Stratifinはubiquitin-specific protease 8を活性化することにより受容体型チロシンキナーゼの分解を抑制する

筑波大学 (University of Tsukuba)201

Top-down, decoupled control of constitutive parameters in electromagnetic metamaterials with dielectric resonators of internal anisotropy

A meta-atom platform providing decoupled tuning for the constitutive wave parameters remains as a challenging problem, since the proposition of Pendry. Here we propose an electromagnetic meta-atom design of internal anisotropy (ε_r ≠ ε_θ), as a pathway for decoupling of the effective- permittivity ε_(eff) and permeability μ_(eff). Deriving effective parameters for anisotropic meta-atom from the first principles, and then subsequent inverse-solving the obtained decoupled solution for a target set of ε_(eff) and μ_(eff), we also achieve an analytic, top-down determination for the internal structure of a meta-atom. To realize the anisotropy from isotropic materials, a particle of spatial permittivity modulation in r or θ direction is proposed. As an application example, a matched zero index dielectric meta-atom is demonstrated, to enable the super-funneling of a 50λ-wide flux through a sub-λ slit; unharnessing the flux collection limit dictated by the λ-zone

Nontuberculous mycobacterial infection in a clinical presentation of Fitz-Hugh-Curtis syndrome: a case report with multigene diagnostic approach

BACKGROUND: Fitz-Hugh-Curtis syndrome (FHCS) is caused by inflammation of perihepatic capsules associated with pelvic inflammatory disease. In recent years, infections with nontuberculous mycobacteria (NTM) have been increasingly occurring in immunocompromised and immunocompetent patients. However, NTM has never been reported in patients with FHCS. We present the first case of a patient with extrapulmonary NTM infection in a clinical presentation of FHCS. CASE PRESENTATION: A 26-year-old Korean woman presented with right upper quadrant and suprapubic pain. She was initially suspected to have FHCS. However, she was refractory to conventional antibiotic therapy. Laparoscopy revealed multiple violin-string adhesions of the parietal peritoneum to the liver and miliary-like nodules on the peritoneal surfaces. Diagnosis of NTM was confirmed by the polymerase chain reaction analysis results of biopsy specimens that showed caseating granulomas with positive acid-fast bacilli. Treatment with anti-NTM medications was initiated, and the patient’s symptoms were considerably ameliorated. CONCLUSIONS: An awareness of NTM as potential pathogens, even in previously healthy adults, and efforts to exclude other confounding diseases are important to establish the diagnosis of NTM disease. NTM infection can cause various clinical manifestations, which in the present case, overlapped with the symptoms of perihepatic inflammation seen in FHCS

Analyses of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic imbalance

Complex human traits are influenced by variation in regulatory DNA through mechanisms that are not fully understood. Since regulatory elements are conserved between humans and mice, a thorough annotation of cis regulatory variants in mice could aid in this process. Here we provide a detailed portrait of mouse gene expression across multiple tissues in a three-way diallel. Greater than 80% of mouse genes have cis regulatory variation. These effects influence complex traits and usually extend to the human ortholog. Further, we estimate that at least one in every thousand SNPs creates a cis regulatory effect. We also observe two types of parent-of-origin effects, including classical imprinting and a novel, global allelic imbalance in favor of the paternal allele. We conclude that, as with humans, pervasive regulatory variation influences complex genetic traits in mice and provide a new resource toward understanding the genetic control of transcription in mammals

Phospholipase A2β mediates light-induced stomatal opening in Arabidopsis

Phospholipase A2 (PLA2) catalyses the hydrolysis of phospholipids into lysophospholipids and free fatty acids. Physiological studies have indicated that PLA2 is involved in stomatal movement. However, genetic evidence of a role of PLA2 in guard cell signalling has not yet been reported. To identify PLA2 gene(s) that is (are) involved in light-induced stomatal opening, stomatal movement was examined in Arabidopsis thaliana plants in which the expression of PLA2 isoforms was reduced or knocked-out. Light-induced stomatal opening in PLA2α knockout plants did not differ from wild-type plants. Plants in which PLA2β was silenced by RNA interference exhibited delayed light-induced stomatal opening, and this phenotype was reversed by exogenous lysophospholipids, which are products of PLA2. Stomatal opening in transgenic plants that over-expressed PLA2β was faster than wild-type plants. The expression of PLA2β was localized to the endoplasmic reticulum of guard cells, and increased in response to light in the mature leaf. Aristolochic acid, which inhibits light-induced stomatal opening, inhibited the activity of purified PLA2β. Collectively, these results provide evidence that PLA2β is involved in light-induced stomatal opening in Arabidopsis

Hypothesis-driven candidate genes for schizophrenia compared to genome-wide association results

Candidate gene studies have been a key approach to the genetics of schizophrenia. Results of these studies have been confusing and no genes have been unequivocally implicated. The hypothesis-driven candidate gene literature can be appraised via comparison with the results of genome-wide association studies (GWAS)

Ubiquitin‐specific protease 8 is a novel prognostic marker in early‐stage lung adenocarcinoma

Alterations of epidermal growth factor receptor (EGFR) expression frequently occur in early‐stage lung adenocarcinoma. Ubiquitin‐specific protease 8 (USP8) has been reported to stabilize EGFR protein at the plasma membrane through the recycling pathway. Here, we examined the correlation between USP8 expression and the expression or mutation status of EGFR, as well as the clinicopathological features of lung adenocarcinoma and patient outcome. Expression of EGFR and USP8 in surgically resected specimens of lung adenocarcinoma (82 cases) was examined by immunohistochemistry. Overexpression of EGFR was mutually correlated with that of USP8, and was also associated with clinicopathological features including pathological subtype, lymphatic permeation, and vascular invasion. Moreover, patients who had USP8‐positive tumors had a significantly poorer outcome than those who were USP8‐negative, not only overall but also patients who were EGFR‐negative. Although EGFR was expressed in invasive adenocarcinoma but not in adenocarcinoma in situ (AIS), USP8 was overexpressed in not only invasive adenocarcinoma but also 38.1% of AIS cases. In vitro, USP8 regulated the expression and half‐life of EGFR in immortalized AIS cells, and also cell proliferation. Our findings indicate that overexpression of USP8 in lung adenocarcinoma is an early event during the course of tumor progression, and is related to EGFR expression

Candidate Risk Factors and Mechanisms for Tolvaptan-Induced Liver Injury Are Identified Using a Collaborative Cross Approach

Clinical trials of tolvaptan showed it to be a promising candidate for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) but also revealed potential for idiosyncratic drug-induced liver injury (DILI) in this patient population. To identify risk factors and mechanisms underlying tolvaptan DILI, 8 mice in each of 45 strains of the genetically diverse Collaborative Cross (CC) mouse population were treated with a single oral dose of either tolvaptan or vehicle. Significant elevations in plasma alanine aminotransferase (ALT) were observed in tolvaptan-treated animals in 3 of the 45 strains. Genetic mapping coupled with transcriptomic analysis in the liver was used to identify several candidate susceptibility genes including epoxide hydrolase 2, interferon regulatory factor 3, and mitochondrial fission factor. Gene pathway analysis revealed that oxidative stress and immune response pathways were activated in response to tolvaptan treatment across all strains, but genes involved in regulation of bile acid homeostasis were most associated with tolvaptan-induced elevations in ALT. Secretory leukocyte peptidase inhibitor (Slpi) mRNA was also induced in the susceptible strains and was associated with increased plasma levels of Slpi protein, suggesting a potential serum marker for DILI susceptibility. In summary, tolvaptan induced signs of oxidative stress, mitochondrial dysfunction, and innate immune response in all strains, but variation in bile acid homeostasis was most associated with susceptibility to the liver response. This CC study has indicated potential mechanisms underlying tolvaptan DILI and biomarkers of susceptibility that may be useful in managing the risk of DILI in ADPKD patients