The autophagic roles of Rab small GTPases and their upstream regulators: A review

Macroautophagy is an evolutionarily conserved degradative process of eukaryotic cells. Double-membrane vesicles called autophagosomes sequester portions of cytoplasm and undergo fusion with the endolysosomal pathway in order to degrade their content. There is growing evidence that members of the small GTPase RAB protein family—the well-known regulators of membrane trafficking and fusion events—play key roles in the regulation of the autophagic process. Despite numerous studies focusing on the functions of RAB proteins in autophagy, the importance of their upstream regulators in this process emerged only in the past few years. In this review, we summarize recent advances on the effects of RABs and their upstream modulators in the regulation of autophagy. Moreover, we discuss how impairment of these proteins alters the autophagic process leading to several generally known human diseases.     

Membrane lysis during biological membrane fusion: collateral damage by misregulated fusion machines

In the canonical model of membrane fusion, the integrity of the fusing membranes is never compromised, preserving the identity of fusing compartments. However, recent molecular simulations provided evidence for a pathway to fusion in which holes in the membrane evolve into a fusion pore. Additionally, two biological membrane fusion models—yeast cell mating and in vitro vacuole fusion—have shown that modifying the composition or altering the relative expression levels of membrane fusion complexes can result in membrane lysis. The convergence of these findings showing membrane integrity loss during biological membrane fusion suggests new mechanistic models for membrane fusion and the role of membrane fusion complexes.     

When "In Your Face" Is Not Out of Place: The Effect of Timing of Disclosure of a Same-Sex Dating Partner under Conditions of Contact

In a series of experiments we examined heterosexuals’ reactions to the timing of disclosure of a gender-matched confederate’s same-sex dating partner. Disclosure occurred in a naturalistic context–that is, it occurred when meeting, or expecting to soon meet, a same-sex attracted individual, who voluntarily shared this information with the participant as a natural part of a broader topic of discussion. The confederate, when disclosing early rather than later, was approached more closely (Prestudy) and liked more (Studies 1–2). Those experiencing early disclosure, compared with later, were less drawn to topics of lower intimacy (Study 1), were happier and more excited about meeting the confederate, and more likely to choose to be alone with the confederate for a one-on-one discussion (Study 2). Further, women experiencing early disclosure were more willing to introduce the same-gender confederate to their friends (Study 2). The benefits of knowing sooner, rather than later, continued to apply even when participants were given further time to process the disclosure. To explore the underlying reasons for the more favorable experiences of upfront disclosure, we examined participants’ memory of the information shared by the confederate (Study 3). Results revealed that those who experienced delayed disclosure were more likely to incorrectly recall and negatively embellish information related to the confederate’s sexual orientation, suggesting that early disclosure resulted in a reduced tendency to focus on the confederate’s sexuality as a defining feature. These positive findings for early timing are discussed in light of previous studies that have found benefits for delayed disclosure and those that have failed to investigate the effects of timing of ‘coming out’ under conditions of contact.     

Relationships among Facial Mimicry,Emotional Experience,and Emotion Recognition

Background

The relationships between facial mimicry and subsequent psychological processes remain unclear. We hypothesized that the congruent facial muscle activity would elicit emotional experiences and that the experienced emotion would induce emotion recognition.

Methodology/Principal Findings

To test this hypothesis, we re-analyzed data collected in two previous studies. We recorded facial electromyography (EMG) from the corrugator supercilii and zygomatic major and obtained ratings on scales of valence and arousal for experienced emotions (Study 1) and for experienced and recognized emotions (Study 2) while participants viewed dynamic and static facial expressions of negative and positive emotions. Path analyses showed that the facial EMG activity consistently predicted the valence ratings for the emotions experienced in response to dynamic facial expressions. The experienced valence ratings in turn predicted the recognized valence ratings in Study 2.

Conclusion

These results suggest that facial mimicry influences the sharing and recognition of emotional valence in response to others'' dynamic facial expressions.     

Tuning to the Positive: Age-Related Differences in Subjective Perception of Facial Emotion

Facial expressions aid social transactions and serve as socialization tools, with smiles signaling approval and reward, and angry faces signaling disapproval and punishment. The present study examined whether the subjective experience of positive vs. negative facial expressions differs between children and adults. Specifically, we examined age-related differences in biases toward happy and angry facial expressions. Young children (5–7 years) and young adults (18–29 years) rated the intensity of happy and angry expressions as well as levels of experienced arousal. Results showed that young children—but not young adults—rated happy facial expressions as both more intense and arousing than angry faces. This finding, which we replicated in two independent samples, was not due to differences in the ability to identify facial expressions, and suggests that children are more tuned to information in positive expressions. Together these studies provide evidence that children see unambiguous adult emotional expressions through rose-colored glasses, and suggest that what is emotionally relevant can shift with development.     

Affective loop experiences: designing for interactional embodiment

Involving our corporeal bodies in interaction can create strong affective experiences. Systems that both can be influenced by and influence users corporeally exhibit a use quality we name an affective loop experience. In an affective loop experience, (i) emotions are seen as processes, constructed in the interaction, starting from everyday bodily, cognitive or social experiences; (ii) the system responds in ways that pull the user into the interaction, touching upon end users'' physical experiences; and (iii) throughout the interaction the user is an active, meaning-making individual choosing how to express themselves—the interpretation responsibility does not lie with the system. We have built several systems that attempt to create affective loop experiences with more or less successful results. For example, eMoto lets users send text messages between mobile phones, but in addition to text, the messages also have colourful and animated shapes in the background chosen through emotion-gestures with a sensor-enabled stylus pen. Affective Diary is a digital diary with which users can scribble their notes, but it also allows for bodily memorabilia to be recorded from body sensors mapping to users'' movement and arousal and placed along a timeline. Users can see patterns in their bodily reactions and relate them to various events going on in their lives.The experiences of building and deploying these systems gave us insights into design requirements for addressing affective loop experiences, such as how to design for turn-taking between user and system, how to create for ‘open’ surfaces in the design that can carry users'' own meaning-making processes, how to combine modalities to create for a ‘unity’ of expression, and the importance of mirroring user experience in familiar ways that touch upon their everyday social and corporeal experiences.But a more important lesson gained from deploying the systems is how emotion processes are co-constructed and experienced inseparable from all other aspects of everyday life. Emotion processes are part of our social ways of being in the world; they dye our dreams, hopes and bodily experiences of the world. If we aim to design for affective interaction experiences, we need to place them into this larger picture.     

The Effect of Framing and Normative Messages in Building Support for Climate Policies

Deep cuts in greenhouse gas emissions are required to mitigate climate change. However, there is low willingness amongst the public to prioritise climate policies for reducing emissions. Here we show that the extent to which Australians are prepared to reduce their country''s CO₂ emissions is greater when the costs to future national income are framed as a “foregone-gain”—incomes rise in the future but not by as much as in the absence of emission cuts—rather than as a “loss”—incomes decrease relative to the baseline expected future levels (Studies 1 & 2). The provision of a normative message identifying Australia as one of the world''s largest CO₂ emitters did not increase the amount by which individuals were prepared to reduce emissions (Study 1), whereas a normative message revealing the emission policy preferences of other Australians did (Study 2). The results suggest that framing the costs of reducing emissions as a smaller increase in future income and communicating normative information about others'' emission policy preferences are effective methods for leveraging public support for emission cuts.     

Adaptive molecular networks controlling chemotactic migration: dynamic inputs and selection of the network architecture

Eukaryotic signalling networks underlying the cell''s ability to sense the gradient of chemotactic cues frequently have the dual property of perfect adaptation to spatially homogeneous inputs, and persistent activation by inputs that are spatially graded. This property is also shared by bacterial chemotaxis networks, raising the question of whether these two types of chemotactic processes also have similar organization of the underlying biomolecular processes. Interestingly, perfect adaptation can only be achieved robustly by a handful of mechanisms, and while eukaryotic chemotactic networks appear to rely on one of these—the incoherent feed-forward loop, bacterial chemotaxis depends on another—the negative feedback loop. In this review, we discuss how this conclusion can be reached even if the details of the molecular networks are incompletely understood. Furthermore, we argue that the use of distinct network architectures is not accidental and may be a consequence of the nature of the signalling inputs and the limitations of the sensory properties of different cell types.     

Experimental evidence that extra-pair mating drives asymmetrical introgression of a sexual trait

Theory suggests that traits under positive selection may introgress asymmetrically across a hybrid zone, potentially driven by sexual selection. Two subspecies of the red-backed fairy-wren (Malurus melanocephalus) differ primarily in a sexual signal used in mate choice—red versus orange male back plumage colour—but phylogeographic analyses suggest asymmetrical introgression of red plumage into the genetic background of the orange subspecies. We hypothesized that this asymmetrical introgression may be facilitated by sexual selection if red males have a mating advantage over orange males. We tested this hypothesis with correlational data and a plumage manipulation experiment where we reddened the back plumage of a subset of orange males to mimic males of the red subspecies. There was no correlational evidence of a mating advantage to naturally redder males in this population. Experimentally reddened males sired a similar amount of within-pair young and lost paternity at the same rate as orange males, but they sired significantly more extra-pair young, leading to substantially higher total reproductive success. Thus, we conclude that sexual selection via extra-pair mating is a likely mechanism responsible for the asymmetrical introgression of plumage colour in this system, and is potentially driven by a sensory bias for the red plumage signal.     

Mammalian development does not recapitulate suspected key transformations in the evolutionary detachment of the mammalian middle ear

The ectotympanic, malleus and incus of the developing mammalian middle ear (ME) are initially attached to the dentary via Meckel''s cartilage, betraying their origins from the primary jaw joint of land vertebrates. This recapitulation has prompted mostly unquantified suggestions that several suspected—but similarly unquantified—key evolutionary transformations leading to the mammalian ME are recapitulated in development, through negative allometry and posterior/medial displacement of ME bones relative to the jaw joint. Here we show, using µCT reconstructions, that neither allometric nor topological change is quantifiable in the pre-detachment ME development of six marsupials and two monotremes. Also, differential ME positioning in the two monotreme species is not recapitulated. This challenges the developmental prerequisites of widely cited evolutionary scenarios of definitive mammalian middle ear (DMME) evolution, highlighting the requirement for further fossil evidence to test these hypotheses. Possible association between rear molar eruption, full ME ossification and ME detachment in marsupials suggests functional divergence between dentary and ME as a trigger for developmental, and possibly also evolutionary, ME detachment. The stable positioning of the dentary and ME supports suggestions that a ‘partial mammalian middle ear’ as found in many mammaliaforms—probably with a cartilaginous Meckel''s cartilage—represents the only developmentally plausible evolutionary DMME precursor.     

Broad supernatural punishment but not moralizing high gods precede the evolution of political complexity in Austronesia

Supernatural belief presents an explanatory challenge to evolutionary theorists—it is both costly and prevalent. One influential functional explanation claims that the imagined threat of supernatural punishment can suppress selfishness and enhance cooperation. Specifically, morally concerned supreme deities or ‘moralizing high gods'' have been argued to reduce free-riding in large social groups, enabling believers to build the kind of complex societies that define modern humanity. Previous cross-cultural studies claiming to support the MHG hypothesis rely on correlational analyses only and do not correct for the statistical non-independence of sampled cultures. Here we use a Bayesian phylogenetic approach with a sample of 96 Austronesian cultures to test the MHG hypothesis as well as an alternative supernatural punishment hypothesis that allows punishment by a broad range of moralizing agents. We find evidence that broad supernatural punishment drives political complexity, whereas MHGs follow political complexity. We suggest that the concept of MHGs diffused as part of a suite of traits arising from cultural exchange between complex societies. Our results show the power of phylogenetic methods to address long-standing debates about the origins and functions of religion in human society.     

Cell Lineages and the Logic of Proliferative Control

It is widely accepted that the growth and regeneration of tissues and organs is tightly controlled. Although experimental studies are beginning to reveal molecular mechanisms underlying such control, there is still very little known about the control strategies themselves. Here, we consider how secreted negative feedback factors (“chalones”) may be used to control the output of multistage cell lineages, as exemplified by the actions of GDF11 and activin in a self-renewing neural tissue, the mammalian olfactory epithelium (OE). We begin by specifying performance objectives—what, precisely, is being controlled, and to what degree—and go on to calculate how well different types of feedback configurations, feedback sensitivities, and tissue architectures achieve control. Ultimately, we show that many features of the OE—the number of feedback loops, the cellular processes targeted by feedback, even the location of progenitor cells within the tissue—fit with expectations for the best possible control. In so doing, we also show that certain distinctions that are commonly drawn among cells and molecules—such as whether a cell is a stem cell or transit-amplifying cell, or whether a molecule is a growth inhibitor or stimulator—may be the consequences of control, and not a reflection of intrinsic differences in cellular or molecular character.     

Constraints and variation in food web link-species space

Predicting food web structure in future climates is a pressing goal of ecology. These predictions may be impossible without a solid understanding of the factors that structure current food webs. The most fundamental aspect of food web structure—the relationship between the number of links and species—is still poorly understood. Some species interactions may be physically or physiologically ‘forbidden''—like consumption by non-consumer species—with possible consequences for food web structure. We show that accounting for these ‘forbidden interactions'' constrains the feasible link-species space, in tight agreement with empirical data. Rather than following one particular scaling relationship, food webs are distributed throughout this space according to shared biotic and abiotic features. Our study provides new insights into the long-standing question of which factors determine this fundamental aspect of food web structure.     

The Social Explanatory Styles Questionnaire: Assessing Moderators of Basic Social-Cognitive Phenomena Including Spontaneous Trait Inference,the Fundamental Attribution Error,and Moral Blame

Why is he poor? Why is she failing academically? Why is he so generous? Why is she so conscientious? Answers to such everyday questions—social explanations—have powerful effects on relationships at the interpersonal and societal levels. How do people select an explanation in particular cases? We suggest that, often, explanations are selected based on the individual''s pre-existing general theories of social causality. More specifically, we suggest that over time individuals develop general beliefs regarding the causes of social events. We refer to these beliefs as social explanatory styles. Our goal in the present article is to offer and validate a measure of individual differences in social explanatory styles. Accordingly, we offer the Social Explanatory Styles Questionnaire (SESQ), which measures three independent dimensions of social explanatory style: Dispositionism, historicism, and controllability. Studies 1–3 examine basic psychometric properties of the SESQ and provide positive evidence regarding internal consistency, factor structure, and both convergent and divergent validity. Studies 4–6 examine predictive validity for each subscale: Does each explanatory dimension moderate an important phenomenon of social cognition? Results suggest that they do. In Study 4, we show that SESQ dispositionism moderates the tendency to make spontaneous trait inferences. In Study 5, we show that SESQ historicism moderates the tendency to commit the Fundamental Attribution Error. Finally, in Study 6 we show that SESQ controllability predicts polarization of moral blame judgments: Heightened blaming toward controllable stigmas (assimilation), and attenuated blaming toward uncontrollable stigmas (contrast). Decades of research suggest that explanatory style regarding the self is a powerful predictor of self-functioning. We think it is likely that social explanatory styles—perhaps comprising interactive combinations of the basic dimensions tapped by the SESQ—will be similarly potent predictors of social functioning. We hope the SESQ will be a useful tool for exploring that possibility.     

Multiple modes of selection can influence the role of phenotypic plasticity in species' invasions: Evidence from a manipulative field experiment

In exploring the roles of phenotypic plasticity in the establishment and early evolution of invading species, little empirical attention has been given to the importance of correlational selection acting upon suites of functionally related plastic traits in nature. We illustrate how this lack of attention has limited our ability to evaluate plasticity''s role during invasion and also, the costs and benefits of plasticity. We addressed these issues by transplanting clones of European‐derived Plantago lanceolata L. genotypes into two temporally variable habitats in the species'' introduced range in North America. Phenotypic selection analyses were performed for each habitat to estimate linear, quadratic, and correlational selection on phenotypic trait values and plasticities in the reproductive traits: flowering onset and spike and scape lengths. Also, we measured pairwise genetic correlations for our “colonists.” Results showed that (a) correlational selection acted on trait plasticity after transplantation, (b) selection favored certain combinations of genetically correlated and uncorrelated trait values and plasticities, and (c) using signed, instead of absolute, values of plasticity in analyses facilitated the detection of correlational selection on trait value‐plasticity combinations and their adaptive value. Based on our results, we urge future studies on species invasions to (a) measure correlational selection and (b) retain signed values of plasticity in order to better discriminate between adaptive and maladaptive plasticity.     

Spermatophore consumption in a cephalopod

An individual''s gametes can represent a nourishing food source for a manipulative mate. Here, we provide evidence of ejaculate and sperm consumption in a cephalopod. Through labelling male spermatophores with ¹⁴C radiolabel, we found that female squid, Sepiadarium austrinum, consumed the spermatophores of their partners and directed the nutrients received into both somatic maintenance and egg production. We further show that in this species—where fertilization occurs externally in the female''s buccal cavity—sperm storage is short-term (less than 21 days). The combination of female spermatophore consumption and short-term external sperm storage has the potential to exert strong selection on male ejaculates and reproductive strategies.     

Reconciling competing mechanisms posited to underlie auditory verbal hallucinations

Perception is not the passive registration of incoming sensory data. Rather, it involves some analysis by synthesis, based on past experiences and context. One adaptive consequence of this arrangement is imagination—the ability to richly simulate sensory experiences, interrogate and manipulate those simulations, in service of action and decision making. In this paper, we will discuss one possible cost of this adaptation, namely hallucinations—perceptions without sensory stimulation, which characterize serious mental illnesses like schizophrenia, but which also occur in neurological illnesses, and—crucially for the present piece—are common also in the non-treatment-seeking population. We will draw upon a framework for imagination that distinguishes voluntary from non-voluntary experiences and explore the extent to which the varieties and features of hallucinations map onto this distinction, with a focus on auditory-verbal hallucinations (AVHs)—colloquially, hearing voices. We will propose that sense of agency for the act of imagining is key to meaningfully dissecting different forms and features of AVHs, and we will outline the neural, cognitive and phenomenological sequelae of this sense. We will conclude that a compelling unifying framework for action, perception and belief—predictive processing—can incorporate observations regarding sense of agency, imagination and hallucination.This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.     

The Weight of a Guilty Conscience: Subjective Body Weight as an Embodiment of Guilt

Guilt is an important social and moral emotion. In addition to feeling unpleasant, guilt is metaphorically described as a “weight on one''s conscience.” Evidence from the field of embodied cognition suggests that abstract metaphors may be grounded in bodily experiences, but no prior research has examined the embodiment of guilt. Across four studies we examine whether i) unethical acts increase subjective experiences of weight, ii) feelings of guilt explain this effect, and iii) whether there are consequences of the weight of guilt. Studies 1–3 demonstrated that unethical acts led to more subjective body weight compared to control conditions. Studies 2 and 3 indicated that heightened feelings of guilt mediated the effect, whereas other negative emotions did not. Study 4 demonstrated a perceptual consequence. Specifically, an induction of guilt affected the perceived effort necessary to complete tasks that were physical in nature, compared to minimally physical tasks.     

Estimation of Parameters in the Two-Compartment Model for Exhaled Nitric Oxide

The fractional concentration of exhaled nitric oxide (FeNO) is a biomarker of airway inflammation that is being increasingly considered in clinical, occupational, and epidemiological applications ranging from asthma management to the detection of air pollution health effects. FeNO depends strongly on exhalation flow rate. This dependency has allowed for the development of mathematical models whose parameters quantify airway and alveolar compartment contributions to FeNO. Numerous methods have been proposed to estimate these parameters using FeNO measured at multiple flow rates. These methods—which allow for non-invasive assessment of localized airway inflammation—have the potential to provide important insights on inflammatory mechanisms. However, different estimation methods produce different results and a serious barrier to progress in this field is the lack of a single recommended method. With the goal of resolving this methodological problem, we have developed a unifying framework in which to present a comprehensive set of existing and novel statistical methods for estimating parameters in the simple two-compartment model. We compared statistical properties of the estimators in simulation studies and investigated model fit and parameter estimate sensitivity across methods using data from 1507 schoolchildren from the Southern California Children''s Health Study, one of the largest multiple flow FeNO studies to date. We recommend a novel nonlinear least squares model with natural log transformation on both sides that produced estimators with good properties, satisfied model assumptions, and fit the Children''s Health Study data well.     

Social network- and community-level influences on contraceptive use: evidence from rural Poland

The diffusion of ‘modern’ contraceptives—as a proxy for the spread of low-fertility norms—has long interested researchers wishing to understand global fertility decline. A fundamental question is how local cultural norms and other people''s behaviour influence the probability of contraceptive use, independent of women''s socioeconomic and life-history characteristics. However, few studies have combined data at individual, social network and community levels to simultaneously capture multiple levels of influence. Fewer still have tested if the same predictors matter for different contraceptive types. Here, we use new data from 22 high-fertility communities in Poland to compare predictors of the use of (i) any contraceptives—a proxy for the decision to control fertility—with those of (ii) ‘artificial’ contraceptives—a subset of more culturally taboo methods. We find that the contraceptive behaviour of friends and family is more influential than are women''s own characteristics and that community level characteristics additionally influence contraceptive use. Highly educated neighbours accelerate women''s contraceptive use overall, but not their artificial method use. Highly religious neighbours slow women''s artificial method use, but not their contraceptive use overall. Our results highlight different dimensions of sociocultural influence on contraceptive diffusion and suggest that these may be more influential than are individual characteristics. A comparative multilevel framework is needed to understand these dynamics.