Antibody validation of immunohistochemistry for biomarker discovery: Recommendations of a consortium of academic and pharmaceutical based histopathology researchers

As biomarker discovery takes centre-stage, the role of immunohistochemistry within that process is increasing. At the same time, the number of antibodies being produced for ‘‘research use’’ continues to rise and it is important that antibodies to be used as biomarkers are validated for specificity and sensitivity before use. This guideline seeks to provide a stepwise approach for the validation of an antibody for immunohistochemical assays, reflecting the views of a consortium of academic and pharmaceutical based histopathology researchers. We propose that antibodies are placed into a tier system, level 1–3, based on evidence of their usage in immunohistochemistry, and that the degree of validation required is proportionate to their place on that tier

Seasonal speedup of a Greenland marine-terminating outlet glacier forced by surface melt–induced changes in subglacial hydrology

Peer reviewedPublisher PD

Extensive retreat of Greenland tidewater glaciers 2000-2010

Overall mass loss from the Greenland ice sheet nearly doubled during the early 2000s resulting in an increased contribution to sea-level rise, with this step-change being mainly attributed to the widespread frontal retreat and accompanying dynamic thinning of tidewater glaciers. Changes in glacier calving-front positions are easily derived from remotely sensed imagery and provide a record of dynamic change. However, ice-sheet-wide studies of calving fronts have been either spatially or temporally limited. In this study multiple calving-front positions were derived for 199 Greenland marine-terminating outlet glaciers with width greater than 1 km using Landsat imagery for the 11-year period 2000–2010 in order to identify regional seasonal and inter-annual variations. During this period, outlet glaciers were characterized by sustained and substantial retreat summing to more than 267 km, with only 11 glaciers showing overall advance. In general, the pattern of mass loss detected by GRACE (Gravity Recovery and Climate Experiment) and other measurements is reflected in the calving record of Greenland glaciers. Our results suggest several regions in the south and east of the ice sheet likely share controls on their dynamic changes, but no simple single control is apparent

Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

Heterogeneity of luminal breast cancer characterised by immunohistochemical expression of basal markers

Background: Luminal A breast cancer defined as hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative is known to be heterogeneous. Previous study showed that luminal A tumours with the expression of basal markers ((cytokeratin (CK) 5 or CK5/6) or epidermal growth factor receptor (EGFR)) were associated with poorer prognosis compared with those that stained negative for basal markers. Prompted by this study, we assessed whether tumour characteristics and risk factors differed by basal marker status within luminal A tumours. Methods: We pooled 5040 luminal A cases defined by immunohistochemistry (4490 basal-negative ((CK5 (or CK5/6))− and EGFR−) and 550 basal-positive ((CK5 (or CK5/6+)) or EGFR+)) from eight studies participating in the Breast Cancer Association Consortium. Case–case comparison was performed using unconditional logistic regression. Results: Tumour characteristics and risk factors did not vary significantly by the expression of basal markers, although results suggested that basal-positive luminal tumours tended to be smaller and node negative, and were more common in women with a positive family history and lower body mass index. Conclusions: Most established breast cancer risk factors were similar in basal-positive and basal-negative luminal A tumours. The non-significant but suggestive differences in tumour features and family history warrant further investigations

Elevation change of the Greenland Ice Sheet due to surface mass balance and firn processes, 1960–2014

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in The Cryosphere 9 (2015): 2009-2025, doi:10.5194/tc-9-2009-2015.Observed changes in the surface elevation of the Greenland Ice Sheet are caused by ice dynamics, basal elevation change, basal melt, surface mass balance (SMB) variability, and by compaction of the overlying firn. The last two contributions are quantified here using a firn model that includes compaction, meltwater percolation, and refreezing. The model is forced with surface mass fluxes and temperature from a regional climate model for the period 1960–2014. The model results agree with observations of surface density, density profiles from 62 firn cores, and altimetric observations from regions where ice-dynamical surface height changes are likely small. In areas with strong surface melt, the firn model overestimates density. We find that the firn layer in the high interior is generally thickening slowly (1–5 cm yr−1). In the percolation and ablation areas, firn and SMB processes account for a surface elevation lowering of up to 20–50 cm yr−1. Most of this firn-induced marginal thinning is caused by an increase in melt since the mid-1990s and partly compensated by an increase in the accumulation of fresh snow around most of the ice sheet. The total firn and ice volume change between 1980 and 2014 is estimated at −3295 ± 1030 km3 due to firn and SMB changes, corresponding to an ice-sheet average thinning of 1.96 ± 0.61 m. Most of this volume decrease occurred after 1995. The computed changes in surface elevation can be used to partition altimetrically observed volume change into surface mass balance and ice-dynamically related mass changes.P. Kuipers Munneke received financial support from the Netherlands Polar Programme (NPP) of the Netherlands Institute for Scientific Research (NWO). ECMWF at Reading (UK) is acknowledged for use of the Cray supercomputing system. The J. E. Box contribution is supported by Det Frie Forskningsråd grant 4002-00234 and Geocenter Denmark

Minimal Holocene retreat of large tidewater glaciers in Køge Bugt, southeast Greenland

Abstract Køge Bugt, in southeast Greenland, hosts three of the largest glaciers of the Greenland Ice Sheet; these have been major contributors to ice loss in the last two decades. Despite its importance, the Holocene history of this area has not been investigated. We present a 9100 year sediment core record of glaciological and oceanographic changes from analysis of foraminiferal assemblages, the abundance of ice-rafted debris, and sortable silt grain size data. Results show that ice-rafted debris accumulated constantly throughout the core; this demonstrates that glaciers in Køge Bugt remained in tidewater settings throughout the last 9100 years. This observation constrains maximum Holocene glacier retreat here to less than 6 km from present-day positions. Retreat was minimal despite oceanic and climatic conditions during the early-Holocene that were at least as warm as the present-day. The limited Holocene retreat of glaciers in Køge Bugt was controlled by the subglacial topography of the area; the steeply sloping bed allowed glaciers here to stabilise during retreat. These findings underscore the need to account for individual glacier geometry when predicting future behaviour. We anticipate that glaciers in Køge Bugt will remain in stable configurations in the near-future, despite the predicted continuation of atmospheric and oceanic warming

The 1958–2009 Greenland ice sheet surface melt and the mid-tropospheric atmospheric circulation

peer reviewedaudience: researcherIn order to assess the impact of the mid-tropospheric circulation over the Greenland ice sheet (GrIS) on surface melt, as simulated by the regional climate model MAR, an automatic Circulation type classification (CTC) based on 500 hPa geopotential height from reanalyses is developed. General circulation correlates significantly with the surface melt anomalies for the summers in the period 1958–2009. The record surface melt events observed during the summers of 2007–2009 are linked to the exceptional persistence of atmospheric circulations favouring warm air advection. The CTC emphasizes that summer 500 hPa circulation patterns have changed since the beginning of the 2000s; this process is partly responsible for the recent warming observed over the GrIS

Towards Constraining Glacial Isostatic Adjustment in Greenland Using ICESat and GPS Observations

Constraining glacial isostatic adjustment (GIA) i.e. the Earth’s viscoelastic response to past ice changes, is an important task, because GIA is a significant correction in gravity-based ice sheet mass balance estimates. Here, we investigate how temporal variations in the observed and modeled crustal displacements due to the Earth’s response to ongoing ice mass changes can contribute to the process of constraining GIA. We use mass change grids of the Greenland ice sheet (GrIS) derived from NASA’s high resolution Ice, Cloud and land Elevation Satellite (ICESat) data in three overlapping time spans covering the period 2004–2009 to estimate temporal variations in the elastic response due to present day ice mass loss. The modeled crustal displacements (elastic + GIA) are compared with GPS time series from five permanent sites (KELY, KULU, QAQ1, THU2, and SCOR). We find, that the modeled pattern of elastic crustal displacements shows pronounced variation during the observation period, where an increase in elastic displacement is found at the northwest coast of Greenland, while a decrease is found at the southeast coast. This pattern of temporal changes is supported by the GPS observations. We find, that the temporal behavior of the ICESat-based modeled elastic response agrees well with the GPS observations at the sites KELY, QAQ1, and SCOR. This suggests, that our elastic models are able to resolve the temporal changes in the observed uplift, which indicates that the elastic uplift models are reliable at these sites. Therefore, we conclude that these sites are useful for constraining GIA