A novel ENU-induced mutation in Myo6 causes vestibular dysfunction and deafness

Mouse N-ethyl-N-nitrosourea (ENU) mutagenesis has generated many useful animal models for human diseases. Here we describe the identification of a novel ENU-induced mouse mutant strain Turner (Tur) that displays circling and headtossing behavior and progressive hearing loss. Tur/Tur homozygous animals lack Preyer and righting reflexes and display severe headtossing and reaching response defect. We mapped the Tur mutation to a critical region of 11 cM on chromosome 9 that includes myosin VI. Direct sequence analysis revealed a c.820A>T substitution in exon 8 of the Myo6 gene that changes amino acid Asn200 to Ile (p.N200I) in the motor domain. Analysis of inner ear hair cells by immunohistochemistry, scanning electron microscopy and histology revealed degeneration of hair cells in the inner ear and structural malformation of the stereocilia in the cochlea of Turner homozygous mutant mice. Our data indicate that this novel mouse strain provides a useful model for future studies on the function of myosin VI in mammalian auditory and non-auditory systems and in human syndromes.published_or_final_versio

Iron-Catalyzed Nitrene Insertion Reaction for Facile Construction of Amide Compounds

A facile method for the construction of amide compounds from aldehydes by an iron-catalyzed nitrene insertion reaction has been developed. Both aryl and aliphatic aldehydes can directly afford the corresponding amides with an iron(II)-terpyridine (tpy) complex formed in situ as catalyst, and PhI=NTs as nitrogen source under mild reaction conditions. An ESI-MS study revealed the formation of [Fe(tpy)NTs)]+ as a reaction intermediate. © Georg Thieme Verlag Stuttgart - New York.postprin

Wavelength-routed networks with lightpath data interchanges

We observe that tunable wavelength converters (TWCs) that are traditionally installed in wavelength-routed (WR) networks for wavelength contention resolution can be further utilized to provide fast data switching between lightpaths. This allows us to route a data unit through a sequence of lightpaths from source to destination if a direct single lightpath connection is not available or if we want to minimize the overhead of setting up new lightpaths. Since TWCs have a tuning time of picoseconds, it may be possible to use the installed TWCs as lightpath data interchanges (LPIs) to improve the performance of WR networks without significant optical hardware upgrade. Compared with the multihop electronic grooming approach of lightpath networks, the LPI approach has a simpler WR node architecture, does not need expensive high-speed electrical multiplexers/routers, and does not sacrifice the bit-rate/format transparency of data between the source and destination. Our simulation results show that WR networks with LPIs can have much lower blocking probability than WR networks without LPIs if the traffic duration is short. We show that LPIs can also be used to provide new data transportation services such as optical time division multiplexing access (OTDMA) time-slotted service in WR networks. © 2010 OSA.published_or_final_versio

Magneto-Stokes Flow in a Shallow Free-Surface Annulus

We analyse a magnetohydrodynamic flow inspired by the kinematic reversibility of viscous Taylor-Couette flows. The system considered here shares the cylindrical-annular geometry of the Taylor-Couette cell, but uses applied electromagnetic forces to drive "magneto-Stokes" flow in a shallow, free-surface layer of electrolyte. An analytical solution is presented and validated with coupled laboratory and numerical experiments. The dominant balance of Lorentz forcing and basal viscous drag reproduces the kinematic reversibility observed by G.I. Taylor with precise electromagnetic control. Induced fluid deformation may be undone by simply reversing the polarity of electric current through the system. We illustrate this analogy with theory and experiment, and we draw a further connection to potential flow using the Hele-Shaw approximation. The stability and controllability of the magneto-Stokes system make it an attractive tool for investigating shear flows in a variety of settings from industrial to astrophysical. In addition, the set-up's simplicity and robustness make magneto-Stokes flow a good candidate for PIV calibration and for educational demonstrations of magnetohydrodynamics, boundary layers, and flow transition

The depth-profiled carrier concentration and scattering mechanism in undoped GaN film grown on sapphire

The carrier concentration and scattering mechanism in undoped GaN film grown on sapphire were investigated. The film was grown on sapphire using metal organic chemical vapor deposition (MOCVD). Confocal micro-Raman spectroscopic measurements and temperature-dependant Hall (TDH) measurements were performed for the study of the depth distribution of the carrier density across the GaN film. The existence of a nonuniform spatial distribution of free carriers in the film with a highly conductive layer of ∼1 μm thickness near the GaN sapphire boundary was confirmed from the study. The electron mobility limiting effect of nitrogen vacancies on GaN bulk film was also discussed.published_or_final_versio

Priming Leukemia with 5-Azacytidine Enhances CAR T Cell Therapy

Purpose: Despite the success of chimeric antigen receptor (CAR) T cells in clinical studies, a significant proportion of responding patients eventually relapsed, with the latter correlating with low CAR T cell expansion and persistence. Methods and Results: Using patient-derived xenograft (PDX) mouse models of CD19+ B cell acute lymphoblastic leukemia (B-ALL), we show that priming leukemia-bearing mice with 5-azacytidine (AZA) enhances CAR T cell therapy. AZA given 1 day prior to CAR T cell infusion delayed leukemia growth and promoted CAR T cell expansion and effector function. Priming leukemia cells with AZA increased CAR T cell/target cell conjugation and target cell killing, promoted CAR T cell divisions and expanded IFNγ+ effector T cells in co-cultures with CD19+ leukemia Nalm-6 and Raji cells. Transcriptome analysis revealed activation of diverse immune pathways in leukemia cells isolated from mice treated with AZA. We propose that epigenetic priming with AZA induces transcriptional changes that sensitize tumor cells to subsequent CAR T cell treatment. Among the candidate genes up-regulated by AZA is TNFSF4 which encodes OX40L, one of the strongest T cell co-stimulatory ligands. OX40L binds OX40, the TNF receptor superfamily member highly specific for activated T cells. TNFSF4 is heterogeneously expressed in a panel of pediatric PDXs, and high TNFSF4 expression correlated with increased CAR T cell numbers identified in co-cultures with individual PDXs. High OX40L expression in Nalm-6 cells increased their susceptibility to CAR T cell killing while OX40L blockade reduced leukemia cell killing. Conclusion: We propose that treatment with AZA activates OX40L/OX40 co-stimulatory signaling in CAR T cells. Our data suggest that the clinical use of AZA before CAR T cells could be considered

Plasma fibrinogen level as a predictor of incident metabolic syndrome in a community-based prospective study in Hong Kong Chinese

BACKGROUND AND AIMS: Metabolic syndrome (MS) comprises a constellation of metabolic abnormalities associated with a high risk of developing diabetes and cardiovascular diseases. Central obesity, with related insulin resistance and inflammation are considered the core of the underlying pathogenesis of MS. Fibrinogen, an acute-phase reactant in the coagulation cascade, has been shown to play pivotal role in determining the extent of local or systemic inflammation. In this study, we examined whether plasma fibrinogen was predictive of incident MS in a community-based Chinese cohort. MATERIALS AND METHODS: Subjects were recruited from the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISPS) cohort. 2780 subjects were recruited in 1995-6 with baseline assessment performed. 1416 subjects without MS at …postprin

The clinical genetics of multiple endocrine neoplasia type 1 in Chinese

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Allitridi Inhibits Multiple Cardiac Potassium Channels Expressed in HEK 293 Cells

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Pertactin-negative and filamentous hemagglutinin-negative Bordetella pertussis, Australia, 2013-2017

During the 2008-2012 pertussis epidemic in Australia, pertactin (Prn)-negative Bordetella pertussis emerged. We analyzed 78 isolates from the 2013-2017 epidemic and documented continued expansion of Prn-negative ptxP3 B. pertussis strains. We also detected a filamentous hemagglutinin- negative and Prn-negative B. pertussis isolate