Red Nuggets at z~1.5: Compact passive galaxies and the formation of the Kormendy Relation

We present the results of NICMOS imaging of a sample of 16 high mass passively evolving galaxies with 1.3<z<2, taken primarily from the Gemini Deep Deep Survey. Around 80% of galaxies in our sample have spectra dominated by stars with ages >1 Gyr. Our rest-frame R-band images show that most of these objects have compact regular morphologies which follow the classical R^1/4 law. These galaxies scatter along a tight sequence in the Kormendy relation. Around one-third of the massive red objects are extraordinarily compact, with effective radii under one kiloparsec. Our NICMOS observations allow the detection of such systems more robustly than is possible with optical (rest-frame UV) data, and while similar systems have been seen at z>2, this is the first time such systems have been detected in a rest-frame optical survey at 1.3<z<2. We refer to these compact galaxies as "red nuggets". Similarly compact massive galaxies are completely absent in the nearby Universe. We introduce a new "stellar mass Kormendy relation" (stellar mass density vs size) which isolates the effects of size evolution from those of luminosity and color evolution. The 1.1 < z < 2 passive galaxies have mass densities that are an order of magnitude larger then early type galaxies today and are comparable to the compact distant red galaxies at 2 < z < 3. We briefly consider mechanisms for size evolution in contemporary models focusing on equal-mass mergers and adiabatic expansion driven by stellar mass loss. Neither of these mechanisms appears able to transform the high-redshift Kormendy relation into its local counterpart. Comment: Accepted version (to appear in ApJ

Prostate-specific antigen (PSA) screening and follow-up investigations in Māori and non-Māori men in New Zealand

Text. Pairwise sequence alignment between human SCN9A and homologous genes. (DOCX 34 kb

Growth rate after limb deformity correction by the Ilizarov method with or without knee joint distraction: Lengthening in 30 children followed for at least 2 years

Background and purpose Growth inhibition and stimulation have both been reported after juvenile limb lengthening. Distraction of a joint usually suspends and unloads the growth plate and may stimulate growth. We investigated the influence of knee joint distraction on the speed of growth after limb lengthening

Huntingtin facilitates polycomb repressive complex 2

Huntington's disease (HD) is caused by expansion of the polymorphic polyglutamine segment in the huntingtin protein. Full-length huntingtin is thought to be a predominant HEAT repeat α-solenoid, implying a role as a facilitator of macromolecular complexes. Here we have investigated huntingtin's domain structure and potential intersection with epigenetic silencer polycomb repressive complex 2 (PRC2), suggested by shared embryonic deficiency phenotypes. Analysis of a set of full-length recombinant huntingtins, with different polyglutamine regions, demonstrated dramatic conformational flexibility, with an accessible hinge separating two large α-helical domains. Moreover, embryos lacking huntingtin exhibited impaired PRC2 regulation of Hox gene expression, trophoblast giant cell differentiation, paternal X chromosome inactivation and histone H3K27 tri-methylation, while full-length endogenous nuclear huntingtin in wild-type embryoid bodies (EBs) was associated with PRC2 subunits and was detected with trimethylated histone H3K27 at Hoxb9. Supporting a direct stimulatory role, full-length recombinant huntingtin significantly increased the histone H3K27 tri-methylase activity of reconstituted PRC2 in vitro, and structure–function analysis demonstrated that the polyglutamine region augmented full-length huntingtin PRC2 stimulation, both in HdhQ111 EBs and in vitro, with reconstituted PRC2. Knowledge of full-length huntingtin's α-helical organization and role as a facilitator of the multi-subunit PRC2 complex provides a novel starting point for studying PRC2 regulation, implicates this chromatin repressive complex in a neurodegenerative disorder and sets the stage for further study of huntingtin's molecular function and the impact of its modulatory polyglutamine region

Correction: Protocol of the Healthy Brain Study:An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context

[This corrects the article DOI: 10.1371/journal.pone.0260952.]

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes