Apoptosis‐inducing factor (AIF) is expelled from mitochondria after some apoptotic stimuli and translocates to the nucleus, which may contribute to DNA and nuclear fragmentation in some non‐physiological mammalian cell deaths. Conversely, the requirement for mitochondrial AIF in oxidative phosphorylation and energy generation provides a plausible explanation for the embryonic lethality or neurodegeneration that has been found in different AIF‐deficient mouse models. These findings may help illuminate the ability of mitochondrial AIF to suppress cytoplasmic stress granule formation and to promote the (...) tumorigenic growth of cancer cells. AIF is ideally located in the mitochondrion to perform a vital normal function in energy production. Once it translocates to the nucleus, however, the cell might die either of energy failure or nuclear fragmentation (or both). We propose that the main function of AIF is to support energy production in both normal and transformed cell physiology, whereas nuclear‐translocated AIF might contribute to stress‐induced or pathological cell death in certain scenarios. BioEssays 28: 834–843, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Many nuclear proteins have been found recently to interact with short conserved sequences which are involved in regulating the transcription of various genes. Nuclear transcription factors may be arbitrarily subdivided into two groups, ubiquitous and tissue‐specific. The transcription of one gene is usually regulated by several factors which interact with different sequences located either in the promoter region of the gene or outside it. The appearance or disappearance of transcription factors for some genes corresponds to certain phases of cell differentiation (...) or dedifferentiation and even to individual stages of the cell cycle. (shrink)

BackgroundThe U.S. Food and Drug Administration traditionally has kept confidential significant amounts of information relevant to the approval or non-approval of specific drugs, devices, and biologics and about the regulatory status of such medical products in FDA’s pipeline.ObjectiveTo develop practical recommendations for FDA to improve its transparency to the public that FDA could implement by rulemaking or other regulatory processes without further congressional authorization. These recommendations would build on the work of FDA’s Transparency Task Force in 2010.MethodsIn 2016-2017, we convened (...) a team of academic faculty from Harvard Medical School, Brigham and Women’s Hospital, Yale Medical School, Yale Law School, and Johns Hopkins Bloomberg School of Public Health to develop recommendations through an iterative process of reviewing FDA’s practices, considering the legal and policy constraints on FDA in expanding transparency, and obtaining insights from independent observers of FDA.ResultsThe team developed 18 specific recommendations for improving FDA’s transparency to the public. FDA could adopt all these recommendations without further congressional action.FundingThe development of the Blueprint for Transparency at the U.S. Food and Drug Administration was funded by the Laura and John Arnold Foundation. (shrink)

‘Alexander, it is said, starting from Amphipolis and keeping on his left the city Philippi and the mountain Orbelus, invaded Thrace, that part occupied by the so-called self-governing Thracians. He crossed the river Nestus, and in ten days, they say, he reached the mountain Haemus.’.

‘Alexander, it is said, starting from Amphipolis and keeping on his left the city Philippi and the mountain Orbelus, invaded Thrace, that part occupied by the so-called self-governing Thracians. He crossed the river Nestus, and in ten days, they say, he reached the mountain Haemus.’.

Arrian was better qualified to understand the nature and significance of ‘the pursuit’ in Macedonian warfare than any modern scholar. He had himself fought and commanded in a very similar kind of warfare, and he was keenly interested in the study of military tactics. He was also better informed about the pursuits which Alexander had conducted, because he was able to use the accounts of Alexander's contemporaries, Ptolemy and Aristobulus. Anyone today who wishes to question the veracity of (...) Arrian's reports of these pursuits cannot do so of his own experience. He should therefore turn to comparable pursuits of recent times which have been reported accurately beyond any shadow of doubt. (shrink)

Arrian was better qualified to understand the nature and significance of ‘the pursuit’ in Macedonian warfare than any modern scholar. He had himself fought and commanded in a very similar kind of warfare, and he was keenly interested in the study of military tactics. He was also better informed about the pursuits which Alexander had conducted, because he was able to use the accounts of Alexander's contemporaries, Ptolemy and Aristobulus. Anyone today who wishes to question the veracity of (...) Arrian's reports of these pursuits cannot do so of his own experience. He should therefore turn to comparable pursuits of recent times which have been reported accurately beyond any shadow of doubt. (shrink)

Two recently published inscriptions afford new insights into this subject. They were published separately and independently within a year or two of one another. Much is now to be gained by considering them together. The first inscription, found at Philippi in 1936, published by C. Vatin in Proc. 8th Epigr. Conf. , 259–70, and published with a fuller commentary by L. Missitzis in The Ancient World 12 , 3–14, records the decision by Alexander the Great on the use of (...) lands given by his father, Philip II, and in some cases confirmed by himself. The second inscription, found at the site of ancient Kalindoia in 1982, was published with exemplary speed and an excellent commentary by I. P. Vokotopoulou in Ancient Macedonia 4 , 87–114. It records the names of the priests of Asclepius on a stele dedicated to Apollo; and in the preamble it mentions the name of Alexander, being Alexander the Great. Philippi and Kalindoia were both within the limits of the kingdom of Philip and Alexander. (shrink)

Despite promising early work into the role of immune cells such as eosinophils in adipose tissue (AT) homeostasis, recent findings revealed that elevating the number of eosinophils in AT alone is insufficient for improving metabolic impairments in obese mice. Eosinophils are primarily recognized for their role in allergic immunity and defence against parasitic worms. They have also been detected in AT and appear to contribute to adipose homeostasis and drive energy expenditure, but the underlying mechanisms remain elusive. It has long (...) been recognized that immune cells such as macrophages respond to external signals to regulate adipose homeostasis and energy balance, however, less is known about the relevance of eosinophil activity in AT. As the authors propose in this review, given recent debate over the relative importance of their tissue‐specific abundance, the stage is now set for exploring the functionality and activation states of AT eosinophils. (shrink)

It was a characteristic of Macedonian custom that a name was used in a special and in a general sense. For example, ‘Foot-Companions’ was the name of a Bodyguard of Philip and also of the men of the Phalanx-Brigades from Lower Macedonia, and ‘Hypaspists’ was the name of Infantry-Guardsmen of Alexander and also of the men of three Hypaspist Phalanx-Brigades. Geographical names were repeated: there were at least two regions and two cities called ‘Emathia’, two or three regions called (...) ‘Doberus’, four cites called Philippi or Philippopolis, and Alexandrias galore. To a modern mind this makes for confusion. That is certainly the case with the names ‘Macedonia’ and ‘Macedones’, which I shall treat separately in this article. (shrink)

The authors conducted a baseline survey of baccalaureate and graduate degree health humanities programs in the United States and Canada. The object of the survey was to formally assess the current state of the field, to gauge what kind of resources individual programs are receiving, and to assess their self-identified needs to become or remain programmatically sustainable, including their views on the potential benefits of program accreditation. A 56-question baseline survey was sent to 111 institutions with baccalaureate programs and 20 (...) institutions with graduate programs. Respondents were asked about three areas: (1) program administration (managing unit, paid director, faculty lines, paid staff, funding sources); (2) educational program (curricular structure, CIP code usage, completion rates); and (3) views on accreditation for the field. A clear majority of respondents agreed that some form of accreditation or consultation service could address resource and sustainability issues. Overall, the survey responses to staffing, curricular structure, and support suggest the need for developing a sustainable infrastructure for health humanities. (shrink)

Presents a plethora of approaches to developing human potential in areas not conventionally addressed. Organized in two parts, this international collection of essays provides viable educational alternatives to those currently holding sway in an era of high-stakes accountability.

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

The article discusses the issue of the nature of analytic philosophy. It is shown that in the 1920s–1940s it was a certain philosophical school, whose representatives were united by some initial principles. Analytic philosophers saw the main task of philosophy in the analysis of the language of natural sciences, in establishing logical connections between scientific propositions, in the empirical substantiation of scientific theories and in the elimination of speculative concepts and proposals from the language of science. The tool for such (...) analysis was the mathematical logic created at the beginning of the 20th century by G. Frege, A.N. Whitehead, B. Russell. Another characteristic feature of the analytic tradition was a negative attitude toward philosophical speculation. Adherents of this tradition believed that philosophy does not provide knowledge about the world, therefore, it is not a science. Analytic philosophers have made a significant contribution to the methodology of scientific knowledge, offering an accurate description of the hypothetical-deductive structure of scientific theory, methods of scientific explanation and prediction, verification, confirmation and refutation of scientific statements. In the late 1930s, most of the analytic philosophers emigrated to England and the United States. The analytic movement is gradually losing its integrity and loses the features of a philosophical school. There is a rejection of mathematical logic as the main means of analysis, the connection with the natural sciences has been lost. In the second half of the 20th century, analytic philosophy from a specific philosophical school turns into a certain style of thinking of the philosophers of various philosophical research areas and orientations. (shrink)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

Perceptual learning involves an improvement in perceptual judgment with practice, which is often specific to stimulus or task factors. Perceptual learning has been shown on a range of visual tasks but very little research has explored chromatic perceptual learning. Here, we use two low level perceptual threshold tasks and a supra-threshold target detection task to assess chromatic perceptual learning and category effects. Experiment 1 investigates whether chromatic thresholds reduce as a result of training and at what level of analysis learning (...) effects occur. Experiment 2 explores the effect of category training on chromatic thresholds, whether training of this nature is category specific and whether it can induce categorical responding. Experiment 3 investigates the effect of category training on a higher level, lateralized target detection task, previously found to be sensitive to category effects. The findings indicate that performance on a perceptual threshold task improves following training but improvements do not transfer across retinal location or hue. Therefore, chromatic perceptual learning is category specific and can occur at relatively early stages of visual analysis. Additionally, category training does not induce category effects on a low level perceptual threshold task, as indicated by comparable discrimination thresholds at the newly learned hue boundary and adjacent test points. However, category training does induce category effects on a supra-threshold target detection task. Whilst chromatic perceptual learning is possible, learnt category effects appear to be a product of left hemisphere processing, and may require the input of higher level linguistic coding processes in order to manifest. (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)

The dorsal anterior cingulate cortex is a key node in the human salience network. It has been ascribed motor, pain-processing and affective functions. However, the dynamics of information flow in this complex region and how it responds to inputs remain unclear and are difficult to study using non-invasive electrophysiology. The area is targeted by neurosurgery to treat neuropathic pain. During deep brain stimulation surgery, we recorded local field potentials from this region in humans during a decision-making task requiring motor output. (...) We investigated the spatial and temporal distribution of information flow within the dACC. We demonstrate the existence of a distributed network within the anterior cingulate cortex where discrete nodes demonstrate directed communication following inputs. We show that this network anticipates and responds to the valence of feedback to actions. We further show that these network dynamics adapt following learning. Our results provide evidence for the integration of learning and the response to feedback in a key cognitive region. (shrink)

Hackles have been raised in biosemiotic circles by T. L. Short’s assertion that semiosis, as defined by Peirce, entails “acting for purposes” and therefore is not found below the level of the organism (2007a:174–177). This paper examines Short’s teleology and theory of purposeful behavior and offers a remedy to the disagreement. Remediation becomes possible when the issue is reframed in the terms of the complexity sciences, which allows intentionality to be understood as the interplay between local and global aspects of (...) a system within a system. What is called “acting for purposes” is not itself a type of behavior so much as a relationship between a dynamic system that “exists for a purpose” and its microprocesses that “serve purposes.” The “intentional object” of philosophy is recast here as the holistic self-organized dynamics of a system, which exists for the purpose of self-maintenance, and that constrains the parts’ behaviors, which serve the purpose of forming the system. (A “system” can be any emergent, e.g. an abiotic form, an adapted species, a self, a conditioned response, thought, or a set of ideas.) The self-organized whole, which is represented to the parts in their own constrained behaviors, assumes the guiding function so long attributed to the mysterious “intentional object.” If emergent self-causation is not disallowed, creative originality, as well as directionality, becomes part of the definition of purposeful behavior. Thus, key tools used here, required for understanding emergence, come from poetics rather than semoitics. In the microprocesses of self-organization, I find what I call “accidental” indices and icons — which are poetic in the sense that they involve mere metonymic contiguity and metaphoric similarity — and which are preferentially selected under constrained conditions allowing radically new connections to habituate into an “intentional” self-organized system that, not coincidentally, has some of the emergent characteristics of a conventional symbolic system. (shrink)

TABLE OF CONTENTS Introduction: Pragmatists in Venice Alexander Kremer... 5 I. Philosophy and human evolution Persons as Natural Artifacts Joseph Margolis... 8 II. Cultural politics and democracy Is Marx a Pragmatist? Tom Rockmore... 24 The waxing and waning of democracy as a way of life : Some of the economic underpinnings Jane Skinner... 33 Redefining the Meaning of 'Morality': A Chapter in the Cultural Politics of Capitalism Kenneth W. Stikkers... 42 Imperial Irony: Rorty, Richard Henry Pratt and the American (...) Indian Genocide Scott L Pratt... 48 Bruno Latour, American Pragmatism, and the Idea of Non-Human Democracy Leszek Koczanowicz... 59 Beyond culturalism: A Deweyan reading of the expansion of 'Ndrangheta Matteo Santarelli... 66 Philosophy as Cultural Politics in Rorty, Shusterman, And Pragmatism Alexander Kremer... 79 III. Food, Semiotics, Society John Dewey: A Culinary Perspective Dorota Koczanowicz... 88 De-Subjectification in Semiotics: Argumentations, Self-Defense and Signs of Opposing Forces Martin Svantner... 95 IV. Book Reviews Democracy and Consensus: Review Essay of Leszek Koczanowicz's POLITICS OF DIALOGUE John Ryder... 111 Pragmatism Hotel. R. Calcaterra, G. Maddalena & G. Marchetti : lL PRAGMATISMO. DALLE ORIGINI AGLI SVILUPPI CONTEMPORANEl Brunella Antomarini... 117. (shrink)