Phagosome Escape of Rough Mycobacterium abscessus Strains in Murine Macrophage via Phagosomal Rupture Can Lead to Type I Interferon Production and Their Cell-To-Cell Spread

Mycobacterium abscessus complex (MAB) is a rapidly growing mycobacterium(RGM) whose clinical significance as an emerging human pathogen has been increasing worldwide. It has two types of colony morphology, a smooth (S) type, producing high glycopeptidolipid (GPL) content, and a rough (R) type, which produces low levels of GPLs and is associated with increased virulence. However, the mechanism responsible for their difference in virulence is poorly known. By ultrastructural examination of murine macrophages infected, we found that MAB-R strains could replicate more actively in the macrophage phagosome than the S variants and that they could escape into cytosol via phagosomal rupture. The cytosolic access of MAB-R strains via phagosomal rupture led to enhanced Type I interferon (IFN) production and cell death, which resulted in their cell-to-cell spreading. This behavior can provide an additional niche for the survival of MAB-R strains. In addition, we found that their enhancement of cell death mediated cell spreading are dependent on Type I IFN signaling via comparison of wild-type and IFNAR1 knockout mice. In conclusion, our data indicated that a transition of MAB-S strains into MAB-R variants increased their virulence via enhanced Type I IFN production, which led to enhanced survival in infected macrophage via cell death mediated cell-to-cell spreading. This result provides not only a novel insight into the difference in virulence between MAB-R and -S variants but also hints to their treatment strategy

Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. It has demonstrated neuroprotective properties against many forms of dementia. In this study, we assessed cognitively enhancing property of taurine in transgenic mouse model of AD. We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages.MIT International Science and Technology InitiativesKorea Health Industry Development Institute (H14C04660000)Korea Institute of Science and Technology (Open Research 2E24582)Korea Institute of Science and Technology (Flagship 2E25023

Rough colony morphology of Mycobacterium massiliense Type II genotype is due to the deletion of glycopeptidolipid locus within its genome

Background: Recently, we introduced the complete genome sequence of Mycobacterium massiliense clinical isolates, Asan 50594 belonging to Type II genotype with rough colony morphology. Here, to address the issue of whether the rough colony morphotype of M. massiliense Type II genotype is genetically determined or not, we compared polymorphisms of the glycopeptidolipid (GPL) gene locus between M. massiliense Type II Asan 50594 and other rapidly growing mycobacteria (RGM) strains via analysis of genome databases.Results: We found deletions of 10 genes (24.8 kb), in the GPL biosynthesis related gene cluster of Asan 50594 genome, but no deletions in those of other smooth RGMs. To check the presence of deletions of GPL biosynthesis related genes in Mycobacterium abscessus - complex strains, PCRs targeting 12 different GPL genes (10 genes deleted in Asan 50594 genome as well as 2 conserved genes) were applied into 76 clinical strains of the M. abscessus complex strains [54 strains (Type I: 33, and Type II: 21) of M. massiliense and 22 strains (rough morphoype: 11 and smooth morphotype: 11) of M. abscessus]. No strains of the Type II genotype produced PCR amplicons in a total of 10 deleted GPL genes, suggesting loss of GPL biosynthesis genes in the genome of M. massiliense type II genotype strains.Conclusions: Our data suggested that the rough colony morphotype of the M. massiliense Type II genotype may be acquired via deletion events at the GPL gene locus for evolutionary adaptation between the host and pathogen.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000006653/7SEQ:7PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000006653ADJUST_YN:YEMP_ID:A077651DEPT_CD:806CITE_RATE:4.397FILENAME:rough colony morphology of mycobacterium.pdfDEPT_NM:의과학과SCOPUS_YN:YCONFIRM:

Pneumocephalus in Patients With Orthostatic Headache

Cerebrospinal fluid (CSF) leak or shunt overdrainage is a well-known cause of orthostatic headaches and low CSF pressures. We report two cases of orthostatic headache with pneumocephalus on brain imaging. The orthostatic headache developed after drainage of spinal operation site and epidural block. Brain MRI revealed characteristic findings of CSF hypovolemia including pachymeningeal enhancement and mild subdural fluid collections. Air was also observed in the ventricular or subarachnoid space in both patients, which might enter the subarachnoid or ventricular space during a procedure via the pressure gradient or an injection

Therapeutic effects of a novel synthetic α-secretase

Excessive accumulation of amyloid-β (Aβ) has been associated with the pathogenesis of Alzheimer’s disease (AD). Clinical studies have further proven that elimination of Aβ can be a viable therapeutic option. In the current study, we conceptualized a fusion membrane protein, referred to as synthetic α-secretase (SAS), that can cleave amyloid precursor protein (APP) and Aβ specifically at the α-site. In mammalian cells, SAS indeed cleaved APP and Aβ at the α-site. Overexpression of SAS in the hippocampus was achieved by direct injection of recombinant adeno-associated virus serotype 9 (AAV9) that expresses SAS (AAV9-SAS) into the bilateral ventricles of mouse brains. SAS enhanced the non-amyloidogenic processing of APP, thus reducing the levels of soluble Aβ and plaques in the 5xFAD mice. In addition, SAS significantly attenuated the cognitive deficits in 5xFAD mice, as demonstrated by novel object recognition and Morris water maze tests. Unlike other Aβ-cleaving proteases, SAS has highly strict substrate specificity. We propose that SAS can be an efficient modality to eliminate excessive Aβ from diseased brains

Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy

Recessive mutations in chromosome 10 open reading frame 2 (C10orf2) are relevant in infantile-onset spinocerebellar ataxia (IOSCA). In this study, we investigated the causative mutation in a Korean family with combined phenotypes of IOSCA, sensorimotor polyneuropathy, and myopathy. We investigated recessive mutations in a Korean family with two individuals affected by IOSCA. Causative mutations were investigated using whole exome sequencing. Electrophysiological analyses and muscle and nerve biopsies were performed, along with magnetic resonance imaging (MRI) of the brain and lower extremities. Compound heterozygous mutations c.1460C>T and c.1485-1G>A in C10orf2 were identified as causative of IOSCA. Skeletal muscle showed mitochondrial DNA (mtDNA) deletions. Both patients showed a period of normal development until 12–15 months, followed by ataxia, athetosis, hearing loss, and intellectual disability. Electrophysiological findings indicated motor and sensory polyneuropathies. Muscle biopsy revealed variations in the size and shape of myofibers with scattered, small, and angulated degenerating myofibers containing abnormal mitochondria; these observations are consistent with myopathy and may be the result of mtDNA deletions. Sural nerve biopsy revealed an axonal neuropathy. High-signal-intensity lesions in the middle cerebellar peduncles were correlated with clinical severity, and MRI of the lower legs was compatible with the hypothesis of length-dependent axonal degeneration. We identified novel compound heterozygous mutations of the C10orf2 gene as the cause of IOSCA with sensorimotor polyneuropathy and myopathy. Signs of motor neuropathy and myopathy were discovered for the first time in IOSCA patients with C10orf2 mutations. These results suggest that the clinical spectrum of IOSCA caused by C10orf2 mutations may be more variable than previously reported. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-014-0405-1) contains supplementary material, which is available to authorized users

Synergistic surface modification for high-efficiency perovskite nanocrystal light-emitting diodes: divalent metal ion doping and halide-based ligand passivation

Surface defects of metal halide perovskite nanocrystals (PNCs) substantially compromise the optoelectronic performances of the materials and devices via undesired charge recombination. However, those defects, mainly the vacancies, are structurally entangled with each other in the PNC lattice, necessitating a delicately designed strategy for effective passivation. Here, a synergistic metal ion doping and surface ligand exchange strategy is proposed to passivate the surface defects of CsPbBr3 PNCs with various divalent metal (e.g., Cd2+, Zn2+, and Hg2+) acetate salts and didodecyldimethylammonium (DDA+) via one-step post-treatment. The addition of metal acetate salts to PNCs is demonstrated to suppress the defect formation energy effectively via the ab initio calculations. The developed PNCs not only have near-unity photoluminescence quantum yield and excellent stability but also show luminance of 1175 cd m−2, current efficiency of 65.48 cd A−1, external quantum efficiency of 20.79%, wavelength of 514 nm in optimized PNC light-emitting diodes with Cd2+ passivator and DDA ligand. The “organic–inorganic” hybrid engineering approach is completely general and can be straightforwardly applied to any combination of quaternary ammonium ligands and source of metal, which will be useful in PNC-based optoelectronic devices such as solar cells, photodetectors, and transistors

The Multifunctional Building of Passive Standard

Import 26/02/2015Tato diplomová práce je zaměřena na vyprojektování multifunkčního domu, ve kterém bude zajištěno strojní větrání a zajištěno vytápění pomocí alternativního zdroje tepla. Multifunkční dům podsklepený a má čtyři nadzemní podlaží s pochozí terasou. Objekt je navržen ze sortimentu firmy Porotherm. Funkčně je navržen tak, že v prvním podzemním podlaží se nachází technické zázemí a kóje bytů, první nadzemní podlaží tvoří dvě nezávislé prodejní plochy. Ve druhém patře jsou umístěny kancelářské prostory. Druhou horní polovinu objektu , třetí a čtvrté nadzemní podlaží, tvoří bytové jednotky. Základním kamenem pro nutnou výměnu vzduchu v objektu jsou tři vzduchotechnické systémy, které se starají o dodávku a výměnu vzduchu ve třech celcích. První celkem je jednotka pro prodejní plochy v prvním nadzemním podlaží a kancelářské prostory ve druhém nadzemním podlaží. Druhá jednotka má na starosti byty ve třetím a čtvrtém podlaží a poslední, třetí, jednotka zajišťuje přívod čerstvého vzduchu do společných prostor a odvod odpadního vzduchu do exteriéru. Všechny jednotky jsou vybaveny rekuperátorem. V objektu je také řešeno vytápění pomocí alternativních zdrojů. Jako alternativní zdroje energie jsou použity tepelné čerpadlo vzduch – voda a solární kolektory. Tepelné čerpadlo se stará o pokrytí tepelných ztrát prostupem, větráním a přípravou teplé vody. Solární kolektory umístěné na terase pomáhají s ohřevem teplé vody v objektu.This Master thesis is focused on the projection Multifunctional building, which will ensure mechanical ventilation and heating ensured by using alternative heat sources. Multifunctional building basement and has four floors with walkable terrace. The building is designed from company Porotherm. Functionally, it is designed so that on the first floor there is a technical background and cubicle apartments, first floor consists of two independent sales area. On the second floor there are office spaces. The second half of the upper house, the third and fourth floors, consists of residential units. The cornerstone for the necessary air exchange in the building are three air handling systems that are responsible for the delivery and exchange of air in three units. The first is the total unit sales area on the first floor and office space on the second floor. The second unit is in charge of flats in the third and fourth floors and the last third unit provides fresh air to the common area and the exhaust to the exterior. All units are equipped with a recuperator. There is also heating solutions using alternative sources. As alternative energy sources are used heat pump air - water and solar collectors. The heat pump takes care of the cover heat losses through transmission, ventilation and hot water. Solar collectors located on the terrace help with hot water in the building.Prezenční229 - Katedra prostředí staveb a TZBvýborn

Aspergillus as a multi-purpose cell factory: current status and perspectives

Aspergilli have a long history in biotechnology as expression platforms for the production of food ingredients, pharmaceuticals and enzymes. The achievements made during the last years, however, have the potential to revolutionize Aspergillus biotechnology and to assure Aspergillus a dominant place among microbial cell factories. This mini-review will highlight most recent breakthroughs in fundamental and applied Aspergillus research with a focus on new molecular tools, techniques and products. New trends and concepts related to Aspergillus genomics and systems biology will be discussed as well as the challenges that have to be met to integrate omics data with metabolic engineering attempts