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1.
Changing the visual body appearance by use of as virtual reality system, funny mirror, or binocular glasses has been reported to be helpful in rehabilitation of pain. However, there are interindividual differences in the analgesic effect of changing the visual body image. We hypothesized that a negative body image associated with changing the visual body appearance causes interindividual differences in the analgesic effect although the relationship between the visual body appearance and analgesic effect has not been clarified. We investigated whether a negative body image associated with changes in the visual body appearance increased pain. Twenty-five healthy individuals participated in this study. To evoke a negative body image, we applied the method of rubber hand illusion. We created an “injured rubber hand” to evoke unpleasantness associated with pain, a “hairy rubber hand” to evoke unpleasantness associated with embarrassment, and a “twisted rubber hand” to evoke unpleasantness associated with deviation from the concept of normality. We also created a “normal rubber hand” as a control. The pain threshold was measured while the participant observed the rubber hand using a device that measured pain caused by thermal stimuli. Body ownership experiences were elicited by observation of the injured rubber hand and hairy rubber hand as well as the normal rubber hand. Participants felt more unpleasantness by observing the injured rubber hand and hairy rubber hand than the normal rubber hand and twisted rubber hand (p<0.001). The pain threshold was lower under the injured rubber hand condition than with the other conditions (p<0.001). We conclude that a negative body appearance associated with pain can increase pain sensitivity.  相似文献   

2.
We aimed to predict how hard subjects work for financial rewards from their general trait and state reward-motivation. We specifically asked 1) whether individuals high in general trait “reward responsiveness” work harder 2) whether task-irrelevant cues can make people work harder, by increasing general motivation. Each trial of our task contained a 1 second earning interval in which male subjects earned money for each button press. This was preceded by one of three predictive cues: an erotic picture of a woman, a man, or a geometric figure. We found that individuals high in trait “reward responsiveness” worked harder and earned more, irrespective of the predictive cue. Because female predictive cues are more rewarding, we expected them to increase general motivation in our male subjects and invigorate work, but found a more complex pattern.  相似文献   

3.
Though the hippocampus typically has been implicated in processes related to associative binding, special types of associations – such as those created by integrative mental imagery – may be supported by processes implemented in other medial temporal-lobe or sensory processing regions. Here, we investigated what neural mechanisms underlie the formation and subsequent retrieval of integrated mental images, and whether those mechanisms differ based on the emotionality of the integration (i.e., whether it contains an emotional item or not). Participants viewed pairs of words while undergoing a functional MRI scan. They were instructed to imagine the two items separately from one another (“non-integrative” study) or as a single, integrated mental image (“integrative” study). They provided ratings of how successful they were at generating vivid images that fit the instructions. They were then given a surprise associative recognition test, also while undergoing an fMRI scan. The cuneus showed parametric correspondence to increasing imagery success selectively during encoding and retrieval of emotional integrations, while the parahippocampal gyri and prefrontal cortices showed parametric correspondence during the encoding and retrieval of non-emotional integrations. Connectivity analysis revealed that selectively during negative integration, left amygdala activity was negatively correlated with frontal and hippocampal activity. These data indicate that individuals utilize two different neural routes for forming and retrieving integrations depending on their emotional content, and they suggest a potentially disruptive role for the amygdala on frontal and medial-temporal regions during negative integration.  相似文献   

4.
Microbes acquire DNA from a variety of sources. The last decades, which have seen the development of genome sequencing, have revealed that horizontal gene transfer has been a major evolutionary force that has constantly reshaped genomes throughout evolution. However, because the history of life must ultimately be deduced from gene phylogenies, the lack of methods to account for horizontal gene transfer has thrown into confusion the very concept of the tree of life. As a result, many questions remain open, but emerging methodological developments promise to use information conveyed by horizontal gene transfer that remains unexploited today.The discovery of the existence of prokaryotic microbes dates back more than 300 years. Since then, our picture of our distant microscopic relatives has undergone several revolutions: from being the living “proofs” of the existence of spontaneous generation, they became later the “archaic” representatives of our distant ancestors, to finally be legitimately recognized as exceptionally diverse organisms, keystone to any ecosystem, including the most familiar and the most hostile environments on Earth. Similarly, although they were first seen as elementary and unbreakable bricks of life, they are now seen as genetically composite bodies, heavyweight champions of “gene robbery.” The most recent of these revolutions has indeed been the realization of their unparalleled ability to integrate genetic material coming from more or less evolutionarily distant organisms. This mechanism is called “horizontal gene transfer” as opposed to vertical transmission from mother to daughter cell.  相似文献   

5.
It has been a long-standing goal in systems biology to find relations between the topological properties and functional features of protein networks. However, most of the focus in network studies has been on highly connected proteins (“hubs”). As a complementary notion, it is possible to define bottlenecks as proteins with a high betweenness centrality (i.e., network nodes that have many “shortest paths” going through them, analogous to major bridges and tunnels on a highway map). Bottlenecks are, in fact, key connector proteins with surprising functional and dynamic properties. In particular, they are more likely to be essential proteins. In fact, in regulatory and other directed networks, betweenness (i.e., “bottleneck-ness”) is a much more significant indicator of essentiality than degree (i.e., “hub-ness”). Furthermore, bottlenecks correspond to the dynamic components of the interaction network—they are significantly less well coexpressed with their neighbors than nonbottlenecks, implying that expression dynamics is wired into the network topology.  相似文献   

6.
Observers can rapidly perform a variety of visual tasks such as categorizing a scene as open, as outdoor, or as a beach. Although we know that different tasks are typically associated with systematic differences in behavioral responses, to date, little is known about the underlying mechanisms. Here, we implemented a single integrated paradigm that links perceptual processes with categorization processes. Using a large image database of natural scenes, we trained machine-learning classifiers to derive quantitative measures of task-specific perceptual discriminability based on the distance between individual images and different categorization boundaries. We showed that the resulting discriminability measure accurately predicts variations in behavioral responses across categorization tasks and stimulus sets. We further used the model to design an experiment, which challenged previous interpretations of the so-called “superordinate advantage.” Overall, our study suggests that observed differences in behavioral responses across rapid categorization tasks reflect natural variations in perceptual discriminability.  相似文献   

7.
Epithelial tissues respond to a wide variety of environmental and genotoxic stresses. As an adaptive mechanism, cells can deviate from their natural paths to acquire new identities, both within and across lineages. Under extreme conditions, epithelial tissues can utilize “shape‐shifting” mechanisms whereby they alter their form and function at a tissue‐wide scale. Mounting evidence suggests that in order to acquire these alternate tissue identities, cells follow a core set of “tissue logic” principles based on developmental paradigms. Here, we review the terminology and the concepts that have been put forward to describe cell plasticity. We also provide insights into various cell intrinsic and extrinsic factors, including genetic mutations, inflammation, microbiota, and therapeutic agents that contribute to cell plasticity. Additionally, we discuss recent studies that have sought to decode the “syntax” of plasticity—i.e., the cellular and molecular principles through which cells acquire new identities in both homeostatic and malignant epithelial tissues—and how these processes can be manipulated for developing novel cancer therapeutics.  相似文献   

8.

Background

GABAergic signals to the nucleus accumbens (NAc) shell arise from predominantly subcortical sources whereas glutamatergic signals arise mainly from cortical-related sources. Here we contrasted GABAergic and glutamatergic generation of hedonics versus motivation processes, as a proxy for comparing subcortical and cortical controls of emotion. Local disruptions of either signals in medial shell of NAc generate intense motivated behaviors corresponding to desire and/or dread, along a rostrocaudal gradient. GABA or glutamate disruptions in rostral shell generate appetitive motivation whereas disruptions in caudal shell elicit fearful motivation. However, GABA and glutamate signals in NAc differ in important ways, despite the similarity of their rostrocaudal motivation gradients.

Methodology/Principal Findings

Microinjections of a GABAA agonist (muscimol), or of a glutamate AMPA antagonist (DNQX) in medial shell of rats were assessed for generation of hedonic “liking” or “disliking” by measuring orofacial affective reactions to sucrose-quinine taste. Motivation generation was independently assessed measuring effects on eating versus natural defensive behaviors. For GABAergic microinjections, we found that the desire-dread motivation gradient was mirrored by an equivalent hedonic gradient that amplified affective taste “liking” (at rostral sites) versus “disliking” (at caudal sites). However, manipulation of glutamatergic signals completely failed to alter pleasure-displeasure reactions to sensory hedonic impact, despite producing a strong rostrocaudal gradient of motivation.

Conclusions/Significance

We conclude that the nucleus accumbens contains two functional affective keyboards for amino-acid signals: a motivation-generating keyboard and a hedonic-generating keyboard. Corticolimbic glutamate signals and subcortical GABA signals equivalently engage the motivation keyboard to generate desire and-or dread. Only subcortical GABA signals additionally engage the hedonic keyboard to amplify affective “liking” and “disliking” reactions. We thus suggest that top-down cortical glutamate signals powerfully regulate motivation components, but are relatively unable to penetrate core hedonic components of emotion. That may carry implications of limits to therapeutic regulation of pathological emotions.  相似文献   

9.
Why is Real-World Visual Object Recognition Hard?   总被引:1,自引:0,他引:1  
Progress in understanding the brain mechanisms underlying vision requires the construction of computational models that not only emulate the brain's anatomy and physiology, but ultimately match its performance on visual tasks. In recent years, “natural” images have become popular in the study of vision and have been used to show apparently impressive progress in building such models. Here, we challenge the use of uncontrolled “natural” images in guiding that progress. In particular, we show that a simple V1-like model—a neuroscientist's “null” model, which should perform poorly at real-world visual object recognition tasks—outperforms state-of-the-art object recognition systems (biologically inspired and otherwise) on a standard, ostensibly natural image recognition test. As a counterpoint, we designed a “simpler” recognition test to better span the real-world variation in object pose, position, and scale, and we show that this test correctly exposes the inadequacy of the V1-like model. Taken together, these results demonstrate that tests based on uncontrolled natural images can be seriously misleading, potentially guiding progress in the wrong direction. Instead, we reexamine what it means for images to be natural and argue for a renewed focus on the core problem of object recognition—real-world image variation.  相似文献   

10.
Several steering models in the visual science literature attempt to capture the visual strategies in curve driving. Some of them are based on steering points on the future path (FP), others on tangent points (TP). It is, however, challenging to differentiate between the models’ predictions in real–world contexts. Analysis of optokinetic nystagmus (OKN) parameters is one useful measure, as the different strategies predict measurably different OKN patterns. Here, we directly test this prediction by asking drivers to either a) “drive as they normally would” or b) to “look at the TP”. The design of the experiment is similar to a previous study by Kandil et al., but uses more sophisticated methods of eye–movement analysis. We find that the eye-movement patterns in the “normal” condition are indeed markedly different from the “tp” condition, and consistent with drivers looking at waypoints on the future path. This is the case for both overall fixation distribution, as well as the more informative fixation–by–fixation analysis of OKN. We find that the horizontal gaze speed during OKN corresponds well to the quantitative prediction of the future path models. The results also definitively rule out the alternative explanation that the OKN is produced by an involuntary reflex even while the driver is “trying” to look at the TP. The results are discussed in terms of the sequential organization of curve driving.  相似文献   

11.

Aims

Temperament and impulsivity are powerful predictors of addiction treatment outcomes. However, a comprehensive assessment of these features has not been examined in relation to smoking cessation outcomes.

Methods

Naturalistic prospective study. Treatment-seeking smokers (n = 140) were recruited as they engaged in an occupational health clinic providing smoking cessation treatment between 2009 and 2013. Participants were assessed at baseline with measures of temperament (Temperament and Character Inventory), trait impulsivity (Barratt Impulsivity Scale), and cognitive impulsivity (Go/No Go, Delay Discounting and Iowa Gambling Task). The outcome measure was treatment status, coded as “dropout” versus “relapse” versus “abstinence” at 3, 6, and 12 months endpoints. Participants were telephonically contacted and reminded of follow-up face to face assessments at each endpoint. The participants that failed to answer the phone calls or self-reported discontinuation of treatment and failed to attend the upcoming follow-up session were coded as dropouts. The participants that self-reported continuing treatment, and successfully attended the upcoming follow-up session were coded as either “relapse” or “abstinence”, based on the results of smoking behavior self-reports cross-validated with co-oximetry hemoglobin levels. Multinomial regression models were conducted to test whether temperament and impulsivity measures predicted dropout and relapse relative to abstinence outcomes.

Results

Higher scores on temperament dimensions of novelty seeking and reward dependence predicted poorer retention across endpoints, whereas only higher scores on persistence predicted greater relapse. Higher scores on the trait dimension of non-planning impulsivity but not performance on cognitive impulsivity predicted poorer retention. Higher non-planning impulsivity and poorer performance in the Iowa Gambling Task predicted greater relapse at 3 and 6 months and 6 months respectively.

Conclusion

Temperament measures, and specifically novelty seeking and reward dependence, predict smoking cessation treatment retention, whereas persistence, non-planning impulsivity and poor decision-making predict smoking relapse.  相似文献   

12.
Allosteric regulation is a ubiquitous phenomenon exploited in biological processes to control cells in a myriad of ways. It is also of emerging interest in the design of functional proteins and therapeutics. Even though allostery was proposed over 50 years ago and has been studied intensively from a structural perspective, many key details of allosteric mechanisms remain mysterious. Over the last decade significant attention has been paid to the “dynamic component” of allostery, as opposed to the analysis of rigid structures. Nuclear magnetic resonance spectroscopy and its ability to detect conformationally dynamic processes at atomic resolution have played an important role in expanding our understanding of allosteric mechanisms and opening up new questions. This article focuses on work that highlights how protein dynamics can factor into allosteric processes in distinct ways. Two cases are contrasted. The first considers the “traditionally allosteric” protein CheY, which undergoes a conformational change as a key element of its allostery. The second considers the more rarely observed “dynamic allostery” in a PDZ domain, in which allosteric behavior arises from changes in internal structural dynamics. Interestingly, the dynamic processes in these two contrasting examples occur on different timescales. In the case of the PDZ domain, subsequent experimental and computational work is reviewed to reveal a more complete picture of this interesting case of allostery.  相似文献   

13.
D1 and D2 dopamine receptors are structurally homologous G protein–coupled receptors that serve distinct physiological functions both in neurons and nonneural cell types. We have observed that these receptors are selectively endocytosed in HEK293 cells by distinct dynamin-dependent and -independent mechanisms. Although these endocytic mechanisms operate with similarly rapid kinetics, they differ in their regulation by agonist and deliver D1 and D2 receptors specifically to different primary endocytic vesicles. After this segregation into different endocytic membranes, both D1 and D2 receptors recycle to the plasma membrane. Similar results are observed in Neuro2A neuroblastoma cells coexpressing both receptors at high levels. These findings establish that “classical” dynamin-dependent and “alternative” dynamin-independent endocytic mechanisms differ in their physiological regulation, sort structurally homologous signaling receptors in the plasma membrane, and mediate distinct early endocytic pathways leading to recycling endosomes. Our results also refute the previous hypothesis that dynamin-independent endocytosis targets G protein–coupled receptors selectively to lysosomes, and they suggest a new role of endocytic sorting mechanisms in physically segregating structurally homologous signaling receptors at the cell surface.  相似文献   

14.
Phylogenomic analysis of the occurrence and abundance of protein domains in proteomes has recently showed that the α/β architecture is probably the oldest fold design. This holds important implications for the origins of biochemistry. Here we explore structure-function relationships addressing the use of chemical mechanisms by ancestral enzymes. We test the hypothesis that the oldest folds used the most mechanisms. We start by tracing biocatalytic mechanisms operating in metabolic enzymes along a phylogenetic timeline of the first appearance of homologous superfamilies of protein domain structures from CATH. A total of 335 enzyme reactions were retrieved from MACiE and were mapped over fold age. We define a mechanistic step type as one of the 51 mechanistic annotations given in MACiE, and each step of each of the 335 mechanisms was described using one or more of these annotations. We find that the first two folds, the P-loop containing nucleotide triphosphate hydrolase and the NAD(P)-binding Rossmann-like homologous superfamilies, were α/β architectures responsible for introducing 35% (18/51) of the known mechanistic step types. We find that these two oldest structures in the phylogenomic analysis of protein domains introduced many mechanistic step types that were later combinatorially spread in catalytic history. The most common mechanistic step types included fundamental building blocks of enzyme chemistry: “Proton transfer,” “Bimolecular nucleophilic addition,” “Bimolecular nucleophilic substitution,” and “Unimolecular elimination by the conjugate base.” They were associated with the most ancestral fold structure typical of P-loop containing nucleotide triphosphate hydrolases. Over half of the mechanistic step types were introduced in the evolutionary timeline before the appearance of structures specific to diversified organisms, during a period of architectural diversification. The other half unfolded gradually after organismal diversification and during a period that spanned ∼2 billion years of evolutionary history.  相似文献   

15.

Background

Sri Lankan rural doctors based in isolated peripheral hospitals routinely resuscitate critically ill patients but have difficulty accessing training. We tested a train-the-trainer model that could be utilised in isolated rural hospitals.

Methods

Eight selected rural hospital non-specialist doctors attended a 2-day instructor course. These “trained trainers” educated their colleagues in advanced cardiac life support at peripheral hospital workshops and we tested their students in resuscitation knowledge and skills pre and post training, and at 6- and 12-weeks. Knowledge was assessed through 30 multiple choice questions (MCQ), and resuscitation skills were assessed by performance in a video recorded simulated scenario of a cardiac arrest using a Resuci Anne Skill Trainer mannequin.

Results/Discussion/Conclusion

Fifty seven doctors were trained. Pre and post training assessment was possible in 51 participants, and 6-week and 12-week follow up was possible for 43, and 38 participants respectively. Mean MCQ scores significantly improved over time (p<0.001), and a significant improvement was noted in “average ventilation volume”, “compression count”, and “compressions with no error”, “adequate depth”, “average depth”, and “compression rate” (p<0.01). The proportion of participants with compression depth ≥40mm increased post intervention (p<0.05) and at 12-week follow up (p<0.05), and proportion of ventilation volumes between 400-1000mls increased post intervention (p<0.001). A significant increase in the proportion of participants who “checked for responsiveness”, “opened the airway”, “performed a breathing check”, who used the “correct compression ratio”, and who used an “appropriate facemask technique” was also noted (p<0.001). A train-the-trainer model of resuscitation education was effective in improving resuscitation knowledge and skills in Sri Lankan rural peripheral hospital doctors. Improvement was sustained to 12 weeks for most components of resuscitation knowledge and skills. Further research is needed to identify which components of training are most effective in leading to sustained improvement in resuscitation.  相似文献   

16.
A recent paper by Oh and Sakata investigates the “incompletely solved mystery” of how the three cone responses map onto perceived hue, and particularly the S cone’s well-known problematic contribution to blueness and redness. Citing previous workers, they argue the twentieth century traditional multistage model does not satisfactorily account for color appearance. In their experiment, increasing S cone excitation with shortening wavelength from about 480–460 nm increased perceived blueness up to the unique Blue point at 470 nm, when (a) it began decreasing and (b) redness perception began increasing. The authors asked, What mechanism can be responsible for such functions? I demonstrate a solution. First, it is shown the problem does not lie in the traditional opponent color chromatic responses yellow-blue, red-green (y-b, r-g, which accurately predict the above functions), but in the traditional multistage model of mapping cone responses to chromatic response functions. Arguably, this is due to the S cone’s hypothetically signaling both blueness and redness by the same mechanism rather than by different, independent, mechanisms. Hence a new distinction or mechanism is proposed for a more accurate model, that introduces the new terms primary and secondary cone outputs. However, this distinction requires that the cones S, M, L each directly produce one of the three spectral chromatic responses b, g, y. Such a model was recently published, based on extremely high correlation of SML cone responsivities with the three spectral (bgy) chromatic responses. This model encodes the former directly onto the latter one-to-one as cone primary outputs, whilst S and L cones have a further or secondary function where each produces one of the two spectral lobes of r chromatic response. The proposed distinction between primary and secondary cone outputs is a new concept and useful tool in detailing cone outputs to chromatic channels, and provides a solution to the above “incompletely solved mystery.” Thus the S cone has a primary output producing the total b chromatic response and a secondary output that shares with the L cone the production of r chromatic response, thus aligning with Oh and Sokata’s results. The model similarly maps L cone to yellowness as primary output and to redness as secondary output.  相似文献   

17.
Within the range of images that we might categorize as a “beach”, for example, some will be more representative of that category than others. Here we first confirmed that humans could categorize “good” exemplars better than “bad” exemplars of six scene categories and then explored whether brain regions previously implicated in natural scene categorization showed a similar sensitivity to how well an image exemplifies a category. In a behavioral experiment participants were more accurate and faster at categorizing good than bad exemplars of natural scenes. In an fMRI experiment participants passively viewed blocks of good or bad exemplars from the same six categories. A multi-voxel pattern classifier trained to discriminate among category blocks showed higher decoding accuracy for good than bad exemplars in the PPA, RSC and V1. This difference in decoding accuracy cannot be explained by differences in overall BOLD signal, as average BOLD activity was either equivalent or higher for bad than good scenes in these areas. These results provide further evidence that V1, RSC and the PPA not only contain information relevant for natural scene categorization, but their activity patterns mirror the fundamentally graded nature of human categories. Analysis of the image statistics of our good and bad exemplars shows that variability in low-level features and image structure is higher among bad than good exemplars. A simulation of our neuroimaging experiment suggests that such a difference in variance could account for the observed differences in decoding accuracy. These results are consistent with both low-level models of scene categorization and models that build categories around a prototype.  相似文献   

18.
In laboratory work which involves the large-scale routine assay of biologically-active substances the sponsors of “alternative” (in vitro) methods and the scientists have a common aim: a reduction in the use of living animals. In vitro methods are usually more accurate, easier to perform, and cheaper. Animals are no longer required for the production of certain antiviral vaccines.Those engaged in medical research where new knowledge is being sought also need no incentive to develop in vitro methods because they make refined analysis possible. Nevertheless, such in vitro methods are usually not alternatives in the sense that they substitute for animals; they complement experiments on animals. A legal requirement “that no experiment on a living animal may be performed if the purpose of the experiment can be achieved by alternative means not involving an experiment on a living animal” would be unenforceable.  相似文献   

19.
Plant–soil feedback (PSF) has gained attention as a mechanism promoting plant growth and coexistence. However, most PSF research has measured monoculture growth in greenhouse conditions. Translating PSFs into effects on plant growth in field communities remains an important frontier for PSF research. Using a 4‐year, factorial field experiment in Jena, Germany, we measured the growth of nine grassland species on soils conditioned by each of the target species (i.e., 72 PSFs). Plant community models were parameterized with or without these PSF effects, and model predictions were compared to plant biomass production in diversity–productivity experiments. Plants created soils that changed subsequent plant biomass by 40%. However, because they were both positive and negative, the average PSF effect was 14% less growth on “home” than on “away” soils. Nine‐species plant communities produced 29 to 37% more biomass for polycultures than for monocultures due primarily to selection effects. With or without PSF, plant community models predicted 28%–29% more biomass for polycultures than for monocultures, again due primarily to selection effects. Synthesis: Despite causing 40% changes in plant biomass, PSFs had little effect on model predictions of plant community biomass across a range of species richness. While somewhat surprising, a lack of a PSF effect was appropriate in this site because species richness effects in this study were caused by selection effects and not complementarity effects (PSFs are a complementarity mechanism). Our plant community models helped us describe several reasons that even large PSF may not affect plant productivity. Notably, we found that dominant species demonstrated small PSF, suggesting there may be selective pressure for plants to create neutral PSF. Broadly, testing PSFs in plant communities in field conditions provided a more realistic understanding of how PSFs affect plant growth in communities in the context of other species traits.  相似文献   

20.
Animals with rudimentary innate abilities require substantial learning to transform those abilities into useful skills, where a skill can be considered as a set of sensory–motor associations. Using linear neural network models, it is proved that if skills are stored as distributed representations, then within-lifetime learning of part of a skill can induce automatic learning of the remaining parts of that skill. More importantly, it is shown that this “free-lunch” learning (FLL) is responsible for accelerated evolution of skills, when compared with networks which either 1) cannot benefit from FLL or 2) cannot learn. Specifically, it is shown that FLL accelerates the appearance of adaptive behaviour, both in its innate form and as FLL-induced behaviour, and that FLL can accelerate the rate at which learned behaviours become innate.  相似文献   

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