Cytoplasmic chromatin triggers inflammation in senescence and cancer

Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders

The abolition of the General Teaching Council for England and the future of teacher discipline

With the abolition of the General Teaching Council for England in the 2011 Education Act, this article considers the future of teacher discipline in England. It provides a critique of the changes to the regulation of teacher misconduct and incompetence that draws on a Foucauldian framework, especially concerning the issue of public displays of discipline and the concomitant movement to more hidden forms. In addition, the external context of accountability that accompanies the reforms to teacher discipline are considered including the perfection of the panoptic metaphor presented by the changes to Ofsted practices such as the introduction of zero-notice inspections. The article concludes that the reforms will further move teachers from being occupational professionals to being organisational professionals marking them apart from comparable professions in medicine and law

Pancreas and islet cell transplantation

Currently, for the patient with type 1 diabetes, a definitive treatment without resorting to the use of exogenous insulin can be achieved only with pancreas or islet cell transplantation. These means of restoring β-cell mass can completely maintain essentially normal long-term glucose homeostasis, although the need for powerful immunosuppressive regimens limits their application to only a subgroup of adult patients. Apart from the shortage of donors that has limited all kinds of transplantation, however, the widespread use of β-cell replacement has been precluded until recently by the drawbacks associated with both organ and islet cell transplantation. Although the study of recurrence of diabetes has generated attention, the fundamental obstacle to pancreas and islet transplantation has been, and remains, the alloimmune response. With a better elucidation of the mechanisms of alloengraftment achieved during the last 3 years, the stage has been set for further advances

MANUSCRIPT IN PRESS: DEMENTIA & GERIATRIC COGNITIVE DISORDERS: Molecular Neuropsychology: Creation of Test-Specific Blood Biomarker Algorithms

Prior work on the link between blood-based biomarkers and cognitive status has largely been based on dichotomous classifications rather than detailed neuropsychological functioning. The current project was designed to create serum-based biomarker algorithms that predict neuropsychological test performance

Community Development for Adaptation

Council-community engagement for a climate-impacted future – research brief. Many of New Zealand’s urban settlements are likely to be impacted by climate-induced hazards such as coastal erosion, flooding and rising groundwater levels. Affected communities will face physical, social, financial and emotional challenges. To ensure successful adaptation, local authorities will need to adopt new approaches to engagement with communities that are exposed to these hazards. This summary forms part of the research findings of the Climate-Adaptive Communities project of the Deep South National Science Challenge. We have drawn from the stories and insights shared with the research team by community members, iwi members and council staff

Parasitism as a Driver of Trophic Niche Specialisation.

The population trophic niche of free-living species can be subdivided into smaller niches comprising individuals specialising on specific food items. The roles of parasites in creating these specialised subgroups remain unclear. Intrapopulation differences in parasite infections can develop from specialist individuals within populations. Their differences in morphology and habitat can increase their exposure to intermediate hosts via infected prey, altering their parasite fauna. However, we also suggest that parasite infections can drive this niche specialisation. Through mechanisms including parasite manipulation, altered host phenotypes, and/ or parasite-mediated competition, parasites can alter the resource availability of their hosts, altering their trophic niches. Thus, trophic niche specialisations could result from parasitism via varying influences on host traits, raising questions for future research

MICE: The muon ionization cooling experiment. Step I: First measurement of emittance with particle physics detectors

Copyright @ 2011 APSThe Muon Ionization Cooling Experiment (MICE) is a strategic R&D project intended to demonstrate the only practical solution to providing high brilliance beams necessary for a neutrino factory or muon collider. MICE is under development at the Rutherford Appleton Laboratory (RAL) in the United Kingdom. It comprises a dedicated beamline to generate a range of input muon emittances and momenta, with time-of-flight and Cherenkov detectors to ensure a pure muon beam. The emittance of the incoming beam will be measured in the upstream magnetic spectrometer with a scintillating fiber tracker. A cooling cell will then follow, alternating energy loss in Liquid Hydrogen (LH2) absorbers to RF cavity acceleration. A second spectrometer, identical to the first, and a second muon identification system will measure the outgoing emittance. In the 2010 run at RAL the muon beamline and most detectors were fully commissioned and a first measurement of the emittance of the muon beam with particle physics (time-of-flight) detectors was performed. The analysis of these data was recently completed and is discussed in this paper. Future steps for MICE, where beam emittance and emittance reduction (cooling) are to be measured with greater accuracy, are also presented.This work was supported by NSF grant PHY-0842798

Assessing the uncertainties of model estimates of primary productivity in the tropical Pacific Ocean

Author Posting. © Elsevier B.V., 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Journal of Marine Systems 76 (2009): 113-133, doi:10.1016/j.jmarsys.2008.05.010.Depth-integrated primary productivity (PP) estimates obtained from satellite ocean color based models (SatPPMs) and those generated from biogeochemical ocean general circulation models (BOGCMs) represent a key resource for biogeochemical and ecological studies at global as well as regional scales. Calibration and validation of these PP models are not straightforward, however, and comparative studies show large differences between model estimates. The goal of this paper is to compare PP estimates obtained from 30 different models (21 SatPPMs and 9 BOGCMs) to a tropical Pacific PP database consisting of ~1000 14C measurements spanning more than a decade (1983- 1996). Primary findings include: skill varied significantly between models, but performance was not a function of model complexity or type (i.e. SatPPM vs. BOGCM); nearly all models underestimated the observed variance of PP, specifically yielding too few low PP (< 0.2 gC m-2d-2) values; more than half of the total root-mean-squared model-data differences associated with the satellite-based PP models might be accounted for by uncertainties in the input variables and/or the PP data; and the tropical Pacific database captures a broad scale shift from low biomass-normalized productivity in the 1980s to higher biomass-normalized productivity in the 1990s, which was not successfully captured by any of the models. This latter result suggests that interdecadal and global changes will be a significant challenge for both SatPPMs and BOGCMs. Finally, average root-mean-squared differences between in situ PP data on the equator at 140°W and PP estimates from the satellite-based productivity models were 58% lower than analogous values computed in a previous PP model comparison six years ago. The success of these types of comparison exercises is illustrated by the continual modification and improvement of the participating models and the resulting increase in model skill.This research was supported by a grant from the National Aeronautics and Space Agency Ocean Biology and Biogeochemistry program (NNG06GA03G), as well as by numerous other grants to the various participating investigator

Structured Expert Consensus on Actinic Keratosis:Treatment Algorithm Focusing on Daylight PDT

BACKGROUND: A practical and up-to-date consensus among experts is paramount to further improve patient care in actinic keratosis (AK). OBJECTIVES: To develop a structured consensus statement on the diagnosis, classification, and practical management of AK based on up-to-date information. METHODS: A systematic review of AK clinical guidelines was conducted. This informed the preparation of a 3-round Delphi procedure followed by a consensus meeting, which combined the opinions of 16 clinical experts from 13 countries, to construct a structured consensus statement and a treatment algorithm positioning daylight photodynamic therapy (dl-PDT) among other AK treatment options. RESULTS: The systematic review found deficiencies in current guidelines with respect to new AK treatments such as ingenol mebutate and dl-PDT. The Delphi panel established consensus statements across definition, diagnosis, classification, and management of AK. While the diagnosis of AK essentially rests on the nature of lesions, treatment decisions are based on several clinical and nonclinical patient factors and diverse environmental attributes. Participants agreed on ranked treatment preferences for the management of AK and on classifying AK in 3 clinical situations: isolated AK lesions requiring lesion-directed treatment, multiple lesions within a small field, and multiple lesions within a large field, both requiring specific treatment approaches. Different AK treatment options were discussed for each clinical situation. CONCLUSIONS: The results provide practical recommendations for the treatment of AK, which are readily transferable to clinical practice, and incorporate the physician's clinical judgement. The structured consensus statement positioned dl-PDT as a valuable option for patients with multiple AKs in small or large fields