Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

A moist benchmark calculation for atmospheric general circulation models

A benchmark calculation is designed to compare the climate and climate sensitivity of atmospheric general circulation models (AGCMs). The experimental setup basically follows that of the aquaplanet experiment (APE) proposed by Neale and Hoskins, but a simple mixed layer ocean is embedded to enable air-sea coupling and the prediction of surface temperature. In calculations with several AGCMs, this idealization produces very strong zonal-mean flow and exaggerated ITCZ strength, but the model simulations remain sufficiently realistic to justify the use of this framework in isolating key differences between models. Because surface temperatures are free to respond to model differences, the simulation of the cloud distribution, especially in the subtropics, affects many other aspects of the simulations. The analysis of the simulated tropical transients highlights the importance of convection inhibition and air-sea coupling as affected by the depth of the mixed layer. These preliminary comparisons demonstrate that this idealized benchmark provides a discriminating framework for understanding the implications of differing physics parameterization in AGCMs.open101

Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development

The Arctic freshwater system : changes and impacts

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 112 (2007): G04S54, doi:10.1029/2006JG000353.Dramatic changes have been observed in the Arctic over the last century. Many of these involve the storage and cycling of fresh water. On land, precipitation and river discharge, lake abundance and size, glacier area and volume, soil moisture, and a variety of permafrost characteristics have changed. In the ocean, sea ice thickness and areal coverage have decreased and water mass circulation patterns have shifted, changing freshwater pathways and sea ice cover dynamics. Precipitation onto the ocean surface has also changed. Such changes are expected to continue, and perhaps accelerate, in the coming century, enhanced by complex feedbacks between the oceanic, atmospheric, and terrestrial freshwater systems. Change to the arctic freshwater system heralds changes for our global physical and ecological environment as well as human activities in the Arctic. In this paper we review observed changes in the arctic freshwater system over the last century in terrestrial, atmospheric, and oceanic systems.The authors gratefully acknowledge the National Science Foundation (NSF) for funding this synthesis work. This paper is principally the work of authors funded under the NSF-funded Freshwater Integration (FWI) study

The Origins of AGN Obscuration: The 'Torus' as a Dynamical, Unstable Driver of Accretion

Multi-scale simulations have made it possible to follow gas inflows onto massive black holes (BHs) from galactic scales to the accretion disk. When sufficient gas is driven towards the BH, gravitational instabilities generically form lopsided, eccentric disks that propagate inwards. The lopsided stellar disk exerts a strong torque on the gas disk, driving inflows that fuel rapid BH growth. Here, we investigate whether the same gas disk is the 'torus' invoked to explain obscured AGN. The disk is generically thick and has characteristic ~1-10 pc sizes and masses resembling those required of the torus. The scale heights and obscured fractions of the predicted torii are substantial even in the absence of strong stellar feedback providing the vertical support. Rather, they can be maintained by strong bending modes and warps excited by the inflow-generating instabilities. Other properties commonly attributed to feedback processes may be explained by dynamical effects: misalignment between torus and host galaxy, correlations between local SFR and turbulent gas velocities, and dependence of obscured fractions on AGN luminosity or SFR. We compare the predicted torus properties with observations of gas surface density profiles, kinematics, scale heights, and SFR densities in AGN nuclei, and find that they are consistent. We argue that it is not possible to reproduce these observations and the observed column density (N_H) distribution without a clumpy gas distribution, but allowing for clumping on small scales the predicted N_H distribution is in good agreement with observations from 10^20-27 cm^-2. We examine how N_H scales with galaxy and AGN properties, and find that AGN feedback may be necessary to explain some trends with luminosity and/or redshift. The torus is not merely a bystander or passive fuel source for accretion, but is itself the mechanism driving accretion.Comment: 20 pages, 10 figures, accepted to MNRAS (matches accepted version

Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers : results from the Consortium of Investigators of Modifiers of BRCA1/2.

Abstract Introduction Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. Methods We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. Results The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. Conclusions The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers

Very Now at London College of Communication

Co-curated with Max Houghton to coincide with the college’s Festival of Art and Journalism, Very Now explores the intersection of these two fields with works from an array of artists who blend the disseminative and conceptual strategies of art with the timeliness and real world concerns of journalism. Very Now includes work by Jeremy Deller, Edmund Clark, Adam Broomberg and Oliver Chanarin, Peter Kennard and Cat Phillips, Laura El-Tantawy, David Birkin, and Lewis Bush. Displayed alongside pieces by these artists and photographers are projects by groups of UAL students who worked reactively to produce new work on the theme of art and journalism. These projects included a reactive photograph which dynamically responds to viewer comments, an animation about insect drones and a large scale display of slides from the Snowden archive of leaked NSA documents

Embedding Anti-Racism and Decolonisation into LCC curricula

Four academics will discuss how they have been embedding anti-racism and decolonisation into aspects of curricula at LCC. They will show and contextualise examples, discuss what worked well, what was learnt and gained and what they found challenging: Lucy Panesar on embedding LCC Changemakers and Decolonising Wikipedia Network in the curriculum; Justyna Kabala and Tara Langford, Course Leaders for BA Design for Art Direction, on embedding ‘decolonising the classroom’ into the year one Locating Practice Unit; Max Houghton, Course Leader for MA Photojournalism Documentary Photography, on embedding anti-racism and the Decolonising Wikipedia Network into the Collaborative Unit