On the formation of hot Neptunes and super-Earths

The discovery of short-period Neptune-mass objects, now including the remarkable system HD69830 (Lovis et al. 2006) with three Neptune analogues, raises difficult questions about current formation models which may require a global treatment of the protoplanetary disc. Several formation scenarios have been proposed, where most combine the canonical oligarchic picture of core accretion with type I migration (e.g. Terquem & Papaloizou 2007) and planetary atmosphere physics (e.g. Alibert et al. 2006). To date, published studies have considered only a small number of progenitors at late times. This leaves unaddressed important questions about the global viability of the models. We seek to determine whether the most natural model -- namely, taking the canonical oligarchic picture of core accretion and introducing type I migration -- can succeed in forming objects of 10 Earth masses and more in the innermost parts of the disc. This problem is investigated using both traditional semianalytic methods for modelling oligarchic growth as well as a new parallel multi-zone N-body code designed specifically for treating planetary formation problems with large dynamic range (McNeil & Nelson 2009). We find that it is extremely difficult for oligarchic tidal migration models to reproduce the observed distribution. Even under many variations of the typical parameters, we form no objects of mass greater than 8 Earth masses. By comparison, it is relatively straightforward to form icy super-Earths. We conclude that either the initial conditions of the protoplanetary discs in short-period Neptune systems were substantially different from the standard disc models we used, or there is important physics yet to be understood.Comment: 19 pages, 18 figures. Final version accepted to MNRAS 30 September 200

Making the Earth: Combining Dynamics and Chemistry in the Solar System

No terrestrial planet formation simulation completed to date has considered the detailed chemical composition of the planets produced. While many have considered possible water contents and late veneer compositions, none have examined the bulk elemental abundances of the planets produced as an important check of formation models. Here we report on the first study of this type. Bulk elemental abundances based on disk equilibrium studies have been determined for the simulated terrestrial planets of O'Brien et al. (2006). These abundances are in excellent agreement with observed planetary values, indicating that the models of O'Brien et al. (2006) are successfully producing planets comparable to those of the Solar System in terms of both their dynamical and chemical properties. Significant amounts of water are accreted in the present simulations, implying that the terrestrial planets form "wet" and do not need significant water delivery from other sources. Under the assumption of equilibrium controlled chemistry, the biogenic species N and C still need to be delivered to the Earth as they are not accreted in significant proportions during the formation process. Negligible solar photospheric pollution is produced by the planetary formation process. Assuming similar levels of pollution in other planetary systems, this in turn implies that the high metallicity trend observed in extrasolar planetary systems is in fact primordial.Comment: 61 pages (including online material), 12 figures (7 in paper, 5 online). Accepted to Icaru

Orbital migration and the period distribution of exoplanets

We use the model for the migration of planets introduced in Del Popolo, Yesilyurt & Ercan (2003) to calculate the observed mass and semimajor axis distribution of extra-solar planets. The assumption that the surface density in planetesimals is proportional to that of gas is relaxed, and in order to describe disc evolution we use a method which, using a series of simplifying assumptions, is able to simultaneously follow the evolution of gas and solid particles for up to $10^7 {\rm yr}$. The distribution of planetesimals obtained after $10^7 {\rm yr}$ is used to study the migration rate of a giant planet through the model of this paper. The disk and migration models are used to calculate the distribution of planets as function of mass and semimajor axis. The results show that the model can give a reasonable prediction of planets' semi-major axes and mass distribution. In particular there is a pile-up of planets at $a \simeq 0.05$ AU, a minimum near 0.3 AU, indicating a paucity of planets at that distance, and a rise for semi-major axes larger than 0.3 AU, out to 3 AU. The semi-major axis distribution shows that the more massive planets (typically, masses larger than $4 M_{\rm J}$) form preferentially in the outer regions and do not migrate much. Intermediate-mass objects migrate more easily whatever the distance they form, and that the lighter planets (masses from sub-Saturnian to Jovian) migrate easily.Comment: published in A&

Structure-based development of specific inhibitors for individual cathepsins and their medical applications

Specific inhibitors for individual cathepsins have been developed based on their tertiary structures of X-ray crystallography. Cathepsin B-specific inhibitors, CA-074 and CA-030, and cathepsin L specific inhibitors, CLIK-148 and CLIK-195, were designed as the epoxysuccinate derivatives. Cathepsin S inhibitor, CLIK-060, and cathepsin K inhibitor, CLIK-166, were synthesized. These inhibitors can use in vitro and also in vivo, and show no toxicity for experimental animals by the amounts used as the cathepsin inhibitor

Simple Synthesis of a Variety of Nano-structures Using Silicide Alloys with Ga Droplets

A variety of nano-structures, such as nanofibers, nanotubes, nanocapsules, nanoribbons and nanorods, were synthesized using silicide alloys with Ga droplets. It was found that the growth morphology and the structural property of the nanostructures significantly depended on the silicides seed materials. In addition, the amorphous SiO x nanofibers show strong ultraviolet and/or visible light emissions, and the PL spectra of the nanofibers depended on the seed materials. For some of the nanofiber syntheses, the formation of nanoflakes or nanoribbons of β-Ga 2 O 3 occurs, and a variety of growth morphologies for the β-Ga 2 O 3 nanostructures was obtained. The series of morphological and structural images are shown for a variety of nanostructures. The obtained SiO x nanofibers are expected to be materials for use in cheap, abundant and safe luminescent devices for visible light applications

SCF Ensures Meiotic Chromosome Segregation Through a Resolution of Meiotic Recombination Intermediates

The SCF (Skp1-Cul1-F-box) complex contributes to a variety of cellular events including meiotic cell cycle control, but its function during meiosis is not understood well. Here we describe a novel function of SCF/Skp1 in meiotic recombination and subsequent chromosome segregation. The skp1 temperature-sensitive mutant exhibited abnormal distribution of spindle microtubules in meiosis II, which turned out to originate from abnormal bending of the spindle in meiosis I. Bent spindles were reported in mitosis of this mutant, but it remained unknown how SCF could affect spindle morphology. We found that the meiotic bent spindle in skp1 cells was due to a hypertension generated by chromosome entanglement. The spindle bending was suppressed by inhibiting double strand break (DSB) formation, indicating that the entanglement was generated by the meiotic recombination machinery. Consistently, Rhp51/Rad51-Rad22/Rad52 foci persisted until meiosis I in skp1 cells, proving accumulation of recombination intermediates. Intriguingly bent spindles were also observed in the mutant of Fbh1, an F-box protein containing the DNA helicase domain, which is involved in meiotic recombination. Genetic evidence suggested its cooperation with SCF/Skp1. Thus, SCF/Skp1 together with Fbh1 is likely to function in the resolution of meiotic recombination intermediates, thereby ensuring proper chromosome segregation

Vgl1, a multi-KH domain protein, is a novel component of the fission yeast stress granules required for cell survival under thermal stress

Multiple KH-domain proteins, collectively known as vigilins, are evolutionarily highly conserved proteins that are present in eukaryotic organisms from yeast to metazoa. Proposed roles for vigilins include chromosome segregation, messenger RNA (mRNA) metabolism, translation and tRNA transport. As a step toward understanding its biological function, we have identified the fission yeast vigilin, designated Vgl1, and have investigated its role in cellular response to environmental stress. Unlike its counterpart in Saccharomyces cerevisiae, we found no indication that Vgl1 is required for the maintenance of cell ploidy in Schizosaccharomyces pombe. Instead, Vgl1 is required for cell survival under thermal stress, and vgl1Δ mutants lose their viability more rapidly than wild-type cells when incubated at high temperature. As for Scp160 in S. cerevisiae, Vgl1 bound polysomes accumulated at endoplasmic reticulum (ER) but in a microtubule-independent manner. Under thermal stress, Vgl1 is rapidly relocalized from the ER to cytoplasmic foci that are distinct from P-bodies but contain stress granule markers such as poly(A)-binding protein and components of the translation initiation factor eIF3. Together, these observations demonstrated in S. pombe the presence of RNA granules with similar composition as mammalian stress granules and identified Vgl1 as a novel component that required for cell survival under thermal stress

Clinical and Genetic Characteristics of 18 Patients from 13 Japanese Families with CRX-associated retinal disorder: Identification of Genotype-phenotype Association

Inherited retinal disorder (IRD) is a leading cause of blindness, and CRX is one of a number of genes reported to harbour autosomal dominant (AD) and recessive (AR) causative variants. Eighteen patients from 13 families with CRX-associated retinal disorder (CRX-RD) were identified from 730 Japanese families with IRD. Ophthalmological examinations and phenotype subgroup classification were performed. The median age of onset/latest examination was 45.0/62.5 years (range, 15–77/25–94). The median visual acuity in the right/left eye was 0.52/0.40 (range, −0.08–2.00/−0.18–1.70) logarithm of the minimum angle of resolution (LogMAR) units. There was one family with macular dystrophy, nine with cone-rod dystrophy (CORD), and three with retinitis pigmentosa. In silico analysis of CRX variants was conducted for genotype subgroup classification based on inheritance and the presence of truncating variants. Eight pathogenic CRX variants were identified, including three novel heterozygous variants (p.R43H, p.P145Lfs*42, and p.P197Afs*22). A trend of a genotype-phenotype association was revealed between the phenotype and genotype subgroups. A considerably high proportion of CRX-RD in ADCORD was determined in the Japanese cohort (39.1%), often showing the mild phenotype (CORD) with late-onset disease (sixth decade). Frequently found heterozygous missense variants located within the homeodomain underlie this mild phenotype. This large cohort study delineates the disease spectrum of CRX-RD in the Japanese population

Genetic Spectrum of EYS-associated Retinal Disease in a Large Japanese Cohort: Identification of Disease-associated Variants with Relatively High Allele Frequency

Biallelic variants in the EYS gene are a major cause of autosomal recessive inherited retinal disease (IRD), with a high prevalence in the Asian population. The purpose of this study was to identify pathogenic EYS variants, to determine the clinical/genetic spectrum of EYS-associated retinal disease (EYS-RD), and to discover disease-associated variants with relatively high allele frequency (1%-10%) in a nationwide Japanese cohort. Sixty-six affected subjects from 61 families with biallelic or multiple pathogenic/disease-associated EYS variants were ascertained by whole-exome sequencing. Three phenotype groups were identified in EYS-RD: retinitis pigmentosa (RP; 85.94%), cone-rod dystrophy (CORD; 10.94%), and Leber congenital amaurosis (LCA; 3.12%). Twenty-six pathogenic/disease-associated EYS variants were identified, including seven novel variants. The two most prevalent variants, p.(Gly843Glu) and p.(Thr2465Ser) were found in 26 and twelve families (42.6%, 19.7%), respectively, for which the allele frequency (AF) in the Japanese population was 2.2% and 3.0%, respectively. These results expand the phenotypic and genotypic spectrum of EYS-RD, accounting for a high proportion of EYS-RD both in autosomal recessive RP (23.4%) and autosomal recessive CORD (9.9%) in the Japanese population. The presence of EYS variants with relatively high AF highlights the importance of considering the pathogenicity of non-rare variants in relatively prevalent Mendelian disorders