We developed new methods for parameter estimation-in-context and, with the help of 125 authors, built the AmP (Add-my-Pet) database of Dynamic Energy Budget (DEB) models, parameters and referenced ...underlying data for animals, where each species constitutes one database entry. The combination of DEB parameters covers all aspects of energetics throughout the full organism's life cycle, from the start of embryo development to death by aging. The species-specific parameter values capture biodiversity and can now, for the first time, be compared between animals species. An important insight brought by the AmP project is the classification of animal energetics according to a family of related DEB models that is structured on the basis of the mode of metabolic acceleration, which links up with the development of larval stages. We discuss the evolution of metabolism in this context, among animals in general, and ray-finned fish, mollusks and crustaceans in particular. New DEBtool code for estimating DEB parameters from data has been written. AmPtool code for analyzing patterns in parameter values has also been created. A new web-interface supports multiple ways to visualize data, parameters, and implied properties from the entire collection as well as on an entry by entry basis. The DEB models proved to fit data well, the median relative error is only 0.07, for the 1035 animal species at 2018/03/12, including some extinct ones, from all large phyla and all chordate orders, spanning a range of body masses of 16 orders of magnitude. This study is a first step to include evolutionary aspects into parameter estimation, allowing to infer properties of species for which very little is known.
Our understanding of the molecular properties of kainate receptors and their involvement in synaptic physiology has progressed significantly over the last 30 years. A plethora of studies indicate ...that kainate receptors are important mediators of the pre- and postsynaptic actions of glutamate, although the mechanisms underlying such effects are still often a topic for discussion. Three clear fields related to their behavior have emerged: there are a number of interacting proteins that pace the properties of kainate receptors; their activity is unconventional since they can also signal through G proteins, behaving like metabotropic receptors; they seem to be linked to some devastating brain diseases. Despite the significant progress in their importance in brain function, kainate receptors remain somewhat puzzling. Here we examine discoveries linking these receptors to physiology and their probable implications in disease, in particular mood disorders, and propose some ideas to obtain a deeper understanding of these intriguing proteins.
Kainate receptors are important mediators of the actions of glutamate, but the mechanisms underlying their effects are often a topic of debate. Here, Lerma and Marques examine discoveries linking these receptors to physiology and consider their probable implications for disease.
Glycolysis is a tightly regulated process in which several enzymes, such as Hexokinases (HKs), play crucial roles. Cancer cells are characterized by specific expression levels of several isoenzymes ...in different metabolic pathways and these features offer possibilities for therapeutic interventions. Overexpression of HKs (mostly of the HK2 isoform) have been consistently reported in numerous types of cancer. Moreover, deletion of HK2 has been shown to decrease cancer cell proliferation without explicit side effects in animal models, which suggests that targeting HK2 is a viable strategy for cancer therapy. HK2 inhibition causes a substantial decrease of glycolysis that affects multiple pathways of central metabolism and also destabilizes the mitochondrial outer membrane, ultimately enhancing cell death. Although glycolysis inhibition has met limited success, partly due to low selectivity for specific isoforms and excessive side effects of the reported HK inhibitors, there is ample ground for progress. The current review is focused on HK2 inhibition, envisaging the development of potent and selective anticancer agents. The information on function, expression, and activity of HKs is presented, along with their structures, known inhibitors, and reported effects of HK2 ablation/inhibition. The structural features of the different isozymes are discussed, aiming to stimulate a more rational approach to the design of selective HK2 inhibitors with appropriate drug-like properties. Particular attention is dedicated to a structural and sequence comparison of the structurally similar HK1 and HK2 isoforms, aiming to unveil differences that could be explored therapeutically. Finally, several additional catalytic- and non-catalytic roles on different pathways and diseases, recently attributed to HK2, are reviewed and their implications briefly discussed.
This book is about the social psychological dynamics and phenomenology of social inclusion and exclusion. The editors take as their starting point the assumption that social life is conducted in a ...framework of relationships in which individuals seek inclusion and belongingness. Relationships necessarily include others, but equally they have boundaries that exclude. Frequently these boundaries are challenged or crossed. The book will draw together research on individual motivation, small group processes, stigmatization and intergroup relations, to provide a comprehensive social psychological account of social inclusion and exclusion.
Acknowledgements
Contributors
Chapter 1. A Social Psychological Framework for Understanding Social Inclusion and Exclusion
Dominic Abrams, Michael A. Hogg and José M. Marques
SECTION A: INDIVIDUAL INCLUSION AND EXCLUSION
Chapter 2. Social Exclusion Increases Aggression and Self-defeating Behavior while Reducing Intelligent Thought and Prosocial Behavior
Jean M. Twenge and Roy F. Baumeister
Chapter 3. Reacting to Ostracism: Retaliation or Reconciliation?
Kipling D. Williams and Cassandra L. Govan
Chapter 4. Stigma and Social Exclusion
Brenda Major and Collette P. Eccleston
Chapter 5. The Role of Exclusion in Maintaining Ingroup Inclusion
Cynthia L. Pickett and Marilynn B. Brewer
Chapter 6. Exclusion of the Self by Close Others and by Groups: Implications of the Self-Expansion Model
Tracy McGlaughlin-Volpe, Art Aron, Stephen C. Wright and Gary W. Lewandowski Jr.
SECTION B: GROUP DYNAMICS OF INCLUSION AND EXCLUSION
Chapter 7. Managing Group Composition: Inclusive and Exclusive Role Transitions
John M. Levine, Richard L. Moreland, and Leslie R. M. Hausmann
Chapter 8. When Bad Becomes Good (and Vice Versa): Why Social Exclusion Is Not Based on Difference
Dominic Abrams, Georgina Randsley de Moura, Paul Hutchison and G.Tendayi Viki
Chapter 9. Fringe Dwellers: Processes of Deviance and Marginalization in Groups Michael A. Hogg and Kelly S. Fielding and John Darley
Chapter 10. Delinquency: Cause or consequence of social exclusion?
Nicholas Emler and Stephen Reicher
SECTION C: INTERGROUP INCLUSION AND EXCLUSION
Chapter 11. Social Inclusion and Exclusion: Recategorization and the Perception of Intergroup Boundaries
John F. Dovidio, Samuel L. Gaertner, Gordon Hodson, Melissa A. Houlette and Kelly M. Johnson
Chapter 12. Intergroup Contact in a Divided Society: Challenging Segregation in Northern Ireland
Miles Hewstone, Ed Cairns, Alberto Voci, Stefania Paolini, Frances McLernon, Richard J. Crisp, Ulrike, Niens and Jean Craig
Chapter 13. Cognitive Representations and Exclusion of Immigrants: Why Red-Nosed Reindeer Don't Play Games
Diana R. Rice and Brian Mullen
Chapter 14. Attitudes toward Immigrants and Immigration: The Role of National and International Identity
Victoria M. Esses, John F. Dovidio, Antoinette Semenya and Lynne M. Jackson
Author Index
Subject Index
"This volume spans the full range from global to personal analysis of people in the process of including and excluding each other. The editors have assembled an impressive array of experts who shed light on people in (and out) of groups. Policy implications leap out from every chapter. A crucial book for all of us concerned with the current, unprecedented intergroup challenges to the human social condition." - Susan T. Fiske, Princeton University
"The Social Psychology of Inclusion and Exclusion is an important and timely publication. With 14 pointed chapters written by leading social psychologists, this edited volume provides a summary of where the intergroup field stands at present. I especially like the focus on social inclusion and exclusion at all three levels of analysis – micro-individual, meso-group, and macro-societal. Thus, this volume covers the effects of exclusion from laboratory studies on individuals to survey studies of Northern Ireland. In short, this volume can be highly recommended for all who are concerned with intergroup phenomena." - Thomas F. Pettigrew, University of California at Santa Cruz
To reverse the effects of deforestation, tropical areas have expanded restoration efforts in recent years. As ecological restoration positively affects the structure and function of degraded ...ecosystems, understanding to what extent restoration recovers ecosystem services (ES) is an important step in directing large-scale restoration actions. We evaluated the effect of restoration in increasing the provision of ES in tropical forests. We performed a global meta-analysis of ecological indicators of the ES provided in restored areas, degraded areas and reference ecosystems. We tested for the effects of different restoration strategies, different types of degradation and for the effects of restoration over time. Overall, restoration actions contributed to a significant increase in levels of ecological indicators of ES (carbon pool, soil attributes and biodiversity protection) compared to disturbed areas. Among the restoration strategies, the natural regeneration was the most effective. Biodiversity protection and carbon recovered better than soil attributes. All other restoration strategies recovered ES to a substantially lesser degree, and reforestation with exotics decreased the ES of areas degraded by agriculture. In areas degraded by pasture, restoration was more effective in recovering the biodiversity protection, whereas in areas degraded by agriculture, the restoration recovered mainly the carbon pool. Our results show that by choosing the correct strategy, restoration can recover much of the ES lost by the degradation of tropical forests. These results should be considered for large-scale conservation and management efforts for this biome.
Water and alcohol, such as methanol or ethanol, are miscible and, individually, good solvents for poly(N-isopropylacrylamide) (PNIPAm), but this polymer precipitates in water-alcohol mixtures. The ...intriguing behaviour of solvent mixtures that cannot dissolve a given polymer or a given protein, while the same macromolecule dissolves well in each of the cosolvents, is called cononsolvency. It is a widespread phenomenon, relevant for many formulation steps in the physicochemical and pharmaceutical industry, that is usually explained by invoking specific chemical details of the mixtures: as such, it has so far eluded any generic explanation. Here, by using a combination of simulations and theory, we present a simple and universal treatment that requires only the preferential interaction of one of the cosolvents with the polymer. The results show striking quantitative agreement with experiments and chemically specific simulations, opening a new perspective towards an operational understanding of macromolecular solubility.
•Enzymes are increasingly used in technological applications but often require prior optimization.•Computational tools save time and effort in protein engineering endeavours.•Web-based tools make ...computational enzyme design accessible to a broad user community.•The recent enzyme engineering web-tools are described and classified by engineering purpose.
Enzymes are in high demand for very diverse biotechnological applications. However, natural biocatalysts often need to be engineered for fine-tuning their properties towards the end applications, such as the activity, selectivity, stability to temperature or co-solvents, and solubility. Computational methods are increasingly used in this task, providing predictions that narrow down the space of possible mutations significantly and can enormously reduce the experimental burden. Many computational tools are available as web-based platforms, making them accessible to non-expert users. These platforms are typically user-friendly, contain walk-throughs, and do not require deep expertise and installations. Here we describe some of the most recent outstanding web-tools for enzyme engineering and formulate future perspectives in this field.
Increased efficiency of energy harvest, due to alterations in the gut microbiota (increased Firmicutes and decreased Bacteroidetes), has been implicated in obesity in mice and humans. However, a ...causal relationship is unproven and contributory variables include diet, genetics and age. Therefore, we explored the effect of a high-fat (HF) diet and genetically determined obesity (ob/ob) for changes in microbiota and energy harvesting capacity over time.
Seven-week-old male ob/ob mice were fed a low-fat diet and wild-type mice were fed either a low-fat diet or a HF-diet for 8 weeks (n=8/group). They were assessed at 7, 11 and 15 weeks of age for: fat and lean body mass (by NMR); faecal and caecal short-chain fatty acids (SCFA, by gas chromatography); faecal energy content (by bomb calorimetry) and microbial composition (by metagenomic pyrosequencing).
A progressive increase in Firmicutes was confirmed in both HF-fed and ob/ob mice reaching statistical significance in the former, but this phylum was unchanged over time in the lean controls. Reductions in Bacteroidetes were also found in ob/ob mice. However, changes in the microbiota were dissociated from markers of energy harvest. Thus, although the faecal energy in the ob/ob mice was significantly decreased at 7 weeks, and caecal SCFA increased, these did not persist and faecal acetate diminished over time in both ob/ob and HF-fed mice, but not in lean controls. Furthermore, the proportion of the major phyla did not correlate with energy harvest markers.
The relationship between the microbial composition and energy harvesting capacity is more complex than previously considered. While compositional changes in the faecal microbiota were confirmed, this was primarily a feature of high-fat feeding rather than genetically induced obesity. In addition, changes in the proportions of the major phyla were unrelated to markers of energy harvest which changed over time. The possibility of microbial adaptation to diet and time should be considered in future studies.
Objectives The purpose of this study was to examine the relationship between changes in pulmonary vascular resistance (PVR) and right ventricular ejection fraction (RVEF) and survival in patients ...with pulmonary arterial hypertension (PAH) under PAH-targeted therapies. Background Despite the fact that medical therapies reduce PVR, the prognosis of patients with PAH is still poor. The primary cause of death is right ventricular (RV) failure. One possible explanation for this apparent paradox is the fact that a reduction in PVR is not automatically followed by an improvement in RV function. Methods A cohort of 110 patients with incident PAH underwent baseline right heart catheterization, cardiac magnetic resonance imaging, and 6-min walk testing. These measurements were repeated in 76 patients after 12 months of therapy. Results Two patients underwent lung transplantation, 13 patients died during the first year, and 17 patients died in the subsequent follow-up of 47 months. Baseline RVEF (hazard ratio HR: 0.938; p = 0.001) and PVR (HR: 1.001; p = 0.031) were predictors of mortality. During the first 12 months, changes in PVR were moderately correlated with changes in RVEF (R = 0.330; p = 0.005). Changes in RVEF (HR: 0.929; p = 0.014) were associated with survival, but changes in PVR (HR: 1.000; p = 0.820) were not. In 68% of patients, PVR decreased after medical therapy. Twenty-five percent of those patients with decreased PVR showed a deterioration of RV function and had a poor prognosis. Conclusions After PAH-targeted therapy, RV function can deteriorate despite a reduction in PVR. Loss of RV function is associated with a poor outcome, irrespective of any changes in PVR.
The understanding of acclimation strategies to low temperature and water availability is decisive to ensure coffee crop sustainability, since these environmental conditions determine the suitability ...of cultivation areas. In this context, the impacts of single and combined exposure to drought and cold were evaluated in three genotypes of the two major cropped species, Coffea arabica cv. Icatu, Coffea canephora cv. Apoatã, and the hybrid Obatã. Crucial traits of plant resilience to environmental stresses have been examined: photosynthesis, lipoperoxidation and the antioxidant response. Drought and/or cold promoted leaf dehydration, which was accompanied by stomatal and mesophyll limitations that impaired leaf C-assimilation in all genotypes. However, Icatu showed a lower impact upon stress exposure and a faster and complete photosynthetic recovery. Although lipoperoxidation was increased by drought (Icatu) and cold (all genotypes), it was greatly reduced by stress interaction, especially in Icatu. In fact, although the antioxidative system was reinforced under single drought and cold exposure (e.g., activity of enzymes as Cu,Zn-superoxide dismutase, ascorbate peroxidase, APX, glutathione reductase and catalase, CAT), the stronger increases were observed upon the simultaneous exposure to both stresses, which was accompanied with a transcriptional response of some genes, namely related to APX. Complementary, non-enzyme antioxidant molecules were promoted mostly by cold and the stress interaction, including α-tocopherol (in C. arabica plants), ascorbate (ASC), zeaxanthin, and phenolic compounds (all genotypes). In general, drought promoted antioxidant enzymes activity, whereas cold enhanced the synthesis of both enzyme and non-enzyme antioxidants, the latter likely related to a higher need of antioxidative capability when enzyme reactions were probably quite repressed by low temperature. Icatu showed the wider antioxidative capability, with the triggering of all studied antioxidative molecules by drought (except CAT), cold, and, particularly, stress interaction (except ASC), revealing a clear stress cross-tolerance. This justified the lower impacts on membrane lipoperoxidation and photosynthetic capacity under stress interaction conditions, related to a better ROS control. These findings are also relevant to coffee water management, showing that watering in the cold season should be largely avoided.
PDF
