Calcium storage is one of the functions commonly attributed to the endoplasmic reticulum (ER) in non‐muscle cells. Several recent studies have added support to this concept. Analysis of reticuloplasm, the luminal ER content, has shown that it contains several proteins (reticuloplasmins) which are prospective calcium storage proteins. One of these, calreticulin, is also present in the sarcoplasmic reticulum (SR). In sea urchin eggs, a calsequestrin‐like protein has been clearly localised to the ER. The recent demonstration that the IP3 receptor, which (...) has similarities with the calcium release channel in the SR is also localised in the ER membrane suggests that calcium stored in the ER is important for intracellular signalling. The alternative view, that the physiologically important calcium store is a specialised organelle, the calciosome, is not supported by these observations. Recent evidence also suggests that ER calcium might be important in ER structure and in the retention of the luminal ER proteins. (shrink)

Transcription factor (TF) signaling regulates gene transcription and requires a complex network of proteins. This network includes co‐activators, co‐repressors, multiple TFs, histone‐modifying complexes, and the basal transcription machinery. It has been widely appreciated that pioneer factors, such as FoxA1 and GATA1, play an important role in opening closed chromatin regions, thereby allowing binding of a secondary factor. In this review we will focus on a newly proposed model wherein multiple TFs, such as steroid receptors (SRs), can function in a pioneering (...) role. This model, termed dynamic assisted loading, integrates data from widely divergent methodologies, including genome wide ChIP‐Seq, digital genomic footprinting, DHS‐Seq, live cell protein dynamics, and biochemical studies of ATP‐dependent remodeling complexes, to present a real time view of TF chromatin interactions. Under this view, many TFs can act as initiating factors for chromatin landscape programming. Furthermore, enhancer and promoter states are more accurately described as energy‐dependent, non‐equilibrium steady states. (shrink)

There have been recent concerns about an “epidemic of loneliness” during the pandemic, given the pervasiveness of loneliness in the population and its harmful effects on health and well-being. Therefore, it is important to establish the correlates of loneliness. The purpose of the current study was to explore how loneliness relates to a construct termed mattering, which is the feeling of being important to other people. Mattering was assessed with multiple measures in the current study (e.g., mattering in general, fears (...) of not mattering, and mattering to peers). A sample of 172 female psychology undergraduate students aged 18–25 years completed self-report measures of general mattering, mattering to peers, anti-mattering, fear of not mattering, and state and trait loneliness. As predicted, lower levels of both general mattering and mattering to peers were associated with higher state loneliness. Higher feelings of anti-mattering (feelings of being invisible and insignificant to others) and fears of not mattering were associated with greater trait loneliness, as well as a reduced sense of mattering to friends. The findings illustrate that feeling as though one does not matter to others (i.e., feeling insignificant and unimportant) is associated with increased state and trait loneliness among young women. Implications are discussed for loneliness theory and how these results can enhance both clinical understanding and practice. (shrink)

A special issue of_ New German Critique_ The posthumous publication of Theodor W. Adorno’s works on music continues to reveal the special relationship between music and philosophy in his thinking. These important works have not, however, received as much scholarly attention as they deserve. Contributors to this issue seek to provide insight into some of the key themes raised in these works, including the sociology of musical genre, the historical transformation of music from the "heroic" or high-bourgeois era to late (...) modernity, the meaning of both performance and listening in the era of mass communication, and the specific challenges or deformations of the radio on musical form, a theme that implicates many of the digital practices of our own age. There is much left to discover in these new publications, and they pose again, with renewed vigor, the question of Adorno’s _Aktualität_—his polyvalent, untranslatable term for, among other things, the intellectual relationship between the present and the past. Contributors Daniel K. L. Chua, Lydia Goehr, Peter E. Gordon, Martin Jay, Brian Kane, Max Paddison, Alexander Rehding, Fred Rush, Martin Scherzinger. (shrink)

In this article we review the emerging literature on the self-transcendent emotions. We discuss how the self-transcendent emotions differ from other positive emotions and outline the defining features of this category. We then provide an analysis of three specific self-transcendent emotions—compassion, gratitude, and awe—detailing what has been learned about their expressive behavior, physiology, and likely evolutionary origins. We propose that these emotions emerged to help humans solve unique problems related to caretaking, cooperation, and group coordination in social interactions. In our (...) final section we offer predictions about the self-transcendent emotions that can guide future research. (shrink)

Human clinical research has become a huge economic enterprise (Morin et al. 2002; Noah 2002). Because the human subject at the center can be so easily marginalized, many commentators recommend spec...

For forty years, successive editions of Ethical Theory and Business have helped to define the field of business ethics. The 10th edition reflects the current, multidisciplinary nature of the field by explicitly embracing a variety of perspectives on business ethics, including philosophy, management, and legal studies. Chapters integrate theoretical readings, case studies, and summaries of key legal cases to guide students to a rich understanding of business ethics, corporate responsibility, and sustainability. The 10th edition has been entirely updated, ensuring that (...) students are exposed to key ethical questions in the current business environment. New chapters cover the ethics of IT, ethical markets, and ethical management and leadership. Coverage includes climate change, sustainability, international business ethics, sexual harassment, diversity, and LGBTQ discrimination. New case studies draw students directly into recent business ethics controversies, such as sexual harassment at Fox News, consumer fraud at Wells Fargo, and business practices at Uber. (shrink)

We introduce and discuss a concept of approximation of a topological algebraic system A by finite algebraic systems from a given class K. If A is discrete, this concept agrees with the familiar notion of a local embedding of A in a class K of algebraic systems. One characterization of this concept states that A is locally embedded in K iff it is a subsystem of an ultraproduct of systems from K. In this paper we obtain a similar characterization of (...) approximability of a locally compact system A by systems from K using the language of nonstandard analysis. In the signature of A we introduce positive bounded formulas and their approximations; these are similar to those introduced by Henson [14] for Banach space structures (see also [15, 16]). We prove that a positive bounded formula φ holds in A if and only if all precise enough approximations of φ hold in all precise enough approximations of A. We also prove that a locally compact field cannot be approximated arbitrarily closely by finite (associative) rings (even if the rings are allowed to be non-commutative). Finite approximations of the field R can be considered as possible computer systems for real arithmetic. Thus, our results show that there do not exist arbitrarily accurate computer arithmetics for the reals that are associative rings. (shrink)

How does creolization fare as a social-scientific concept? While Jane Gordon seeks to underscore the potential such a concept might have in the social sciences and philosophy, her discussants Gopal Guru, Kipton E. Jensen, Mickaella Perina, and Sundar Sarukkai draw attention to descriptive and normative issues that need to be addressed before arguments formulating and enacting creolization processes can be brought into domains of life from which they have been historically excluded.

Darwinian Evolution and Classical Liberalism brings together a collection of new essays that examine the multifaceted ferment between Darwinian biology and classical liberalism.

This article argues that we could improve the design of research protocols by developing an awareness of and a responsiveness to the social contexts of all the actors in the research enterprise, including subjects, investigators, sponsors, and members of the community in which the research will be conducted. “Social context” refers to the settings in which the actors are situated, including, but not limited to, their social, economic, political, cultural, and technological features. The utility of thinking about social contexts is (...) introduced and exemplified by the presentation of a hypothetical case in which one central issue is limitation of the probability of injury to subjects by selection of individuals who are not expected to live long enough for the known risks of the study to become manifest as harms. Benefits of such considerations may include enhanced subject satisfaction and cooperation, community acceptance, and improved data quality, among other desirable consequences. (shrink)

How should pragmatists respond to and contribute to the resolution of one of America's greatest and most enduring problems? Given that the most important thinkers of the pragmatist movement—Charles S. Peirce, William James, John Dewey, and George Herbert Mead—said little about the problem of race, how does their distinctly American way of thinking confront the hardship and brutality that characterizes the experience of many African Americans in this country? In 12 thoughtful and provocative essays, contemporary American pragmatists connect ideas with (...) action and theory with practice to come to terms with this seemingly intractable problem. Exploring themes such as racism and social change, the value of the concept of race, the role of education in ameliorating racism, and the place of democracy in dealing with the tragedy of race, the voices gathered in this volume consider how pragmatism can focus new attention on the problem of race. Contributors are Michael Eldridge, Eddie S. Glaude, Jr., Judith M. Green, D. Micah Hester, Donald F. Koch, Bill E. Lawson, David E. McClean, Gregory F. Pappas, Scott L. Pratt, Alfred E. Prettyman, John R. Shook, Paul C. Taylor, and Cornel West. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

This article argues that we could improve the design of research protocols by developing an awareness of and a responsiveness to the social contexts of all the actors in the research enterprise, including subjects, investigators, sponsors, and members of the community in which the research will be conducted. ?Social context? refers to the settings in which the actors are situated, including, but not limited to, their social, economic, political, cultural, and technological features. The utility of thinking about social contexts is (...) introduced and exemplified by the presentation of a hypothetical case in which one central issue is limitation of the probability of injury to subjects by selection of individuals who are not expected to live long enough for the known risks of the study to become manifest as harms. Benefits of such considerations may include enhanced subject satisfaction and cooperation, community acceptance, and improved data quality, among other desirable consequences. (shrink)

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5-6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor (...) evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation. (shrink)

Reading speed matters in most real-world contexts, and it is a robust and easy aspect of reading to measure. Theories of reading should account for speed.

Background and AimsEnd-of-life discussions can be difficult for seriously ill adolescents and young adults. Researchers aimed to determine whether completing Voicing My CHOiCES —a research-informed advance care planning guide—increased communication with family, friends, or health care providers, and to evaluate the experience of those with whom VMC was shared.MethodsFamily, friends, or HCPs who the AYAs had shared their completed VMC with were administered structured interviews to assess their perception of the ACP discussion, changes in their relationship, conversation quality, and whether (...) the discussion prompted changes in care. Open-ended responses underwent thematic analysis.ResultsOne-month post-completion, 65.1% of AYA had shared VMC completion with a family member, 22.6% with a friend, and 8.9% with an HCP. Among a sample of respondents, family and friends reported a positive change in their relationship with the AYA. Participant descriptions of the experience fell into five themes: positive experience, difficult experience, appreciated a guide to facilitate discussion, provided relief, and created worry/anxiety. Only 1 HCP noted a treatment change. Family, friends, and HCP did not think the AYA would have discussed EoL preferences without completing VMC.ConclusionsVMC has potential to enhance communication about ACP between AYA and their family and friends, though less frequently with HCPs. Participants reported a positive change in their relationship with the AYA after discussing VMC, and described experiencing the conversation as favorable, even when also emotionally difficult. (shrink)

Using a sample of 652 college students, we examined several implications of the hypothesis that the shape of the human penis evolved to enable males to substitute their semen for those of their rivals. The incidence of double mating by females appears sufficient to make semen displacement adaptive (e.g., one in four females acknowledge infidelity, one in eight admit having sex with two or more males in a 24-hour period, and one in 12 report involvement in one or more sexual (...) threesomes with two males). We also document several changes in post-ejaculatory behavior (e.g., reduced thrusting, penis withdrawal, loss of an erection) which may have evolved to minimize displacement of the male’s own semen. Consistent with predictions derived from a theoretical model (Gallup and Burch 2006), we discovered that most females report waiting at least 48 hours following an instance of infidelity before resuming sex with their in-pair partners. (shrink)

The co-occurrence of stress-induced posttraumatic stress disorder and obesity is common, particularly among military personnel but the link between these conditions is unclear. Individuals with comorbid PTSD and obesity manifest other physical and psychological problems, which significantly diminish their quality of life. Current understanding of the pathways connecting stress to PTSD and obesity is focused largely on behavioral mediators alone with little consideration of the biological regulatory mechanisms that underlie their co-occurrence. In this work, we leverage prior knowledge to systematically (...) highlight such bio-behavioral mechanisms and inform on the design of confirmatory pilot studies. We use natural language processing to extract documented regulatory interactions involved in the metabolic response to stress and its impact on obesity and PTSD from over 8 million peer-reviewed papers. The resulting network describes the propagation of stress to PTSD and obesity through 34 metabolic mediators using 302 documented regulatory interactions supported by over 10,000 citations. Stress jointly affected both conditions through 21 distinct pathways involving only two intermediate metabolic mediators out of a total of 76 available paths through this network. Moreover, oxytocin, Neuropeptide-Y, and cortisol supported an almost direct propagation of stress to PTSD and obesity with different net effects. Although stress upregulated both NPY and cortisol, the downstream effects of both markers are reported to relieve PTSD severity but exacerbate obesity. The stress-mediated release of oxytocin, however, was found to concurrently downregulate the severity of both conditions. These findings highlight how a network-informed approach that leverages prior knowledge might be used effectively in identifying key mediators like OXT though experimental verification of signal transmission dynamics through each path will be needed to determine the actual likelihood and extent of each marker’s participation. (shrink)

Apoptosis is now widely recognized as a common form of cell death and represents a mechanism of cell clearance in many physiological situations where deletion of cells is required. Peptide growth factors, initially characterised as stimulators of cell proliferation, have now been shown to inhibit death in many cell types. Deprivation of growth factors leads to the induction of apoptosis, i.e. condensation of chromatin and degradation in oligonucleosomesized fragments, formation of plasma and nuclear membrane blebs and cell fragmentation into apoptotic (...) bodies which can be taken up by neighbouring cells. Here we discuss the mechanism(;s) by which growth factors may inhibit apoptosis. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

L'opera di Primo Levi presenta un caso straordinariamente ricco e in qualche modo enigmatico di intertestualità. Con questo volume si è cercato di tracciare i lineamenti di una mappa immaginaria, uno schema degli innesti, intertesti e trapianti che collegano l'opera leviana ai libri altrui.

Squeezed between increasing entitlement expenditures and static or declining real revenues, state‐funded urban development is increasingly perceived as an unaffordable luxury. At the same time, the power and significance of the banking sector is giving way to new kinds of financial institutions that have little or no interest in community development. Not surprisingly, it is often argued that pension funds ought to be more sensitive to community needs. However, some analysts argue that pension funds are properly only the agents of (...) plan beneficiaries; any investment that took into account community needs would be, in effect, an unjustified tax on individuals’ future welfare. Furthermore, analysts are very doubtful about the integrity of public pension plan investment decision‐making. In this paper, I set out a morally informed justification of public pension plan investment in community development. In doing so, I develop a model of community development that stresses the reciprocal nature of the obligations embedded in the relationship between the community and pension plan beneficiaries. This approach also has significant implications for a wide variety of private sponsored plans. The paper begins with an assessment of pension fund decision‐making and the practices of the investment management industry, drawing upon related research on pension fund capitalism. It goes on to issues of social obligation, referencing recent research on the nature of social contracts. To give the analysis empirical relevance I refer to the much disputed decision of the West Virginia legislature to require their public pension funds’ Investment Management Board to invest in the state government's corrections authority. (shrink)

Un livre pour défaire le régime esthétique de l'image, en vue d'une nouvelle pensée diagrammatique, après Deleuze et Guattari, entre art et philosophie : un ouvrage introductif et spéculatif sans équivalent qui, partant de la rupture opérée par Matisse et Duchamp avec la phénoménologie picturale de l'image esthétique, constitue une archéologie de l'art contemporain qui passe par Daniel Buren, Gordon Matta-Clark, Günter Brus et le néoconcrétisme brésilien.

Prey-catching behavior (PCB) in frogs and toads has been the focus of intense neuroethological research from the mid-twentieth century to the present and epitomizes some major themes in science and philosophy during this period. It reflects the movement from simple reflexology to more complex views of instinctive behavior, but it also displays a neural reductionism that denies subjectivity and individual agency The present article engages contemporary PCB research but provides a philosophically more promising picture of it based on Whitehead's nonreductionist (...) "philosophy of organism," which proposes that the flow of events from stimulus to response in organisms of all kinds is mediated by "the intervening touch of mentality " This approach resolves some basic mind-body and mind-nature issues that have long bedeviled modern philosophy and presents an image of a postmodern frog for a constructively postmodern science. (shrink)

Perspectives on the difficult topic of the evolution of language can be differentiated to a large extent based on how much relevant continuity or discontinuity they see between humans and nonhuman animals. In general, biologists and psychologists tend to have a broad definition of “language” that highlights significant continuities, whereas linguists tend to define “language” more narrowly, in accord with their emphasis on the uniqueness of human capacities. This article examines the value of Whitehead's innovative theory of language, which is (...) grounded in his account of the fundamental symbolic element in basic perceptual processes, mainly for understanding the continuities between animal and human perceptual and symbolic activity but also for accommodating the discontinuity, or at least the pivotal difference, evident in the full flowering of human language. It will focus particularly on applying Whitehead's approach to gain a new understanding of the emergence, with the rise of amphibians, of the first vocalization in the history of life. (shrink)

Light can kill the photoreceptors of the eye, not only very bright direct sunlight, but more moderate illumination if the light is present continuously. Recent experiments show that rod apoptosis can be triggered by strong and constant activation of transduction, and that death can be prevented if transduction is inhibited even though the eye is illuminated. Vitamin A deficiency and genetically inherited diseases, such as some forms of retinitis pigmentosa and Leber congenital amaurosis, appear to kill like this: transduction is (...) activated at a high rate and continuously, and this causes the rods to die. Why does transduction kill? Our best guess is that continuous activation produces a prolonged lowering of the Ca2+ concentration, which is also thought to kill neurons in tissue culture and during the development of the nervous system. To prevent death in constant light, rods have evolved protective mechanisms including modulation of channels and ion transport to keep the Ca2+ from going too low. Prolonged light exposure also causes migration of transduction proteins from one part of the cell to another and a reversible shortening of the rod outer segments, the part of the cell that contains the pigment rhodopsin. All of these mechanisms are at work in the normal eye to reduce transduction and prevent the Ca2+ concentration from dropping too low for too long a time. That most of us retain our vision our entire lives is a testament to their effectiveness. BioEssays 28: 344–354, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

This work addresses corruption in politics and the public services, arguing that corrupt public officials should be exposed, prosecuted and gaoled, just like their colleagues in the private sector. It covers ethical standards in the public service, both state and federal; the practice of government; the relationships between officials; their advisors and the public; the interplay between politics and personal behaviour, and offering explanations as to what can be done about corruption in public service through asking questions like; how does (...) corruption gain a foothold in public affairs?; how can public trust be rebuilt between bureaucrats, the politicians and the people who vote for them?; and how can we improve accoutability over the cover-ups? (shrink)

'Origin of Species is a must read for Christians in our secularized, Darwin-saturated society. From a factual foundation, Charles Darwin persuasively extrapolates an erroneous explanation of life's diversity and complexity apart from God's handiwork, although there's a lot Darwin argues that his modern-day proponents ignore. Christians, using Scripture and science, should study this profoundly influential book thoroughly and cautiously'--from Dr. Wilson's guide. The Worldview Guides from the Canon Classics Literature Series provide an aesthetic and thematic Christian perspective on the most (...) definitive and daunting works of Western Literature. Each Worldview Guide presents the big picture (both the good and the bad) without neglecting the details. Each Worldview Guide is a friendly literary coach--and a treasure map, and a compass, and a key--to help teachers, parents, and students appreciate, critique, and begin to master the classics. (shrink)