ALBERT

Description: We present evidence for a strong relationship between galaxy size and environment for the quiescent population in the redshift range 1 〈  z  〈 2. Environments were measured using projected galaxy overdensities on a scale of 400 kpc, as determined from ~96 000 K -band-selected galaxies from the UKIDSS Ultra Deep Survey (UDS). Sizes were determined from ground-based K -band imaging, calibrated using space-based CANDELS HST observations in the centre of the UDS field, with photometric redshifts and stellar masses derived from 11-band photometric fitting. From the resulting size–mass relation, we confirm that quiescent galaxies at a given stellar mass were typically ~50 per cent smaller at z  ~ 1.4 compared to the present day. At a given epoch, however, we find that passive galaxies in denser environments are on average significantly larger at a given stellar mass. The most massive quiescent galaxies ( M *  〉 2 10 11  M ) at z  〉 1 are typically 50 per cent larger in the highest density environments compared to those in the lowest density environments. Using Monte Carlo simulations, we reject the null hypothesis that the size–mass relation is independent of environment at a significance 〉4.8 for the redshift range 1 〈  z  〈 2. In contrast, the evidence for a relationship between size and environment is much weaker for star-forming galaxies.

Description: Familial medullary thyroid cancer (MTC) and its precursor, C cell hyperplasia (CCH), is associated with germline RET mutations causing multiple endocrine neoplasia type 2. However, some rare families with apparent MTC/CCH predisposition do not have a detectable RET mutation. To identify novel MTC/CCH predisposition genes we undertook exome resequencing studies in a family with apparent predisposition to MTC/CCH and no identifiable RET mutation. We identified a novel ESR2 frameshift mutation, c.948delT, which segregated with histological diagnosis following thyroid surgery in family members and demonstrated loss of ESR2 -encoded ERβ expression in the MTC tumour. ERα and ERβ form heterodimers binding DNA at specific oestrogen-responsive elements (EREs) to regulate gene transcription. ERβ represses ERα-mediated activation of the ERE and the RET promoter contains three EREs . In vitro , we showed that ESR2 c.948delT results in unopposed ERα mediated increased cellular proliferation, activation of the ERE and increased RET expression. In vivo , immunostaining of CCH and MTC using an anti-RET antibody demonstrated increased RET expression. Together these findings identify germline ESR2 mutation as a novel cause of familial MTC/CCH and provide important insights into a novel mechanism causing increased RET expression in tumourigenesis.

Description: Disrupted-In-Schizophrenia 1 ( DISC1 ) was identified as a risk factor for psychiatric illness through its disruption by a balanced chromosomal translocation, t(1;11)(q42.1;q14.3), that co-segregates with schizophrenia, bipolar disorder and depression. We previously reported that the translocation reduces DISC1 expression, consistent with a haploinsufficiency disease model. Here we report that, in lymphoblastoid cell lines, the translocation additionally results in the production of abnormal transcripts due to the fusion of DISC1 with a disrupted gene on chromosome 11 ( DISC1FP1/Boymaw ). These chimeric transcripts encode abnormal proteins, designated CP1, CP60 and CP69, consisting of DISC1 amino acids 1–597 plus 1, 60 or 69 amino acids, respectively. The novel 69 amino acids in CP69 induce increased α-helical content and formation of large stable protein assemblies. The same is predicted for CP60. Both CP60 and CP69 exhibit profoundly altered functional properties within cell lines and neurons. Both are predominantly targeted to mitochondria, where they induce clustering and loss of membrane potential, indicative of severe mitochondrial dysfunction. There is currently no access to neural material from translocation carriers to confirm these findings, but there is no reason to suppose that these chimeric transcripts will not also be expressed in the brain. There is thus potential for the production of abnormal chimeric proteins in the brains of translocation carriers, although at substantially lower levels than for native DISC1. The mechanism by which inheritance of the translocation increases risk of psychiatric illness may therefore involve both DISC1 haploinsufficiency and mitochondrial deficiency due to the effects of abnormal chimeric protein expression. GenBank accession numbers: DISC1FP1 (EU302123), Boymaw (GU134617), der 11 chimeric transcript DISC1FP1 exon 2 to DISC1 exon 9 (JQ650115), der 1 chimeric transcript DISC1 exon 4 to DISC1FP1 exon 4 (JQ650116), der 1 chimeric transcript DISC1 exon 6 to DISC1FP1 exon 3a (JQ650117).

Description: Aims Australia is among one of the world’s wealthiest nations; yet, its relatively small human population (22.5 million) has been responsible for extensive deforestation and forest degradation since European settlement in the late 18th century. Despite most (~75%) of Australia’s 7.6 million-km 2 area being covered in inhospitable deserts or arid lands generally unsuitable to forest growth, the coastal periphery has witnessed a rapid decline in forest cover and quality, especially over the last 60 years. Here I document the rates of forest loss and degradation in Australia based on a thorough review of existing literature and unpublished data. Important Findings Overall, Australia has lost nearly 40% of its forests, but much of the remaining native vegetation is highly fragmented. As European colonists expanded in the late 18th and the early 19th centuries, deforestation occurred mainly on the most fertile soils nearest to the coast. In the 1950s, southwestern Western Australia was largely cleared for wheat production, subsequently leading to its designation as a Global Biodiversity Hotspot given its high number of endemic plant species and rapid clearing rates. Since the 1970s, the greatest rates of forest clearance have been in southeastern Queensland and northern New South Wales, although Victoria is the most cleared state. Today, degradation is occurring in the largely forested tropical north due to rapidly expanding invasive weed species and altered fire regimes. Without clear policies to regenerate degraded forests and protect existing tracts at a massive scale, Australia stands to lose a large proportion of its remaining endemic biodiversity. The most important implications of the degree to which Australian forests have disappeared or been degraded are that management must emphasize the maintenance of existing primary forest patches, as well as focus on the regeneration of matrix areas between fragments to increase native habitat area, connectivity and ecosystem functions.

Description: We previously demonstrated that the Alzheimer's disease (AD) associated risk allele, rs3865444 C , results in a higher surface density of CD33 on monocytes. Here, we find alternative splicing of exon 2 to be the primary mechanism of the genetically driven differential expression of CD33 protein. We report that the risk allele, rs3865444 C , is associated with greater cell surface expression of CD33 in both subjects of European and African–American ancestry and that there is a single haplotype influencing CD33 surface expression. A meta-analysis of the two populations narrowed the number of significant SNPs in high linkage disequilibrium (LD) ( r 2 〉 0.8) with rs3865444 to just five putative causal variants associated with increased protein expression. Using gene expression data from flow-sorted CD14 + CD16 – monocytes from 398 healthy subjects of three populations, we show that the rs3865444 C risk allele is strongly associated with greater expression of CD33 exon 2 ( p META = 2.36 x 10 –60 ). Western blotting confirms increased protein expression of the full-length CD33 isoform containing exon 2 relative to the rs3865444 C allele ( P 〈 0.0001). Of the variants in strong LD with rs3865444, rs12459419, which is located in a putative SRSF2 splice site of exon 2, is the most likely candidate to mediate the altered alternative splicing of CD33's Immunoglobulin V-set domain 2 and ultimately influence AD susceptibility.

Description: We present a new method to classify the broad-band optical–near-infrared spectral energy distributions (SEDs) of galaxies using three shape parameters (super-colours) based on a principal component analysis of model SEDs. As well as providing a compact representation of the wide variety of SED shapes, the method allows for easy visualization of information loss and biases caused by the incomplete sampling of the rest-frame SED as a function of redshift. We apply the method to galaxies in the United Kingdom Infrared Telescope Infrared Deep Sky Survey Ultra Deep Survey with 0.9 〈  z  〈 1.2, and confirm our classifications by stacking rest-frame optical spectra for a fraction of objects in each class. As well as cleanly separating a tight red sequence from star-forming galaxies, three unusual populations are identifiable by their unique colours: very dusty star-forming galaxies with high metallicity and old mean stellar age; post-starburst galaxies which have formed 10 per cent of their mass in a recent unsustained starburst event; and metal-poor quiescent dwarf galaxies. We find that quiescent galaxies account for 45 per cent of galaxies with log M */M 〉 11, declining steadily to 13 per cent at log M */M = 10. The properties and mass function of the post-starburst galaxies are consistent with a scenario in which gas-rich mergers contribute to the growth of the low- and intermediate-mass range of the red sequence.

Description: Schizophrenia is a chronic illness of heterogenous biological origin. We hypothesized that, similar to chronic progressive brain conditions, persistent functional disturbances of neurons would result in disturbed proteostasis in the brains of schizophrenia patients, leading to increased abundance of specific misfolded, insoluble proteins. Identification of such proteins would facilitate the elucidation of molecular processes underlying these devastating conditions. We therefore generated antibodies against pooled insoluble proteome of post-mortem brains from schizophrenia patients in order to identify unique, disease-specific epitopes. We successfully identified such an epitope to be present on collapsin-response mediator protein 1 (CRMP1) in biochemically purified, insoluble brain fractions. A genetic association analysis for the CRMP1 gene in a large Finnish population cohort ( n = 4651) corroborated the association of physical and social anhedonia with the CRMP1 locus in a DISC1 ( Disrupted-in-schizophrenia 1 )-dependent manner. Physical and social anhedonia are heritable traits, present as chronic, negative symptoms of schizophrenia and severe major depression, thus constituting serious vulnerability factors for mental disease. Strikingly, lymphoblastoid cell lines derived from schizophrenia patients mirrored aberrant CRMP1 immunoreactivity by showing an increase of CRMP1 expression, suggesting its potential role as a blood-based diagnostic marker. CRMP1 is a novel candidate protein for schizophrenia traits at the intersection of the reelin and DISC1 pathways that directly and functionally interacts with DISC1. We demonstrate the impact of an interdisciplinary approach where the identification of a disease-associated epitope in post-mortem brains, powered by a genetic association study, is rapidly translated into a potential blood-based diagnostic marker.

Description: We use the United Kingdom Infrared Telescope Deep Sky Survey (UKIDSS) Ultra Deep Survey (UDS), the deepest degree-scale near-infrared survey to date, to investigate the clustering of star-forming and passive galaxies to z  ~ 3.5. Our new measurements include the first determination of the clustering for passive galaxies at z  〉 2, which we achieve using a cross-correlation technique. We find that passive galaxies are the most strongly clustered, typically hosted by massive dark matter haloes with M halo  〉 5  x 10 12 M irrespective of redshift or stellar mass. Our findings are consistent with models in which a critical halo mass determines the transition from star-forming to passive galaxies. Star-forming galaxies show no strong correlation between stellar mass and halo mass, but passive galaxies show evidence for an anticorrelation; low-mass passive galaxies appear, on average, to be located in the most massive haloes. These results can be understood if the termination of star formation is most efficient for galaxies of low stellar mass in very dense environments.

Description: We investigate galactic-scale outflows in the redshift range 0.71 ≤ z ≤ 1.63, using 413 K -band selected galaxies observed in the spectroscopic follow-up of the UKIDSS Ultra-Deep Survey (UDSz). The galaxies have an average stellar mass of ~10 9.5 M and span a wide range in rest-frame colours, representing typical star-forming galaxies at this epoch. We stack the spectra by various galaxy properties, including stellar mass, [O ii ] equivalent width, star formation rate, specific star formation rate and rest-frame spectral indices. We find that outflows are present in virtually all spectral stacks, with velocities ranging from 100 to 1000 km s –1 , indicating that large-scale outflowing winds are a common property at these redshifts. The highest velocity outflows (〉500 km s –1 ) are found in galaxies with the highest stellar masses and the youngest stellar populations. Our findings suggest that high-velocity galactic outflows are mostly driven by star-forming processes rather than active galactic nuclei, with implied mass outflow rates comparable to the rates of star formation. Such behaviour is consistent with models required to reproduce the high-redshift mass–metallicity relation.

Description: Aims We aim to quantify the relative importance of various endogenous and exogenous processes influencing the spatial distribution of the individuals of plant species at different temporal and spatial scales in a species-rich and high-cover meadow in the eastern Tibetan Plateau. Methods We calculated Green’s index of dispersion to infer the spatial distribution patterns of 73 herbaceous species at two scales (0.25 and 1.0 m 2 ). We constructed a series of generalized linear models to test the hypotheses that different species traits such as mean plant stem density, per capita dry biomass, maximum plant height and mean seed mass contribute to their spatial distribution. We used the first principal component of soil C, N and P to explain abundance variation across quadrats and sub-plots. Important Findings The individuals of the species studied were highly spatially aggregated. At both spatial scales, biomass and stem density explained the most variation in aggregation, but there was no evidence for an effect of mean seed mass on aggregation intensity. The effects of soil carbon, nitrogen and phosphorus at different depths affected plant abundance mostly at the broader spatial scale. Our results demonstrate that self-thinning and habitat heterogeneity all contribute to determine the spatial aggregation patterns of plant individuals in alpine meadow vegetation in the eastern Tibetan Plateau.