Joyful by nature: approaches to investigate the evolution and function of joy in non-human animals

The nature and evolution of positive emotion is a major question remaining unanswered in science and philosophy. The study of feelings and emotions in humans and animals is dominated by discussion of affective states that have negative valence. Given the clinical and social significance of negative affect, such as depression, it is unsurprising that these emotions have received more attention from scientists. Compared to negative emotions, such as fear that leads to fleeing or avoidance, positive emotions are less likely to result in specific, identifiable, behaviours being expressed by an animal. This makes it particularly challenging to quantify and study positive affect. However, bursts of intense positive emotion (joy) are more likely to be accompanied by externally visible markers, like vocalisations or movement patterns, which make it more amenable to scientific study and more resilient to concerns about anthropomorphism. We define joy as intense, brief, and event-driven (i.e. a response to something), which permits investigation into how animals react to a variety of situations that would provoke joy in humans. This means that behavioural correlates of joy are measurable, either through newly discovered ‘laughter’ vocalisations, increases in play behaviour, or reactions to cognitive bias tests that can be used across species. There are a range of potential situations that cause joy in humans that have not been studied in other animals, such as whether animals feel joy on sunny days, when they accomplish a difficult feat, or when they are reunited with a familiar companion after a prolonged absence. Observations of species-specific calls and play behaviour can be combined with biometric markers and reactions to ambiguous stimuli in order to enable comparisons of affect between phylogenetically distant taxonomic groups. Identifying positive affect is also important for animal welfare because knowledge of positive emotional states would allow us to monitor animal well-being better. Additionally, measuring if phylogenetically and ecologically distant animals play more, laugh more, or act more optimistically after certain kinds of experiences will also provide insight into the mechanisms underlying the evolution of joy and other positive emotions, and potentially even into the evolution of consciousness.     

A Physician's Perspective on the Incorporation of Pictograms as a Supplement to Medical Instructions in Chile: A Pilot Study

Introduction and objectivesCurrent models of health care are progressively migrating to more participatory models, where for treatment to achieve results that last over time, there must be effective communication between the patient, his or her caregivers, and health professionals. Although the use of pictograms in the context of medical instructions has been widely studied, in our country, there are no studies about their usefulness, or which set of symbols should be used by the systems. This work aims to present the first step towards the development of platforms that automatically suggest pictograms to supplement medical instructions for primary care settings in Chile.Materials and methodsIn this pilot study, we collected and analyzed the physicians' opinions on the selection of medical instructions that later will automatically be supplemented by the software that is under construction. We designed an expert validation survey using a set of 66 medical instructions with pictograms. This survey provided three rating options for each medical instruction: Not necessary (supplementing the instruction with a pictogram does not carry any value), Useful (supplementing the instruction with a pictogram may help patients to understand and remember the instruction), and Essential (supplementing the instruction with a pictogram is essential). Seventy-one physicians responded to the survey.Results22 out of 66 medical instructions were considered “essential” by >=51% of the experts, and 12 of the 66 were considered to be “useful but not essential” by >=51% of the experts.ConclusionResults of our survey validate the potential use of pictograms as a complement to better comprehension of medical instructions in our country.     

Peptide modification by introduction ofα-trifluoromethyl substituted amino acids

Summary Methodology for the synthesis and incorporation of-trifluoromethyl substituted amino acids into N- and C-terminal position of peptides is described. The incorporation of-trifluoromethyl substituted amino acids into strategical positions of peptides enhances proteolytic stability and lipophilicity. Furthermore, it improves transport rates in vivo and permeability through certain body barriers.     

Metal-directed affinity labeling of zinc(II), cobalt(II) and cadmium(II) horse liver alcohol dehydrogenases

The active site metal in horse liver alcohol dehydrogenase has been studied by metal-directed affinity labeling of the native zinc(II) enzyme and that substituted with cobalt(II) or cadmium(II). Reversible binding of bromoimidazolyl propionic acid to the cobalt enzyme blueshifts the visible absorption band originating from the catalytic cobalt atom at 655 to 630 nm. Binding of imidazole to the cobalt(II) enzyme redshifts the 655 nm band to 667 nm. Addition of bromoimidazolyl propionic acid blueshifts this 667 nm band back to 630 nm. This proves direct binding of the label to the active site metal in competition with imidazole. The affinity of the label for the reversible binding site in the three enzymes follows the order Zn ? Cd ? Co. After reversible complex formation, bromoimidazolyl propionic acid alkylates cysteine-46, one of the protein ligands to the active site metal. The nucleophilic reactivity of this metal-mercaptide bond in each reversible complex follows the order Co ? Zn ? Cd.     

Synthesis and Antiproliferative Activities of Novel Substituted 5‐Anilino‐α‐Glucofuranose Derivatives

In order to find novel antitumor candidate agents with high efficiency and low toxicity, 14 novel substituted 5‐anilino‐α‐glucofuranose derivatives have been designed, synthesized and evaluated for antiproliferative activities in vitro. Their structures were characterized by NMR (¹H and ¹³C) and HR‐MS, and configuration (R/S) at C(5) was identified by two‐dimensional ¹H,¹H‐NOESY‐NMR spectrum. Their antiproliferative activities against human tumor cells were investigated by MTT assay. The results demonstrated that most of the synthesized compounds had antiproliferative effects comparable to the reference drugs gefitinib and lapatinib. In particular, (5R)‐5‐O‐(3‐chloro‐4‐{[5‐(4‐fluorophenyl)thiophen‐2‐yl]methyl}anilino)‐5‐deoxy‐1,2‐O‐(1‐methylethylidene)‐α‐glucofuranose ( 9da ) showed the most potent antiproliferative effects against SW480, A431 and A549 cells, with IC₅₀ values of 8.57, 5.15 and 15.24 μm , respectively. This work suggested 5‐anilino‐α‐glucofuranose as an antitumor core structure that may open a new way to develop more potent anti‐cancer agents.     

Non-human primate token use shows possibilities but also limitations for establishing a form of currency

Non-human primates evaluate choices based on quantitative information and subjective valuation of options. Non-human primates can learn to value tokens as placeholders for primary rewards (such as food). With those tokens established as a potential form of ‘currency’, it is then possible to examine how they respond to opportunities to earn and use tokens in ways such as accumulating tokens or exchanging tokens with each other or with human experimenters to gain primary rewards. Sometimes, individuals make efficient and beneficial choices to obtain tokens and then exchange them at the right moments to gain optimal reward. Sometimes, they even accumulate such rewards through extended delay of gratification, or through other exchange-based interactions. Thus, non-human primates are capable of associating value to arbitrary tokens that may function as currency-like stimuli, but there also are strong limitations on how non-human primates can integrate such tokens into choice situations or use such tokens to fully ‘symbolize’ economic decision-making. These limitations are important to acknowledge when considering the evolutionary emergence of currency use in our species.This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.     

Integrating GIS and expert judgment in a multi-criteria analysis to map and develop a habitat suitability index: A case study of large mammals on the Malayan Peninsula

Many habitat patches in tropical landscapes have become less suitable for wildlife due to an increase in anthropogenic disturbances. An index of habitat suitability based on the ecological factors that collectively determine the suitability of an organism's habitat is important for conservation planning. However, a widely accepted and comprehensive multi-criteria habitat suitability index for umbrella species is still lacking, particularly in areas where information related to the biology and ecology of the species of interest is not available. Therefore we develop preliminary habitat maps and measure the degree of habitat suitability for large mammals, focusing on four umbrella species in the State of Selangor, Peninsular Malaysia: Panthera tigris jacksoni (Malayan tiger), Tapirus indicus (Malayan tapir), Helarctos malayanus malayanus (Malayan sun bear), and Rusa unicolor cambojensis (sambar deer). The former two are endangered and the latter two are vulnerable according to the IUCN Red List. The suitability of habitat patches for each species was measured across the entire study area as well as in nine wildlife protected areas by integrating GIS data and expert opinion. Expert opinions were used as the source of information regarding the stresses faced by the species because there was insufficient information available from ground surveys.We developed an index and maps of habitat suitability for each species, which were then integrated to represent a combined index (ranging from 0 to 27) and spatially explicit maps of the area's habitat suitability for large mammals. The average large mammal habitat suitability index value of the State of Selangor (9) indicates that many habitat patches have become unsuitable for such species. Of the nine wildlife protected areas, Fraser's Hill (22), Sungai Dusun (22), and Bukit Kutu (21) are very suitable; Klang Gate (20) and Templers Park (17) are suitable; and the remaining four are unsuitable for large mammals. We assume that this preliminary habitat suitability index and mapping are useful for conservation planning of wildlife habitats at both landscape and regional scales, as well as providing an initial foundation for revision by future research with significant new information.     

3D-QSAR studies of checkpoint kinase 1 inhibitors based on molecular docking and CoMFA

Three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were performed on a series of substituted 1,4-dihydroindeno[1,2-c]pyrazoles inhibitors, using molecular docking and comparative molecular field analysis (CoMFA). The docking results from GOLD 3.0.1 provide a reliable conformational alignment scheme for the 3D-QSAR model. Based on the docking conformations and alignments, highly predictive CoMFA model was built with cross-validated q ² value of 0.534 and non-cross-validated partial least-squares analysis with the optimum components of six showed a conventional r ² value of 0.911. The predictive ability of this model was validated by the testing set with a conventional r ² value of 0.812. Based on the docking and CoMFA, we have identified some key features of the 1,4-dihydroindeno[1,2-c]pyrazoles derivatives that are responsible for checkpoint kinase 1 inhibitory activity. The analyses may be used to design more potent 1,4-dihydroindeno[1,2-c]pyrazoles derivatives and predict their activity prior to synthesis.     

Racial regimes,comparative politics,and the problem of judgment

This review essay examines the practice of judgment that characterized the subfield of comparative politics from its origins in openly racist ideas of the capacity for self-rule through to its twentieth-century behavioralist and positivist iterations. Though continually faced with new political phenomena that called into question its inherited criteria of judgment, comparative politics tended to practice determinative rather than reflective judgment, that is, to subsume the particulars of other cultures under known rules. Further, the essay examines the racialized conception of self-rule described by Michael Hanchard as embedded in a larger problem of Western political thinking: the flight from action into rule and tendency to think of politics wholly in terms of ruling and being ruled.     

A single beta subunit M2 domain residue controls the picrotoxin sensitivity of alphabeta heteromeric glycine receptor chloride channels

This study investigated the residues responsible for the reduced picrotoxin sensitivity of the alphabeta heteromeric glycine receptor relative to the alpha homomeric receptor. By analogy with structurally related receptors, the beta subunit M2 domain residues P278 and F282 were considered the most likely candidates for mediating this effect. These residues align with G254 and T258 of the alpha subunit. The T258A, T258C and T258F mutations dramatically reduced the picrotoxin sensitivity of the alpha homomeric receptor. Furthermore, the converse F282T mutation in the beta subunit increased the picrotoxin sensitivity of the alphabeta heteromeric receptor. The P278G mutation in the beta subunit did not affect the picrotoxin sensitivity of the alphabeta heteromer. Thus, a ring of five threonines at the M2 domain depth corresponding to alpha subunit T258 is specifically required for picrotoxin sensitivity. Mutations to alpha subunit T258 also profoundly influenced the apparent glycine affinity. A substituted cysteine accessibility analysis revealed that the T258C sidechain increases its pore exposure in the channel open state. This provides further evidence for an allosteric mechanism of picrotoxin inhibition, but renders it unlikely that picrotoxin (as an allosterically acting 'competitive' antagonist) binds to this residue.