Non-perturbative Effect on Thermal Relic Abundance of Dark Matter

We point out that thermal relic abundance of the dark matter is strongly altered by a non-perturbative effect called the Sommerfeld enhancement, when constituent particles of the dark matter are non-singlet under the SU(2)_L gauge interaction and much heavier than the weak gauge bosons. Typical candidates for such dark matter particles are the heavy wino- and higgsino-like neutralinos. We investigate the non-perturbative effect on the relic abundance of dark matter for the wino-like neutralino as an example. We show that its thermal abundance is reduced by 50% compared to the perturbative result. The wino-like neutralino mass consistent with the observed dark matter abundance turns out to be 2.7 TeV < m < 3.0 TeV.Comment: 10 pages, 2 figure

MicroRNAs in systemic rheumatic diseases

MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNAs about 21 nucleotides in length. miRNAs have been shown to regulate gene expression and thus influence a wide range of physiological and pathological processes. Moreover, they are detected in a variety of sources, including tissues, serum, and other body fluids, such as saliva. The role of miRNAs is evident in various malignant and nonmalignant diseases, and there is accumulating evidence also for an important role of miRNAs in systemic rheumatic diseases. Abnormal expression of miRNAs has been reported in autoimmune diseases, mainly in systemic lupus erythematosus and rheumatoid arthritis. miRNAs can be aberrantly expressed even in the different stages of disease progression, allowing miRNAs to be important biomarkers, to help understand the pathogenesis of the disease, and to monitor disease activity and effects of treatment. Different groups have demonstrated a link between miRNA expression and disease activity, as in the case of renal flares in lupus patients. Moreover, miRNAs are emerging as potential targets for new therapeutic strategies of autoimmune disorders. Taken together, recent data demonstrate that miRNAs can influence mechanisms involved in the pathogenesis, relapse, and specific organ involvement of autoimmune diseases. The ultimate goal is the identification of a miRNA target or targets that could be manipulated through specific therapies, aiming at activation or inhibition of specific miRNAs responsible for the development of disease

Stability of Metastable Vacua in Gauge Mediated SUSY Breaking Models with Ultra Light Gravitino

Recently Murayama and Nomura proposed a simple scheme to construct the gauge mediation models, using metastable supersymmetry breaking vacua. It has a possibility to predict the ultra light gravitino mass m_{3/2} \lesssim 16 eV, while such a light gravitino may destabilize the metastable vacua. We investigate stability of the metastable vacuum of their model. The transition rate from the false vacuum to true ones is evaluated by numerical calculation, including the Coleman-Weinberg potential destabilizing the metastable vacuum. It is found that when the messenger sector is minimal, stability of the metastable vacuum imposes an upperbound on squark mass M_{\tilde q} for the ultra light gravitino as M_{\tilde q} \lesssim 1800 GeV at most. Squarks with this mass may be found in the LHC experiments.Comment: 11 pages, 3 figure

Electric Dipole Moments in PseudoDirac Gauginos

The SUSY CP problem is one of serious problems in construction of realistic supersymmetric standard models. We consider the problem in a framework in which adjoint chiral multiplets are introduced and gauginos have Dirac mass terms induced by a U(1) gauge interaction in the hidden sector. This is realized in hidden sector models without singlet chiral multiplets, which are favored from a recent study of the Polonyi problem. We find that the dominant contributions to electron and neutron electric dipole moments (EDMs) in the model come from phases in the supersymmetric adjoint mass terms. When the supersymmetric adjoint masses are suppressed by a factor of \sim 100 compared with the Dirac ones, the electron and neutron EDMs are suppressed below the experimental bound even if the SUSY particle masses are around 1 TeV. Thus, this model works as a framework to solve the SUSY CP problem.Comment: 17 pages, 2 figures; typos are corrected; accepted for Phys. Lett.

内因性プロゲステロン分泌は、合成プロゲステロン製剤を用いたホルモン補充凍結胚移植周期において妊娠予後予測因子になり得る

Purpose: A retrospective, cohort study was conducted between 2009 and 2017 in a private infertility center to determine the predictive value of endogenous estrogen (E2) and progesterone (P4) levels in hormone‐replacement frozen embryo replacement (FER) treatment cycles. Methods: A total of 120 consecutive, infertile patients who became pregnant after FER cycles were analyzed (age: 37.4 ± 4.4 years). Electively vitrified blastocysts were created during natural cycle IVF or mild ovarian stimulation treatments and subsequently transferred through delayed vitrified‐thawed blastocyst transfer cycles supplemented with estrogens and a combination of synthetic progestogens. Serum E2 and progesterone P4 levels were intensively monitored every five days (from the day after embryo transfer until 9w1d of pregnancy) and compared among patients with a subsequent live birth (n = 76) or first‐trimester pregnancy loss (n = 44). Results: Endogenous placental activity started as early as 5‐6th pregnancy week differing significantly according to pregnancy outcome. For P4, the exponential rise from 6w2d onwards allowed distinguishing between failing and successful conceptions. For P4, lower quartiles of the live birth group did not intersect with upper quartiles of the miscarriage group. Conclusions: Innovative FER protocols incorporating synthetic progestogens allow the correct measurement of endogenous placental activity and could help to monitor early first‐trimester ART pregnancies

The selective continued linkage of centromeres from mitosis to interphase in the absence of mammalian separase

Separase is an evolutionarily conserved protease that is essential for chromosome segregation and cleaves cohesin Scc1/Rad21, which joins the sister chromatids together. Although mammalian separase also functions in chromosome segregation, our understanding of this process in mammals is still incomplete. We generated separase knockout mice, reporting an essential function for mammalian separase. Separase-deficient mouse embryonic fibroblasts exhibited severely restrained increases in cell number, polyploid chromosomes, and amplified centrosomes. Chromosome spreads demonstrated that multiple chromosomes connected to a centromeric region. Live observation demonstrated that the chromosomes of separase-deficient cells condensed, but failed to segregate, although subsequent cytokinesis and chromosome decondensation proceeded normally. These results establish that mammalian separase is essential for the separation of centromeres, but not of the arm regions of chromosomes. Other cell cycle events, such as mitotic exit, DNA replication, and centrosome duplication appear to occur normally. We also demonstrated that heterozygous separase-deficient cells exhibited severely restrained increases in cell number with apparently normal mitosis in the absence of securin, which is an inhibitory partner of separase

Clinical association of serum interleukin 17 levels in systemic sclerosis: Is systemic sclerosis a Th17 disease?

金沢大学医薬保健研究域医学

A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients

The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. Graphical Abstract

Analysis of cell cycle-related proteins in gastric intramucosal differentiated-type cancers based on mucin phenotypes: a novel hypothesis of early gastric carcinogenesis based on mucin phenotype

<p>Abstract</p> <p>Background</p> <p>Abnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. However, recent studies have shown that gastric cancer tumorigenesis was characterized by mucin expression. Thus, expression patterns of cell cycle-related proteins were investigated in the early phase of differentiated-type gastric cancers to ascertain any mechanistic relationships with mucin phenotypes.</p> <p>Methods</p> <p>Immunostaining for Cyclins D1, A, E, and p21, p27, p53 and β-catenin was used to examine impairments of the cell cycle in 190 gastric intramucosal differentiated-type cancers. Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10. A Ki-67 positive rate (PR) was also examined.</p> <p>Results</p> <p>Overexpressions of p53, cyclin D1 and cyclin A were significantly more frequent in a gastric phenotype than an intestinal phenotype. Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype. Reduction of p21 was a common feature of the gastric intramucosal differentiated-type cancers examined.</p> <p>Conclusions</p> <p>Our results suggest that the levels of some cell cycle regulators appear to be associated with mucin phenotypes of early gastric differentiated-type cancers.</p

Overexpression of optineurin E50K disrupts Rab8 interaction and leads to a progressive retinal degeneration in mice

Glaucoma is one of the leading causes of bilateral blindness affecting nearly 8 million people worldwide. Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) and is often associated with elevated intraocular pressure (IOP). However, patients with normal tension glaucoma (NTG), a subtype of primary open-angle glaucoma (POAG), develop the disease without IOP elevation. The molecular pathways leading to the pathology of NTG and POAG are still unclear. Here, we describe the phenotypic characteristics of transgenic mice overexpressing wild-type (Wt) or mutated optineurin (Optn). Mutations E50K, H486R and Optn with a deletion of the first (amino acids 153–174) or second (amino acids 426–461) leucine zipper were used for overexpression. After 16 months, histological abnormalities were exclusively observed in the retina of E50K mutant mice with loss of RGCs and connecting synapses in the peripheral retina leading to a thinning of the nerve fiber layer at the optic nerve head at normal IOP. E50K mice also showed massive apoptosis and degeneration of entire retina, leading to approximately a 28% reduction of the retina thickness. At the molecular level, introduction of the E50K mutation disrupts the interaction between Optn and Rab8 GTPase, a protein involved in the regulation of vesicle transport from Golgi to plasma membrane. Wt Optn and an active GTP-bound form of Rab8 complex were localized at the Golgi complex. These data suggest that alternation of the Optn sequence can initiate significant retinal degeneration in mice