Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Reframing reporting of childhood sexual exploitation: three journalists reflect

This article explores three national and local journalists’ experiences of reporting on child sexual exploitation by so-called “Asian street grooming gangs” in UK towns and cities, with a particular emphasis on journalists framing journalists. In response to coverage of a series of cases, journalists have been accused by academics, policymakers and rival media organizations of fixating on perpetrators’ ethnicity and creating distorted, racist media frames. Few, if any, studies have garnered practitioners’ perspectives on how framing occurs, so we interview three prominent journalists who have covered such cases in order to deepen our understanding of the processes and causative factors behind particular editorial angles. While offering only a snapshot view, our findings reveal these individual journalists to be caught at the nexus of a range of factors that impact upon their work, both internally and externally driven

Analysis of Lake Ontario Lower Aquatic food web Assessment (LOLA 2003 and 2008) within the context of long-term ecological change

Lake Ontario is the 13th largest lake in the world with a surface area of 18,500 km² (Reynolds et al. 2000), has a population in the watershed of over 8 million, and provides a range of ecosystem services to the people in the watershed (freshwater for various uses, shipping, fisheries, and recreation). Currently, extensive surveys for each Great Lake occur on a rotating five-year schedule. This report presents the status of Lake Ontario’s lower trophic levels in 2008 and a detailed comparison with similarly collected in 2003 and with data collected by the collaborating agencies and Cornell University and discuss observed changes in relation to changes in nutrient concentration and food web configuration in Lake Ontario. There has been a spatial restructuring of the Lake Ontario offshore ecosystem through the increase in the deep chlorophyll layer and associated zooplankton. This has resulted in a Lake Ontario that in 2008 is more similar to Lakes Superior, Huron and Michigan than to the Lake Ontario of the 1990s. Major findings are Nutrients: Spring offshore total phosphorus and soluble reactive phosphorus increased from 2003 to 2008, but summer levels did not. Lake-wide average total phosphorus levels remained at or below the target level of 10 µg/L in all three seasons of 2008. Lake-wide nutrient concentrations have declined since the 1960s. However, phosphorus concentrations have been stable (~7-10 µg/L) since the mid-1990s. Spring silica was similar in 2003 and 2008 and was depleted by the summer in both years. This indicates continued spring diatom production in Lake Ontario. Phytoplankton: Summer epilimnetic chlorophyll-a increased by a factor of 2, the proportion of autotrophic algae increased, and summer water clarity declined from 2003 to 2008. Summer chlorophyll-a levels in 2008 were similar to the concentrations in the 1981-1995 time period. However, the trend towards mesotrophy in the summer of 2008 may be limited to that year as it was not followed by increased values in 2009 to 2011. Most of the chlorophyll in the water column was located in a deep chlorophyll layer in the thermocline. Zooplankton: Offshore epilimnetic zooplankton density and biomass declined from 2003 to 2008 by a factor of 5 to 12 in the summer and by a factor of 1.5 to 2.6 in the fall. This is consistent with long-term trends of declining epilimnetic zooplankton abundance including a larger decline in 2004-2005 coincident with an increase in the predatory Bythotrephes. Whole water column zooplankton density also declined from 2003 to 2008 in the summer and fall, but zooplankton biomass only declined in the fall. Large changes in whole water column zooplankton community composition occurred between 2003 and 2008 from a cyclopoid/bosminid dominated system in 2003 to a calanoid dominated system in 2008. Mysids, Diporeia and Mussels Mysid densities were similar in 2003 and 2008 indicating continued high biomass of mysids in Lake Ontario. In July of 2008, the biomass of Mysis diluviana was 17% of the crustacean zooplankton biomass in the offshore of Lake Ontario (depth >30m). Mysid densities appear stable in Lake Ontario. The native benthic amphipod Diporeia declined further in 2008 and is almost extirpated from Lake Ontario. Quagga mussels are very abundant as deep as 90 m, but populations in shallow water declined from 2003 to 2008. Few zebra mussels were present in either 2003 or 2008.Report for the GLRI funded project Improving Lake Ontario Environmental Management Decisions (Grant ID # 97220700-0

PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels

I ndividual genomes contain millions of genetic variants. When considering which variants may be causative for a given rare genetic disease, applying filtering criteria (such as allele frequency, predicted variant consequence, familial segregation and mode of inheritance) decreases this number to hundreds of variants. However, such a number remains labor intensive for a diagnostic genetic testing laboratory to interpret as part of routine service for each patient or family. A list of genes with evidence of disease causation in the condition being assessed aids in prioritizing and ranking the variants. This prioritization decreases the number of candidates that laboratories or clinical geneticists must assess to identify the likely causative variants for clinical reporting. Established lists of genes with clear evidence of disease causation (referred to herein as virtual gene panels) are therefore a highly effective tool in variant prioritization.M. Caulfield was funded by the National Institute for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Center at Barts and The London School of Medicine and Dentistry. He is supported as an NIHR senior investigator, and this work was funded by the MRC eMedLab award. This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health). The 100,000 Genomes Project is funded by the NIHR and NHSE. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructur