Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and rapidly transported into the organelle by a complex machinery. The data gathered in recent years suggest that this machinery operates through a syringe-like mechanism, in which the shuttling receptor PEX5 − the “plunger” − pushes a newly synthesized protein all the way through a peroxisomal transmembrane protein complex − the “barrel” − into the matrix of the organelle. Notably, insertion of cargo-loaded receptor into the “barrel” is an ATP-independent process, whereas extraction (...) of the receptor back into the cytosol requires its monoubiquitination and the action of ATP-dependent mechanoenzymes. Here, we review the main data behind this model. The peroxin PEX5 is the peroxisomal matrix protein receptor. It shuttles between the cytosol and the organelle membrane, where it gets inserted into the docking/translocation module, thus pushing the cargo-protein into the peroxisome lumen. Resetting the system involves PEX5 monoubiquitination and its extraction from the membrane by the AAA-ATPases, PEX1/PEX6. (shrink)

Prominent tuberculosis (TB) actors are invoking solidarity to motivate and justify collective action to address TB, including through intensified development and implementation (D&I) of technologies such as drugs and diagnostics. We characterize the ethical challenges associated with D&I of new TB technologies by drawing on stakeholder perspectives from 23 key informant interviews and we articulate the ethical implications of solidarity for TB technology D&I. The fundamental ethical issue facing TB technological D&I is a failure within and beyond the TB community (...) to stand in solidarity with persons with TB in addressing the complex sociopolitical contexts of technological D&I. The failure in solidarity relates to two further ethical challenges raised by respondents: skewed power dynamics that hinder D&I and uncertainties around weighing risks and benefits associated with new technologies. Respondents identified advocacy and participatory research practices as necessary to address such challenges and to motivate sustained collective action to accelerate toward TB elimination. We present the first empirical examination of bioethical accounts of solidarity in public and global health. Our study suggests that solidarity allows us better to understand and address the ethical challenges that arrest the D&I of new TB technologies. Solidarity lends credence to policies and practices that address the relational nature of illness and health through collective action. (shrink)

ABSTRACTHow do we perceive voices coming from different spatial locations, and how is this affected by emotion? The current study probed the interplay between space and emotion during voice percept...

Este artículo presenta una descripción fonético-fonológica del criollo haitiano hablado por hablantes nativos de esta lengua residentes en la Provincia de Concepción. Para la elicitación de los datos se utilizó una lista léxica de 133 ítems y, en algunas ocasiones, un set de imágenes _ad hoc_. La muestra estuvo constituida por seis colaboradores (cuatro de sexo masculino y dos de sexo femenino). El marco de referencia teórico-metodológico es el (neo)distribucionalismo, utilizado habitualmente en la descripción de vernáculos en Chile. Algunas conclusiones (...) prominentes de este artículo son las siguientes: la abertura y nasalización tienen estatus fonémico en algunas vocales (/e, o/, versus / ɛ, ɔ /; /a, e, o/ versus /ã, ẽ, õ/), existe una alta alofonía en algunas consonantes (por ejemplo, en los fonemas /p, t, k/), hay una oposición fonológica entre consonante fricativas sordas y fricativas sonoras (/f/ versus /v/, /s/ versus /z/ y / ʃ / versus / ʒ /), y no hay realizaciones aproximantes de los fonemas oclusivos sonoros. (shrink)

ObjectiveTo identify the ethical challenges associated with the development and implementation of new tuberculosis drugs and diagnostics.MethodsTwenty-three semi-structured qualitative interviews conducted between December 2015 and September 2016 with programme administrators, healthcare workers, advocates, policymakers, and funders based in the Americas, Europe, and Africa. Interviews were analysed using thematic analysis.ResultsDivergent interests and responsibilities, coupled with power imbalances, are a primary source of ethical challenges; the uncertain risk profiles of new drugs present an additional one. Although this challenge can be partially mitigated (...) through stringent pharmacovigilance, respondents highlighted that high-burden countries tend to lack the resources to facilitate safe implementation. Increased advocacy and community engagement are considered an ethical imperative for future TB development and implementation.ConclusionsThis project helps identify some of the ethical challenges of new TB technologies. It demonstrates that investigating ethical challenges through qualitative research is one way to apprehend the difficulty of implementing new TB technologies. Addressing this difficulty will require that those in positions of power reconsider their interests in relation to disempowered communities.Policy implicationsEfforts to build consensus regarding what values should underpin the global governance of TB research, prevention, and care are essential to facilitate the ethical implementation of new TB technologies. (shrink)

Psychological interest in Meritocracy as an important social norm regulating most of the western democratic societies has significantly increased over the years. However, the way Meritocracy has been conceptualized and operationalized in experimental studies has advanced in significant ways. As a result, a variety of paradigms arose to understand the social consequences of Meritocracy for intergroup relations; in particular, to understand the adverse consequences of Meritocracy for disadvantaged group members. The present research seeks to understand whether there is strong support (...) for the idea that (manipulated) Meritocracy disproportionally affects members of low status groups, and also to understand which specific components of this norm have been successfully manipulated and to what consequences. And this is particularly important given the recent call for greater transparency in how the success of experimental manipulations is reported. Thus, we carried out a systematic review examining the content of different prime tasks, summarizing prime manipulation checks’ effectiveness, and analyzing whether priming Meritocracy leads to less favorable orientations toward low status groups. Results across 33 studies revealed that despite the existing differences in the components highlighted, the salience of any of the Meritocracy dimensions facilitates the use of internal causal attributions, negative evaluations and stereotyping towards low status groups, affecting negatively decisions involving low-status group members, particularly in specific domains, as organizational contexts. These results carry both practical and theoretical implications for future research on the role of Meritocracy in intergroup settings. (shrink)

Famous Brazilian educational and social theorist Paulo Freire presents his ideas on community solidarity in moving toward social justice in schools and society in a set of talks and interviews shortly before his death, supplemented with ...

Voices are a complex and rich acoustic signal processed in an extensive cortical brain network. Specialized regions within this network support voice perception and production and may be differentially affected in pathological voice processing. For example, the experience of hallucinating voices has been linked to hyperactivity in temporal and extra-temporal voice areas, possibly extending into regions associated with vocalization. Predominant self-monitoring hypotheses ascribe a primary role of voice production regions to auditory verbal hallucinations. Alternative postulations view a generalized perceptual salience (...) bias as causal to AVH. These theories are not mutually exclusive as both ascribe the emergence and phenomenology of AVH to unbalanced top-down and bottom-up signal processing. The focus of the current study was to investigate the neurocognitive mechanisms underlying predisposition brain states for emergent hallucinations, detached from the effects of inner speech. Using the temporal voice area localizer task, we explored putative hypersalient responses to passively presented sounds in relation to hallucination proneness. Furthermore, to avoid confounds commonly found in in clinical samples, we employed the Launay-Slade Hallucination Scale for the quantification of HP levels in healthy people across an experiential continuum spanning the general population. We report increased activation in the right posterior superior temporal gyrus during the perception of voice features that positively correlates with increased HP scores. In line with prior results, we propose that this right-lateralized pSTG activation might indicate early hypersensitivity to acoustic features coding speaker identity that extends beyond own voice production to perception in healthy participants prone to experience AVH. (shrink)

There is widespread interest in the possibility that music training enhances nonmusical abilities. This possibility has been examined primarily for speech perception and domain-general abilities su...

Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23, selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type mice at the (...) same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated. (shrink)

The amygdala is a key brain area regulating responses to stress and emotional stimuli, so improving our understanding of how it is regulated could offer novel strategies for treating disturbances in emotion regulation. As we review here, a growing body of evidence indicates that the gut microbiota may contribute to a range of amygdala-dependent brain functions from pain sensitivity to social behavior, emotion regulation, and therefore, psychiatric health. In addition, it appears that the microbiota is necessary for normal development of (...) the amygdala at both the structural and functional levels. While further investigations are needed to elucidate the exact mechanisms of microbiota-to-amygdala communication, ultimately, this work raises the intriguing possibility that the gut microbiota may become a viable treatment target in disorders associated with amygdala dysregulation, including visceral pain, post-traumatic stress disorder, and beyond. Also see the video abstract here: https://youtu.be/O5gvxVJjX18 The amygdala plays a central role in regulating many aspects of behavior in rodents and humans, from pain responding to social interaction and psychiatric function. Accumulating evidence suggests microbiota-to-amygdala communication along the gut-brain axis is a key modulator of these amygdala-dependent behaviors, with critical implications for health and disease. (shrink)

This book highlights some of the most pressing safety, ethical, legal and societal issues related to the diverse contexts in which robotic technologies apply. Focusing on the essential concept of well-being, it addresses topics that are fundamental not only for research, but also for industry and end-users, discussing the challenges in a wide variety of applications, including domestic robots, autonomous manufacturing, personal care robots and drones.

Background: Coronavirus disease 2019 has resulted in an increase in known risk factors for mental health problems. Mexico adopted lockdown and physical distancing as a containment strategy with potential consequences on day to day life, such as social isolation, loss of income and loneliness that can have important consequences in terms of mental health.Objective: We aimed to examine the effect of the initial phases of the COVID-19 pandemic on psychological distress, well-being and perceived physical health among Mexican-base respondents and to (...) examine whether coping strategies would play a potential intermediating role in relation to these variables. Under the Existential Positive Psychology perspective, an emphasis was made on meaning-centered coping.Methods: A cross-sectional study was conducted between April 30 and June 16th 2020 among 604 Mexicans-base respondents of which 471 were women and 132 men. Data was collected by using online questionnaires. Psychological distress was measured using the Depression, Anxiety, and Stress Scale. The Brief COPE Inventory was used to assess problem-focused and emotion-focused coping strategies. We also used the Meaning-Centered Coping Scale. PERMA-Profiler was used to assess well-being, perceived physical health, and loneliness. Profiler and Descriptive analyses and bivariate linear regression were performed to examine the association of variables.Results: 45.9% of the participants reported moderate to extremely severe psychological distress. Our results demonstrate that problem-focused and emotion-focused coping were positively related to psychological distress, whereas meaning-centered coping was negatively associated with distress. Furthermore, psychological distress played a potential negative role in the perceived physical health, while meaning-centered coping and well-being buffered the negative influence of psychological distress on perceived physical health (completely standardized indirect effect = –0.01, SE: 0.012, 95% CI [−0.065; −0.017].Conclusion: Meaning-centered coping was found to suppress the negative influence of psychological distress on sensation of decreased physical health corroborating the critical role of meaning in life in promoting well-being. Future studies can further examine the value of the critical role of meaning in life in promoting well-being as a protective factor against severe distress during traumatic events. Findings of this study can be used to orient policies and interventions aimed to alleviate suffering in the midst of the COVID-19 pandemic. (shrink)

Purpose: Studies of reactive and proactive modes of inhibitory control tend to show age-related declines and are accompanied by abnormalities in the prefrontal cortex. We explored which mode of inhibitory control would be more amenable to change and accrue greater benefits following engagement in a 4-week theater acting intervention in older adults. These gains were evaluated by performance on the AX-CPT task. We hypothesized that an increase in proactive control would relate to an increase in AY errors and a decrease (...) in BX errors. In contrast, an increase in reactive control would be associated with a decrease in AY errors, no change in AY reaction time, and an increase in BX response time. Further, we posited that an increase in behavioral proactive control would accompany greater cue versus probe activity for previously identified regions in the prefrontal cortex. In contrast, an increase in behavioral reactive control would be accompanied by greater probe activation in these identified brain areas.Materials and Methods: The participants were 179 community-dwelling adults aged 60–89 years who were on average, college-educated. Participants were pseudo-randomly assigned to either an active-experiencing acting intervention condition or the active control condition ; participant assignment was subject to time of enrollment. Participants in both groups were trained by theater-actor researchers with expertise in acting interventions. In contrast to the active control participants who attended a course on theater acting, the acting-intervention group was required to consistently deploy proactive and reactive control mechanisms. Both groups met two times/week for 75-min for 4 weeks. Participant brain-behavioral performance on the AX-CPT task was evaluated prior to and after this four-week period.Results: No intervention effects were found in favor of proactive control. Behavioral evidence in favor of reactive control was weak. Brain-related benefits to reactive control was illustrated by greater probe-activation in Brodmann areas 6 and 8, relative to controls and pre-intervention.Conclusion: We found some evidence for improvements in reactive control via brain measures, attributed to engagement in the acting intervention. (shrink)

How can we feel at home in this world without clinging to false certainties? This book offers a humanist re-reading of philosophical pragmatism and explores its potentials for a worldview that relies only on human resources. Thinking along with authors like William James and F.C.S. Schiller, it highlights a fundamentally humanist strand of pragmatism aimed at fostering human creativity and transformative action. It is grounded in everyday experience and underlines our responsibility to strive for the better. Ana Honnacker traces perspectives (...) on science, religion, and ethics in the light of a pragmatic understanding of humanism. Furthermore, she suggests how to address the existential challenges we face today. Thus, pragmatic humanism is explored not only as a philosophy for critical minds, but also as a way of life. (shrink)

Research involving transgender and gender diverse people (TGD) increased in the last years, mostly concerning healthcare associated to this population. Few studies dedicated their analysis to the impact of parental support on transgender people, even though this is an important aspect in creating a safe environment on which these individuals can build their identity. In addition, the link between family support, TGD identity and homelessness is not completely established. Thus, due to the specificities of the family context of TGD individuals, (...) the aim of this study is to investigate the association between family support and TGD in different moments of the process of gender affirmation. In addition, this study also aims to explore the relationship between a lack of social support and low self-esteem, home abandonment, and dwelling in the street. The survey was designed based on the TransPULSE project and was made available in electronic format. The sample was constituted of 423 TGD residents in two Brazilian states. A Structural Equation Model analysis suggested that the impact of gender affirmation status on homelessness was mediated by parental support, through self-esteem, and the need to move from home. The association between the status of the gender affirmation procedures, family support and self-esteem was significant and indicated that the further TGD individuals advanced in gender affirmation, the more self-esteem and family support they would have. The association between family support and self-esteem indicated that family support was associated with higher self-esteem. Low family support was associated with the willingness to move from home due to one’s TGD status and there was also a significant correlation between low self-esteem and the willingness to move from home due to one’s TGD status. Finally, homelessness was associated with the willingness to move with a large effect size. Limitations include the sample that was constituted by individuals with Internet access and who had more contact with TGD communities. The findings indicate directions for interventions involving TGD people and their families, considering the parental relationship as a critical variable to improve TGD quality of life in the process of gender affirmation. (shrink)

Humanism is charged with fostering a harmful anthropocentrism that has led to the exploitation of non-human beings and the environment. Posthumanist and transhumanist ideas prominently aim at rethinking our self-understanding and human-nature relations. Yet these approaches turn out to be flawed when it comes to addressing the challenges of the “age of the humanity”, the Anthropocene. Whereas posthumanism fails in acknowledging the exceptional role of human beings with regard to political agency and responsibility, transhumanism overemphasizes human capabilities of controlling nature (...) and only deepens the human-nature dualism. Therefore, a critical and humble version of humanism is suggested as a viable alternative. Drawing on pragmatist thinkers William James and F.C.S. Schiller, a resource for de-centering the human being is provided that critically reflects our role in the larger ecosystem and underlines human potentials as well as human responsibilities. (shrink)

This w ork ana l yses the response that the Spanish State as a Nation-State, is g i ving to int e g ration of the immi g rant as citizen. Contra r y to those w ho consider that residence has to be the access w a y to citizenship in the f ace of the crisis of the Nation-State and the ge o g raphical mobility that the global econ o m y imposes on people, here the political (...) rel e v ance of nationality is defende d , as an und i vided ind i vidual share of belonging to the constituent p ow er in a harmonious relation with the fl e xi b le concept of residence. This research is d i vided into f i v e sections, in w hich nationality and the constituent p ow e r , the w a ys of access to Spanish nationali t y , the conflict of Nation or State, the characteristics of original nationality and f inal l y , the criteria used b y States to select the potential immi g rant. Th e critical ana l ysis of the Spanish l e gislation on nationality and citizenship t o gether with the theoretical debates, h a v e ena b led us to conclude with a proposal of l e g e fe r enda focussed on a radical refo r m of the concept of nationali t y. (shrink)

Philosophical pragmatism takes human experience as the touchstone of any theorizing. Authors like William James and F.C.S. Schiller suggested to transform philosophy into a critical and emancipatory project, turning the quest for truth into a project of creative and responsible world-making. Their basic insight that man is the measure of all things demands for being actively engaged in building a better world. As pragmatism denies objective criteria for critique, listening to a plurality of voices and their experiences becomes crucial. This (...) chapter offers a humanist re-reading of philosophical pragmatism and explores its challenges and prospects. With pointing out problematic assumptions in the work of James and Schiller, the unfinished agenda of their pragmatic humanism becomes visible. (shrink)

A partir del conocido pasaje del Vom Ich de F.W.J. Schelling el texto propone una lectura del conocido como “resto irreductible” para dar cuenta del terror y de sus mecanismos de control. Se propone, en crítica a lo que Žižek hace con Hegel, una lectura lacaniana de Schelling que muestra, hasta qué punto, el “Hegel” presentado por Žižek no solo es un Hegel pasado por Lacan, sino también por Schelling.

Issues of institutional identity and integrity in Roman Catholic health care institutions have been addressed at the level of individual institutions as well as by organizations of Catholic health care providers and at various levels in the Church hierarchy. The papers by Carol Taylor, C.S.F.N, Thomas Shannon, Kevin O’Rourke, O.P., Gerard Magill in this volume provide a significant contribution to concerns of Roman Catholic health care institutions as they face the challenges of providing health care in a secular, pluralistic, market-driven (...) economy. One way to understand institutional integrity is as a measure of the coherence between what an institution identifies as its commitments (its stated moral character), what an institution does (its manifest moral character) and an institution’s fundamental moral commitments (its deep moral character). The essays in this volume support this model of integrity. Although it is not their explicit focus, the four essays together provide a vision of institutional integrity for Catholic health care institutions. Each author focuses on one of the three central aspects of integrity: what one identifies as one’s commitments (Taylor), how one's actions reflect one’s values (Shannon and Magill), and what one is or what one values at a deep level (O’Rourke). I will offer a brief overview of the ways in which the integrity of Catholic health care institutions has been addressed. Then I will consider the four essays and show how each offers an analysis of one of the three critical elements of integrity. (shrink)

Esta investigación presenta los fonemas segmentales y realizaciones alofónicas del mapudungun hablado en Los Álamos, VIII Región del Biobío. Es un estudio de carácter descriptivo, realizado de acuerdo con el formato estándar del descriptivismo norteamericano. Los datos fueron entregados por seis adultos hablantes de las localidades rurales de Pangue y Sara de Lebu. Los instrumentos utilizados fueron dos listas léxicas ad hoc. Luego de presentar el inventario de fonemas y alófonos, este artículo se focaliza en los segmentos de estatus controversial (...) [t̟]/[n̟]/[l̟], [ʃ]/[tʃ], [ɣ], [v]/[f] y [ð]/[θ]. Los principales resultados obtenidos incluyen la ausencia de estatus fonémico de [n̟] y [l̟]; el estatus fonémico de [t̟], [ʃ] y [ɣ]; la tendencia a realizar con sonoridad los segmentos fricativos labiodental e interdental ; y la ocurrencia de algunos segmentos que podrían ser atribuidos de manera plausible a la influencia de la fonología segmental del español. (shrink)

El artículo trata de analizar las repercusiones que tiene nuestro tiempo de “sociedad del espectáculo” en la construcción de realidades históricas. Para ello se analizarán las propuestas de S. Zizek y de J. Baudrillard en torno a lo Real, la realidad y el simulacro, empleando algunos planteamientos de la filosofía de F.W.J. Schelling, mostrando así la relevancia de la filosofía schellinguiana para entender para entender esta construcción.

The article brings up an analysis of the notion of the Real and the notion of Reality in contemporary thought in order to show the influence and relevance of the concept of “Grund” and “Remainder” by Schelling in ŽiŽek. The paper proposes from Schelling´s perspective a reading of something “which does not exist, [but] continues to insist” that explains the conformation of Real and reality and reality and simulacrum.

The highly sophisticated techniques of modern engineering are normally conceived of in practical terms. Corresponding to the instrumental function of technology, they are designed to direct the forces of nature according to human purposes. Yet, as soon as the realm of mere skills is exceeded, the intended useful results can only be achieved through planned and preconceived action processes involving the deliberately considered application of well designed tools and devices. This is to say that in all complex cases theoretical reasoning (...) becomes an indispensable means to accomplish the pragmatic technological aims. Hence the abstracting from the actual concrete function of technology opens the way to concentrate attention on the general conceptual framework involved. If this approach is adopted the relevant knowledge and the procedures applied clearly exhibit a logic of their own. This point of view leads to a methodological and even an epistemological analysis of the theoretical structure and the specific methods of procedure characteristic of modern technology. Investigations of this kind, that can be described as belonging to an ana lytical philosophy of technology, form the topic of this anthology. The type of research in question here is closely akin to that of the philosophy of science. But it is an astonishing fact that the commonly accepted and carefully investigated philosophy of science has not yet found its counterpart in an established philosophy of technology. (shrink)