Evolution of Antarctic ozone in September-December predicted by CCMVal-2 model simulations for the 21st century

Chemistry-Climate Model Validation phase 2 (CCMVal-2) model simulations are used to analyze Antarctic ozone increases in 2000–2100 during local spring and early summer, both vertically integrated and at several pressure levels in the lower stratosphere. Multi-model median trends of monthly zonal mean total ozone column (TOC), ozone volume mixing ratio (VMR), wind speed and temperature poleward of 60° S are investigated. Median values are used to account for large variability in models, and the associated uncertainty is calculated using a bootstrapping technique. According to the trend derived from the twelve CCMVal-2 models selected, Antarctic TOC will not return to a 1965 baseline, an average of 1960–1969 values, by the end of the 21st century in September–November, but will return in ~2080 in December. The speed of December ozone depletion before 2000 was slower compared to spring months, and thus the decadal rate of December TOC increase after 2000 is also slower. Projected trends in December ozone VMR at 20–100 hPa show a much slower rate of ozone recovery, particularly at 50–70 hPa, than for spring months. Trends in temperature and winds at 20–150 hPa are also analyzed in order to attribute the projected slow increase of December ozone and to investigate future changes in the Antarctic atmosphere in general, including some aspects of the polar vortex breakup.J. M. Siddaway, S. V. Petelina, D. J. Karoly, A. R. Klekociuk, and R. J. Dargavill

Mitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis with v-ATPase and TORC1

Post-print (lokagerð höfundar)The v-ATPase is a fundamental eukaryotic enzyme that is central to cellular homeostasis. Although its impact on key metabolic regulators such as TORC1 is well documented, our knowledge of mechanisms that regulate v-ATPase activity is limited. Here, we report that the Drosophila transcription factor Mitf is a master regulator of this holoenzyme. Mitf directly controls transcription of all 15 v-ATPase components through M-box cis-sites and this coordinated regulation affects holoenzyme activity in vivo. In addition, through the v-ATPase, Mitf promotes the activity of TORC1, which in turn negatively regulates Mitf. We provide evidence that Mitf, v-ATPase and TORC1 form a negative regulatory loop that maintains each of these important metabolic regulators in relative balance. Interestingly, direct regulation of v-ATPase genes by human MITF also occurs in cells of the melanocytic lineage, showing mechanistic conservation in the regulation of the v-ATPase by MITF family proteins in fly and mammals. Collectively, this evidence points to an ancient module comprising Mitf, v-ATPase and TORC1 that serves as a dynamic modulator of metabolism for cellular homeostasis.This work was supported by the National Institutes of Health, National Eye Institute [grant number R01EY017097 to F.P.]; an RPB Unrestricted Grant and Lions District 20-Y1 award to the Dept. of Ophthalmology, SUNY-UMU (F.P.); the Icelandic Research Fund [grant numbers 130230-053 and 152715-051 to E.S.] a PHC Jules Verne 2014 grant [grant number 31891VM to E.S. and L.L.]; a grant from the Ligue Nationale Contre le Cancer (Equipe labellisee), INCa, Canceropole, Ile de France and Labex CelTisPhyBio [grant number ANR-11-LBX-0038 to L.L.]; and the Ludwig Institute for Cancer Research and the Harry J Lloyd Trust (to C.G.).Peer Reviewe

Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells

Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. To understand how MITF regulates transcription, we used tandem affinity purification and mass spectrometry to define a comprehensive MITF interactome identifying novel cofactors involved in transcription, DNA replication and repair, and chromatin organisation. We show that MITF interacts with a PBAF chromatin remodelling complex comprising BRG1 and CHD7. BRG1 is essential for melanoma cell proliferation in vitro and for normal melanocyte development in vivo. MITF and SOX10 actively recruit BRG1 to a set of MITF-associated regulatory elements (MAREs) at active enhancers. Combinations of MITF, SOX10, TFAP2A, and YY1 bind between two BRG1-occupied nucleosomes thus defining both a signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of the regulatory elements they occupy. BRG1 also regulates the dynamics of MITF genomic occupancy. MITF-BRG1 interplay thus plays an essential role in transcription regulation in melanoma

Fractional solubility of aerosol iron : synthesis of a global-scale data set

Aerosol deposition provides a major input of the essential micronutrient iron to the open ocean. A critical parameter with respect to bioavailability is the proportion of aerosol iron that enters the oceanic dissolved iron pool – the so-called fractional solubility of aerosol iron (%FeS). Here we present a global-scale compilation of total aerosol iron loading (FeT) and %FeS values for ~1100 samples collected over the open ocean, the coastal ocean, and some continental sites, including new data from the Atlantic Ocean. The global-scale compilation reveals a remarkably consistent trend in the fractional solubility of aerosol iron as a function of total aerosol iron loading, with the great bulk of the data falling along an inverse hyperbolic trend. The large dynamic range in %FeS (0-95%) varies with FeT in a manner similar to that identified for aerosols collected in the Sargasso Sea by Sedwick et al. (2007), who posit that the trend reflects near-conservative mixing between air masses that carry lithogenic mineral dust (with high FeT and low %FeS) and non-soil-dust aerosols such as anthropogenic combustion emissions (with low FeT and high %FeS), respectively. An increasing body of empirical evidence points to the importance of aerosol source and composition in determining the fractional solubility of aerosol iron, such that anthropogenic combustion emissions appear to play a critical role in determining this parameter in the bulk marine aerosol. The robust global-scale relationship between %FeS and FeT may provide a simple heuristic method for estimating aerosol iron solubility at the regional to global scale

Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas

© The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.info:eu-repo/semantics/publishedVersio

Automatic Detection of User Abilities through the SmartAbility Framework

This paper presents a proposed smartphone application for the unique SmartAbility Framework that supports interaction with technology for people with reduced physical ability, through focusing on the actions that they can perform independently. The Framework is a culmination of knowledge obtained through previously conducted technology feasibility trials and controlled usability evaluations involving the user community. The Framework is an example of ability-based design that focuses on the abilities of users instead of their disabilities. The paper includes a summary of Versions 1 and 2 of the Framework, including the results of a two-phased validation approach, conducted at the UK Mobility Roadshow and via a focus group of domain experts. A holistic model developed by adapting the House of Quality (HoQ) matrix of the Quality Function Deployment (QFD) approach is also described. A systematic literature review of sensor technologies built into smart devices establishes the capabilities of sensors in the Android and iOS operating systems. The review defines a set of inclusion and exclusion criteria, as well as search terms used to elicit literature from online repositories. The key contribution is the mapping of ability-based sensor technologies onto the Framework, to enable the future implementation of a smartphone application. Through the exploitation of the SmartAbility application, the Framework will increase technology amongst people with reduced physical ability and provide a promotional tool for assistive technology manufacturers

Tuning transcription factor availability through acetylation-mediated genomic redistribution

It is widely assumed that decreasing transcription factor DNA-binding affinity reduces transcription initiation by diminishing occupancy of sequence-specific regulatory elements. However, in vivo transcription factors find their binding sites while confronted with a large excess of low-affinity degenerate motifs. Here, using the melanoma lineage survival oncogene MITF as a model, we show that low-affinity binding sites act as a competitive reservoir in vivo from which transcription factors are released by mitogen-activated protein kinase (MAPK)-stimulated acetylation to promote increased occupancy of their regulatory elements. Consequently, a low-DNA-binding-affinity acetylation-mimetic MITF mutation supports melanocyte development and drives tumorigenesis, whereas a high-affinity non-acetylatable mutant does not. The results reveal a paradoxical acetylation-mediated molecular clutch that tunes transcription factor availability via genome-wide redistribution and couples BRAF to tumorigenesis. Our results further suggest that p300/CREB-binding protein-mediated transcription factor acetylation may represent a common mechanism to control transcription factor availability

Role and regulation of MITF in melanocytes and melanoma

One key to understanding how cells integrate and how they respond to diverse stimuli in order to direct a transcriptional response is knowing how a transcription factor may be directed to an appropriate subset of its target genes. One mechanism with which this may be achieved is by modulation of the transcription factor’s post-translational modification status. The microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage, and it is also a lineage addiction gene in melanoma. Low or high levels of MITF expression induce a reversible cell cycle arrest. Invasive behaviour is characteristic of low MITF expression; differentiation a product of high MITF activity; and moderate levels of MITF expression promote proliferation. A major, unaddressed problem is how DNA binding by MITF may be differentially directed such that it regulates either a proliferation-associated or a differentiation-associated gene expression programme appropriate to the cellular microenvironment. This thesis explores the function and regulation of the signalling pathways controlling novel post-translational modifications of MITF. One such modification, in the DNA binding domain of MITF, defines a key switch that controls MITF’s DNA binding affinity and specificity. Moreover, a novel set of MITF target genes are revealed that extend its control beyond pigmentation and cell cycle regulation to implicate MITF as an overall regulator of cell behaviour in the melanocyte lineage.</p

Learning on the Front Line : Can Personal Development During Problem-Based Learning Facilitate Professional Development in Trainee Clinical Psychologists?

Problem-based learning (PBL) is a form of self-directed learning that has been employed for over 30 years within a variety of disciplines and professional training programmes. This paper focuses on the acquisition of skills and knowledge gained through experiential learning components of the academic programme, namely Problem-Based Learning, of a Clinical Psychology training programme. This paper explores the learning experiences of a PBL group on this programme, reflecting on the impact of an experience early on in their group formation (presenting a personal in-vivo version of their PBL experience and subsequent negative evaluation). These narratives were written after their 3rd PBL exercise (the latter two were formally evaluated). This paper then goes on to consider how they then managed PBL including factors that may have helped or hindered their ability to learn and work together effectively. We conclude with what we may learn for the benefit of other learning contextsPeer reviewe

sj-docx-1-pdp-10.1177_10935266231199928 – Supplemental material for The Incidence of Multiple Fusions in a Series of Pediatric Soft Tissue and Bone Tumors

Supplemental material, sj-docx-1-pdp-10.1177_10935266231199928 for The Incidence of Multiple Fusions in a Series of Pediatric Soft Tissue and Bone Tumors by Anastasia MacKeracher, Anthony Arnoldo, Robert Siddaway, Lea F. Surrey and Gino R. Somers in Pediatric and Developmental Pathology</p