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Myotonic dystrophy type 1 (DM1) is an autosomal dominant myopathic CTG triplet repeat disorder that affects the muscles, eyes, heart, endocrine system and central nervous system. DM1 can be broadly classified into at least four subtypes based on the patient’s clinical presentation: congenital

We propose an interface with two novel techniques to visualize occluded graph nodes and edges that help the user edit map data with a 2.5D geographical structure (e.g., multi-floor indoor maps). We first design a visualization technique -Repel Signification- that employs micro-animation to signify the graph elements that are overlapping with each other (and potentially erroneous). We also design a technique that enables the user to edit the occluded components with Expansion Interaction, which simultaneously visualizes both in-floor and across-floor occluded connections between the map elements. The combination of the two methods would enable the map editors (non-experts) to effectively find and fix erroneous data in 2.5D maps without changing the operation manner from the existing 2D map-editing interface.

We present “Be Bait!”, a unique virtual fishing experience that allows the user to become a bait by lying on the hammocks, instead of holding a fishing rod. We implement the hammock-based locomotion method with haptic feedback mechanisms. In our demonstration, users can enjoy exploring a virtual underwater world and fighting with fishes in direct and intuitive ways.

Budding yeast has dozens of prions, which are mutually dependent on each other for the de novo prion formation. In addition to the interactions among prions, transmissions of prions are strictly dependent on two chaperone systems: the Hsp104 and the Hsp70/Hsp40 (J-protein) systems, both of which cooperatively remodel the prion aggregates to ensure the multiplication of prion entities. Since it has been postulated that prions and the remodeling factors constitute complex networks in cells, a quantitative approach to describe the interactions in live cells would be required. Here, the researchers applied dual-color fluorescence cross-correlation spectroscopy to investigate the molecular network of interaction in single live cells. The findings demonstrate that yeast prions and remodeling factors constitute a network through heterogeneous protein-protein interactions. [BMB Reports 2017; 50(9): 478-483].

An efficient and versatile synthesis of 5- N -acetylardeemin ( 1a ) and sixteen 2-, 3- and 13-substituted derivatives 1b – q was achieved through Ugi three-component reaction of 3,3a,8,8a-tetrahydropyrrolo[2,3- b ]indole and cyclization/epimerization. Their inhibitory activity on the drug efflux of breast cancer resistance protein (ABCG2) was evaluated by flow cytometric analysis of accumulation of Hoechst 33342 stain in Flp-In-293/ABCG2 cells. Most of the derivatives exhibited a stronger ABCG2 inhibitory effect compared with natural product 1a . The derivative 1m with a 4-tolyl substituent at the C-13 position exhibited the most potent ABCG2 inhibition. This preliminary structure–activity relationship study indicates that an electron-rich aryl moiety as the 13-substituent is key to increasing the inhibitory activity.

Three tetracyclic antidepressants, mianserin, mirtazapine, and setiptiline, were extracted from human plasma samples using a new micropipette solid-phase extraction tip containing a monolithic silica gel packing material, the MonoTip C18. The plasma samples (0.1 ml), which contained mianserin, mirtazapine, and setiptiline, were mixed with 330 μl of distilled water and 50 μl of 0.5 M glycine–sodium hydroxide buffer solution (pH 8). After centrifugation, the supernatant was extracted onto the C18 phase of the tip (pipette tip volume, 200 μl) by 25 sequential aspirating/dispensing cycles. The three analytes retained in the C18 phase were eluted with methanol by 5 aspirating/dispensing cycles. The eluate was subjected to measurements by gas chromatography (GC) with nitrogen–phosphorus detection (NPD). The recoveries of the three antidepressants were 84.6–99.6% and the limits of detection for each drug were between 2.4 and 15 ng/ml of plasma. The maximum intraday and interday coefficients of variation for the drugs was below 10.6%. Regression equations for the three drugs showed excellent linearity in the range of 50–5000 ng/ml for mianserin and mirtazapine and 50–10 000 ng/ml for setiptiline. The antidepressants were stable for at least 12 h at 4°C, 4 weeks at −80°C, and through three freeze–thaw cycles in plasma. The validated method was successfully used to quantify the plasma concentrations of mirtazapine in a human subject after oral administration of the drug. Although we achieved analyte detection with GC-NPD, the present monolithic micropipette extraction method for tetracyclic antidepressants seems to be very useful for combining it with GC–mass spectrometry (MS) and/or liquid chromatography–tandem MS to secure high simplicity, purification, reproducibility, and sensitivity.

We report a 25-year-old woman who developed optic neuritis and encephalomyelitis following primary Sjögren's syndrome (SjS). SjS began with Sicca syndrome when she was 8 years old, and neurological involvement subsequently developed at the age of 10 with right hemiparesis. Based on clinical symptoms, serum positive for SS-A and SS-B antibodies and pathological findings of the salivary gland, we confirmed a diagnosis of primary SjS. Magnetic resonance imaging (MRI) revealed multiple lesions in the brain and the spinal cord. These led diagnosis of SjS with central nervous system involvement (CNS-SjS) and initiated steroid therapy. At the age of 25, the patient developed left visual loss due to retrobulbar optic neuritis, left lower quadrantic hemianopia, numbness of the right upper limb, and weakness of both legs. Laboratory examinations showed that her serum was positive for SS-A and SS-B antibodies, and her cerebrospinal fluid had elevated levels of total protein and myelin basic protein without pleocytosis. Her brain MRI revealed multiple T2-high-intensity lesions bilaterally in the frontal subcortical white matter and in the right temporo-parietal subcortical white matter. The lesions included a tumefactive lesion and an active lesion. Additionally, the spinal MRI revealed a severely atrophied spinal cord with T2-high-intensity lesions extending longitudinally and centromedullary in the spinal cord. These findings led us to examine the patient's serum for anti-aquaporin (AQP) 4 antibodies and the test confirmed that her serum was positive for the antibodies. After administering intravenous high-dose methylprednisolone (1,000 mg/day for 3 days), her symptoms markedly improved with normalization of myelin basic protein. However, her serum remained positive for AQP 4 antibodies. We think that the patient's diagnosis belongs to the neuromyelitis optica (NMO) spectrum disorders associated with autoimmune disorders. This is a rare case in that the initial presentation was SjS and occurred at a very young age.

We report a 59-year-old immunocompetent man presenting with slowly progressive gait unsteadiness, dysarthria, and clumsiness in writing over 6 months. There were bilateral pyramidal signs, pseudobulbar palsy, and attention deficits. Cerebrospinal fluid examination showed mild mononuclear pleocytosis, and magnetic resonance imaging revealed pachymeningeal pattern of contrast enhancement beneath the calvarium and the posterior cranial fossa. Interferon-gamma release assay in whole blood after stimulation by specific tuberculosis antigens was positive and repeat polymerase chain reaction assay detected Mycobacterium tuberculosis genome in the cerebrospinal fluid. After combination therapy with anti-tuberculous agents and corticosteroids, the patient's pachymeningitis regressed. Tuberculous cranial pachymeningitis may present with chronic diffuse brain dysfunction without headache, fever, or cranial nerve dysfunction.