Molecular phylogenetic status of Siberian roe deer （Capreolus pygargus） based on mitochondrial cytochrome b from Jeju Island in Korea

In order to elucidate the genetic diversity and taxonomic status of Siberian roe deer （Capreolus pygar- gus） from the Korean peninsula, partial sequences of the mitochondrial cytochrome b gene were analyzed. We col- lected 57 roe deer samples from Mainland and Jeju Island between July 2004 and June 2009. A total of 50 sequences （1,070 bp） were obtained, and seven haplotypes were defined. Five haplotypes were found from Mainland, and two were discovered from Jeju Island. The genetic diver- sity was lower in the Jeju Island population than in the Mainland population. In addition, both the consensus neighbor-joining tree and maximum parsimony tree showed an identical topology between the Mainland and Jeju Island clades. Based on the results, two subspecies of the Korean roe deer were confirmed. Siberian roe deer in Jeju Island showed a distinct difference in the cytochrome b gene compared with other Siberian roe deer, being aunique native species inhabiting only Jeju Island in Korea. Because Siberian roe deer in Jeju Island can be classified at subspecies level, the new subspecies in Jeju was named Capreolus pygargus jejuensis in this study. For this new subspecies, reasonable conservation and management effort is needed in the future.     

Large protein complexes retained in the ER are dislocated by non-COPII vesicles and degraded by selective autophagy

Multisubunit protein complexes are assembled in the endoplasmic reticulum (ER). Existing pools of single subunits and assembly intermediates ensure the efficient and rapid formation of complete complexes. While being kinetically beneficial, surplus components must be eliminated to prevent potentially harmful accumulation in the ER. Surplus single chains are cleared by the ubiquitin–proteasome system. However, the fate of not secreted assembly intermediates of multisubunit proteins remains elusive. Here we show by high-resolution double-label confocal immunofluorescence and immunogold electron microscopy that naturally occurring surplus fibrinogen Aα–γ assembly intermediates in HepG2 cells are dislocated together with EDEM1 from the ER to the cytoplasm in ER-derived vesicles not corresponding to COPII-coated vesicles originating from the transitional ER. This route corresponds to the novel ER exit path we have previously identified for EDEM1 (Zuber et al. Proc Natl Acad Sci USA 104:4407–4412, 2007). In the cytoplasm, detergent-insoluble aggregates of fibrinogen Aα–γ dimers develop that are targeted by the selective autophagy cargo receptors p62/SQSTM1 and NBR1. These aggregates are degraded by selective autophagy as directly demonstrated by high-resolution microscopy as well as biochemical analysis and inhibition of autophagy by siRNA and kinase inhibitors. Our findings demonstrate that different pathways exist in parallel for ER-to-cytoplasm dislocation and subsequent proteolytic degradation of large luminal protein complexes and of surplus luminal single-chain proteins. This implies that ER-associated protein degradation (ERAD) has a broader function in ER proteostasis and is not limited to the elimination of misfolded glycoproteins.     

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ～ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10??), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.     

A non-spherical core in the explosion of supernova SN 2004dj

An important and perhaps critical clue to the mechanism driving the explosion of massive stars as supernovae is provided by the accumulating evidence for asymmetry in the explosion. Indirect evidence comes from high pulsar velocities, associations of supernovae with long-soft gamma-ray bursts, and asymmetries in late-time emission-line profiles. Spectropolarimetry provides a direct probe of young supernova geometry, with higher polarization generally indicating a greater departure from spherical symmetry. Large polarizations have been measured for 'stripped-envelope' (that is, type Ic; ref. 7) supernovae, which confirms their non-spherical morphology; but the explosions of massive stars with intact hydrogen envelopes (type II-P supernovae) have shown only weak polarizations at the early times observed. Here we report multi-epoch spectropolarimetry of a classic type II-P supernova that reveals the abrupt appearance of significant polarization when the inner core is first exposed in the thinning ejecta (approximately 90 days after explosion). We infer a departure from spherical symmetry of at least 30 per cent for the inner ejecta. Combined with earlier results, this suggests that a strongly non-spherical explosion may be a generic feature of core-collapse supernovae of all types, where the asphericity in type II-P supernovae is cloaked at early times by the massive, opaque, hydrogen envelope.     

Abduction and Estimation in Animals

One of the most pressing issues in understanding abduction is whether it is an instinct or an inference. For many commentators find it paradoxical that new ideas are products of an instinct and products of an inference at the same time. Fortunately, Lorenzo Magnani’s recent discussion of animal abduction sheds light on both instinctual and inferential character of Peircean abduction. But, exactly for what reasons are Peirce and Magnani so convinced that animal abduction can provide us with a novel perspective? Inspired by Peirce’s and Magnani’s discussions of animal abduction, I propose to compare Peirce’s and Magnani’s views of animal abduction with the estimative power of non-human animals and humans, which was one of the internal senses in medieval psychology.     

Microring-Assisted Coupling Between Dissimilar Waveguides

The use of microring resonators to assist in the evanescent field coupling between dissimilar waveguides is proposed and analyzed. Theoretical analysis based on the coupled mode theory and nu-merical example show that complete cross power transfers can be obtained near the microring resonances. Applications of the device include power dividers, low-power thermo-optic or electro-optic switches, and modulators.     

Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits

To identify the genetic bases for nine metabolic traits, we conducted a meta-analysis combining Korean genome-wide association results from the KARE project (n = 8,842) and the HEXA shared control study (n = 3,703). We verified the associations of the loci selected from the discovery meta-analysis in the replication stage (30,395 individuals from the BioBank Japan genome-wide association study and individuals comprising the Health2 and Shanghai Jiao Tong University Diabetes cohorts). We identified ten genome-wide significant signals newly associated with traits from an overall meta-analysis. The most compelling associations involved 12q24.11 (near MYL2) and 12q24.13 (in C12orf51) for high-density lipoprotein cholesterol, 2p21 (near SIX2-SIX3) for fasting plasma glucose, 19q13.33 (in RPS11) and 6q22.33 (in RSPO3) for renal traits, and 12q24.11 (near MYL2), 12q24.13 (in C12orf51 and near OAS1), 4q31.22 (in ZNF827) and 7q11.23 (near TBL2-BCL7B) for hepatic traits. These findings highlight previously unknown biological pathways for metabolic traits investigated in this study.     

Fine mapping of regulatory loci for mammalian gene expression using radiation hybrids

We mapped regulatory loci for nearly all protein-coding genes in mammals using comparative genomic hybridization and expression array measurements from a panel of mouse-hamster radiation hybrid cell lines. The large number of breaks in the mouse chromosomes and the dense genotyping of the panel allowed extremely sharp mapping of loci. As the regulatory loci result from extra gene dosage, we call them copy number expression quantitative trait loci, or ceQTLs. The -2log10P support interval for the ceQTLs was <150 kb, containing an average of <2-3 genes. We identified 29,769 trans ceQTLs with -log10P > 4, including 13 hotspots each regulating >100 genes in trans. Further, this work identifies 2,761 trans ceQTLs harboring no known genes, and provides evidence for a mode of gene expression autoregulation specific to the X chromosome.     

Optimization of specificity in a cellular protein interaction network by negative selection

Most proteins that participate in cellular signalling networks contain modular protein-interaction domains. Multiple versions of such domains are present within a given organism: the yeast proteome, for example, contains 27 different Src homology 3 (SH3) domains. This raises the potential problem of cross-reaction. It is generally thought that isolated domain-ligand pairs lack sufficient information to encode biologically unique interactions, and that specificity is instead encoded by the context in which the interaction pairs are presented. Here we show that an isolated peptide ligand from the yeast protein Pbs2 recognizes its biological partner, the SH3 domain from Sho1, with near-absolute specificity--no other SH3 domain present in the yeast genome cross-reacts with the Pbs2 peptide, in vivo or in vitro. Such high specificity, however, is not observed in a set of non-yeast SH3 domains, and Pbs2 motif variants that cross-react with other SH3 domains confer a fitness defect, indicating that the Pbs2 motif might have been optimized to minimize interaction with competing domains specifically found in yeast. System-wide negative selection is a subtle but powerful evolutionary mechanism to optimize specificity within an interaction network composed of overlapping recognition elements.