A role for SUMO modification in transcriptional repression and activation

Since the discovery of the SUMO (small ubiquitin-like modifier) family of proteins just over a decade ago, a plethora of substrates have been uncovered including many regulators of transcription. Conjugation of SUMO to target proteins has generally been considered as a repressive modification. However, there are now a growing number of examples where sumoylation has been shown to activate transcription. Here we discuss whether there is something intrinsically repressive about sumoylation, or if the outcome of this modification in the context of transcription will prove to be largely substrate-dependent. We highlight some of the technical challenges that will be faced by attempting to answer this question

Why 'scaffolding' is the wrong metaphor : the cognitive usefulness of mathematical representations.

The metaphor of scaffolding has become current in discussions of the cognitive help we get from artefacts, environmental affordances and each other. Consideration of mathematical tools and representations indicates that in these cases at least (and plausibly for others), scaffolding is the wrong picture, because scaffolding in good order is immobile, temporary and crude. Mathematical representations can be manipulated, are not temporary structures to aid development, and are refined. Reflection on examples from elementary algebra indicates that Menary is on the right track with his ‘enculturation’ view of mathematical cognition. Moreover, these examples allow us to elaborate his remarks on the uniqueness of mathematical representations and their role in the emergence of new thoughts.Peer reviewe

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

Empathy, engagement, entrainment: the interaction dynamics of aesthetic experience

A recent version of the view that aesthetic experience is based in empathy as inner imitation explains aesthetic experience as the automatic simulation of actions, emotions, and bodily sensations depicted in an artwork by motor neurons in the brain. Criticizing the simulation theory for committing to an erroneous concept of empathy and failing to distinguish regular from aesthetic experiences of art, I advance an alternative, dynamic approach and claim that aesthetic experience is enacted and skillful, based in the recognition of others’ experiences as distinct from one’s own. In combining insights from mainly psychology, phenomenology, and cognitive science, the dynamic approach aims to explain the emergence of aesthetic experience in terms of the reciprocal interaction between viewer and artwork. I argue that aesthetic experience emerges by participatory sense-making and revolves around movement as a means for creating meaning. While entrainment merely plays a preparatory part in this, aesthetic engagement constitutes the phenomenological side of coupling to an artwork and provides the context for exploration, and eventually for moving, seeing, and feeling with art. I submit that aesthetic experience emerges from bodily and emotional engagement with works of art via the complementary processes of the perception–action and motion–emotion loops. The former involves the embodied visual exploration of an artwork in physical space, and progressively structures and organizes visual experience by way of perceptual feedback from body movements made in response to the artwork. The latter concerns the movement qualities and shapes of implicit and explicit bodily responses to an artwork that cue emotion and thereby modulate over-all affect and attitude. The two processes cause the viewer to bodily and emotionally move with and be moved by individual works of art, and consequently to recognize another psychological orientation than her own, which explains how art can cause feelings of insight or awe and disclose aspects of life that are unfamiliar or novel to the viewer

Diagnostic Algorithm for Joint Pain in Patients with Inflammatory Bowel Disorders

Aim. An algorithm development for joint pain differential diagnosis in patients with inflammatory bowel disorders (IBD) and its validation in clinical practice.Materials and methods. A total of 349 IBD patients hospitalised for gastroenterological complaints at the Chelyabinsk Regional Clinical Hospital during 2017–2020 have been examined.Results. Upon survey, 97 (27.8%) IBD patients complained of joint pain. Ulcerative colitis (UC) predominated (79 patients; 81.4%), Crohn’s disease (CD) had a 18.6% incidence. In survey, 27% UC and 32.1% CD patients reported joint pain (p = 0.26). Among IBD patients, 52.6% had mechanical, and 47.4% — inflammatory pain. The inflammatory back pain (IBP) rate in survey cohort was 23.7%. Use of a diagnostic algorithm allowed concomitant rheumatic disease detection in 7 (7.2%) patients from the IBD–joint pain cohort: 2 patients were diagnosed with psoriatic spondyloarthritis, 2 — rheumatoid arthritis, 1 — gout and 2 — with ankylosing spondylitis. IBD-associated arthritis was diagnosed in 41 (42.3%) cases, osteoarthritis — in 38 (39.2%) IBD patients with joint pain, arthralgia with no objective inflammation, impaired joint function or lesions in X-ray and/or ultrasound — in 13 (13.4%) patients.Conclusion. Joint pain complaints are common in IBD patients and require a multispecialty rheumatologists-involving approach to proceed with differential diagnosis and opting for treatment tactics. A clinically verified algorithm coupled with laboratory tests and instrumental imaging facilitates diagnosis and optimal therapy selection in IBD patients with complaints of joint pain

The cognitive integration of scientific instruments: Information, situated cognition, and scientific practice

Researchers in the biological and biomedical sciences, particularly those working in laboratories, use a variety of artifacts to help them perform their cognitive tasks. This paper analyses the relationship between researchers and cognitive artifacts in terms of integration. It first distinguishes different categories of cognitive artifacts used in biological practice on the basis of their informational properties. This results in a novel classification of scientific instruments, conducive to an analysis of the cognitive interactions between researchers and artifacts. It then uses a multidimensional framework in line with complementarity-based extended and distributed cognition theory to conceptualize how deeply instruments in different informational categories are integrated into the cognitive systems of their users. The paper concludes that the degree of integration depends on various factors, including the amount of informational malleability, the intensity and kind of information flow between agent and artifact, the trustworthiness of the information, the procedural and informational transparency, and the degree of individualisation

The effects of nonconcurrent and concurrent relaxation training on cardiovascular reactivity to a psychological stressor

Eight patients in a cardiac rehabilitation program, after exposure to two psychological stressors approximately equivalent with respect to cardiovascular reactivity, were given nonconcurrent progressive muscle relaxation training and retested for reactivity. They were then provided with relaxation training concurrently with one of the stressors and exposed again to the two stressors. No significant effects for nonconcurrent progressive muscle relaxation training were detected. Concurrent training, in contrast, produced reductions in both systolic and diastolic blood pressure. Reductions resulting from training on the target stressor showed little tendency to generalize to the nontarget stressor; the discrimination was particularly well defined for systolic blood pressure. We conclude that muscle relaxation techniques are maximally effective in reducing reactivity to psychological stressors when relaxation training is provided concurrently with the stressor. Our findings further suggest that to inculcate the relaxation response reliably across different situations, specific training to enhance generalization may be needed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44813/1/10865_2004_Article_BF00844731.pd

Spatially resolved submm imaging of the HR 8799 debris disk

Dynamical interactions between planets and debris disks may sculpt the disk structure and impact planetary orbits, but only a few systems with both imaged planets and spatially resolved debris disks are known. With the Caltech Submm Observatory (CSO), we have observed the HR 8799 debris disk at 350{\mu}m. The 350{\mu}m map is the first spatially resolved measurement of the debris disk encircling the HR 8799 planetary system at this wavelength. Both the flux and size of the emission are consistent with a Kuiper belt of dust extending from ~100-300 AU. Although the resolution of the current map is limited, the map shows an indication of offset asymmetric emission, and several scenarios for this possibility are explored with radiative transfer calculations of a star-disk system and N-body numerical simulations of planet-disk interactions with parameters representative of the HR 8799 system.Comment: 5 pages, 4 figures, Accepted for publication in Astronomy and Astrophysic

Angular momentum exchange during secular migration of two-planet systems

We investigate the secular dynamics of two-planet coplanar systems evolving under mutual gravitational interactions and dissipative forces. We consider two mechanisms responsible for the planetary migration: star-planet (or planet-satellite) tidal interactions and interactions of a planet with a gaseous disc. We show that each migration mechanism is characterized by a specific law of orbital angular momentum exchange. Calculating stationary solutions of the conservative secular problem and taking into account the orbital angular momentum leakage, we trace the evolutionary routes followed by the planet pairs during the migration process. This procedure allows us to recover the dynamical history of two-planet systems and constrain parameters of the involved physical processes.Comment: 20 pages, 9 figures, accepted for publication in Celestial Mechanics and Dynamical Astronomy (special issue on Exoplanets

Aspirin use and survival after the diagnosis of breast cancer:a population-based cohort study

Background: Aspirin use has been associated with a reduced cancer incidence and fewer deaths from cancer. This study examined whether women with breast cancer prescribed aspirin postdiagnosis had improved survival.Methods:An observational, population cohort study was undertaken using data linkage of cancer registry, dispensed prescriptions and death records in Tayside, Scotland. All community prescriptions for aspirin in women with breast cancer were extracted and use postdiagnosis for each individual examined using Cox's proportional hazard models. The main outcome measures were all-cause mortality and breast cancer-specific mortality.Results:Four thousand six hundred and twenty-seven patients diagnosed with breast cancer between 1 January 1998 and 31 December 2008 were followed up until 28 February 2010. Median age at diagnosis was 62 (IQR 52-74). One thousand eight hundred and two (39%) deaths were recorded, with 815 (18%) attributed to breast cancer. One thousand and thirty-five (22%) patients were prescribed aspirin postdiagnosis. Such aspirin use was associated with lower risk of all-cause mortality (HR=0.53, 95% CI=0.45-0.63, P<0.001) and breast cancer-specific mortality (HR=0.42, 95% CI=0.31-0.55, P<0.001) after adjusting for age, socioeconomic status, TNM stage, tumour grade, oestrogen receptor status, surgery, radiotherapy, chemotherapy, adjuvant endocrine therapy and aspirin use prediagnosis. Conclusions:Aspirin use postdiagnosis of breast cancer may reduce both all-cause and breast cancer-specific mortality. Further investigation seeking a causal relationship and which subgroups of patients benefit most await ongoing randomised controlled trials.Publisher PDFPeer reviewe