to be undertaken, while considering the complexity of reaction products occurring during the roasting phase of the post-harvest processing. Finally, the utilization of partially processed cocoa beans (e.g., fermented, conciliatory thermal treatment) can be recommended, providing a large reservoir of bioactive potentials arising from the protein components that could be instrumented in functionalizing foods.
Accumulating behavioral and neurophysiological evidence supports the idea of language being grounded in sensorimotor processes, with indications of a functional role of motor, sensory and emotional systems in processing both concrete and abstract linguistic concepts. However, most of the available studies focused on native language speakers (L1), with only a limited number of investigations testing embodied language processing in the case of a second language (L2). In this paper we review the available evidence on embodied effects in L2 and discuss their possible integration into existing models of linguistic processing in L1 and L2. Finally, we discuss possible avenues for future research towards an integrated model of L1 and L2 sensorimotor and emotional grounding.
Sortases are enzymes occurring in the cell wall of Gram-positive bacteria. Sortase A (SrtA), the best studied sortase class, plays a key role in anchoring surface proteins with the recognition sequence LPXTG covalently to oligoglycine units of the bacterial cell wall. This unique transpeptidase activity renders SrtA attractive for various purposes and motivated researchers to study multiple in vivo and in vitro ligations in the last decades. This ligation technique is known as sortase-mediated ligation (SML) or sortagging and developed to a frequently used method in basic research. The advantages are manifold: extremely high substrate specificity, simple access to substrates and enzyme, robust nature and easy handling of sortase A. In addition to the ligation of two proteins or peptides, early studies already included at least one artificial (peptide equipped) substrate into sortagging reactions - which demonstrates the versatility and broad applicability of SML. Thus, SML is not only a biology-related technique, but has found prominence as a major interdisciplinary research tool. In this review, we provide an overview about the use of sortase A in interdisciplinary research, mainly for protein modification, synthesis of protein-polymer conjugates and immobilization of proteins on surfaces.
Arboreal epiphytes (plants residing in forest canopies) are present across all major climate zones and play important roles in forest biogeochemistry. The substantial water storage capacity per unit area of the epiphyte "bucket" is a key attribute underlying their capability to influence forest hydrological processes and their related mass and energy flows. It is commonly assumed that the epiphyte bucket remains saturated, or near-saturated, most of the time; thus, epiphytes (particularly vascular epiphytes) can store little precipitation, limiting their impact on the forest canopy water budget. We present evidence that contradicts this common assumption from (i) an examination of past research; (ii) new datasets on vascular epiphyte and epi-soil water relations at a tropical montane cloud forest (Monteverde, Costa Rica); and (iii) a global evaluation of non-vascular epiphyte saturation state using a process-based vegetation model, LiBry. All analyses found that the external and internal water storage capacity of epiphyte communities is highly dynamic and frequently available to intercept precipitation. Globally, non-vascular epiphytes spend <20% of their time near saturation and regionally, including the humid tropics, model results found that non-vascular epiphytes spend similar to 1/3 of their time in the dry state (0-10% of water storage capacity). Even data from Costa Rican cloud forest sites found the epiphyte community was saturated only 1/3 of the time and that internal leaf water storage was temporally dynamic enough to aid in precipitation interception. Analysis of the epi-soils associated with epiphytes further revealed the extent to which the epiphyte bucket emptied-as even the canopy soils were often <50% saturated (29-53% of all days observed). Results clearly show that the epiphyte bucket is more dynamic than currently assumed, meriting further research on epiphyte roles in precipitation interception, redistribution to the surface and chemical composition of "net" precipitation waters reaching the surface.
Malnutrition is widespread in older people and represents a major geriatric syndrome with multifactorial etiology and severe consequences for health outcomes and quality of life. The aim of the present paper is to describe current approaches and evidence regarding malnutrition treatment and to highlight relevant knowledge gaps that need to be addressed. Recently published guidelines of the European Society for Clinical Nutrition and Metabolism (ESPEN) provide a summary of the available evidence and highlight the wide range of different measures that can be taken—from the identification and elimination of potential causes to enteral and parenteral nutrition—depending on the patient’s abilities and needs. However, more than half of the recommendations therein are based on expert consensus because of a lack of evidence, and only three are concern patient-centred outcomes. Future research should further clarify the etiology of malnutrition and identify the most relevant causes in order to prevent malnutrition. Based on limited and partly conflicting evidence and the limitations of existing studies, it remains unclear which interventions are most effective in which patient groups, and if specific situations, diseases or etiologies of malnutrition require specific approaches. Patient-relevant outcomes such as functionality and quality of life need more attention, and research methodology should be harmonised to allow for the comparability of studies.