Dose-Dependent Rescue of KO Amelogenin Enamel by Transgenes in Vivo.

Science.gov (United States)

Bidlack, Felicitas B; Xia, Yan; Pugach, Megan K

2017-01-01

Mice lacking amelogenin (KO) have hypoplastic enamel. Overexpression of the most abundant amelogenin splice variant M180 and LRAP transgenes can substantially improve KO enamel, but only ~40% of the incisor thickness is recovered and the prisms are not as tightly woven as in WT enamel. This implies that the compositional complexity of the enamel matrix is required for different aspects of enamel formation, such as organizational structure and thickness. The question arises, therefore, how important the ratio of different matrix components, and in particular amelogenin splice products, is in enamel formation. Can optimal expression levels of amelogenin transgenes representing both the most abundant splice variants and cleavage product at protein levels similar to that of WT improve the enamel phenotype of KO mice? Addressing this question, our objective was here to understand dosage effects of amelogenin transgenes ( Tg ) representing the major splice variants M180 and LRAP and cleavage product CTRNC on enamel properties. Amelogenin KO mice were mated with M180 Tg , CTRNC Tg and LRAP Tg mice to generate M180 Tg and CTRNC Tg double transgene and M180 Tg , CTRNC Tg , LRAP Tg triple transgene mice with transgene hemizygosity (on one allelle) or homozygosity (on both alleles). Transgene homo- vs. hemizygosity was determined by qPCR and relative transgene expression confirmed by Western blot. Enamel volume and mineral density were analyzed by microCT, thickness and structure by SEM, and mechanical properties by Vickers microhardness testing. There were no differences in incisor enamel thickness between amelogenin KO mice with three or two different transgenes, but mice homozygous for a given transgene had significantly thinner enamel than mice hemizygous for the transgene ( p structure, but only up to a maximum of ~80% that of molar and ~40% that of incisor wild-type enamel.

Ekološko oblikovana embalaža za naravno kozmetiko

OpenAIRE

Šepec, Urša

2017-01-01

Namen diplomskega dela je bil raziskati področje ekološkega oblikovanja, zahteve in priporočila pri embaliranju na področju kozmetične industrije ter načrtovati in izdelati inovativno ekološko oblikovano funkcionalno embalažo za kolekcijo trdnih mil in šamponov, ki po odprtju služi kot podstavek za milo na umivalniku. Poleg embalaže smo izdelali tudi etikete za ostale kozmetične izdelke, kot so losjoni, kreme in mazila. V teoretičnem delu je opredeljeno ekološko oblikovanje embalaže ter s...

The founder of the church of Saint George at Pološko

Directory of Open Access Journals (Sweden)

Pavlović Dragana

2015-01-01

Full Text Available The paper seeks to establish who was the founder of the church of Saint George at Pološko and revise the conclusions of previous researchers regarding this issue. According to the opinion commonly adopted in the scholarly literature, Jovan Dragušin, a cousin of King Dušan, had merely undertaken the construction of church at Pološko, whereas his mother was responsible for the completion of construction and painting of frescoes in the church. Through an analysis of written and visual sources the conclusion is reached that the sole person responsible for the construction and painting of the church at Pološko was the nun Maria, the mother of Jovan Dragušin. [Projekat Ministarstva nauke Republike Srbije, br. 177036: Srpska srednjovekovna umetnost i njen evropski kontekst

Altered Immune Cytokine Expression Associated with KoRV B Infection and Season in Captive Koalas

Science.gov (United States)

Higgins, Damien P.

2016-01-01

Koala (Phascolarctos cinereus) populations are increasingly vulnerable and one of the main threats is chlamydial infection. Koala retrovirus (KoRV) has been proposed as an underlying cause of the koala’s susceptibility to infection with Chlamydia and high rates of lymphoid neoplasia; however, the regionally ubiquitous, endogenous nature of this virus suggests that KoRV A infection is not sufficient for immune suppression to occur. A recently discovered exogenous variant of KoRV, KoRV B, has several structural elements that cause increased pathogenicity in related retroviruses and was associated with lymphoid neoplasia in one study. The present study assesses whether KoRV B infection is associated with alterations in immune function. Cytokine gene expression by mitogen stimulated lymphocytes of KoRV B positive (n = 5–6) and negative (n = 6–7) captive koalas was evaluated by qPCR four times (April 2014-February 2015) to control for seasonal variation. Key immune genes in the Th1 pathway (IFNγ, TNFα), Th2 pathway (IL 10, IL4, IL6) and Th17 pathway (IL17A), along with CD4:CD8 ratio, were assessed. KoRV B positive koalas showed significantly increased up-regulation of IL17A and IL10 in three out of four sampling periods and IFNγ, IL6, IL4 and TNFα in two out of four. IL17A is an immune marker for chlamydial pathogenesis in the koala; increased expression of IL17A in KoRV B positive koalas, and concurrent immune dysregulation, may explain the differences in susceptibility to chlamydial infection and severity of disease seen between individuals and populations. There was also marked seasonal variation in up-regulation for most of the cytokines and the CD4:CD8 ratio. The up-regulation in both Th1 and Th2 cytokines mirrors changes associated with immune dysregulation in humans and felids as a result of retroviral infections. This is the first report of altered immune expression in koalas infected by an exogenous variant of KoRV and also the first report of

Region-Specific Defects of Respiratory Capacities in the Ndufs4(KO Mouse Brain.

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Ernst-Bernhard Kayser

Full Text Available Lack of NDUFS4, a subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase, causes Leigh syndrome (LS, a progressive encephalomyopathy. Knocking out Ndufs4, either systemically or in brain only, elicits LS in mice. In patients as well as in KO mice distinct regions of the brain degenerate while surrounding tissue survives despite systemic complex I dysfunction. For the understanding of disease etiology and ultimately for the development of rationale treatments for LS, it appears important to uncover the mechanisms that govern focal neurodegeneration.Here we used the Ndufs4(KO mouse to investigate whether regional and temporal differences in respiratory capacity of the brain could be correlated with neurodegeneration. In the KO the respiratory capacity of synaptosomes from the degeneration prone regions olfactory bulb, brainstem and cerebellum was significantly decreased. The difference was measurable even before the onset of neurological symptoms. Furthermore, neither compensating nor exacerbating changes in glycolytic capacity of the synaptosomes were found. By contrast, the KO retained near normal levels of synaptosomal respiration in the degeneration-resistant/resilient "rest" of the brain. We also investigated non-synaptic mitochondria. The KO expectedly had diminished capacity for oxidative phosphorylation (state 3 respiration with complex I dependent substrate combinations pyruvate/malate and glutamate/malate but surprisingly had normal activity with α-ketoglutarate/malate. No correlation between oxidative phosphorylation (pyruvate/malate driven state 3 respiration and neurodegeneration was found: Notably, state 3 remained constant in the KO while in controls it tended to increase with time leading to significant differences between the genotypes in older mice in both vulnerable and resilient brain regions. Neither regional ROS damage, measured as HNE-modified protein, nor regional complex I stability, assessed by blue native

Heat Flux Tests of the ITER FWQMs at KoHLT-1

International Nuclear Information System (INIS)

Bae, Young Dug; Kim, Suk Kwon; Shin, Hee Yun; Lee, Dong Won; Hong, Bong Guen

2009-05-01

As a party of the ITER, especially as a procurement party of the ITER blanket, we have designed the First Wall Qualification Mockup (FWQM) and fabricated five FWQMs. Two of them have been tested up to 12,690/12,020 cycles at a heat flux higher than 0.625 MW/m 2 at the KoHLT-1 facility established in the Korea Atomic Energy Research Institute (KAERI). Two KO FWQMs successfully passed the normal heat flux tests, and there was no indication of defect in the Be-to-CuCrZr joints

Function of brain α2B-adrenergic receptor characterized with subtype-selective α2B antagonist and KO mice.

Science.gov (United States)

Luhrs, Lauren; Manlapaz, Cynthia; Kedzie, Karen; Rao, Sandhya; Cabrera-Ghayouri, Sara; Donello, John; Gil, Daniel

2016-12-17

Noradrenergic signaling, through the α 2A and α 2C adrenergic receptors modulates the cognitive and behavioral symptoms of disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and addiction. However, it is unknown whether the α 2B receptor has any significant role in CNS function. The present study elucidates the potential role of the α 2B receptor in CNS function via the discovery and use of the first subtype-selective α 2B antagonist (AGN-209419), and behavioral analyses of α-receptor knockout (KO) mice. Using AGN-209419 as radioligand, α 2B receptor binding sites were identified within the olfactory bulb, cortex, thalamus, cerebellum, and striatum. Based on the observed expression patterns of α 2 subtypes in the brain, we compared α 2B KO, α 2A KO and α 2C KO mice behavioral phenotypes with their respective wild-type lines in anxiety (plus maze), compulsive (marble burying), and sensorimotor (prepulse inhibition) tasks. α 2B KO mice exhibited increased marble burying and α 2C KO mice exhibited an increased startle response to a pulse stimulus, but otherwise intact prepulse inhibition. To further explore compulsive behavior, we evaluated novelty-induced locomotor hyperactivity and found that α 2B KO and α 2C KO mice exhibited increased locomotion in the open field. Interestingly, when challenged with amphetamine, α 2C KO mice increased activity at lower doses relative to either α 2A KO or WT mice. However, α 2B KO mice exhibited stereotypy at doses of amphetamine that were only locomotor stimulatory to all other genotypes. Following co-administration of AGN-209419 with low-dose amphetamine in WT mice, stereotypy was observed, mimicking the α 2B KO phenotype. These findings suggest that the α 2B receptor is involved in CNS behaviors associated with sensorimotor gating and compulsivity, and may be therapeutically relevant for disorders such as schizophrenia, ADHD, post-traumatic stress disorder, addiction, and

Estrogen receptor-independent catechol estrogen binding activity: protein binding studies in wild-type, Estrogen receptor-alpha KO, and aromatase KO mice tissues.

Science.gov (United States)

Philips, Brian J; Ansell, Pete J; Newton, Leslie G; Harada, Nobuhiro; Honda, Shin-Ichiro; Ganjam, Venkataseshu K; Rottinghaus, George E; Welshons, Wade V; Lubahn, Dennis B

2004-06-01

Primary evidence for novel estrogen signaling pathways is based upon well-documented estrogenic responses not inhibited by estrogen receptor antagonists. In addition to 17beta-E2, the catechol estrogen 4-hydroxyestradiol (4OHE2) has been shown to elicit biological responses independent of classical estrogen receptors in estrogen receptor-alpha knockout (ERalphaKO) mice. Consequently, our research was designed to biochemically characterize the protein(s) that could be mediating the biological effects of catechol estrogens using enzymatically synthesized, radiolabeled 4-hydroxyestrone (4OHE1) and 4OHE2. Scatchard analyses identified a single class of high-affinity (K(d) approximately 1.6 nM), saturable cytosolic binding sites in several ERalphaKO estrogen-responsive tissues. Specific catechol estrogen binding was competitively inhibited by unlabeled catechol estrogens, but not by 17beta-E2 or the estrogen receptor antagonist ICI 182,780. Tissue distribution studies indicated significant binding differences both within and among various tissues in wild-type, ERalphaKO, and aromatase knockout female mice. Ligand metabolism experiments revealed extensive metabolism of labeled catechol estrogen, suggesting that catechol estrogen metabolites were responsible for the specific binding. Collectively, our data provide compelling evidence for the interaction of catechol estrogen metabolites with a novel binding protein that exhibits high affinity, specificity, and selective tissue distribution. The extensive biochemical characterization of this binding protein indicates that this protein may be a receptor, and thus may mediate ERalpha/beta-independent effects of catechol estrogens and their metabolites.

Mixed municipal solid waste (MSW) treatment in Waste centre Spodnji Stari Grad, Krško

OpenAIRE

Kortnik, Jože; Leskovar, Jože

2015-01-01

Review paper Received: October 25, 2013 Accepted: November 7, 2013 Mixed municipal solid waste (MSW) treatment in Waste centre Spodnji Stari Grad, Krško Ravnanje z mešanimi komunalnimi odpadki v Zbirnem centru Spodnji Stari Grad, Krško Jože Kortnik1'*, Jože Leskovar2 University of Ljubljana, Faculty of Natural Sciences and Engineering, Department of Mining and Geotechnology, Aškerčeva 12, 1000 Ljubljana, Slovenia 2Kostak, d. d., Leskovška cesta 2a, 8270 Krško, Slovenia Correspo...

Spin-orbital superexchange physics emerging from interacting oxygen molecules in KO2

International Nuclear Information System (INIS)

Solovyev, I V

2008-01-01

We propose that the spin-orbital-lattice coupled phenomena, widely known for the transition-metal oxides, can be realized in molecular solids, comprising of orbitally degenerate magnetic O 2 - ions. KO 2 is one such system. Using the first-principles electronic structure calculations, we set-up an effective spin-orbital superexchange model for the low-energy molecular bands and argue that many anomalous properties of KO 2 indeed replicate the status of its orbital system in different temperature regimes

Explosive hazards analysis of the eutectic solution NaK and KO2

International Nuclear Information System (INIS)

Commander, J.C.

1975-06-01

Planning, preparation, conductance, and evaluation of field tests are reported to determine the explosive hazards associated with the combining of the sodium-potassium eutectic alloy (NaK) with the superoxide of potassium (KO 2 ) under various conditions of state, contamination, and detonation initiation. The planning and preparation was conducted by Aerojet Nuclear Company (ANC) at the Idaho National Engineering Laboratory, and the explosive hazards testing was done by Cook Associates, Inc., at IRECO Chemicals Pelican Point Research and Development facility in Utah. The test results showed that binary combinations of pure NaK and KO 2 could not be made to detonate, although the mixtures will spontaneously ignite and burn. However, tertiary combinations of NaK, KO 2 plus a water or hydrocarbon contaminant produced explosive hazards under a variety of conditions. The work was performed as part of the Decontamination and Decommissioning (D and D) of the first Experimental Breeder Reactor (EBR-I) and was funded by 189c I-215. (U.S.)

Pielāgojama norēķinu sistēma mākoņskaitļošanas pakalpojumiem

OpenAIRE

Surženko, Dmitrijs

2013-01-01

Šajā darbā apskatīts mākoņskaitļošanas jēdziens un mākoņskaitļošanas mākoņu veidi un to funkcionālā klasifikācija. Apskatīti norēķinu sistēmas pamati balstoties uz telekomunikāciju norēķinu sistēmas pamatiem. Aprakstīta uzņēmuma N mākoņa pārvaldības infrastruktūra. Definētas mākoņskaitļošanas brokera prasības uz uzņēmuma N piemēra. Veikts vairāku mākoņskaitļošanas pakalpojumu norēķinu sistēmas apskats un aprakstīta to atbilstība pielāgojamai norēķinu sistēmai un mākoņskaitļošanas brokera pras...

Model validation of GAMMA code with heat transfer experiment for KO TBM in ITER

International Nuclear Information System (INIS)

Yum, Soo Been; Lee, Eo Hwak; Lee, Dong Won; Park, Goon Cherl

2013-01-01

Highlights: ► In this study, helium supplying system was constructed. ► Preparation for heat transfer experiment in KO TBM condition using helium supplying system was progressed. ► To get more applicable results, test matrix was made to cover the condition for KO TBM. ► Using CFD code; CFX 11, validation and modification for system code GAMMA was performed. -- Abstract: By considering the requirements for a DEMO-relevant blanket concept, Korea (KO) has proposed a He cooled molten lithium (HCML) test blanket module (TBM) for testing in ITER. A performance analysis for the thermal–hydraulics and a safety analysis for the KO TBM have been carried out using a commercial CFD code, ANSYS-CFX, and a system code, GAMMA (GAs multicomponent mixture analysis), which was developed by the gas cooled reactor in Korea. To verify the codes, a preliminary study was performed by Lee using a single TBM first wall (FW) mock-up made from the same material as the KO TBM, ferritic martensitic steel, using a 6 MPa nitrogen gas loop. The test was performed at pressures of 1.1, 1.9 and 2.9 MPa, and under various ranges of flow rate from 0.0105 to 0.0407 kg/s with a constant wall temperature condition. In the present study, a thermal–hydraulic test was performed with the newly constructed helium supplying system, in which the design pressure and temperature were 9 MPa and 500 °C, respectively. In the experiment, the same mock-up was used, and the test was performed under the conditions of 3 MPa pressure, 30 °C inlet temperature and 70 m/s helium velocity, which are almost same conditions of the KO TBM FW. One side of the mock-up was heated with a constant heat flux of 0.3–0.5 MW/m 2 using a graphite heating system, KoHLT-2 (Korea heat load test facility-2). Because the comparison result between CFX 11 and GAMMA showed a difference tendency, the modification of heat transfer correlation included in GAMMA was performed. And the modified GAMMA showed the strong parity with CFX

Gul'ko, descriptive, and Gruenhage compact spaces

Czech Academy of Sciences Publication Activity Database

Fabian, Marián; Montesinos, V.; Zizler, Václav

2010-01-01

Roč. 104, č. 2 (2010), s. 201-220 ISSN 1578-7303 R&D Projects: GA AV ČR IAA100190901; GA AV ČR(CZ) IAA100190610 Institutional research plan: CEZ:AV0Z10190503 Keywords : Gul'ko * descriptive * fragmentable compact spaces * network Subject RIV: BA - General Mathematics Impact factor: 0.400, year: 2010 http://link.springer.com/article/10.5052%2FRACSAM.2010.14

Perbandingan Ko-kultur 2D dan 3D dengan Metode Hanging Drop untuk Menghasilkan Micro-environment yang Lebih Relevan Secara Klinis

Directory of Open Access Journals (Sweden)

Radiana Dhewayani Antarianto

2017-09-01

Full Text Available Ko-kultur sel 2 dimensi (2D kurang menyerupai micro-environment seperti in vivo sedangkan ko-kultur 3 dimensi (3D membentuk mikromassa yang lebih mirip micro-environment in vivo sehingga bermanfaat dalam penelitian biologi dasar. Penelitian ini membandingkan ko-kultur 2D dan 3D sel punca serta sel stelata hepatik dengan metode hanging drop untuk menilai morfologi sel dan pembentukan sferoid dari mikromassa yang terbentuk. Studi in vitro ini dilakukan di Pusat Virologi dan Kanker Patobiologi (PRVKP UI dan laboratorium histologi FKUI pada bulan September 2015 sampai Oktober 2016 menggunakan sel punca yang diisolasi dari darah tali pusat manusia dan sel lestari LX2 (stelata hepatik manusia. Darah tali pusat disortir dengan MACS CD34 dan dianalisis flowcytometry. Ko-kultur sel punca sumsum tulang atau darah tali pusat dan LX2 dilakukan dengan metode hanging drop untuk ko-kultur 2D dan ko-kultur 3D. Triplikasi eksperimen dilakukan untuk tiap set ko-kultur. Hasilnya menunjukkan terdapat perbedaan morfologi ko-kultur 2D dan 3D hanging drop dibandingkan monokultur. Di ko-kultur 2D terdapat mikromassa dan di monokultur 2D tidak terbentuk mikromassa. Di ko-kultur 3D hanging drop, terdapat sferoid yang lebih kecil dibandingkan monokultur 3D hanging drop. Morfologi sel ko-kultur 2D dan 3D dengan metode hanging drop dibandingkan monokultur menunjukkan perubahan fenotip sel-sel yang tergabung dalam mikromassa. Normal 0 false false false false IN X-NONE X-NONE Normal 0 false false false false IN X-NONE X-NONE Heavy metals in the air between Krompachy and Košice

Directory of Open Access Journals (Sweden)

Slanèo Pavel

2000-09-01

Full Text Available The metallurgic activity of Kovohuty Krompachy (Non-ferrous Metal Works in Krompachy in the past left its visible devastation sign on the nature. It was evident that the dispersion of some elements, especially Cu, Pb, Sb and As, in the air was caused by the activity of metal works and their point sources. The properties of these metals may cause changes in health of biological objects as a result of long-term effect on the natural or communal spheres. After the treatment activities in ŽB Rudòany enterprise ended, Kovohuty Krompachy bought a treatment concentrate from ŽB Rudòany, which was freed from mercury. This concentrate still contained a lot of Cu, Sb, As, Bi and it should have been processed in Kovohuty to the so called black copper. The Municipality of the city of Košice, its department of the environment, expressed its apprehension of the possibility that this processing could cause that heavy metals may be spread in a direction of prevailing winds, i.e. south-east direction, where the city of Košice is situated. This was a reason for a task to monitor movement and occurrence of heavy metals on the route between Krompachy and Košice, as well as to monitor the share of individual sources of pollution on the quality of air in Košice urban agglomeration.Two methods applied were chosen for research purposes. The dust deposition was monitored, i.e. dust that sediments from air, its value is stated in g.m-2. 30 days-1. Another method used was the so called aspiration dust content, when air is sucked through a suitable filter and the value is stated in mg.m-3. In the given locality, there were 15 newly built or renovated sedimentation stations, where samples of sedimented dust were taken by the end of 1999 in six stages. They are marked by letters A to F. The samples of dust were analysed by atomic absorption spectrophotometry. The presented paper shows the results of phases A and D, or B and D.Aspiration method was used for fine

Anti-Trichomonas vaginalis properties of the oil of Amomum tsao-ko and its major component, geraniol.

Science.gov (United States)

Dai, Min; Peng, Cheng; Peng, Fu; Xie, Chengbin; Wang, Pinjia; Sun, Fenghui

2016-01-01

Trichomonosis, caused by the flagellate protozoan Trichomonas vaginalis, is the most common non-viral sexually transmitted disease (STD) and 5-nitroimidazole drugs are used for the treatment. However, a growing number of T. vaginalis isolates are resistant to these drugs, which make it becomes an urgent issue. The current study was designed to evaluate the anti-T. vaginalis activity of the essential oil from A. tsao-ko used in traditional Chinese medicine and as a spice and its main component, geraniol. The anti-T. vaginalis activities of A. tsao-ko essential oil and geraniol were evaluated by the minimum lethal concentration (MLC) and 50% inhibitory concentration (IC50) in vitro. The morphological changes of T. vaginalis were observed by transmission electron microscopy (TEM). Additionally, sub-MLC concentration treatment with sub-MLC A. tsao-ko essential oil and geraniol was also performed. This study shows that MLC/IC50 of A. tsao-ko essential oil was 44.97 µg/ml/22.49 µg/ml for T. vaginalis isolate Tv1, and 89.93 µg/ml/44.97 µg/ml for T. vaginalis isolate Tv2. Those of geraniol were 342.96 µg/ml/171.48 µg/ml, respectively. After A. tsao-ko essential oil or geraniol treatment, obvious similar morphological changes of T. vaginalis were observed by TEM: the nuclear membrane was damaged, nuclei were dissolved, and the chromatin was accumulated; in the cytoplasm, numerous vacuoles appeared, rough endoplasmic reticulum dilated, the number of ribosomes were reduced, organelles disintegrated, the cell membrane was partially damaged, with cytoplasmic leakage, and cell disintegration was observed. The action time did not increase the effect of A. tsao-ko essential oil or geraniol against T. vaginalis, as no significant difference was observed after sub-MLC concentration treatment for 1, 3, and 5 h with A. tsao-ko essential oil and geraniol. The study describes the first report on the activity and morphological changes of A. tsao-ko essential oil and

Magnetic properties of the alkali metal ozonides KO3, RbO3, and CsO3

International Nuclear Information System (INIS)

Lueken, H.; Deussen, M.; Jansen, M.; Hesse, W.; Schnick, W.

1987-01-01

The magnetic susceptibilities of KO 3 , RbO 3 and CsO 3 have been determined between 3.6 and 250 K. Above 50 K Curie-Weiss behaviour is observed. Magnetic moments of 1.74 μ B (KO 3 , CsO 3 ) and 1.80 μ B (RbO 3 ) calculated from the Curie-Weiss straight lines correspond with spin-only moments expected for isolated O 3 - species with one unpaired electron. The Weiss constants Θ are -34 K (KO 3 ), -23 K (RbO 3 ) and -10 K (CsO 3 ). The low temperature behaviour of KO 3 and RbO 3 (broad maxima in susceptibility at 20 and 17 K, respectively, and minima at 6 K) is typical of systems which show with decreasing temperature low-dimensional antiferromagnetic and three-dimensional magnetic ordering. Inspecting the intermolecular distances between oxygen atoms the pathways of exchange interactions are discussed. (author)

Paluch koślawy w stopie reumatycznej – leczenie operacyjne i rehabilitacja

Directory of Open Access Journals (Sweden)

Agnieszka Prusinowska

2011-04-01

Full Text Available Paluch koślawy jest deformacją stopy często występującą u chorychreumatycznych (ryc. 1. W znacznym stopniu zaburza funkcjępodporową w czasie chodu oraz czynności związane z większymdynamicznym obciążeniem stopy (bieganie, skakanie. Deformacjata nasila ból, który wynika również z niedopasowania obuwia.Usprawnianie chorych z rozpoznaniem reumatoidalnego zapaleniastawów (RZS zawsze jest uzależnione od aktualnego stanu funkcjonalnegopacjenta i przeprowadzonego zabiegu operacyjnego.W artykule opisano mechanizm powstawania typowych zniekształceńprzodostopia w przebiegu RZS oraz przegląd technikoperacyjnych stosowanych w leczeniu palucha koślawego (ryc. 2.Autorzy skoncentrowali się na przedstawieniu usprawniania pokorekcji palucha koślawego z wykorzystaniem zarówno metod stosowanychw celu zmniejszenia obrzęków pooperacyjnych, jak i stabilizacjiskorygowanego chirurgicznie stawu. Do metod tych zaliczasię zarówno zabiegi z zakresu fizykoterapii, jak i ćwiczenia czynneze wsparciem kinesiotapingu (ryc. 3.

Öko tähendab edu / Liis Kängsepp

Index Scriptorium Estoniae

Kängsepp, Liis, 1981-

2008-01-01

Kaubandusturul on populaarsust kogumas mahe- ja ausalt toodetud (fair trade) kaubad. Vt. samas: Mis on mahetoit; Fair Trade; Roheline liikumine: tarbi vähem!; Mätas: pane öko peale ja müüb!; Treener Kristel Tamm jõudis ökoni oma lapsele head pakkuda tahtes

Promjene na koži lica inducirane UV-zračenjem

OpenAIRE

Bojčić, Zrinka

2016-01-01

Promjene inducirane UV zračenjem obuhvaćaju različite kliničke entitete. Zbog svoje biološke aktivnosti i sposobnosti da induciraju oštećenje DNK, UV-B zrake najvažniji su etiološki čimbenik u nastanku opeklina i karcinoma kože. Iako je UV-A zračenje glavna komponenta ultraljubičastog zračenja, manje je biološki aktivna od UV-B. UV-A zračenje ima posebno važnu ulogu u fotostarenju kože. Klinička slika akutnih promjena induciranih UV zračenjem ovisi o količini energije apsorbirane u jednoj ...

Implementation of KoHLT-EB DAQ System using compact RIO with EPICS

Energy Technology Data Exchange (ETDEWEB)

Chang, Dae-Sik; Kim, Suk-Kwon; Lee, Dong Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Cho, Seungyon [National Fusion Research Institute, Daejeon (Korea, Republic of)

2016-10-15

EPICS (Experimental Physics and Industrial Control System) is a collection of software tools collaboratively developed which can be integrated to provide a comprehensive and scalable control system. Currently there is an increase in use of such systems in large Physics experiments like KSTAR, ITER and DAIC (Daejeon Accelerator Ion Complex). The Korean heat load test facility (KoHLT-EB) was installed at KAERI. This facility is utilized for a qualification test of the plasma facing component (PFC) for the ITER first wall and DEMO divertor, and the thermo-hydraulic experiments. The existing data acquisition device was Agilent 34980A multifunction switch and measurement unit and controlled by Agilent VEE. In the present paper, we report the EPICS based newly upgraded KoHLT-EB DAQ system which is the advanced data acquisition system using FPGA-based reconfigurable DAQ devices like compact RIO. The operator interface of KoHLT-EB DAQ system is composed of Control-System Studio (CSS) and another server is able to archive the related data using the standalone archive tool and the archiveviewer can retrieve that data at any time in the infra-network.

NCKX3 was compensated by calcium transporting genes and bone resorption in a NCKX3 KO mouse model.

Science.gov (United States)

Yang, Hyun; Ahn, Changhwan; Shin, Eun-Kyeong; Lee, Ji-Sun; An, Beum-Soo; Jeung, Eui-Bae

2017-10-15

Gene knockout is the most powerful tool for determination of gene function or permanent modification of the phenotypic characteristics of an animal. Existing methods for gene disruption are limited by their efficiency, time required for completion and potential for confounding off-target effects. In this study, a rapid single-step approach to knockout of a targeted gene in mice using zinc-finger nucleases (ZFNs) was demonstrated for generation of mutant (knockout; KO) alleles. Specifically, ZFNs to target the sodium/calcium/potassium exchanger3 (NCKX3) gene in C57bl/6j were designed using the concept of this approach. NCKX3 KO mice were generated and the phenotypic characterization and molecular regulation of active calcium transporting genes was assessed when mice were fed different calcium diets during growth. General phenotypes such as body weight and plasma ion level showed no distinct abnormalities. Thus, the potassium/sodium/calcium exchanger of NCKX3 KO mice proceeded normally in this study. As a result, the compensatory molecular regulation of this mechanism was elucidated. Renal TRPV5 mRNA of NCKX3 KO mice increased in both male and female mice. Expression of TRPV6 mRNA was only down-regulated in the duodenum of male KO mice. Renal- and duodenal expression of PTHR and VDR were not changed; however, GR mRNA expression was increased in the kidney of NCKX3 KO mice. Depletion of the NCKX3 gene in a KO mouse model showed loss of bone mineral contents and increased plasma parathyroid hormone, suggesting that NCKX3 may play a role in regulating calcium homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Advanced RF-KO slow-extraction method for the reduction of spill ripple

CERN Document Server

Noda, K; Shibuya, S; Uesugi, T; Muramatsu, M; Kanazawa, M; Takada, E; Yamada, S

2002-01-01

Two advanced RF-knockout (RF-KO) slow-extraction methods have been developed at HIMAC in order to reduce the spill ripple for accurate heavy-ion cancer therapy: the dual frequency modulation (FM) method and the separated function method. As a result of simulations and experiments, it was verified that the spill ripple could be considerably reduced using these advanced methods, compared with the ordinary RF-KO method. The dual FM method and the separated function method bring about a low spill ripple within standard deviations of around 25% and of 15% during beam extraction within around 2 s, respectively, which are in good agreement with the simulation results.

Mākoņdatošanas izmantošana informātikas priekšmetā vidusskolā.

OpenAIRE

Jēkabsone, Kristīne

2013-01-01

Izanalizējot informātikas standartu vidusskolā izpētīta mākoņdatošanas izmantošanas iespējas vidusskolā. Veikta aptauja vidusskolas klases skolēnu vidū. Aplūkots vidusskolas izglītojamo pieejamais tehnoloģiju klāsts. Meklēta atbilde uz pētniecisko jautājumu: kādas ir mākoņdatošanas izmantošanas iespējas informātikas priekšmeta apguvē vidusskolā? Sniegti ieteikumi skolotājiem strādājot ar mākoņdatošanu. Atslēgas vārdi: informātika, mākoņdatošana, Google Drive, Skydrive, Dropbox....

Depressed nNOS expression during spine transition in the developing hippocampus of FMR1 KO mice

International Nuclear Information System (INIS)

Xu, Qin; Zhu, Zhiwei; Xu, Jialu; Gu, Weizhong; Zhao, Zhengyan

2012-01-01

Nitric oxide (NO), synthesized as needed by NO synthase (NOS), is involved in spinogenesis and synaptogenesis. Immature spine morphology is characteristic of fragile X syndrome (FXS). The objective of this research was to investigate and compare changes of postnatal neuronal NOS (nNOS) expression in the hippocampus of male fragile X mental retardation 1 gene knockout mice (FMR1 KO mice, the animal model of FXS) and male wild-type mice (WT) at postnatal day 7 (P7), P14, P21, and P28. nNOS mRNA levels were analyzed by real-time quantitative PCR (N = 4-7) and nNOS protein was estimated by Western blot (N = 3) and immunohistochemistry (N = 1). In the PCR assessment, primers 5′-GTGGCCATCGTGTCCTACCATAC-3′ and 5′-GTTTCGAGGCAGGTGGAAGCTA-3′ were used for the detection of nNOS and primers 5′-CCGTTTCTCCTGGCTCAGTTTA-3′ and 5′-CCCCAATACCACATCATCCAT-3′ were used for the detection of β-actin. Compared to the WT group, nNOS mRNA expression was significantly decreased in FMR1 KO mice at P21 (KO: 0.2857 ± 0.0150, WT: 0.5646 ± 0.0657; P < 0.05). Consistently, nNOS immunoreactivity also revealed reduced staining intensity at P21 in the FMR1 KO group. Western blot analysis validated the immunostaining results by demonstrating a significant reduction in nNOS protein levels in the FMR1 KO group compared to the WT group at P21 (KO: 0.3015 ± 0.0897, WT: 1.7542 ± 0.5455; P < 0.05). These results suggest that nNOS was involved in the postnatal development of the hippocampus in FXS and impaired NO production may retard spine maturation in FXS

Depressed nNOS expression during spine transition in the developing hippocampus of FMR1 KO mice

Energy Technology Data Exchange (ETDEWEB)

Xu, Qin; Zhu, Zhiwei; Xu, Jialu [Department of Children' s Health Care, Children' s Hospital, Zhejiang University, Hangzhou Zhejiang (China); Gu, Weizhong [Department of Pathology, Children' s Hospital, Zhejiang University, Hangzhou Zhejiang (China); Zhao, Zhengyan [Department of Children' s Health Care, Children' s Hospital, Zhejiang University, Hangzhou Zhejiang (China)

2012-10-05

Nitric oxide (NO), synthesized as needed by NO synthase (NOS), is involved in spinogenesis and synaptogenesis. Immature spine morphology is characteristic of fragile X syndrome (FXS). The objective of this research was to investigate and compare changes of postnatal neuronal NOS (nNOS) expression in the hippocampus of male fragile X mental retardation 1 gene knockout mice (FMR1 KO mice, the animal model of FXS) and male wild-type mice (WT) at postnatal day 7 (P7), P14, P21, and P28. nNOS mRNA levels were analyzed by real-time quantitative PCR (N = 4-7) and nNOS protein was estimated by Western blot (N = 3) and immunohistochemistry (N = 1). In the PCR assessment, primers 5′-GTGGCCATCGTGTCCTACCATAC-3′ and 5′-GTTTCGAGGCAGGTGGAAGCTA-3′ were used for the detection of nNOS and primers 5′-CCGTTTCTCCTGGCTCAGTTTA-3′ and 5′-CCCCAATACCACATCATCCAT-3′ were used for the detection of β-actin. Compared to the WT group, nNOS mRNA expression was significantly decreased in FMR1 KO mice at P21 (KO: 0.2857 ± 0.0150, WT: 0.5646 ± 0.0657; P < 0.05). Consistently, nNOS immunoreactivity also revealed reduced staining intensity at P21 in the FMR1 KO group. Western blot analysis validated the immunostaining results by demonstrating a significant reduction in nNOS protein levels in the FMR1 KO group compared to the WT group at P21 (KO: 0.3015 ± 0.0897, WT: 1.7542 ± 0.5455; P < 0.05). These results suggest that nNOS was involved in the postnatal development of the hippocampus in FXS and impaired NO production may retard spine maturation in FXS.

Depressed nNOS expression during spine transition in the developing hippocampus of FMR1 KO mice

Directory of Open Access Journals (Sweden)

Qin Xu

2012-12-01

Full Text Available Nitric oxide (NO, synthesized as needed by NO synthase (NOS, is involved in spinogenesis and synaptogenesis. Immature spine morphology is characteristic of fragile X syndrome (FXS. The objective of this research was to investigate and compare changes of postnatal neuronal NOS (nNOS expression in the hippocampus of male fragile X mental retardation 1 gene knockout mice (FMR1 KO mice, the animal model of FXS and male wild-type mice (WT at postnatal day 7 (P7, P14, P21, and P28. nNOS mRNA levels were analyzed by real-time quantitative PCR (N = 4-7 and nNOS protein was estimated by Western blot (N = 3 and immunohistochemistry (N = 1. In the PCR assessment, primers 5’-GTGGCCATCGTGTCCTACCATAC-3’ and 5’-GTTTCGAGGCAGGTGGAAGCTA-3’ were used for the detection of nNOS and primers 5’-CCGTTTCTCCTGGCTCAGTTTA-3’ and 5’-CCCCAATACCACATCATCCAT-3’ were used for the detection of β-actin. Compared to the WT group, nNOS mRNA expression was significantly decreased in FMR1 KO mice at P21 (KO: 0.2857 ± 0.0150, WT: 0.5646 ± 0.0657; P < 0.05. Consistently, nNOS immunoreactivity also revealed reduced staining intensity at P21 in the FMR1 KO group. Western blot analysis validated the immunostaining results by demonstrating a significant reduction in nNOS protein levels in the FMR1 KO group compared to the WT group at P21 (KO: 0.3015 ± 0.0897, WT: 1.7542 ± 0.5455; P < 0.05. These results suggest that nNOS was involved in the postnatal development of the hippocampus in FXS and impaired NO production may retard spine maturation in FXS.

Martwica kości szczęk związana ze stosowaniem bifosfonianów. Opis przypadków

Directory of Open Access Journals (Sweden)

Wojciech Leśniak

2013-06-01

Full Text Available Bifosfoniany należą do silnych inhibitorów osteoklastów. Znajdują szerokie zastosowanie w leczeniu chorób przebiegających ze wzmożoną resorpcją kości: osteoporozy, choroby Pageta i osteogenesis imperfecta. Leki te zmniejszają adhezję komórek nowotworowych do kości, ograniczają osteolizę wywołaną nowotworem i hiper‑ kalcemię. Zmniejszają dolegliwości bólowe w szpiczaku mnogim i w przerzutach do kości. Powszechnie panu‑ jące przekonanie o bezpieczeństwie spowodowało rozszerzenie wskazań do ich stosowania. Pacjenci onkolo‑ giczni przyjmujący bifosfoniany dożylnie, w wysokich dawkach są bardziej narażeni na działania niepożądane terapii niż pacjenci przyjmujący je doustnie. Jednym z najpoważniejszych powikłań jest martwica kości szczęk. W 2003 roku opisano po raz pierwszy związek pomiędzy terapią bifosfonianami a martwicą kości szczęk. W piśmiennictwie znajdujemy coraz więcej przykładów tego działania niepożądanego, także po stosowaniu leków doustnie. Mogą pojawiać się ból, obrzęk, owrzodzenie, odsłonięcie kości, przetoki, złamania patologiczne, uciążliwe dla pacjenta i obniżające jakość życia. Leczenie martwicy kości szczęk jest trudne i rzadko przynosi spodziewany efekt. Główną rolę odgrywa leczenie zachowawcze i redukcja objawów. Odstawienie bifosfonia‑ nów nie ma bezpośredniego wpływu na przebieg martwicy kości szczęk, ze względu na kumulację leku w kości. Istotne jest przygotowanie pacjenta przed rozpoczęciem podawania bifosfonianów, wymagające stałej współ‑ pracy pomiędzy lekarzami onkologami, ortopedami i chirurgami szczękowo-twarzowymi. Higiena jamy ustnej i leczenie chorób współistniejących stanowi ważny element postępowania. Celem pracy jest przedstawienie trzech przypadków martwicy kości szczęk u pacjentów poddanych leczeniu bifosfonianami.

Rate constant and thermochemistry for K + O2 + N2 = KO2 + N2

DEFF Research Database (Denmark)

Sorvajärvi, Tapio; Viljanen, Jan; Toivonen, Juha

2015-01-01

in the form of double exponential decays of [K], which yielded both kR1 and the equilibrium constant for KO2 formation. kR1 can be summarized as 1.07 × 10-30(T/1000 K)-0.733 cm6 molecule-2 s-1. Combination with literature values leads to a recommended kR1 of 5.5 × 10-26T-1.55 exp(-10/T) cm6 molecule-2 s-1...... over 250-1320 K, with an error limit of a factor of 1.5. A vant Hoff analysis constrained to fit the computed ΔS298 yields a K-O2 bond dissociation enthalpy of 184.2 ± 4.0 kJ mol-1 at 298 K and ΔfH298(KO2) = -95.2 ± 4.1 kJ mol-1. The corresponding D0 is 181.5 ± 4.0 kJ mol-1. This value compares well...

V labyrintech Holanovy pozdní lyriky : Nad knihou Zdeňka Kožmína

OpenAIRE

Křivánek, Vladimír

2005-01-01

This essay on the late lyric verse of Vladimír Holan, inspired by Zdeněk Kožmín’s Existencionalita, also presents an overview of previous important interpretations of Holan’s work – apart from Kožmín, it mentions the work of Přemysl Blažíček and Jiří Opelík.

The Growth Hormone Receptor Gene-Disrupted (GHR-KO) Mouse Fails to Respond to an Intermittent Fasting (IF) Diet

Science.gov (United States)

Arum, Oge; Bonkowski, Michael S.; Rocha, Juliana S.; Bartke, Andrzej

2009-01-01

SUMMARY The interaction of longevity-conferring genes with longevity-conferring diets is poorly understood. The growth hormone receptor gene-disrupted (GHR-KO) mouse is long-lived; and this longevity is not responsive to 30% caloric restriction (CR), in contrast to wild-type animals from the same strain. To determine whether this may have been limited to a particular level of dietary restriction (DR), we subjected GHR-KO mice to a different dietary restriction regimen, an intermittent fasting (IF) diet. The IF diet increased the survivorship and improved insulin sensitivity of normal males, but failed to affect either parameter in GHR-KO mice. From the results of two paradigms of dietary restriction we postulate that GHR-KO mice would be resistant to any manner of DR; potentially due to their inability to further enhance insulin sensitivity. Insulin sensitivity may be a mechanism and/or a marker of the lifespan-extending potential of an intervention. PMID:19747233

Farklı stres koşullarında Rhodotorula glutinis’ten antioksidan üretimi için biyoproses koşullarının geliştirilmesi

OpenAIRE

ÜNLÜ BÜYÜKTOPÇU, Ayşe Ezgi

2012-01-01

Source of spill ripple in the RF-KO slow-extraction method with FM and AM

International Nuclear Information System (INIS)

Noda, K.; Furukawa, T.; Shibuya, S.; Muramatsu, M.; Uesugi, T.; Kanazawa, M.; Torikoshi, M.; Takada, E.; Yamada, S.

2002-01-01

The RF-knockout (RF-KO) slow-extraction method with frequency modulation (FM) and amplitude modulation (AM) has brought high-accuracy irradiation to the treatment of a cancer tumor moving with respiration, because of a quick response to beam start/stop. However, a beam spill extracted from a synchrotron ring through RF-KO slow-extraction has a huge ripple with a frequency of around 1 kHz related to the FM. The spill ripple will disturb the lateral dose distribution in the beam scanning methods. Thus, the source of the spill ripple has been investigated through experiments and simulations. There are two tune regions for the extraction process through the RF-KO method: the extraction region and the diffusion region. The particles in the extraction region can be extracted due to amplitude growth through the transverse RF field, only when its frequency matches with the tune in the extraction region. For a large chromaticity, however, the particles in the extraction region can be extracted through the synchrotron oscillation, even when the frequency does not match with the tune in the extraction region. Thus, the spill structure during one period of the FM strongly depends on the horizontal chromaticity. They are repeated with the repetition frequency of the FM, which is the very source of the spill ripple in the RF-KO method

Scyntygrafia kości w diagnostyce reumatoidalnego zapalenia stawów

Directory of Open Access Journals (Sweden)

Witold Tłustochowicz

2010-04-01

Full Text Available Celem pracy była ocena przydatności trójfazowej dynamicznejscyntygrafii kości w diagnostyce reumatoidalnego zapalenia stawów.Badaniem objęto 39 chorych hospitalizowanych i diagnozowanychz powodu dolegliwości stawowych. Przeprowadzono diagnostykęobejmującą: badanie podmiotowe, przedmiotowe, badania laboratoryjneoraz obrazowe, w tym trójfazową scyntygrafię kości z użyciemtechnetu 99m. Scyntygraficzne cechy zapalenia stawówstwierdzano, gdy obserwowano wzmożone gromadzenie znacznikawe wszystkich trzech fazach badania.Po ukończeniu diagnostyki rozpoznano u 13 chorych wczesne reumatoidalnezapalenie stawów, u 4 reumatoidalne zapalenie stawów(łącznie 17 pacjentów, a u 1 niezróżnicowane zapalenie stawów.Scyntygrafia kości wykazała cechy zapalenia stawów u 13spośród nich (72,2%, u 4 osób (22,2% wzmożone gromadzeniestwierdzono tylko w fazie statycznej, a u 1 pacjenta (5,6% uzyskanoprawidłowy wynik badania. U 21 chorych wykluczono chorobęzapalną stawów (u 19 rozpoznano fibromialgię, u 2 chorobęzwyrodnieniową. W grupie bez zapalenia stawów u 14 pacjentów(66,6% nie stwierdzono istotnych nieprawidłowości w obraziescyntygraficznym, u 6 (28,6% występowało wzmożone gromadzenieznacznika w badaniu statycznym, a u 1 chorego (4,8% opisanoscyntygraficzne cechy zapalenia stawów.Wbadanej grupie czułość scyntygrafii dynamicznej kości w wykrywaniuzapalenia stawów wynosiła 72,2% (95% CI: 57,5–76,8, a swoistość 95,2% (95% CI: 82,8–99,1. Dodatni wynik badaniadynamicznego wskazuje z dużym prawdopodobieństwem naobecność zapalenia stawów [PPV 92,9% (95% CI: 74,2–98,7].Mniej wiarygodny był ujemny wynik badania [NPV 80% (95% CI:69,5–83,3]. Wyniki niniejszej pracy wskazują, że trójfazowa scyntygrafia dynamicznakości może mieć zastosowanie w diagnostyce reumatoidalnegozapalenia stawów.

A Note on Ko-Type O-Ending Syllables in Old Japanese

Science.gov (United States)

Unger, J. Marshall

1975-01-01

Further evidence is offered to support the argument that ko-type o-ending syllables may have been secondary in nature in Old Japanese. Pre-Old Japanese indicates the */uwa/ sequence was manifested as /uwe/ and /uwu/ endings of o-ending syllable verbs. (SCC)

Source of spill ripple in the RF-KO slow-extraction method with FM and AM

CERN Document Server

Noda, K; Shibuya, S; Muramatsu, M; Uesugi, T; Kanazawa, M; Torikoshi, M; Takada, E; Yamada, S

2002-01-01

The RF-knockout (RF-KO) slow-extraction method with frequency modulation (FM) and amplitude modulation (AM) has brought high-accuracy irradiation to the treatment of a cancer tumor moving with respiration, because of a quick response to beam start/stop. However, a beam spill extracted from a synchrotron ring through RF-KO slow-extraction has a huge ripple with a frequency of around 1 kHz related to the FM. The spill ripple will disturb the lateral dose distribution in the beam scanning methods. Thus, the source of the spill ripple has been investigated through experiments and simulations. There are two tune regions for the extraction process through the RF-KO method: the extraction region and the diffusion region. The particles in the extraction region can be extracted due to amplitude growth through the transverse RF field, only when its frequency matches with the tune in the extraction region. For a large chromaticity, however, the particles in the extraction region can be extracted through the synchrotron ...

Ethanol production from marine algal hydrolysates using Escherichia coli KO11.

Science.gov (United States)

Kim, Nag-Jong; Li, Hui; Jung, Kwonsu; Chang, Ho Nam; Lee, Pyung Cheon

2011-08-01

Algae biomass is a potential raw material for the production of biofuels and other chemicals. In this study, biomass of the marine algae, Ulva lactuca, Gelidium amansii,Laminaria japonica, and Sargassum fulvellum, was treated with acid and commercially available hydrolytic enzymes. The hydrolysates contained glucose, mannose, galactose, and mannitol, among other sugars, at different ratios. The Laminaria japonica hydrolysate contained up to 30.5% mannitol and 6.98% glucose in the hydrolysate solids. Ethanogenic recombinant Escherichia coli KO11 was able to utilize both mannitol and glucose and produced 0.4g ethanol per g of carbohydrate when cultured in L. japonica hydrolysate supplemented with Luria-Bertani medium and hydrolytic enzymes. The strategy of acid hydrolysis followed by simultaneous enzyme treatment and inoculation with E. coli KO11 could be a viable strategy to produce ethanol from marine alga biomass. Copyright © 2011 Elsevier Ltd. All rights reserved.

Key on demand (KoD) for software-defined optical networks secured by quantum key distribution (QKD).

Science.gov (United States)

Cao, Yuan; Zhao, Yongli; Colman-Meixner, Carlos; Yu, Xiaosong; Zhang, Jie

2017-10-30

Software-defined optical networking (SDON) will become the next generation optical network architecture. However, the optical layer and control layer of SDON are vulnerable to cyberattacks. While, data encryption is an effective method to minimize the negative effects of cyberattacks, secure key interchange is its major challenge which can be addressed by the quantum key distribution (QKD) technique. Hence, in this paper we discuss the integration of QKD with WDM optical networks to secure the SDON architecture by introducing a novel key on demand (KoD) scheme which is enabled by a novel routing, wavelength and key assignment (RWKA) algorithm. The QKD over SDON with KoD model follows two steps to provide security: i) quantum key pools (QKPs) construction for securing the control channels (CChs) and data channels (DChs); ii) the KoD scheme uses RWKA algorithm to allocate and update secret keys for different security requirements. To test our model, we define a security probability index which measures the security gain in CChs and DChs. Simulation results indicate that the security performance of CChs and DChs can be enhanced by provisioning sufficient secret keys in QKPs and performing key-updating considering potential cyberattacks. Also, KoD is beneficial to achieve a positive balance between security requirements and key resource usage.

„Nekad su mi znali reći da nisam bolja od svog sina“ - stigma obitelji temeljem intelektualnih teškoća člana obitelji

OpenAIRE

Buljevac, Marko; Leutar, Zdravka

2017-01-01

Rad se bavi stigmom obitelji temeljem intelektualnih teškoća člana obitelji. Cilj ovog istraživanja bio je dobiti uvid u perspektive članova uže obitelji osoba s različitim stupnjem intelektualnih teškoća o stigmi obitelji temeljem intelektualnih teškoća. Istraživačko pitanje bilo je: „Kako članovi obitelji osoba s intelektualnim teškoćama doživljavaju stigmu obitelji?“. Sudionici istraživanja bile se 22 osobe koje su članovi uže obitelji osoba s različitim stupnjem intelektualnih teškoća (10...

Cluster and principal component analysis based on SSR markers of Amomum tsao-ko in Jinping County of Yunnan Province

Science.gov (United States)

Ma, Mengli; Lei, En; Meng, Hengling; Wang, Tiantao; Xie, Linyan; Shen, Dong; Xianwang, Zhou; Lu, Bingyue

2017-08-01

Amomum tsao-ko is a commercial plant that used for various purposes in medicinal and food industries. For the present investigation, 44 germplasm samples were collected from Jinping County of Yunnan Province. Clusters analysis and 2-dimensional principal component analysis (PCA) was used to represent the genetic relations among Amomum tsao-ko by using simple sequence repeat (SSR) markers. Clustering analysis clearly distinguished the samples groups. Two major clusters were formed; first (Cluster I) consisted of 34 individuals, the second (Cluster II) consisted of 10 individuals, Cluster I as the main group contained multiple sub-clusters. PCA also showed 2 groups: PCA Group 1 included 29 individuals, PCA Group 2 included 12 individuals, consistent with the results of cluster analysis. The purpose of the present investigation was to provide information on genetic relationship of Amomum tsao-ko germplasm resources in main producing areas, also provide a theoretical basis for the protection and utilization of Amomum tsao-ko resources.

Experimental transmission of AA amyloidosis by injecting the AA amyloid protein into interleukin-1 receptor antagonist knockout (IL-1raKO) mice.

Science.gov (United States)

Watanabe, K; Uchida, K; Chambers, J K; Tei, M; Shoji, A; Ushio, N; Nakayama, H

2015-05-01

The incidence of AA amyloidosis is high in humans with rheumatoid arthritis and several animal species, including cats and cattle with prolonged inflammation. AA amyloidosis can be experimentally induced in mice using severe inflammatory stimuli and a coinjection of AA amyloid; however, difficulties have been associated with transmitting AA amyloidosis to a different animal species, and this has been attributed to the "species barrier." The interleukin-1 receptor antagonist knockout (IL-1raKO) mouse, a rodent model of human rheumatoid arthritis, has been used in the transmission of AA amyloid. When IL-1raKO and BALB/c mice were intraperitoneally injected with mouse AA amyloid together with a subcutaneous pretreatment of 2% AgNO3, all mice from both strains that were injected with crude or purified murine AA amyloid developed AA amyloidosis. However, the amyloid index, which was determined by the intensity of AA amyloid deposition, was significantly higher in IL-1raKO mice than in BALB/c mice. When IL-1raKO and BALB/c mice were injected with crude or purified bovine AA amyloid together with the pretreatment, 83% (5/6 cases) and 38% (3/8 cases) of IL-1raKO mice and 17% (1/6 cases) and 0% (0/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. Similarly, when IL-1raKO and BALB/c mice were injected with crude or purified feline AA amyloid, 33% (2/6 cases) and 88% (7/8 cases) of IL-1raKO mice and 0% (0/6 cases) and 29% (2/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. These results indicated that IL-1raKO mice are a useful animal model for investigating AA amyloidogenesis. © The Author(s) 2014.

Liver steatosis study_PFAA treated Wild type and PPAR KO mouse data

Data.gov (United States)

U.S. Environmental Protection Agency — Data set 1 consists of the experimental data for the Wild Type and PPAR KO animal study and includes data used to prepare Figures 1-4 and Table 1 of the Das et al,...

Staranje cevi uparjalnikov v Jedrski elektrarni Krško: Aging of tubes in the Krško nuclear power plant's steam generators:

OpenAIRE

Androjna, Ferdo; Cizelj, Leon

2000-01-01

The paper reviews the domestic efforts devoted to the safe and reliable operation of the Krško nuclear power plant (NPP) at full power, close to the design limit of the steam generators (18% of plugged tubes) for a full decade. This includes an overview of the recent status and history of the degradation processes, discussion of repair criteria, defining the acceptable size of defects and selected results from safety analyses supporting the operation of degraded steam generator (SG) tubes. It...

Zdeněk Kožmín a strukturalismus

Czech Academy of Sciences Publication Activity Database

Sládek, Ondřej

2016-01-01

Roč. 19, č. 2 (2016), s. 32-48 ISSN 1213-2144 Institutional support: RVO:68378068 Keywords : Kožmín, Zdeněk * Mukařovský, Jan * Structural ism * Structural poetics and aesthetics * TheoryofInterpretation * Philosophy and Literature * Mukařovský, Jan * Structural ism * Structural poetics and aesthetics * Theory of Interpretation * Philosophy and Literature Subject RIV: AJ - Letters, Mass-media, Audiovision

The experiences to improve plant performance and reliability of Ko-Ri nuclear power plants

International Nuclear Information System (INIS)

Kang, Ho Weon

1998-01-01

This paper provides a discussion of the lessons learned from operational experience and the future plans to improve performance of the Ko-Ri plant. To operate nuclear power plants safely with good performance is the only way to mitigate the negative image of nuclear power generation to the public and to enhance the economical benefit compared to other electrical generation method. Therefore, in a continuous effort to overcome a negative challenge from outside, we have driven an aggressive 'OCTF' campaign as part of safety. As a result of our efforts, the following remarkable achievements have been accomplished. (1) 3 times of OCTF during recent three years (2) Selected twice as a top notch power plant on the list of NEI magazine in terms of plant capacity factor (3) No scram recorded in 1997 for all 4 units at Ko-Ri site. Ko-Ri is now undergoing the large scale plant betterment projects for retaking-off our operating performance to the level of new challenge target. Such improvement of critical components in the reactor coolant system and turbine system greatly contribute to increase the safety and reliability of the plant and to shortening of the planned outage period as well as to reduction of radiation exposure and radwaste. (Cho, G. S.). 5 tabs., 10 figs

[Rehabilitation in the View of Small and Midsized Enterprises: Knowledge, Appreciation and Possibilities to Cooperate - Results of the KoRB-Project

DEFF Research Database (Denmark)

Hesse, B.; Heuer, J.; Gebauer, E.

2008-01-01

The experiences of small and midsized enterprises (SME) with medical rehabilitation were investigated in the KoRB-Study (KoRB= KOoperation Rehabilitation und Betrieb) for the first time. Opportunities for a targeted cooperation between the statutory pension insurance and these enterprises were...

Inner boundary reform in Košice: The most fragmented city in Slovakia

Directory of Open Access Journals (Sweden)

Csachová Stela

2016-01-01

Full Text Available In the first part of the paper the aim is to provide the reader with a theoretical insight into models of government structure at the local level and provide evidence from European countries that underwent reforms during the second half of the 20th century. In the Slovak Republic (Slovakia the renewal of local self-government in 1990 brought changes to the administrative boundary map with more than 200 municipalities reestablished bringing the current number to 2,929 local administrative units. This has resulted in some discussion regarding a reduction in the number of local government units in this country. The second part of the paper is focused on Košice; the second largest city in Slovakia with 234,000 in­habitants. The city is organised at two administrative levels; one covering the whole city, the other covering 22 wards. When compared to cities of a similar size, Košice has been criticised for its high number of city wards and councillors, with the concomitant financial inefficiency it can bring. There has been an ongoing debate on reducing their number since 2010. The paper reports on the search for an admin­istrative structure that would best tailor to the citizens' needs and provide effective management in Košice. It uses traditional methods of qualitative research (historical method, content analysis and syn­thesis accompanied by statistical data organised in tables and figures.

[Andreeva, E. and Belobrovtseva, I. "Tol'ko Vy poimete sleduiushchii tekst..."] / Avril Pyman

Index Scriptorium Estoniae

Pyman, Avril

2014-01-01

Arvustus: Andreeva, E. and Belobrovtseva, I. "Tol'ko Vy poimete sleduiushchii tekst...". Perepiska N. E. Andreeva i L. F. Zurova. Baltiiskii arkhiv: Russkaia kult'tura v Pribaltike, 13. Tallinna Ülikooli Slaavi Keelte ja Kultuuride Instituut, Tallinn, 2013

Functional consequences of brain glycogen deficiency on the sleep-wake cycle regulation in PTG-KO mice

KAUST Repository

Burlet-Godinot, S.

2017-12-31

Introduction: In the CNS, glycogen is mainly localized in astrocytes where its levels are linked to neuronal activity. Astrocytic glycogen synthesis is regulated by glycogen synthase (GS) activity that is positively controlled by protein targeting to glycogen (PTG) expression levels. Although the role of glycogen in sleep/wake regulation is still poorly understood, we have previously demonstrated that, following a 6 hour gentle sleep deprivation (GSD), PTG mRNA expression and GS activity increased in the brain in mice while glycogen levels were paradoxically maintained and not affected. In order to gain further insight on the role of PTG in this process, we studied the sleep/wake cycle parameters in PTG knockout (PTG-KO) mice under baseline conditions and after a 6 hour GSD. Glycogen levels as well as mRNAs expression of genes related to energy metabolism were also determined in several brain areas. Materials and methods: Adult male C57BL/6J (WT) and PTG-KO mice were sleep-recorded under baseline conditions (24 h recordings, 12 h light/dark cycle) and following 6 hours GSD from ZT00 to ZT06. Vigilance states were visually scored (4 s temporal window). Spectral analysis of the EEG signal was performed using a discrete Fourier transformation. Glycogen measurements and gene expression analysis were assessed using a biochemical assay and quantitative RT-PCR respectively, on separate cohorts in WT vs PTG-KO mice at the end of the 6 hours GSD or in control animals (CTL) in different brain structures. Results: Quantitative analysis of the sleep/wake cycle under baseline conditions did not reveal major differences between the WT and the PTG-KO mice. However, during the dark period, the PTG-KO mice showed a significant increase in the number of wake and slow wave sleep episodes (respectively +26.5±8% and +26.1±8%; p< 0.05) together with a significant shortening in their duration (-21.6±7.2% and -14.3±2.8%; p< 0.01). No such quantitative changes were observed during

Infection with koala retrovirus subgroup B (KoRV-B), but not KoRV-A, is associated with chlamydial disease in free-ranging koalas (Phascolarctos cinereus)

OpenAIRE

Waugh, Courtney A.; Hanger, Jonathan; Loader, Joanne; King, Andrew; Hobbs, Matthew; Johnson, Rebecca; Timms, Peter

2017-01-01

The virulence of chlamydial infection in wild koalas is highly variable between individuals. Some koalas can be infected (PCR positive) with Chlamydia for long periods but remain asymptomatic, whereas others develop clinical disease. Chlamydia in the koala has traditionally been studied without regard to coinfection with other pathogens, although koalas are usually subject to infection with koala retrovirus (KoRV). Retroviruses can be immunosuppressive, and there is evidence of an immunosuppr...

The experiences to improve plant performance and reliability of Ko-Ri nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Kang, Ho Weon [Korea Electric Power Corp. Ko-Ri nuclear power division, Ko-Ri (Korea, Republic of)

1998-07-01

This paper provides a discussion of the lessons learned from operational experience and the future plans to improve performance of the Ko-Ri plant. To operate nuclear power plants safely with good performance is the only way to mitigate the negative image of nuclear power generation to the public and to enhance the economical benefit compared to other electrical generation method. Therefore, in a continuous effort to overcome a negative challenge from outside, we have driven an aggressive 'OCTF' campaign as part of safety. As a result of our efforts, the following remarkable achievements have been accomplished. (1) 3 times of OCTF during recent three years (2) Selected twice as a top notch power plant on the list of NEI magazine in terms of plant capacity factor (3) No scram recorded in 1997 for all 4 units at Ko-Ri site. Ko-Ri is now undergoing the large scale plant betterment projects for retaking-off our operating performance to the level of new challenge target. Such improvement of critical components in the reactor coolant system and turbine system greatly contribute to increase the safety and reliability of the plant and to shortening of the planned outage period as well as to reduction of radiation exposure and radwaste. (Cho, G. S.). 5 tabs., 10 figs.

Maria Avdjuško väntab Priimäest filmi / Verni Leivak

Index Scriptorium Estoniae

Leivak, Verni, 1966-

2009-01-01

Näitlejanna debüteerib režissöörina, vändates lühimängufilmi, kus Linnar Priimägi peategelasena kehastab iseennast. Operaatoriks on Istvan Borbas Rootsist, näitlejateks veel M. Avdjuško ja Taavi Eelmaa

Professor Krystyna Kotełko and her contribution to the study of Proteus endotoxin.

Science.gov (United States)

Różalski, Antoni W

2018-04-01

Professor Krystyna Kotełko was working as a microbiologist at the University of Łódź (Poland). Her main object of study was the LPS (endotoxin) of opportunistic urinary pathogens from the genus Proteus. She demonstrated, for the first time, the presence of uronic acids and amino acids, as well as two heptoses (L- glycero-D- manno-heptose and D- glycero-D- manno-heptose) and hexosamines in Proteus LPS, and developed a classification scheme of the Proteus LPS into chemotypes. Prof Kotełko also initiated studies on the chemical structure of Proteus O-specific polysaccharide and investigations on the serological specificity of this part of LPS, as well its core region. She also analysed the virulence factors of these bacteria, such as haemolysin and invasiveness.

The essential oil of Amomum tsao-ko Crevost et Lemarie from Vietnam

NARCIS (Netherlands)

Dung, N.X.; Bien, Le Kiem; Leclercq, P.A.

1992-01-01

The essential oil of the seeds of A. tsao-ko of Vietnamese origin was analyzed by a combination of gas chromatog. and gas chromatog./mass spectrometry. Twenty-one components were identified, of which the major ones were 1,8-cineole (30.6%), 2-decenal (17.3%), geranial (10.6%), and neural (7.0%)

MicroRNA and Transcriptomic Profiling Showed miRNA-Dependent Impairment of Systemic Regulation and Synthesis of Biomolecules in Rag2 KO Mice.

Science.gov (United States)

Reza, Abu Musa Md Talimur; Choi, Yun-Jung; Kim, Jin-Hoi

2018-02-27

The Rag2 knockout (KO) mouse is a well-established immune-compromised animal model for biomedical research. A comparative study identified the deregulated expression of microRNAs (miRNAs) and messenger RNAs (mRNAs) in Rag2 KO mice. However, the interaction between deregulated genes and miRNAs in the alteration of systemic (cardiac, renal, hepatic, nervous, and hematopoietic) regulations and the synthesis of biomolecules (such as l-tryptophan, serotonin, melatonin, dopamine, alcohol, noradrenaline, putrescine, and acetate) are unclear. In this study, we analyzed both miRNA and mRNA expression microarray data from Rag2 KO and wild type mice to investigate the possible role of miRNAs in systemic regulation and biomolecule synthesis. A notable finding obtained from this analysis is that the upregulation of several genes which are target molecules of the downregulated miRNAs in Rag2 KO mice, can potentially trigger the degradation of l-tryptophan, thereby leading to the systemic impairment and alteration of biomolecules synthesis as well as changes in behavioral patterns (such as stress and fear responses, and social recognition memory) in Rag2 gene-depleted mice. These findings were either not observed or not explicitly described in other published Rag2 KO transcriptome analyses. In conclusion, we have provided an indication of miRNA-dependent regulations of clinical and pathological conditions in cardiac, renal, hepatic, nervous, and hematopoietic systems in Rag2 KO mice. These results may significantly contribute to the prediction of clinical disease caused by Rag2 deficiency.

MicroRNA and Transcriptomic Profiling Showed miRNA-Dependent Impairment of Systemic Regulation and Synthesis of Biomolecules in Rag2 KO Mice

Directory of Open Access Journals (Sweden)

Abu Musa Md Talimur Reza

2018-02-01

Full Text Available The Rag2 knockout (KO mouse is a well-established immune-compromised animal model for biomedical research. A comparative study identified the deregulated expression of microRNAs (miRNAs and messenger RNAs (mRNAs in Rag2 KO mice. However, the interaction between deregulated genes and miRNAs in the alteration of systemic (cardiac, renal, hepatic, nervous, and hematopoietic regulations and the synthesis of biomolecules (such as l-tryptophan, serotonin, melatonin, dopamine, alcohol, noradrenaline, putrescine, and acetate are unclear. In this study, we analyzed both miRNA and mRNA expression microarray data from Rag2 KO and wild type mice to investigate the possible role of miRNAs in systemic regulation and biomolecule synthesis. A notable finding obtained from this analysis is that the upregulation of several genes which are target molecules of the downregulated miRNAs in Rag2 KO mice, can potentially trigger the degradation of l-tryptophan, thereby leading to the systemic impairment and alteration of biomolecules synthesis as well as changes in behavioral patterns (such as stress and fear responses, and social recognition memory in Rag2 gene-depleted mice. These findings were either not observed or not explicitly described in other published Rag2 KO transcriptome analyses. In conclusion, we have provided an indication of miRNA-dependent regulations of clinical and pathological conditions in cardiac, renal, hepatic, nervous, and hematopoietic systems in Rag2 KO mice. These results may significantly contribute to the prediction of clinical disease caused by Rag2 deficiency.

Kampen om den røde ko - dominerende temaer i dansk kvægavl i 1800-tallets slutning

DEFF Research Database (Denmark)

Gjerløff, Anne Katrine

2009-01-01

En analyse af kvægavlslitteratur fra 1800-tallets anden halvdel viser spændingerne mellem avlernes ønske om profit og hensynene til racerenhed og national og regional identitet. Ideen om den perfekte ko var omdiskuteret og modsætningerne mellem koens udseende og dens ydelse er tydelige i periodens...... bedømmelser af "den gode ko". Artiklen komkluserer at et fokus på opfattelser og brug af dyr kan give nye vinkler på traditionelle historiske emnefelter. Udgivelsesdato: april...

Transport systems of Ventricaria ventricosa: I/V analysis of both membranes in series as a function of [K(+)](o).

Science.gov (United States)

Beilby, M J; Bisson, M A

1999-09-01

The current-voltage (I/V) profiles of Ventricaria (formerly Valonia) membranes were measured at a range of external potassium concentrations, [K(+)](o), from 0.1 to 100 mm. The conductance-voltage (G/V) characteristics were computed to facilitate better resolution of the profile change with time after exposure to different [K(+)](o). The resistance-voltage (R/V) characteristics were computed to attempt resolution of plasmalemma and tonoplast. Four basic electrophysiological stages emerged: (1) Uniform low resistance between -60 and +60 mV after the cell impalement. (2) High resistance between +50 and +150 for [K(+)](o) from 0.1 to 1.0 mm and hypotonic media. (3) High resistance between -150 and -20 mV for [K(+)](o) of 10 mm (close to natural seawater) and hypertonic media. (4) High resistance between -150 and +170 mV at [K(+)](o) of 100 mm. The changes between these states were slow, requiring minutes to hours and sometimes exhibiting spontaneous oscillations of the membrane p.d. (potential difference). Our analysis of the I/V data supports a previous hypothesis, that Ventricaria tonoplast is the more resistive membrane containing a pump, which transports K(+) into the vacuole to regulate turgor. We associate state (1) with the plasmalemma conductance being dominant and the K(+) pump at the tonoplast short-circuited probably by a K(+) channel, state (2) with the K(+) pump "off" or short-circuited at p.d.s more negative than +50 mV, state (3) with the K(+) pump "on, " and state (4) with the pump dominant, but affected by high K(+). A model for the Ventricaria membrane system is proposed.

Citation analysis of The Korean Journal of Internal Medicine from KoMCI, Web of Science, and Scopus.

Science.gov (United States)

Huh, Sun

2011-03-01

The Korean Journal of Internal Medicine (KJIM) is the international journal published in English by the Korean Association of Internal Medicine. To understand the position of the journal in three different databases, the citation indicators were elucidated. From databases such as Korean Medical Citation Index (KoMCI), Web of Science, and Scopus, citation indicators such as the impact factor, SCImago journal rank (SJR), or Hirsch Index were calculated according to the year and the results were drawn. The KJIM 2010 impact factor increased to 0.623 in Web of Science. That of year 2009 in KoMCI was a 0.149. The 2009 SJR in Scopus was 0.073, with a ranking of 27/72 (37.5%) in the category of internal medicine and 414/1,618 (25.6%) in the category of medicine, miscellaneous. The Hirsch Index from KoMCI, Web of Science and Scopus were 5, 14, and 16, respectively. The KJIM is now cited more by international researchers than Korean researchers, indicating that the content of the journal is now valued at the international level.

PROTEKSI VAKSIN MONOVALEN DAN KOKTAIL SEL UTUH TERHADAP KO-INFEKSI Mycobacterium fortuitum DAN Aeromonas hydrophila PADA IKAN GURAME, Osphronemus gouramy Uni

Directory of Open Access Journals (Sweden)

Uni Purwaningsih

2014-08-01

serangan agen patogen. Pemberian vaksin diharapkan dapat merangsang respons imun spesifik dan non spesifik pada ikan. Keberhasilan vaksinasi dipengaruhi oleh konsentrasi antigen, reaksi silang dan kompetisi di antara antigen yang berbeda. Penelitian ini bertujuan untuk menganalisis level proteksi vaksin monovalen dan koktail sel utuh terhadap ko-infeksi M. fortuitum dan A. hydrophila pada ikan gurame. Respons imun perlakuan vaksin monovalen maupun koktail pada gurame pasca ko-infeksi menunjukkan nilai parameter-parameter yaitu: hematokrit, hemoglobin, indeks fagositik, persentase fagositik, titer antibodi, uji respiratory burst (NBT, aktivitas komplemen, dan diferensial leukosit yang berbeda nyata (P<0,05 dibanding kontrol. Vaksin monovalen A. hydrophila menunjukkan nilai RPS sebesar 92,3% dan monovalen M. fortuitum sebesar 78,6% setelah ditantang dengan infeksi tunggal bakteri homolog namun menunjukkan proteksi yang rendah terhadap ko-infeksi. Vaksin koktail 50Mf :50Ah memberikan proteksi yang lebih baik dari vaksin monovalen pasca uji tantang dengan ko-infeksi bakteri M. fortuitum dan A. hydrophila.

KoVariome: Korean National Standard Reference Variome database of whole genomes with comprehensive SNV, indel, CNV, and SV analyses.

Science.gov (United States)

Kim, Jungeun; Weber, Jessica A; Jho, Sungwoong; Jang, Jinho; Jun, JeHoon; Cho, Yun Sung; Kim, Hak-Min; Kim, Hyunho; Kim, Yumi; Chung, OkSung; Kim, Chang Geun; Lee, HyeJin; Kim, Byung Chul; Han, Kyudong; Koh, InSong; Chae, Kyun Shik; Lee, Semin; Edwards, Jeremy S; Bhak, Jong

2018-04-04

High-coverage whole-genome sequencing data of a single ethnicity can provide a useful catalogue of population-specific genetic variations, and provides a critical resource that can be used to more accurately identify pathogenic genetic variants. We report a comprehensive analysis of the Korean population, and present the Korean National Standard Reference Variome (KoVariome). As a part of the Korean Personal Genome Project (KPGP), we constructed the KoVariome database using 5.5 terabases of whole genome sequence data from 50 healthy Korean individuals in order to characterize the benign ethnicity-relevant genetic variation present in the Korean population. In total, KoVariome includes 12.7M single-nucleotide variants (SNVs), 1.7M short insertions and deletions (indels), 4K structural variations (SVs), and 3.6K copy number variations (CNVs). Among them, 2.4M (19%) SNVs and 0.4M (24%) indels were identified as novel. We also discovered selective enrichment of 3.8M SNVs and 0.5M indels in Korean individuals, which were used to filter out 1,271 coding-SNVs not originally removed from the 1,000 Genomes Project when prioritizing disease-causing variants. KoVariome health records were used to identify novel disease-causing variants in the Korean population, demonstrating the value of high-quality ethnic variation databases for the accurate interpretation of individual genomes and the precise characterization of genetic variations.

Both chronic treatments by epothilone D and fluoxetine increase the short-term memory and differentially alter the mood status of STOP/MAP6 KO mice.

Science.gov (United States)

Fournet, Vincent; de Lavilléon, Gaetan; Schweitzer, Annie; Giros, Bruno; Andrieux, Annie; Martres, Marie-Pascale

2012-12-01

Recent evidence underlines the crucial role of neuronal cytoskeleton in the pathophysiology of psychiatric diseases. In this line, the deletion of STOP/MAP6 (Stable Tubule Only Polypeptide), a microtubule-stabilizing protein, triggers various neurotransmission and behavioral defects, suggesting that STOP knockout (KO) mice could be a relevant experimental model for schizoaffective symptoms. To establish the predictive validity of such a mouse line, in which the brain serotonergic tone is dramatically imbalanced, the effects of a chronic fluoxetine treatment on the mood status of STOP KO mice were characterized. Moreover, we determined the impact, on mood, of a chronic treatment by epothilone D, a taxol-like microtubule-stabilizing compound that has previously been shown to improve the synaptic plasticity deficits of STOP KO mice. We demonstrated that chronic fluoxetine was either antidepressive and anxiolytic, or pro-depressive and anxiogenic, depending on the paradigm used to test treated mutant mice. Furthermore, control-treated STOP KO mice exhibited paradoxical behaviors, compared with their clear-cut basal mood status. Paradoxical fluoxetine effects and control-treated STOP KO behaviors could be because of their hyper-reactivity to acute and chronic stress. Interestingly, both epothilone D and fluoxetine chronic treatments improved the short-term memory of STOP KO mice. Such treatments did not affect the serotonin and norepinephrine transporter densities in cerebral areas of mice. Altogether, these data demonstrated that STOP KO mice could represent a useful model to study the relationship between cytoskeleton, mood, and stress, and to test innovative mood treatments, such as microtubule-stabilizing compounds. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Provenience studies of the Ko-Kutani ware by neutron activation analysis

International Nuclear Information System (INIS)

Kawashima, Tatsuro.

1990-01-01

The instrumental neutron activation analysis has been applied to the multielemental analysis of eight samples of the Ko-Kutani ware including the Aote's that is one of semi-porcelain body. Each sample was compared with concentration of the useful index element, such as Ta, Sc, Ba, Hf, Th and rare earth, to discriminate the Arita group from the Kutani group. Eight samples were judged as products of the Arita, just as in previous paper. (author)

Genetic diversity analysis of Amomum tsao-ko in Jinping County of Yunnan Province using SSR markers

Science.gov (United States)

Ma, Mengli; Wang, Tiantao; Lei, En; Meng, Hengling; Xie, Linyan; Zhu, Kunlong; Duan, Shaoze; Li, Wenqiang; Lu, Bingyue

2017-08-01

Genetic diversity analysis is very important for germplasm resources conservation and utilization. The objective of this study was to assess the genetic diversity among 44 individuals of Amomum tsao-ko from Jinping County of Yunnan Province using 5 selected SSR (simple sequence repeat) markers. A total of 23 polymorphic loci were detected among these germplasms, with an average of 4.6 polymorphic loci per SSR primer combination. The percentage of polymorphic loci was 100%, whereas the mean effective number of alleles (Ne), observed heterozygosity(Ho), expected heterozygosity (He), Shannon's information index (I), and the mean polymorphism information content (PIC) were 3. 410, 0. 491, 0. 679, 1.266 and 0. 672, respectively, indicating that the Amomum tsao-ko germplasms from Jinping County had high genetic diversity.

Beta3 adrenoceptors substitute the role of M(2) muscarinic receptor in coping with cold stress in the heart: evidence from M(2)KO mice.

Science.gov (United States)

Benes, Jan; Novakova, Martina; Rotkova, Jana; Farar, Vladimir; Kvetnansky, Richard; Riljak, Vladimir; Myslivecek, Jaromir

2012-07-01

We investigated the role of beta3-adrenoceptors (AR) in cold stress (1 or 7 days in cold) in animals lacking main cardioinhibitive receptors-M2 muscarinic receptors (M(2)KO). There was no change in receptor number in the right ventricles. In the left ventricles, there was decrease in binding to all cardiostimulative receptors (beta1-, and beta2-AR) and increase in cardiodepressive receptors (beta3-AR) in unstressed KO in comparison to WT. The cold stress in WT animals resulted in decrease in binding to beta1- and beta2-AR (to 37%/35% after 1 day in cold and to 27%/28% after 7 days in cold) while beta3-AR were increased (to 216% of control) when 7 days cold was applied. MR were reduced to 46% and 58%, respectively. Gene expression of M2 MR in WT was not changed due to stress, while M3 was changed. The reaction of beta1- and beta2-AR (binding) to cold was similar in KO and WT animals, and beta3-AR in stressed KO animals did not change. Adenylyl cyclase activity was affected by beta3-agonist CL316243 in cold stressed WT animals but CL316243 had almost no effects on adenylyl cyclase activity in stressed KO. Nitric oxide activity (NOS) was not affected by BRL37344 (beta3-agonist) both in WT and KO animals. Similarly, the stress had no effects on NOS activity in WT animals and in KO animals. We conclude that the function of M2 MR is substituted by beta3-AR and that these effects are mediated via adenylyl cyclase rather than NOS.

Contemporary population and development challenges in the Municipality of Dubrovačko Primorje, Croatia

Directory of Open Access Journals (Sweden)

Helena Karlić Mujo

2010-06-01

Full Text Available The purpose of this paper is to define the basic issues and opportunities challenging the modern development of the Municipality of Dubrovačko Primorje, their causes and effects. The processes of depopulation affected this poorly developed rural region since 1960s, which had been influenced by various factors: development polarisation caused by intensive development of tourism, the poor traffic infrastructure in the highland-area of the Municipality and the unsolved water supply issue. In 1990s a series of events intensified negative demographic trends as follows: aggression on Croatia, occupation during which residential, economic and infrastructural buildings were destroyed and burnt, as well as an earthquake which happened after the return of the refugees. The long-lasting rural emigration from this region towards Dubrovnik caused not only an instantaneous decrease of population but also a contraction of the renewing basis and an accelerated decrease of natural growth in the Municipality of Dubrovačko Primorje. In that way the emigrational depopulation as a consequence of a specific socioeconomic development, became the cause of the current biological depopulation. The intensity of the depopulation processes has been established by an analysis of a total population dynamics and the changes in biological and economic population structure. The conclusion of the study indicates activities which have promising development in the Municipality of Dubrovačko Primorje and which might partly stop the negative demographic trends. Those are mainly traditional activities in this region which are not commercially used enough. They should prevent any further emigration and perhaps even attract those who immigrated, back to their place of birth.

Contemporary population and development challenges in the Municipality of Dubrovačko Primorje, Croatia

Directory of Open Access Journals (Sweden)

Helena Karlić Mujo

2010-01-01

Full Text Available The purpose of this paper is to define the basic issues and opportunities challenging the modern development of the Municipality of Dubrovačko Primorje, their causes and effects. The processes of depopulation affected this poorly developed rural region since 1960s, which had been influenced by various factors: development polarisation caused by intensive development of tourism, the poor traffic infrastructure in the highland-area of the Municipality and the unsolved water supply issue. In 1990s a series of events intensified negative demographic trends as follows: aggression on Croatia, occupation during which residential, economic and infrastructural buildings were destroyed and burnt, as well as an earthquake which happened after the return of the refugees. The long-lasting rural emigration from this region towards Dubrovnik caused not only an instantaneous decrease of population but also a contraction of the renewing basis and an accelerated decrease of natural growth in the Municipality of Dubrovačko Primorje. In that way the emigrational depopulation as a consequence of a specific socioeconomic development, became the cause of the current biological depopulation. The intensity of the depopulation processes has been established by an analysis of a total population dynamics and the changes in biological and economic population structure. The conclusion of the study indicates activities which have promising development in the Municipality of Dubrovačko Primorje and which might partly stop the negative demographic trends. Those are mainly traditional activities in this region which are not commercially used enough. They should prevent any further emigration and perhaps even attract those who immigrated, back to their place of birth.

Experience of Ko-Ri Unit 1 water chemistry

International Nuclear Information System (INIS)

Tae Il Lee

1983-01-01

The main focus is placed on operational experience in secondary system water chemistry (especially the steam generator) of the Ko-Ri nuclear power plant Unit 1, Republic of Korea, but primary side chemistry is also discussed. The major concern of secondary water chemistry in a PWR is that the condition of the steam generator be well maintained. Full flow deep bed condensate polishers have recently been installed and operation started in July 1982. Boric acid treatment of the steam generator was stopped and only the all volatile treatment method was used thereafter. A review of steam generator integrity, the chemistry control programme, secondary water quality, etc. is considered to be of great value regarding the operation of Unit 1 and future units now under startup testing or construction in the Republic of Korea. (author)

Phase analysis of Košice meteorite: Preliminary results

Science.gov (United States)

Sitek, J.; Dekan, J.; Degmová, J.; Sedlačková, K.

2012-10-01

Meteorite fall was observed by the Košice town in Slovakia in February 2010 and it was classified as an ordinary chondrite H5. The samples were prepared in powder form scratched from the surface. Mossbauer spectra were measured at room temperature and liquid nitrogen temperature. Spectra consist of components related to iron-bearing phases with different content. Non-magnetic part was fitted with three quadrupole doublets. According to its parameters, we identified olivine, pyroxene, and traces of Fe3+ phases. Magnetic part consists of an iron-rich Fe-Ni alloy with hyperfine magnetic field similar to kamacite α-Fe(Ni,Co) and troilite. Main elements were also determined by X-ray fluorescence spectroscopy.

Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice

Directory of Open Access Journals (Sweden)

Zhao Yarui

2011-01-01

Full Text Available Abstract Background Sphingomyelin synthase 2 (SMS2 contributes to de novo sphingomyelin (SM biosynthesis. Its activity is related to SM levels in the plasma and the cell membrane. In this study, we investigated the possibility of a direct relationship between SMS and atherosclerosis. Methods The Adenovirus containing SMS2 gene was given into 10-week ApoE KO C57BL/6J mice by femoral intravenous injection. In the control group, the Adenovirus containing GFP was given. To confirm this model, we took both mRNA level examination (RT-PCR and protein level examination (SMS activity assay. Result We generated recombinant adenovirus vectors containing either human SMS2 cDNA (AdV-SMS2 or GFP cDNA (AdV-GFP. On day six after intravenous infusion of 2 × 1011 particle numbers into ten-week-old apoE KO mice, AdV-SMS2 treatment significantly increased liver SMS2 mRNA levels and SMS activity (by 2.7-fold, 2.3-fold, p Conclusions Our results present direct morphological evidence for the pro-atherogenic capabilities of SMS2. SMS2 could be a potential target for treating atherosclerosis.

Abnormal type I collagen post-translational modification and crosslinking in a cyclophilin B KO mouse model of recessive osteogenesis imperfecta.

Science.gov (United States)

Cabral, Wayne A; Perdivara, Irina; Weis, MaryAnn; Terajima, Masahiko; Blissett, Angela R; Chang, Weizhong; Perosky, Joseph E; Makareeva, Elena N; Mertz, Edward L; Leikin, Sergey; Tomer, Kenneth B; Kozloff, Kenneth M; Eyre, David R; Yamauchi, Mitsuo; Marini, Joan C

2014-06-01

Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause recessively inherited osteogenesis imperfecta type IX, a moderately severe to lethal bone dysplasia. To investigate the role of CyPB in collagen folding and post-translational modifications, we generated Ppib-/- mice that recapitulate the OI phenotype. Knock-out (KO) mice are small, with reduced femoral areal bone mineral density (aBMD), bone volume per total volume (BV/TV) and mechanical properties, as well as increased femoral brittleness. Ppib transcripts are absent in skin, fibroblasts, femora and calvarial osteoblasts, and CyPB is absent from KO osteoblasts and fibroblasts on western blots. Only residual (2-11%) collagen prolyl 3-hydroxylation is detectable in KO cells and tissues. Collagen folds more slowly in the absence of CyPB, supporting its rate-limiting role in folding. However, treatment of KO cells with cyclosporine A causes further delay in folding, indicating the potential existence of another collagen PPIase. We confirmed and extended the reported role of CyPB in supporting collagen lysyl hydroxylase (LH1) activity. Ppib-/- fibroblast and osteoblast collagen has normal total lysyl hydroxylation, while increased collagen diglycosylation is observed. Liquid chromatography/mass spectrometry (LC/MS) analysis of bone and osteoblast type I collagen revealed site-specific alterations of helical lysine hydroxylation, in particular, significantly reduced hydroxylation of helical crosslinking residue K87. Consequently, underhydroxylated forms of di- and trivalent crosslinks are strikingly increased in KO bone, leading to increased total crosslinks and decreased helical hydroxylysine- to lysine-derived crosslink ratios. The altered crosslink

Humanized HLA-DR4.RagKO.IL2RγcKO.NOD (DRAG) mice sustain the complex vertebrate life cycle of Plasmodium falciparum malaria.

Science.gov (United States)

Wijayalath, Wathsala; Majji, Sai; Villasante, Eileen F; Brumeanu, Teodor D; Richie, Thomas L; Casares, Sofia

2014-09-30

Malaria is a deadly infectious disease affecting millions of people in tropical and sub-tropical countries. Among the five species of Plasmodium parasites that infect humans, Plasmodium falciparum accounts for the highest morbidity and mortality associated with malaria. Since humans are the only natural hosts for P. falciparum, the lack of convenient animal models has hindered the understanding of disease pathogenesis and prompted the need of testing anti-malarial drugs and vaccines directly in human trials. Humanized mice hosting human cells represent new pre-clinical models for infectious diseases that affect only humans. In this study, the ability of human-immune-system humanized HLA-DR4.RagKO.IL2RγcKO.NOD (DRAG) mice to sustain infection with P. falciparum was explored. Four week-old DRAG mice were infused with HLA-matched human haematopoietic stem cells (HSC) and examined for reconstitution of human liver cells and erythrocytes. Upon challenge with infectious P. falciparum sporozoites (NF54 strain) humanized DRAG mice were examined for liver stage infection, blood stage infection, and transmission to Anopheles stephensi mosquitoes. Humanized DRAG mice reconstituted human hepatocytes, Kupffer cells, liver endothelial cells, and erythrocytes. Upon intravenous challenge with P. falciparum sporozoites, DRAG mice sustained liver to blood stage infection (average 3-5 parasites/microlitre blood) and allowed transmission to An. stephensi mosquitoes. Infected DRAG mice elicited antibody and cellular responses to the blood stage parasites and self-cured the infection by day 45 post-challenge. DRAG mice represent the first human-immune-system humanized mouse model that sustains the complex vertebrate life cycle of P. falciparum without the need of exogenous injection of human hepatocytes/erythrocytes or P. falciparum parasite adaptation. The ability of DRAG mice to elicit specific human immune responses to P. falciparum parasites may help deciphering immune correlates

Application of analytic hierarchy process in landscape management: Case study area Košutnjak park-forest

Directory of Open Access Journals (Sweden)

Lakićević Milena

2011-01-01

Full Text Available Proper management is one of key elements of the natural landscape protection strategy. Park-forests with protected and conserved natural elements represent attractive eco-tourism urban zones. Košutnjak is the most visited park-forest in Serbian capitol Belgrade, unfortunately with increasing number of degraded and devastated areas as a consequence of negative human impacts in the past. In order to conserve natural values in this popular forested city area, and to improve its tourism potential, we found that in achieving that goal, it is meaningful to asses possible management practices and identify the most desired one by applying the analytic hierarchy process (AHP, scientifically sound multi-criteria decision making tool. Based on the obtained results, a recommended strategy is to renovate natural vegetation and to promote recreational and tourism offer in Košutnjak with respect of the sustainability principle.

PF-KO system for single bunch mode operation of a storage ring

International Nuclear Information System (INIS)

Ohgaki, H.; Sugiyama, S.; Mikado, T.; Chiwaki, M.; Yamada, K.; Suzuki, R.; Sei, N.; Noguchi, T.; Yamazaki, T.

1994-01-01

A new RF-KO (RF knockout) system for the single bunch mode operation of a storage ring has been developed. The knockout signal is modulated by the sum signal of the RF acceleration frequency of the storage ring and a bunch selection signal. We do not need any special device or a timing unit with this method. We obtain a high purity of bunch structure in a short knock out time. The single bunch impurity of 0.2% has been achieved. (author)

Studies of N ~ 40 Ni isotopes via neutron-knockout (nKO) and deep-inelastic (DI) reactions

Science.gov (United States)

Chiara, C. J.; Recchia, F.; Gade, A.; Janssens, R. V. F.; Walters, W. B.

2013-10-01

V. BADER, T. BAUGHER, D. BAZIN, J.S. BERRYMAN, B.A. BROWN, C. LANGER, N. LARSON, S.N. LIDDICK, E. LUNDERBERG, S. NOJI, C. PROKOP, S.R. STROBERG, S. SUCHYTA, D. WEISSHAAR, S. WILLIAMS, NSCL/MSU, M. ALBERS, M. ALCORTA, P.F. BERTONE, M.P. CARPENTER, J. CHEN, C.R. HOFFMAN, F.G. KONDEV, T. LAURITSEN, A.M. ROGERS, D. SEWERYNIAK, S. ZHU, ANL, C.M. CAMPBELL, LBNL, H.M. DAVID, D.T. DOHERTY, U. of Edinburgh/ANL, A. KORICHI, CSNSM-IN2P3/ANL, C.J. LISTER, U. of Mass.-Lowell, K. WIMMER, Central Mich. U. -- Excited states in 68Ni were populated in 2nKO reactions at NSCL. Prompt γ rays were detected with the GRETINA array located in front of the S800 separator. A hodoscope at the S800 focal plane captured the 68Ni ions, where isomeric decays could be correlated with prompt γ rays. Decay of the first excited state, a 0+ isomer, was observed, confirming that its energy substantially differs from the literature value. Comparing the decay patterns of excited states with shell-model calculations provides insight into their underlying structure. Data from 70Zn + 208Pb DI reactions studied with Gammasphere provide results consistent with the 2nKO. Single-particle strengths are also under investigation in the odd- A Ni isotopes via 1nKO reactions. Supported in part by the DoE (DE-FG02-94ER40834, DE-AC02-06CH11357), NSF (PHY-1102511), and NNSA (DE-NA0000979).

Functional consequences of brain glycogen deficiency on the sleep-wake cycle regulation in PTG-KO mice

KAUST Repository

Burlet-Godinot, S.; Allaman, I.; Grenningloh, G.; Roach, P.J.; Depaoli-Roach, A.A.; Magistretti, Pierre J.; Petit, J.-M.

2017-01-01

in the brain in mice while glycogen levels were paradoxically maintained and not affected. In order to gain further insight on the role of PTG in this process, we studied the sleep/wake cycle parameters in PTG knockout (PTG-KO) mice under baseline conditions

Abnormal type I collagen post-translational modification and crosslinking in a cyclophilin B KO mouse model of recessive osteogenesis imperfecta.

Directory of Open Access Journals (Sweden)

Wayne A Cabral

2014-06-01

Full Text Available Cyclophilin B (CyPB, encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause recessively inherited osteogenesis imperfecta type IX, a moderately severe to lethal bone dysplasia. To investigate the role of CyPB in collagen folding and post-translational modifications, we generated Ppib-/- mice that recapitulate the OI phenotype. Knock-out (KO mice are small, with reduced femoral areal bone mineral density (aBMD, bone volume per total volume (BV/TV and mechanical properties, as well as increased femoral brittleness. Ppib transcripts are absent in skin, fibroblasts, femora and calvarial osteoblasts, and CyPB is absent from KO osteoblasts and fibroblasts on western blots. Only residual (2-11% collagen prolyl 3-hydroxylation is detectable in KO cells and tissues. Collagen folds more slowly in the absence of CyPB, supporting its rate-limiting role in folding. However, treatment of KO cells with cyclosporine A causes further delay in folding, indicating the potential existence of another collagen PPIase. We confirmed and extended the reported role of CyPB in supporting collagen lysyl hydroxylase (LH1 activity. Ppib-/- fibroblast and osteoblast collagen has normal total lysyl hydroxylation, while increased collagen diglycosylation is observed. Liquid chromatography/mass spectrometry (LC/MS analysis of bone and osteoblast type I collagen revealed site-specific alterations of helical lysine hydroxylation, in particular, significantly reduced hydroxylation of helical crosslinking residue K87. Consequently, underhydroxylated forms of di- and trivalent crosslinks are strikingly increased in KO bone, leading to increased total crosslinks and decreased helical hydroxylysine- to lysine-derived crosslink ratios. The altered

Abnormal Type I Collagen Post-translational Modification and Crosslinking in a Cyclophilin B KO Mouse Model of Recessive Osteogenesis Imperfecta

Science.gov (United States)

Cabral, Wayne A.; Perdivara, Irina; Weis, MaryAnn; Terajima, Masahiko; Blissett, Angela R.; Chang, Weizhong; Perosky, Joseph E.; Makareeva, Elena N.; Mertz, Edward L.; Leikin, Sergey; Tomer, Kenneth B.; Kozloff, Kenneth M.; Eyre, David R.; Yamauchi, Mitsuo; Marini, Joan C.

2014-01-01

Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause recessively inherited osteogenesis imperfecta type IX, a moderately severe to lethal bone dysplasia. To investigate the role of CyPB in collagen folding and post-translational modifications, we generated Ppib−/− mice that recapitulate the OI phenotype. Knock-out (KO) mice are small, with reduced femoral areal bone mineral density (aBMD), bone volume per total volume (BV/TV) and mechanical properties, as well as increased femoral brittleness. Ppib transcripts are absent in skin, fibroblasts, femora and calvarial osteoblasts, and CyPB is absent from KO osteoblasts and fibroblasts on western blots. Only residual (2–11%) collagen prolyl 3-hydroxylation is detectable in KO cells and tissues. Collagen folds more slowly in the absence of CyPB, supporting its rate-limiting role in folding. However, treatment of KO cells with cyclosporine A causes further delay in folding, indicating the potential existence of another collagen PPIase. We confirmed and extended the reported role of CyPB in supporting collagen lysyl hydroxylase (LH1) activity. Ppib−/− fibroblast and osteoblast collagen has normal total lysyl hydroxylation, while increased collagen diglycosylation is observed. Liquid chromatography/mass spectrometry (LC/MS) analysis of bone and osteoblast type I collagen revealed site-specific alterations of helical lysine hydroxylation, in particular, significantly reduced hydroxylation of helical crosslinking residue K87. Consequently, underhydroxylated forms of di- and trivalent crosslinks are strikingly increased in KO bone, leading to increased total crosslinks and decreased helical hydroxylysine- to lysine-derived crosslink ratios. The altered

Digital technical map of Košice city

Directory of Open Access Journals (Sweden)

Štefan Kuzevič

2007-06-01

Full Text Available The digital map of a city is comprised complex of the map. Process of creation of the digital map of a city is time consuming and financially demanding. The digital map is created as co-operation of the local authority, technology network administrator, companies, and local government. The exact and current digital map of the city utilizable for multilateral applications is the result of this co-operation. The digital map of city catch all important phenomenon and objects which are needed for making decisions and planning to all grades controlling the local authority. The Geographic information systems tools make possible updating digital map, analyses and syntheses spatial phenomena and theirs relationships. The digital map of city is created step by step. The digital technical map of city is one of very important part of the digital map. Illustration of the part digital technical map of Košice is showed in the Fig. 1.

Fus1 KO Mouse As a Model of Oxidative Stress-Mediated Sporadic Alzheimer's Disease: Circadian Disruption and Long-Term Spatial and Olfactory Memory Impairments.

Science.gov (United States)

Coronas-Samano, Guillermo; Baker, Keeley L; Tan, Winston J T; Ivanova, Alla V; Verhagen, Justus V

2016-01-01

Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology. Here we characterize and propose the Fus1 KO mice that lack a mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance, we assessed sAD related deficits in Fus1 KO and WT adult mice of 4-5 months old, the equivalent human age when the earliest cognitive and olfactory sAD symptoms arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased levels of PRDX1), disruption of metabolic homeostasis (decreased levels of ACC2, increased phosphorylation of AMPK), autophagy (decreased levels of LC3-II), PKC (decreased levels of RACK1) and calcium signaling (decreased levels of Calb2) in the olfactory bulb and/or hippocampus. Mice were behaviorally tested using objective and accurate video tracking (Noldus), in which Fus1 KO mice showed clear deficits in olfactory memory (decreased habituation/cross-habituation in the short and long term), olfactory guided navigation memory (inability to reduce their latency to find the hidden cookie), spatial memory (learning impairments on finding the platform in the Morris water maze) and showed more sleep time during the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory perception (cross-habituation), association memory (passive avoidance) or in species-typical behavior (nest building) and no increased anxiety (open field, light-dark box) or depression/anhedonia (sucrose preference) at this relatively young age. These neurobehavioral

Further Development of Ko Displacement Theory for Deformed Shape Predictions of Nonuniform Aerospace Structures

Science.gov (United States)

Ko, William L.; Fleischer, Van Tran

2009-01-01

The Ko displacement theory previously formulated for deformed shape predictions of nonuniform beam structures is further developed mathematically. The further-developed displacement equations are expressed explicitly in terms of geometrical parameters of the beam and bending strains at equally spaced strain-sensing stations along the multiplexed fiber-optic sensor line installed on the bottom surface of the beam. The bending strain data can then be input into the displacement equations for calculations of local slopes, deflections, and cross-sectional twist angles for generating the overall deformed shapes of the nonuniform beam. The further-developed displacement theory can also be applied to the deformed shape predictions of nonuniform two-point supported beams, nonuniform panels, nonuniform aircraft wings and fuselages, and so forth. The high degree of accuracy of the further-developed displacement theory for nonuniform beams is validated by finite-element analysis of various nonuniform beam structures. Such structures include tapered tubular beams, depth-tapered unswept and swept wing boxes, width-tapered wing boxes, and double-tapered wing boxes, all under combined bending and torsional loads. The Ko displacement theory, combined with the fiber-optic strain-sensing system, provide a powerful tool for in-flight deformed shape monitoring of unmanned aerospace vehicles by ground-based pilots to maintain safe flights.

Field measurement of the piping system vibration of Ko-Ri unit 4 during the load-following operation

International Nuclear Information System (INIS)

Chung, Tae-Young; Hong, Sung-Yull; Kim, Bum-Nyun.

1989-01-01

During the load-following operation of nuclear power plants, flow rate, temperature, and pressure in the piping system can be varied by changing the electric power output level, and these variations can cause different vibration phenomena in the piping system. The piping system vibration is important because it is directly related to the dynamic stress of the piping system and can affect the life of the piping system through structural fatigue. An assessment of vibration levels for the classes II and III piping systems of the Ko-Ri Unit 4950-MW nuclear power plant was performed according to the given pattern of the load-following operation to study its feasibility from the viewpoint of piping system vibration. The classes II and III piping system vibration of the Ko-Ri Unit 4 may not cause any potential problem under the given pattern of the load-following operation; however, it is recommended that long-term operation in the 85 to 95% power range be avoided as much as possible

Generation and testing anti-influenza human monoclonal antibodies in a new humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO. IL-2Rγc KO. NOD).

Science.gov (United States)

Mendoza, Mirian; Ballesteros, Angela; Qiu, Qi; Pow Sang, Luis; Shashikumar, Soumya; Casares, Sofia; Brumeanu, Teodor-D

2018-02-01

Pandemic outbreaks of influenza type A viruses have resulted in numerous fatalities around the globe. Since the conventional influenza vaccines (CIV) provide less than 20% protection for individuals with weak immune system, it has been considered that broadly cross-neutralizing antibodies may provide a better protection. Herein, we showed that a recently generated humanized mouse (DRAGA mouse; HLA-A2. HLA-DR4. Rag1KO. IL-2Rgc KO. NOD) that lacks the murine immune system and expresses a functional human immune system can be used to generate cross-reactive, human anti-influenza monoclonal antibodies (hu-mAb). DRAGA mouse was also found to be suitable for influenza virus infection, as it can clear a sub-lethal infection and sustain a lethal infection with PR8/A/34 influenza virus. The hu-mAbs were designed for targeting a human B-cell epitope ( 180 WGIHHPPNSKEQ QNLY 195 ) of hemagglutinin (HA) envelope protein of PR8/A/34 (H1N1) virus with high homology among seven influenza type A viruses. A single administration of HA 180-195 specific hu-mAb in PR8-infected DRAGA mice significantly delayed the lethality by reducing the lung damage. The results demonstrated that DRAGA mouse is a suitable tool to (i) generate heterotype cross-reactive, anti-influenza human monoclonal antibodies, (ii) serve as a humanized mouse model for influenza infection, and (iii) assess the efficacy of anti-influenza antibody-based therapeutics for human use.

Żydzi w dyskursie Kościoła katolickiego

Directory of Open Access Journals (Sweden)

Marzena Makuchowska

2016-01-01

anti-Semitism. After 1989 in Poland anti-Jewish inclinations returned, especially in the circle of the so callled Catholicism of the Maryja Radio. Again Jews are accused of causing damage to Poles, and the language of those statements is very much like in the discourse before the Council.   Żydzi w dyskursie Kościoła katolickiego Artykuł opisuje ważne zmiany w dyskursie Kościoła katolickiego w odniesieniu do wyznawców judaizmu, które pojawiły się po Soborze Watykańskim II. Jedną z nich jest różnica pomiędzy stanem tekstów w dwóch różnych momentach: przed i po soborze. Dlatego pierwszą część artykułu autorka poświęca charakterystyce przedsoborowego (i w większości przedwojennego dyskursu na temat Żydów, a część drugą – głównym kierunkom zmian spowodowanym realizacją postulatów soboru. Część trzecia pokazuje objawy kontynuacji starych, głęboko zakorzenionych schematów. Analiza częściowo odnosi się do ogólnych tekstów Kościoła, a częściowo do tekstów Kościoła publikowanych w Polsce. Polski przedsoborowy dyskurs o Żydach był wyjątkowo negatywny. Liturgia katolicka przedstawiała Żydów jako tych, którzy torturowali i zabili Jezusa (mit bogobójcy. W kazaniach, listach duszpasterskich i katolickiej prasie Żydów pokazywano jako wrogów nie tylko chrześcijan, lecz szczególnie Polaków, ponieważ Kościół w Polsce zaangażował się w kreowanie narodowo i religijnie homogenicznego kraju pod sloganem „Polska dla Polaków”. Reprodukowano wszystkie tradycyjne mity (Żydzi jako szkodnicy, spiskowcy, rozpustnicy itd. Używano wiele środków lingwistycznych, by zdegradować Żydów, np. zdrobnienia, animalizację (czyli mówienie o Żydach jako o zwierzętach czy tak zwany kakofemizm (czyli używanie słów o pejoratywnym znaczeniu, aby sprowokować uczucie moralnego i fizycznego obrzydzenia. Po Vaticanum II treści reprodukujące przedstawienie Żydów jako bogobójców zostały usunięte z liturgii

Fus1 KO mouse as a model of oxidative stress-mediated sporadic Alzheimer’s disease: circadian disruption and long-term spatial and olfactory memory impairments.

Directory of Open Access Journals (Sweden)

Guillermo Coronas-Samano

2016-11-01

Full Text Available Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology. Here we characterize and propose the Fus1 KO mice that lack a mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance, we assessed sAD related deficits in Fus1 KO and WT adult mice of 4-5 months old, the equivalent human age when the earliest cognitive and olfactory sAD symptoms arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased levels of PRDX1, disruption of metabolic homeostasis (decreased levels of ACC2, increased phosphorylation of AMPK, autophagy (decreased levels of LC3-II, PKC (decreased levels of RACK1 and calcium signaling (decreased levels of Calb2 in the olfactory bulb and/or hippocampus. Mice were behaviorally tested using objective and accurate video tracking (Noldus, in which Fus1 KO mice showed clear deficits in olfactory memory (decreased habituation/cross-habituation in the short and long term, olfactory guided navigation memory (inability to reduce their latency to find the hidden cookie, spatial memory (learning impairments on finding the platform in the Morris water maze and showed more sleep time during the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory perception (cross-habituation, association memory (passive avoidance or in species-typical behavior (nest building and no increased anxiety (open field, light-dark box or depression/anhedonia (sucrose preference at this relatively young age. These

Habitat Characteristics of Bracken-Covered Areas Intended for Afforestation in Ličko Sredogorje

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Zvonko Seletković

2013-12-01

Full Text Available Background and Purpose: Forest cultures in continental part of Croatia are mainly based on bracken-covered areas and moors on deserted agriculture soils and pastures. Successful afforestation i.e. establishment of forest cultures depends among other things on the understanding of habitats and ecology of forest trees. The choice of best species of forest trees for afforestation needs to be based on the research in soil and climate characteristics of target habitats. The aims of this research were to show mesoclimatic characteristics of Ličko sredogorje and microclimatic and pedological characteristics of Ličko polje. Also, based on habitat characteristics and ecology of forest trees, the aim was to determine species of forest trees suitable for afforestation of bracken-covered areas. Materials and Methods: Climate, microclimate, pedological and plant nutrition researches were done at the area of Lika highlands. Climate analysis was done according to air temperatures, amount of precipitation, relative air humidity and other climate elements and appearances. Composite soil samples were taken from the depth of 0-30 cm in order to determine plant nutrition potential. Samples were prepared for further analysis in the laboratory. Results: The highest average annual air temperature of 9.6 °C was found at weather station Gračac and the lowest at Korenica station (8.1 °C. Average amount of precipitation for this region was around 1500 mm. Monthly rain factors were ranging from arid to perhumid. Considering thermal character of the climate, the area has moderately warm climate. Average volumetric soil humidity is 14.2 %. Soil has strong acid reaction, is very humus, good to richly supplied with total nitrogen, content of physiologically active phosphorus and potassium is low, and C/N ration normal. Conclusions: According to habitat characteristics in the area of Ličko sredogorje and ecological demands of forest tree species, forest cultures of Common

Fizičko-hemijske i detonacione karakteristike nitraminskih eksploziva - RDX, HMX i CL-20

OpenAIRE

Anđelković-Lukić Mirjana

2002-01-01

U radu su prikazane fizičko-hemijske i detonacione karakteristike nitraminskih brizantnih eksploziva, heksogena i oktogena, uporedene sa osobinama novog cikličnog nitraminskog eksploziva CL-20. Novi visokobrizantni eksploziv CL-20 postoji u četiri kristalne forme, stabilne na različitim temepraturama. Ima bolje detonacione karakteristike od heksogena i oktogena veću gustinu i brzinu detonacije, all mnogo veću osetljivost na udar i trenje, reda PETN. Zbog toga se ovaj eksploziv flegmatizuje sa...

First case of human babesiosis in Korea: detection and characterization of a novel type of Babesia sp. (KO1) similar to ovine babesia.

Science.gov (United States)

Kim, Jung-Yeon; Cho, Shin-Hyeong; Joo, Hyun-Na; Tsuji, Masayoshi; Cho, Sung-Ran; Park, Il-Joong; Chung, Gyung-Tae; Ju, Jung-Won; Cheun, Hyeng-Il; Lee, Hyeong-Woo; Lee, Young-Hee; Kim, Tong-Soo

2007-06-01

We report on the first case of human babesiosis in Korea. The intraerythrocytic parasite (KO1) in the patient's blood mainly appeared as paired pyriforms and ring forms; but Maltese cross forms were not seen, and the parasite showed morphological features consistent with those of the genus Babesia sensu stricto. The sequence of the 18S rRNA gene of KO1 was closely related to that of Babesia spp. isolated from sheep in China (similarity, 98%). The present study provides the first evidence of the presence of a hitherto unidentified, new type of Babesia parasite capable of infecting humans.

Revisiting T2KK and T2KO physics potential and ν{sub μ}- anti ν{sub μ} beam ratio

Energy Technology Data Exchange (ETDEWEB)

Hagiwara, Kaoru [Theory Center, KEK, Tsukuba, Ibaraki (Japan); Sokendai, Department of Accelerator Science, Tsukuba, Ibaraki (Japan); Ko, Pyungwon [KIAS, School of Physics, Seoul (Korea, Republic of); Okamura, Naotoshi [International University of Health and Welfare, Department of Radiological Sciences, Ohtawara, Tochigi (Japan); Takaesu, Yoshitaro [University of Tokyo, Department of Physics, Tokyo (Japan)

2017-03-15

We revisit the sensitivity study of the Tokai-to-Kamioka-and-Korea (T2KK) and Tokai-to-Kamioka-and-Oki (T2KO) proposals where a water Cerenkov detector with the 100 kton fiducial volume is placed in Korea (L = 1000 km) and Oki island (L = 653 km) in Japan, respectively, in addition to the Super-Kamiokande for determination of the neutrino mass hierarchy and leptonic CP phase (δ{sub CP}). We systematically study the running ratio of the ν{sub μ} and anti ν{sub μ} focusing beams with dedicated background estimation for the ν{sub e} appearance and ν{sub μ} disappearance signals, especially improving treatment of the neutral-current π{sup 0} backgrounds. Using a ν{sub μ}- anti ν{sub μ} beam ratio between 3:2 and 2.5:2.5 (in units of 10{sup 21}POT with the proton energy of 40 GeV), the mass-hierarchy determination with the median sensitivity of 3-5 σ by the T2KK and 1-4 σ by the T2KO experiment are expected when sin{sup 2}θ{sub 23} = 0.5, depending on the mass-hierarchy pattern and CP phase. These sensitivities are enhanced (reduced) by 30-40% in Δχ{sup 2} when sin{sup 2}θ{sub 23} = 0.6 (0.4). The CP phase is measured with the uncertainty of 20 {sup circle} -50 {sup circle} by the T2KK and T2KO using the ν{sub μ}- anti ν{sub μ} focusing beam ratio between 3.5:1.5 and 1.5:3.5. These findings indicate that inclusion of the anti ν{sub μ} focusing beam improves the sensitivities of the T2KK and T2KO experiments to both the mass-hierarchy determination and the leptonic CP phase measurement simultaneously with the preferred beam ratio being between 3:2-2.5:2.5 (x 10{sup 21}POT). (orig.)

Analysis of Košice Meteorite by Mössbauer Spectroscopy

Science.gov (United States)

Sitek, Jozef; Dekan, Július; Sedlačková, Katarína

2016-07-01

The 57Fe Mössbauer spectroscopy method was used to investigate iron-containing compounds in town Košice meteorite fallen on the territory of Slovakia in February 2010. The results showed that the Mössbauer spectra consisted of magnetic and non-magnetic components related to different iron-bearing phases. The non-magnetic phase includes olivine, pyroxene and traces of Fe3+ phase and the magnetic component comprises troilite (FeS) and iron-rich Fe-Ni alloy with hyperfine magnetic field typical for kamacite. Samples from meteorite were obtained in powder from different depths to inspect its heterogeneous composition. The content of kamacite increases to the detriment of troilite from the surface toward the centre of the sample. Measurements at liquid nitrogen temperature confirmed phase composition of investigated meteorite. Main constituent elements of studied samples were also determined by X-ray fluorescence analysis.

Pemanfaatan Teknik Ko-Kristalisasi Untuk Produksi Serbuk Ekstrak Sirsak

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Lukman Junaidi

2013-12-01

Full Text Available Research on application of co-crystallization technique on production of soursop extract powder conducted to diversify soursop product that could be used as industrial commodity. Treatment on this research was influence of: (1 anti-caking magnesium oxide (MO, magnesium carbonate (MC, and magnesium silicate (MS, and (2 storage period (0, 1, 2, and 3 months, on the characteristics of soursop powder quality. The results showed co-crystallization could be applied to produce soursop powder that met the requirements of SNI 01-4320-1996. Based on its quality characteristics, soursop powder oursop powder MC resulted a better quality compared to s MO and s MS. MC had a quality characteristics: oursop powder Soursop powder water content 1.89%, pH 4.17, sugar content 83.75%, vitamin C 42.7  total soluble solids 98.1%, TPC mg/100g, 55 colonies/g, soursop powder until coliform < 3 MPN, and contain no mold and yeast. Storage of 3 months increased water content, pH, and TPC, and contrarily decreased sugar content, vitamin C  total soluble solids.  Based on the quality characteristics, soursop powder that , and was stored for 3 months still met the SNI 01-4320-1996 requirements.ABSTRAK Penelitian pemanfaatan teknik ko-kristalisasi untuk produksi serbuk ekstrak sirsak dilakukan untuk diversifikasi produk olahan buah sirsak yang dapat dijadikan komoditas industri. Perlakuan yang diamati meliputi pengaruh: (1 penggunaan jenis anti-kempal magnesium oksida (MO, magnesium karbonat (MC, dan magnesium silikat (MS dan (2 masa simpan (0, 1, 2, dan 3 bulan terhadap karakteristik mutu serbuk sirsak. Hasil penelitian menunjuk-kan bahwa teknik ko-kristalisasi dapat dimanfaatkan untuk menghasilkan serbuk sirsak yang memenuhi persyaratan mutu SNI 01-4320-1996. Berdasarkan karakteristik mutunya, serbuk sirsak MC memberikan hasil yang lebih baik dibandingkan dengan serbuk sirsak MS dan serbuk sirsak MO.  Serbuk sirsak MC memiliki karakteristik mutu: kadar air 1,89%, pH 4

Differential Impact of miR-21 on Pain and Associated Affective and Cognitive Behavior after Spared Nerve Injury in B7-H1 ko Mouse

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Franziska Karl

2017-07-01

Full Text Available MicroRNAs (miRNAs are increasingly recognized as regulators of immune and neuronal gene expression and are potential master switches in neuropathic pain pathophysiology. miR-21 is a promising candidate that may link the immune and the pain system. To investigate the pathophysiological role of miR-21 in neuropathic pain, we assessed mice deficient of B7 homolog 1 (B7-H1, a major inhibitor of inflammatory responses. In previous studies, an upregulation of miR-21 had been shown in mouse lymphocytes. Young (8 weeks, middle-aged (6 months, and old (12 months B7-H1 ko mice and wildtype littermates (WT received a spared nerve injury (SNI. We assessed thermal withdrawal latencies and mechanical withdrawal thresholds. Further, we performed tests for anxiety-like and cognitive behavior. Quantitative real time PCR was used to determine miR-21 relative expression in peripheral nerves, and dorsal root ganglia (DRG at distinct time points after SNI. We found mechanical hyposensitivity with increasing age of naïve B7-H1 ko mice. Young and middle-aged B7-H1 ko mice were more sensitive to mechanical stimuli compared to WT mice (young: p < 0.01, middle-aged: p < 0.05. Both genotypes developed mechanical and heat hypersensitivity (p < 0.05 after SNI, without intergroup differences. No relevant differences were found after SNI in three tests for anxiety like behavior in B7-H1 ko and WT mice. Also, SNI had no effect on cognition. B7-H1 ko and WT mice showed a higher miR-21 expression (p < 0.05 and invasion of macrophages and T cells in the injured nerve 7 days after SNI without intergroup differences. Our study reveals that increased miR-21 expression in peripheral nerves after SNI is associated with reduced mechanical and heat withdrawal thresholds. These results point to a role of miR-21 in the pathophysiology of neuropathic pain, while affective behavior and cognition seem to be spared. Contrary to expectations, B7-H1 ko mice did not show higher miR-21

Amomum tsao-ko suppresses lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages via Nrf2-dependent heme oxygenase-1 expression.

Science.gov (United States)

Li, Bin; Choi, Hee-Jin; Lee, Dong-Sung; Oh, Hyuncheol; Kim, Youn-Chul; Moon, Jin-Young; Park, Won-Hwan; Park, Sun-Dong; Kim, Jai-Eun

2014-01-01

Amomum tsao-ko Crevost et Lemaire, used as a spice in Asia, is an important source of Chinese cuisine and traditional Chinese medicines. A. tsao-ko is reported to exert a variety of biological and pharmacological activities, including anti-proliferative, anti-oxidative and neuroprotective effects. In this study, NNMBS227, consisting of the ethanol extract of A. tsao-ko, exhibited potent anti-inflammatory activities in RAW264.7 macrophages. We investigated the effect of NNMBS227 in the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-1β) in LPS stimulated macrophages. NNMBS227 also inhibited the phosphorylation and degradation of IκB-α, as well as the nuclear translocation of nuclear factor kappa B (NF-κB) p65 caused by stimulation with LPS. In addition, NNMBS227 induced heme oxygenase (HO)-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. Using tin protoporphyrin (SnPP), an HO activity inhibitor, we confirmed an association between the anti-inflammatory effects of NNMBS227 and the up-regulation of HO-1. These findings suggest that Nrf2-dependent increases in the expression of HO-1 induced by NNMBS227 conferred anti-inflammatory activities in LPS stimulated RAW264.7 macrophages.

Long-term total solar radiation variability at the Polish Baltic coast in Kołobrzeg within the period 1964-2013

Czech Academy of Sciences Publication Activity Database

Kleniewska, M.; Chojnicki, B. H.; Acosta, Manuel

2016-01-01

Roč. 4, č. 2 (2016), s. 35-40 ISSN 2299-3835 R&D Projects: GA MŠk(CZ) LO1415 Institutional support: RVO:67179843 Keywords : total solar radiation * Kołobrzeg * dimming * brightening Subject RIV: EH - Ecology, Behaviour

[Evaluation of the Musical Concentration Training with Pepe (MusiKo mit Pepe) for children with attention deficits].

Science.gov (United States)

Rothmann, Kathrin; Hillmer, Jana-Mareike; Hosser, Daniela

2014-09-01

This study evaluates the Musical Concentration Training with Pepe ("MusiKo mit Pepe") for children aged 5 to 10 years with attention deficits. Using a pre-post-control design (N = 108), changes in attention capacity are measured by the Test of Attentional Performance for Children (KiTAP), whereas changes in the quality of life are assessed with the Children's Questionnaire (KINDL-R). Additionally, we utilized the Symptom Checklist for Attention Deficit Hyperactivity Disorders (FBB-ADHS) and for Conduct Disorder (FBB-SSV) of the Diagnostic System of Mental Disorders in Children and Adolescents II based on ICD-10 and DSM-IV as well as the Child Behavior Checklist and the Teacher's Report Form (CBCL, TRF). Significant pre-post effects were found in both attention and quality of life for children treated by the training compared to controls. Moreover, significant reductions were detected in ADHD symptomatology in parents' and teachers' ratings, and in internal problems in parents' ratings. The effectiveness of the intervention was not affected by age, sex, intelligence, or migration background. The music-based training "MusiKo mit Pepe" is an effective intervention for children with attention deficits, pending replication of these findings in future studies.

The Idea of an Innovated Concept of the Košice Geothermal Project

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Bujanská Alena

2015-11-01

Full Text Available Slovakia has very limited amounts of fossil resources. However, it has a relatively high potential of geothermal energy which use is far below its possibilities. The most abundant geothermal resource, not only in Slovakia but throughout the central Europe, is Košice basin. Since the publication of the first ideas about the ambitious goal to exploit the geothermal potential of this site, 20 years has passed and three geothermal wells has been made but without any progress. In the article the authors present the idea of a fundamental change in the approach to improve the energy and economic efficiency of the project.

The Czech national long distances measuring standard Koštice - State of play

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Ladislav Červinka

2009-11-01

Full Text Available This article gives information about new Czech national long distances measuring standard, which has been preparedat the distance base near the Koštice village. Submitter of the project is the Czech Office for Standards, Metrology and Testing.Research and document preparation for creation of the measuring standard were ensured by the Research Institute of Geodesy,Topography and Cartography. Interlaboratory comparisons were made by staff of the Bundeswehr University in Munich. The paperreports about works, which will be carried out on national standard in the second half of this year. Purpose of this works is to improvecharacteristics of accuracy of national etalon.

Three dimensional visualisation chosen part of Košice city

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Miroslav Šimčák

2007-06-01

Full Text Available With development of informatization and internetization in Slovakia go up interest cities and central villages to present themselves by way of web portal. Creation of the virtual cities is a modern trend in the foreign countries. This paper makes possible navigation potential visitors along the significant cultural and historical seightseens. It’s opening possibilities for creation of the virtual shopping centre. It could be interested for business in the city. In the first phase of solution it is creating the digital model of Main Street in Košice city, which is situated in the centre of city, and it is one of the most frequent place in the city. We use GIS tools for creation of 3D model. The basis is creation of the digital model of house buildings. Buildings are described by a simplification like 3D object regular shaped. We use an aerial photograph and photos buildings for creation complex of the digital model of the city.

Pravna priroda obveza iz komercijalne djelatnosti prijevoznika - tumačenje Čl.III 2 Haško-Visbyjskih pravila : (prikaz presude

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Ivana Oršulić

2009-08-01

Full Text Available Prema common law-u prijevoznik je prima facie dužan krcati, slagati i iskrcavati teret, ali je on ovlašten te svoje obveze prenijeti na drugu osobu. Odredba čl. III 2 Haško-Visbyskih pravila kojom se propisuje dužnost prijevoznika “uredno i brižljivo ukrcavati, rukovati, slagati, prevoziti, čuvati, brinuti se i iskrcavati robu” ne utvrđuje strogo osobnu, neprenosivu obvezu prijevoznika da izvrši navedene radnje već postavlja standard urednog i brižljivog postupanja koji je prijevoznik dužan poštovati ukoliko ugovorom uistinu preuzme obvezu izvođenja kargo operacija. Zbog toga se na ugovorne odredbe kojima se prijevoznik oslobađa odgovornosti za ukrcaj, slaganje i iskrcaj ne može primijeniti čl. III 8 Haško-Visbyskih pravila.

New updated results of paleomagnetic dating of cave deposits exposed in Za Hájovnou Cave, Javoříčko Karst

Czech Academy of Sciences Publication Activity Database

Kadlec, Jaroslav; Čížková, Kristýna; Šlechta, Stanislav

2014-01-01

Roč. 70, 1-2 (2014), s. 27-34 ISSN 0036-5343 Institutional support: RVO:67985530 ; RVO:67985831 Keywords : Javoříčko Karst * Za Hájovnou Cave * Early and Middle Pleistocene * paleomagnetic dating Subject RIV: DB - Geology ; Mineralogy

Rapid extraction of Amomum tsao-ko essential oil and determination of its chemical composition, antioxidant and antimicrobial activities.

Science.gov (United States)

Cui, Qi; Wang, Li-Tao; Liu, Ju-Zhao; Wang, Hui-Mei; Guo, Na; Gu, Cheng-Bo; Fu, Yu-Jie

2017-09-01

A simple, green and efficient extraction method named modified-solvent free microwave extraction (M-SFME) was employed for the extraction of essential oils (EOs) from Amomun tsao-ko. The process of M-SFME was optimized with the prominent preponderance of such higher extraction yield (1.13%) than those of solvent free microwave extraction (SFME, 0.91%) and hydrodistillation (HD, 0.84%) under the optimal parameters. Thirty-four volatile substances representing 95.4% were identified. The IC 50 values of EOs determined by DPPH radical scavenging activity and β-carotene/linoleic acid bleaching assay were 5.27 and 0.63mg/ml. Furthermore, the EOs exhibited moderate to potent broad-spectrum antimicrobial activity against all tested strains including five gram-positive and two gram-negative bacteria (MIC: 2.94-5.86mg/ml). In general, M-SFME is a potential and desirable alternative for the extraction of EOs from aromatic herbs, and the EOs obtained from A. tsao-ko can be explored as a potent natural antimicrobial and antioxidant preservative ingredient in food industry from the technological and economical points of view. Copyright © 2017 Elsevier B.V. All rights reserved.

[Ecclesia et civitatis : kościoł i życie religije w mieście średniowiecznym] / Raimo Pullat

Index Scriptorium Estoniae

Pullat, Raimo, 1935-

2009-01-01

Arvustus: Ecclesia et civitatis : kościoł i życie religije w mieście średniowiecznym. Pod redakcją Haliny Manikowskiej i Hanny Zaremskiej. Colloquia Mediaevalia Varsoviensia III. Warszawa : Instytut Historii PAN, 2002. Kollokviumi materjalide publikatsioonis käsitletakse peamiselt Sileesia, Preisimaa ja Pommeri linnu, mis käsitletaval perioodil kuulusid Poola koosseisu. Usuelu uurimise metodoloogiast.

Analýza a návrh marketingové komunikace Košík.cz

OpenAIRE

Krupka, Radim

2017-01-01

This Masters thesis deals with the topic of marketing communication. The first part of this thesis is devoted to the theory of marketing, marketing tools, marketing and promotion mix, marketing communication, e-commerce and STDC framework. In the following part of thesis are used the tools and analysis described in the theoretical part and applied on online grocery store Košík.cz. At first there is the application of situation analysis, then application of analysis of marketing mix, current m...

Srečko Kosovel and Rabindranath Tagore: Points of Departure and Identification

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Ana Jelnikar

2010-12-01

Full Text Available In this paper I explore some of the connections the Slovene poet Srečko Kosovel (1904–1926 surmised between himself and the Indian poet Rabindranath Tagore (1861–1941. I argue that what linked the two poets into a joint framework across the vastly different cultural and politico-geographic space was not just the fact that Kosovel read Tagore and took inspiration from the Bengali poet at the height of Tagore’s reputation in continental Europe, but that they shared a number of preoccupations, informed by their respective historical positioning. Both wrote from a profound awareness of their region’s subjugated status and endorsed an anti-imperialist stance that rejected nationalism as a viable means of liberation, embracing instead a creative universalist ideal.

Keanakākoʻi Tephra produced by 300 years of explosive eruptions following collapse of Kīlauea's caldera in about 1500 CE

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Swanson, Donald A.; Rose, Timothy R.; Fiske, Richard S.; McGeehin, John P.

2012-01-01

The Keanakākoʻi Tephra at Kīlauea Volcano has previously been interpreted by some as the product of a caldera-forming eruption in 1790 CE. Our study, however, finds stratigraphic and 14C evidence that the tephra instead results from numerous eruptions throughout a 300-year period between about 1500 and 1800. The stratigraphic evidence includes: (1) as many as six pure lithic ash beds interleaved in sand dunes made of earlier Keanakākoʻi vitric ash, (2) three lava flows from Kīlauea and Mauna Loa interbedded with the tephra, (3) buried syneruptive cultural structures, (4) numerous intraformational water-cut gullies, and (5) abundant organic layers rich in charcoal within the tephra section. Interpretation of 97 new accelerator mass spectrometry (AMS) 14C ages and 4 previous conventional ages suggests that explosive eruptions began in 1470–1510 CE, and that explosive activity continued episodically until the early 1800s, probably with two periods of quiescence lasting several decades. Kīlauea's caldera, rather than forming in 1790, predates the first eruption of the Keanakākoʻi and collapsed in 1470–1510, immediately following, and perhaps causing, the end of the 60-year-long, 4–6 km3 ʻAilāʻau eruption from the east side of Kīlauea's summit area. The caldera was several hundred meters deep when the Keanakākoʻi began erupting, consistent with oral tradition, and probably had a volume of 4–6 km3. The caldera formed by collapse, but no eruption of lava coincided with its formation. A large volume of magma may have quickly drained from the summit reservoir and intruded into the east rift zone, perhaps in response to a major south-flank slip event, leading to summit collapse. Alternatively, magma may have slowly drained from the reservoir during the prolonged ʻAilāʻau eruption, causing episodic collapses before the final, largest downdrop took place. Two prolonged periods of episodic explosive eruptions are known at Kīlauea, the Keanakāko

Keanakākoʻi Tephra produced by 300 years of explosive eruptions following collapse of Kīlauea's caldera in about 1500 CE

Science.gov (United States)

Swanson, Donald A.; Rose, Timothy R.; Fiske, Richard S.; McGeehin, John P.

2012-01-01

The Keanakākoʻi Tephra at Kīlauea Volcano has previously been interpreted by some as the product of a caldera-forming eruption in 1790 CE. Our study, however, finds stratigraphic and 14C evidence that the tephra instead results from numerous eruptions throughout a 300-year period between about 1500 and 1800. The stratigraphic evidence includes: (1) as many as six pure lithic ash beds interleaved in sand dunes made of earlier Keanakākoʻi vitric ash, (2) three lava flows from Kīlauea and Mauna Loa interbedded with the tephra, (3) buried syneruptive cultural structures, (4) numerous intraformational water-cut gullies, and (5) abundant organic layers rich in charcoal within the tephra section. Interpretation of 97 new accelerator mass spectrometry (AMS) 14C ages and 4 previous conventional ages suggests that explosive eruptions began in 1470–1510 CE, and that explosive activity continued episodically until the early 1800s, probably with two periods of quiescence lasting several decades. Kīlauea's caldera, rather than forming in 1790, predates the first eruption of the Keanakākoʻi and collapsed in 1470–1510, immediately following, and perhaps causing, the end of the 60-year-long, 4–6 km3 ʻAilāʻau eruption from the east side of Kīlauea's summit area. The caldera was several hundred meters deep when the Keanakākoʻi began erupting, consistent with oral tradition, and probably had a volume of 4–6 km3. The caldera formed by collapse, but no eruption of lava coincided with its formation. A large volume of magma may have quickly drained from the summit reservoir and intruded into the east rift zone, perhaps in response to a major south-flank slip event, leading to summit collapse. Alternatively, magma may have slowly drained from the reservoir during the prolonged ʻAilāʻau eruption, causing episodic collapses before the final, largest downdrop took place. Two prolonged periods of episodic explosive eruptions are known at Kīlauea, the Keanakāko

DRAGON and CORD-2 nuclear calculation of the NPP Krško fuel assembly

International Nuclear Information System (INIS)

Kromar, Marjan; Kurinčič, Bojan

2012-01-01

Highlights: ▶ Comparison of the DRAGON 4 and CORD-2 calculation of the NPP Krško 16 × 16 fuel assembly has been performed. ▶ Two different enrichments (4.60% and 4.95%), three IFBA configurations (0, 64 and 116 IFBAs) and the burnup up to 60,000 MWd/tU were considered. ▶ Comparison shows that the agreement in the results of both codes is very good. ▶ Regarding efficiency, one CORD-2 assembly depletion calculation takes about 3 min of the CPU time on the typical PC, while the DRAGON calculation runs more than 25 h. - Abstract: The geometry of the reactor core is usually too complex to be solved in one step. Therefore, a solution for the whole core in 3-D geometry is sought in several steps, where some kind of homogenization procedure of neutron few-group cross sections is applied. Usually, assembly-homogenized effective two-group cross sections are determined, which are suitable for solving the diffusion equation for the whole core by a coarse mesh nodal methods. In this paper DRAGON 4 and CORD-2 codes are used for the calculation of NPP Krško 16 × 16 fuel assemblies without and with IFBA rods. DRAGON code was selected, since it can use the same cross-section library as the WIMS-D5 code employed in the CORD-2 system. Different results arise therefore solely from the different models used in the calculations. The heterogeneous depletion calculation was performed up to burnup of 60,000 MWd/tU. Results of both codes are compared for the infinite multiplication factor, fast to thermal spectral ratio and pin power distributions.

Elementary analysis and energetic potential of the municipal sewage sludges from the Gdańsk and Kościerzyna WWTPs

Science.gov (United States)

Ostojski, Arkadiusz

2018-01-01

This paper aims to present municipal sewage sludge (MSS) elementary analysis and energetic potential based on measurement of heat of combustion (higher heating value HHV) and calculation of calorific values (lower heating value LHV). The analysis takes into the consideration water content in sewage sludge, at different utilization stages, in wastewater treatment plants in Gdańsk Wschód and Kościerzyna - Pomeranian Voivodeship. The study yielded the following results (in % dry matter): ash 19÷31 %, C - 31÷36 %, H - 5÷6 %, N - 4÷6 %, O - 28÷32 %, S - 1 %. Calorific value of stabilized sludges in Gdańsk was on average 13.8÷15 MJ/kg. In case of sludges not undergoing digestion from Kościerzyna WWTP, the calorific value was at the level of 17.5 MJ/kg. Thus, sewage sludges are good energy carriers. High water content though is the problem, as it lowers the useful effect of heat. There is no alternative for thermal sewage sludge neutralization, which is in conformity with valid Polish National Waste Management Plan (KPGO 2022).

Knjiga in njen pomen v nemško govorečem pregnanstvu 1933–1945

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Johann Georg Lughofer

2010-12-01

Full Text Available Članek skuša s pomočjo različnih literarnih odlomkov pokazati na pomembno mesto, ki ga je imela knjiga – kot objekt in subjekt – v literarni produkciji nemško govorečih pregnancev. Kot razloge za to obravnava funkcije literature kot so antifašistični boj, izobraževanje, dokumentiranje, terapija in samoterapija. Osredotoči se na sežiganja knjig v Nemčiji leta 1933 in pokaže, kako so ti zgodovinski dogodki iz knjige naredili simbol antifašističnega pregnanstva.

Od ciężkości astmy do kontroli astmy. Metody oceny kontroli astmy

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Joanna Mikołajczyk

2009-09-01

Full Text Available Według pierwszych wytycznych dotyczących postępowania w astmie leczenie astmy zależy od stopnia jej cięż- kości, określonej na podstawie objawów klinicznych i wskaźników czynności płuc. Ponieważ astma jest chorobą o zmiennym przebiegu, duże znaczenie ma jej ciągła ocena kliniczna i dostosowana do niej modyfikacja leczenia. Niestety, stopień ciężkości nie dopasowuje się elastycznie do odpowiedzi na leczenie. Biorąc ten fakt pod uwagę, światowi eksperci zalecają zmianę w postępowaniu z astmą, przedkładając uzyskanie klinicznej kontroli astmy nad ustaleniem stopnia jej ciężkości, wyróżniając astmę kontrolowaną, częściowo kontrolowaną i niekontrolowaną. Uzyskanie stanu pełnej kontroli astmy formułuje się w raporcie GINA 2006 jako główny cel leczenia. Kontrola astmy odnosi się do stopnia opanowania objawów i byłoby najlepiej, gdyby dotyczyła też markerów zapalenia i patofizjologicznych wykładników choroby. Określenie stopnia kontroli choroby zgodnie z obecnymi założeniami stanowi podstawę wyboru i modyfikacji leczenia – właściwe ustalenie stopnia kontroli astmy wpływa na skuteczność leczenia. Obecnie dostępnych jest wiele metod oceny kontroli astmy, wtym ocena parametrów klinicznych (objawy w ciągu dnia, objawy nocne, stosowanie leków rozszerzających oskrzela, ocena czynności płuc (PEF i FEV1, określenie zaawansowania zapalenia w drogach oddechowych (nieswoista nadreaktywność oskrzeli, stężenie tlenku azotu w powietrzu wydechowym, liczba eozynofili w plwocinie indukowanej. Dostępne są także subiektywnie oceniające kontrolę astmy kwestionariusze badawcze oraz szybkie testy kontroli astmy (ACT, ACQ, ATAQ. Z drugiej strony wciąż nie wypracowano jednoznacznego stanowiska, który z parametrów lub jakie połączenia parametrów najbardziej wiarygodnie określają kontrolę astmy. Ze względu na wieloczynnikową patogenezę astmy wydaje się, iż uzyskanie pe

Reversal of fragile X phenotypes by manipulation of AβPP/Aβ levels in Fmr1KO mice.

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Cara J Westmark

Full Text Available Fragile X syndrome (FXS is the most common form of inherited intellectual disability and the leading known genetic cause of autism. Fragile X mental retardation protein (FMRP, which is absent or expressed at substantially reduced levels in FXS, binds to and controls the postsynaptic translation of amyloid β-protein precursor (AβPP mRNA. Cleavage of AβPP can produce β-amyloid (Aβ, a 39-43 amino acid peptide mis-expressed in Alzheimer's disease (AD and Down syndrome (DS. Aβ is over-expressed in the brain of Fmr1(KO mice, suggesting a pathogenic role in FXS. To determine if genetic reduction of AβPP/Aβ rescues characteristic FXS phenotypes, we assessed audiogenic seizures (AGS, anxiety, the ratio of mature versus immature dendritic spines and metabotropic glutamate receptor (mGluR-mediated long-term depression (LTD in Fmr1(KO mice after removal of one App allele. All of these phenotypes were partially or completely reverted to normal. Plasma Aβ(1-42 was significantly reduced in full-mutation FXS males compared to age-matched controls while cortical and hippocampal levels were somewhat increased, suggesting that Aβ is sequestered in the brain. Evolving therapies directed at reducing Aβ in AD may be applicable to FXS and Aβ may serve as a plasma-based biomarker to facilitate disease diagnosis or assess therapeutic efficacy.

Interpretace je víc než interpretace. K reflexi hermeneutického pohybu u Zdeňka Kožmína

Czech Academy of Sciences Publication Activity Database

Kanda, Roman

2015-01-01

Roč. 2, č. 4 (2015), s. 20-25 Institutional support: RVO:68378068 Keywords : Kožmín, Zdeněk * hermeneutics * interpretation Subject RIV: AJ - Letters, Mass-media, Audiovision https://issuu.com/pulsystudentskaliterarnirevue/docs/pulsy_4_issuu

Passage of radiation through inhomogeneous, moving media. XIII. Causality, analyticity, group speed, transparency, and allied phenomena with emphasis on some recent calculations by Ko and Chuang

International Nuclear Information System (INIS)

Lerche, I.

1978-01-01

A critical examination is made of some recent calculations by Ko and Chuang. They seek to show that original work by ourselves, and others, concerning the behavior of light propagating through differentially moving media is in error and that the fundamental structure of the results is, in fact, very different from the results we obtained: not excluding reversal of sign of some of the effects. We demonstrate that the results reported by Ko and Chuang are a consequence of two basic kinds of errors in their analysis. The first, and paramount, error is their use of fundamental basic kinds of errors in their analysis. The first, and paramount error is their use of fundamental relations in physics (such as the Kramers-Kronig dispersion relation) without due regard being given to the conditons imposed in arriving at the basic relationship in the first place, and thier use of particular relationships far outside their domains of validity as though they still held true.The second basic error is in a particular form of the refractive index, n, that Ko and Chuang use to illustrate their general points (which already suffer from the first basic error). The particular refractive index they use has the following unsatisfactory features: (i) it contains unstable modes in the upper half complex frequency plane: contrary to the conventional Kramers-Kronig relationship they invoke as a general principle; (ii) n 2 0 [n 2 (ω)-1]dω=0; (iii) the imaginary part of the dielectric positive (corresponding to absorption), yet the real part contains unstable modes, and the whole of the complex dielectric constant is nonanalytic in the upper half complex frequency plane; (iv) the form of n given by Ko and Chuang is purported to represent a warm, isotropic, Maxwellian plasma which is well known to be absolutely stable, so that no unstable modes can exist

En könsstereotyp frivård : Frivårdsinspektörers beskrivningar av kvinnliga klienter

OpenAIRE

Andersson, Josefin

2014-01-01

Tidigare forskning tyder på att det finns kunskapsluckor om och stereotypa bilder av kvinnliga klienter inom kriminalvården som dessutom påverkar hur arbetet med kvinnliga klienter ser ut. I denna studie ska därför frivårdsinspektörers beskrivningar av kvinnliga klienters problem, behov och resurser granskas. Det undersöks också huruvida dessa beskrivningar kan betraktas som könsstereotypa. För att ta reda på detta har semistrukturerade intervjuer gjorts med frivårdsinspektörer ...

Als2 mRNA splicing variants detected in KO mice rescue severe motor dysfunction phenotype in Als2 knock-down zebrafish.

Science.gov (United States)

Gros-Louis, Francois; Kriz, Jasna; Kabashi, Edor; McDearmid, Jonathan; Millecamps, Stéphanie; Urushitani, Makoto; Lin, Li; Dion, Patrick; Zhu, Qinzhang; Drapeau, Pierre; Julien, Jean-Pierre; Rouleau, Guy A

2008-09-01

Recessive ALS2 mutations are linked to three related but slightly different neurodegenerative disorders: amyotrophic lateral sclerosis, hereditary spastic paraplegia and primary lateral sclerosis. To investigate the function of the ALS2 encoded protein, we generated Als2 knock-out (KO) mice and zAls2 knock-down zebrafish. The Als2(-/-) mice lacking exon 2 and part of exon 3 developed mild signs of neurodegeneration compatible with axonal transport deficiency. In contrast, zAls2 knock-down zebrafish had severe developmental abnormalities, swimming deficits and motor neuron perturbation. We identified, by RT-PCR, northern and western blotting novel Als2 transcripts in mouse central nervous system. These Als2 transcripts were present in Als2 null mice as well as in wild-type littermates and some rescued the zebrafish phenotype. Thus, we speculate that the newly identified Als2 mRNA species prevent the Als2 KO mice from developing severe neurodegenerative disease and might also regulate the severity of the motor neurons phenotype observed in ALS2 patients.

Elementary analysis and energetic potential of the municipal sewage sludges from the Gdańsk and Kościerzyna WWTPs

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Ostojski Arkadiusz

2018-01-01

Full Text Available This paper aims to present municipal sewage sludge (MSS elementary analysis and energetic potential based on measurement of heat of combustion (higher heating value HHV and calculation of calorific values (lower heating value LHV. The analysis takes into the consideration water content in sewage sludge, at different utilization stages, in wastewater treatment plants in Gdańsk Wschód and Kościerzyna – Pomeranian Voivodeship. The study yielded the following results (in % dry matter: ash 19÷31 %, C - 31÷36 %, H - 5÷6 %, N - 4÷6 %, O - 28÷32 %, S – 1 %. Calorific value of stabilized sludges in Gdańsk was on average 13.8÷15 MJ/kg. In case of sludges not undergoing digestion from Kościerzyna WWTP, the calorific value was at the level of 17.5 MJ/kg. Thus, sewage sludges are good energy carriers. High water content though is the problem, as it lowers the useful effect of heat. There is no alternative for thermal sewage sludge neutralization, which is in conformity with valid Polish National Waste Management Plan (KPGO 2022.

The collocated station Košetice - Kešín u Pacova, Czech Republic: an important research infrastructure in central Europe

Science.gov (United States)

Dvorska, Alice; Milan, Váňa; Vlastimil, Hanuš; Marian, Pavelka

2013-04-01

The collocated station Košetice - Křešín u Pacova, central Czech Republic, is a major research and monitoring infrastructure in the Czech Republic and central Europe. It consists of two basic components: the observatory Košetice run since 1988 by the Czech Hydrometeorological Institute and the atmospheric station (AS) Křešín u Pacova starting operation in 2013. The AS is built and run by CzechGlobe - Global Change Research Centre, Academy of Sciences of the Czech Republic and is situated 100 m far from the observatory. There are three research and monitoring activities at the collocated station providing data necessary for the research on climate and related changes. The AS Křešín u Pacova consists of a 250 m tall tower serving for ground-based and vertical gradient measurements of (i) concentrations of CO2, CO, CH4, total gaseous mercury and tropospheric ozone (continuously), (ii) elemental and organic carbon (semicontinuously), (iii) carbon and oxygen isotopes, radon, N2O, SF6 and other species (episodically), (iv) optical properties of atmospheric aerosols and (v) meteorological parameters and the boundary layer height. Further, eddy covariance measurements in the nearby agroecosystem provide data on CO2 and H2O fluxes between the atmosphere and the ecosystem. Finally, monitoring activities at the nearby small hydrological catchment Anenské povodí run under the GEOMON network enables studying local hydrological and biogeochemical cycles. These measurements are supported by the long-term monitoring of meteorological and air quality parameters at the observatory Košetice, that are representative for the central European background. The collocated station provides a big research opportunity and challenge due to (i) a broad spectra of monitored chemical species, meteorological, hydrological and other parameters, (ii) measurements in various environmental compartments and especially the atmosphere, (iii) provision of data suitable for conducting

Odprto ognjišče v planšarski koči na prehodnem alpsko-panonskem ozemlju:

OpenAIRE

Cevc, Tone

1998-01-01

The article discusses the type of open fireplace dating from the first half of the 20th century in shepherd's huts on Velika planina in the Kamnik Alps. The fireplace is characteristic of the transitional region between the Alps and the Pannonian plain, where two different ways of cooking meet: on an open fireplace and in an oven. Avtor v svojem prispevku osvetljuje tip odprtega ognjišča iz konca prve polovice 20. stoletja v pastirskih kočah na Veliki planini v Kamniških Alpah. To ognjišče...

Slope Stability Estimation of the Kościuszko Mound in Cracow

Science.gov (United States)

Wrana, Bogumił; Pietrzak, Natalia

2015-06-01

In the paper, the slope stability problem of the Kościuszko Mound in Cracow, Poland is considered. The slope stability analysis was performed using Plaxis FEM program. The outer surface of the mound has complex geometry. The slope of the cone is not uniform in all directions, on the surface of the cone are pedestrian paths. Due to its complicated geometry it was impossible to do computing by Plaxis input pre-procesor. The initial element mesh was generated using Autodesk Autocad 3D and next it was updated by Plaxis program. The soil parameters were adopted in accordance with the detailed geological soil testing performed in 2012. Calculating model includes geogrids. The upper part was covered by MacMat geogrid, while the lower part of the Mound was reinforced using Terramesh Matt geogrid. The slope analysis was performed by successives reduction of φ /c parameters. The total multiplayer ΣMsf is used to define the value of the soil strength parameters. The article presents the results of slope stability before and after the rainfall during 33 days of precipitation in flood of 2010.

Farklı Durum Çeşitlerinden Mahalli ve Laboratuvar Koşullarında Yapılmış Bulguların Bazı Vitamin ve Mineral İçerikleri

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Berrin Özkaya

2015-02-01

Full Text Available Araştırmada 5 farklı durum buğdayının, bunlardan mahalli ve laboratuvar koşullarında yapılan bulguların bazı kimyasal özellikleri ile tiamin, riboflavin ve mineral içerikleri karşılaştırılmıştır. Buğdayların yapımı sırasında buğdayların tiamin, özellikle de riboflavin miktarları azalmıştır. Mahalli koşullarda yapılan bulgurların tiamin ve riboflavin miktarları laboratuvarda yapılanlara kıyasla biraz düşük çıkmıştır. Bulgurların mineral içerikleri (Fe, Cu, Zn, Mn, Ca ve Mg miktarları yapıldıktan buğdaylara kıyasla daha düşük çıkmış, mahalli ve laboratuvar koşullarında yapılan bulgurların mineral madde miktarlarında önemli bir fark görülmemiştir.

From Velvary, Bohemia, to the court in Vienna. The life of the imperial Kapellmeister Leopold Koželuh and a new complete edition of his keyboard sonatas

Czech Academy of Sciences Publication Activity Database

Vytlačil, Lukáš

2016-01-01

Roč. 16, č. 2 (2016), s. 7-11 ISSN 1211-0264 Institutional support: RVO:68378076 Keywords : Leopold Koželuh * composers * classicism * history of music * piano sonatas * complete editions Subject RIV: AL - Art, Architecture, Cultural Heritage

CDKL5 Disorder: a Novel Therapeutic Strategy to Improve Brain Development in a Newly Generated CDKL5 ko Mouse Model

OpenAIRE

De Franceschi, Marianna

2016-01-01

The cyclin-dependent kinase like-5 (CDKL5) disorder is a rare neurodevelopmental disease caused by mutations in the CDKL5 gene, located on the X-chromosome. The consequent unsuccessful CDKL5 protein expression in the nervous system leads to a severe encephalopathy, characterized by mental retardation, reduced motor abilities and early-onset intractable epilepsy. CDKL5 is highly expressed in the brain during the early postnatal stages of development and a recently developed Cdkl5 KO m...

Pojavnost pčelinjih virusa u pčelinjacima Koprivničko-križevačke županije u Hrvatskoj.

OpenAIRE

Tlak Gajger, Ivana; Bičak, Jurica; Belužić, Robert

2014-01-01

Viral honey bee diseases are an increasing beekeeping problem throughout the world because they can cause great economic losses and a reduction in biodiversity in natural ecosystems. Therefore, it is important to promptly identify the causal pathogens of honey bee diseases in order to develop appropriate measures and procedures for their prevention and eradication. In this paper the prevalence and distribution were determined of the five economically most important honey bee viruses in the Ko...

Deformation analyse of the high point field Košická Nová Ves

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Sedlák Vladimír

2003-09-01

Full Text Available From the science point of view the deformation measurements serve to an objective determination of movements and from the technical point of view the deformation measurements serve to a determinantion of the building technologies and the construction procedures. Detrmined movements by means of using the geodetic terrestrial or satellite navigation technologies give informations about displacements in a concrete time information on the base of repeated geodetic measurements in the concrete time intervals (epochs.Level deformation investigation of the point of the monitoring station stabled in the fill slope territory Košická Nová Ves is the main task of the presented paper. Level measurements are realized in autumn 2000 (the epoch 200.9 - it is considered as the first epoch of the deformation measurement, and in spring 2001 (the epoch 2001.3 – it is considered as the second epoch of the deformation measurement.

mTOR regulates the expression of DNA damage response enzymes in long-lived Snell dwarf, GHRKO, and PAPPA-KO mice.

Science.gov (United States)

Dominick, Graham; Bowman, Jacqueline; Li, Xinna; Miller, Richard A; Garcia, Gonzalo G

2017-02-01

Studies of the mTOR pathway have prompted speculation that diminished mTOR complex-1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long-lived mutant mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in this article, mice deficient in the pregnancy-associated protein-A (PAPPA-KO). The ways in which lower mTOR signals slow aging and age-related diseases are, however, not well characterized. Here, we show that Snell, GHKRO, and PAPPA-KO mice express high levels of two proteins involved in DNA repair, O-6-methylguanine-DNA methyltransferase (MGMT) and N-myc downstream-regulated gene 1 (NDRG1). Furthermore, we report that lowering mTOR enhances MGMT and NDRG1 protein expression via post-transcriptional mechanisms. We show that the CCR4-NOT complex, a post-transcriptional regulator of gene expression, is downstream of the mTORC1 pathway and may be responsible for the upregulation of MGMT and NDRG1 in all three varieties of long-lived mice. Our data thus suggest a novel link between DNA repair and mTOR signaling via post-transcriptional regulation involving specific alteration in the CCR4-NOT complex, whose modulation could control multiple aspects of the aging process. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Mito e realtà della letteratura ebraica al femminile in Germania: Anna Seghers e Mascha Kaléko

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Karin Birge Gilardoni-Büch

2014-04-01

Both of them succeed in emigrating and surviving the destruction of the European Jews. Anna Seghers comes back in 1947 to the Soviet occupied zone and will later hold significant offices inside East Germany's cultural life. Mascha Kaléko will however come back only now and then to the German Federal Republic. Did their writing change after the Shoah? And if so, to what extent? Moreover, do the texts mirror the situation in which their authors found themselves? Aren’t they linked to a specific social condition, that of a woman? To what extent do specific female and Jewish experiences take shape in their works?

IT projekta pārcelšana uz Microsoft Azure mākoņa platformu

OpenAIRE

Dzenis, Gvido

2015-01-01

Pēdējo gadu laikā, strauji pieaugot interneta ātrumam un izplatībai, palielinās uzņēmumu interese par projektu izstrādi un uzturēšanu mākonī. Microsoft piedāvā produktu Azure, kas nodrošina ērtu un elastīgu risinājumu projektu uzturēšanai un izstrādei apvienojumā ar iespējām mainīt nepieciešamos datu apstrādes un skaitļošanas resursus, saglabājot salīdzinoši mazas izmaksas. Microsoft Azure piemērots visa izmēra projektiem. Darbā aplūkotas galvenās lietas, par ko jāpadomā pirms sākt projekt...

Produkta izvietošana kinofilmās kā reklāmas veids un tā efektivitāte; 2009. gada 10 skatītāko kinofilmu Latvijā analīze

OpenAIRE

Goģe, Sandra

2010-01-01

Bakalaura darbs „PRODUKTA IZVIETOŠANA KINOFILMĀS KĀ REKLĀMAS VEIDS UN TĀ EFEKTIVITĀTE; 2009. GADA 10 SKATĪTĀKO KINOFILMU LATVIJĀ ANALĪZE” ir izstrādāts ar mērķi aplūkot produkta izvietošanu kinofilmās kā reklāmas veidu. Darba teorētiskajā daļā tiek apskatīta produkta izvietošanas teorija, kino un izklaides industrija, produkta izvietošanas process un atribūcijas teorijas. Darba pētnieciskajā daļā tiek veikta 2009. gada 10 skatītāko kinofilmu Latvijā kontentanalīze, ar eksperimenta palīdzību t...

Influence of organics and silica on Fe(II) oxidation rates and cell-mineral aggregate formation by the green-sulfur Fe(II)-oxidizing bacterium Chlorobium ferrooxidans KoFox - Implications for Fe(II) oxidation in ancient oceans

Science.gov (United States)

Gauger, Tina; Byrne, James M.; Konhauser, Kurt O.; Obst, Martin; Crowe, Sean; Kappler, Andreas

2016-06-01

Most studies on microbial phototrophic Fe(II) oxidation (photoferrotrophy) have focused on purple bacteria, but recent evidence points to the importance of green-sulfur bacteria (GSB). Their recovery from modern ferruginous environments suggests that these photoferrotrophs can offer insights into how their ancient counterparts grew in Archean oceans at the time of banded iron formation (BIF) deposition. It is unknown, however, how Fe(II) oxidation rates, cell-mineral aggregate formation, and Fe-mineralogy vary under environmental conditions reminiscent of the geological past. To address this, we studied the Fe(II)-oxidizer Chlorobium ferrooxidans KoFox, a GSB living in co-culture with the heterotrophic Geospirillum strain KoFum. We investigated the mineralogy of Fe(III) metabolic products at low/high light intensity, and in the presence of dissolved silica and/or fumarate. Silica and fumarate influenced the crystallinity and particle size of the produced Fe(III) minerals. The presence of silica also enhanced Fe(II) oxidation rates, especially at high light intensities, potentially by lowering Fe(II)-toxicity to the cells. Electron microscopic imaging showed no encrustation of either KoFox or KoFum cells with Fe(III)-minerals, though weak associations were observed suggesting co-sedimentation of Fe(III) with at least some biomass via these aggregates, which could support diagenetic Fe(III)-reduction. Given that GSB are presumably one of the most ancient photosynthetic organisms, and pre-date cyanobacteria, our findings, on the one hand, strengthen arguments for photoferrotrophic activity as a likely mechanism for BIF deposition on a predominantly anoxic early Earth, but, on the other hand, also suggest that preservation of remnants of Fe(II)-oxidizing GSB as microfossils in the rock record is unlikely.

»Ko bom velik, bom umetnik.«　Eksperimentalni peskovnik japonske avantgarde

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Klara HRVATIN

2017-01-01

Full Text Available Umetniški center Sōgetsu, ki je eden od pomembnejših avantgardnih središč 60. let 20. stoletja, bi lahko opredelili kot umetniški »eksperimentalni peskovnik«. Japonski umetniki, ki so na svojih področjih danes že mednarodno priznani, so se prav v tem »peskovniku« imeli možnost preizkusiti v krogu interdisciplinarnih umetnikov in najti svoj umetniški slog. Dober primer takšnih ustvarjalcev so: filmski režiser Hiroshi Teshigahara (1927–2001, novelist Kōbō Abe (1924–1993 in glasbenik Tōru Takemitsu (1930–1996. V članku bomo orisali natančen pregled vseh umetniških združenj in njihovih dogodkov, ki so jih oblikovali umetniki v času delovanja Centra, od septembra 1958 (13. septembra je potekalo odprtje Centra do marca 1971, ko je Center prenehal delovati. V ospredje bodo postavljena glavna združenja oziroma aktivnosti, predvsem s področij jazzovske glasbe, sodobne glasbe, eksperimentalnih filmov in animacije. Poiskali bomo skupen imenovalec vseh aktivnosti v tem »peskovniku« ter poudarili novosti, ki so jih glavni akterji gibanja z deli, ki so nastala v Centru, vnesli na področji glasbe in filma.

Pravna priroda obveza iz komercijalne djelatnosti prijevoznika - tumačenje Čl.III 2 Haško-Visbyjskih pravila : (prikaz presude)

OpenAIRE

Oršulić, Ivana

2009-01-01

Prema common law-u prijevoznik je prima facie dužan krcati, slagati i iskrcavati teret, ali je on ovlašten te svoje obveze prenijeti na drugu osobu. Odredba čl. III 2 Haško-Visbyskih pravila kojom se propisuje dužnost prijevoznika “uredno i brižljivo ukrcavati, rukovati, slagati, prevoziti, čuvati, brinuti se i iskrcavati robu” ne utvrđuje strogo osobnu, neprenosivu obvezu prijevoznika da izvrši navedene radnje već postavlja standard urednog i brižljivog postupanja koji je ...

New possibilities and perspectives of building hotwater line from geothermal wells heat exchanger to TEKO Košice

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Marína Sidorová

2006-04-01

Full Text Available Thank to favourable geological conditions, Slovakia is a country abundant in the occurrence of low-enthalpy sources. The government of the state sponsors new renewable of the sources ecological energy,including the geothermal energy. Geothermal water is utilized for recreation (swimming pools, spas, agriculture (heating of greenhouses, fishing and heating of houses. The effectivity of utilisation is about 30 % due to its seasonal use. That is why the annual house-heating and the hot water supply from geothermal sources are supported. Recently, the company Slovgeoterm has initiated heating of greenhouses in Podhajska and hospital and 1231 flats in the town Galanta. Nowadays, a research for the biggest geothermal project in the Middle Europe – construction in Košice basin has started.

Domates Pulpu ve Salçasında Viskozite (Konsistens ve Renk Üzerine Proses Koşullarının Etkisi

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Aziz Ekşi

2015-02-01

Full Text Available Kıvam ve renk, domates pulpu ve salçada kaliteyi belirleyen ve ticarette üzerinde en çok durulan iki önemli etkendir. Domates salçasında renk ve kıvam ile hammaddenin durumu arasında yakın bir ilişki bulunduğu bilinmektedir. Ancak her iki kalite öğesini ve özellikle kıvamı, hammadde olduğu kadar, proses koşulları da etkilemektedir.

Osigurateljev subrogacijski zahtjev prema prijevozniku : tumačenje Čl. III 6A Haško-Visbyjskih pravila : [prikaz presude

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Vesna Skorupan

2003-12-01

Full Text Available Osigurateljev subrogacijski zahtjev prema prijevozniku nije zahtjev za naknadu prema trećoj osobi u smislu čl. III 6A Haško-Visbyjkih pravila. Prijevoznik je tužena strana u sporu s pošiljateljem stvari i činjenica da (subrogacijom osiguratelj zauzima mjesto pošiljatelja ne stavlja prijevoznika u poziciju treće osobe. Položaj prijevoznika se ne mijenja ako pravo osobe koja je s njim sklopila ugovor bude prenijeto na temelju subrogacije na osiguratelja. Zbog toga se i na osiguratelja odnose rokovi zastare koji se primjenjuju prema osiguraniku za tražbine prema prijevozniku.

Izmaksu sistēmas integrācija Openstack mākoņu sistēmā

OpenAIRE

Andruškeviča, Eleonora

2015-01-01

Izmaksu sistēma ir programma priekš OpenStack atvērta pirmkoda mākoņu sistēmai, kas ir uzrakstīta ar Python programmēšanās valodas palīdzību. Programmas izstrādes nolūks ir paplašināt OpenStack platformu ar precīzu izmaksu radītājiem. Sistēma ir domāta tikai OpenStack lietotājiem. Izmaksu programma dod iespēju lietotājam zināt, cik viņām būtu jāmaksā par patērētiem resursiem konkrētajos periodos, ja OpenStack būtu par maksu. Rezultātā tika iegūta programma, kas dabū virtuālu mašīnu st...

Effect of Soil Moisture Content on Growth, Crude Drug "Cho-to-ko" Yield and Oxindole Alkaloid Content of Uncaria rhynchophylla (B. LIVING SCIENCE)

OpenAIRE

川添, 禎浩; 小林, 茂樹; 水上, 元; 大橋, 裕; SADAHIRO, KAWAZOE; SHIGEKI, KOBAYASHI; HAJIME, MIZUKAMI; HIROMU, OHASHI; Laboratory of Environmetal Health and Toxicology, Department of Food Science and Nutrition, Kyoto Prefectural University; Department of Medicinal Plant Research, Faculty of Pharmaceutical Sciences, Nagasaki University; Department of Medicinal Plant Research, Faculty of Pharmaceutical Sciences, Nagasaki University; Department of Medicinal Plant Research, Faculty of Pharmaceutical Sciences, Nagasaki University

1992-01-01

Uncaria rhynchophylla was cultivated by using soil with various moisture contents (20,40,60,80 or 100% of the maximum moisture content retained by soil). Both growth and crude drug "Cho-to-ko" (dried stem with hooks of U. rhynchophylla) yield of the plant were in the following order : 60%> 80%> 40%> 100%> 20%, while oxindole alkaloid content of the stem was in the following order : 20%> 60%> 100%> 40%> 80%. It is concluded that moderately wet soil is suitable for cultivation of U. rhynchophyl...

Fermentation of sweet whey by recombinant Escherichia coli K011 Fermentação de soro de leite por Escherichia coli KO11 recombinante

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Amarildo Ricardo Leite

2000-09-01

Full Text Available The production of ethanol from sweet whey using the recombinant Escherichia coli KO11, in batch fermentation, was tested. The maximum ethanol yield was reached after 96h, representing only 38% of the theoretical yield. The supplementation of whey with components of LB broth increased the maximum yield to 96% in 72h. The addition of 0.5% yeast extract to whey resulted in maximum yield of 74% at 36h and it increased to over 100% when yeast extract and trace metals solution (Fe++, Mn++ and Zn++ were added.A produção de etanol a partir de soro de leite empregando a cepa Escherichia coli KO11 recombinante, em fermentação de batelada, foi testada. O rendimento máximo de etanol foi obtido em 96h, representando apenas 38% do rendimento teórico. A suplementação do soro com os componentes do caldo LB aumentou o rendimento para 96% em 72h. A adição de 0,5% de extrato de levedura ao soro resultou em um rendimento máximo de 74% em 36h que aumentou para acima de 100% quando se adicionou extrato de levedura e uma solução de metais traço (Fe++, Mn++ e Zn++.

Diel tuning of photosynthetic systems in ice algae at Saroma-ko Lagoon, Hokkaido, Japan

Science.gov (United States)

Aikawa, Shimpei; Hattori, Hiroshi; Gomi, Yasushi; Watanabe, Kentaro; Kudoh, Sakae; Kashino, Yasuhiro; Satoh, Kazuhiko

Ice algae are the major primary producers in seasonally ice-covered oceans during the cold season. Diurnal change in solar radiation is inevitable for ice algae, even beneath seasonal sea ice in lower-latitude regions. In this work, we focused on the photosynthetic response of ice algae under diurnally changing irradiance in Saroma-ko Lagoon, Japan. Photosynthetic properties were assessed by pulse-amplitude modulation (PAM) fluorometry. The species composition remained almost the same throughout the investigation. The maximum electron transport rate ( rETRmax), which indicates the capacity of photosynthetic electron transport, increased from sunrise until around noon and decreased toward sunset, with no sign of the afternoon depression commonly observed in other photosynthetic organisms. The level of non-photochemical quenching, which indicates photoprotection activity by dissipating excess light energy via thermal processes, changed with diurnal variations in irradiance. The pigment composition appeared constant, except for xanthophyll cycle pigments, which changed irrespective of irradiance. These results indicate that ice algae tune their photosynthetic system harmonically to achieve efficient photosynthesis under diurnally changing irradiance, while avoiding damage to photosystems. This regulation system may be essential for productive photosynthesis in ice algae.

Extension of Ko Straight-Beam Displacement Theory to Deformed Shape Predictions of Slender Curved Structures

Science.gov (United States)

Ko, William L.; Fleischer, Van Tran

2011-01-01

The Ko displacement theory originally developed for shape predictions of straight beams is extended to shape predictions of curved beams. The surface strains needed for shape predictions were analytically generated from finite-element nodal stress outputs. With the aid of finite-element displacement outputs, mathematical functional forms for curvature-effect correction terms are established and incorporated into straight-beam deflection equations for shape predictions of both cantilever and two-point supported curved beams. The newly established deflection equations for cantilever curved beams could provide quite accurate shape predictions for different cantilever curved beams, including the quarter-circle cantilever beam. Furthermore, the newly formulated deflection equations for two-point supported curved beams could provide accurate shape predictions for a range of two-point supported curved beams, including the full-circular ring. Accuracy of the newly developed curved-beam deflection equations is validated through shape prediction analysis of curved beams embedded in the windward shallow spherical shell of a generic crew exploration vehicle. A single-point collocation method for optimization of shape predictions is discussed in detail

Proceedings of the 11th International Conference on Magnetic Fluids (ICMF 11) (Košice, Slovakia, 23-27 July 2007).

Science.gov (United States)

Kopčanský, Peter; Timko, Milan; Kováč, Josef; Václavíková, Miroslava; Odenbach, Stefan

2008-05-21

The 11th International Conference on Magnetic Fluids (ICMF 11) was held in Košice, Slovakia between 23-27 July 2007. Attendance at the conference was high and its motivation was in line with the ten previous ICMF conferences organized in Udine, Orlando, Bangor, Sendai-Tokyo, Riga, Paris, Bhavnagar, Timisoara, Bremen and Guarujá. The conference in Slovakia reflected the scientific community's enthusiasm and worldwide support, with 256 participants, from 30 countries attending.The main objective of ICMF 11 was to promote progress and knowledge in the field of magnetic fluids regarding their chemistry, physical and magnetic properties, heat and mass transfer, surface phenomena, as well as their technological and biomedical applications. As research on magnetic fluids is essentially interdisciplinary, experts from related areas were invited to present their contributions with a view to increasing knowledge in the field and highlighting new trends. Submitted communications were refereed by members of the Scientific Organizing Committee and abstracts were assembled in a book of abstracts. Participants presented 180 posters in two poster sessions and 56 oral presentations. All presentations contributed to a greater understanding of the area, and helped to bridge the gap between physics, chemistry, technology, biology and medical sciences. Contributions to this conference are presented in 115 scientific papers, with some published in Journal of Physics: Condensed Matter and the rest in Magnetohydrodynamics. The organization of the conference was made possible by generous support from the Institute of Experimental Physics and Institute of Geotechnics of the Slovak Academy of Sciences, the University of Pavol Jozef Šafárik and the Slovak Physical Society. Financial support from Ferrotec, Cryosoft Ltd, Mikrochem, Liquids Research Ltd, Askony and US Steel Košice, is also gratefully acknowledged.

Izlaganje na javni uvid podataka o nekretninama i utvrđivanje prava na zemljištu u funkciji uspostave jedinstvenog registra zemljišta i prava na zemljištu u Brčko distriktu BiH : Public presentation of data on real-estate and determination of rights in function of the establishment of a single registry of real-estate and real rights to real-estate in the Brcko district of B&H

Directory of Open Access Journals (Sweden)

Faruk Latifović

2014-12-01

Full Text Available Zakon o registru zemljišta i prava na zemljištu Brčko distrikta Bosne i Hercegovine je propisao uspostavu jedinstvene evidencije nekretnina i stvarnih prava na nekretninama u Brčko distriktu Bosne i Hercegovine. Poslovi uspostave jedinstvene evidencije, u segmentu izlaganja na javni uvid podataka o nekretninama i utvrđivanje prava, su povjereni Vijeću za izlaganje podataka o nekretninama i utvrđivanje prava na zemljištu Brčko distrikta Bosne i Hercegovine. Autor se, u ovom radu, uz nezaobilazan kraći prikaz historijata javnih evidencija na nekretninama u Bosni i Hercegovini, bavi organizacijom, nadležnostima i načinom rada Vijeća za izlaganje podataka o nekretninama i utvrđivanje prava na zemljištu Brčko distrikta BIH. Nakon što bude uspješno okončan projekat izlaganje podataka o nekretninama i utvrđivanje prava na zemljištu u Brčko distriktu BiH, svi geodetsko – katastarski podaci o nepokretnostima kao i podaci o njihovom pravnom statusu će biti vođeni u Registru zemljišta i prava na zemljištu Osnovnog suda Brčko distrikta BiH. : The Law of Land Registry and Rights over Land of the Brčko District of B&H stipulated the establishment of a single registry of real-estate and real rights to real-estate in the Brčko District of B&H. Activities of the establishment of a single registry, in the segment of public presentation of data on real-estate and determination of rights, were entrusted to the Council for Presentation of Data on Real-estate and Establishment of Rights to Land of the Brčko District of B&H. In this paper, the author presents the inevitable short overview of the history of real-estate registries in Bosnia and Herzegovina and he also deals with organization, competencies and manner of work of the Council for Presentation of Data on Real-estate and Establishment of Rights to Land of the Brčko District of B&H. After a successful completion of the project of presentation of data on real-estate and

Possibilities of utilization of fly ash from the black coal Power Engineering of the U. S. Steel Košice

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Františka Michalíková

2005-11-01

Full Text Available The paper presents modes of a direct utilization of the fly ash by-product of the combustion of black power coal in the slag - bottom boilers of the Division Plant Power Engineering ( DP PE of the U. S. Steel Košice ( next USSK . The properties of fly ash limit its use in metallurgy and foundry industry. The fly ash is directly utilizable in the metallurgical industry as a component of powder cover mixtures and insulation inserts, heat insulation parts and exothermical mixtures. The most important components in the mixtures are light micro spheres – cenospheres and heavy micro spheres – plerospheres. The micro spheres significantly improve properties of the powder cover mixtures.

Welding robot package; Arc yosetsu robot package

Energy Technology Data Exchange (ETDEWEB)

Nishikawa, S. [Yaskawa Electric Corp., Kitakyushu (Japan)

1998-09-01

For the conventional high-speed welding robot, the welding current was controlled mainly for reducing the spatters during short circuits and for stabilizing the beads by the periodic short circuits. However, an increase of deposition amount in response to the speed is required for the high-speed welding. Large-current low-spatter welding current region control was added. Units were integrated into a package by which the arc length is kept in short without dispersion of arc length for welding without defects such as undercut and unequal beads. In automobile industry, use of aluminum parts is extended for the light weight. The welding is very difficult, and automation is not so progressing in spite of the poor environment. Buckling of welding wire is easy to occur, and supply of wire is obstructed by the deposition of chipped powders on the torch cable, which stay within the contact chip resulting in the deposition. Dislocation of locus is easy to occur at the corner of rectangular pipe during the welding. By improving these troubles, an aluminum MIG welding robot package has been developed. 13 figs.

Czynniki ryzyka upadków i złamań kości u pacjentów chorych na reumatoidalne zapalenie stawów

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Krzysztof Tomaszewski

2010-04-01

Full Text Available Cel pracy: Ocena czynników ryzyka i częstości występowaniaupadków i złamań kości u chorych na reumatoidalne zapaleniestawów (RZS. Materiał i metody: Do badania kwalifikowano pacjentów chorychna RZS (spełniających kryteria ACR z 1984 r.. Dane na temat stanuzdrowia zebrano na podstawie ankiety zawierającej Kwestio -nariusz Oceny Stanu Zdrowia (HAQ, pytań dotyczących chorób,przyjmowanych leków, upadków i złamań kości w okresie ostatnich12 miesięcy. Wyniki: Przebadano 167 kobiet (89,8% i 19 mężczyzn (średni wiek± SD 58,5 ±13,8 roku. Średni czas trwania choroby wynosił14,4 ±10,7 roku. Średnia wartość HAQ 1,36 ±0,76. Z grupy 186 osóbupadek przydarzył się 80 badanym (43%. U 28 chorych (35%upadek zakończył się złamaniem bądź złamaniami obwodowymi.Liczba upadków dodatnio korelowała z wynikiem HAQ (r = 0,32;p < 0,05 oraz czasem trwania choroby (r = 0,31; p < 0,05.Głównymi czynnikami ryzyka upadków w badanej grupie byłyzawroty głowy [iloraz szans (OR = 2,68], stosowanie lekówhipotensyjnych (OR = 2,27 i przeciwdepresyjnych (OR = 2,56,deformacje stóp (OR = 3,14 oraz wysoki wskaźnik HAQ(OR = 2,08. Czas trwania RZS (OR = 1,05 i wiek (OR = 1,04 praktycznienie wpływały na ryzyko upadków. Głównymi czynnikamiryzyka złamań kości w badanej grupie były osteoporoza (t-score< –2,5 (OR = 4,70, stosowanie leków hipotensyjnych (OR = 4,98,deformacje stóp (OR = 4,82, zawroty głowy (OR = 3,30 orazwysoki wskaźnik HAQ (OR = 3,12. Wnioski: Upadki są poważnym problemem w przebiegu RZS.Głównymi czynnikami sprzyjającymi upadkom i złamaniomu chorych na RZS są deformacje stóp, zawroty głowy, zażywanieleków obniżających ciśnienie tętnicze oraz wysoka wartość HAQ.

Selection of foraging habitat and diet of the Hoopoe Upupa epops in the mosaic-like cultural landscape of Goričko (NE Slovenia

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Podletnik Mojca

2015-12-01

Full Text Available In 2012 and 2013, the selection of foraging habitats and the diet of the Hoopoe Upupa epops were studied in the Goričko area, where a significant population decline of the species has been recorded in the past 15 years. Goričko is an area with a well-preserved traditional mosaic-like agricultural landscape very rich in biodiversity which, however, is disappearing. The diet was determined using automatic camera recordings of prey brought to chicks by parents. Mole crickets Gryllotalpa gryllotalpa were the most dominant prey (35.4% frequency and 81.3% biomass of prey, followed by Scarab beetles larvae Scarabaeidae, caterpillars Lepidoptera larvae and True flies Diptera. Feeding frequency was highest in the period of most intensive chick growth (between 8 and 21 days of age. Selection of foraging habitat was researched by observation of birds during foraging. Hoopoes foraged mostly in mown meadows and grassy courtyards and, to a lesser extent, on sandy cart tracks and road edges. These habitats were characterized by low vegetation and patches of bare ground that enabled Hoopoes to forage efficiently. Home range size was determined using minimum convex polygons. The maximum home range size was between 42.9 and 57.7 ha, while the percentage of foraging habitats within the home range did not exceed 18%. Based on our results, we propose the following measures for effective Hoopoe conservation in the area: maintaining the present range of existing unimproved meadows, stopping the conversion of meadows into fields, restoring fields to meadows, prohibiting the use of pesticides targeting Mole crickets.

Koolipärimuse kogumisest Noarootsis ja Vormsis 2006. aasta kevadel : Rootsi-Eesti lastenaljade kogumik Det var en ko och det var poängen / Piret Voolaid

Index Scriptorium Estoniae

Voolaid, Piret, 1971-

2007-01-01

Autor käsitleb artiklis Ahvenamaa Põhjamaade Instituudi (Nordens Institut på Åland) eestvedamisel korraldatud lastepärimuse projekti, mille käigus koguti koolipärimust Soomest Ahvenamaalt ja Rootsist Gotlandilt ning Eestist endistelt rannarootsi aladelt. Kogutu põhjal ilmus rootsikeelne antoloogiline naljakogumik Det var en ko och det var poängen. Artiklis keskendutakse välitööde kogumismetoodikale ja tulemustele Eestis. Välitööd toimusid Noarootsi Koolis ja Vormsi Põhikoolis

Preface: Proceedings of the 11th International Conference on Magnetic Fluids (ICMF 11) (Košice, Slovakia, 23 27 July 2007)

Science.gov (United States)

Kopčanský, Peter; Timko, Milan; Kováč, Josef; Václavíková, Miroslava; Odenbach, Stefan

2008-05-01

The 11th International Conference on Magnetic Fluids (ICMF 11) was held in Košice, Slovakia between 23-27 July 2007. Attendance at the conference was high and its motivation was in line with the ten previous ICMF conferences organized in Udine, Orlando, Bangor, Sendai-Tokyo, Riga, Paris, Bhavnagar, Timisoara, Bremen and Guarujá. The conference in Slovakia reflected the scientific community's enthusiasm and worldwide support, with 256 participants, from 30 countries attending.The main objective of ICMF 11 was to promote progress and knowledge in the field of magnetic fluids regarding their chemistry, physical and magnetic properties, heat and mass transfer, surface phenomena, as well as their technological and biomedical applications. As research on magnetic fluids is essentially interdisciplinary, experts from related areas were invited to present their contributions with a view to increasing knowledge in the field and highlighting new trends. Submitted communications were refereed by members of the Scientific Organizing Committee and abstracts were assembled in a book of abstracts. Participants presented 180 posters in two poster sessions and 56 oral presentations. All presentations contributed to a greater understanding of the area, and helped to bridge the gap between physics, chemistry, technology, biology and medical sciences. Contributions to this conference are presented in 115 scientific papers, with some published in Journal of Physics: Condensed Matter and the rest in Magnetohydrodynamics. The organization of the conference was made possible by generous support from the Institute of Experimental Physics and Institute of Geotechnics of the Slovak Academy of Sciences, the University of Pavol Jozef Šafárik and the Slovak Physical Society. Financial support from Ferrotec, Cryosoft Ltd, Mikrochem, Liquids Research Ltd, Askony and US Steel Košice, is also gratefully acknowledged.

Utjecaj tretiranja različitim koncentracijama fitohormona na ožiljavanje reznica odabranih maslina Dubrovačko neretvanske županije (Velika sitnjaka, Sitnica, Uljarica, Kalamata)

OpenAIRE

Marić, Mara; Marinović-Peričević, Marija; Mračić, Iva

2017-01-01

U radu su prikazani rezultati praćenja proizvodnje reznica sorti masline Velike sitnjake, Sitnice, Uljarice i Kalamate u 2016. godini pod utjecajem tretiranja različitim koncentracijama fitohormona IBA (2000, 3000, 4000 i 5000 ppm) te su uspoređeni s rezultatima dobivenim u 2015. godine za iste sorte. Istraživanja su dio projekta Identifikacija i gospodarenje genfondom maslina na području Dubrovačko neretvanske županije” i provedena su na Zavodu za mediteranske kulture Sveučilišta u Dubrovnik...

Odrębność postępowania kinezyterapeutycznego u pacjentów po amputacjach naczyniowych w obrębie kończyn dolnych = Separation kinesiotherapeutic proceedings in patients with vascular amputations in the lower legs

Directory of Open Access Journals (Sweden)

Agnieszka Radzimińska

2017-02-01

3.      Uniwersytet Kazimierza Wielkiego w Bydgoszczy, Bydgoszcz, Polska     Słowa kluczowe: kinezyterapia, pacjent, amputacje naczyniowe, kończyny dolne. Key words: kinesiotherapy, patient, vascular amputations, lower limbs.   Streszczenie             Amputacja, czyli operacyjne odjęcie kończyny lub jej części, jest jednym z najstarszych zabiegów w historii medycyny. Obecnie, przeważająca część amputacji (ok. 80-90% odbywa się z powodu powikłań chorób naczyniowych. W zależności od obszaru dotkniętego zmianami tkanek oraz rozległości tego procesu, chirurg podejmuje decyzję o poziomie odjęcia kończyny. Po amputacji istnieje ryzyko wystąpienia wielu powikłań, m.in.: zakażenie beztlenowcami, rozejście się rany, martwica skóry, obrzęk oraz przykurcze. W przypadku amputacji planowych ćwiczenia powinno się rozpocząć jeszcze przed operacją, aby przygotować organizm pacjenta do nadchodzących zmian. Kinezyterapia ma na celu wzmocnienie kończyn, zarówno tej, której część zostanie usunięta, a także zdrowej kończyn, która będzie  musiała  przejąć ciężar ciała do czasu zaprotezowania oraz nauczenia pacjenta posługiwania się protezą. Zaleca się ćwiczenia czynne oraz czynne z oporem kończyn górnych, dolnych oraz tułowia, a także ćwiczenia oddechowe. Niezwykle istotne jest przygotowanie psychiczne pacjenta do amputacji poprzez ukazania  możliwości funkcjonowania jak przed operacją. Jednym z jej elementów jest profilaktyka przeciwzakrzepowa, w której skład wchodzą: wysokie ułożenie kończyny, manualny drenaż limfatyczny oraz ćwiczenia bierne i czynne,  pobudzające pompę mięśniową. Przykurcze są jednym z najczęstszych problemów po amputacji, które wpływają negatywnie na proces protezowania. Działaniem zapobiegającym powstaniu przykurczy są pozycje ułożeniowe, które nie powodują patologicznego ustawienia kończyny. Innymi zabiegami, które wykonuje  fizjoterapeuta

Elektrokoagülasyon Prosesi İle Gıda Endüstrisi Atıksuyunun Arıtımında Optimum Koşulların Belirlenmesi

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Sevil VELİ

2018-03-01

Full Text Available Bu çalışmada bir gıda endüstrisi atıksuyunun alüminyum elektrot kullanılarak kesikli sistemde elektrokoagülasyon yöntemi ile arıtımı incelenmiştir. Anaerobik arıtma çıkışından alınan atıksuyun özellikleri 504 mg/L KOI, 100 mg/L TOK, 3.37 mS/cm iletkenlik ve 7.8 pH parametreleri ile karakterize edilmiştir. Elektrokoagülasyon prosesinin etkinliği KOİ parametresindeki değişim gözlenerek değerlendirilmiştir. Çalışmada pH, iletkenlik, akım yoğunluğu ve reaksiyon süresinin etkisi incelenmiştir. Elde edilen sonuçlardan optimum koşullar pH=7, iletkenlik=3.5 mS/cm, akım yoğunluğu =1.83 mA/cm2 ve süre=30 dak. olarak belirlenmiştir. Bu koşullarda %95 KOİ giderim verimi elde edilirken işletme maliyeti de 0.98 TL/m3 arıtılan atıksu olarak belirlenmiştir.

Current Status and Performance Tests of Korea Heat Load Test Facility KoHLT-EB

Energy Technology Data Exchange (ETDEWEB)

Kim, Sukkwon; Jin, Hyunggon; Shin, Kyuin; Choi, Boguen; Lee, Eohwak; Yoon, Jaesung; Lee, Dongwon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Duckhoi; Cho, Seungyon [National Fusion Research Institute, Daejeon (Korea, Republic of)

2013-05-15

A commissioning test has been scheduled to establish the installation and preliminary performance experiments of the copper hypervapotron mockups. And a qualification test will be performed to evaluate the CuCrZr duct liner in the ITER neutral beam injection facility and the ITER first wall small-scale mockups of the semi-prototype, at up to 1.5 and 5 MW/m{sup 2} high heat flux. Also, this system will be used to test other PFCs for ITER and materials for tokamak reactors. Korean high heat flux test facility(KoHLT-EB; Korea Heat Load Test facility - Electron Beam) by using an electron beam system has been constructed in KAERI to perform the qualification test for ITER blanket FW semi-prototype mockups, hypervapotron cooling devices in fusion devices, and other ITER plasma facing components. The commissioning and performance tests with the supplier of e-gun system have been performed on November 2012. The high heat flux test for hypervapotron cooling device and calorimetry were performed to measure the surface heat flux, the temperature profile and cooling performance. Korean high heat flux test facility for the plasma facing components of nuclear fusion machines will be constructed to evaluate the performance of each component. This facility for the plasma facing materials will be equipped with an electron beam system with a 60 kV acceleration gun.

Heterozygous Che-1 KO mice show deficiencies in object recognition memory persistence.

Science.gov (United States)

Zalcman, Gisela; Corbi, Nicoletta; Di Certo, Maria Grazia; Mattei, Elisabetta; Federman, Noel; Romano, Arturo

2016-10-06

Transcriptional regulation is a key process in the formation of long-term memories. Che-1 is a protein involved in the regulation of gene transcription that has recently been proved to bind the transcription factor NF-κB, which is known to be involved in many memory-related molecular events. This evidence prompted us to investigate the putative role of Che-1 in memory processes. For this study we newly generated a line of Che-1(+/-) heterozygous mice. Che-1 homozygous KO mouse is lethal during development, but Che-1(+/-) heterozygous mouse is normal in its general anatomical and physiological characteristics. We analyzed the behavioral characteristic and memory performance of Che-1(+/-) mice in two NF-κB dependent types of memory. We found that Che-1(+/-) mice show similar locomotor activity and thigmotactic behavior than wild type (WT) mice in an open field. In a similar way, no differences were found in anxiety-like behavior between Che-1(+/-) and WT mice in an elevated plus maze as well as in fear response in a contextual fear conditioning (CFC) and object exploration in a novel object recognition (NOR) task. No differences were found between WT and Che-1(+/-) mice performance in CFC training and when tested at 24h or 7days after training. Similar performance was found between groups in NOR task, both in training and 24h testing performance. However, we found that object recognition memory persistence at 7days was impaired in Che-1(+/-) heterozygous mice. This is the first evidence showing that Che-1 is involved in memory processes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Rehabilitation in the view of small and midsized enterprises: knowledge, appreciation and possibilities to cooperate - results of the KoRB-project].

Science.gov (United States)

Hesse, B; Heuer, J; Gebauer, E

2008-12-01

The experiences of small and midsized enterprises (SME) with medical rehabilitation were investigated in the KoRB-Study (KoRB= KOoperation Rehabilitation und Betrieb) for the first time. Opportunities for a targeted cooperation between the statutory pension insurance and these enterprises were explored. Based on explorative interviews, Westphalian employers, members of the works council, occupational health practitioners and employees were interrogated about the image of and their appreciation of medical rehabilitation in the work setting. Experience with rehabilitation and the level of information on rehabilitation were recorded as well as the compatibility of rehabilitation with operative processes in the working site. In addition rehab hospitals were asked about their experience in cooperating with enterprises. 697 employers of small and midsized enterprises, 458 members of the works councils, 73 occupational health practitioners, 47 rehab hospitals and 3 509 employees, who are members of the German Pension Fund of Westphalia, took part in the survey. Especially employers perceived rehabilitation positively and reported good experiences. Among the employees, those who had taken part in rehabilitation showed the highest appreciation. Occupational health practitioners were more restrained in their appraisal. Some of them complained about a lack of sustainability. The different target groups of the survey felt differently well informed about rehabilitation - best ratings came from the occupational health practitioners, worst ratings from the employees. All groups would welcome more accessible information in case of need. Medical rehabilitation in its standard form of "3 weeks full-time" often causes severe logistic problems in SME (e. g., replacement of employee, loss of experience). However the financial burden is perceived as less problematic. Employers favour alternative rehab models, which allow part-time working. Many employees, who expressed a need for

ABCG2-mediated suppression of chlorin e6 accumulation and photodynamic therapy efficiency in glioblastoma cell lines can be reversed by KO143.

Science.gov (United States)

Abdel Gaber, Sara A; Müller, Patricia; Zimmermann, Wolfgang; Hüttenberger, Dirk; Wittig, Rainer; Abdel Kader, Mahmoud H; Stepp, Herbert

2018-01-01

Photodynamic therapy (PDT) of malignant brain tumors is a promising adjunct to standard treatment, especially if tumor stem cells thought to be responsible for tumor progression and therapy resistance were also susceptible to this kind of treatment. However, some photosensitizers have been reported to be substrates of ABCG2, one of the membrane transporters mediating resistance to chemotherapy. Here we investigate, whether inhibition of ABCG2 can restore sensitivity to photosensitizer chlorin e6-mediated PDT. Accumulation of chlorin e6 in wild type U87 and doxycycline-inducible U251 glioblastoma cells with or without induction of ABCG2 expression or ABCG2 inhibition by KO143 was analyzed using flow cytometry. In U251 cells, ABCG2 was inducible by doxycycline after stable transfection with a tet-on expression plasmid. Tumor sphere cultivation under low attachment conditions was used to enrich for cells with stem cell-like properties. PDT was done on monolayer cell cultures by irradiation with laser light at 665nm. Elevated levels of ABCG2 in U87 cells grown as tumor spheres or in U251 cells after ABCG2 induction led to a 6-fold lower accumulation of chlorin e6 and the light dose needed to reduce cell viability by 50% (LD50) was 2.5 to 4-fold higher. Both accumulation and PDT response can be restored by KO143, an efficient non-toxic inhibitor of ABCG2. Glioblastoma stem cells might escape phototoxic destruction by ABCG2-mediated reduction of photosensitizer accumulation. Inhibition of ABCG2 during photosensitizer accumulation and irradiation promises to restore full susceptibility of this crucial tumor cell population to photodynamic treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Adaptation Of Forgotten Buildings The Example Of The Ruins Of The Kościelec Protestant Church In Piaski

Science.gov (United States)

Gleń, Piotr; Jarocka-Mikrut, Aleksandra

2015-12-01

Small towns in the Lublin Province are abundant with buildings possessed of outstanding historical and architectural values, representing the culture of past generations. Piaski, about 30 km east of Lublin, also boasts some of the remarkable characteristic of small towns. Not only does it feature post-Jewish tenements, but also a palace and complexes of religious buildings situated on its outskirts. This article focuses on the Kościelec - an unused, dilapidated former Protestant church. Now, works are being carried out that have inspired the Piaski town authorities to try to find a best-use scenario for the former church, in order to preserve its architectural values for future generations. The authors of this article aim to prove the necessity of research and analysis in finding the best new functions for properties whose function has already been imposed. The example of successfully completed revitalisation works at the palace and park complex in Gardzienice, located not far from the baroque Protestant church in Piaski, illustrates the advantages of some of the adaptation processes that can be employed in such buildings.

Tehnološko projektovanje pretovarno-skladišnih procesa / Technological design of loading/unloading and warehousing processes

Directory of Open Access Journals (Sweden)

Momčilo Miljuš

2004-05-01

Full Text Available Tehnološko projektovanje logističkih sistema karakteriše veoma visok stepen kompleksnosti, a od njegovog kvaliteta u znatnoj meri zavisi i efikasnost i ekonomičnost realizacije logističkih procesa u praksi. Pretovarno-skladišne procese (PSP u okviru odgovarajućih logističkih podsistema, a posebno u okviru realizacije tokova materijala, karakteriše niz specifičnosti koje u znatnoj meri usložavaju tipične PSP. Da bi se ostvarili preduslovi za adekvatno realizovanje PSP, u ovom radu je dat pregled metodologije tehnološkog projektovanja ovih sistema. / Design of technological processes is one of the most complex tasks in the field of design in general. This type of design is also involved in logistic system design as these systems are typically very complex so that quality of design solution has a great influence on efficiency and economical level of logistic processes efficiency in practice. Loading/unloading and warehousing processes (LUWP within some logistics systems, especially in material flows require specific efforts which complicate typical LUWP. Aiming to consider adequate realization of LUWP, this paper shows the methodology of design of these systems.

Skuteczność kompleksowej fizjoterapii ambulatoryjnej u chorych z rozpoznaniem zapalenia nadkłykcia bocznego kości ramiennej = The efficiency of complex outpatient physiotherapy in patients diagnosed with lateral epicondylitis

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Klaudia Pasiud

2016-08-01

3Indywidualna Praktyka Fizjoterapeutyczna w Szczecinie   A. przygotowanie projektu badawczego; B. zbieranie danych; C. analiza statystyczna; D. interpretacja danych; E. przygotowanie manuskryptu; F. opracowanie piśmiennictwa; G. pozyskanie funduszy.               Autor do korespondencji: dr n. o zdr. Wojciech Garczyński Indywidualna Praktyka Fizjoterapeutyczna ul. Biskupa Bandurskiego 71/17 71-685 Szczecin mail: w.garczynski@gmail.com     STRESZCZENIE WSTĘP. Zapalenie nadkłykcia bocznego kości ramiennej, zwane powszechnie „łokciem tenisisty” jest jedną z najczęściej rozpoznawanych dolegliwości w okolicy stawu łokciowego u osób między 30 a 65 rokiem życia. Schorzenie to występuje wśród 1-3% populacji, a jej główną przyczyną są przeciążenia mięśni prostowników przedramienia w wyniku długotrwałej pracy dynamicznej lub statycznej o niewielkim obciążeniu. Osoby, które zawodowo wykonują czynności manualne są szczególnie predysponowane do powstania tego schorzenia. CEL. Celem przeprowadzonych badań była ocena skuteczności kompleksowej fizjoterapii u pacjentów z rozpoznaniem zapalenia nadkłycia bocznego kości ramiennej. MATERIAŁ I METODY. Badanie przeprowadzono w grupie 40 osób (25 mężczyzn i 15 kobiet z rozpoznaniem zapalenia nadkłycia bocznego kości ramiennej, u których dolegliwości bólowe utrzymywały się od 4 do 6 miesięcy. Średni wiek grupy badanej to 44 lata ± 10,22. W badaniu wykorzystano metodę sondażu diagnostycznego w oparciu o autorski kwestionariusz ankiety oraz standaryzowany kwestionariusz dotyczący niesprawności kończyny górnej DASH (Disability of the Arm, Shoulder and Hand. Poziom dolegliwości bólowych oceniono za pomocą skali NRS (Numerical Rating Scale. Ponadto u badanych wykonano trzy testy funkcjonalne: test Thomsona, test Cozena i test Milla. Do analizy wyników wykorzystano arkusz kalkulacyjny Excel i program Statistica 12. WYNIKI. Najczęściej zlecanymi zabiegami

Probna istraživanja na trasi buduće autoceste A5 Beli Manastir – Osijek – Svilaj, dionica Beli Manastir – Osijek, arheološko nalazište AN 8 Beli Manastir – Atar, Napuštene njive

OpenAIRE

Buzov, Marija

2014-01-01

Institut za arheologiju proveo je probna arheološka istraživanja sustavom probnih rovova na trasi buduće autoceste A5 Beli Manastir – Osijek – Svilaj, dionica Beli Manastir – Osijek, arheološko nalazište AN 8 Beli Manastir – Atar, Napuštene njive.

Theoretical studies of the local structure and electron paramagnetic resonance parameters for tetragonal VO{sup 2+} in C{sub 6}H{sub 7}KO{sub 7}

Energy Technology Data Exchange (ETDEWEB)

Zhou, Ping [Chongqing Jiaotong Univ. (China). School of Science; Li, Ling [Sichuan University of Arts and Science, Dazhou (China). Dept. of Maths and Finance-Economics

2015-07-01

The optical spectra, electron paramagnetic resonance parameters (i.e., the spin Hamiltonian parameters, including paramagnetic g factors and the hyperfine structure constants A{sub i}) and the local distortion structure for the tetragonal VO{sup 2+} in C{sub 6}H{sub 7}KO{sub 7} are theoretically studied based on the crystal-field theory and three-order perturbation formulas of a 3d{sup 1} centre in tetragonal site. The magnitude of orbital reduction factor, core polarisation constant κ, and local structure parameters are obtained by fitting the calculated optical spectra and electron paramagnetic resonance parameters to the experimental values. The theoretical results are in reasonable agreement with the experimental values.

Determination of concentrations of minor and micro elements in ancient bronze drums artifacts samples by KO-standardization method of neutron activation analysis

International Nuclear Information System (INIS)

Nguyen Tac Anh; Ho Manh Dung; Diep Dinh Hoa; Cao Dong Vu

2000-01-01

The study aims to get a lot information about manufacturers of ancient bronze artifacts and ancient civilization. By KO-standardization method of neutron activation analysis developed in the Nuclear Research Institute, the concentrations of Au, Ag, As, Zn, Sb, Sn elements in ancient bronze alloy samples of 99 bronze artifacts from many excavated archaeological sites at the provinces in Vietnam were determined with uncertainties about ±10%. These elemental concentrations have been utilized in a statistical analysis procedure in order to determine similarities and correlation between the various samples. Th abnormal high of concentrations of noble metals as Au, Ag in ancient bronze indicates that the ancient metallurgists had been interested in role of these metals on sound quality of bronze artifacts. Especially, the concentrations of As in many samples are very high even at about 10%. This gives an evidence that in ancient time the humankind could use bronze As alloy in order to improve quality when they had produced bronze artifacts. (author)

Eskişehir koşullarında yetiştirilen Reyhan (Ocimum basilicum L.) bitkisinin bazı bitkisel özelliklerin ve diurnal varyabilitesinin belirlenmesi

OpenAIRE

Kulan, Engin Gökhan

2013-01-01

Bu çalışma Eskişehir Osmangazi Üniversitesi Ziraat Fakültesi Tarla Bitkileri Bölümü deneme alanında 2010 yılında yürütülmüştür. Denemede Eskişehir ekolojik koşullarında yetiştirilen reyhan (Ocimum basilicum L.) bitkisinin verim ve verim özellikleri ile farklı biçim saatlerinin reyhanın uçucu yağı ve uçucu yağ bileşimi üzerine olan etkileri incelenmiştir. Tesadüf bloklarında bölünmüş parseller deneme desenine göre 3 tekerrürlü olarak kurulan denemede reyhan bitkileri çiçeklen...

Oriental medicine Kyung-Ok-Ko prevents and alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats.

Directory of Open Access Journals (Sweden)

Minhee Jang

Full Text Available Kyung-Ok-Ko (KOK, a traditional herbal prescription composed of Rehmannia glutinosa Liboschitz var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey, has been widely used in traditional Oriental medicine as a vitalizing medicine or as the prescription for patients with age-associated disorders such as amnesia and stroke. However, the potential protective value of KOK for the treatment of polycystic ovarian syndrome (PCOS is largely unknown. We investigated whether pre-administration (daily from 2 hours before PCOS induction and post-administration (daily after induction of PCOS of KOK (0.5, 1.0, and 2.0 g/kg/day, p.o. could have a protective effect in a dehydroepiandrosterone (DHEA, s.c.-induced PCOS rat model. Pre-administration of KOK significantly decreased the elevated body weight and ovary weight, elevated size and number of follicular cysts, elevated level of serum glucose, and estradiol after DHEA injection. KOK reduced the elevated percentage of CD8 (+ T lymphocytes in lymph nodes, the elevated mRNA expression of CD11b and CD3 in ovaries, and infiltration of macrophages in ovarian tissue with PCOS. KOK diminished the increased mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, chemokines (IL-8, MCP-1, and iNOS in the ovaries, and increased the reduced mRNA expression of growth factors (EGF, TGF-β by DHEA injection. Post-administration of KOK also improved the DHEA-induced PCOS-like symptoms, generally similar to those evident from pre-administration of KOK. KOK may effectively prevent and improve DHEA-induced PCOS via anti-inflammatory action, indicating its preventive and therapeutic potential for suppressing PCOS.

Dual AAV/IL-10 Plus STAT3 Anti-Inflammatory Gene Delivery Lowers Atherosclerosis in LDLR KO Mice, but without Increased Benefit

Directory of Open Access Journals (Sweden)

Maohua Cao

2012-01-01

Full Text Available Both IL-10 and STAT3 are in the same signal transduction pathway, with IL-10-bound IL10 receptor (R acting through STAT3 for anti-inflammatory effect. To investigate possible therapeutic synergism, we delivered both full-length wild-type human (h STAT3 and hIL-10 genes by separate adenoassociated virus type 8 (AAV8 tail vein injection into LDLR KO on HCD. Compared to control Neo gene-treated animals, individual hSTAT3 and hIL-10 delivery resulted in significant reduction in atherogenesis, as determined by larger aortic lumen size, thinner aortic wall thickness, and lower blood velocity (all statistically significant. However, dual hSTAT3/hIL-10 delivery offered no improvement in therapeutic effect. Plasma cholesterol levels in dual hSTAT3/hIL-10-treated animals were statistically higher compared to hIL-10 alone. While no advantage was seen in this case, we consider that the dual gene approach has intrinsic merit, but properly chosen partnered genes must be used.

Jałowe martwice kości, charakterystyka choroby i postępowanie fizykalne – przegląd literatury = Sterile necrosis of bone, the characteristics of the illness and physical examination - a literature review

OpenAIRE

Radzimińska, Agnieszka; Zimmermann, Agnieszka Anna; Weber-Rajek, Magdalena; Strojek, Katarzyna; Bułatowicz, Irena; Goch, Aleksander; Zukow, Walery

2015-01-01

Radzimińska Agnieszka, Zimmermann Agnieszka Anna, Weber-Rajek Magdalena, Strojek Katarzyna, Bułatowicz Irena, Goch Aleksander, Zukow Walery. Jałowe martwice kości, charakterystyka choroby i postępowanie fizykalne – przegląd literatury = Sterile necrosis of bone, the characteristics of the illness and physical examination - a literature review. Journal of Education, Health and Sport. 2015;5(10):108-120. ISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.32518 http://ojs.ukw.edu.pl/index....

Effect of a Traditional Herbal Prescription, Kyung-Ok-Ko, on Male Mouse Spermatogenic Ability after Heat-Induced Damage

Directory of Open Access Journals (Sweden)

Deok-Sang Hwang

2015-01-01

Full Text Available Kyung-Ok-Ko (KOK, a well-known traditional Korean medicinal formula, has long been used to invigorate the essential qi. This use of KOK may be associated with reproductive ability as a more modern concept. The protective effect of KOK was evaluated against deterioration of testicular function induced by heat exposure in male mice. Male fertility was disrupted by scrotal heat stress at 43°C for 5 weeks. KOK (0.25, 0.50, and 2.00 g/kg/day was administered orally at 3 h after the stress. To evaluate the protective effect of KOK, body weight, testicular weight, sperm count, sperm motility, and histopathological changes in the testes were evaluated. KOK-treated mice significantly recovered their general health, as evidenced by body weight. KOK-treated mice also showed significantly higher testes weights, sperm counts, and sperm motility than did the heat stress group. KOK-treated mice significantly recovered the morphological appearance of the seminiferous tubules and seminiferous epithelium. Furthermore, KOK-treated mice significantly increased antioxidant enzyme activities and reduced the protein expressions of apoptosis in the testes. KOK significantly protects against heat-induced damage to testicular function in male mice by inhibiting oxidative stress and apoptosis, indicating that KOK may be an effective agent for treatment of heat-induced male infertility.

Search for B Decays into KO-anti-KO

Energy Technology Data Exchange (ETDEWEB)

Aubert, B.

2004-02-12

We present preliminary results of a search for B{sup 0} {yields} K{sup 0}{bar K}{sup 0} decays in the K{sub s}{sup 0}K{sub s}{sup 0} final state using a sample of approximately 23 million B{bar B} pairs collected by the BABAR detector at the PEP-II asymmetric B Factory at SLAC. We find no evidence for a signal and set an upper limit on the branching fraction of 7.3 x 10{sup -6} at the 90% confidence level.

Anti-platelet and anti-thrombotic effect of a traditional herbal medicine Kyung-Ok-Ko.

Science.gov (United States)

Kim, Tae-Ho; Lee, Kyoung Mee; Hong, Nam Doo; Jung, Yi-Sook

2016-02-03

Kyung-Ok-Ko (KOK), a traditional herbal prescription, contains six main ingredients; Rehmannia glutinosa var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey. KOK has been widely taken as a traditional oriental medicine for improving blood circulation or age-related symptoms, such as dementia and stroke. However, the effect of KOK on platelet activity has not been clarified. To evaluate the effect of KOK on platelet function, we evaluated its effect on functional markers of platelet activation such as aggregation and shape change. As a mechanism study for the effect of KOK, we examined its effect on granule secretion, intracellular Ca(2+) increase, and PLCγ and Akt activation. To investigate the effect of orally administered KOK (0.5, 1, 2 g/kg), we examined its ex vivo effect on platelet aggregation in rat, and its in vivo anti-thrombotic effect in mice thromboembolism model. Furthermore, the effect of KOK on bleeding time was examined to estimate its potential side effect. KOK (0.3, 1, 3, 10 mg/ml) inhibited collagen-induced platelet aggregation and shape change in rat platelets in a concentration-dependent manner. The mechanism for the anti-platelet effect of KOK seems to involve the inhibition of ATP release, intracellular Ca(2+) elevation, and the phosphorylation of PLCγ and Akt. In rat ex vivo study, KOK (2 g/kg, p.o. for 1 day, and 0.5, 1, 2 g/kg, p.o. for 7 days) also had significant inhibitory effects on collagen-induced platelet aggregation. In addition, KOK showed a significant protective effect against thrombosis attack in mice. The prolongation of bleeding time by KOK was much less than that by ASA, suggesting a beneficial potential of KOK than ASA in view of side effect. These findings suggest that KOK elicits remarkable anti-platelet and anti-thrombotic effects with less side effect of bleeding, and therefore, it may have a therapeutic potential for the prevention of platelet-associated cardiovascular diseases

³⁵Sulphate incorporation assay as a new tool for measuring early cartilage degradation following blood exposure in vitro and in vivo in f8 ko rats

DEFF Research Database (Denmark)

Pulles, A. E.; Christensen, K. R.; Coeleveld, K.

2017-01-01

hours after euthanasia the cartilage of six healthy F8 KO rats was obtained by shaving off cartilage fragments of the tibia plateau by use of a scalpel. All cartilage explants were then cultured for four days; in addition to culture medium, half of the cartilage samples were cultured with 50% v/v whole...... blood. After four days proteoglycan synthesis rate was determined by adding 35SO42- to the cultures for four hours. The 35SO42- becomes incorporated in new synthesized proteoglycans. After digesting the cartilage pieces, cetylpyridinium chloride was added to the samples to precipitate the proteoglycans...

Menemen Ekolojik Koşullarında Lavanta (Lavandula spp.) Tür ve Çeşitlerinin Morfolojik, Verim ve Kalite Özelliklerinin Belirlenmesi

OpenAIRE

Karık, Ünal; Çiçek, Fatih; Çınar, Orçun

2017-01-01

Bu çalışma Menemen ekolojik koşullarında lavanta (Lavandula spp.) tür ve çeşitlerininmorfolojik, verim ve kalite özelliklerini belirlemek amacı ile 2015-2016yılları arasında yürütülmüştür. Çalışmada 2 farklı türe ait 8 farklı ticarilavanta çeşidi kullanılmıştır. 2 yıl sonucunda elde edilen veriler ışığında türve çeşitler arasında önemli farklılıklar bulunduğu tespit edilmiştir. Lavandintipi çeşitler, verim özellikleri açısından lavander tipi çeşitlerin önünegeçerken,  uçucu yağ oranı ve uçucu...

From the Herľany geyser to prove sources of geothermal potential in the Košice basin

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Juraj Ďurove

2007-01-01

Full Text Available Slovakia is a watering place known in the past. A little but very benefit spa lies near the village Herľany below the foothil of the western slopes of the Slanské vrchy Mts. When mineral springs were not able to cover the consumption of the mineral waters in 1870 a well resulting in nowadays unique „ Herľany geyser“ was drilled by Viliam Zsigmondy. In the second half of the 20th century a geological prospecting on oil and natural gas realised in the Košice basin and East Slovakian Neogene basin was. Based on the results, of prospecting structural boreholes, aimed at hydrocarbon prospection, geophysical inestigation and hydrogeological investigation a geothermal potential of this part of the area was confirmed. The geothermal boreholes (GTD-1, GTD-2 and GTD-3 were drilled after 30 years after it. The results from these wells were very positive because the discharge reached 150 litres per second and the temperature of water was 126 °C on the borehole mouth.The time flies and the heasty attested geothermal source in the meantime isn´t utilized enough. The history as well as the today story is known but the perspective of this spring in the future is not clear. Possibilities of its exploitation as an alternative energy source are great but a grand investor is needed. Maybe, the EU-founds will be the only objective future for a prosperity of our followers.

Effect of corn silage and quantitative feed restriction on growth performance, body measurements, and carcass tissue composition in White Kołuda W31 geese.

Science.gov (United States)

Kokoszyński, D; Bernacki, Z; Grabowicz, M; Stańczak, K

2014-08-01

The objective of this study was to determine the effect of corn silage and quantitative feed restriction on BW, ADG, feed conversion, and carcass composition of White Kołuda W31 geese. Two diets were fed during the rearing period from 22 to 98 d of age: 1) a commercial diet ad libitum, and 2) restricted amounts of a commercial diet and corn silage ad libitum. Each treatment had 2 replicates of 16 birds each. From 99 to 119 d of age, all birds were fattened with whole oat grain alone. Incorporation of corn silage reduced weight gains and caused statistically significant differences in BW at the end of the rearing period (14 wk, 6,625.0 vs. 6,050.0 g; P 0.05). Daily weight gains varied with week of growth, being lowest at 12 wk of age. Birds fed the commercial diet and corn silage had a significantly longer trunk (29.2 vs. 31.0 cm, P dressing percentage (65.0 vs. 74.7%, P Poultry Science Association Inc.

Performance Test of Korea Heat Load Test Facility (KoHLT-EB) for the Plasma Facing Components of Fusion Reactor

International Nuclear Information System (INIS)

Kim, Suk-Kwon; Jin, Hyung Gon; Lee, Eo Hwak; Yoon, Jae-Sung; Lee, Dong Won; Cho, Seungyon

2014-01-01

The main components of the plasma facing components (PFCs) in the tokamak are the blanket first wall and divertor, which include the armour materials, the heat sink with the cooling mechanism, and the diagnostics devices for the temperature measurement. The Korea Heat Load Test facility by using electron beam (KoHLT-EB) has been operating for the plasma facing components to develop fusion engineering. This electron beam facility was constructed using a 300 kW electron gun and a cylindrical vacuum chamber. Performance tests were carried out for the calorimetric calibrations with Cu dummy mockup and for the heat load test of large Cu module. For the simulation of the heat load test of each mockup, the preliminary thermal-hydraulic analyses with ANSYS-CFX were performed. For the development of the plasma facing components in the fusion reactors, test mockups were fabricated and tested in the high heat flux test facility. To perform a beam profile test, an assessment of the possibility of electron beam Gaussian power density profile and the results of the absorbed power for that profile before the test starts are needed. To assess the possibility of a Gaussian profile, for the qualification test of the Gaussian heat load profile, a calorimeter mockup and large Cu module were manufactured to simulate real heat. For this high-heat flux test, the Korean high-heat flux test facility using an electron beam system was constructed. In this facility, a cyclic heat flux test will be performed to measure the surface heat flux, surface temperature profile, and cooling capacity

Performance Test of Korea Heat Load Test Facility (KoHLT-EB) for the Plasma Facing Components of Fusion Reactor

Energy Technology Data Exchange (ETDEWEB)

Kim, Suk-Kwon; Jin, Hyung Gon; Lee, Eo Hwak; Yoon, Jae-Sung; Lee, Dong Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Cho, Seungyon [National Fusion Research Institute, Daejeon (Korea, Republic of)

2014-10-15

The main components of the plasma facing components (PFCs) in the tokamak are the blanket first wall and divertor, which include the armour materials, the heat sink with the cooling mechanism, and the diagnostics devices for the temperature measurement. The Korea Heat Load Test facility by using electron beam (KoHLT-EB) has been operating for the plasma facing components to develop fusion engineering. This electron beam facility was constructed using a 300 kW electron gun and a cylindrical vacuum chamber. Performance tests were carried out for the calorimetric calibrations with Cu dummy mockup and for the heat load test of large Cu module. For the simulation of the heat load test of each mockup, the preliminary thermal-hydraulic analyses with ANSYS-CFX were performed. For the development of the plasma facing components in the fusion reactors, test mockups were fabricated and tested in the high heat flux test facility. To perform a beam profile test, an assessment of the possibility of electron beam Gaussian power density profile and the results of the absorbed power for that profile before the test starts are needed. To assess the possibility of a Gaussian profile, for the qualification test of the Gaussian heat load profile, a calorimeter mockup and large Cu module were manufactured to simulate real heat. For this high-heat flux test, the Korean high-heat flux test facility using an electron beam system was constructed. In this facility, a cyclic heat flux test will be performed to measure the surface heat flux, surface temperature profile, and cooling capacity.

SPOR YAPAN VE YAPMAYAN ÜNİVERSİTE ÖĞRENCİLERİNİN BENLİK SAYGISI VE ATILGANLIK DÜZEYLERİNİN İNCELENMESİ (Muğla Sıtkı Koçman Üniversitesi Örneği)

OpenAIRE

MOLLAOĞULLARI, Hacalet; ESEN, Cemil Alptuğ

2013-01-01

This research was conducted at Mugla Sıtkı Koçman University on the students who are both doing exercises and who do not in order to explore their self-esteem and assertiveness levels. This study’s population consists of students who are studying at universities in Turkey where its sample consists of 669 students (330 women and 339 men) in total who are studying in various departments (Faculty of Science, Faculty of Letters, and Physical Education and Sports School) of Mugla University. In th...

International Conference on the Conservation of the Lesser Spotted Eagle, Košická Belá, Slovakia, 2014

Directory of Open Access Journals (Sweden)

Guziová Zuzana

2015-06-01

Full Text Available Medzinárodná konferencia o ochrane orla kriklavého (Aquila pomarina sa konala 25. - 27. septembra 2014 v Penzióne Lesanka v Košickej Belej na Slovensku. Zorganizovala ju Ochrana dravcov na Slovensku (RPS v spolupráci s Východoslovenskou energetikou Holding a.s. Konferencia bola zameraná na prípravu podkladov pre aktualizáciu európskeho akcného plánu pre orla kriklavého, zdielanie informácií o biológii a ekológia druhu a na výmenu skúseností s osvedcenými alebo inovatívnymi opatreniami pre zachovanie orla kriklavého. Konferencie sa zúcastnilo celkom 59 úcastníkov zo 14 krajín. Na konferencii odznelo 17 príspevkov a bolo prezentovaných 7 posterov. Niektoré z týchto príspevkov sú publikované v casopise Slovak Raptor Journal 9 (2015, dalších 23 príspevkov sú publikované formou konferencných abstraktov. Program konferencie zahrnal aj 2 exkurzie, pocas ktorých mali úcastníci možnost vidiet ukážku inštalácie konzolových chrániciek na stlpoch 22 kV elektrického vedenia a typické biotopy orla kriklavého. Konferencia bola organizovaná v rámci projektu LIFE09NAT/SK/000396 Ochrana orla kriklavého na Slovensku, ktorý realizovala Ochrana dravcov na Slovensku, Východoslovenská energetika Holding a.s., Stredoslovenská energetika, a.s. a Stredoslovenská energetika-Distribúcia, a.s. Projekt bol spolufinancovaný Európskou úniou prostredníctvom financného nástroja LIFE a Ministerstvom životného prostredia Slovenskej republiky.

Disease: H00238 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available H00238 Fanconi anemia Fanconi anemia (FA), a recessive syndrome with both autosomal and X-linked inheritance, features diverse clinical symptoms, such as progressive bone marrow failures, chromosomal instability and susceptibility to cancer. To date, 13 FA gene products have been identified, which cooperate in a common DNA damage-activated signaling pathway regulating DNA repair (the FA pathway). Hematologic disease FANCA [HSA:2175] [KO:K10888] FANCB [HSA:2187] [KO:K10889] FANCC [HSA:2176] [KO:K10890] BRCA2 [HSA:675] [KO:K08775] FANCD2 [HSA:2177] [KO:K10891] FANCE [HSA:2178] [KO:K10892] FANCF [HSA:2188] [KO:K10893] FANCG [HSA:2189] [KO:K10894] FANCI [HSA:55215] [KO:K10895] BRIP1 [HSA:83990] [KO:K15362] FANCL [HSA:55120] [KO:K10606] FANCM [HSA:57697] [KO:K10896] FANCN [HSA:79728] [KO:K10897] RAD51C [HSA:5889] [KO:K10870] RAD51 [HSA:5888] [KO:K04482] XRCC2 [HSA:7516] [KO:K10879] MAD2L2 [HSA:10459] [KO:K13728] ... ICD-10: D61.0 OMIM: 227650 300514 227645 605724 227646 600901 603467 609053 609054 608111 609644 610832 614082 613390 617244 617247 617243 PMID:18995829 ... AUTHORS ... Cohn MA, D'Andrea AD ... TITLE ... Chromatin recruitment of DNA repair p...roteins: lessons from the fanconi anemia...D, D'Andrea AD, Soulier J ... TITLE ... Biallelic inactivation of REV7 is associated with Fanconi anemia... ... TITLE ... The Fanconi anemia...Kolling FW 4th, Howlett NG

Bērnu mārketinga attīstība Latvijas lielāko pārtikas produktu ražotāju tirgus darbībās

OpenAIRE

Lūse, Ieva

2010-01-01

Uzņēmumi visā pasaulē arvien vairāk sāka apzināties bērnu potenciālu tirgū un aktivizē savu komunikāciju ar bērnu auditoriju. Bērni vienlaicīgi tirgū pilda vairākas lomas kā patērētāji, iniciatori, ietekmētāji un lēmēji par pirkumu un pircēji šodien un nākotnē, kļūstot par daudzu uzņēmumu produkcijas pamata patērētājiem. Ņemot vērā tēmas aktualitāti autore par maģistra darba mērķi izvirza apzināt un analizēt lielāko Latvijas pārtikas produktu ražotāju aktivitāti bērnu mārketing...

KO86 METAR

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

KO87 METAR

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

KO18 METAR

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

KO69 METAR

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

KO57 METAR

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

KO88 METAR

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

KO22 METAR

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

KO54 METAR

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

Třeboňský list rytíře Karla staršího Kořenského z Terešova na Komařicích a Zborově z 18. června 1619 (Příspěvek k poznání politických postojů jihočeské nižší šlechty za stavovského povstání)

Czech Academy of Sciences Publication Activity Database

Sterneck, Tomáš

2012-01-01

Roč. 49, č. 1 (2012), s. 26-49 ISSN 1212-0596 Institutional support: RVO:67985963 Keywords : history * Revolt of the Bohemian Estates * Karel the Elder Kořenský of Terešov Subject RIV: AB - History

Genetic Diversity of Koala Retroviral Envelopes

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Wenqin Xu

2015-03-01

Full Text Available Genetic diversity, attributable to the low fidelity of reverse transcription, recombination and mutation, is an important feature of infectious retroviruses. Under selective pressure, such as that imposed by superinfection interference, gammaretroviruses commonly adapt their envelope proteins to use alternative receptors to overcome this entry block. The first characterized koala retroviruses KoRV subgroup A (KoRV-A were remarkable in their absence of envelope genetic variability. Once it was determined that KoRV-A was present in all koalas in US zoos, regardless of their disease status, we sought to isolate a KoRV variant whose presence correlated with neoplastic malignancies. More than a decade after the identification of KoRV-A, we isolated a second subgroup of KoRV, KoRV-B from koalas with lymphomas. The envelope proteins of KoRV-A and KoRV-B are sufficiently divergent to confer the ability to bind and employ distinct receptors for infection. We have now obtained a number of additional KoRV envelope variants. In the present studies we report these variants, and show that they differ from KoRV-A and KoRV-B envelopes in their host range and superinfection interference properties. Thus, there appears to be considerable variation among KoRVs envelope genes suggesting genetic diversity is a factor following the KoRV-A infection process.

Proceedings of the Spring Meeting of the Society of Naval Architects of Japan (1996). Part 2. Structure, materials, welding, construction, and design; Nihon zosen gakkai (1996 nen) shunki koen ronbun maezuri. 2. Kozo, zairyo, yosetsu, kosaku, sekkei

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-12-31

This is a proceedings of the Spring Meeting of the Society of Naval Architects of Japan made public on May 15 and 16, 1996. In the basic research, the following are included: Basic studies on computer aided concurrent engineering for hull structure design and piping design; Fundamental study on the new method to estimate vibration level on a ship; Flat plate approximation in the three-dimensional slamming; Development of new finite element by source method, etc. As to fracture and cracks, Equivalent CTOD concept based on the local approach and its application to fracture performance evaluation of welded joints; Fracture mechanical modeling of brittle crack propagation and arrest of steel; An evaluation method for ductile crack propagation in pre-strained plates; Multiple fatigue cracks propagating in a stiffened panel, etc. Relating to fatigue strength, Fatigue life estimation of welded joints of an aluminum alloy under superimposed random load waves; Study on unified fatigue strength assessment method for welded structure, etc.

Proceedings of the Spring Meeting of the Society of Naval Architects of Japan (1996). Part 2. Structure, materials, welding, construction, and design; Nihon zosen gakkai (1996 nen) shunki koen ronbun maezuri. 2. Kozo, zairyo, yosetsu, kosaku, sekkei

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-31

This is a proceedings of the Spring Meeting of the Society of Naval Architects of Japan made public on May 15 and 16, 1996. In the basic research, the following are included: Basic studies on computer aided concurrent engineering for hull structure design and piping design; Fundamental study on the new method to estimate vibration level on a ship; Flat plate approximation in the three-dimensional slamming; Development of new finite element by source method, etc. As to fracture and cracks, Equivalent CTOD concept based on the local approach and its application to fracture performance evaluation of welded joints; Fracture mechanical modeling of brittle crack propagation and arrest of steel; An evaluation method for ductile crack propagation in pre-strained plates; Multiple fatigue cracks propagating in a stiffened panel, etc. Relating to fatigue strength, Fatigue life estimation of welded joints of an aluminum alloy under superimposed random load waves; Study on unified fatigue strength assessment method for welded structure, etc.

Comparison of the seasonal variability in abundance of the copepod Pseudocalanus newmani in Lagoon Notoro-ko and a coastal area of the southwestern Okhotsk Sea

Science.gov (United States)

Kitamura, Mitsuaki; Nakagawa, Yoshizumi; Nishino, Yasuto; Segawa, Susumu; Shiomoto, Akihiro

2018-03-01

Replacement of the warm water of the Soya Warm Current (SWC) and the cold water of the East Sakhalin Current (ESC) occurs seasonally along the coast of the southwestern Okhotsk Sea, and sea ice covers the surface during winter. Pseudocalanus newmani is one of the dominant copepods in coastal waters of the northern hemisphere. To better understand the population dynamics of the copepod P. newmani in coastal areas of the southwestern Okhotsk Sea, this study compared the seasonal variation in P. newmani abundance in Lagoon Notoro-ko and a coastal area of the Okhotsk Sea with regard to developmental stage. We sampled P. newmani in the lagoon, including during the ice cover season, and the coastal waters. Pseudocalanus newmani was abundant at both sites in spring. During summer-fall, adults disappeared from the populations at both sites, whereas the early developmental stages were abundant and dominated the population. Total length of adult females decreased toward summer at both sites. Pseudocalanus newmani abundance in the lagoon increased in early winter, and larger females were found in the populations at both sites. These phenomena at both sites corresponded with seasonal variation in water temperature caused by seasonal water-mass replacement and sea ice.

12038_2018_9735_MOESM1_ESM.doc

Indian Academy of Sciences (India)

KEGG ID. Pathway. Total transcripts with pathway annotation (5665). ko01100. Metabolic pathways. (611) [10.78%]. ko01110. Biosynthesis of secondary metabolites. (295) [5.2%]. ko01120. Microbial metabolism in diverse environments. (135) [2.3%]. ko03010. Ribosome. (112) [1.9%]. ko01230. Biosynthesis of amino acids.

KOALA RETROVIRUS: A REVIEW.

Science.gov (United States)

Kinney, Matthew E; Pye, Geoffrey W

2016-06-01

Koala retrovirus (KoRV) is a gammaretrovirus that has been identified in both captive and free-ranging koalas ( Phascolarctos cinereus ) with variable geographic distribution in Australia. KoRV is capable of both exogenous and endogenous transmission, which provides an interesting research platform for scientists to study active retrovirus endogenization into a host genome and offers veterinary scientists an opportunity to examine the clinical consequences of KoRV infection in koalas. Causation between KoRV and frequently recognized clinical conditions associated with immune suppression and neoplasia in koalas has not been definitively established, however research continues to evaluate a potential association. Three KoRV variants, KoRV-A, KoRV-B, and KoRV-J, have been the most thoroughly described and preliminary evidence suggests KoRV variability may be fundamental in host pathogenicity. In addition to reviewing what is currently known about KoRV, this article discusses treatment, management, and future research directions.

Kahramanmaraş Koşullarında Farklı Ekim Zamanlarının Isatis tinctoria ve Isatis buschiana Türlerinin Verim ve Bazı Agronomik Özellikleri Üzerine Etkileri

OpenAIRE

Çömlekcioğlu, N.; Efe, L.; Karaman, Ş.

2014-01-01

Bu çalışma, 2007-2008 ve 2008-2009 yetiştirme sezonunda Kahramanmaraş ekolojik koşullarında, farklı ekim zamanlarının (Ekim, Kasım, Şubat ve Mart) iki Isatis Isatis tinctoria ve Isatis buschiana türünün verim ve kalitesi üzerine etkisini belirlemek amacıyla tesadüf parselleri deneme desenine göre üç tekerrürlü olarak yürütülmüştür. Çalışmada Isatis türlerinin Kahramanmaraş iklim şartlarına en uygun ekim zamanının belirlenmesi amaçlanmıştır. İki yıllık sonuçlara göre, neredeyse incelenen bütün...

The effect of dietary antioxidant on the COPD risk: the community-based KoGES (Ansan–Anseong cohort

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Joshi P

2015-10-01

Full Text Available Pankaj Joshi,1,2 Woo Jin Kim,3,4 Sang-Ah Lee1–3 1Department of Preventive Medicine, 2BIT Medical Convergence Graduate Program, 3Department of Internal Medicine, 4Environmental Health Center, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do, South Korea Background: Dietary antioxidants have been suggested to have protective role against chronic obstructive pulmonary disease (COPD, but few prospective studies examined this relationship. The prospective study was conducted to evaluate the effect of dietary antioxidants on COPD risk and lung function in the Korean population.Methods: The data were collected from the community-based Korean Genome Epidemiology Study (KoGES cohort. To diagnose COPD, forced expiratory volume (FEV1 and forced vital capacity (FVC were measured by spirometry. The dietary intake of antioxidant vitamins was estimated from validated Food-Frequency Questionnaire. For the analysis, 325 COPD patients and 6,781 at risk subjects were selected from the cohort of 10,038 subjects. Multiple logistic regression models were used to examine the odds ratio (OR after adjusting for age, sex, marital status, income, history of asthma, history of tuberculosis, and smoking.Results: The risk of COPD was positively associated with aging, low education, low household income, lower body mass index, and cigarette smoking. The risk of COPD decreased with increase in the dietary vitamin C (ORQ1 vs Q5=0.66, Ptrend=0.03 and vitamin E (ORQ1 vs Q5=0.56, Ptrend=0.05 intake, predominantly, in men (Ptrend=0.01 and 0.05 for vitamins C and E, respectively. In addition, the lung function was significantly improved with increase in vitamins C (FEV1, P=0.04; FVC, P=0.03 and E (FEV1, P=0.03; FVC, P=0.04 intake. No statistically significant interactions were observed between smoking and vitamin C or E intake in relation to COPD risk among men.Conclusion: Our results suggest the independent beneficial effect of antioxidants, particularly

Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: the role of CD4+ T cells and IFN-gamma.

Science.gov (United States)

Day, Yuan-Ji; Huang, Liping; Ye, Hong; Li, Li; Linden, Joel; Okusa, Mark D

2006-03-01

A(2A) adenosine receptor (A(2A)R)-expressing bone marrow (BM)-derived cells contribute to the renal protective effect of A(2A) agonists in renal ischemia-reperfusion injury (IRI). We performed IRI in mice lacking T and B cells to determine whether A(2A)R expressed in CD4+ cells mediate protection from IRI. Rag-1 knockout (KO) mice were protected in comparison to wild-type (WT) mice when subjected to IRI. ATL146e, a selective A(2A) agonist, did not confer additional protection. IFN-gamma is an important early signal in IRI and is thought to contribute to reperfusion injury. Because IFN-gamma is produced by kidney cells and T cells we performed IRI in BM chimeras in which the BM of WT mice was reconstituted with BM from IFN-gamma KO mice (IFN-gamma KO-->WT chimera). We observed marked reduction in IRI in comparison to WT-->WT chimeras providing additional indirect support for the role of T cells. To confirm the role of CD4+ A(2A)R in mediating protection from IRI, Rag-1 KO mice were subjected to ischemia-reperfusion. The protection observed in Rag-1 KO mice was reversed in Rag-1 KO mice that were adoptively transferred WT CD4+ cells (WT CD4+-->Rag-1 KO) or A(2A) KO CD4+ cells (A(2A) KO CD4+-->Rag-1 KO). ATL146e reduced injury in WT CD4+-->Rag-1 KO mice but not in A(2A) KO CD4+-->Rag-1 KO mice. Rag-1 KO mice reconstituted with CD4+ cells derived from IFN-gamma KO mice (IFN-gamma CD4+-->Rag-1 KO) were protected from IRI; ATL146e conferred no additional protection. These studies demonstrate that CD4+ IFN-gamma contributes to IRI and that A(2A) agonists mediate protection from IRI through action on CD4+ cells.

Effect of constitutive inactivation of the myostatin gene on the gain in muscle strength during postnatal growth in two murine models.

Science.gov (United States)

Stantzou, Amalia; Ueberschlag-Pitiot, Vanessa; Thomasson, Remi; Furling, Denis; Bonnieu, Anne; Amthor, Helge; Ferry, Arnaud

2017-02-01

The effect of constitutive inactivation of the gene encoding myostatin on the gain in muscle performance during postnatal growth has not been well characterized. We analyzed 2 murine myostatin knockout (KO) models, (i) the Lee model (KO Lee ) and (ii) the Grobet model (KO Grobet ), and measured the contraction of tibialis anterior muscle in situ. Absolute maximal isometric force was increased in 6-month-old KO Lee and KO Grobet mice, as compared to wild-type mice. Similarly, absolute maximal power was increased in 6-month-old KO Lee mice. In contrast, specific maximal force (relative maximal force per unit of muscle mass was decreased in all 6-month-old male and female KO mice, except in 6-month-old female KO Grobet mice, whereas specific maximal power was reduced only in male KO Lee mice. Genetic inactivation of myostatin increases maximal force and power, but in return it reduces muscle quality, particularly in male mice. Muscle Nerve 55: 254-261, 2017. © 2016 Wiley Periodicals, Inc.

Education of mining engineers with the specialization in Rescue, fire and safety technique at the BERG Faculty of the Technical University of Košice

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Sedlatý Václav

2002-12-01

Full Text Available After the separation of Czechoslovakia, in 1993, the Mining Faculty (now BERG Faculty of the Technical University of Košice started a teaching program with the specialization in mining rescue, fire guard and safety technique at the Detachment in Prievidza, because of all the needs and conditions related to the education of engineers in the mentioned areas. During the last 10 years, the Detachment in Prievidza has been growing in terms of number of students. From the beginning of this period to present days 75 students graduated. The full-time studies last five years and the academic years are divided into two semesters of 15 weeks each. The semesters are finished by examination sessions. The first 2 years, in principle, include basic studies in mathematics, scientific subjects and some subjects related to earth sciences. The third and fourth year are generally devoted to basic technical subjects of mining and underground works, and then to rescue, fire and safety subjects. A practical work experience has to be gained by students in a mine or fire and safety stations. The practical training term is scheduled after the third academic year. During the last two semesters the students are preparing their Master’s degree thesis using a stay in the mine company or other firms to receive the necessary information and data.

Aircraft and ancillary materials. 2. ; Engine materials. Kokuki to sono shuhen zairyo. 2. ; Engine zairyo

Energy Technology Data Exchange (ETDEWEB)

1993-04-05

This paper summarizes materials for aircraft engines. Jet engines are the mainstream today, which are classified according to their operation process into a turbo jet engine, a turbo prop engine, a turbo shaft engine, and a turbo fan engine. Japan has produced 1543 engines in the past decade, almost all of which are supplied to the Defense Agency. Jet engines use mainly Ni-group heat-resistant alloys, titanium alloys and steels. Improvement of engine efficiency has caused turbine inlet temperatures to rise to 1400[degree]C to 1500[degree]C that give rise to grain boundary cracking. To prevent this, discussions are in progress on monocrystal blades replacing the conventional polycrystal precision casts. Intermetallic compounds including Al/Ti are expected especially of use as jet engine constructing materials from their high melting point and formability. Discussions are preceding on ceramics as to coating them intended of improving heat resistance. Composite materials have a problem of insufficient mechanical strength remaining unsolved. 8 figs., 5 tabs.

Mice Deficient in NF-κB p50 and p52 or RANK Have Defective Growth Plate Formation and Post-natal Dwarfism

OpenAIRE

Xing, Lianping; Chen, Di; Boyce, Brendan F.

2013-01-01

NF-κBp50/p52 double knockout (dKO) and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op/Op mice, which form few osteoclasts, and Src KO mice, which have osteoclasts with defective resorptive function, are osteopetrotic, but they are not dwarfed. Here, we compared the morphologic features of long bones from p50/p52 dKO, RANK KO, Op/Op and Src KO mice to attempt to explain the differences in their long bone lengths. We found that growth...

Roles of Toll-like receptors in allogeneic islet transplantation.

Science.gov (United States)

Ro, Han; Hong, Juho; Kim, Beom Seok; Lee, Eun Won; Kim, Myung-Gyu; Han, Kyu Hyun; Yeom, Hye-Jung; Lee, Eun Mi; Jeong, Jong Cheol; Oh, Kook-Hwan; Ahn, Curie; Yang, Jaeseok

2012-11-27

Toll-like receptors (TLRs) are involved in the rejection of solid organ allografts. However, the roles of TLRs in islets are still controversial. We investigated the roles of TLRs in donor islets together with those in recipients in allogeneic islet transplantation. To assess the roles of TLRs in either donor islets or recipients, allogeneic islet transplantation was performed using myeloid differentiation factor 88 (MyD88)-knockout (KO), TLR4-KO, or Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon-β (TRIF)-KO mice. Both polyriboinosinic polyribocytidylic acid and lipopolysaccharide (LPS) stimulation induced the mRNA expression of regulated and normal T cell expressed and secreted, interferon-γ-inducible protein-10, monocyte chemotactic protein-1, interleukin-8, and inducible nitric oxide synthase in murine islets, whereas the induction was attenuated in TRIF-KO, interferon-β promoter stimulator-1-KO, and TLR4-KO mice. When islets from MyD88-KO, TLR4-KO, or TRIF-KO C57BL/6 mice were transplanted to BALB/c recipients, graft survival was not better than that of wild-type (WT) islets. However, the survival of the MyD88-KO islet allograft was significantly prolonged when combined with anti-CD40L. In parallel, LPS stimulation in donor islets interfered with anti-CD40L blockade-mediated long-term survival of islet allografts in TLR4-KO recipients. LPS stimulation increased the perigraft infiltration of both T cells and macrophages. Then again, when islets from WT BALB/c mice were transplanted to MyD88-KO, TRIF-KO, or WT C57BL/6 mice, there was no difference in graft survival, although some of the MyD88-KO recipients obtained long-term graft survival. However, anti-CD40L prolonged graft survival significantly in MyD88-KO recipients. The absence of MyD88 in either donors or recipients decreased the perigraft infiltration of inflammatory cells when combined with anti-CD40L. TLRs in both donor islets and recipients are involved in islet allograft

Batı Karadeniz Bölgesi Düzce Ekolojik Koşulları Altında Bazı Ekmeklik Buğday Çeşitlerinin Yaprak Hastalıklarına Karşı Reaksiyonlarının Belirlenmesi

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Nedim Altın

2017-07-01

Full Text Available Bu çalışma, Batı Karadeniz Bölgesi Düzce ili ekolojik koşulları altında 19 adet ekmeklik buğday çeşidinin doğal enfeksiyon koşullarında yaprak hastalıklarına karşı reaksiyonlarının belirlenmesi amacıyla yürütülmüştür. Deneme tesadüf blokları deneme desenine uygun olarak 4 tekerrürlü olarak kurulmuş ve ekim işlemi 17.11.2015 tarihinde yapılmıştır. Hastalık gözlemleri ile ilgili çalışmalar; Septoria tritici etmeninin neden olduğu septorya yaprak lekesi hastalığı için süt olum dönemi başlangıcında, Puccinia striiformis etmeninin neden olduğu Sarı Pas hastalığı için çiçeklenme dönemi sonunda, Puccinia recondita etmeninin neden olduğu Kahverengi Pas için süt olum dönemi başlangıcında yapılmıştır. Tarla koşullarında doğal bulaşıklığa göre yapılan değerlendirme sonucunda hastalık oranları belirlenmiştir. Belirlenen hastalık şiddetine göre, septorya yaprak lekesi hastalığına karşı en hassas çeşidin % 60 hastalık şiddeti ile “Bereket”, en tolerant çeşidin ise %14 ile “Aslı” olduğu, Sarı Pas hastalığına karşı en hassas çeşidin %45,4 ile “Tekirdağ”, en tolerant çeşidin %0,6 ile “Midas” olduğu ve Kahverengi Pas hastalığına karşı ise en hassas çeşidin %22 ile “Tahirova” en tolerant çeşidin ise %0,2 ile “Midas” olduğu belirlenmiştir. Çalışma sonucunda elde edilen verilere göre septorya yaprak lekesi hastalığına karşı Aldane, Aslı, Konya 2002, Köprü, Masaccio ve Tosunbey, Sarı Pas hastalığına karşı Aslı, Esperia, Kate A1, Karasunya Odeska, Masaccio ve Midas, Kahverengi Pas hastalığına karşı ise Aldane, Aslı, Bereket, Köprü, Masaccio, Midas ve Tekirdağ çeşitlerinin ileride yapılacak ıslah çalışmaları için ümitvar olduğu görülmüştür.

Diacylglycerol lipase a knockout mice demonstrate metabolic and behavioral phenotypes similar to those of cannabinoid receptor 1 knockout mice

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David R Powell

2015-06-01

Full Text Available After creating >4650 knockouts (KOs of independent mouse genes, we screened them by high-throughput phenotyping and found that cannabinoid receptor 1 (Cnr1 KO mice had the same lean phenotype published by others. We asked if our KOs of DAG lipase a or b (Dagla or Daglb, which catalyze biosynthesis of the endocannabinoid (EC 2-Arachidonoylglycerol (2-AG, or Napepld, which catalyzes biosynthesis of the EC anandamide, shared the lean phenotype of Cnr1 KO mice. We found that Dagla KO mice, but not Daglb or Napepld KO mice, were among the leanest of 3651 chow-fed KO lines screened. In confirmatory studies, chow- or high fat diet-fed Dagla and Cnr1 KO mice were leaner than wild type (WT littermates; when data from multiple cohorts of adult mice were combined, body fat was 47% and 45% lower in Dagla and Cnr1 KO mice, respectively, relative to WT values. In contrast, neither Daglb nor Napepld KO mice were lean. Weanling Dagla KO mice ate less than WT mice and had body weight similar to pair-fed WT mice, and adult Dagla KO mice had normal activity and VO2 levels, similar to Cnr1 KO mice. Our Dagla and Cnr1 KO mice also had low fasting insulin, triglyceride and total cholesterol levels, and after a glucose challenge had normal glucose but very low insulin levels. Dagla and Cnr1 KO mice also showed similar responses to a battery of behavioral tests. These data suggest: 1 the lean phenotype of young Dagla and Cnr1 KO mice is mainly due to hypophagia; 2 in pathways where ECs signal through Cnr1 to regulate food intake and other metabolic and behavioral phenotypes observed in Cnr1 KO mice, Dagla alone provides the 2-AG that serves as the EC signal; and 3 small molecule Dagla inhibitors with a pharmacokinetic profile similar to that of Cnr1 inverse agonists are likely to mirror the ability of these Cnr1 inverse agonists to lower body weight and improve glycemic control in obese patients with type 2 diabetes, but may also induce undesirable neuropsychiatric

Loss of PDZK1 causes coronary artery occlusion and myocardial infarction in Paigen diet-fed apolipoprotein E deficient mice.

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Ayce Yesilaltay

2009-12-01

Full Text Available PDZK1 is a four PDZ-domain containing protein that binds to the carboxy terminus of the HDL receptor, scavenger receptor class B type I (SR-BI, and regulates its expression, localization and function in a tissue-specific manner. PDZK1 knockout (KO mice are characterized by a marked reduction of SR-BI protein expression ( approximately 95% in the liver (lesser or no reduction in other organs with a concomitant 1.7 fold increase in plasma cholesterol. PDZK1 has been shown to be atheroprotective using the high fat/high cholesterol ('Western' diet-fed murine apolipoprotein E (apoE KO model of atherosclerosis, presumably because of its role in promoting reverse cholesterol transport via SR-BI.Here, we have examined the effects of PDZK1 deficiency in apoE KO mice fed with the atherogenic 'Paigen' diet for three months. Relative to apoE KO, PDZK1/apoE double KO (dKO mice showed increased plasma lipids (33% increase in total cholesterol; 49 % increase in unesterified cholesterol; and 36% increase in phospholipids and a 26% increase in aortic root lesions. Compared to apoE KO, dKO mice exhibited substantial occlusive coronary artery disease: 375% increase in severe occlusions. Myocardial infarctions, not observed in apoE KO mice (although occasional minimal fibrosis was noted, were seen in 7 of 8 dKO mice, resulting in 12 times greater area of fibrosis in dKO cardiac muscle.These results show that Paigen-diet fed PDZK1/apoE dKO mice represent a new animal model useful for studying coronary heart disease and suggest that PDZK1 may represent a valuable target for therapeutic intervention.

Dgroup: DG02597 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available DG02597 Chemical ... DGroup Brexpiprazole ... D10309 ... Brexpiprazole (JAN/USAN/INN) ... ATC code: N05AX16 Antipsy...chotic DRD2 [HSA:1813] [KO:K04145] HTR1A [HSA:3350] [KO:K04153] HTR2A [HSA:3356] [KO:K04157] HTR7 [HSA:3363] [KO:K04163] ...

Photo catalyst; Ko shokubai

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-07-01

While titanium oxide is excited by the light, electrons of titanium oxide are taken away by the light energy to form positive holes. Water will be decomposed into hydrogen ion and hydroxy radical (OH) by these positive holes. This hydroxy radical is a strong reactive substance called active oxygen, it decomposes organisms. Besides this photo- catalyst function, the titanium oxide can also make surface of a substance superhydrophilic. The super hydrophilicity results in not forming water drops on the glass surface but spreading all over the surface to prevent a covering of fog on the glass surface. The published patents concerning the photo catalysts were 593 from Jan. 1998 to Jan. 1999. The applicant order is the first TOTO 143, the second Daikin Industry 19, the third Toshiba Raitech, Nitto Denko, Hitachi 17 respectively. (NEDO)

Fatigue strength of laser welded joint sheet; Laser yosetsu tsugite no hiro kyodo

Energy Technology Data Exchange (ETDEWEB)

Fujii, A; Yoshimura, T; Tsuboi, M; Takasago, T; Nishio, T [Toyota Motor Corp., Aichi (Japan)

1997-10-01

In this paper, fatigue strength of laser welded butt joint has been investigated. In order to obtain the influence of underfill and pitting, fatigue test was conducted with different sheet thickness and mechanical properties. Fatigue crack initiated at underfill and pitting in the weld metal. Stress concentration factor and hardness of the weld metal were considered to estimate fatigue limit. However, hardness of the weld metal has no significant effect on fatigue strength. As a result, fatigue strength was well estimated by hardness of base metal and stress concentration factor calculated from the shape of underflll and pitting. 7 refs., 9 figs., 5 tabs.

Loss of murine Gfi1 causes neutropenia and induces osteoporosis depending on the pathogen load and systemic inflammation.

Directory of Open Access Journals (Sweden)

Sven Geissler

Full Text Available Gfi1 is a key molecule in hematopoietic lineage development and mutations in GFI1 cause severe congenital neutropenia (SCN. Neutropenia is associated with low bone mass, but the underlying mechanisms are poorly characterized. Using Gfi1 knock-out mice (Gfi1-ko/ko as SCN model, we studied the relationship between neutropenia and bone mass upon different pathogen load conditions. Our analysis reveals that Gfi1-ko/ko mice kept under strict specific pathogen free (SPF conditions demonstrate normal bone mass and survival. However, Gfi1-ko/ko mice with early (nonSPF or late (SPF+nonSPF pathogen exposure develop low bone mass. Gfi1-ko/ko mice demonstrate a striking rise of systemic inflammatory markers according to elevated pathogen exposure and reduced bone mass. Elevated inflammatory cytokines include for instance Il-1b, Il-6, and Tnf-alpha that regulate osteoclast development. We conclude that low bone mass, due to low neutrophil counts, is caused by the degree of systemic inflammation promoting osteoclastogenesis.

Trps1 deficiency inhibits the morphogenesis of secondary hair follicles via decreased Noggin expression

Energy Technology Data Exchange (ETDEWEB)

Sun, Yujing [Department of Pathology, School of Medicine, Shandong University, Jinan Wen Hua Xi Road 44, Jinan 250012 (China); Nakanishi, Masako; Sato, Fuyuki; Oikawa, Kosuke [First Department of Pathology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-0012 (Japan); Muragaki, Yasuteru, E-mail: ymuragak@wakayama-med.ac.jp [First Department of Pathology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-0012 (Japan); Zhou, Gengyin, E-mail: zhougy@sdu.edu.cn [Department of Pathology, School of Medicine, Shandong University, Jinan Wen Hua Xi Road 44, Jinan 250012 (China)

2015-01-16

Highlights: • The number of secondary hair follicles is reduced by half in Trps1 KO embryonic skin compared to wild-type skin. • Noggin expression is significantly decreased and BMP signaling is promoted in Trps1 KO embryonic skin. • Treatment with a Noggin or BMP inhibitor rescued the decreased number of hair follicles in Trps1 KO skin graft cultures. • Cell proliferation and apoptosis of the epidermis were normalized by Noggin treatment. - Abstract: A representative phenotype of patients with tricho-rhino-phalangeal syndrome (TRPS) is sparse hair. To understand the developmental defects of these patient’s hair follicles, we analyzed the development of hair follicles histologically and biochemically using Trps1 deficient (KO) mice. First, we compared the numbers of primary hair follicles in wild-type (WT) and KO embryos at different developmental stages. No differences were observed in the E14.5 skins of WT and KO mice. However, at later time points, KO fetal skin failed to properly develop secondary hair follicles, and the number of secondary hair follicles present in E18.5 KO skin was approximately half compared to that of WT skin. Sonic hedgehog expression was significantly decreased in E17.5 KO skin, whereas no changes were observed in Eda/Edar expression in E14.5 or E17.5 skins. In addition, Noggin expression was significantly decreased in E14.5 and E17.5 KO skin compared to WT skin. In parallel with the suppression of Noggin expression, BMP signaling was promoted in the epidermal cells of KO skins compared to WT skins as determined by immunohistochemistry for phosphorylated Smad1/5/8. The reduced number of secondary hair follicles was restored in skin graft cultures treated with a Noggin and BMP inhibitor. Furthermore, decreased cell proliferation, and increased apoptosis in KO skin was rescued by Noggin treatment. Taken together, we conclude that hair follicle development in Trps1 KO embryos is impaired directly or indirectly by decreased Noggin

Trps1 deficiency inhibits the morphogenesis of secondary hair follicles via decreased Noggin expression

International Nuclear Information System (INIS)

Sun, Yujing; Nakanishi, Masako; Sato, Fuyuki; Oikawa, Kosuke; Muragaki, Yasuteru; Zhou, Gengyin

2015-01-01

Highlights: • The number of secondary hair follicles is reduced by half in Trps1 KO embryonic skin compared to wild-type skin. • Noggin expression is significantly decreased and BMP signaling is promoted in Trps1 KO embryonic skin. • Treatment with a Noggin or BMP inhibitor rescued the decreased number of hair follicles in Trps1 KO skin graft cultures. • Cell proliferation and apoptosis of the epidermis were normalized by Noggin treatment. - Abstract: A representative phenotype of patients with tricho-rhino-phalangeal syndrome (TRPS) is sparse hair. To understand the developmental defects of these patient’s hair follicles, we analyzed the development of hair follicles histologically and biochemically using Trps1 deficient (KO) mice. First, we compared the numbers of primary hair follicles in wild-type (WT) and KO embryos at different developmental stages. No differences were observed in the E14.5 skins of WT and KO mice. However, at later time points, KO fetal skin failed to properly develop secondary hair follicles, and the number of secondary hair follicles present in E18.5 KO skin was approximately half compared to that of WT skin. Sonic hedgehog expression was significantly decreased in E17.5 KO skin, whereas no changes were observed in Eda/Edar expression in E14.5 or E17.5 skins. In addition, Noggin expression was significantly decreased in E14.5 and E17.5 KO skin compared to WT skin. In parallel with the suppression of Noggin expression, BMP signaling was promoted in the epidermal cells of KO skins compared to WT skins as determined by immunohistochemistry for phosphorylated Smad1/5/8. The reduced number of secondary hair follicles was restored in skin graft cultures treated with a Noggin and BMP inhibitor. Furthermore, decreased cell proliferation, and increased apoptosis in KO skin was rescued by Noggin treatment. Taken together, we conclude that hair follicle development in Trps1 KO embryos is impaired directly or indirectly by decreased Noggin

Cabernet Sauvignon ve Merlot Şarapların Resveratrol Düzeyleri ve Ekolojik Koşulların Etkileri

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Belkıs Çaylak Adıgüzel

2015-02-01

Full Text Available Fitoaleksinler bitkilerde patojen enfeksiyonuna bir reaksiyon olarak veya çeşitli biyotik ve abiyotik tetikleyicilerin etkisi sonucu oluşan fenolik madde karakterli, düşük molekül ağırlıklı antimikrobiyal bileşiklerdir. Resveratrol (trans–3,5,4’-trihidroksistilben de bir fitoaleksin olup, asma (Vitis vinifera, yer fıstığı (Arachis hypogaea ve diğer pek çok bitki türünde yaprak veya diğer organlarda yüksek miktarlarda bulunabilmektedir. Resveratrol asmada gövde, sürgün ve yapraklar yanında, özellikle renkli çeşitlerin tane kabuğunda bol miktarda sentezlenebilmekte ve şarap yapımı sırasında şıraya, şıradan da şaraba geçmektedir. Son yıllarda resveratrolün antikanserojen özelliği ve antioksidan karakteri nedeniyle sağlık yararları üzerine yoğun araştırmalar yapılmakta ve günlük diyette alımı önerilmektedir. Bu çalışmada, Ege, Marmara ve Trakya Bölgeleri’nde üretilen kimi bağlardan sağlanan Cabernet sauvignon ve Merlot siyah üzümlerinden üretilmiş şaraplarda bulunan resveratrol miktarları Yüksek Performanslı Sıvı Kromatografisi yöntemi kullanılarak belirlenmiştir. Elde edilen sonuçlar bölgelerin ekolojik koşulları açısından birbirleriyle karşılaştırılmış ve resveratrol miktarı ile bu parametreler arasındaki korelasyon araştırılmıştır. Resveratrol konsantrasyonunun üzüm çeşidi ve bölgelerin iklim şartlarına bağlı olarak farklılıklar gösterebileceği görülmüştür.

The Probiotic Lactobacillus Prevents Citrobacter rodentium-Induced Murine Colitis in a TLR2-Dependent Manner.

Science.gov (United States)

Ryu, Seung-Hyun; Park, Jong-Hyung; Choi, Soo-Young; Jeon, Hee-Yeon; Park, Jin-Il; Kim, Jun-Young; Ham, Seung-Hoon; Choi, Yang-Kyu

2016-07-28

The main objective of this study was to investigate whether Lactobacillus rhamnosus GG (LGG) ameliorated the effects of Citrobactor rodentium infection in Toll-like receptor 2 (TLR2) knockout (KO) and TLR4 KO mice, as well as in wild-type C57BL/6 (B6) mice. TLR2 KO, TLR4 KO, and B6 mice were divided into three groups per each strain. Each group had an uninfected control group (n = 5), C. rodentium-infected group (n = 8), and LGG-pretreated C. rodentium-infected group (n = 8). The survival rate of B6 mice infected with C. rodentium was higher when pretreated with LGG. Pretreatment with LGG ameliorated C. rodentium-induced mucosal hyperplasia in B6 and TLR4 KO mice. However, in C-rodentium-infected TLR2 KO mice, mucosal hyperplasia persisted, regardless of pretreatment with LGG. In addition, LGG-pretreated B6 and TLR4 KO mice showed a decrease in spleen weight and downregulation of tumor necrosis factor alpha, interferon gamma, and monocyte chemotactic protein 1 mRNA expression compared with the non-pretreated group. In contrast, such changes were not observed in TLR2 KO mice, regardless of pretreatment with LGG. From the above results, we conclude that pretreatment with LGG ameliorates C. rodentium-induced colitis in B6 and TLR4 KO mice, but not in TLR2 KO mice. Therefore, LGG protects mice from C. rodentium-induced colitis in a TLR2-dependent manner.

Mice Deficient in NF-κB p50 and p52 or RANK Have Defective Growth Plate Formation and Post-natal Dwarfism.

Science.gov (United States)

Xing, Lianping; Chen, Di; Boyce, Brendan F

2013-12-01

NF-κBp50/p52 double knockout (dKO) and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op/Op mice, which form few osteoclasts, and Src KO mice, which have osteoclasts with defective resorptive function, are osteopetrotic, but they are not dwarfed. Here, we compared the morphologic features of long bones from p50/p52 dKO, RANK KO, Op/Op and Src KO mice to attempt to explain the differences in their long bone lengths. We found that growth plates in p50/p52 dKO and RANK KO mice are significantly thicker than those in WT mice due to a 2-3-fold increase in the hypertrophic chondrocyte zone associated with normal a proliferative chondrocyte zone. This growth plate abnormality disappears when animals become older, but their dwarfism persists. Op/Op or Src KO mice have relatively normal growth plate morphology. In-situ hybridization study of long bones from p50/p52 dKO mice showed marked thickening of the growth plate region containing type 10 collagen-expressing chondrocytes. Treatment of micro-mass chondrocyte cultures with RANKL did not affect expression levels of type 2 collagen and Sox9, markers for proliferative chondrocytes, but RANKL reduced the number of type 10 collagen-expressing hypertrophic chondrocytes. Thus, RANK/NF-κB signaling plays a regulatory role in post-natal endochondral ossification that maintains hypertrophic conversion and prevents dwarfism in normal mice.

Fizičko-hemijske i detonacione karakteristike nitraminskih eksploziva - RDX, HMX i CL-20 / Physico-chemical and detonation properties of nitramine explosives: RDX, HMX and CL-20

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Mirjana Anđelković-Lukić

2002-11-01

Full Text Available U radu su prikazane fizičko-hemijske i detonacione karakteristike nitraminskih brizantnih eksploziva, heksogena i oktogena, uporedene sa osobinama novog cikličnog nitraminskog eksploziva CL-20. Novi visokobrizantni eksploziv CL-20 postoji u četiri kristalne forme, stabilne na različitim temepraturama. Ima bolje detonacione karakteristike od heksogena i oktogena veću gustinu i brzinu detonacije, all mnogo veću osetljivost na udar i trenje, reda PETN. Zbog toga se ovaj eksploziv flegmatizuje sa polimerima etilenvinilacetatom (EVA i estanom. Da bi se povećale energetske performanse eksploziva i smanjila osetljivost na mehanička dejstva eksplozivu CL-20 dodaju se visokoenergetski materijali, fluoronitrojedinjenja (FEFO. / In this paper the physico-chemical and detonation properties of nitramine high explosives, hexogen and octogen, are presented and compared with a polycyclic nitramine high explosive CL-20. This new high explosive CL-20 exists in four crystalline forms, stable at different temperatures. CL-20 has better detonation properties than hexogen and octogen, higher density and detonation rate, but greater impact and friction sensitivity (of PETN class. So it is necessary to bond this explosive with polymers-ethylenvinil acetat (EVA and estane to reduce sensitivity to mechanical effects. CL-20 can be prepared by adding high energy materials-fluoro-nitro compounds (FEFO as regulators of energy performances.

The stretch zone of automotive steel sheets

Indian Academy of Sciences (India)

The stretch zone of automotive steel sheets. L' AMBRIŠKO1,∗ and L PEŠEK2. 1Institute of Structural Engineering, Faculty of Civil Engineering,. Technical University of Košice, Vysokoškolská 4, 042 00 Košice, Slovak Republic. 2Department of Materials Science, Faculty of Metallurgy,. Technical University of Košice, Letná 9, ...

Utilization of a numerical model of the temperature field of a conti-casting and prediction anti-break systems at the continuous caster of the steelworks division plant to improve the production quality at U. S Steel Košice, Ltd.

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Marek Pavol

2003-09-01

Full Text Available The paper presents the optimization elements at the continuous caster (CC from the view of the quality management and the costsavingprogram at U. S. Steel Košice, Ltd. The presented issue represents a partial problem within one step of the production cycle, which isconnected with the quality of slabs and with managing their subsequent processing. The solutions to reduce the occurrence of slab defectsare presented. The authors describe the utilization of anti-break systems of the continuous caster and an original numerical model of thenon-stationary temperature field of a conti-casting for CC#2, which solves current thermo-kinetic problems generally, as well asindividually. This model helps to optimize the primary and secondary cooling at CC#2 and to improve the surface quality of slabs.

Crucial Role of Mesangial Cell-derived Connective Tissue Growth Factor in a Mouse Model of Anti-Glomerular Basement Membrane Glomerulonephritis.

Science.gov (United States)

Toda, Naohiro; Mori, Kiyoshi; Kasahara, Masato; Ishii, Akira; Koga, Kenichi; Ohno, Shoko; Mori, Keita P; Kato, Yukiko; Osaki, Keisuke; Kuwabara, Takashige; Kojima, Katsutoshi; Taura, Daisuke; Sone, Masakatsu; Matsusaka, Taiji; Nakao, Kazuwa; Mukoyama, Masashi; Yanagita, Motoko; Yokoi, Hideki

2017-02-13

Connective tissue growth factor (CTGF) coordinates the signaling of growth factors and promotes fibrosis. Neonatal death of systemic CTGF knockout (KO) mice has hampered analysis of CTGF in adult renal diseases. We established 3 types of CTGF conditional KO (cKO) mice to investigate a role and source of CTGF in anti-glomerular basement membrane (GBM) glomerulonephritis. Tamoxifen-inducible systemic CTGF (Rosa-CTGF) cKO mice exhibited reduced proteinuria with ameliorated crescent formation and mesangial expansion in anti-GBM nephritis after induction. Although CTGF is expressed by podocytes at basal levels, podocyte-specific CTGF (pod-CTGF) cKO mice showed no improvement in renal injury. In contrast, PDGFRα promoter-driven CTGF (Pdgfra-CTGF) cKO mice, which predominantly lack CTGF expression by mesangial cells, exhibited reduced proteinuria with ameliorated histological changes. Glomerular macrophage accumulation, expression of Adgre1 and Ccl2, and ratio of M1/M2 macrophages were all reduced both in Rosa-CTGF cKO and Pdgfra-CTGF cKO mice, but not in pod-CTGF cKO mice. TGF-β1-stimulated Ccl2 upregulation in mesangial cells and macrophage adhesion to activated mesangial cells were decreased by reduction of CTGF. These results reveal a novel mechanism of macrophage migration into glomeruli with nephritis mediated by CTGF derived from mesangial cells, implicating the therapeutic potential of CTGF inhibition in glomerulonephritis.

Wild-type male offspring of fmr-1+/- mothers exhibit characteristics of the fragile X phenotype.

Science.gov (United States)

Zupan, Bojana; Toth, Miklos

2008-10-01

Fragile X syndrome is an X-linked disorder caused by the inactivation of the FMR-1 gene with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities, and hyperactivity. Males are more severely affected than heterozygote (H) females, who, as carriers, have a 50% chance of transmitting the mutated allele in each pregnancy. fmr-1 knockout (KO) mice reproduce fragile X symptoms, including hyperactivity, seizures, and abnormal sensory processing. In contrast to the expectation that wild-type (WT) males born to H (fmr-1(+/-)) mothers (H>WT) are behaviorally normal and indistinguishable from WT males born to WT mothers (WT>WT); here, we show that H>WT offspring are more active than WT>WT offspring and that their hyperactivity is similar to male KO mice born to H or KO (fmr-1(-/-)) mothers (H>KO/KO>KO). H>WT mice, however, do not exhibit seizures or abnormal sensory processing. Consistent with their hyperactivity, the effect of the D2 agonist quinpirole is reduced in H>WT as well as in H>KO and KO>KO mice compared to WT>WT offspring, suggesting a diminished feedback inhibition of dopamine release. Our data indicate that some aspects of hyperactivity and associated dopaminergic changes in 'fragile X' mice are a maternal fmr-1 genotype rather than an offspring fmr-1 genotype effect.

Distorted leukocyte migration, angiogenesis, wound repair and metastasis in Tspan8 and Tspan8/CD151 double knockout mice indicate complementary activities of Tspan8 and CD51.

Science.gov (United States)

Zhao, Kun; Erb, Ulrike; Hackert, Thilo; Zöller, Margot; Yue, Shijing

2018-02-01

The tetraspanin Tspan8 supports via associated integrins and proteases tumor progression and angiogenesis. To shed light on its activities in non-transformed cells, we generated a Tspan8 knockout (ko) mouse, comparing leukocyte migration, angiogenesis, wound healing and tumor growth with wild type, CD151ko and Tspan8/CD151ko (dbko) mice. CD151ko mice were included as CD151 activities resemble that of Tspan8, and dbko mice to exclude mutual substitution. Tspan8ko and dbko mice show no pathological phenotype. However, delayed type hypersensitivity reactions are mitigated in Tspan8ko mice, angiogenesis is severely impaired in Tspan8ko, CD151ko and dbko mice, with Tspan8 mostly affecting lymphangiogenesis. Distinct contributions of CD151 and Tspan8 to skin wound healing rely on preferentially CD151 anchoring basal keratinocytes and Tspan8 promoting motility. Proliferation of wounded skin keratinocytes is not affected. Metastasis formation of a melanoma and a Tspan8-expressing pancreatic cancer line was impaired in Tspan8ko and dbko mice, pointing towards a contribution of host Tspan8 to tumor progression. In line with the importance of tetraspanins in exosome-mediated intercellular communication, defects became mitigated by Tspan8/CD151-competent serum exosomes, which offers a most promising therapeutic option for chronic wounds and arteriosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Inactivation of the maternal fragile X gene results in sensitization of GABAB receptor function in the offspring.

Science.gov (United States)

Zupan, Bojana; Toth, Miklos

2008-12-01

Fragile X syndrome is an X-linked disorder caused by the inactivation of the FMR1 gene, with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities, and hyperactivity. Although fragile X syndrome is considered a typical Mendelian disorder, we have recently reported that the environment, specifically the fmr1(+/-) or fmr1(-/-) [H or knockout (KO)] maternal environment, elicits on its own a partial fragile X-like phenotype and can contribute to the overall phenotype of fmr1(-/0) (KO) male offspring. Genetically fmr1(+/0) (WT) males born to H females (H(maternal) > WT(offspring)), similar to KO male offspring born to H and KO mothers (H > KO and KO > KO), exhibit locomotor hyperactivity. These mice also showed reduced D(2) autoreceptor function, indicating a possible diminished feedback inhibition of dopamine (DA) release in the nigrostriatal and mesolimbic systems. The GABAergic system also regulates DA release, in part via presynaptic GABA(B) receptors (Rs) located on midbrain dopaminergic neurons. Here, we show that the locomotor inhibitory effect of the GABA(B)R agonist baclofen [4-amino-3-(4-chlorophenyl)-butanoic acid] is enhanced in all progeny of mutant mothers (H > WT, H > KO, and KO > KO) compared with WT > WT mice, irrespective of their own genotype. However, increased sensitivity to baclofen was selective and limited to the locomotor response because the muscle-relaxant and sedative effects of the drug were not altered by the maternal environment. These data show that GABA(B)R sensitization, traditionally induced pharmacologically, can also be elicited by the fmr1-deficient maternal environment.

An Essential Physiological Role for MCT8 in Bone in Male Mice.

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Leitch, Victoria D; Di Cosmo, Caterina; Liao, Xiao-Hui; O'Boy, Sam; Galliford, Thomas M; Evans, Holly; Croucher, Peter I; Boyde, Alan; Dumitrescu, Alexandra; Weiss, Roy E; Refetoff, Samuel; Williams, Graham R; Bassett, J H Duncan

2017-09-01

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compound mutants, which additionally lack the ability to convert the prohormone T4 to the active hormone T3. Prenatal skeletal development was normal in both Mct8KO and Mct8D1D2KO mice, whereas postnatal endochondral ossification and linear growth were delayed in both Mct8KO and Mct8D1D2KO mice. Furthermore, bone mass and mineralization were decreased in adult Mct8KO and Mct8D1D2KO mice, and compound mutants also had reduced bone strength. Delayed bone development and maturation in Mct8KO and Mct8D1D2KO mice is consistent with decreased thyroid hormone action in growth plate chondrocytes despite elevated serum T3 concentrations, whereas low bone mass and osteoporosis reflects increased thyroid hormone action in adult bone due to elevated systemic T3 levels. These studies identify an essential physiological requirement for MCT8 in chondrocytes, and demonstrate a role for additional transporters in other skeletal cells during adult bone maintenance.

Fatty acid desaturase 1 knockout mice are lean with improved glycemic control and decreased development of atheromatous plaque

Science.gov (United States)

Powell, David R; Gay, Jason P; Smith, Melinda; Wilganowski, Nathaniel; Harris, Angela; Holland, Autumn; Reyes, Maricela; Kirkham, Laura; Kirkpatrick, Laura L; Zambrowicz, Brian; Hansen, Gwenn; Platt, Kenneth A; van Sligtenhorst, Isaac; Ding, Zhi-Ming; Desai, Urvi

2016-01-01

Delta-5 desaturase (D5D) and delta-6 desaturase (D6D), encoded by fatty acid desaturase 1 (FADS1) and FADS2 genes, respectively, are enzymes in the synthetic pathways for ω3, ω6, and ω9 polyunsaturated fatty acids (PUFAs). Although PUFAs appear to be involved in mammalian metabolic pathways, the physiologic effect of isolated D5D deficiency on these pathways is unclear. After generating >4,650 knockouts (KOs) of independent mouse genes and analyzing them in our high-throughput phenotypic screen, we found that Fads1 KO mice were among the leanest of 3,651 chow-fed KO lines analyzed for body composition and were among the most glucose tolerant of 2,489 high-fat-diet-fed KO lines analyzed by oral glucose tolerance test. In confirmatory studies, chow- or high-fat-diet-fed Fads1 KO mice were leaner than wild-type (WT) littermates; when data from multiple cohorts of adult mice were combined, body fat was 38% and 31% lower in Fads1 male and female KO mice, respectively. Fads1 KO mice also had lower glucose and insulin excursions during oral glucose tolerance tests along with lower fasting glucose, insulin, triglyceride, and total cholesterol levels. In additional studies using a vascular injury model, Fads1 KO mice had significantly decreased femoral artery intima/media ratios consistent with a decreased inflammatory response in their arterial wall. Based on this result, we bred Fads1 KO and WT mice onto an ApoE KO background and fed them a Western diet for 14 weeks; in this atherogenic environment, aortic trees of Fads1 KO mice had 40% less atheromatous plaque compared to WT littermates. Importantly, PUFA levels measured in brain and liver phospholipid fractions of Fads1 KO mice were consistent with decreased D5D activity and normal D6D activity. The beneficial metabolic phenotype demonstrated in Fads1 KO mice suggests that selective D5D inhibitors may be useful in the treatment of human obesity, diabetes, and atherosclerotic cardiovascular disease. PMID:27382320

Global IP6K1 deletion enhances temperature modulated energy expenditure which reduces carbohydrate and fat induced weight gain

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Qingzhang Zhu

2017-01-01

Full Text Available Objective: IP6 kinases (IP6Ks regulate cell metabolism and survival. Mice with global (IP6K1-KO or adipocyte-specific (AdKO deletion of IP6K1 are protected from diet induced obesity (DIO at ambient (23 °C temperature. AdKO mice are lean primarily due to increased AMPK mediated thermogenic energy expenditure (EE. Thus, at thermoneutral (30 °C temperature, high fat diet (HFD-fed AdKO mice expend energy and gain body weight, similar to control mice. IP6K1 is ubiquitously expressed; thus, it is critical to determine to what extent the lean phenotype of global IP6K1-KO mice depends on environmental temperature. Furthermore, it is not known whether IP6K1 regulates AMPK mediated EE in cells, which do not express UCP1. Methods: Q-NMR, GTT, food intake, EE, QRT-PCR, histology, mitochondrial oxygen consumption rate (OCR, fatty acid metabolism assays, and immunoblot studies were conducted in IP6K1-KO and WT mice or cells. Results: Global IP6K1 deletion mediated enhancement in EE is impaired albeit not abolished at 30 °C. As a result, IP6K1-KO mice are protected from DIO, insulin resistance, and fatty liver even at 30 °C. Like AdKO, IP6K1-KO mice display enhanced adipose tissue browning. However, unlike AdKO mice, thermoneutrality only partly abolishes browning in IP6K1-KO mice. Cold (5 °C exposure enhances carbohydrate expenditure, whereas 23 °C and 30 °C promote fat oxidation in HFD-KO mice. Furthermore, IP6K1 deletion diminishes cellular fat accumulation via activation of the AMPK signaling pathway. Conclusions: Global deletion of IP6K1 ameliorates obesity and insulin resistance irrespective of the environmental temperature conditions, which strengthens its validity as an anti-obesity target. Keywords: IP6K, Obesity, Diabetes, Energy expenditure, β-oxidation

Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal phenotypes in rats and mice

Energy Technology Data Exchange (ETDEWEB)

Harrill, Joshua A. [The Hamner Institute for Health Sciences, Institute for Chemical Safety Sciences, RTP, NC 27709 (United States); Hukkanen, Renee R.; Lawson, Marie; Martin, Greg [The Dow Chemical Company, Midland, MI 48640 (United States); Gilger, Brian [North Carolina State University, College of Veterinary Medicine, Raleigh, NC 27606 (United States); Soldatow, Valerie [University of North Carolina, Department of Environmental Sciences and Engineering, Chapel Hill, NC 27599 (United States); LeCluyse, Edward L. [The Hamner Institute for Health Sciences, Institute for Chemical Safety Sciences, RTP, NC 27709 (United States); Budinsky, Robert A.; Rowlands, J. Craig [The Dow Chemical Company, Midland, MI 48640 (United States); Thomas, Russell S., E-mail: RThomas@thehamner.org [The Hamner Institute for Health Sciences, Institute for Chemical Safety Sciences, RTP, NC 27709 (United States)

2013-10-15

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which plays a role in the development of multiple tissues and is activated by a large number of ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to examine the roles of the AHR in both normal biological development and response to environmental chemicals, an AHR knockout (AHR-KO) rat model was created and compared with an existing AHR-KO mouse. AHR-KO rats harboring either 2-bp or 29-bp deletion mutation in exon 2 of the AHR were created on the Sprague–Dawley genetic background using zinc-finger nuclease (ZFN) technology. Rats harboring either mutation type lacked expression of AHR protein in the liver. AHR-KO rats were also insensitive to thymic involution, increased hepatic weight and the induction of AHR-responsive genes (Cyp1a1, Cyp1a2, Cyp1b1, Ahrr) following acute exposure to 25 μg/kg TCDD. AHR-KO rats had lower basal expression of transcripts for these genes and also accumulated ∼ 30–45-fold less TCDD in the liver at 7 days post-exposure. In untreated animals, AHR-KO mice, but not AHR-KO rats, had alterations in serum analytes indicative of compromised hepatic function, patent ductus venosus of the liver and persistent hyaloid arteries in the eye. AHR-KO rats, but not AHR-KO mice, displayed pathological alterations to the urinary tract: bilateral renal dilation (hydronephrosis), secondary medullary tubular and uroepithelial degenerative changes and bilateral ureter dilation (hydroureter). The present data indicate that the AHR may play significantly different roles in tissue development and homeostasis and toxicity across rodent species. - Highlights: • An AHR knockout rat was generated on a Sprague–Dawley outbred background. • AHR-KO rats lack expression of AHR protein. • AHR-KO rats are insensitive to TCDD-mediated effects. • Data suggests difference in the role of AHR in tissue development of rats and mice. • Abnormalities in vascular

Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal phenotypes in rats and mice

International Nuclear Information System (INIS)

Harrill, Joshua A.; Hukkanen, Renee R.; Lawson, Marie; Martin, Greg; Gilger, Brian; Soldatow, Valerie; LeCluyse, Edward L.; Budinsky, Robert A.; Rowlands, J. Craig; Thomas, Russell S.

2013-01-01

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which plays a role in the development of multiple tissues and is activated by a large number of ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to examine the roles of the AHR in both normal biological development and response to environmental chemicals, an AHR knockout (AHR-KO) rat model was created and compared with an existing AHR-KO mouse. AHR-KO rats harboring either 2-bp or 29-bp deletion mutation in exon 2 of the AHR were created on the Sprague–Dawley genetic background using zinc-finger nuclease (ZFN) technology. Rats harboring either mutation type lacked expression of AHR protein in the liver. AHR-KO rats were also insensitive to thymic involution, increased hepatic weight and the induction of AHR-responsive genes (Cyp1a1, Cyp1a2, Cyp1b1, Ahrr) following acute exposure to 25 μg/kg TCDD. AHR-KO rats had lower basal expression of transcripts for these genes and also accumulated ∼ 30–45-fold less TCDD in the liver at 7 days post-exposure. In untreated animals, AHR-KO mice, but not AHR-KO rats, had alterations in serum analytes indicative of compromised hepatic function, patent ductus venosus of the liver and persistent hyaloid arteries in the eye. AHR-KO rats, but not AHR-KO mice, displayed pathological alterations to the urinary tract: bilateral renal dilation (hydronephrosis), secondary medullary tubular and uroepithelial degenerative changes and bilateral ureter dilation (hydroureter). The present data indicate that the AHR may play significantly different roles in tissue development and homeostasis and toxicity across rodent species. - Highlights: • An AHR knockout rat was generated on a Sprague–Dawley outbred background. • AHR-KO rats lack expression of AHR protein. • AHR-KO rats are insensitive to TCDD-mediated effects. • Data suggests difference in the role of AHR in tissue development of rats and mice. • Abnormalities in vascular

Differentiation of Forebrain and Hippocampal Dopamine 1-Class Receptors, D1R and D5R, in Spatial Learning and Memory

Science.gov (United States)

Sariñana, Joshua; Tonegawa, Susumu

2017-01-01

Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R- specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus. D5R mRNA deletion was limited to the mPFC, the CA1 and DG hippocampal subregions. F-D1R/D5R KO mice were given water-maze training and displayed subtle spatial latency differences between genotypes and spatial memory deficits during both regular and reversal training. To differentiate forebrain D1R from D5R activation, forebrain restricted D1R KO (F-D1R KO) and D5R KO (F-D5R KO) mice were trained on the water-maze task. F-D1R KO animals exhibited escape latency deficits throughout regular and reversal training as well as spatial memory deficits during reversal training. F-D1R KO mice also showed perseverative behavior during the reversal spatial memory probe test. In contrast, F-D5R KO animals did not present observable deficits on the water-maze task. Because F-D1R KO mice showed water-maze deficits we tested the necessity of hippocampal D1R activation for spatial learning and memory. We trained DG restricted D1R KO (DG-D1R KO) mice on the water-maze task. DG-D1R KO mice did not present detectable spatial memory deficit, but did show subtle deficits during specific days of training. Our data provides evidence that forebrain D5R activation plays a unique role in spatial learning and memory in conjunction with D1R activation. Moreover, these data suggest that mPFC and striatal, but not DG D1R activation are essential for spatial learning and memory. PMID:26174222

Valid Competency Assessment in Higher Education

Directory of Open Access Journals (Sweden)

Olga Zlatkin-Troitschanskaia

2017-01-01

Full Text Available The aim of the 15 collaborative projects conducted during the new funding phase of the German research program Modeling and Measuring Competencies in Higher Education—Validation and Methodological Innovations (KoKoHs is to make a significant contribution to advancing the field of modeling and valid measurement of competencies acquired in higher education. The KoKoHs research teams assess generic competencies and domain-specific competencies in teacher education, social and economic sciences, and medicine based on findings from and using competency models and assessment instruments developed during the first KoKoHs funding phase. Further, they enhance, validate, and test measurement approaches for use in higher education in Germany. Results and findings are transferred at various levels to national and international research, higher education practice, and education policy.

Proliferation of Endogenous Retroviruses in the Early Stages of a Host Germ Line Invasion

Science.gov (United States)

Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D.; Roca, Alfred L.

2015-01-01

Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire–dam–progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5′- and 3′-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5′-LTR sequence was identical to the 3′-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200–49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. PMID:25261407

Effects of gender on locomotor sensitivity to amphetamine, body weight, and fat mass in regulator of G protein signaling 9 (RGS9) knockout mice.

Science.gov (United States)

Walker, Paul D; Jarosz, Patricia A; Bouhamdan, Mohamad; MacKenzie, Robert G

2015-01-01

Regulator of G-protein signaling (RGS) protein 9-2 is enriched in the striatum where it modulates dopamine and opioid receptor-mediated signaling. RGS9 knockout (KO) mice show increased psychostimulant-induced behavioral sensitization, as well as exhibit higher body weights and greater fat accumulation compared to wild-type (WT) littermates. In the present study, we found gender influences on each of these phenotypic characteristics. Female RGS9 KO mice exhibited greater locomotor sensitization to amphetamine (1.0mg/kg) treatment as compared to male RGS9 KO mice. Male RGS9 KO mice showed increased body weights as compared to male WT littermates, while no such differences were detected in female mice. Quantitative magnetic resonance showed that male RGS9 KO mice accumulated greater fat mass vs. WT littermates at 5months of age. Such observations could not be explained by increased caloric consumption since male and female RGS9 KO mice demonstrated equivalent daily food intake as compared to their respective WT littermates. Although indirect calorimetry methods found decreased oxygen consumption and carbon dioxide production during the 12-hour dark phase in male RGS9 KO vs. WT mice which are indicative of less energy expenditure, male RGS9 KO mice exhibited lower levels of locomotor activity during this period. Genotype had no effect on metabolic activities when KO and WT groups were compared under fasting vs. feeding treatments. In summary, these results highlight the importance of factoring gender into the experimental design since many studies conducted in RGS9 KO mice utilize locomotor activity as a measured outcome. Copyright © 2014. Published by Elsevier Inc.

Serotonin transporter protects the placental cells against apoptosis in caspase 3-independent pathway.

Science.gov (United States)

Hadden, Coedy; Fahmi, Tariq; Cooper, Anthonya; Savenka, Alena V; Lupashin, Vladimir V; Roberts, Drucilla J; Maroteaux, Luc; Hauguel-de Mouzon, Sylvie; Kilic, Fusun

2017-12-01

Serotonin (5-HT) and its specific transporter, SERT play important roles in pregnancy. Using placentas dissected from 18d gestational SERT-knock out (KO), peripheral 5-HT (TPH1)-KO, and wild-type (WT) mice, we explored the role of 5-HT and SERT in placental functions in detail. An abnormal thick band of fibrosis and necrosis under the giant cell layer in SERT-KO placentas appeared only moderately in TPH1-KO and minimally present in WT placentas. The majority of the changes were located at the junctional zone of the placentas in SERT. The etiology of these findings was tested with TUNEL assays. The placentas from SERT-KO and TPH1-KO showed 49- and 8-fold increase in TUNEL-positive cells without a concurrent change in the DNA repair or cell proliferation compared to WT placentas. While the proliferation rate in the embryos of TPH1-KO mice was 16-fold lower than the rate in gestational age matched embryos of WT or SERT-KO mice. These findings highlight an important role of continuous 5-HT signaling on trophoblast cell viability. SERT may contribute to protecting trophoblast cells against cell death via terminating the 5-HT signaling which changes cell death ratio in trophoblast as well as proliferation rate in embryos. However, the cell death in SERT-KO placentas is in caspase 3-independent pathway. © 2017 Wiley Periodicals, Inc.

K⁺-dependent paradoxical membrane depolarization and Na+ overload, major and reversible contributors to weakness by ion channel leaks

DEFF Research Database (Denmark)

Jurkat-Rott, Karin; Weber, Marc-André; Fauler, Michael

2009-01-01

Normal resting potential (P1) of myofibers follows the Nernst equation, exhibiting about -85 mV at a normal extracellular K(+) concentration ([K(+)](o)) of 4 mM. Hyperpolarization occurs with decreased [K(+)](o), although at [K(+)](o)

Cooperation of Rho family proteins Rac1 and Cdc42 in cartilage development and calcified tissue formation.

Science.gov (United States)

Ikehata, Mikiko; Yamada, Atsushi; Fujita, Koji; Yoshida, Yuko; Kato, Tadashi; Sakashita, Akiko; Ogata, Hiroaki; Iijima, Takehiko; Kuroda, Masahiko; Chikazu, Daichi; Kamijo, Ryutaro

2018-04-20

Rac1 and Cdc42, Rho family low molecular weight G proteins, are intracellular signaling factors that transmit various information from outside to inside cells. Primarily, they are known to control various biological activities mediated by actin cytoskeleton reorganization, such as cell proliferation, differentiation, and apoptosis. In order to investigate the functions of Rac1 and Cdc42 in bone formation, we prepared cartilage-specific double conditional knockout mice, Rac1 fl/fl ; Cdc42 fl/fl ; Col2-Cre (Rac1: Cdc42 dcKO mice), which died just after birth, similar to Cdc42 fl/fl ; Col2-Cre mice (Cdc42 cKO mice). Our findings showed that the long tubule bone in Rac1: Cdc42 dcKO mice was shorter than that in Rac1 fl/fl ; Col2-Cre mice (Rac1 cKO mice) and Cdc42 cKO mice. Abnormal skeleton formation was also observed and disordered columnar formation in the growth plate of the Rac1: Cdc42 dcKO mice was more severe as compared to the Rac1 cKO and Cdc42 cKO mice. Together, these results suggest that Rac1 and Cdc42 have cooperating roles in regulation of bone development. Copyright © 2018 Elsevier Inc. All rights reserved.

One hundred twenty years of koala retrovirus evolution determined from museum skins

DEFF Research Database (Denmark)

Avila Arcos, Maria del Carmen; Ho, Simon Y. W.; Ishida, Yasuko

2013-01-01

Although endogenous retroviruses are common across vertebrate genomes, the koala retrovirus (KoRV) is the only retrovirus known to be currently invading the germ line of its host. KoRV is believed to have first infected koalas in northern Australia less than two centuries ago. We examined Ko......RV in 28 koala museum skins collected in the late 19th and 20th centuries and deep sequenced the complete proviral envelope region from five northern Australian specimens. Strikingly, KoRV env sequences were conserved among koalas collected over the span of a century, and two functional motifs that affect...... viral infectivity were fixed across the museum koala specimens. We detected only 20 env polymorphisms among the koalas, likely representing derived mutations subject to purifying selection. Among northern Australian koalas, KoRV was already ubiquitous by the late 19th century, suggesting that Ko...

Dgroup: DG00997 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available ctive disorder ... DG01716 ... Drugs for alcohol dependence ATC code: N07BB04 Alcoholic agent OPRM1 [HSA:4988] [KO:K04215] OPRK1 [HSA:4986] [KO:K04214] OPRD1 [HSA:4985] [KO:K04213] ...

Subunit composition of seed storage proteins in high-protein soybean genotypes Composição de subunidades de proteínas de reserva em genótipos de soja com alto teor de proteína

Directory of Open Access Journals (Sweden)

Ksenija Taski-Ajdukovic

2010-07-01

Full Text Available The objective of this work was to quantify the accumulation of the major seed storage protein subunits, β-conglycinin and glycinin, and how they influence yield and protein and oil contents in high-protein soybean genotypes. The relative accumulation of subunits was calculated by scanning SDS-PAGE gels using densitometry. The protein content of the tested genotypes was higher than control cultivar in the same maturity group. Several genotypes with improved protein content and with unchanged yield or oil content were developed as a result of new breeding initiatives. This research confirmed that high-protein cultivars accumulate higher amounts of glycinin and β-conglycinin. Genotypes KO5427, KO5428, and KO5429, which accumulated lower quantities of all subunits of glycinin and β-conglycinin, were the only exceptions. Attention should be given to genotypes KO5314 and KO5317, which accumulated significantly higher amounts of both subunits of glycinin, and to genotypes KO5425, KO5319, KO539 and KO536, which accumulated significantly higher amounts of β-conglycinin subunits. These findings suggest that some of the tested genotypes could be beneficial in different breeding programs aimed at the production of agronomically viable plants, yielding high-protein seed with specific composition of storage proteins for specific food applications.O objetivo deste trabalho foi quantificar o acúmulo das principais subunidades de proteínas de reserva da soja, β-conglicinina e glicinina, e como elas influenciam a produtividade e os conteúdos de proteína e de óleo em genótipos de soja com alto conteúdo de proteína. A acumulação relativa de subunidades foi calculada por escaneamento em géis SDS-PAGE, com uso de densitometria. O conteúdo de proteínas dos genótipos testados foi maior que o da cultivar controle dentro do mesmo grupo de maturação. Vários genótipos com conteúdo de proteína aumentado, mas com produtividade ou conteúdo de �

Grafičko-analitičko modeliranje maksirnalnih manevarskih sposobnosti zrakoplova u horizontalnoj ravnini

Directory of Open Access Journals (Sweden)

Berislav Grozdanić

2012-10-01

Full Text Available During the Croatian War the military forces of the RepublicofCroatia were faced both with foreseen and unforeseen demandsregarding successful airspace combat actions, requiringfull engagement of all human and physical resources of theCroatian Military Air Force.Military Air Force, the most sophisticated part of thearmed forces, has contributed to the success of the operationsby acting in and from airspace against ground and sea targets.The supersonic aircraft efficiency in combat action overairspace targets can be increased by acquiring knowledge regardingthe maximal maneuvering capabilities, application ofgraphic-analytic modeling during flight preparations, educationof pilots and other participants in order to maximally exploitthe aricraft capabilites applying the forced turn. Graphicanalyticmethod of preparing the pilot for combat mission isone of the methods used at a higher level of psychological, theoreticaland practical realizations of the next flight conditions.It is applied in order to increase the efficiency of air-combatand to reduce one's own losses.

IL-4 deficiency is associated with mechanical hypersensitivity in mice.

Directory of Open Access Journals (Sweden)

Nurcan Üçeyler

Full Text Available Interleukin-4 (IL-4 is an anti-inflammatory and analgesic cytokine that induces opioid receptor transcription. We investigated IL-4 knockout (ko mice to characterize their pain behavior before and after chronic constriction injury (CCI of the sciatic nerve as a model for neuropathic pain. We investigated opioid responsivity and measured cytokine and opioid receptor gene expression in the peripheral and central nervous system (PNS, CNS of IL-4 ko mice in comparison with wildtype (wt mice. Naïve IL-4 ko mice displayed tactile allodynia (wt: 0.45 g; ko: 0.18 g; p<0.001, while responses to heat and cold stimuli and to muscle pressure were not different. No compensatory changes in the gene expression of tumor necrosis factor-alpha (TNF, IL-1β, IL-10, and IL-13 were found in the PNS and CNS of naïve IL-4 ko mice. However, IL-1β gene expression was stronger in the sciatic nerve of IL-4 ko mice (p<0.001 28 days after CCI and only IL-4 ko mice had elevated IL-10 gene expression (p = 0.014. Remarkably, CCI induced TNF (p<0.01, IL-1β (p<0.05, IL-10 (p<0.05, and IL-13 (p<0.001 gene expression exclusively in the ipsilateral spinal cord of IL-4 ko mice. The compensatory overexpression of the anti-inflammatory and analgesic cytokines IL-10 and IL-13 in the spinal cord of IL-4 ko mice may explain the lack of genotype differences for pain behavior after CCI. Additionally, CCI induced gene expression of μ, κ, and δ opioid receptors in the contralateral cortex and thalamus of IL-4 ko mice, paralleled by fast onset of morphine analgesia, but not in wt mice. We conclude that a lack of IL-4 leads to mechanical sensitivity; the compensatory hyperexpression of analgesic cytokines and opioid receptors after CCI, in turn, protects IL-4 ko mice from enhanced pain behavior after nerve lesion.

Mice with a targeted deletion of the type 2 deiodinase are insulin resistant and susceptible to diet induced obesity.

Directory of Open Access Journals (Sweden)

Alessandro Marsili

Full Text Available The type 2 iodothyronine deiodinase (D2 converts the pro-hormone thyroxine into T3 within target tissues. D2 is essential for a full thermogenic response of brown adipose tissue (BAT, and mice with a disrupted Dio2 gene (D2KO have an impaired response to cold. BAT is also activated by overfeeding.After 6-weeks of HFD feeding D2KO mice gained 5.6% more body weight and had 28% more adipose tissue. Oxygen consumption (V0(2 was not different between genotypes, but D2KO mice had an increased respiratory exchange ratio (RER, suggesting preferential use of carbohydrates. Consistent with this, serum free fatty acids and β-hydroxybutyrate were lower in D2KO mice on a HFD, while hepatic triglycerides were increased and glycogen content decreased. Neither genotype showed glucose intolerance, but D2KO mice had significantly higher insulin levels during GTT independent of diet. Accordingly, during ITT testing D2KO mice had a significantly reduced glucose uptake, consistent with insulin resistance. Gene expression levels in liver, muscle, and brown and white adipose tissue showed no differences that could account for the increased weight gain in D2KO mice. However, D2KO mice have higher PEPCK mRNA in liver suggesting increased gluconeogenesis, which could also contribute to their apparent insulin resistance.We conclude that the loss of the Dio2 gene has significant metabolic consequences. D2KO mice gain more weight on a HFD, suggesting a role for D2 in protection from diet-induced obesity. Further, D2KO mice appear to have a greater reliance on carbohydrates as a fuel source, and limited ability to mobilize and to burn fat. This results in increased fat storage in adipose tissue, hepatic steatosis, and depletion of liver glycogen in spite of increased gluconeogenesis. D2KO mice are also less responsive to insulin, independent of diet-induced obesity.

Proliferation of endogenous retroviruses in the early stages of a host germ line invasion.

Science.gov (United States)

Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D; Roca, Alfred L

2015-01-01

Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire-dam-progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5'- and 3'-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5'-LTR sequence was identical to the 3'-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200-49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Analysis of glomerulosclerosis and atherosclerosis in lecithin cholesterol acyltransferase-deficient mice.

Science.gov (United States)

Lambert, G; Sakai, N; Vaisman, B L; Neufeld, E B; Marteyn, B; Chan, C C; Paigen, B; Lupia, E; Thomas, A; Striker, L J; Blanchette-Mackie, J; Csako, G; Brady, J N; Costello, R; Striker, G E; Remaley, A T; Brewer, H B; Santamarina-Fojo, S

2001-05-04

To evaluate the biochemical and molecular mechanisms leading to glomerulosclerosis and the variable development of atherosclerosis in patients with familial lecithin cholesterol acyl transferase (LCAT) deficiency, we generated LCAT knockout (KO) mice and cross-bred them with apolipoprotein (apo) E KO, low density lipoprotein receptor (LDLr) KO, and cholesteryl ester transfer protein transgenic mice. LCAT-KO mice had normochromic normocytic anemia with increased reticulocyte and target cell counts as well as decreased red blood cell osmotic fragility. A subset of LCAT-KO mice accumulated lipoprotein X and developed proteinuria and glomerulosclerosis characterized by mesangial cell proliferation, sclerosis, lipid accumulation, and deposition of electron dense material throughout the glomeruli. LCAT deficiency reduced the plasma high density lipoprotein (HDL) cholesterol (-70 to -94%) and non-HDL cholesterol (-48 to -85%) levels in control, apoE-KO, LDLr-KO, and cholesteryl ester transfer protein-Tg mice. Transcriptome and Western blot analysis demonstrated up-regulation of hepatic LDLr and apoE expression in LCAT-KO mice. Despite decreased HDL, aortic atherosclerosis was significantly reduced (-35% to -99%) in all mouse models with LCAT deficiency. Our studies indicate (i) that the plasma levels of apoB containing lipoproteins rather than HDL may determine the atherogenic risk of patients with hypoalphalipoproteinemia due to LCAT deficiency and (ii) a potential etiological role for lipoproteins X in the development of glomerulosclerosis in LCAT deficiency. The availability of LCAT-KO mice characterized by lipid, hematologic, and renal abnormalities similar to familial LCAT deficiency patients will permit future evaluation of LCAT gene transfer as a possible treatment for glomerulosclerosis in LCAT-deficient states.

Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice.

Science.gov (United States)

Mergia, Evanthia; Thieme, Manuel; Hoch, Henning; Daniil, Georgios; Hering, Lydia; Yakoub, Mina; Scherbaum, Christina Rebecca; Rump, Lars Christian; Koesling, Doris; Stegbauer, Johannes

2018-03-23

Nitric oxide (NO) modulates renal blood flow (RBF) and kidney function and is involved in blood pressure (BP) regulation predominantly via stimulation of the NO-sensitive guanylyl cyclase (NO-GC), existing in two isoforms, NO-GC1 and NO-GC2. Here, we used isoform-specific knockout (KO) mice and investigated their contribution to renal hemodynamics under normotensive and angiotensin II-induced hypertensive conditions. Stimulation of the NO-GCs by S -nitrosoglutathione (GSNO) reduced BP in normotensive and hypertensive wildtype (WT) and NO-GC2-KO mice more efficiently than in NO-GC1-KO. NO-induced increase of RBF in normotensive mice did not differ between the genotypes, but the respective increase under hypertensive conditions was impaired in NO-GC1-KO. Similarly, inhibition of endogenous NO increased BP and reduced RBF to a lesser extent in NO-GC1-KO than in NO-GC2-KO. These findings indicate NO-GC1 as a target of NO to normalize RBF in hypertension. As these effects were not completely abolished in NO-GC1-KO and renal cyclic guanosine monophosphate (cGMP) levels were decreased in both NO-GC1-KO and NO-GC2-KO, the results suggest an additional contribution of NO-GC2. Hence, NO-GC1 plays a predominant role in the regulation of BP and RBF, especially in hypertension. However, renal NO-GC2 appears to compensate the loss of NO-GC1, and is able to regulate renal hemodynamics under physiological conditions.

Serotonin/dopamine interactions in a hyperactive mouse: reduced serotonin receptor 1B activity reverses effects of dopamine transporter knockout.

Directory of Open Access Journals (Sweden)

Frank Scott Hall

Full Text Available Knockout (KO mice that lack the dopamine transporter (SL6A3; DAT display increased locomotion that can be attenuated, under some circumstances, by administration of drugs that normally produce psychostimulant-like effects, such as amphetamine and methylphenidate. These results have led to suggestions that DAT KO mice may model features of attention deficit hyperactivity disorder (ADHD and that these drugs may act upon serotonin (5-HT systems to produce these unusual locomotor decreasing effects. Evidence from patterns of brain expression and initial pharmacologic studies led us to use genetic and pharmacologic approaches to examine the influence of altered 5-HT1B receptor activity on hyperactivity in DAT KO mice. Heterozygous 5-HT1B KO and pharmacologic 5-HT1B antagonism both attenuated locomotor hyperactivity in DAT KO mice. Furthermore, DAT KO mice with reduced, but not eliminated, 5-HT1B receptor expression regained cocaine-stimulated locomotion, which was absent in DAT KO mice with normal levels of 5-HT1B receptor expression. Further experiments demonstrated that the degree of habituation to the testing apparatus determined whether cocaine had no effect on locomotion in DAT KO or reduced locomotion, helping to resolve differences among prior reports. These findings of complementation of the locomotor effects of DAT KO by reducing 5-HT1B receptor activity underscore roles for interactions between specific 5-HT receptors and dopamine (DA systems in basal and cocaine-stimulated locomotion and support evaluation of 5-HT1B antagonists as potential, non-stimulant ADHD therapeutics.

Glycolysis and mitochondrial respiration in mouse LDHC-null sperm.

Science.gov (United States)

Odet, Fanny; Gabel, Scott; London, Robert E; Goldberg, Erwin; Eddy, Edward M

2013-04-01

We demonstrated previously that a knockout (KO) of the lactate dehydrogenase type C (Ldhc) gene disrupted male fertility and caused a considerable reduction in sperm glucose consumption, ATP production, and motility. While that study used mice with a mixed genetic background, the present study used C57BL/6 (B6) and 129S6 (129) Ldhc KO mice. We found that B6 KO males were subfertile and 129 KO males were infertile. Sperm from 129 wild-type (WT) mice have a lower glycolytic rate than sperm from B6 WT mice, resulting in a greater reduction in ATP production in 129 KO sperm than in B6 KO sperm. The lower glycolytic rate in 129 sperm offered a novel opportunity to examine the role of mitochondrial respiration in sperm ATP production and motility. We observed that in media containing a mitochondrial substrate (pyruvate or lactate) as the sole energy source, ATP levels and progressive motility in 129 KO sperm were similar to those in 129 WT sperm. However, when glucose was added, lactate was unable to maintain ATP levels or progressive motility in 129 KO sperm. The rate of respiration (ZO2) was high when 129 KO or WT sperm were incubated with lactate alone, but addition of glucose caused a reduction in ZO2. These results indicate that in the absence of glucose, 129 sperm can produce ATP via oxidative phosphorylation, but in the presence of glucose, oxidative phosphorylation is suppressed and the sperm utilize aerobic glycolysis, a phenomenon known as the Crabtree effect.

Molecular Alterations in a Mouse Cardiac Model of Friedreich Ataxia

DEFF Research Database (Denmark)

Anzovino, Amy; Chiang, Shannon; Brown, Bronwyn E

2017-01-01

mechanisms. Using a mouse conditional frataxin knockout (KO) model in the heart and skeletal muscle, we examined the Nrf2 pathway in these tissues. Frataxin KO results in fatal cardiomyopathy, whereas skeletal muscle was asymptomatic. In the KO heart, protein oxidation and a decreased glutathione...

Disease: H01195 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available 8] [KO:K01110] HOXD13 [HSA:3239] [KO:K09298] ZIC3 [HSA:7547] [KO:K18487] ... Maternal diabetes, uterine vascular pathology, and infertil...ity treatment ... ICD-10: Q87.2 MeSH: C564752 OMIM: 276950 192350 314390 PMID:20849

Akt2/LDLr double knockout mice display impaired glucose tolerance and develop more complex atherosclerotic plaques than LDLr knockout mice

NARCIS (Netherlands)

Rensing, Katrijn L.; de Jager, Saskia C. A.; Stroes, Erik S.; Vos, Mariska; Twickler, Marcel Th B.; Dallinga-Thie, Geesje M.; de Vries, Carlie J. M.; Kuiper, Johan; Bot, Ilze; von der Thüsen, Jan H.

2014-01-01

To characterize the phenotype of Akt2/low-density-lipoprotein receptor double knockout (dKO) (Akt2/LDLr dKO) mice with respect to insulin resistance and features of atherosclerotic plaque progression. Metabolic profile and atherosclerotic plaque progression were compared between LDLr KO mice and

Western Diet-Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment.

Science.gov (United States)

Jena, Prasant K; Sheng, Lili; Liu, Hui-Xin; Kalanetra, Karen M; Mirsoian, Annie; Murphy, William J; French, Samuel W; Krishnan, Viswanathan V; Mills, David A; Wan, Yu-Jui Yvonne

2017-08-01

Patients who have liver cirrhosis and liver cancer also have reduced farnesoid X receptor (FXR). The current study analyzes the effect of diet through microbiota that affect hepatic inflammation in FXR knockout (KO) mice. Wild-type and FXR KO mice were on a control (CD) or Western diet (WD) for 10 months. In addition, both CD- and WD-fed FXR KO male mice, which had hepatic lymphocyte and neutrophil infiltration, were treated by vancomycin, polymyxin B, and Abx (ampicillin, neomycin, metronidazole, and vancomycin). Mice were subjected to morphological analysis as well as gut microbiota and bile acid profiling. Male WD-fed FXR KO mice had the most severe steatohepatitis. FXR KO also had reduced Firmicutes and increased Proteobacteria, which could be reversed by Abx. In addition, Abx eliminated hepatic neutrophils and lymphocytes in CD-fed, but not WD-fed, FXR KO mice. Proteobacteria and Bacteroidetes persisted in WD-fed FXR KO mice even after Abx treatment. Only polymyxin B could reduce hepatic lymphocytes in WD-fed FXR KO mice. The reduced hepatic inflammation by antibiotics was accompanied by decreased free and conjugated secondary bile acids as well as changes in gut microbiota. Our data revealed that Lactococcus, Lactobacillus, and Coprococcus protect the liver from inflammation. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A cell-death-defying factor, anamorsin mediates cell growth through inactivation of PKC and p38MAPK

International Nuclear Information System (INIS)

Saito, Yuri; Shibayama, Hirohiko; Tanaka, Hirokazu; Tanimura, Akira; Kanakura, Yuzuru

2011-01-01

Research highlights: → Anamorsin (AM) (also called CIAPIN-1) is a cell-death-defying factor. → Biological mechanisms of AM functions have not been elucidated yet. → PKCθ , PKCδ and p38MAPK were more phosphorylated in AM deficient MEF cells. → AM may negatively regulates PKCs and p38MAPK in MEF cells. -- Abstract: Anamorsin (AM) plays crucial roles in hematopoiesis and embryogenesis. AM deficient (AM KO) mice die during late gestation; AM KO embryos are anemic and very small compared to wild type (WT) embryos. To determine which signaling pathways AM utilizes for these functions, we used murine embryonic fibroblast (MEF) cells generated from E-14.5 AM KO or WT embryos. Proliferation of AM KO MEF cells was markedly retarded, and PKCθ, PKCδ, and p38MAPK were more highly phosphorylated in AM KO MEF cells. Expression of cyclinD1, the target molecule of p38MAPK, was down-regulated in AM KO MEF cells. p38MAPK inhibitor as well as PKC inhibitor restored expression of cyclinD1 and cell growth in AM KO MEF cells. These data suggest that PKCθ, PKCδ, and p38MAPK activation lead to cell cycle retardation in AM KO MEF cells, and that AM may negatively regulate novel PKCs and p38MAPK in MEF cells.

One Hundred Twenty Years of Koala Retrovirus Evolution Determined from Museum Skins

OpenAIRE

?vila-Arcos, Mar?a C.; Ho, Simon Y.W.; Ishida, Yasuko; Nikolaidis, Nikolas; Tsangaras, Kyriakos; H?nig, Karin; Medina, Rebeca; Rasmussen, Morten; Fordyce, Sarah L.; Calvignac-Spencer, S?bastien; Willerslev, Eske; Gilbert, M. Thomas P.; Helgen, Kristofer M.; Roca, Alfred L.; Greenwood, Alex D.

2013-01-01

Although endogenous retroviruses are common across vertebrate genomes, the koala retrovirus (KoRV) is the only retrovirus known to be currently invading the germ line of its host. KoRV is believed to have first infected koalas in northern Australia less than two centuries ago. We examined KoRV in 28 koala museum skins collected in the late 19th and 20th centuries and deep sequenced the complete proviral envelope region from five northern Australian specimens. Strikingly, KoRV env sequences we...

Mechanized and robotized welding in shipbuilding; Zosen ni okeru yosetsu no jidoka robot ka

Energy Technology Data Exchange (ETDEWEB)

Kanda, Y. [Ishikawajima-Harima Heavy Industries Co. Ltd., Tokyo (Japan)

1997-12-01

Large-scale ships such as VLCC are built at the Kure No.1 Works of IHI (Ishikawajima-Harima Heavy Industry). This paper introduces current status of mechanized and robotized welding at the works. For the sub-assembly with short weld length and horizontal fillet, simplified automatic welders are used in which mag-welding method using CO2 is adopted. The frequent wound welding of member ends can be automatically conducted using welders developed by IHI. In the large-scale assembly processes, remarkable rationalization and highly accurate assembly of flat plate welding have been promoted. Tankers, container ships, and bulk carriers can be treated at the same time. Teaching times of welding robots can be greatly reduced by a technique called parametric treatment. In the future, it is essential to enhance the accuracy of members by introducing the laser cutting during machining processes. Completely self-type mechanization is required as well as large-output laser welding and sensor technology. 3 refs., 12 figs., 2 tabs.

Drug: D09600 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available ulfide bridge: 2-7) ... Chemical group: DG01352 ... Davalintide is a Amylin [HSA:3375] [KO:K08039] mimetic peptide. Treatment of obesity... and obesity-related disorders CALCR [HSA:799] [KO:K04576]; CALCRL [HSA:10203] [KO:K04577] ... CAS: 863919-85-1 PubChem: 124490340 ...

Increased lipolysis and energy expenditure in a mouse model with severely impaired glucagon secretion

DEFF Research Database (Denmark)

Lou, Phing-How; Gustavsson, Natalia; Wang, Yue

2011-01-01

and increased capacity for fatty acid transport and oxidation in synaptotagmin-7 KO mice. Furthermore, expression of uncoupling protein 3 (UCP3) in skeletal muscle was approximately doubled in the KO mice compared with control mice. CONCLUSIONS: These results show that the lean phenotype in synaptotagmin-7 KO...

DBI/ACBP loss-of-function does not affect anxiety-like behaviour but reduces anxiolytic responses to diazepam in mice

DEFF Research Database (Denmark)

Budry, Lionel; Bouyakdan, Khalil; Tobin, Stephanie

2016-01-01

. Male and female ACBP(GFAP) KO and ACBP KO mice do not show significant changes in anxiety-like behaviour compared to control littermates during elevated plus maze (EPM) and open field (OF) tests. Surprisingly, ACBP(GFAP) KO and ACBP KO mice were unresponsive to the anxiolytic effect of a low dose...... of diazepam during EPM tests. In conclusion, our experiments using genetic ACBP loss-of-function models suggest that endozepines deficiency does not affect anxiety-like behaviour in mice and impairs the anxiolytic action of diazepam....

Konserve Nar Kalitesi Üzerine Dolgu Sıvısı ve Depolama Koşullarının Etkileri

Directory of Open Access Journals (Sweden)

Hakan Benli

2015-02-01

Full Text Available Bu çalışmada dane nar konservesi üzerine, üç farklı dolgu sıvısı (şurup, şurup ve meyve suyu karışımı (1:1, w/w, meyve suyu kullanımının, iki farklı depolama sıcaklığının (oda sıcaklığı ve +5°C ve saklama süresinin (8 ay etkilerinin belirlenmesi amaçlanmıştır. Bu amaçla Hicaz ve Silifke Aşısı çeşitleri kullanılmıştır. Çalışmada, taze narların bazı fiziksel ve kimyasal özellikleri ile; nar konservelerinin pH, titrasyon asitliği, toplam fenolik madde, antosiyanin, renk yoğunluğu ve renk tonu değerleri belirlenmiştir. Dolgu sıvısı şurup olan örneklerin en düşük renk tonu değerlerine sahip olduğu saptanmıştır. Soğukta depolanan nar konservelerinin, antosiyanin ve toplam fenolik madde miktarlarının daha yüksek olduğu belirlenmiştir. Ayrıca soğukta depolanan örneklerin, renk yoğunluğu değerlerinin daha yüksek ve renk tonu değerlerinin daha düşük olduğu tespit edilmiştir. Depolama süresince antosiyanin miktarlarında azalma, renk yoğunluğu değerlerinde düşme ve renk tonu değerlerinde artış belirlenmiştir. Çalışmada, tüm koşullarda nar danesinin bütünlüğünün büyük ölçüde korunduğu belirlenmiştir. Yapılan duyusal analiz sonucunda en yüksek beğeniyi soğuk depoda saklanan ve dolgu sıvısı şurup olan örnekler kazanmıştır.

Timescales of mixing and storage for Keanakāko`i Tephra magmas (1500-1820 C.E.), Kīlauea Volcano, Hawai`i

Science.gov (United States)

Lynn, Kendra J.; Garcia, Michael O.; Shea, Thomas; Costa, Fidel; Swanson, Donald A.

2017-09-01

The last 2500 years of activity at Kīlauea Volcano (Hawai`i) have been characterized by centuries-long periods dominated by either effusive or explosive eruptions. The most recent period of explosive activity produced the Keanakāko`i Tephra (KT; ca. 1500-1820 C.E.) and occurred after the collapse of the summit caldera (1470-1510 C.E.). Previous studies suggest that KT magmas may have ascended rapidly to the surface, bypassing storage in crustal reservoirs. The storage conditions and rapid ascent hypothesis are tested here using chemical zoning in olivine crystals and thermodynamic modeling. Forsterite contents (Fo; [Mg/(Mg + Fe) × 100]) of olivine core and rim populations are used to identify melt components in Kīlauea's prehistoric (i.e., pre-1823) plumbing system. Primitive (≥Fo88) cores occur throughout the 300+ years of the KT period; they originated from mantle-derived magmas that were first mixed and stored in a deep crustal reservoir. Bimodal olivine populations (≥Fo88 and Fo83-84) record repeated mixing of primitive magmas and more differentiated reservoir components shallower in the system, producing a hybrid composition (Fo85-87). Phase equilibria modeling using MELTS shows that liquidus olivine is not stable at depths >17 km. Thus, calculated timescales likely record mixing and storage within the crust. Modeling of Fe-Mg and Ni zoning patterns (normal, reverse, complex) reveal that KT magmas were mixed and stored for a few weeks to several years before eruption, illustrating a more complex storage history than direct and rapid ascent from the mantle as previously inferred for KT magmas. Complexly zoned crystals also have smoothed compositional reversals in the outer 5-20 µm rims that are out of Fe-Mg equilibrium with surrounding glasses. Diffusion models suggest that these rims formed within a few hours to a few days, indicating that at least one additional, late-stage mixing event may have occurred shortly prior to eruption. Our study

Evaluating mice lacking serum carboxylesterase as a behavioral model for nerve agent intoxication.

Science.gov (United States)

Dunn, Emily N; Ferrara-Bowens, Teresa M; Chachich, Mark E; Honnold, Cary L; Rothwell, Cristin C; Hoard-Fruchey, Heidi M; Lesyna, Catherine A; Johnson, Erik A; Cerasoli, Douglas M; McDonough, John H; Cadieux, C Linn

2018-06-07

Mice and other rodents are typically utilized for chemical warfare nerve agent research. Rodents have large amounts of carboxylesterase in their blood, while humans do not. Carboxylesterase nonspecifically binds to and detoxifies nerve agent. The presence of this natural bioscavenger makes mice and other rodents poor models for studies identifying therapeutics to treat humans exposed to nerve agents. To obviate this problem, a serum carboxylesterase knockout (Es1 KO) mouse was created. In this study, Es1 KO and wild type (WT) mice were assessed for differences in gene expression, nerve agent (soman; GD) median lethal dose (MLD) values, and behavior prior to and following nerve agent exposure. No expression differences were detected between Es1 KO and WT mice in more than 34 000 mouse genes tested. There was a significant difference between Es1 KO and WT mice in MLD values, as the MLD for GD-exposed WT mice was significantly higher than the MLD for GD-exposed Es1 KO mice. Behavioral assessments of Es1 KO and WT mice included an open field test, a zero maze, a Barnes maze, and a sucrose preference test (SPT). While sex differences were observed in various measures of these tests, overall, Es1 KO mice behaved similarly to WT mice. The two genotypes also showed virtually identical neuropathological changes following GD exposure. Es1 KO mice appear to have an enhanced susceptibility to GD toxicity while retaining all other behavioral and physiological responses to this nerve agent, making the Es1 KO mouse a more human-like model for nerve agent research.

Koala retroviruses: characterization and impact on the life of koalas

Science.gov (United States)

2013-01-01

Koala retroviruses (KoRV) have been isolated from wild and captive koalas in Australia as well as from koala populations held in zoos in other countries. They are members of the genus Gammaretrovirus, are most closely related to gibbon ape leukemia virus (GaLV), feline leukemia virus (FeLV) and porcine endogenous retrovirus (PERV) and are likely the result of a relatively recent trans-species transmission from rodents or bats. The first KoRV to be isolated, KoRV-A, is widely distributed in the koala population in both integrated endogenous and infectious exogenous forms with evidence from museum specimens older than 150 years, indicating a relatively long engagement with the koala population. More recently, additional subtypes of KoRV that are not endogenized have been identified based on sequence differences and host cell receptor specificity (KoRV-B and KoRV-J). A specific association with fatal lymphoma and leukemia has been recently suggested for KoRV-B. In addition, it has been proposed that the high viral loads found in many animals may lead to immunomodulation resulting in a higher incidence of diseases such as chlamydiosis. Although the molecular basis of this immunomodulation is still unclear, purified KoRV particles and a peptide corresponding to a highly conserved domain in the envelope protein have been shown to modulate cytokine expression in vitro, similar to that induced by other gammaretroviruses. While much is still to be learned, KoRV induced lymphoma/leukemia and opportunistic disease arising as a consequence of immunomodulation are likely to play an important role in the stability of koala populations both in the wild and in captivity. PMID:24148555

Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER) leads to left ventricular dysfunction and adverse remodeling: A sex-specific gene profiling analysis.

Science.gov (United States)

Wang, Hao; Sun, Xuming; Chou, Jeff; Lin, Marina; Ferrario, Carlos M; Zapata-Sudo, Gisele; Groban, Leanne

2017-08-01

Activation of G protein-coupled estrogen receptor (GPER) by its agonist, G1, protects the heart from stressors such as pressure-overload, ischemia, a high-salt diet, estrogen loss, and aging, in various male and female animal models. Due to nonspecific effects of G1, the exact functions of cardiac GPER cannot be concluded from studies using systemic G1 administration. Moreover, global knockdown of GPER affects glucose homeostasis, blood pressure, and many other cardiovascular-related systems, thereby confounding interpretation of its direct cardiac actions. We generated a cardiomyocyte-specific GPER knockout (KO) mouse model to specifically investigate the functions of GPER in cardiomyocytes. Compared to wild type mice, cardiomyocyte-specific GPER KO mice exhibited adverse alterations in cardiac structure and impaired systolic and diastolic function, as measured by echocardiography. Gene deletion effects on left ventricular dimensions were more profound in male KO mice compared to female KO mice. Analysis of DNA microarray data from isolated cardiomyocytes of wild type and KO mice revealed sex-based differences in gene expression profiles affecting multiple transcriptional networks. Gene Set Enrichment Analysis (GSEA) revealed that mitochondrial genes are enriched in GPER KO females, whereas inflammatory response genes are enriched in GPER KO males, compared to their wild type counterparts of the same sex. The cardiomyocyte-specific GPER KO mouse model provides us with a powerful tool to study the functions of GPER in cardiomyocytes. The gene expression profiles of the GPER KO mice provide foundational information for further study of the mechanisms underlying sex-specific cardioprotection by GPER. Copyright © 2016 Elsevier B.V. All rights reserved.

Koala retroviruses: characterization and impact on the life of koalas.

Science.gov (United States)

Denner, Joachim; Young, Paul R

2013-10-23

Koala retroviruses (KoRV) have been isolated from wild and captive koalas in Australia as well as from koala populations held in zoos in other countries. They are members of the genus Gammaretrovirus, are most closely related to gibbon ape leukemia virus (GaLV), feline leukemia virus (FeLV) and porcine endogenous retrovirus (PERV) and are likely the result of a relatively recent trans-species transmission from rodents or bats. The first KoRV to be isolated, KoRV-A, is widely distributed in the koala population in both integrated endogenous and infectious exogenous forms with evidence from museum specimens older than 150 years, indicating a relatively long engagement with the koala population. More recently, additional subtypes of KoRV that are not endogenized have been identified based on sequence differences and host cell receptor specificity (KoRV-B and KoRV-J). A specific association with fatal lymphoma and leukemia has been recently suggested for KoRV-B. In addition, it has been proposed that the high viral loads found in many animals may lead to immunomodulation resulting in a higher incidence of diseases such as chlamydiosis. Although the molecular basis of this immunomodulation is still unclear, purified KoRV particles and a peptide corresponding to a highly conserved domain in the envelope protein have been shown to modulate cytokine expression in vitro, similar to that induced by other gammaretroviruses. While much is still to be learned, KoRV induced lymphoma/leukemia and opportunistic disease arising as a consequence of immunomodulation are likely to play an important role in the stability of koala populations both in the wild and in captivity.

The role of DNA polymerase ζ in translesion synthesis across bulky DNA adducts and cross-links in human cells

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Tetsuya, E-mail: suzukite@hiroshima-u.ac.jp [Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Grúz, Petr; Honma, Masamitsu [Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Adachi, Noritaka [Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027 (Japan); Nohmi, Takehiko [Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan)

2016-09-15

Highlights: • Human cells knockout (KO) and expressing catalytically dead (CD) variant of DNA polymerase ζ (Pol ζ) have been established by gene targeting techniques with Nalm-6 cells. • Both Pol ζ KO and CD cells displayed prolonged cell cycle and higher incidence of micronucleus formation than the wild-type cells in the absence of exogenous genotoxic treatments. • Pol ζ protects human cells from genotoxic stresses that induce bulky DNA lesions and cross-links. • Pol ζ plays quite limited roles in protection against strand-breaks in DNA. - Abstract: Translesion DNA synthesis (TLS) is a cellular defense mechanism against genotoxins. Defects or mutations in specialized DNA polymerases (Pols) involved in TLS are believed to result in hypersensitivity to various genotoxic stresses. Here, DNA polymerase ζ (Pol ζ)-deficient (KO: knockout) and Pol ζ catalytically dead (CD) human cells were established and their sensitivity towards cytotoxic activities of various genotoxins was examined. The CD cells were engineered by altering the DNA sequence encoding two amino acids essential for the catalytic activity of Pol ζ, i.e., D2781 and D2783, to alanines. Both Pol ζ KO and CD cells displayed a prolonged cell cycle and higher incidence of micronuclei formation than the wild-type (WT) cells in the absence of exogenous genotoxic treatments, and the order of abnormality was CD > KO > WT cells. Both KO and CD cells exhibited higher sensitivity towards the killing effects of benzo[a]pyrene diol epoxide, mitomycin C, potassium bromate, N-methyl-N′-nitro-N-nitrosoguanidine, and ultraviolet C irradiation than WT cells, and there were no differences between the sensitivities of KO and CD cells. Interestingly, neither KO nor CD cells were sensitive to the cytotoxic effects of hydrogen peroxide. Since KO and CD cells displayed similar sensitivities to the genotoxins, we employed only KO cells to further examine their sensitivity to other genotoxic agents. KO cells were

The role of DNA polymerase ζ in translesion synthesis across bulky DNA adducts and cross-links in human cells

International Nuclear Information System (INIS)

Suzuki, Tetsuya; Grúz, Petr; Honma, Masamitsu; Adachi, Noritaka; Nohmi, Takehiko

2016-01-01

Highlights: • Human cells knockout (KO) and expressing catalytically dead (CD) variant of DNA polymerase ζ (Pol ζ) have been established by gene targeting techniques with Nalm-6 cells. • Both Pol ζ KO and CD cells displayed prolonged cell cycle and higher incidence of micronucleus formation than the wild-type cells in the absence of exogenous genotoxic treatments. • Pol ζ protects human cells from genotoxic stresses that induce bulky DNA lesions and cross-links. • Pol ζ plays quite limited roles in protection against strand-breaks in DNA. - Abstract: Translesion DNA synthesis (TLS) is a cellular defense mechanism against genotoxins. Defects or mutations in specialized DNA polymerases (Pols) involved in TLS are believed to result in hypersensitivity to various genotoxic stresses. Here, DNA polymerase ζ (Pol ζ)-deficient (KO: knockout) and Pol ζ catalytically dead (CD) human cells were established and their sensitivity towards cytotoxic activities of various genotoxins was examined. The CD cells were engineered by altering the DNA sequence encoding two amino acids essential for the catalytic activity of Pol ζ, i.e., D2781 and D2783, to alanines. Both Pol ζ KO and CD cells displayed a prolonged cell cycle and higher incidence of micronuclei formation than the wild-type (WT) cells in the absence of exogenous genotoxic treatments, and the order of abnormality was CD > KO > WT cells. Both KO and CD cells exhibited higher sensitivity towards the killing effects of benzo[a]pyrene diol epoxide, mitomycin C, potassium bromate, N-methyl-N′-nitro-N-nitrosoguanidine, and ultraviolet C irradiation than WT cells, and there were no differences between the sensitivities of KO and CD cells. Interestingly, neither KO nor CD cells were sensitive to the cytotoxic effects of hydrogen peroxide. Since KO and CD cells displayed similar sensitivities to the genotoxins, we employed only KO cells to further examine their sensitivity to other genotoxic agents. KO cells were

Modelling genetic reorganization in the mouse spinal cord affecting left-right coordination during locomotion

DEFF Research Database (Denmark)

Rybak, Ilya A.; Shevtsova, Natalia A.; Kiehn, Ole

2013-01-01

glutamatergic interneurons, whose axon guidance involves the EphA4 receptor. In EphA4 knockout (KO) and Netrin-1 KO mice, the normal left-right alternating pattern is replaced with a synchronized hopping gait, and the cord of DCC KO mice exhibits uncoordinated left and right oscillations. To investigate...

Loss of TGF-β signaling in osteoblasts increases basic-FGF and promotes prostate cancer bone metastasis.

Science.gov (United States)

Meng, Xiangqi; Vander Ark, Alexandra; Daft, Paul; Woodford, Erica; Wang, Jie; Madaj, Zachary; Li, Xiaohong

2018-04-01

TGF-β plays a central role in prostate cancer (PCa) bone metastasis, and it is crucial to understand the bone cell-specific role of TGF-β signaling in this process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2 gene specifically in osteoblasts (Tgfbr2 Col1CreERT KO) or in osteoclasts (Tgfbr2 LysMCre KO). We found that PCa-induced bone lesion development was promoted in the Tgfbr2 Col1CreERT KO mice, but was inhibited in the Tgfbr2 LysMCre KO mice, relative to their respective control Tgfbr2 FloxE2 littermates. Since metastatic PCa cells attach to osteoblasts when colonized in the bone microenvironment, we focused on the mechanistic studies using the Tgfbr2 Col1CreERT KO mouse model. We found that bFGF was upregulated in osteoblasts from PC3-injected tibiae of Tgfbr2 Col1CreERT KO mice and correlated with increased tumor cell proliferation, angiogenesis, amounts of cancer-associated fibroblasts and osteoclasts. In vitro studies showed that osteoblastogenesis was inhibited, osteoclastogenesis was stimulated, but PC3 viability was not affected, by bFGF treatments. Lastly, the increased PC3-induced bone lesions in Tgfbr2 Col1CreERT KO mice were significantly attenuated by blocking bFGF using neutralizing antibody, suggesting bFGF is a promising target inhibiting bone metastasis. Copyright © 2018 Elsevier B.V. All rights reserved.

Contribution of PPARγ in modulation of acrolein-induced inflammatory signaling in gp91phox knock-out mice.

Science.gov (United States)

Yousefipour, Zivar; Chug, Neha; Marek, Katarzyna; Nesbary, Alicia; Mathew, Joseph; Ranganna, Kasturi; Newaz, Mohammad A

2017-08-01

Oxidative stress and inflammation are major contributors to acrolein toxicity. Peroxisome proliferator activated receptor gamma (PPARγ) has antioxidant and anti-inflammatory effects. We investigated the contribution of PPARγ ligand GW1929 to the attenuation of oxidative stress in acrolein-induced insult. Male gp91 phox knock-out (KO) mice were treated with acrolein (0.5 mg·(kg body mass) -1 by intraperitoneal injection for 7 days) with or without GW1929 (GW; 0.5 mg·(kg body mass) -1 ·day -1 , orally, for 10 days). The livers were processed for further analyses. Acrolein significantly increased 8-isoprostane and reduced PPARγ activity (P acrolein-treated WT mice, and was reduced by GW1929 (by 65%). KO mice exhibited higher xanthine oxidase (XO). Acrolein increased XO and COX in WT mice and XO in KO mice. GW1929 significantly reduced COX in WT and KO mice and reduced XO in KO mice. Acrolein significantly reduced the total antioxidant status in WT and KO mice (P acrolein-treated WT mice. GW1929 reduced NF-κB levels (by 51%) in KO mice. Acrolein increased CD36 in KO mice (by 43%), which was blunted with GW1929. Data confirms that the generation of free radicals by acrolein is mainly through NAD(P)H, but other oxygenates play a role too. GW1929 may alleviate the toxicity of acrolein by attenuating NF-κB, COX, and CD36.

Citation trend and suggestions for improvement of impact factor of Journal of Korean Therapeutic Radiology and Oncology

International Nuclear Information System (INIS)

Kim, Seong Hwan; Hwang, Seong Su; Ahn, Myeong Im; Jeong, So Na

2006-01-01

To analyze the recent citation trend and to find a way to improve impact factor (IF) of the Journal of Korean Therapeutic Radiology and Oncology (JKSTRO) by analysis of Korean Medical Citation index (KoMCI) citation data of JKSTRO and comparison with that of mean citation data of all journals enlisted on KoMCI (KoMCI journals) during 2000-2005. All citation data of entire journals enlisted on KoMCI and JKSTRO from 2000 to 2005 were obtained from KoMCI. The trend of total and annual number of published articles and reference citations, total citations and self-citations per paper, IF and impact factor excluding self-citations (ZIF) were described and compared on both KoMCI journals an JKSTRO. Annual number of published articles was decreased for 6 years on both KoMCI journals and JKSTRO (32% and 38% reduction rate). The number of Korean journal references per article is 1.6 papers of JKSTRO comparing to 2.0 papers on KoMCI journals. The percentage of Korean references/total references increased from 5.0% in 2000 to 7.7% in 2005 on JKSTRO and from 8.5% in 2000 to 10.1% on KoMCI journals. The number of total citations received/paper on JKSTRO (average 1.333) is smaller than that of KoMCI journals (average 1.694), there was an increased rate of 67% in 2005 comparing to 2000. The percentage of self-citations/total citations (average 72%) on JKSTRO is slightly higher than that of KoMCI journals (average 61%)/ IF of JKSTRO was gradually improved and 0.144, 0.125, 0.088, 0.107, 0.187 and 0.203 in 2000-2005 respectively. However, ZIF of JKSTRO is steadily decreased from 0.038 in 2000 to 0.013 in 2005 except 0.044 in 2004. IF of JKSTRO was slightly improved but had some innate problem of smaller number of citations received . To make JKSTRO as a highly cited journal, the awareness of academic status of JKSTRO and active participation of every member of JKSTRO including encouraging self-citations of papers published recent 2 years and submission of English written papers, and

Zmiany czynności kory ruchowej mózgu po leczeniu botuliną u pacjentów ze stwardnieniem rozsianym i spazmem kończyn dolnych

Directory of Open Access Journals (Sweden)

Pavel Hok

2011-12-01

Full Text Available Miejscowe skurcze toniczne to powszechnie spotykany objaw stwardnienia rozsianego (łac. sclerosis multiplex, SM. Do ich zwalczania coraz częściej stosowany jest zastrzyk domięśniowy botuliny typu A. Do analizy statystycznej zaakceptowaliśmy 4 z 10 badanych pacjentów z SM i spastycznością kończyn dolnych oraz 5 zdrowych wolontariuszy. Pacjenci zostali poddani badaniu fMRI trzykrotnie: w tygodniu przed zastrzykiem botuliny A, a następnie w 4. i 12. tygodniu po iniekcji. Podczas badań fMRI probanci wykonywali zginanie i prostowanie stawu kolanowego według planu blokowego, przy czym faza czynna zamieniała się z fazą spoczynku w 15-sekundowych odstępach. Obraz przeciętnej aktywacji pacjentów podczas pierwszej sesji wskazywał, w porównaniu z grupą kontrolną, na istotny wzrost aktywacji obustronnej kory czuciowo-ruchowej płatu czołowego i ciemieniowego. Podczas drugiej sesji w 4. tygodniu aktywacja zmalała do tego stopnia, że statystycznie nie różniła się od zdrowej kontroli. Z kolei w obrazach trzeciej sesji po 12 tygodniach odnotowano w związku z wygaśnięciem efektu botuliny A ponowny wzrost aktywacji niemal do objętości pierwotnej. Wnioski: Stwierdzamy, że aktywacja kory ruchowej odzwierciedla zmiany w obwodowym układzie nerwowym zachodzące podczas leczenia za pomocą botuliny A, w czym prawdopodobnie pośredniczą zmiany w aferentacji. Jest to nowe odkrycie, aczkolwiek nie wykracza poza stwierdzenia podobnych badań przeprowadzonych innymi metodami.

Kıvırcık Cüce Koşin (Gallus gallus Testisindeki Bazı Glikokonjugatların Lektin Histokimyasal Olarak Belirlenmesi

Directory of Open Access Journals (Sweden)

Şeyda BÜYÜKYILDIRIM

2016-07-01

Full Text Available Bu çalışmada Kıvırcık Cüce Koşin (Gallus gallus testisindeki bazı glikokonjugatların lektin histokimyasal yöntemle belirlenmesi amaçlandı.  Glikokonjugat içeriğinin belirlenmesi amacıyla alınan doku kesitleri horseradish peroxidase  (HRP bağlı Canavalia ensiformis aglutinin (Con A, Glycine max aglutinin (SBA, Ulex europaeus aglutinin (UEA-I, Arachis hypogaea aglutinin (PNA ve Triticum vulgaris aglutinin (WGA lektinleri ile inkübe edildi. Uygulanan lektin histokimyasal yöntemler sonucunda spermatagonyum ve Leydig hücrelerinde çok güçlü Con A reaksiyonu gözlenirken, lamina proprianın peritübüler hücrelerinde reaksiyona rastlanmadı. Primer spermatositlerde orta yoğunlukta PNA, çok güçlü WGA reaksiyonu gözlendi. Buna karşılık bazal laminada SBA’ya karşı reaksiyon gözlenmezken, UEA-I’e karşı çok güçlü reaksiyon saptandı. Sertoli hücrelerinde Con A, SBA ve UEA I lektinlerinde orta yoğunlukta, PNA ve WGA’ da ise zayıf reaksiyon tespit edildi. Sonuç olarak sekonder spermatosit ve erken dönem spermatid aşamasındaki hücrelerdeki glikokonjugatların α-D-Mannoz (α-D-Man, α-D-Glikoz  (α-D-Glc ve α-L-Fukoz (α-L-Fuc içeriğinin diğer spermatojenik hücrelere göre az olduğu, tüm spermatojenik hücrelerdeki glikokonjugatın yoğun miktarda siyalik asit içerdiği saptandı. Leydig hücrelerindeki glikokonjugatın ise dağılımı araştırılan tüm şeker rezidülerine sahip olduğu belirlendi.

Dopamine D5 receptor modulates male and female sexual behavior in mice.

Science.gov (United States)

Kudwa, A E; Dominguez-Salazar, E; Cabrera, D M; Sibley, D R; Rissman, E F

2005-07-01

Dopamine exerts its actions through at least five receptor (DAR) isoforms. In female rats, D5 DAR may be involved in expression of sexual behavior. We used a D5 knockout (D5KO) mouse to assess the role of D5 DAR in mouse sexual behavior. Both sexes of D5KO mice are fertile and exhibit only minor disruptions in exploratory locomotion, startle, and prepulse inhibition responses. This study was conducted to characterize the sexual behavior of male and female D5KO mice relative to their WT littermates. Female WT and D5KO littermates were ovariectomized and given a series of sexual behavior tests after treatment with estradiol benzoate (EB) and progesterone (P). Once sexual performance was optimal the dopamine agonist, apomorphine (APO), was substituted for P. Male mice were observed in pair- and trio- sexual behavior tests. To assess whether the D5 DAR is involved in rewarding aspects of sexual behavior, WT and D5KO male mice were tested for conditioned place preference. Both WT and D5KO females can display receptivity after treatment with EB and P, but APO was only able to facilitate receptivity in EB-primed WT, not in D5KO, mice. Male D5KO mice display normal masculine sexual behavior in mating tests. In conditioned preference tests, WT males formed a conditioned preference for context associated with either intromissions alone or ejaculation as the unconditioned stimulus. In contrast, D5KO males only showed a place preference when ejaculation was paired with the context. In females, the D5 DAR is essential for the actions of dopamine on receptivity. In males, D5 DAR influences rewarding aspects of intromissions. Taken together, the work suggests that the D5 receptor mediates dopamine's action on sexual behavior in both sexes, perhaps via a reward pathway.

Fluoxetine protection in decompression sickness in mice is enhanced by blocking TREK-1 potassium channel with the spadin antidepressant.

Directory of Open Access Journals (Sweden)

Nicolas eVallée

2016-02-01

Full Text Available In mice, disseminated coagulation, inflammation and ischemia induce neurological damages that can lead to the death. These symptoms result from circulating bubbles generated by a pathogenic decompression. An acute fluoxetine treatment or the presence of the TREK-1 potassium channel increased the survival rate when mice are subjected to an experimental dive/decompression protocol. This is a paradox because fluoxetine is a blocker of TREK-1 channels. First, we studied the effects of an acute dose of fluoxetine (50mg/kg in wild-type (WT and TREK-1 deficient mice (Knockout homozygous KO and heterozygous HET. Then, we combined the same fluoxetine treatment with a five-day treatment by spadin, in order to specifically block TREK-1 activity (KO-like mice. KO and KO-like mice could be regarded as antidepressed models.167 mice (45 WTcont 46 WTflux 30 HETflux and 46 KOflux constituting the flux-pool and 113 supplementary mice (27 KO-like 24 WTflux2 24 KO-likeflux 21 WTcont2 17 WTno dive constituting the spad-pool were included in this study. Only 7% of KO-TREK-1 treated with fluoxetine (KOflux and 4% of mice treated with both spadin and fluoxetine (KO-likeflux died from decompression sickness (DCS symptoms. These values are much lower than those of WT control (62% or KO-like mice (41%. After the decompression protocol, mice showed a significant consumption of their circulating platelets and leukocytes.Spadin antidepressed mice were more likely to declare DCS. Nevertheless, which had both blocked TREK-1 channel and were treated with fluoxetine were better protected against DCS. We conclude that the protective effect of such an acute dose of fluoxetine is enhanced when TREK-1 is inhibited. We confirmed that antidepressed models may have worse DCS outcomes, but a concomitant fluoxetine treatment not only decreases DCS severity but increases the survival rate.

Deletion of AMPKα1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release.

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Almabrouk, Tarek A M; Ugusman, Azizah B; Katwan, Omar J; Salt, Ian P; Kennedy, Simon

2017-10-01

Perivascular adipose tissue (PVAT) surrounds most blood vessels and secretes numerous active substances, including adiponectin, which produce a net anticontractile effect in healthy individuals. AMPK is a key mediator of cellular energy balance and may mediate the vascular effects of adiponectin. In this study, we investigated the role of AMPK within PVAT in mediating the anticontractile effect of PVAT. Endothelium-denuded aortic rings from wild-type (WT; Sv129) and α 1 AMPK knockout (KO) mice were mounted on a wire myograph. Dose-response curves to the AMPK-independent vasodilator cromakalim were studied in vessels with and without PVAT, and effect of pre-incubation with conditioned media and adiponectin on relaxation was also studied. The effect of AMPKα1 KO on the secretory profile of PVAT was assessed by elisa. Thoracic aortic PVAT from KO mice was morphologically indistinct from that of WT and primarily composed of brown adipose tissue. PVAT augmented relaxation to cromakalim in WT but not KO aortic rings. Addition of WT PVAT augmented relaxation in KO aortic rings but KO PVAT had no effect in WT rings. PVAT from KO mice secreted significantly less adiponectin and addition of adiponectin to either KO or WT aortic rings without PVAT augmented relaxation to cromakalim. An adiponectin blocking peptide significantly attenuated relaxation in WT rings with PVAT but not in KO rings. AMPKα1 has a critical role in maintaining the anticontractile actions of PVAT; an effect independent of the endothelium but likely mediated through altered adiponectin secretion or sensitivity. This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc. © 2016 The British Pharmacological Society.

Secreted protein acidic and rich in cysteine functions in colitis via IL17A regulation in mucosal CD4+ T cells.

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Tanaka, Makoto; Takagi, Tomohisa; Naito, Yuji; Uchiyama, Kazuhiko; Hotta, Yuma; Toyokawa, Yuki; Ushiroda, Chihiro; Hirai, Yasuko; Aoi, Wataru; Higashimura, Yasuki; Mizushima, Katsura; Okayama, Tetsuya; Katada, Kazuhiro; Kamada, Kazuhiro; Ishikawa, Takeshi; Handa, Osamu; Itoh, Yoshito

2018-03-01

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycol that regulates cell proliferation, tissue repair, and tumorigenesis. Despite evidence linking SPARC to inflammation, the mechanisms are unclear. Accordingly, the role of SPARC in intestinal inflammation was investigated. Colitis was induced in wild-type (WT) and SPARC knockout (KO) mice using trinitrobenzene sulfonic acid (TNBS). Colons were assessed for damage; leukocyte infiltration; Tnf, Ifng, Il17a, and Il10 mRNA expression; and histology. Cytokine profiling of colonic lamina propria mononuclear cells (LPMCs) was performed by flow cytometry. Naïve CD4 + T cells were isolated from WT and SPARC KO mouse spleens, and the effect of SPARC on Th17 cell differentiation was examined. Recombination activating gene 1 knockout (RAG1 KO) mice reconstituted with T cells from either WT or SPARC KO mice were investigated. Trinitrobenzene sulfonic acid exposure significantly reduced bodyweight and increased mucosal inflammation, leukocyte infiltration, and Il17a mRNA expression in WT relative to SPARC KO mice. The percentage of IL17A-producing CD4 + T cells among LPMCs from KO mice was lower than that in WT mice when both groups were exposed to TNBS. Th17 cell differentiation was suppressed in cells from SPARC KO mice. In the T cell transfer colitis model, RAG1 KO mice receiving T cells from WT mice were more severely affected than those reconstituted with cells from SPARC KO mice. Secreted protein acidic and rich in cysteine accelerates colonic mucosal inflammation via modulation of IL17A-producing CD4 + T cells. SPARC is a potential therapeutic target for conditions involving intestinal inflammation. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Both cardiomyocyte and endothelial cell Nox4 mediate protection against hemodynamic overload-induced remodelling.

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Zhang, Min; Mongue-Din, Heloise; Martin, Daniel; Catibog, Norman; Smyrnias, Ioannis; Zhang, Xiaohong; Yu, Bin; Wang, Minshu; Brandes, Ralf P; Schröder, Katrin; Shah, Ajay M

2018-03-01

NADPH oxidase-4 (Nox4) is an important reactive oxygen species (ROS) source that is upregulated in the haemodynamically overloaded heart. Our previous studies using global Nox4 knockout (Nox4KO) mice demonstrated a protective role of Nox4 during chronic abdominal aortic banding, involving a paracrine enhancement of myocardial capillary density. However, other authors who studied cardiac-specific Nox4KO mice reported detrimental effects of Nox4 in response to transverse aortic constriction (TAC). It has been speculated that these divergent results are due to cell-specific actions of Nox4 (i.e. cardiomyocyte Nox4 detrimental but endothelial Nox4 beneficial) and/or differences in the model of pressure overload (i.e. abdominal banding vs. TAC). This study aimed to (i) investigate whether the effects of Nox4 on pressure overload-induced cardiac remodelling vary according to the pressure overload model and (ii) compare the roles of cardiomyocyte vs. endothelial cell Nox4. Global Nox4KO mice subjected to TAC developed worse cardiac remodelling and contractile dysfunction than wild-type littermates, consistent with our previous results with abdominal aortic banding. Next, we generated inducible cardiomyocyte-specific Nox4 KO mice (Cardio-Nox4KO) and endothelial-specific Nox4 KO mice (Endo-Nox4KO) and studied their responses to pressure overload. Both Cardio-Nox4KO and Endo-Nox4KO developed worse pressure overload-induced cardiac remodelling and dysfunction than wild-type littermates, associated with significant decrease in protein levels of HIF1α and VEGF and impairment of myocardial capillarization. Cardiomyocyte as well as endothelial cell Nox4 contributes to protection against chronic hemodynamic overload-induced cardiac remodelling, at least in part through common effects on myocardial capillary density. © The Author 2017 Published by Oxford University Press on behalf of the European Society of Cardiology.

RECG maintains plastid and mitochondrial genome stability by suppressing extensive recombination between short dispersed repeats.

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Masaki Odahara

2015-03-01

Full Text Available Maintenance of plastid and mitochondrial genome stability is crucial for photosynthesis and respiration, respectively. Recently, we have reported that RECA1 maintains mitochondrial genome stability by suppressing gross rearrangements induced by aberrant recombination between short dispersed repeats in the moss Physcomitrella patens. In this study, we studied a newly identified P. patens homolog of bacterial RecG helicase, RECG, some of which is localized in both plastid and mitochondrial nucleoids. RECG partially complements recG deficiency in Escherichia coli cells. A knockout (KO mutation of RECG caused characteristic phenotypes including growth delay and developmental and mitochondrial defects, which are similar to those of the RECA1 KO mutant. The RECG KO cells showed heterogeneity in these phenotypes. Analyses of RECG KO plants showed that mitochondrial genome was destabilized due to a recombination between 8-79 bp repeats and the pattern of the recombination partly differed from that observed in the RECA1 KO mutants. The mitochondrial DNA (mtDNA instability was greater in severe phenotypic RECG KO cells than that in mild phenotypic ones. This result suggests that mitochondrial genomic instability is responsible for the defective phenotypes of RECG KO plants. Some of the induced recombination caused efficient genomic rearrangements in RECG KO mitochondria. Such loci were sometimes associated with a decrease in the levels of normal mtDNA and significant decrease in the number of transcripts derived from the loci. In addition, the RECG KO mutation caused remarkable plastid abnormalities and induced recombination between short repeats (12-63 bp in the plastid DNA. These results suggest that RECG plays a role in the maintenance of both plastid and mitochondrial genome stability by suppressing aberrant recombination between dispersed short repeats; this role is crucial for plastid and mitochondrial functions.

Large-conductance Ca2+-activated K+ channel β1-subunit knockout mice are not hypertensive

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Garver, Hannah; Galligan, James J.; Fink, Gregory D.

2011-01-01

Large-conductance Ca2+-activated K+ (BK) channels are composed of pore-forming α-subunits and accessory β1-subunits that modulate Ca2+ sensitivity. BK channels regulate arterial myogenic tone and renal Na+ clearance/K+ reabsorption. Previous studies using indirect or short-term blood pressure measurements found that BK channel β1-subunit knockout (BK β1-KO) mice were hypertensive. We evaluated 24-h mean arterial pressure (MAP) and heart rate in BK β1-KO mice using radiotelemetry. BK β1-KO mice did not have a higher 24-h average MAP when compared with wild-type (WT) mice, although MAP was ∼10 mmHg higher at night. The dose-dependent peak declines in MAP by nifedipine were only slightly larger in BK β1-KO mice. In BK β1-KO mice, giving 1% NaCl to mice to drink for 7 days caused a transient (5 days) elevation of MAP (∼5 mmHg); MAP returned to pre-saline levels by day 6. BK β1-KO mesenteric arteries in vitro demonstrated diminished contractile responses to paxilline, increased reactivity to Bay K 8644 and norepinephrine (NE), and maintained relaxation to isoproterenol. Paxilline and Bay K 8644 did not constrict WT or BK β1-KO mesenteric veins (MV). BK β1-subunits are not expressed in MV. The results indicate that BK β1-KO mice are not hypertensive on normal or high-salt intake. BK channel deficiency increases arterial reactivity to NE and L-type Ca2+ channel function in vitro, but the L-type Ca2+ channel modulation of MAP is not altered in BK β1-KO mice. BK and L-type Ca2+ channels do not modulate murine venous tone. It appears that selective loss of BK channel function in arteries only is not sufficient to cause sustained hypertension. PMID:21131476

Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight.

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Shamansurova, Zulaykho; Tan, Paul; Ahmed, Basma; Pepin, Emilie; Seda, Ondrej; Lavoie, Julie L

2016-10-01

We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (P)RR gene would prevent weight gain and insulin resistance. An adipose tissue-specific (P)RR knockout (KO) mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD) to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. KO mice had lower body weights compared to wild-types (WT). Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (P)RR. (P)RR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes.

Bach2 Controls Homeostasis of Eosinophils by Restricting the Type-2 Helper Function of T Cells.

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Sato, Yuki; Kato, Hiroki; Ebina-Shibuya, Risa; Itoh-Nakadai, Ari; Okuyama, Ryuhei; Igarashi, Kazuhiko

2017-03-01

Bach2 is a transcription factor which represses its target genes and plays important roles in the differentiation of B and T lymphoid cells. Bach2-deficient (KO) mice develop severe pulmonary alveolar proteinosis, which is associated with increased numbers of granulocytes and T cells. Bach2 is essential for the regulation of T cells, but its role in the regulation of granulocytes is not clear. Here, we observed increased numbers of eosinophils but not neutrophils in the bone marrow, spleen, peripheral blood, and bronchoalveolar lavage fluids of Bach2 KO mice compared with those of wild-type (WT) mice. Upon co-transplantation of the bone marrow cells from CD45.2 Bach2 KO and CD45.1/CD45.2 double-positive WT mice to irradiated WT CD45.1/CD45.2 mice, the reconstituted numbers of eosinophils were similar between Bach2 KO and WT cells. These results showed that the deficiency of Bach2 in eosinophils did not directly drive the differentiation of eosinophils. To investigate the effect of Bach2 KO CD4 + T cells upon eosinophils, we analyzed Rag2/Bach2-double deficient (dKO) mice which lack lymphocytes including CD4 + T cells. Rag2/Bach2 dKO mice did not show any increase in the numbers of eosinophils. Importantly, Bach2 KO mice showed an increase of interleukin-5 (Il-5) in the sera compared with WT mice. These results suggest that up-regulated functions of CD4 + T cells including secretion of Il-5 resulted in proliferation and/or migration to peripheral tissues of eosinophils in Bach2 KO mice. We propose that Bach2 controls homeostasis of eosinophils via restricting the production of Il-5 in CD4 + T cells.

Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats

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Yonglu Tian

2017-08-01

Full Text Available Fragile X syndrome (FXS is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP. In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated protein 9 (Cas9 technology to generate Fmr1 knockout (KO rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1exon4-KO. Electrophysiological analysis revealed that the theta-burst stimulation (TBS–induced long-term potentiation (LTP and the low-frequency stimulus (LFS–induced long-term depression (LTD were decreased in the hippocampal Schaffer collateral pathway of the Fmr1exon4-KO rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR was also impaired. Consistent with previous reports, the Fmr1exon4-KO rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG–induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1exon4-KO rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1exon4-KO rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1exon4-KO rats constitute a novel rat model of FXS that complements existing mouse models.

Effects of Krill Oil on serum lipids of hyperlipidemic rats and human SW480 cells

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Qian Wen-Bin

2008-08-01

Full Text Available Abstract Background Cardiovascular disease (CVD and colon cancer incidence are known to be closely related to dietary factors. This article evaluated effects of krill oil (KO on serum lipids of hyperlipidemia rats and human colon cancer cells (SW480. Serum lipids of rats fed with high fat diet (HFD and different doses of KO were measured by automatic analyzer. Effect of KO on viability of cells was determined by methyl thiazolyl tetrazolium (MTT assay. Results Except for higher dose group, body weights decreased significantly. Total cholesterol (TC, LDL-cholesterol (LDL-C of all dose groups, Triglycerides (TG of low and mid dose groups descended significantly, while there were no significant differences of HDL-cholesterol (HDL-C, compared with control group. Treatment of colon cancer cells with KO also resulted in time-dependent inhibition of cell growth. Conclusion Our findings indicated that the consumption of KO may provide benefits to control serum lipid levels in certain diseases and inhibit growth of colon cancer cells. Therefore, KO may be a good candidate for development as a functional food and nutraceutical.

Enhanced radiosensitivity in 1,25-dihydroxyvitamin D3 deficient mice

International Nuclear Information System (INIS)

Zhang Zengli; Ding Xiaofei; Tong Jian; Li Bingyan

2011-01-01

To investigate whether impaired osteogenesis resulting from vitamin D deficiency can influence hematopoiesis recovery after radiation, the 25-hydroxyvitamin D-1α-hydroxylase (1α-hydroxylase) gene knockout (KO) mice and wild type (WT) mice were subjected to different doses of gamma ray. The survival rates, peripheral blood cell counts and bone marrow cellularity were studied after irradiation (IR). The survival rates of the KO mice were significantly lower than that of WT mice after 6 or 8 Gy dose of radiation. The recovery of white blood cells in KO mice was significantly delayed compared with that in WT mice after radiation. The red blood cell number in WT mice was observed to increase more than that in KO mice at days 14 and 28 after radiation. The nadir platelet count in KO mice was nearly half of that in WT mice. Dramatically higher bone marrow cell numbers were found in WT mice compared with KO mice. Our findings demonstrate the enhanced radiosensitivity in 1,25-dihydroxyvitamin D3 (1,25-(OH) 2 D 3 ) deficient mice. (author)

Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation

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Reno, Candace M.; Puente, Erwin C.; Sheng, Zhenyu; Daphna-Iken, Dorit; Bree, Adam J.; Routh, Vanessa H.; Kahn, Barbara B.

2017-01-01

GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. PMID:27797912

Dgroup: DG01803 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available DG01803 DGroup Antidiabetic, alpha-glucosidase inhibitor -bose ... D00216 ... Acarbose (...e (USAN) D09779 ... Emiglitate (JAN/INN) Antidiabetic agent ... DG01663 ... alpha-Glucosidase inhibitor Unclassified ... DG02044 ... Hypoglycemics ATC code: A10BF Antidiabetics GAA [HSA:2548] [KO:K12316] GANC [HSA:2595] [KO:K12317] MGAM [HSA:8972] [KO:K12047] ...

Nitric Oxide Induces Cardiac Protection by Preventing Extracellular Matrix Degradation through the Complex Caveolin-3/EMMPRIN in Cardiac Myocytes.

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Irene Cuadrado

Full Text Available Inhibition of Extracellular Matrix degradation by nitric oxide (NO induces cardiac protection against coronary ischemia/reperfusion (IR. Glycosylation of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN stimulates enzymatic activation of matrix metalloproteinases (MMPs in the heart, although the mechanisms leading to EMMPRIN glycosylation are poorly understood. We sought to determine if NO may induce cardiac protection by preventing glycosylation of EMMPRIN in a mouse model of IR. Here we found that Caveolin-3 binds to low glycosylated EMMPRIN (LG-EMMPRIN in cardiac cells and in the hearts of healthy mice, whereas IR disrupted the complex in nitric oxide synthase 2 (NOS2 knockout (KO mice. By contrast, the binding was partially restored when mice were fed with an NO donor (DEA-NO in the drinking water, showing a significant reduction on infarct size (NOS2KO: 34.6±5 vs NOS2KO+DEA-NO: 20.7±9, in expression of matrix metalloproteinases, and cardiac performance was improved (left ventricular ejection fraction (LVEF. NOS2KO: 31±4 vs NOS2KO+DEA-NO: 46±6. The role of Caveolin-3/EMMPRIN in NO-mediated cardiac protection was further assayed in Caveolin-3 KO mice, showing no significant improvement on infarct size (Caveolin-3 KO: 34.8±3 vs Caveolin-3 KO+DEA-NO:33.7±5, or in the expression of MMPs, suggesting that stabilization of the complex Caveolin-3/LG-EMMPRIN may play a significant role in the cardioprotective effect of NO against IR.

Nitric Oxide Induces Cardiac Protection by Preventing Extracellular Matrix Degradation through the Complex Caveolin-3/EMMPRIN in Cardiac Myocytes.

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Cuadrado, Irene; Castejon, Borja; Martin, Ana M; Saura, Marta; Reventun-Torralba, Paula; Zamorano, Jose Luis; Zaragoza, Carlos

2016-01-01

Inhibition of Extracellular Matrix degradation by nitric oxide (NO) induces cardiac protection against coronary ischemia/reperfusion (IR). Glycosylation of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) stimulates enzymatic activation of matrix metalloproteinases (MMPs) in the heart, although the mechanisms leading to EMMPRIN glycosylation are poorly understood. We sought to determine if NO may induce cardiac protection by preventing glycosylation of EMMPRIN in a mouse model of IR. Here we found that Caveolin-3 binds to low glycosylated EMMPRIN (LG-EMMPRIN) in cardiac cells and in the hearts of healthy mice, whereas IR disrupted the complex in nitric oxide synthase 2 (NOS2) knockout (KO) mice. By contrast, the binding was partially restored when mice were fed with an NO donor (DEA-NO) in the drinking water, showing a significant reduction on infarct size (NOS2KO: 34.6±5 vs NOS2KO+DEA-NO: 20.7±9), in expression of matrix metalloproteinases, and cardiac performance was improved (left ventricular ejection fraction (LVEF). NOS2KO: 31±4 vs NOS2KO+DEA-NO: 46±6). The role of Caveolin-3/EMMPRIN in NO-mediated cardiac protection was further assayed in Caveolin-3 KO mice, showing no significant improvement on infarct size (Caveolin-3 KO: 34.8±3 vs Caveolin-3 KO+DEA-NO:33.7±5), or in the expression of MMPs, suggesting that stabilization of the complex Caveolin-3/LG-EMMPRIN may play a significant role in the cardioprotective effect of NO against IR.

Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

KAUST Repository

Lavoie, Suzie

2016-04-21

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

Endogenous nociceptin modulates diet preference independent of motivation and reward.

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Koizumi, Miwako; Cagniard, Barbara; Murphy, Niall P

2009-04-20

Previous studies show that the opioid peptide nociceptin stimulates food intake. Here, we studied nociceptin receptor knockout (NOP KO) mice in various behavioral paradigms designed to differentiate psychological and physiological loci at which endogenous nociceptin might control feeding. When presented a choice under food restriction, NOP KO mice displayed reduced preference for high sucrose diet, but lower intake of high fat diet under no-choice conditions. These responses were absent under ad libitum feeding conditions. Conditioned place preference to high fat diet under food-deprived conditions was unaltered in NOP KO mice, suggesting no difference in reward responses. Furthermore, operant food self-administration under a variety of conditions showed no genotype-dependent differences, suggesting no differences in the motivational properties of food. Taste reactivity to sucrose was unchanged in NOP KO mice, though NOP KO mice had altered aversive reactions to quinine solutions under ad libitum feeding, suggesting minor differences in the affective impact of palatable and unpalatable tastants. Although NOP KO mice re-fed following food-deprivation showed normal increases in plasma glucose and insulin, multidimensional scaling analysis showed that the relationship between these measures, body weight and plasma leptin was substantially disrupted in NOP KO, particularly in fasted mice. Additionally, the typical positive relationship between body weight and plasma leptin was considerably weaker in NOP KO mice. Together, these findings suggest that endogenous nociceptin differentially modulates diet preference depending on macronutrient content and homeostatic state, independently of the motivating, rewarding or orosensory properties of food, but may involve metabolic or postingestive processes.

Disruption of BCAA metabolism in mice impairs exercise metabolism and endurance.

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She, Pengxiang; Zhou, Yingsheng; Zhang, Zhiyou; Griffin, Kathleen; Gowda, Kavitha; Lynch, Christopher J

2010-04-01

Exercise enhances branched-chain amino acid (BCAA) catabolism, and BCAA supplementation influences exercise metabolism. However, it remains controversial whether BCAA supplementation improves exercise endurance, and unknown whether the exercise endurance effect of BCAA supplementation requires catabolism of these amino acids. Therefore, we examined exercise capacity and intermediary metabolism in skeletal muscle of knockout (KO) mice of mitochondrial branched-chain aminotransferase (BCATm), which catalyzes the first step of BCAA catabolism. We found that BCATm KO mice were exercise intolerant with markedly decreased endurance to exhaustion. Their plasma lactate and lactate-to-pyruvate ratio in skeletal muscle during exercise and lactate release from hindlimb perfused with high concentrations of insulin and glucose were significantly higher in KO than wild-type (WT) mice. Plasma and muscle ammonia concentrations were also markedly higher in KO than WT mice during a brief bout of exercise. BCATm KO mice exhibited 43-79% declines in the muscle concentration of alanine, glutamine, aspartate, and glutamate at rest and during exercise. In response to exercise, the increments in muscle malate and alpha-ketoglutarate were greater in KO than WT mice. While muscle ATP concentration tended to be lower, muscle IMP concentration was sevenfold higher in KO compared with WT mice after a brief bout of exercise, suggesting elevated ammonia in KO is derived from the purine nucleotide cycle. These data suggest that disruption of BCAA transamination causes impaired malate/aspartate shuttle, thereby resulting in decreased alanine and glutamine formation, as well as increases in lactate-to-pyruvate ratio and ammonia in skeletal muscle. Thus BCAA metabolism may regulate exercise capacity in mice.

New insight into the role of MMP14 in metabolic balance

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Hidetoshi Mori

2016-07-01

Full Text Available Membrane-anchored matrix metalloproteinase 14 (MMP14 is involved broadly in organ development through both its proteolytic and signal-transducing functions. Knockout of Mmp14 (KO in mice results in a dramatic reduction of body size and wasting followed by premature death, the mechanism of which is poorly understood. Since the mammary gland develops after birth and is thus dependent for its functional progression on systemic and local cues, we chose it as an organ model for understanding why KO mice fail to thrive. A global analysis of the mammary glands’ proteome in the wild type (WT and KO mice provided insight into an unexpected role of MMP14 in maintaining metabolism and homeostasis. We performed mass spectrometry and quantitative proteomics to determine the protein signatures of mammary glands from 7 to 11 days old WT and KO mice and found that KO rudiments had a significantly higher level of rate-limiting enzymes involved in catabolic pathways. Glycogen and lipid levels in KO rudiments were reduced, and the circulating levels of triglycerides and glucose were lower. Analysis of the ultrastructure of mammary glands imaged by electron microscopy revealed a significant increase in autophagy signatures in KO mice. Finally, Mmp14 silenced mammary epithelial cells displayed enhanced autophagy. Applied to a systemic level, these findings indicate that MMP14 is a crucial regulator of tissue homeostasis. If operative on a systemic level, these findings could explain how Mmp14KO litter fail to thrive due to disorder in metabolism.

Loss of TRPV4 Function Suppresses Inflammatory Fibrosis Induced by Alkali-Burning Mouse Corneas.

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Yuka Okada

Full Text Available In humans suffering from pulmonary disease and a mouse model, transient receptor potential vanilloid 4 (TRPV4 channel activation contributes to fibrosis. As a corneal alkali burn induces the same response, we determined if such an effect is also attributable to TRPV4 activation in mice. Accordingly, we determined if the alkali burn wound healing responses in wild-type (WT mice are different than those in their TRPV4-null (KO counterpart. Stromal opacification due to fibrosis in KO (n = 128 mice was markedly reduced after 20 days relative to that in WT (n = 157 mice. Immunohistochemistry revealed that increases in polymorphonuclear leukocytes and macrophage infiltration declined in KO mice. Semi-quantitative real time RT-PCR of ocular KO fibroblast cultures identified increases in proinflammatory and monocyte chemoattractant protein-1 chemoattractant gene expression after injury. Biomarker gene expression of fibrosis, collagen1a1 and α-smooth muscle actin were attenuated along with macrophage release of interleukin-6 whereas transforming growth factor β, release was unchanged. Tail vein reciprocal bone marrow transplantation between WT and KO chimera mouse models mice showed that reduced scarring and inflammation in KO mice are due to loss of TRPV4 expression on both corneal resident immune cells, fibroblasts and infiltrating polymorphonuclear leukocytes and macrophages. Intraperitoneal TRPV4 receptor antagonist injection of HC-067047 (10 mg/kg, daily into WT mice reproduced the KO-phenotype. Taken together, alkali-induced TRPV4 activation contributes to inducing fibrosis and inflammation since corneal transparency recovery was markedly improved in KO mice.

Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

KAUST Repository

Lavoie, Suzie; Steullet, Pascal; Kulak, Anita; Preitner, Frederic; Do, Kim Q.; Magistretti, Pierre J.

2016-01-01

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli.

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Hasen, Nina S; Gammie, Stephen C

2011-03-01

The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female. Copyright © 2010 Elsevier B.V. All rights reserved.

Loss of TRPV4 Function Suppresses Inflammatory Fibrosis Induced by Alkali-Burning Mouse Corneas.

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Okada, Yuka; Shirai, Kumi; Miyajima, Masayasu; Reinach, Peter S; Yamanaka, Osamu; Sumioka, Takayoshi; Kokado, Masahide; Tomoyose, Katsuo; Saika, Shizuya

2016-01-01

In humans suffering from pulmonary disease and a mouse model, transient receptor potential vanilloid 4 (TRPV4) channel activation contributes to fibrosis. As a corneal alkali burn induces the same response, we determined if such an effect is also attributable to TRPV4 activation in mice. Accordingly, we determined if the alkali burn wound healing responses in wild-type (WT) mice are different than those in their TRPV4-null (KO) counterpart. Stromal opacification due to fibrosis in KO (n = 128) mice was markedly reduced after 20 days relative to that in WT (n = 157) mice. Immunohistochemistry revealed that increases in polymorphonuclear leukocytes and macrophage infiltration declined in KO mice. Semi-quantitative real time RT-PCR of ocular KO fibroblast cultures identified increases in proinflammatory and monocyte chemoattractant protein-1 chemoattractant gene expression after injury. Biomarker gene expression of fibrosis, collagen1a1 and α-smooth muscle actin were attenuated along with macrophage release of interleukin-6 whereas transforming growth factor β, release was unchanged. Tail vein reciprocal bone marrow transplantation between WT and KO chimera mouse models mice showed that reduced scarring and inflammation in KO mice are due to loss of TRPV4 expression on both corneal resident immune cells, fibroblasts and infiltrating polymorphonuclear leukocytes and macrophages. Intraperitoneal TRPV4 receptor antagonist injection of HC-067047 (10 mg/kg, daily) into WT mice reproduced the KO-phenotype. Taken together, alkali-induced TRPV4 activation contributes to inducing fibrosis and inflammation since corneal transparency recovery was markedly improved in KO mice.

Comments on "Determination and Analysis of the Theoretical Production of a Bucket Wheel Excavator" / Uwagi I Komentarze Do Pracy: "Określanie I Analiza Teoretycznej Wydajności Pracy Koparki Wielonaczyniowej Kołowej"

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Bošnjak, Srđan M.

2015-03-01

This paper comments on the recently published work dealing with the problem in the determination of the theoretical output of the bucket wheel excavator. It also includes remarks on the inadequacy in the problem approach and highlights the mistakes in the mathematical model. This work emphasizes the demand for a much wider and deeper approach to the problem of determining the output of the bucket wheel excavator. Opublikowany niedawno artykuł autorstwa Che i Chena (2014) poświecony jest ważnej kwestii jaką jest określenie teoretycznej wydajności koparki kołowej wielonaczyniowej. W załączonym przeglądzie literatury Che i Chen (2014) nie umieścili pozycji odnoszących się do metod urabiania, parametrów pracy koparki oraz teoretycznej wydajności wydobycia i być może to właśnie jest przyczyną pewnych niedokładności powstałych w trakcie rozwiązywania problemu. Intencją autora obecnej publikacji było: • Odniesienie się do krytycyzmu wyrażonego przez Che i Chena (2014) dotyczącego procedury obliczania prędkości w ruchu łukowym podanej w cytowanej literaturze przedmiotu (Pajer i in., 1971; Vetrov, 1971; Rasper, 1975; Durst i Vogt, 1988); • Zbadanie różnic pomiędzy procedurą określania teoretycznej wydajności zaproponowaną w pracy Che i Chena (2014) a odpowiednimi rozwiązaniami podanymi w literaturze; • Określenie prawidłowości i stosowalności teorii zaprezentowanej w pracy Che i Chena (2014) poprzez porównanie wyników uzyskanych z wykorzystaniem ich teorii oraz teorii podanych w wymienionych pozycjach literatury. W rozdziale 2 pracy (Che i Chen 2014) zatytułowanym " Uprzednio stosowane metody określania teoretycznej wydajności pracy koparki kołowej wielonaczyniowej" autorzy nie podali głównych odniesień literaturowych z których zaczerpnięte zostały równania (1)-(6)**. Ponadto, nie podali charakterystyki modelu działania koparki, na podstawie którego wyprowadzone zostały rzeczone równania, co stanowi powa

FIZIOLOGIJA KOŠARKAŠKE IGRE

OpenAIRE

Matković, Branka; Matković, Bojan; Knjaz, Damir

2005-01-01

Suvremenu košarkašku igru karakterizira visoki intenzitet aktivnosti kroz praktički svih četrdeset minuta njenog trajanja, zahtijeva od igrača/ica široku paletu osnovnih i specifičnih funkcionalnih i motoričkih sposobnosti. Gotovo je nemoguće izolirati neku koja u određenoj mjeri ne sudjeluju u uspjehu u igri. Ovaj rad daje pregled fiziološke pozadine košarkaške igre te analizu kretanja tijekom utakmice. Nadalje daje pregled aerobnih, anaerobnih i motoričkih sposobnosti košarkaša i košarkašic...

PRIMERJALNA ANALIZA STROŠKOV DELA V SLOVENIJI GLEDE NA VRSTE ZAPOSLITEV

OpenAIRE

Krošel, Marina

2015-01-01

V času, ko gospodarstvu posel ne gre najbolje, ko se trgi spreminjajo mesečno, ko se letnih planov ne da z gotovostjo napovedovati, ko ne le, da se dobički manjšajo, ampak jih več sploh ni, je trg dela pomembna komponenta varčevanja v gospodarstvu. V tem času na trg dela vstopam tudi sama. Kakšno obliko zaposlitve naj pričakujem? Katera je za delodajalca najbolj sprejemljiva? Kakšna je zakonodaja na tem področju? Ali me varuje Zakon o delovnih razmerjih? Kolektivna pogodba? Sindikati? Kaj ...

Fiscal 2000 achievement report on development of high-efficiency high-reliability welding technology through improvement on welding techniques; 2000 nendo yosetsu gijutsu no kodoka ni yoru kokoritsu koshinraisei yosetsu gijutsu no kaihatsu seika hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-04-01

Efforts are made to develop a welding design support system capable of increasing reliability and enhancing welding efficiency. Activities are conducted in the six fields of (1) the development of welding process simulation models, (2) development of welded section structure simulation models, (3) development of simulation models for predicting welding caused deformation, (4) integration of the models, (5) analysis of the welding phenomenon, and (6) the elucidation of the defect generation mechanism. In field (1), efforts are made to develop an arc plasma model, a molten pool convective heat transportation model, and a welding process model. In the effort to develop an arc plasma model, studies are made about a stationary axisymmetric arc in its steady state and about a constitutive equation and computation algorithm for developing a model in which a tungsten electrode (cathode) and an arc plasma welding pool (anode) are integrated. Furthermore, the simulation outcomes are experimentally verified. Satisfactory models are obtained as far as qualitative properties are concerned. (NEDO)

Japan's healthcare policy for the elderly through the concepts of self-help (Ji-jo), mutual aid (Go-jo), social solidarity care (Kyo-jo), and governmental care (Ko-jo).

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Sudo, Kyoko; Kobayashi, Jun; Noda, Shinichiro; Fukuda, Yoshiharu; Takahashi, Kenzo

2018-03-18

Elderly care is an emerging global issue threatening both developed and developing countries. The elderly in Japan increased to 26.7% of the population in 2015, and Japan is classified as a super-aged society. In this article, we introduce the financial aspects of the medical care and welfare services policy for the elderly in Japan. Japan's universal health insurance coverage system has been in place since 1961. Long-term care includes welfare services, which were separated from the medical care insurance scheme in 2000 when Japan was already recognized as an aging society. Since then, the percentage of the population over 65 has increased dramatically, with the productive-age population on the decrease. The Japanese government, therefore, is seeking to implement "The Community-based Integrated Care System" with the aim of building comprehensive up-to-the-end-of-life support services in each community. The system has four proposed elements: self-help (Ji-jo), mutual aid (Go-jo), social solidarity care (Kyo-jo), and government care (Ko-jo). From the financial perspective, as the government struggles against the financial burdens of an aging population, they are considering self-help and mutual aid. Based on Japan's present situation, both elements could lead to positive results. The Japanese government must also entrust the responsibility for implementing preventive support to municipalities through strongly required regional autonomy. As Japan has resolved this new challenge through several discussions over a long period of time, other aging countries could learn from the Japanese experience of solving barriers to healthcare policy for the elderly.

The α-fetoprotein knock-out mouse model suggests that parental behavior is sexually differentiated under the influence of prenatal estradiol

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Keller, Matthieu; Pawluski, Jodi L.; Brock, Olivier; Douhard, Quentin; Bakker, Julie

2010-01-01

In rodent species, sexual differentiation of the brain for many reproductive processes depends largely on estradiol. This was recently confirmed again by using the α-fetoprotein knockout (AFP-KO) mouse model, which lacks the protective actions of α-fetoprotein against maternal estradiol and as a result represents a good model to determine the contribution of prenatal estradiol to the sexual differentiation of the brain and behavior. Female AFP-KO mice were defeminized and masculinized with regard to their neuroendocrine responses as well as sexual behavior. Since parental behavior is also strongly sexually differentiated in mice, we used the AFP-KO mouse model here to ask whether parental responses are differentiated prenatally under the influence of estradiol. It was found that AFP-KO females showed longer latencies to retrieve pups to the nest and also exhibited lower levels of crouching over the pups in the nest in comparison to WT females. In fact, they resembled males (WT and AFP-KO). Other measures of maternal behavior, for example the incidence of infanticide, tended to be higher in AFP-KO females than in WT females but this increase failed to reach statistical significance. The deficits observed in parental behavior of AFP-KO females could not be explained by any changes in olfactory function, novelty recognition or anxiety. Thus our results suggest that prenatal estradiol defeminizes the parental brain in mice. PMID:20109458

CREB binding protein is required for both short-term and long-term memory formation.

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Chen, Guiquan; Zou, Xiaoyan; Watanabe, Hirotaka; van Deursen, Jan M; Shen, Jie

2010-09-29

CREB binding protein (CBP) is a transcriptional coactivator with histone acetyltransferase activity. Our prior study suggested that CBP might be a key target of presenilins in the regulation of memory formation and neuronal survival. To elucidate the role of CBP in the adult brain, we generated conditional knock-out (cKO) mice in which CBP is completely inactivated in excitatory neurons of the postnatal forebrain. Histological analysis revealed normal neuronal morphology and absence of age-dependent neuronal degeneration in the CBP cKO cerebral cortex. CBP cKO mice exhibited robust impairment in the formation of spatial, associative, and object-recognition memory. In addition to impaired long-term memory, CBP cKO mice also displayed deficits in short-term associative and object-recognition memory. Administration of a histone deacetylase inhibitor, trichostatin A, rescued the reduction of acetylated histones in the CBP cKO cortex but failed to rescue either short- or long-term memory deficits, suggesting that the memory impairment may not be caused by general reduction of histone acetyltransferase activity in CBP cKO mice. Further microarray and Western analysis showed decreased expression of calcium-calmodulin-dependent kinase isoforms and NMDA and AMPA receptor subunits in the cerebral cortex of CBP cKO mice. Collectively, these findings suggest a crucial role for CBP in the formation of both short- and long-term memory.

Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

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LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

2016-02-01

The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

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Zhu Zhu

2016-01-01

Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

A Convenient Cas9-based Conditional Knockout Strategy for Simultaneously Targeting Multiple Genes in Mouse.

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Chen, Jiang; Du, Yinan; He, Xueyan; Huang, Xingxu; Shi, Yun S

2017-03-31

The most powerful way to probe protein function is to characterize the consequence of its deletion. Compared to conventional gene knockout (KO), conditional knockout (cKO) provides an advanced gene targeting strategy with which gene deletion can be performed in a spatially and temporally restricted manner. However, for most species that are amphiploid, the widely used Cre-flox conditional KO (cKO) system would need targeting loci in both alleles to be loxP flanked, which in practice, requires time and labor consuming breeding. This is considerably significant when one is dealing with multiple genes. CRISPR/Cas9 genome modulation system is advantaged in its capability in targeting multiple sites simultaneously. Here we propose a strategy that could achieve conditional KO of multiple genes in mouse with Cre recombinase dependent Cas9 expression. By transgenic construction of loxP-stop-loxP (LSL) controlled Cas9 (LSL-Cas9) together with sgRNAs targeting EGFP, we showed that the fluorescence molecule could be eliminated in a Cre-dependent manner. We further verified the efficacy of this novel strategy to target multiple sites by deleting c-Maf and MafB simultaneously in macrophages specifically. Compared to the traditional Cre-flox cKO strategy, this sgRNAs-LSL-Cas9 cKO system is simpler and faster, and would make conditional manipulation of multiple genes feasible.

Stem cell antigen-1 in skeletal muscle function.

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Bernstein, Harold S; Samad, Tahmina; Cholsiripunlert, Sompob; Khalifian, Saami; Gong, Wenhui; Ritner, Carissa; Aurigui, Julian; Ling, Vivian; Wilschut, Karlijn J; Bennett, Stephen; Hoffman, Julien; Oishi, Peter

2013-08-15

Stem cell antigen-1 (Sca-1) is a member of the Ly-6 multigene family encoding highly homologous, glycosyl-phosphatidylinositol-anchored membrane proteins. Sca-1 is expressed on muscle-derived stem cells and myogenic precursors recruited to sites of muscle injury. We previously reported that inhibition of Sca-1 expression stimulated myoblast proliferation in vitro and regulated the tempo of muscle repair in vivo. Despite its function in myoblast expansion during muscle repair, a role for Sca-1 in normal, post-natal muscle has not been thoroughly investigated. We systematically compared Sca-1-/- (KO) and Sca-1+/+ (WT) mice and hindlimb muscles to elucidate the tissue, contractile, and functional effects of Sca-1 in young and aging animals. Comparison of muscle volume, fibrosis, myofiber cross-sectional area, and Pax7+ myoblast number showed little differences between ages or genotypes. Exercise protocols, however, demonstrated decreased stamina in KO versus WT mice, with young KO mice achieving results similar to aging WT animals. In addition, KO mice did not improve with practice, while WT animals demonstrated conditioning over time. Surprisingly, myomechanical analysis of isolated muscles showed that KO young muscle generated more force and experienced less fatigue. However, KO muscle also demonstrated incomplete relaxation with fatigue. These findings suggest that Sca-1 is necessary for muscle conditioning with exercise, and that deficient conditioning in Sca-1 KO animals becomes more pronounced with age.

ACAT1 deletion in murine macrophages associated with cytotoxicity and decreased expression of collagen type 3A1

International Nuclear Information System (INIS)

Rodriguez, Annabelle; Ashen, M. Dominique; Chen, Edward S.

2005-01-01

In contrast to some published studies of murine macrophages, we previously showed that ACAT inhibitors appeared to be anti-atherogenic in primary human macrophages in that they decreased foam cell formation without inducing cytotoxicity. Herein, we examined foam cell formation and cytotoxicity in murine ACAT1 knockout (KO) macrophages in an attempt to resolve the discrepancies. Elicited peritoneal macrophages from normal C57BL6 and ACAT1 KO mice were incubated with DMEM containing acetylated LDL (acLDL, 100 μg protein/ml) for 48 h. Cells became cholesterol enriched and there were no differences in the total cholesterol mass. Esterified cholesterol mass was lower in ACAT1 KO foam cells compared to normal macrophages (p 14 C]adenine from macrophages, was approximately 2-fold greater in ACAT1 KO macrophages as compared to normal macrophages (p < 0.0001), and this was independent of cholesterol enrichment. cDNA microarray analysis showed that ACAT1 KO macrophages expressed substantially less collagen type 3A1 (26-fold), which was confirmed by RT-PCR. Total collagen content was also significantly reduced (57%) in lung homogenates isolated from ACAT1 KO mice (p < 0.02). Thus, ACAT1 KO macrophages show biochemical changes consistent with increased cytotoxicity and also a novel association with decreased expression of collagen type 3A1

Differential regulation of morphine antinociceptive effects by endogenous enkephalinergic system in the forebrain of mice

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Sun Wei-Zen

2008-09-01

Full Text Available Abstract Background Mice lacking the preproenkephalin (ppENK gene are hyperalgesic and show more anxiety and aggression than wild-type (WT mice. The marked behavioral changes in ppENK knock-out (KO mice appeared to occur in supraspinal response to painful stimuli. However the functional role of enkephalins in the supraspinal nociceptive processing and their underlying mechanism is not clear. The aim of present study was to compare supraspinal nociceptive and morphine antinociceptive responses between WT and ppENK KO mice. Results The genotypes of bred KO mice were confirmed by PCR. Met-enkephalin immunoreactive neurons were labeled in the caudate-putamen, intermediated part of lateral septum, lateral globus pallidus, intermediated part of lateral septum, hypothalamus, and amygdala of WT mice. Met-enkephalin immunoreactive neurons were not found in the same brain areas in KO mice. Tail withdrawal and von Frey test results did not differ between WT and KO mice. KO mice had shorter latency to start paw licking than WT mice in the hot plate test. The maximal percent effect of morphine treatments (5 mg/kg and 10 mg/kg, i.p. differed between WT and KO mice in hot plate test. The current source density (CSD profiles evoked by peripheral noxious stimuli in the primary somatosenstory cortex (S1 and anterior cingulate cortex (ACC were similar in WT and KO mice. After morphine injection, the amplitude of the laser-evoked sink currents was decreased in S1 while the amplitude of electrical-evoked sink currents was increased in the ACC. These differential morphine effects in S1 and ACC were enhanced in KO mice. Facilitation of synaptic currents in the ACC is mediated by GABA inhibitory interneurons in the local circuitry. Percent increases in opioid receptor binding in S1 and ACC were 5.1% and 5.8%, respectively. Conclusion The present results indicate that the endogenous enkephalin system is not involved in acute nociceptive transmission in the spinal cord

Distinct motor impairments of dopamine D1 and D2 receptor knockout mice revealed by three types of motor behavior

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Toru eNakamura

2014-07-01

Full Text Available Both D1R and D2R knock out (KO mice of the major dopamine receptors show significant motor impairments. However, there are some discrepant reports, which may be due to the differences in genetic background and experimental procedures. In addition, only few studies directly compared the motor performance of D1R and D2R KO mice. In this paper, we examined the behavioral difference among N10 congenic D1R and D2R KO, and wild type (WT mice. First, we examined spontaneous motor activity in the home cage environment for consecutive five days. Second, we examined motor performance using the rota-rod task, a standard motor task in rodents. Third, we examined motor ability with the Step-Wheel task in which mice were trained to run in a motor-driven turning wheel adjusting their steps on foothold pegs to drink water. The results showed clear differences among the mice of three genotypes in three different types of behavior. In monitoring spontaneous motor activities, D1R and D2R KO mice showed higher and lower 24 h activities, respectively, than WT mice. In the rota-rod tasks, at a low speed, D1R KO mice showed poor performance but later improved, whereas D2R KO mice showed a good performance at early days without further improvement. When first subjected to a high speed task, the D2R KO mice showed poorer rota-rod performance at a low speed than the D1R KO mice. In the Step-Wheel task, across daily sessions, D2R KO mice increased the duration that mice run sufficiently close to the spout to drink water, and decreased time to touch the floor due to missing the peg steps and number of times the wheel was stopped, which performance was much better than that of D1R KO mice. These incongruent results between the two tasks for D1R and D2R KO mice may be due to the differences in the motivation for the rota-rod and Step-Wheel tasks, aversion- and reward-driven, respectively. The Step-Wheel system may become a useful tool for assessing the motor ability of WT

Adenylyl cyclase-5 in the dorsal striatum function as a molecular switch for the generation of behavioral preferences for cue-directed food choices.

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Kim, Hannah; Kim, Tae-Kyung; Kim, Ji-Eun; Park, Jin-Young; Lee, Yunjin; Kang, Minkyung; Kim, Kyoung-Shim; Han, Pyung-Lim

2014-11-07

Behavioral choices in habits and innate behaviors occur automatically in the absence of conscious selection. These behaviors are not easily modified by learning. Similar types of behaviors also occur in various mental illnesses including drug addiction, obsessive-compulsive disorder, schizophrenia, and autism. However, underlying mechanisms are not clearly understood. In the present study, we investigated the molecular mechanisms regulating unconditioned preferred behaviors in food-choices. Mice lacking adenylyl cyclase-5 (AC5 KO mice), which is preferentially expressed in the dorsal striatum, consumed food pellets nearly one after another in cages. AC5 KO mice showed aversive behaviors to bitter tasting quinine, but they compulsively chose quinine-containing AC5 KO-pellets over fresh pellets. The unusual food-choice behaviors in AC5 KO mice were due to the gain of behavioral preferences for food pellets containing an olfactory cue, which wild-type mice normally ignored. Such food-choice behaviors in AC5 KO mice disappeared when whiskers were trimmed. Conversely, whisker trimming in wildtype mice induced behavioral preferences for AC5 KO food pellets, indicating that preferred food-choices were not learned through prior experience. Both AC5 KO mice and wildtype mice with trimmed whiskers had increased glutamatergic input from the barrel cortex into the dorsal striatum, resulting in an increase in the mGluR1-dependent signaling cascade. The siRNA-mediated inhibition of mGluR1 in the dorsal striatum in AC5 KO mice and wildtype mice with trimmed whiskers abolished preferred choices for AC5 KO food pellets, whereas siRNA-mediated inhibition of mGluR3 glutamate receptors in the dorsal striatum in wildtype mice induced behavioral preferences for AC5 KO food pellets, thus mimicking AC5 KO phenotypes. Our results show that the gain and loss of behavioral preferences for a specific cue-directed option were regulated by specific cellular factors in the dorsal striatum, such

Resilience to audiogenic seizures is associated with p-ERK1/2 dephosphorylation in the subiculum of Fmr1 knockout mice

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Giulia eCuria

2013-04-01

Full Text Available Young, but not adult, Fmr1 knockout (KO mice display audiogenic seizures (AGS that can be prevented by inhibiting extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation. In order to identify the cerebral regions involved in these phenomena, we characterized the response to AGS in Fmr1 KO mice and wild type (WT controls at postnatal day (P 45 and P90. To characterize the diverse response to AGS in various cerebral regions, we evaluated the activity markers FosB/ΔFosB and phosphorylated ERK1/2 (p-ERK1/2. Wild running (100% of tested mice followed by clonic/tonic seizures (30% were observed in P45 Fmr1 KO mice, but not in WT mice. In P90 Fmr1 KO mice, wild running was only present in 25% of tested animals. Basal FosB/ΔFosB immunoreactivity was higher (P<0.01 vs WT in the CA1 and subiculum of P45 Fmr1 KO mice. Following the AGS test, FosB/ΔFosB expression consistently increased in most of the analyzed regions in both groups at P45, but not at P90. Interestingly, FosB/ΔFosB immunoreactivity was significantly higher in P45 Fmr1 KO mice in the medial geniculate body (P<0.05 vs WT and CA3 (P<0.01. Neurons presenting with immunopositivity to p-ERK1/2 were more abundant in the subiculum of Fmr1 KO mice in control condition (P<0.05 vs WT, in both age groups. In this region, p-ERK1/2-immunopositive cells significantly decreased (-75%, P<0.01 in P90 Fmr1 KO mice exposed to the AGS test, but no changes were found in P45 mice or in other brain regions. In both age groups of WT mice, p-ERK1/2-immunopositive cells increased in the subiculum after exposure to the acoustic test. Our findings illustrate that FosB/ΔFosB markers are overexpressed in the medial geniculate body and CA3 in Fmr1 KO mice experiencing AGS, and that p-ERK1/2 is markedly decreased in the subiculum of Fmr1 KO mice resistant to AGS induction. These findings suggest that resilience to AGS is associated with dephosphorylation of p-ERK1/2 in the subiculum of mature Fmr1 KO mice.

Associations between urinary phthalate metabolites and bisphenol A levels, and serum thyroid hormones among the Korean adult population - Korean National Environmental Health Survey (KoNEHS) 2012-2014.

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Park, Choonghee; Choi, Wookhee; Hwang, Moonyoung; Lee, Youngmee; Kim, Suejin; Yu, Seungdo; Lee, Inae; Paek, Domyung; Choi, Kyungho

2017-04-15

Phthalates and bisphenol A (BPA) have been used extensively in many consumer products, resulting in widespread exposure in the general population. Studies have suggested associations between exposure to phthalates and BPA, and serum thyroid hormone levels, but confirmation on larger human populations is warranted. Data obtained from nationally representative Korean adults (n=6003) recruited for the second round of the Korean National Environmental Health Survey (KoNEHS), 2012-2014, were employed. Three di-(2-ethylhexyl) phthalate (DEHP) metabolites, along with benzyl-butyl phthalate (BBzP) and di-butyl phthalate (DBP) metabolites, and BPA were measured in subjects' urine. Thyroxine (T4), total triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured in serum. The associations between urinary phthalates or BPA and thyroid hormone levels were determined. Urinary phthalate metabolites were generally associated with lowered total T4 or T3, or increased TSH levels in serum. Interquartile range (IQR) increases of mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were associated with a 3.7% increase of TSH, and a 1.7% decrease of total T4 levels, respectively. When grouped by sex, urinary MEHHP levels were inversely associated with T4 only among males. Among females, mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP) levels were inversely associated with TSH and T3, respectively. In addition, negative association between BPA and TSH was observed. Several phthalates and BPA exposures were associated with altered circulatory thyroid hormone levels among general Korean adult population. Considering the importance of thyroid hormones, public health implications of such alteration warrant further studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Metabotropic glutamate receptor subtype 7 has critical roles in regulation of the endocrine system and social behaviours.

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Masugi-Tokita, M; Yoshida, T; Kageyama, S; Kawata, M; Kawauchi, A

2018-03-01

Metabotropic glutamate receptor subtype 7 (mGluR7) is one of the group III mGluRs, which are negatively coupled to adenylate cyclase via Gi/Go proteins and localised to presynaptic active zones of the mammalian central nervous system. We previously reported that mGluR7 is essential for intermale aggression and amygdala-dependent fear learning. To elucidate the role of mGluR7 in the neuroendocrine system, we performed biochemical analyses and found a significant reduction of testosterone levels in mGluR7 knockout (KO) mice. Testosterone replacement restored intermale aggressive behaviour in castrated wild-type mice to the level of gonadally intact wild-type mice. However, given the same dosage of testosterone replacement, mGluR7 KO mice showed almost no aggressive behaviour. These results indicate that reduction of plasma testosterone is unrelated to the deficit in intermale aggression in mGluR7 KO mice. Social investigating behaviour of intact mGluR7 KO mice also differed from that of wild-type mice; e.g. the KO mice showing less frequent anogenital sniffing and more frequent grooming behaviour. Testosterone replacement increased anogenital sniffing and grooming behaviour in castrated mGluR7 KO mice, while the differences were still present between castrated wild-type mice and KO mice after both underwent testosterone replacement. These results imply that reduction of plasma testosterone may partially inhibit social investigating behaviours in intact mGluR7 KO mice. Furthermore, castrated mGluR7 KO mice have smaller seminal vesicles than those of castrated wild-type mice, although seminal vesicle weights were normal in intact mice. These observations suggest that, besides testicular testosterone, some other hormone levels may be dysregulated in mGluR7 KO mice, and indicate a critical role of mGluR7 in the endocrine system. Taken together, our findings demonstrate that mGluR7 is essential for the regulation of the endocrine system, in addition to innate behaviours

Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.

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Hiromi Toyoda

Full Text Available Narcolepsy is caused by the loss of hypocretin (Hcrt neurons and is associated with multiple genetic and environmental factors. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. We previously reported chemokine (C-C motif receptor 3 (CCR3 as a novel susceptibility gene for narcolepsy. To understand the role of CCR3 in the development of narcolepsy, we investigated sleep-wake patterns of Ccr3 knockout (KO mice. Ccr3 KO mice exhibited fragmented sleep patterns in the light phase, whereas the overall sleep structure in the dark phase did not differ between Ccr3 KO mice and wild-type (WT littermates. Intraperitoneal injection of lipopolysaccharide (LPS promoted wakefulness and suppressed both REM and NREM sleep in the light phase in both Ccr3 KO and WT mice. Conversely, LPS suppressed wakefulness and promoted NREM sleep in the dark phase in both genotypes. After LPS administration, the proportion of time spent in wakefulness was higher, and the proportion of time spent in NREM sleep was lower in Ccr3 KO compared to WT mice only in the light phase. LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, we quantified the number of Hcrt neurons and found that Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice. We found abnormalities in sleep patterns in the resting phase and in the number of Hcrt neurons in Ccr3 KO mice. These observations suggest a role for CCR3 in sleep-wake regulation in narcolepsy patients.

Glutathione-deficient Plasmodium berghei parasites exhibit growth delay and nuclear DNA damage.

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Padín-Irizarry, Vivian; Colón-Lorenzo, Emilee E; Vega-Rodríguez, Joel; Castro, María Del R; González-Méndez, Ricardo; Ayala-Peña, Sylvette; Serrano, Adelfa E

2016-06-01

Plasmodium parasites are exposed to endogenous and exogenous oxidative stress during their complex life cycle. To minimize oxidative damage, the parasites use glutathione (GSH) and thioredoxin (Trx) as primary antioxidants. We previously showed that disruption of the Plasmodium berghei gamma-glutamylcysteine synthetase (pbggcs-ko) or the glutathione reductase (pbgr-ko) genes resulted in a significant reduction of GSH in intraerythrocytic stages, and a defect in growth in the pbggcs-ko parasites. In this report, time course experiments of parasite intraerythrocytic development and morphological studies showed a growth delay during the ring to schizont progression. Morphological analysis shows a significant reduction in size (diameter) of trophozoites and schizonts with increased number of cytoplasmic vacuoles in the pbggcs-ko parasites in comparison to the wild type (WT). Furthermore, the pbggcs-ko mutants exhibited an impaired response to oxidative stress and increased levels of nuclear DNA (nDNA) damage. Reduced GSH levels did not result in mitochondrial DNA (mtDNA) damage or protein carbonylations in neither pbggcs-ko nor pbgr-ko parasites. In addition, the pbggcs-ko mutant parasites showed an increase in mRNA expression of genes involved in oxidative stress detoxification and DNA synthesis, suggesting a potential compensatory mechanism to allow for parasite proliferation. These results reveal that low GSH levels affect parasite development through the impairment of oxidative stress reduction systems and damage to the nDNA. Our studies provide new insights into the role of the GSH antioxidant system in the intraerythrocytic development of Plasmodium parasites, with potential translation into novel pharmacological interventions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of GPR84 deletion on obesity and diabetes development in mice fed long chain or medium chain fatty acid rich diets.

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Du Toit, Eugene; Browne, Liam; Irving-Rodgers, Helen; Massa, Helen M; Fozzard, Nicolette; Jennings, Michael P; Peak, Ian R

2017-04-20

Although there is good evidence showing that diets rich in medium chain fatty acids (MCFAs) have less marked obesogenic and diabetogenic effects than diets rich in long chain fatty acids (LCFAs), the role of the pro-inflammatory, medium chain fatty acid receptor (GPR84) in the aetiology of obesity and glucose intolerance is not well characterised. We set out to determine whether GPR84 expression influences obesity and glucose intolerance susceptibility in MCFA and LCFA rich diet fed mice. Wild type (WT) and GPR84 knockout (KO) mice were fed a control, MCFA or LCFA diet, and body mass, heart, liver and epididymal fat mass was assessed, as well as glucose tolerance and adipocyte size. LCFA diets increased body mass and decreased glucose tolerance in both WT and GPR84 KO animals while MCFA diets had no effect on these parameters. There were no differences in body weight when comparing WT and GPR84 KO mice on the respective diets. Glucose tolerance was also similar in WT and GPR84 KO mice irrespective of diet. Liver mass was increased following LCFA feeding in WT but not GPR84 KO mice. Hepatic triglyceride content was increased in GPR84 KO animals fed MCFA, and myocardial triglyceride content was increased in GPR84 KO animals fed LCFA. GPR84 deletion had no effects on body weight or glucose tolerance in mice fed either a high MCFA or LCFA diet. GPR84 may influence lipid metabolism, as GPR84 KO mice had smaller livers and increased myocardial triglyceride accumulation when fed LCFA diets, and increased liver triglyceride accumulation in responses to increased dietary MCFAs.

Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice

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Tanda Koichi

2009-06-01

Full Text Available Abstract Background Neuronal nitric oxide synthase (nNOS is involved in the regulation of a diverse population of intracellular messenger systems in the brain. In humans, abnormal NOS/nitric oxide metabolism is suggested to contribute to the pathogenesis and pathophysiology of some neuropsychiatric disorders, such as schizophrenia and bipolar disorder. Mice with targeted disruption of the nNOS gene exhibit abnormal behaviors. Here, we subjected nNOS knockout (KO mice to a battery of behavioral tests to further investigate the role of nNOS in neuropsychiatric functions. We also examined the role of nNOS in dopamine/DARPP-32 signaling in striatal slices from nNOS KO mice and the effects of the administration of a dopamine D1 receptor agonist on behavior in nNOS KO mice. Results nNOS KO mice showed hyperlocomotor activity in a novel environment, increased social interaction in their home cage, decreased depression-related behavior, and impaired spatial memory retention. In striatal slices from nNOS KO mice, the effects of a dopamine D1 receptor agonist, SKF81297, on the phosphorylation of DARPP-32 and AMPA receptor subunit GluR1 at protein kinase A sites were enhanced. Consistent with the biochemical results, intraperitoneal injection of a low dose of SKF81297 significantly decreased prepulse inhibition in nNOS KO mice, but not in wild-type mice. Conclusion These findings indicate that nNOS KO upregulates dopamine D1 receptor signaling, and induces abnormal social behavior, hyperactivity and impaired remote spatial memory. nNOS KO mice may serve as a unique animal model of psychiatric disorders.

A conditioned aversion study of sucrose and SC45647 taste in TRPM5 knockout mice.

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Eddy, Meghan C; Eschle, Benjamin K; Peterson, Darlene; Lauras, Nathan; Margolskee, Robert F; Delay, Eugene R

2012-06-01

Previously, published studies have reported mixed results regarding the role of the TRPM5 cation channel in signaling sweet taste by taste sensory cells. Some studies have reported a complete loss of sweet taste preference in TRPM5 knockout (KO) mice, whereas others have reported only a partial loss of sweet taste preference. This study reports the results of conditioned aversion studies designed to motivate wild-type (WT) and KO mice to respond to sweet substances. In conditioned taste aversion experiments, WT mice showed nearly complete LiCl-induced response suppression to sucrose and SC45647. In contrast, TRPM5 KO mice showed a much smaller conditioned aversion to either sweet substance, suggesting a compromised, but not absent, ability to detect sweet taste. A subsequent conditioned flavor aversion experiment was conducted to determine if TRPM5 KO mice were impaired in their ability to learn a conditioned aversion. In this experiment, KO and WT mice were conditioned to a mixture of SC45647 and amyl acetate (an odor cue). Although WT mice avoided both components of the stimulus mixture, they avoided SC45647 more than the odor cue. The KO mice also avoided both stimuli, but they avoided the odor component more than SC45647, suggesting that while the KO mice are capable of learning an aversion, to them the odor cue was more salient than the taste cue. Collectively, these findings suggest the TRPM5 KO mice have some residual ability to detect SC45647 and sucrose, and, like bitter, there may be a TRPM5-independent transduction pathway for detecting these substances.

Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation.

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Reno, Candace M; Puente, Erwin C; Sheng, Zhenyu; Daphna-Iken, Dorit; Bree, Adam J; Routh, Vanessa H; Kahn, Barbara B; Fisher, Simon J

2017-03-01

GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose. © 2017 by the American Diabetes Association.

Hybridization Capture Reveals Evolution and Conservation across the Entire Koala Retrovirus Genome

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Ishida, Yasuko; Cui, Pin; Vielgrader, Hanna; Helgen, Kristofer M.; Roca, Alfred L.; Greenwood, Alex D.

2014-01-01

The koala retrovirus (KoRV) is the only retrovirus known to be in the midst of invading the germ line of its host species. Hybridization capture and next generation sequencing were used on modern and museum DNA samples of koala (Phascolarctos cinereus) to examine ca. 130 years of evolution across the full KoRV genome. Overall, the entire proviral genome appeared to be conserved across time in sequence, protein structure and transcriptional binding sites. A total of 138 polymorphisms were detected, of which 72 were found in more than one individual. At every polymorphic site in the museum koalas, one of the character states matched that of modern KoRV. Among non-synonymous polymorphisms, radical substitutions involving large physiochemical differences between amino acids were elevated in env, potentially reflecting anti-viral immune pressure or avoidance of receptor interference. Polymorphisms were not detected within two functional regions believed to affect infectivity. Host sequences flanking proviral integration sites were also captured; with few proviral loci shared among koalas. Recently described variants of KoRV, designated KoRV-B and KoRV-J, were not detected in museum samples, suggesting that these variants may be of recent origin. PMID:24752422

Hybridization capture reveals evolution and conservation across the entire Koala retrovirus genome.

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Kyriakos Tsangaras

Full Text Available The koala retrovirus (KoRV is the only retrovirus known to be in the midst of invading the germ line of its host species. Hybridization capture and next generation sequencing were used on modern and museum DNA samples of koala (Phascolarctos cinereus to examine ca. 130 years of evolution across the full KoRV genome. Overall, the entire proviral genome appeared to be conserved across time in sequence, protein structure and transcriptional binding sites. A total of 138 polymorphisms were detected, of which 72 were found in more than one individual. At every polymorphic site in the museum koalas, one of the character states matched that of modern KoRV. Among non-synonymous polymorphisms, radical substitutions involving large physiochemical differences between amino acids were elevated in env, potentially reflecting anti-viral immune pressure or avoidance of receptor interference. Polymorphisms were not detected within two functional regions believed to affect infectivity. Host sequences flanking proviral integration sites were also captured; with few proviral loci shared among koalas. Recently described variants of KoRV, designated KoRV-B and KoRV-J, were not detected in museum samples, suggesting that these variants may be of recent origin.

Recent trends of citation status and suggestions for improved the academic authority of the journal of the Korean radiological society during 2000-2005: analysis of all citations using KoMCI

International Nuclear Information System (INIS)

Park, Soo Youn; Kim, Hyun Jin; Ihn, Yon Kwon; Cha, Eun Suk; Hwang, Seong Su

2006-01-01

We wanted to analyze the citation trend and to find a way to improve the impact factor (IF) of the Journal of the Korean Radiological Society (JKRS). The number of articles and references, the total citations and self-citations, the IF and the IF excluding self-citations (ZIF) were described by an analysis of Korean Medical Citation Index (KoMCI) during 2000-2005. The total and self citations of the JKRS were compared to that of the Top 5 journals. There was a 57% decrease of papers for 6 years. The Korean references/paper ranged from 0.98-0.85. The number of total citations received steadily decreased from 394 in 2000 to 180 in 2005. The IF (ZF) of the JKRS has been gradually lowered from 0.142 (0.049) in 2000 to 0.063 (0.059) in 2005. Although the total citations that cited all papers published/the annual number of papers was 55% of that of the top 5 journals, the total citations citing papers published within the recent two years was only 24% of that of the top 5 journals. The citation status of the JKRS has steadily decreased for the recent 6 years, and the IF of the JKRS was very low among all the Korean medical journals. To improve the IF, active advertising for the journal members of the importance of the IF is needed to encourage citing JKRS papers that have been published within the recent two years

Computer simulation of range and damage distributions of He ions in SiC

International Nuclear Information System (INIS)

Miyagawa, Yoshiko; Ato, Yasuro; Miyagawa, Soji

1984-01-01

The experimental projected ranges of various heavy ions in an amorphous Si target in the energy region where the nuclear stopping dominates are compared with calculations using the computer simulation program SASAMAL with the Lenz-Jensen, Moliere, Thomas-Fermi and Kalbitzer-Oetzmann (KO) screening parameters. In most cases. the best agreement was obtained with the KO screening parameters. The projected range distributions of He ions implanted in an SiC target were calculated using SASAMAL with KO screening parameters. The agreement between the SASAMAL(KO) results and our experimental data was satisfactory when the electronic stopping parameter k=1.3 k sub(NS) was used. The energy and the depth distributions of the primary knock-on atoms and the depth distributions of the recoil energy density with various values of the displacement energy Esub(d) were also calculated using SASAMAL(KO) for He ions in SiC. (author)

Computer aided materials design; Keisanki zairyo sekkei

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-03-01

The questionnaire survey on the computer aided materials design (CAMD), and the survey of current domestic and overseas software concerned were carried out to clarify developmental issues. The current elementary technology of CAMD was also surveyed to study its several problems caused with a progress of material design technology due to drastic diffusion of CAMD. This project aims at establishment of a new demanded software, computer chemistry, focusing attention on functional materials such as catalyst, polymer and non-linear electronic materials. Microscopic simulation technology was mainly surveyed in fiscal 1996. Although some fruitful results have been obtained in the fields of medical and agricultural chemicals, organic compounds, proteins, catalysts and electronic materials, such some problems are pointed out as `CAMD cannot handle an actual size of the target system` and `commercially available software are very expensive.` Reliable tool development as elementary technology, and the verification of its applications are thus required. Meso-dynamics, polymers, surface reaction and integrated technological environment attract users` attention. 27 refs., 16 figs., 2 tabs.

OBLIKOVANJE EKOLOŠKE EMBALAŽE

OpenAIRE

Vehovar, Barbara

2012-01-01

V diplomskem delu smo predstavili ekološko oblikovanje embalaže, ki je vidno skozi grafično podobo in pomen le-tega za okolje. Najprej smo se posvetili embalaži in njenim značilnostim ter nadaljevali z ekološkim vidikom embalaže. Nato smo se osredotočili na ekološko oblikovanje ter elemente, ki asociirajo na ekološkost. Za konec smo analizirali nekaj embalaž kozmetičnih izdelkov ter oblikovali ekološko embalažo za enega od analiziranih, ki je po našem mnenju imel najmanj ekološko embalažo....

Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development

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Congyu Xu

2017-10-01

Full Text Available Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study in vivo function of PDK1 in neuron survival during cortical development, we generate forebrain-specific PDK1 conditional knockout (cKO mice. We demonstrate that PDK1 cKO mice display striking neuron loss and increased apoptosis. We report that PDK1 cKO mice exhibit deficits on several behavioral tasks. Moreover, PDK1 cKO mice show decreased activities for Akt and mTOR. These results highlight an essential role of endogenous PDK1 in the maintenance of neuronal survival during cortical development.

Disease: H01027 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available H01027 Anophthalmia and microphthalmia (A/M); Nanophthalmia/ Nanophthalmos Anophth...BP4 [HSA:5950] [KO:K18271] (isolated) RAX [HSA:30062] [KO:K09332] (isolated/nanophthalmia) MFRP [HSA:83552] ...(isolated) PRSS56 [HSA:646960] (isolated) ALDH1A3 [HSA:220] [KO:K00129] (nanophthalmia...ent misuse ... Simple microphthalmia refers to a structurally normal, small eye, and has been used interchangeably with nanophthalmia

Increased consumption of ethanol and sugar water in mice lacking the dopamine D2 long receptor.

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Bulwa, Zachary B; Sharlin, Jordan A; Clark, Peter J; Bhattacharya, Tushar K; Kilby, Chessa N; Wang, Yanyan; Rhodes, Justin S

2011-11-01

Individual differences in dopamine D2 receptor (D2R) expression in the brain are thought to influence motivation and reinforcement for ethanol and other rewards. D2R exists in two isoforms, D2 long (D2LR) and D2 short (D2SR), produced by alternative splicing of the same gene. The relative contributions of D2LR versus D2SR to ethanol and sugar water drinking are not known. Genetic engineering was used to produce a line of knockout (KO) mice that lack D2LR and consequently have increased expression of D2SR. KO and wild-type (WT) mice of both sexes were tested for intake of 20% ethanol, 10% sugar water and plain tap water using established drinking-in-the-dark procedures. Mice were also tested for effects of the D2 antagonist eticlopride on intake of ethanol to determine whether KO responses were caused by lack of D2LR or overrepresentation of D2SR. Locomotor activity on running wheels and in cages without wheels was also measured for comparison. D2L KO mice drank significantly more ethanol than WT in both sexes. KO mice drank more sugar water than WT in females but not in males. Eticlopride dose dependently decreased ethanol intake in all groups except male KO. KO mice were less physically active than WT in cages with or without running wheels. Results suggest that overrepresentation of D2SR contributes to increased intake of ethanol in the KO mice. Decreasing wheel running and general levels of physical activity in the KO mice rules out the possibility that higher intake results from higher motor activity. Results extend the literature implicating altered expression of D2R in risk for addiction by delineating the contribution of individual D2R isoforms. These findings suggest that D2LR and D2SR play differential roles in consumption of alcohol and sugar rewards. Copyright © 2011 Elsevier Inc. All rights reserved.

Podocyte-specific deletion of Rac1 leads to aggravation of renal injury in STZ-induced diabetic mice

International Nuclear Information System (INIS)

Ishizaka, Masanori; Gohda, Tomohito; Takagi, Miyuki; Omote, Keisuke; Sonoda, Yuji; Oliva Trejo, Juan Alejandro; Asao, Rin; Hidaka, Teruo; Asanuma, Katsuhiko; Horikoshi, Satoshi; Tomino, Yasuhiko

2015-01-01

Rac1, a GTPase of the Rho subfamily, has a crucial role in cytoskeletal architecture, as well as the regulation of cell migration and growth. However, renal injury in mice with podocyte-specific deletion of Rac1 has yet to be elucidated fully due to conflicting findings. Herein, we identified a possible role for Rac1 in podocytes of streptozotocin- (STZ) induced diabetic mice. The urinary albumin/creatinine ratio (ACR) in the knockout (KO) group was significantly higher than that in the wild type (WT) group at any week of age. A more marked ACR increase was observed in STZ/KO group than STZ/WT group, although ACR did increase with weeks of age in both diabetic groups. The kidney sections from diabetic mice revealed a glomerular hypertrophy with mesangial expansion, but there was no appreciable difference in glomerular findings under a light microscope between STZ/WT and STZ/KO mice. However, an electron microscopy analysis revealed that regardless of the presence or absence of diabetes, both KO (KO and STZ/KO) groups had a higher rate of foot process effacement compared with both WT (WT and STZ/WT) groups. The expression levels of the slit diaphragm protein, podocin, was reduced with the induction of diabetes, and the levels in the STZ/KO group experienced a further reduction compared with the STZ/WT group. The number of WT1-positive cells in the STZ/KO group was more significantly decreased than that in the other three groups. In contrast, the numbers of cleaved caspase 3- and TUNEL-positive cells in the glomeruli of the STZ/KO group were more increased than those in the STZ/WT group. Thus, this study provides evidence that podocyte-specific deletion of Rac1 results in morphological alteration in podocytes, and that the induction of apoptosis or decreased expression of the slit diaphragm proteins by hyperglycemic stimuli are associated with the progression of diabetic nephropathy.

Seipin knockout in mice impairs stem cell proliferation and progenitor cell differentiation in the adult hippocampal dentate gyrus via reduced levels of PPARγ

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Guoxi Li

2015-12-01

Full Text Available The seipin gene (BSCL2 was originally identified in humans as a loss-of-function gene associated with congenital generalized lipodystrophy type 2 (CGL2. Neuronal seipin-knockout (seipin-nKO mice display a depression-like phenotype with a reduced level of hippocampal peroxisome proliferator-activated receptor gamma (PPARγ. The present study investigated the influence of seipin deficiency on adult neurogenesis in the hippocampal dentate gyrus (DG and the underlying mechanisms of the effects. We show that the proliferative capability of stem cells in seipin-nKO mice was substantially reduced compared to in wild-type (WT mice, and that this could be rescued by the PPARγ agonist rosiglitazone (rosi. In seipin-nKO mice, neuronal differentiation of progenitor cells was inhibited, with the enhancement of astrogliogenesis; both of these effects were recovered by rosi treatment during early stages of progenitor cell differentiation. In addition, rosi treatment could correct the decline in hippocampal ERK2 phosphorylation and cyclin A mRNA level in seipin-nKO mice. The MEK inhibitor U0126 abolished the rosi-rescued cell proliferation and cyclin A expression in seipin-nKO mice. In seipin-nKO mice, the hippocampal Wnt3 protein level was less than that in WT mice, and there was a reduction of neurogenin 1 (Neurog1 and neurogenic differentiation 1 (NeuroD1 mRNA, levels of which were corrected by rosi treatment. STAT3 phosphorylation (Tyr705 was enhanced in seipin-nKO mice, and was further elevated by rosi treatment. Finally, rosi treatment for 10 days could alleviate the depression-like phenotype in seipin-nKO mice, and this alleviation was blocked by the MEK inhibitor U0126. The results indicate that, by reducing PPARγ, seipin deficiency impairs proliferation and differentiation of neural stem and progenitor cells, respectively, in the adult DG, which might be responsible for the production of the depression-like phenotype in seipin-nKO mice.

Osbpl8 deficiency in mouse causes an elevation of high-density lipoproteins and gender-specific alterations of lipid metabolism.

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Olivier Béaslas

Full Text Available OSBP-related protein 8 (ORP8 encoded by Osbpl8 is an endoplasmic reticulum sterol sensor implicated in cellular lipid metabolism. We generated an Osbpl8(-/- (KO C57Bl/6 mouse strain. Wild-type and Osbpl8KO animals at the age of 13-weeks were fed for 5 weeks either chow or high-fat diet, and their plasma lipids/lipoproteins and hepatic lipids were analyzed. The chow-fed Osbpl8KO male mice showed a marked elevation of high-density lipoprotein (HDL cholesterol (+79% and phospholipids (+35%, while only minor increase of apolipoprotein A-I (apoA-I was detected. In chow-fed female KO mice a less prominent increase of HDL cholesterol (+27% was observed, while on western diet the HDL increment was prominent in both genders. The HDL increase was accompanied by an elevated level of HDL-associated apolipoprotein E in male, but not female KO animals. No differences between genotypes were observed in lecithin:cholesterol acyltransferase (LCAT or hepatic lipase (HL activity, or in the fractional catabolic rate of fluorescently labeled mouse HDL injected in chow-diet fed animals. The Osbpl8KO mice of both genders displayed reduced phospholipid transfer protein (PLTP activity, but only on chow diet. These findings are consistent with a model in which Osbpl8 deficiency results in altered biosynthesis of HDL. Consistent with this hypothesis, ORP8 depleted mouse hepatocytes secreted an increased amount of nascent HDL into the culture medium. In addition to the HDL phenotype, distinct gender-specific alterations in lipid metabolism were detected: Female KO animals on chow diet showed reduced lipoprotein lipase (LPL activity and increased plasma triglycerides, while the male KO mice displayed elevated plasma cholesterol biosynthetic markers cholestenol, desmosterol, and lathosterol. Moreover, modest gender-specific alterations in the hepatic expression of lipid homeostatic genes were observed. In conclusion, we report the first viable OsbplKO mouse model

Adipose tissue (PRR regulates insulin sensitivity, fat mass and body weight

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Zulaykho Shamansurova

2016-10-01

Full Text Available Objective: We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(PRR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (PRR gene would prevent weight gain and insulin resistance. Methods: An adipose tissue-specific (PRR knockout (KO mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (PRR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. Results: KO mice had lower body weights compared to wild-types (WT. Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (PRR. Conclusions: (PRR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes. Keywords: (Prorenin receptor, Renin-angiotensin system, Adipose

Effects of targeted deletion of A1 adenosine receptors on postischemic cardiac function and expression of adenosine receptor subtypes.

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Morrison, R Ray; Teng, Bunyen; Oldenburg, Peter J; Katwa, Laxmansa C; Schnermann, Jurgen B; Mustafa, S Jamal

2006-10-01

To examine ischemic tolerance in the absence of A(1) adenosine receptors (A(1)ARs), isolated wild-type (WT) and A(1)AR knockout (A(1)KO) murine hearts underwent global ischemia-reperfusion, and injury was measured in terms of functional recovery and efflux of lactate dehydrogenase (LDH). Hearts were analyzed by real-time RT-PCR both at baseline and at intervals during ischemia-reperfusion to determine whether compensatory expression of other adenosine receptor subtypes occurs with either A(1)AR deletion and/or ischemia-reperfusion. A(1)KO hearts had higher baseline coronary flow (CF) and left ventricular developed pressure (LVDP) than WT hearts, whereas heart rate was unchanged by A(1)AR deletion. After 20 min of ischemia, CF was attenuated in A(1)KO compared with WT hearts, and this reduction persisted throughout reperfusion. Final recovery of LVDP was decreased in A(1)KO hearts (54.4 +/- 5.1 vs. WT 81.1 +/- 3.4% preischemic baseline) and correlated with higher diastolic pressure during reperfusion. Postischemic efflux of LDH was greater in A(1)KO compared with WT hearts. Real-time RT-PCR demonstrated the absence of A(1)AR transcript in A(1)KO hearts, and the message for A(2A), A(2B), and A(3) adenosine receptors was similar in uninstrumented A(1)KO and WT hearts. Ischemia-reperfusion increased A(2B) mRNA expression 2.5-fold in both WT and A(1)KO hearts without changing A(1) or A(3) expression. In WT hearts, ischemia transiently doubled A(2A) mRNA, which returned to preischemic level upon reperfusion, a pattern not observed in A(1)KO hearts. Together, these data affirm the cardioprotective role of A(1)ARs and suggest that induced expression of other adenosine receptor subtypes may participate in the response to ischemia-reperfusion in isolated murine hearts.

High ethanol and acetaldehyde impair spatial memory in mouse models: opposite effects of aldehyde dehydrogenase 2 and apolipoprotein E on memory.

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Jamal, Mostofa; Ameno, Kiyoshi; Miki, Takanori; Tanaka, Naoko; Ono, Junichiro; Shirakami, Gotaro; Sultana, Ruby; Yu, Nakamura; Kinoshita, Hiroshi

2012-05-01

Aldehyde dehydrogenase 2 deficiency may directly contribute to excess acetaldehyde (AcH) accumulation after ethanol (EtOH) drinking and AcH mediates some of the behavioral effects of EtOH. Apolipoprotein E has been suggested to be involved in the alteration of attention and memory. We have chosen Aldh2-knockout (Aldh2-KO), ApoE-KO, and their wild-type (WT) control mice to examine the effects of EtOH and AcH on spatial memory and to compare the possible relationship between genetic deficiency and memory using two behavioral assessments. Mice were trained for 4 days, with EtOH (0.5, 1.0, 2.0 g/kg) being given intraperitoneally on day 4. A probe trial was given on day 5 in the non-EtOH state in the Morris water maze (MWM). The results showed that 2.0 g/kg EtOH increased errors, indicating memory impairment on the eight-arm radial maze (RAM) for all the mice studied. One gram per kilogram EtOH impaired the performance of Aldh2-KO and ApoE-KO mice, but not WT mice. We found similar effects of EtOH on the MWM performance, with 2.0 g/kg EtOH increasing the latencies. One gram per kilogram EtOH increased the latencies of Aldh2-KO and WT mice, but not ApoE-KO mice. The 2.0 g/kg EtOH-induced memory impairment in Aldh2-KO mice was greater, suggesting an AcH effect. Furthermore, time spent on the probe trial was shorter in mice that had previously received 2.0 g/kg EtOH. ApoE-KO mice learned more slowly, while Aldh2-KO mice learned more quickly. Both the RAM and MWM results suggest that high EtOH and AcH impair spatial memory in mice, while lower doses do not have consistent memory effects. In addition, we conclude that genetic differences might underlie some of EtOH's effects on memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Podocyte-specific deletion of Rac1 leads to aggravation of renal injury in STZ-induced diabetic mice

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Ishizaka, Masanori [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Gohda, Tomohito, E-mail: goda@juntendo.ac.jp [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Takagi, Miyuki; Omote, Keisuke; Sonoda, Yuji [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Oliva Trejo, Juan Alejandro [Laboratory for Kidney Research (TMK Project), Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8397 (Japan); Asao, Rin; Hidaka, Teruo [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Asanuma, Katsuhiko [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Laboratory for Kidney Research (TMK Project), Medical Innovation Center, Kyoto University Graduate School of Medicine, 53 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8397 (Japan); Horikoshi, Satoshi [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Tomino, Yasuhiko [Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Medical Corporation SHOWAKAI, 3-12-12 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023 (Japan)

2015-11-20

Rac1, a GTPase of the Rho subfamily, has a crucial role in cytoskeletal architecture, as well as the regulation of cell migration and growth. However, renal injury in mice with podocyte-specific deletion of Rac1 has yet to be elucidated fully due to conflicting findings. Herein, we identified a possible role for Rac1 in podocytes of streptozotocin- (STZ) induced diabetic mice. The urinary albumin/creatinine ratio (ACR) in the knockout (KO) group was significantly higher than that in the wild type (WT) group at any week of age. A more marked ACR increase was observed in STZ/KO group than STZ/WT group, although ACR did increase with weeks of age in both diabetic groups. The kidney sections from diabetic mice revealed a glomerular hypertrophy with mesangial expansion, but there was no appreciable difference in glomerular findings under a light microscope between STZ/WT and STZ/KO mice. However, an electron microscopy analysis revealed that regardless of the presence or absence of diabetes, both KO (KO and STZ/KO) groups had a higher rate of foot process effacement compared with both WT (WT and STZ/WT) groups. The expression levels of the slit diaphragm protein, podocin, was reduced with the induction of diabetes, and the levels in the STZ/KO group experienced a further reduction compared with the STZ/WT group. The number of WT1-positive cells in the STZ/KO group was more significantly decreased than that in the other three groups. In contrast, the numbers of cleaved caspase 3- and TUNEL-positive cells in the glomeruli of the STZ/KO group were more increased than those in the STZ/WT group. Thus, this study provides evidence that podocyte-specific deletion of Rac1 results in morphological alteration in podocytes, and that the induction of apoptosis or decreased expression of the slit diaphragm proteins by hyperglycemic stimuli are associated with the progression of diabetic nephropathy.

Accumulation of cytolytic CD8{sup +} T cells in B16-melanoma and proliferation of mature T cells in TIS21-knockout mice after T cell receptor stimulation

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Ryu, Min Sook [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Woo, Min-Yeong [Department of Microbiology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Department of Biomedical Sciences, The Graduate School, Ajou University (Korea, Republic of); Kwon, Daeho [Department of Microbiology, Kwandong University College of Medicine, Gangneung, Gangwon-do 210-701 (Korea, Republic of); Hong, Allen E. [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Song, Kye Yong [Department of Pathology, Chung-Ang University College of Medicine, Dongjak-gu, Seoul 156-756 (Korea, Republic of); Park, Sun [Department of Microbiology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Lim, In Kyoung [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of)

2014-10-01

In vivo and in vitro effects of TIS21 gene on the mature T cell activation and antitumor activities were explored by employing MO5 melanoma orthograft and splenocytes isolated from the TIS21-knockout (KO) mice. Proliferation and survival of mature T cells were significantly increased in the KO than the wild type (WT) cells, indicating that TIS21 inhibits the rate of mature T cell proliferation and its survival. In MO5 melanoma orthograft model, the KO mice recruited much more CD8{sup +} T cells into the tumors at around day 14 after tumor cell injection along with reduced tumor volumes compared with the WT. The increased frequency of granzyme B{sup +} CD8{sup +} T cells in splenocytes of the KO mice compared with the WT may account for antitumor-immunity of TIS21 gene in the melanoma orthograft. In contrast, reduced frequencies of CD107a{sup +} CD8{sup +} T cells in the splenocytes of KO mice may affect the loss of CD8{sup +} T cell infiltration in the orthograft at around day 19. These results indicate that TIS21 exhibits antiproliferative and proapoptotic effects in mature T cells, and differentially affects the frequencies of granzyme B{sup +} CD8{sup +} T-cells and CD107a{sup +} CD8{sup +} T-cells, thus transiently regulating in vivo anti-tumor immunity. - Highlights: • Constitutive expression of TIS21 in splenocytes and upregulation by TCR stimulation. • Proliferation of mature T-cells in spleen of TIS21KO mice after TCR stimulation. • Inhibition of cell death in mature T-cells of TIS21KO mice compared with the wild type. • Inhibition of melanoma growth in TIS21KO mice and CD8{sup +} T cell infiltration in tumor. • Reduction of CD 107{sup +}CD8{sup +} T cells, but increased granzyme B{sup +} CD8{sup +} T cells in TIS21KO mice.

Phg1/TM9 proteins control intracellular killing of bacteria by determining cellular levels of the Kil1 sulfotransferase in Dictyostelium.

Directory of Open Access Journals (Sweden)

Marion Le Coadic

Full Text Available Dictyostelium discoideum has largely been used to study phagocytosis and intracellular killing of bacteria. Previous studies have shown that Phg1A, Kil1 and Kil2 proteins are necessary for efficient intracellular killing of Klebsiella bacteria. Here we show that in phg1a KO cells, cellular levels of lysosomal glycosidases and lysozyme are decreased, and lysosomal pH is increased. Surprisingly, overexpression of Kil1 restores efficient killing in phg1a KO cells without correcting these lysosomal anomalies. Conversely, kil1 KO cells are defective for killing, but their enzymatic content and lysosomal pH are indistinguishable from WT cells. The killing defect of phg1a KO cells can be accounted for by the observation that in these cells the stability and the cellular amount of Kil1 are markedly reduced. Since Kil1 is the only sulfotransferase characterized in Dictyostelium, an (unidentified sulfated factor, defective in both phg1a and kil1 KO cells, may play a key role in intracellular killing of Klebsiella bacteria. In addition, Phg1B plays a redundant role with Phg1A in controlling cellular amounts of Kil1 and intracellular killing. Finally, cellular levels of Kil1 are unaffected in kil2 KO cells, and Kil1 overexpression does not correct the killing defect of kil2 KO cells, suggesting that Kil2 plays a distinct role in intracellular killing.

Long-lasting Effects of Minocycline on Behavior in Young but not Adult Fragile X Mice

Science.gov (United States)

Dansie, Lorraine E.; Phommahaxay, Kelly; Okusanya, Ayodeji G.; Uwadia, Jessica; Huang, Mike; Rotschafer, Sarah E.; Razak, Khaleel A.; Ethell, Douglas W.; Ethell, Iryna M.

2013-01-01

Fragile X Syndrome (FXS) is the most common single-gene inherited form of intellectual disability with behaviors characteristic of autism. People with FXS display childhood seizures, hyperactivity, anxiety, developmental delay, attention deficits, and visual-spatial memory impairment, as well as a propensity for obsessive-compulsive disorder (OCD). Several of these aberrant behaviors and FXS-associated synaptic irregularities also occur in “fragile X mental retardation gene” knock-out (Fmr1 KO) mice. We previously reported that minocycline promotes the maturation of dendritic spines - postsynaptic sites for excitatory synapses - in the developing hippocampus of Fmr1 KO mice, which may underlie the beneficial effects of minocycline on anxiolytic behavior in young Fmr1 KO mice. In this study, we compared the effectiveness of minocycline treatment in young and adult Fmr1 KO mice, and determined the dependence of behavioral improvements on short-term versus long-term minocycline administration. We found that 4 and 8 week long treatments significantly reduced locomotor activity in both young and adult Fmr1 KO mice. Some behavioral improvements persisted in young mice post-treatment, but in adults the beneficial effects were lost soon after minocycline treatment was stopped. We also show, for the first time, that minocycline treatment partially attenuates the number and severity of audiogenic seizures in Fmr1 KO mice. This report provides further evidence that minocycline treatment has immediate and long-lasting benefits on FXS-associated behaviors in the Fmr1 KO mouse model. PMID:23660195

The metabotropic glutamate 5 receptor modulates extinction and reinstatement of methamphetamine-seeking in mice.

Directory of Open Access Journals (Sweden)

Rose Chesworth

Full Text Available Methamphetamine (METH is a highly addictive psychostimulant with no therapeutics registered to assist addicts in discontinuing use. Glutamatergic dysfunction has been implicated in the development and maintenance of addiction. We sought to assess the involvement of the metabotropic glutamate 5 receptor (mGlu5 in behaviours relevant to METH addiction because this receptor has been implicated in the actions of other drugs of abuse, including alcohol, cocaine and opiates. mGlu5 knockout (KO mice were tested in intravenous self-administration, conditioned place preference and locomotor sensitization. Self-administration of sucrose was used to assess the response of KO mice to a natural reward. Acquisition and maintenance of self-administration, as well as the motivation to self-administer METH was intact in mGlu5 KO mice. Importantly, mGlu5 KO mice required more extinction sessions to extinguish the operant response for METH, and exhibited an enhanced propensity to reinstate operant responding following exposure to drug-associated cues. This phenotype was not present when KO mice were tested in an equivalent paradigm assessing operant responding for sucrose. Development of conditioned place preference and locomotor sensitization were intact in KO mice; however, conditioned hyperactivity to the context previously paired with drug was elevated in KO mice. These data demonstrate a role for mGlu5 in the extinction and reinstatement of METH-seeking, and suggests a role for mGlu5 in regulating contextual salience.

Angiotensin-(1-7)/Mas axis modulates fear memory and extinction in mice.

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Lazaroni, Thiago Luiz do Nascimento; Bastos, Cristiane Perácio; Moraes, Márcio Flávio Dutra; Santos, Robson Souza; Pereira, Grace Schenatto

2016-01-01

Inappropriate defense-alerting reaction to fear is a common feature of neuropsychiatric diseases. Therefore, impairments in brain circuits, as well as in molecular pathways underlying the neurovegetative adjustments to fear may play an essential role on developing neuropsychiatric disorders. Here we tested the hypothesis that interfering with angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis homeostasis, which appears to be essential to arterial pressure control, would affect fear memory and extinction. Mas knockout (MasKO) mice, in FVB/N background, showed normal cued fear memory and extinction, but increased freezing in response to context. Next, as FVB/N has poor performance in contextual fear memory, we tested MasKO in mixed 129xC57BL/6 background. MasKO mice behaved similarly to wild-type (WT), but memory extinction was slower in contextual fear conditioning to a weak protocol (1CS/US). In addition, delayed extinction in MasKO mice was even more pronounced after a stronger protocol (3CS/US). We showed previously that Angiotensin II receptor AT1 antagonist, losantan, rescued object recognition memory deficit in MasKO mice. Here, losartan was also effective. Memory extinction was accelerated in MasKO mice after treatment with losartan. In conclusion, we showed for the first time that Ang-(1-7)/Mas axis may modulate fear memory extinction. Furthermore, we suggest MasKO mice as an animal model to study post-traumatic stress disorder (PTSD). Copyright © 2015 Elsevier Inc. All rights reserved.

Welding mechanization in shipyard CIM; Zosen ni okeru yosetsu no jidoka robot ka CIM ka

Energy Technology Data Exchange (ETDEWEB)

Miyazaki, T. [Hitachi Zosen Corp., Osaka (Japan)

1997-12-01

This paper explains development and examples of application of automated welding devices from a viewpoint of an element technology constituting computer integrated manufacturing (CIM), based on the history of modernization of shipyards that has been achieved to date. In the first step of promoting the modernization, elevating cutting accuracy in the uppermost stream process was thought a starting point of rationalization. What have been achieved therefrom are adoption of the most advanced NC plasma cutting machine, and improvement in the computer aided system for the cutting machines. In addition, a twenty-electrode line welder has been developed, which does not create angle deformation in welding longerons, and can be operated even by unskilled workers. The welder has successfully realized a construction method in which robots can be applied more easily. Further developments have been made on a robot to weld cells, advanced CAD/CAM operation techniques which are linked with data from design, an automatic one-side welding device which can achieve a speed 2.5 times greater than by conventional devices, and an automation device for three-dimensionally bent blocks, whose automation has been regarded difficult. 11 figs., 1 tab.

Lithium chloride ameliorates learning and memory ability and inhibits glycogen synthase kinase-3 beta activity in a mouse model of fragile X syndrome

Institute of Scientific and Technical Information of China (English)

Shengqiang Chen; Xuegang Luo; Quan Yang; Weiwen Sun; Kaiyi Cao; Xi Chen; Yueling Huang; Lijun Dai; Yonghong Yi

2011-01-01

In the present study, Fmr1 knockout mice (KO mice) were used as the model for fragile X syndrome. The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error counts, indicating a learning and memory disorder. After treatment with 30, 60, 90, 120, or 200 mg/kg lithium chloride, the learning and memory abilities of the Fmr1 KO mice were significantly ameliorated, in particular, the 200 mg/kg lithium chloride treatment had the most significant effect. Western blot analysis showed that lithium chloride significantly enhanced the expression of phosphorylated glycogen synthase kinase 3 beta, an inactive form of glycogen synthase kinase 3 beta, in the cerebral cortex and hippocampus of the Fmr1 KO mice. These results indicated that lithium chloride improved learning and memory in the Fmr1 KO mice, possibly by inhibiting glycogen synthase kinase 3 beta activity.

Murine Colitis is Mediated by Vimentin

OpenAIRE

Mor-Vaknin, Nirit; Legendre, Maureen; Yu, Yue; Serezani, Carlos H. C.; Garg, Sanjay K.; Jatzek, Anna; Swanson, Michael D.; Gonzalez-Hernandez, Marta J.; Teitz-Tennenbaum, Seagal; Punturieri, Antonello; Engleberg, N. Cary; Banerjee, Ruma; Peters-Golden, Marc; Kao, John Y.; Markovitz, David M.

2013-01-01

Vimentin, an abundant intermediate filament protein, presumably has an important role in stabilizing intracellular architecture, but its function is otherwise poorly understood. In a vimentin knockout (Vim KO) mouse model, we note that Vim KO mice challenged with intraperitoneal Escherichia coli control bacterial infection better than do wild-type (WT) mice. In vitro, Vim KO phagocytes show significantly increased capacity to mediate bacterial killing by abundant production of reactive oxygen...

Genetic disruption of the pHi-regulating proteins Na+/H+ exchanger 1 (SLC9A1) and carbonic anhydrase 9 severely reduces growth of colon cancer cells.

Science.gov (United States)

Parks, Scott K; Cormerais, Yann; Durivault, Jerome; Pouyssegur, Jacques

2017-02-07

Hypoxia and extracellular acidosis are pathophysiological hallmarks of aggressive solid tumors. Regulation of intracellular pH (pHi) is essential for the maintenance of tumor cell metabolism and proliferation in this microenvironment and key proteins involved in pHi regulation are of interest for therapeutic development. Carbonic anhydrase 9 (CA9) is one of the most robustly regulated proteins by the hypoxia inducible factor (HIF) and contributes to pHi regulation. Here, we have investigated for the first time, the role of CA9 via complete genomic knockout (ko) and compared its impact on tumor cell physiology with the essential pHi regulator Na+/H+ exchanger 1 (NHE1). Initially, we established NHE1-ko LS174 cells with inducible CA9 knockdown. While increased sensitivity to acidosis for cell survival in 2-dimensions was not observed, clonogenic proliferation and 3-dimensional spheroid growth in particular were greatly reduced. To avoid potential confounding variables with use of tetracycline-inducible CA9 knockdown, we established CA9-ko and NHE1/CA9-dko cells. NHE1-ko abolished recovery from NH4Cl pre-pulse cellular acid loading while both NHE1 and CA9 knockout reduced resting pHi. NHE1-ko significantly reduced tumor cell proliferation both in normoxia and hypoxia while CA9-ko dramatically reduced growth in hypoxic conditions. Tumor xenografts revealed substantial reductions in tumor growth for both NHE1-ko and CA9-ko. A notable induction of CA12 occurred in NHE1/CA9-dko tumors indicating a potential means to compensate for loss of pH regulating proteins to maintain growth. Overall, these genomic knockout results strengthen the pursuit of targeting tumor cell pH regulation as an effective anti-cancer strategy.

Oral aversion to dietary sugar, ethanol and glycerol correlates with alterations in specific hepatic metabolites in a mouse model of human citrin deficiency.

Science.gov (United States)

Saheki, Takeyori; Inoue, Kanako; Ono, Hiromi; Fujimoto, Yuki; Furuie, Sumie; Yamamura, Ken-Ichi; Kuroda, Eishi; Ushikai, Miharu; Asakawa, Akihiro; Inui, Akio; Eto, Kazuhiro; Kadowaki, Takashi; Moriyama, Mitsuaki; Sinasac, David S; Yamamoto, Takashi; Furukawa, Tatsuhiko; Kobayashi, Keiko

2017-04-01

Mice carrying simultaneous homozygous mutations in the genes encoding citrin, the mitochondrial aspartate-glutamate carrier 2 (AGC2) protein, and mitochondrial glycerol-3-phosphate dehydrogenase (mGPD), are a phenotypically representative model of human citrin (a.k.a., AGC2) deficiency. In this study, we investigated the voluntary oral intake and preference for sucrose, glycerol or ethanol solutions by wild-type, citrin (Ctrn)-knockout (KO), mGPD-KO, and Ctrn/mGPD double-KO mice; all substances that are known or suspected precipitating factors in the pathogenesis of human citrin deficiency. The double-KO mice showed clear suppressed intake of sucrose, consuming less with progressively higher concentrations compared to the other mice. Similar observations were made when glycerol or ethanol were given. The preference of Ctrn-KO and mGPD-KO mice varied with the different treatments; essentially no differences were observed for sucrose, while an intermediate intake or similar to that of the double-KO mice was observed for glycerol and ethanol. We next examined the hepatic glycerol 3-phosphate, citrate, citrulline, lysine, glutamate and adenine nucleotide levels following forced enteral administration of these solutions. A strong correlation between the simultaneous increased hepatic glycerol 3-phosphate and decreased ATP or total adenine nucleotide content and observed aversion of the mice during evaluation of their voluntary preferences was found. Overall, our results suggest that the aversion observed in the double-KO mice to these solutions is initiated and/or mediated by hepatic metabolic perturbations, resulting in a behavioral response to increased hepatic cytosolic NADH and a decreased cellular adenine nucleotide pool. These findings may underlie the dietary predilections observed in human citrin deficient patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Behavioral Phenotyping of Dopamine Transporter Knockout Rats: Compulsive Traits, Motor Stereotypies, and Anhedonia

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Stefano Cinque

2018-02-01

Full Text Available Alterations in dopamine neurotransmission are generally associated with diseases such as attention-deficit/hyperactivity disorder (ADHD and obsessive-compulsive disorder (OCD. Such diseases typically feature poor decision making and lack of control on executive functions and have been studied through the years using many animal models. Dopamine transporter (DAT knockout (KO and heterozygous (HET mice, in particular, have been widely used to study ADHD. Recently, a strain of DAT KO rats has been developed (1. Here, we provide a phenotypic characterization of reward sensitivity and compulsive choice by adult rats born from DAT–HET dams bred with DAT–HET males, in order to further validate DAT KO rats as an animal model for preclinical research. We first tested DAT KO rats’ sensitivity to rewarding stimuli, provided by highly appetitive food or sweet water; then, we tested their choice behavior with an Intolerance-to-Delay Task (IDT. During these tests, DAT KO rats appeared less sensitive to rewarding stimuli than wild-type (WT and HET rats: they also showed a prominent hyperactive behavior with a rigid choice pattern and a wide number of compulsive stereotypies. Moreover, during the IDT, we tested the effects of amphetamine (AMPH and RO-5203648, a trace amine-associated receptor 1 (TAAR1 partial agonist. AMPH accentuated impulsive behaviors in WT and HET rats, while it had no effect in DAT KO rats. Finally, we measured the levels of tyrosine hydroxylase, dopamine receptor 2 (D2, serotonin transporter, and TAAR1 mRNA transcripts in samples of ventral striatum, finding no significant differences between WT and KO genotypes. Throughout this study, DAT KO rats showed alterations in decision-making processes and in motivational states, as well as prominent motor and oral stereotypies: more studies are warranted to fully characterize and efficiently use them in preclinical research.

Differential response of nNOS knockout mice to MDMA ("ecstasy")- and methamphetamine-induced psychomotor sensitization and neurotoxicity.

Science.gov (United States)

Itzhak, Yossef; Anderson, Karen L; Ali, Syed F

2004-10-01

It has been shown that mice deficient in neuronal nitric oxide synthase (nNOS) gene are resistant to cocaine-induced psychomotor sensitization and methamphetamine (METH)-induced dopaminergic neurotoxicity. The present study was undertaken to investigate the hypothesis that nNOS has a major role in dopamine (DA)- but not serotonin (5-hydroxytryptamine; 5-HT)-mediated effects of psychostimulants. The response of nNOS knockout (KO) and wild-type (WT) mice to the psychomotor-stimulating and neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and METH were investigated. Repeated administration of MDMA for 5 days resulted in psychomotor sensitization in both WT and nNOS KO mice, while repeated administration of METH caused psychomotor sensitization in WT but not in KO mice. Sensitization to both MDMA and METH was persistent for 40 days in WT mice, but not in nNOS KO mice. These findings suggest that the induction of psychomotor sensitization to MDMA and METH is NO independent and NO dependent, respectively, while the persistence of sensitization to both drugs is NO dependent. For the neurochemical studies, a high dose of MDMA caused marked depletion of 5-HT in several brain regions of both WT and KO mice, suggesting that the absence of the nNOS gene did not afford protection against MDMA-induced depletion of 5-HT. Striatal dopaminergic neurotoxicity caused by high doses of MDMA and METH in WT mice was partially prevented in KO mice administered with MDMA, but it was fully precluded in KO mice administered with METH. The differential response of nNOS KO mice to the behavioral and neurotoxic effects of MDMA and METH suggests that the nNOS gene is required for the expression and persistence of DA-mediated effects of METH and MDMA, while 5-HT-mediated effects of MDMA (induction of sensitization and 5-HT depletion) are not dependent on nNOS.

Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

Science.gov (United States)

Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

2005-09-08

It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

A new human photosensitive subject with a defect in the recovery of DNA synthesis after ultraviolet-light irradiation

International Nuclear Information System (INIS)

Fujiwara, Y.; Ichihashi, M.; Kano, Y.; Goto, K.; Shimizu, K.

1981-01-01

A non-sensitive, 8-yr-old male patient (termed UV81KO) with only acute recurrent sunburns and without any other physical or neuromental retardations was studied. The patient's skin exhibited lowered minimal erythema doses between 280 and 300 nm monochromatic wavelengths without delayed peaking of erythema. UV81KO skin fibroblasts in culture was 5-fold more sensitive to 254 nm UV killing than normal cells, though the response of obligatory heterozygotes was normal. UV81KO cells were also more sensitive to killings by fluorescent sunlamp (295-300 nm UV-B) radiation, 4-nitroquinoline-1-oxide, and N-hydroxy-acetyl aminofluorene, but not by monofunctional decarbamoyl mitomycin C, bifunctional mitomycin C, and alkylating agents (methyl methanesulfonate, ethyl methanesulfonate, N-methyl-N-nitrosourea). Assays for unscheduled DNA synthesis, T4 endonuclease V-susceptible sites (pyrimidine dimers), endogenous excision-break accumulation by arabinofuranosyl cytosine-plus-hydroxyurea, single-strand-break rejoining, and molecular-weight increase of pulse-chased DNA in irradiated cells indicated no apparently detectable defects in nucleotide-excision repair processes and in replicative bypass in UV81KO cells. Despite the repair proficiency as such, UV81KO cells showed the defective recovery of DNA synthesis after 254 nm UV irradiation with 1 and 5 J/m2, at which dose the recovery occurred in normal cells. The base line level of sister-chromatid exchanges (SCEs) was higher in UV81KO cells (10-12 SCEs/cell) than in normal cells (5 SCEs/cell), although the induction rate of SCEs by 254 nm UV in UV81KO cells was the same as in normal cells. Such clinical, cellular and molecular characteristics and comparison to those in the other photodermatoses (xeroderma pigmentosum, Cockayne's syndrome, the 11961 disorder, Bloom's syndrome) can make a clear distinction of UV81KO from the others

Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level

Directory of Open Access Journals (Sweden)

Wang Jia

2009-11-01

Full Text Available Abstract Background Protein kinase C interacting protein (PKCI/HINT1 is a small protein belonging to the histidine triad (HIT family proteins. Its brain immunoreactivity is located in neurons and neuronal processes. PKCI/HINT1 gene knockout (KO mice display hyper-locomotion in response to D-amphetamine which is considered a positive symptom of schizophrenia in animal models. Postmortem studies identified PKCI/HINT1 as a candidate molecule for schizophrenia and bipolar disorder. We investigated the hypothesis that the PKCI/HINT1 gene may play an important role in regulating mood function in the CNS. We submitted PKCI/HINT1 KO mice and their wild type (WT littermates to behavioral tests used to study anti-depressant, anxiety like behaviors, and goal-oriented behavior. Additionally, as many mood disorders coincide with modifications of hypothalamic-pituitary-adrenal (HPA axis function, we assessed the HPA activity through measurement of plasma corticosterone levels. Results Compared to the WT controls, KO mice exhibited less immobility in the forced swim (FST and the tail suspension (TST tests. Activity in the TST tended to be attenuated by acute treatment with valproate at 300 mg/kg in KO mice. The PKCI/HINT1 KO mice presented less thigmotaxis in the Morris water maze and spent progressively more time in the lit compartment in the light/dark test. In a place navigation task, KO mice exhibited enhanced acquisition and retention. Furthermore, the afternoon basal plasma corticosterone level in PKCI/HINT1 KO mice was significantly higher than in the WT. Conclusion PKCI/HINT1 KO mice displayed a phenotype of behavioral and endocrine features which indicate changes of mood function, including anxiolytic-like and anti-depressant like behaviors, in conjunction with an elevated corticosterone level in plasma. These results suggest that the PKCI/HINT 1 gene could be important for the mood regulation function in the CNS.

β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

Science.gov (United States)

Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

2016-07-01

We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity.

Sex differences in insulin resistance in GABAB1 knockout mice.

Science.gov (United States)

Bonaventura, M M; Rodriguez, D; Ferreira, M L; Crivello, M; Repetto, E M; Bettler, B; Libertun, C; Lux-Lantos, V A

2013-02-27

We have previously demonstrated that the absence of functional GABA B receptors (GABABRs) disturbs glucose homeostasis in GABAB1KO mice. The aim of this work was to extend our studies of these alterations in GABAB1KO mice and investigate the sexual differences therein. Male and female, GABAB1KO and WT mice were used. Glucose and insulin tolerance tests (GTT and ITT), and insulin and glucagon secretion tests (IST and GST) were performed. Blood glucose, serum insulin and hyperglycemic hormones were determined, and HOMA-IR calculated. Skeletal muscle insulin receptor β subunit (IRβ), insulin receptor substrates 1/2 (IRS1, IRS2) and hexokinase-II levels were determined by Western blot. Skeletal muscle insulin sensitivity was assessed by in vivo insulin-induced Akt phosphorylation (Western blot). Food intake and hypothalamic NPY mRNA expression (by qPCR) were also evaluated. Fasted insulin and HOMA-IR were augmented in GABAB1KO males, with no alterations in females. Areas under the curve (AUC) for GTT and ITT were increased in GABAB1KO mice of both genders, indicating compromised insulin sensitivity. No genotype differences were observed in IST, GST or in IRβ, IRS1, IRS2 and hexokinase-II expression. Akt activation was severely impaired in GABAB1KO males while no alterations were observed in females. GABAB1KO mice showed increased food intake and NPY expression. Glucose metabolism and energy balance disruptions were more pronounced in GABAB1KO males, which develop peripheral insulin resistance probably due to augmented insulin secretion. Metabolic alterations in females were milder and possibly due to previously described reproductive disorders, such as persistent estrus. Copyright © 2012 Elsevier Inc. All rights reserved.

Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

Science.gov (United States)

Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

2017-09-01

The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes

Science.gov (United States)

Werneck-de-Castro, Joao P.; Fonseca, Tatiana L.; Ignacio, Daniele L.; Fernandes, Gustavo W.; Andrade-Feraud, Cristina M.; Lartey, Lattoya J.; Ribeiro, Marcelo B.; Ribeiro, Miriam O.; Gereben, Balazs

2015-01-01

The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50% in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured soleus T3 content and found it to be normal. We also looked at the expression of T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, α-actin, myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2 activity in control animals. In adult soleus the baseline level of D2 activity was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals performed indistinguishably from controls on a treadmill test, running for approximately 16 minutes and reached a speed of about 23 m/min; muscle strength was about 0.3 mN/m·g body weight in SKM-D2KO and control ankle muscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers. PMID:26214036

A new human photosensitive subject with a defect in the recovery of DNA synthesis after ultraviolet-light irradiation

Energy Technology Data Exchange (ETDEWEB)

Fujiwara, Y.; Ichihashi, M.; Kano, Y.; Goto, K.; Shimizu, K.

1981-09-01

A non-sensitive, 8-yr-old male patient (termed UV81KO) with only acute recurrent sunburns and without any other physical or neuromental retardations was studied. The patient's skin exhibited lowered minimal erythema doses between 280 and 300 nm monochromatic wavelengths without delayed peaking of erythema. UV81KO skin fibroblasts in culture was 5-fold more sensitive to 254 nm UV killing than normal cells, though the response of obligatory heterozygotes was normal. UV81KO cells were also more sensitive to killings by fluorescent sunlamp (295-300 nm UV-B) radiation, 4-nitroquinoline-1-oxide, and N-hydroxy-acetyl aminofluorene, but not by monofunctional decarbamoyl mitomycin C, bifunctional mitomycin C, and alkylating agents (methyl methanesulfonate, ethyl methanesulfonate, N-methyl-N-nitrosourea). Assays for unscheduled DNA synthesis, T4 endonuclease V-susceptible sites (pyrimidine dimers), endogenous excision-break accumulation by arabinofuranosyl cytosine-plus-hydroxyurea, single-strand-break rejoining, and molecular-weight increase of pulse-chased DNA in irradiated cells indicated no apparently detectable defects in nucleotide-excision repair processes and in replicative bypass in UV81KO cells. Despite the repair proficiency as such, UV81KO cells showed the defective recovery of DNA synthesis after 254 nm UV irradiation with 1 and 5 J/m2, at which dose the recovery occurred in normal cells. The base line level of sister-chromatid exchanges (SCEs) was higher in UV81KO cells (10-12 SCEs/cell) than in normal cells (5 SCEs/cell), although the induction rate of SCEs by 254 nm UV in UV81KO cells was the same as in normal cells. Such clinical, cellular and molecular characteristics and comparison to those in the other photodermatoses (xeroderma pigmentosum, Cockayne's syndrome, the 11961 disorder, Bloom's syndrome) can make a clear distinction of UV81KO from the others.

Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

International Nuclear Information System (INIS)

Becks, Lisa; Shi, Runhua; McLarty, Jerry; Pruitt, Kevin; Zhang, Songlin; Kleiner-Hancock, Heather E; Prince, Misty; Burson, Hannah; Christophe, Christopher; Broadway, Mason; Itoh, Ken; Yamamoto, Masayuki; Mathis, Michael; Orchard, Elysse

2010-01-01

Activation of nuclear factor erythroid 2-related factor (Nrf2), which belongs to the basic leucine zipper transcription factor family, is a strategy for cancer chemopreventive phytochemicals. It is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1 and peroxiredoxin 1, by activating the antioxidant response element (ARE). We hypothesized that (1) the citrus coumarin auraptene may suppress premalignant mammary lesions via activation of Nrf2/ARE, and (2) that Nrf2 knockout (KO) mice would be more susceptible to mammary carcinogenesis. Premalignant lesions and mammary carcinomas were induced by medroxyprogesterone acetate and 7,12-dimethylbenz[a]anthracene treatment. The 10-week pre-malignant study was performed in which 8 groups of 10 each female wild-type (WT) and KO mice were fed either control diet or diets containing auraptene (500 ppm). A carcinogenesis study was also conducted in KO vs. WT mice (n = 30-34). Comparisons between groups were evaluated using ANOVA and Kaplan-Meier Survival statistics, and the Mann-Whitney U-test. All mice treated with carcinogen exhibited premalignant lesions but there were no differences by genotype or diet. In the KO mice, there was a dramatic increase in mammary carcinoma growth rate, size, and weight. Although there was no difference in overall survival, the KO mice had significantly lower mammary tumor-free survival. Also, in the KO mammary carcinomas, the active forms of NF-κB and β-catenin were increased ~2-fold whereas no differences in oxidized proteins were observed. Many other tumors were observed, including lymphomas. Interestingly, the incidences of lung adenomas in the KO mice were significantly higher than in the WT mice. We report, for the first time, that there was no apparent difference in the formation of premalignant lesions, but rather, the KO mice exhibited rapid, aggressive mammary carcinoma progression

Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

International Nuclear Information System (INIS)

Zhang, Pengpeng; Shan, Tizhong; Liang, Xinrong; Deng, Changyan; Kuang, Shihuan

2014-01-01

Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor flox/flox mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor flox/flox mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function

Unusual social behavior in HPC-1/syntaxin1A knockout mice is caused by disruption of the oxytocinergic neural system.

Science.gov (United States)

Fujiwara, Tomonori; Sanada, Masumi; Kofuji, Takefumi; Akagawa, Kimio

2016-07-01

HPC-1/syntaxin1A (STX1A), a neuronal soluble N-ethylmaleimide-sensitive fusion attachment protein receptor, contributes to neural function in the CNS by regulating transmitter release. Recent studies reported that STX1A is associated with human neuropsychological disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder. Previously, we showed that STX1A null mutant mice (STX1A KO) exhibit neuropsychological abnormalities, such as fear memory deficits, attenuation of latent inhibition, and unusual social behavior. These observations suggested that STX1A may be involved in the neuropsychological basis of these abnormalities. Here, to study the neural basis of social behavior, we analyzed the profile of unusual social behavior in STX1A KO with a social novelty preference test, which is a useful method for quantification of social behavior. Interestingly, the unusual social behavior in STX1A KO was partially rescued by intracerebroventricular administration of oxytocin (OXT). In vivo microdialysis studies revealed that the extracellular OXT concentration in the CNS of STX1A KO was significantly lower compared with wild-type mice. Furthermore, dopamine-induced OXT release was reduced in STX1A KO. These results suggested that STX1A plays an important role in social behavior through regulation of the OXTergic neural system. Dopamine (DA) release is reduced in CNS of syntaxin1A null mutant mice (STX1A KO). Unusual social behavior was observed in STX1A KO. We found that oxytocin (OXT) release, which was stimulated by DA, was reduced and was rescued the unusual social behavior in STX1A KO was rescued by OXT. These results indicated that STX1A plays an important role in promoting social behavior through regulation of DA-induced OXT release in amygdala. © 2016 International Society for Neurochemistry.

Neutron Spectrum Parameters In Inner Irradiation Channel Of The Nigeria Research Reactor-1 (NIRR-1) For Use In Absolute And KO-NAA Methods

International Nuclear Information System (INIS)

Jonah, S.A; Balogun, G.I; Mayaki, M.C.

2004-01-01

In Nigeria, the first Nuclear Reactor achieved critically on February 03, 2004 at about 11:35 GMT and has been commissioned or training and research. It is a Miniature Neutron Source Reactor (MNSR), code-named Nigeria Research Reactor-1 (NIRR-1). NIRR-1 has a tan-in-pool structural configuration and a nominal thermal power rating of 30 Kw. With a built-in clean old core excess reactivity of 3.77 mk determined during the on-site zero and critically experimental, the reactor can operate for a n.cm-2 .s-1 in the inner irradiation channels). Under these conditions, the reactor can operate with the same fuel loading for over ten years with a burn-up of <1%. A detailed description of operating characteristics for NIRR-1, measured during the on-site zero-power and criticality experiments has been given elsewhere. In order to extend its utilization to include absolute and ko-NAA methods, the neutron spectrum parameters in the irradiation channels: power and critically experiments has been given elsewhere. In order to extend it's the irradiation channels: thermal-to-epithermal flux ration, F; and epithermal flux shape factor, a in both the inner and outer irradiation channels must be determined experimentally. In this work, we have developed and experimental procedure for monitoring the neutron spectrum parameters in an inner irradiation channel based on irradiation and gamma-ray counting of detector foils via (n,y), (n,p) and (n,a) dosimetry reactions. Results obtained indicate that a thermal neutron flux of (5.14+-0.02) x 1011 n/c m2.s determined by foil activation method in the inner irradiation channel, B2, at a power level of 15.5 kw corresponds to the flux indicators on the control console and the micro-computer control system respectively. Other parameters of the neutron spectrum determined for inner irradiation channel B2, are: a -0.0502+0.003; 18.92+-0.14; F = 3.87=0.23. The method was validated through the comparison of our result with published neutron spectrum

Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: a study on enzyme knockout mice

DEFF Research Database (Denmark)

Zhang, Yao; Cheng, Yajun; Hansen, Gert H

2011-01-01

) and KO mice were fed ³H-palmitic acid labeled SM together with milk SM by gavage. The lipids in intestinal content, intestinal tissues, serum, and liver were analyzed by TLC. In KO mice, nondigested ³H-SM in the intestinal content increased by 6-fold and the formation of ³H-ceramide decreased markedly....... The KO mice also showed significantly decreased radioactivity in liver and serum. Furthermore, alkaline phosphatase activity in the mucosa was reduced by 50% and histological comparison of two female littermates preliminarily suggested mucosal hypertrophy in KO mice. This study provides definite proof...... for crucial roles of alk-SMase in SM digestion and points to possible roles in regulating mucosal growth and alkaline phosphatase function....

Hyperactivity and lack of social discrimination in the adolescent Fmr1 knockout mouse.

Science.gov (United States)

Sørensen, Emilie M; Bertelsen, Freja; Weikop, Pia; Skovborg, Maria M; Banke, Tue; Drasbek, Kim R; Scheel-Krüger, Jørgen

2015-12-01

The aims of this study were to investigate behaviour relevant to human autism spectrum disorder (ASD) and the fragile X syndrome in adolescent Fmr1 knockout (KO) mice and to evaluate the tissue levels of striatal monoamines. Fmr1 KO mice were evaluated in the open field, marble burying and three-chamber test for the presence of hyperactivity, anxiety, repetitive behaviour, sociability and observation of social novelty compared with wild-type (WT) mice. The Fmr1 KO mice expressed anxiety and hyperactivity in the open field compared with WT mice. This increased level of hyperactivity was confirmed in the three-chamber test. Fmr1 KO mice spent more time with stranger mice compared with the WT. However, after a correction for hyperactivity, their apparent increase in sociability became identical to that of the WT. Furthermore, the Fmr1 KO mice could not differentiate between a familiar or a novel mouse. Monoamines were measured by HPLC: Fmr1 KO mice showed an increase in the striatal dopamine level. We conclude that the fragile X syndrome model seems to be useful for understanding certain aspects of ASD and may have translational interest for studies of social behaviour when hyperactivity coexists in ASD patients.

Nepro is localized in the nucleolus and essential for preimplantation development in mice.

Science.gov (United States)

Hashimoto, Masakazu; Sato, Tatsuya; Muroyama, Yuko; Fujimura, Lisa; Hatano, Masahiko; Saito, Tetsuichiro

2015-09-01

We generated knockout (KO) mice of Nepro, which has been shown to be necessary to maintain neural progenitor cells downstream of Notch in the mouse developing neocortex by using knockdown experiments, to explore its function in embryogenesis. Nepro KO embryos were morphologically indistinguishable from wild type (WT) embryos until the morula stage but failed in blastocyst formation, and many cells of the KO embryos resulted in apoptosis. We found that Nepro was localized in the nucleolus at the blastocyst stage. The number of nucleolus precursor bodies (NPBs) and nucleoli per nucleus was significantly higher in Nepro KO embryos compared with WT embryos later than the 2-cell stage. Furthermore, at the morula stage, whereas 18S rRNA and ribosomal protein S6 (rpS6), which are components of the ribosome, were distributed to the cytoplasm in WT embryos, they were mainly localized in the nucleoli in Nepro KO embryos. In addition, in Nepro KO embryos, the amount of the mitochondria-associated p53 protein increased, and Cytochrome c was distributed in the cytoplasm. These findings indicate that Nepro is a nucleolus-associated protein, and its loss leads to the apoptosis before blastocyst formation in mice. © 2015 Japanese Society of Developmental Biologists.

Age-Dependent Long-Term Potentiation Deficits in the Prefrontal Cortex of the Fmr1 Knockout Mouse Model of Fragile X Syndrome.

Science.gov (United States)

Martin, Henry G S; Lassalle, Olivier; Brown, Jonathan T; Manzoni, Olivier J

2016-05-01

The most common inherited monogenetic cause of intellectual disability is Fragile X syndrome (FXS). The clinical symptoms of FXS evolve with age during adulthood; however, neurophysiological data exploring this phenomenon are limited. The Fmr1 knockout (Fmr1KO) mouse models FXS, but studies in these mice of prefrontal cortex (PFC) function are underrepresented, and aging linked data are absent. We studied synaptic physiology and activity-dependent synaptic plasticity in the medial PFC of Fmr1KO mice from 2 to 12 months. In young adult Fmr1KO mice, NMDA receptor (NMDAR)-mediated long-term potentiation (LTP) is intact; however, in 12-month-old mice this LTP is impaired. In parallel, there was an increase in the AMPAR/NMDAR ratio and a concomitant decrease of synaptic NMDAR currents in 12-month-old Fmr1KO mice. We found that acute pharmacological blockade of mGlu5 receptor in 12-month-old Fmr1KO mice restored a normal AMPAR/NMDAR ratio and LTP. Taken together, the data reveal an age-dependent deficit in LTP in Fmr1KO mice, which may correlate to some of the complex age-related deficits in FXS. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A krill oil supplemented diet suppresses hepatic steatosis in high-fat fed rats.

Science.gov (United States)

Ferramosca, Alessandra; Conte, Annalea; Burri, Lena; Berge, Kjetil; De Nuccio, Francesco; Giudetti, Anna Maria; Zara, Vincenzo

2012-01-01

Krill oil (KO) is a dietary source of n-3 polyunsaturated fatty acids, mainly represented by eicosapentaenoic acid and docosahexaenoic acid bound to phospholipids. The supplementation of a high-fat diet with 2.5% KO efficiently prevented triglyceride and cholesterol accumulation in liver of treated rats. This effect was accompanied by a parallel reduction of the plasma levels of triglycerides and glucose and by the prevention of a plasma insulin increase. The investigation of the molecular mechanisms of KO action in high-fat fed animals revealed a strong decrease in the activities of the mitochondrial citrate carrier and of the cytosolic acetyl-CoA carboxylase and fatty acid synthetase, which are both involved in hepatic de novo lipogenesis. In these animals a significant increase in the activity of carnitine palmitoyl-transferase I and in the levels of carnitine was also observed, suggesting a concomitant stimulation of hepatic fatty acid oxidation. The KO supplemented animals also retained an efficient mitochondrial oxidative phosphorylation, most probably as a consequence of a KO-induced arrest of the uncoupling effects of a high-fat diet. Lastly, the KO supplementation prevented an increase in body weight, as well as oxidative damage of lipids and proteins, which is often found in high-fat fed animals.

Increased anxiety-related behaviour in Hint1 knockout mice.

Science.gov (United States)

Varadarajulu, Jeeva; Lebar, Maria; Krishnamoorthy, Gurumoorthy; Habelt, Sonja; Lu, Jia; Bernard Weinstein, I; Li, Haiyang; Holsboer, Florian; Turck, Christoph W; Touma, Chadi

2011-07-07

Several reports have implicated a role for the histidine triad nucleotide-binding protein-1 (Hint1) in psychiatric disorders. We have studied the emotional behaviour of male Hint1 knockout (Hint1 KO) mice in a battery of tests and performed biochemical analyses on brain tissue. The behavioural analysis revealed that Hint1 KO mice exhibit an increased emotionality phenotype compared to wildtype (WT) mice, while no significant differences in locomotion or general exploratory activity were noted. In the elevated plus-maze (EPM) test, the Hint1 KO animals entered the open arms of the apparatus less often than WT littermates. Similarly, in the dark-light box test, Hint1 KO mice spent less time in the lit compartment and the number of entries were reduced, which further confirmed an increased anxiety-related behaviour. Moreover, the Hint1 KO animals showed significantly more struggling and less floating behaviour in the forced swim test (FST), indicating an increased emotional arousal in aversive situations. Hint1 is known as a protein kinase C (PKC) interacting protein. Western blot analysis showed that PKCγ expression was elevated in Hint1 KO compared to WT mice. Interestingly, PKCγ mRNA levels of the two groups did not show a significant difference, implying a post-transcriptional PKCγ regulation. In addition, PKC enzymatic activity was increased in Hint1 KO compared to WT mice. In summary, our results indicate a role for Hint1 and PKCγ in modulating anxiety-related and stress-coping behaviour in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

Clinical characteristics of keratosis obturans and external auditory canal cholesteatoma.

Science.gov (United States)

Park, So Young; Jung, Young Hoon; Oh, Jeong-Hoon

2015-02-01

Keratosis obturans (KO) and external auditory canal cholesteatoma (EACC) have been considered separate entities. While the disorders are distinct, they share many overlapping characteristics, making a correct diagnosis difficult. In the present study, we compared their clinical characteristics and radiological features to clarify the diagnostic criteria. Retrospective case series. Academic medical center. The clinical data of 23 cases of EACC and KO were retrospectively reviewed. The following clinical characteristics were compared between the 2 groups: sex, age, onset of symptoms, follow-up period, audiometric results, and imaging findings on temporal bone computed tomography including bilaterality, location, and the presence of extension to adjacent tissue. The mean age of the EACC group was significantly older than that of the KO group. All of the cases of EACC occurred unilaterally, and bilateral occurrences of KO were observed in 4 of 9 cases. All of the lesions in the KO group were circumferential, and no lesion in the EACC group invaded the superior canal wall. No significant differences in symptoms, such as acute otalgia, otorrhea, and hearing loss, were noted between the 2 groups. The incidence of conductive hearing impairment more than 10 dB was higher in the KO group than in the EACC group. Thus, KO and EACC are 2 distinct disease entities that share common features in clinical characteristics except for predominant age and bilaterality. Conservative treatment with meticulous cleaning of the lesion was successful in most cases with a long-term follow-up. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Increased lipolysis and energy expenditure in a mouse model with severely impaired glucagon secretion.

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Phing-How Lou

Full Text Available BACKGROUND: Secretion of insulin and glucagon is triggered by elevated intracellular calcium levels. Although the precise mechanism by which the calcium signal is coupled to insulin and glucagon granule exocytosis is unclear, synaptotagmin-7 has been shown to be a positive regulator of calcium-dependent insulin and glucagon secretion, and may function as a calcium sensor for insulin and glucagon granule exocytosis. Deletion of synaptotagmin-7 leads to impaired glucose-stimulated insulin secretion and nearly abolished Ca(2+-dependent glucagon secretion in mice. Under non-stressed resting state, however, synaptotagmin-7 KO mice exhibit normal insulin level but severely reduced glucagon level. METHODOLOGY/PRINCIPAL FINDINGS: We studied energy expenditure and metabolism in synaptotagmin-7 KO and control mice using indirect calorimetry and biochemical techniques. Synaptotagmin-7 KO mice had lower body weight and body fat content, and exhibited higher oxygen consumption and basal metabolic rate. Respiratory exchange ratio (RER was lower in synaptotagmin-7 KO mice, suggesting an increased use of lipid in their energy production. Consistent with lower RER, gene expression profiles suggest enhanced lipolysis and increased capacity for fatty acid transport and oxidation in synaptotagmin-7 KO mice. Furthermore, expression of uncoupling protein 3 (UCP3 in skeletal muscle was approximately doubled in the KO mice compared with control mice. CONCLUSIONS: These results show that the lean phenotype in synaptotagmin-7 KO mice was mostly attributed to increased lipolysis and energy expenditure, and suggest that reduced glucagon level may have broad influence on the overall metabolism in the mouse model.

Epinephrine increases contextual learning through activation of peripheral β2-adrenoceptors.

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Alves, Ester; Lukoyanov, Nikolay; Serrão, Paula; Moura, Daniel; Moreira-Rodrigues, Mónica

2016-06-01

Phenylethanolamine-N-methyltransferase knockout (Pnmt-KO) mice are unable to synthesize epinephrine and display reduced contextual fear. However, the precise mechanism responsible for impaired contextual fear learning in these mice is unknown. Our aim was to study the mechanism of epinephrine-dependent contextual learning. Wild-type (WT) or Pnmt-KO (129x1/SvJ) mice were submitted to a fear conditioning test either in the absence or in the presence of epinephrine, isoprenaline (non-selective β-adrenoceptor agonist), fenoterol (selective β2-adrenoceptor agonist), epinephrine plus sotalol (non-selective β-adrenoceptor antagonist), and dobutamine (selective β1-adrenoceptor agonist). Catecholamines were separated by reverse-phase HPLC and quantified by electrochemical detection. Blood glucose was measured by coulometry. Re-exposure to shock context induced higher freezing in WT and Pnmt-KO mice treated with epinephrine and fenoterol than in mice treated with vehicle. In addition, freezing response in Pnmt-KO mice was much lower than in WT mice. Freezing induced by epinephrine was blocked by sotalol in Pnmt-KO mice. Epinephrine and fenoterol treatment restored glycemic response in Pnmt-KO mice. Re-exposure to shock context did not induce a significant difference in freezing in Pnmt-KO mice treated with dobutamine and vehicle. Aversive memories are best retained if moderately high plasma epinephrine concentrations occur at the same moment as the aversive stimulus. In addition, epinephrine increases context fear learning by acting on peripheral β2-adrenoceptors, which may induce high levels of blood glucose. Since glucose crosses the blood-brain barrier, it may enhance hippocampal-dependent contextual learning.

Selective effects of potassium elevations on glutamate signaling and action potential conduction in hippocampus.

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Meeks, Julian P; Mennerick, Steven

2004-01-07

High-frequency synaptic transmission is depressed by moderate rises in the extracellular potassium concentration ([K+]o). Previous reports have indicated that depression of action potential signaling may underlie the synaptic depression. Here, we investigated the specific contribution of K+-induced action potential changes to synaptic depression. We found that glutamatergic transmission in the hippocampal area CA1 was significantly depressed by 8-10 mM [K+]o, but that GABAergic transmission remained intact. Riluzole, a drug that slows recovery from inactivation of voltage-gated sodium channels (NaChs), interacts with subthreshold [K+]o to depress afferent volleys and EPSCs strongly. Thus, elevated [K+]o likely depresses synapses by slowing NaCh recovery from inactivation. It is unclear from previous studies whether [K+]o-induced action potential depression is caused by changes in initiation, reliability, or waveform. We investigated these possibilities explicitly. [K+]o-induced afferent volley depression was independent of stimulus strength, suggesting that changes in action potential initiation do not explain [K+]o-induced depression. Measurements of action potentials from single axons revealed that 8 mM [K+]o increased conduction failures in a subpopulation of fibers and depressed action potential amplitude in all fibers. Together, these changes quantitatively account for the afferent volley depression. We estimate that conduction failure explains more than half of the synaptic depression observed at 8 mM [K+]o, with the remaining depression likely explained by waveform changes. These mechanisms of selective sensitivity of glutamate release to [K+]o accumulation represent a unique neuromodulatory mechanism and a brake on runaway excitation.

Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+ 3 oxidation state) methyltransferase knockout mice. A preliminary report

International Nuclear Information System (INIS)

Yokohira, Masanao; Arnold, Lora L.; Pennington, Karen L.; Suzuki, Shugo; Kakiuchi-Kiyota, Satoko; Herbin-Davis, Karen; Thomas, David J.; Cohen, Samuel M.

2010-01-01

Arsenic (+ 3 oxidation state) methyltransferase (As3mt) catalyzes reactions which convert inorganic arsenic to methylated metabolites. This study determined whether the As3mt null genotype in the mouse modifies cytotoxic and proliferative effects seen in urinary bladders of wild type mice after exposure to inorganic arsenic. Female wild type C57BL/6 mice and As3mt KO mice were divided into 3 groups each (n = 8) with free access to a diet containing 0, 100 or 150 ppm of arsenic as arsenite (As III ). During the first week of As III exposure, As3mt KO mice exhibited severe and lethal systemic toxicity. At termination, urinary bladders of both As3mt KO and wild type mice showed hyperplasia by light microscopy. As expected, arsenic-containing granules were found in the superficial urothelial layer of wild type mice. In As3mt KO mice these granules were present in all layers of the bladder epithelium and were more abundant and larger than in wild type mice. Scanning electron microscopy of the bladder urothelium of As3mt KO mice treated with 100 ppm As III showed extensive superficial necrosis and hyperplastic changes. In As3mt KO mice, livers showed severe acute inflammatory changes and spleen size and lymphoid areas were decreased compared with wild type mice. Thus, diminished arsenic methylation in As3mt KO mice exacerbates systemic toxicity and the effects of As III on the bladder epithelium, showing that altered kinetic and dynamic behavior of arsenic can affect its toxicity.

Efficient CRISPR/Cas9-Mediated Versatile, Predictable, and Donor-Free Gene Knockout in Human Pluripotent Stem Cells.

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Liu, Zhongliang; Hui, Yi; Shi, Lei; Chen, Zhenyu; Xu, Xiangjie; Chi, Liankai; Fan, Beibei; Fang, Yujiang; Liu, Yang; Ma, Lin; Wang, Yiran; Xiao, Lei; Zhang, Quanbin; Jin, Guohua; Liu, Ling; Zhang, Xiaoqing

2016-09-13

Loss-of-function studies in human pluripotent stem cells (hPSCs) require efficient methodologies for lesion of genes of interest. Here, we introduce a donor-free paired gRNA-guided CRISPR/Cas9 knockout strategy (paired-KO) for efficient and rapid gene ablation in hPSCs. Through paired-KO, we succeeded in targeting all genes of interest with high biallelic targeting efficiencies. More importantly, during paired-KO, the cleaved DNA was repaired mostly through direct end joining without insertions/deletions (precise ligation), and thus makes the lesion product predictable. The paired-KO remained highly efficient for one-step targeting of multiple genes and was also efficient for targeting of microRNA, while for long non-coding RNA over 8 kb, cleavage of a short fragment of the core promoter region was sufficient to eradicate downstream gene transcription. This work suggests that the paired-KO strategy is a simple and robust system for loss-of-function studies for both coding and non-coding genes in hPSCs. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Characterization of ent-kaurene synthase and kaurene oxidase involved in gibberellin biosynthesis from Scoparia dulcis.

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Yamamura, Yoshimi; Taguchi, Yukari; Ichitani, Kei; Umebara, Io; Ohshita, Ayako; Kurosaki, Fumiya; Lee, Jung-Bum

2018-03-01

Gibberellins (GAs) are ubiquitous diterpenoids in higher plants, whereas some higher plants produce unique species-specific diterpenoids. In GA biosynthesis, ent-kaurene synthase (KS) and ent-kaurene oxidase (KO) are key players which catalyze early step(s) of the cyclization and oxidation reactions. We have studied the functional characterization of gene products of a KS (SdKS) and two KOs (SdKO1 and SdKO2) involved in GA biosynthesis in Scoparia dulcis. Using an in vivo heterologous expression system of Escherichia coli, we found that SdKS catalyzed a cyclization reaction from ent-CPP to ent-kaurene and that the SdKOs oxidized ent-kaurene to ent-kaurenoic acid after modification of the N-terminal region for adaptation to the E. coli expression system. The real-time PCR results showed that the SdKS, SdKO1 and SdKO2 genes were mainly expressed in the root and lateral root systems, which are elongating tissues. Based on these results, we suggest that these three genes may be responsible for the metabolism of GAs in S. dulcis.

Knockout of Murine Mamld1 Impairs Testicular Growth and Daily Sperm Production but Permits Normal Postnatal Androgen Production and Fertility.

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Miyado, Mami; Yoshida, Kaoru; Miyado, Kenji; Katsumi, Momori; Saito, Kazuki; Nakamura, Shigeru; Ogata, Tsutomu; Fukami, Maki

2017-06-19

MAMLD1 has been implicated in testicular function in both human and mouse fetuses. Although three patients with MAMLD1 mutations were reported to have hypergonadotropic hypogonadism in their teens, the functional significance of MAMLD1 in the postnatal testis remains unclear. Here, we analyzed the phenotype of Mamld1 knockout (KO) male mice at reproductive ages. The reproductive organs of KO male mice were morphologically unremarkable, except for relatively small testes. Seminiferous tubule size and number of proliferating spermatogonia/spermatocytes were reduced in the KO testis. Daily sperm production of KO mice was mildly attenuated, whereas total sperm counts in epididymal semen remained normal. Sperm motility and morphology, as well as androgen levels in serum and testicular tissues and the number of pups born from cross-mated wildtype (WT) female mice, were comparable between WT and KO male mice. These results indicate that MAMLD1 contributes to the maintenance of postnatal testicular growth and daily sperm production but is dispensable for androgen biosynthesis and fertility. MAMLD1 likely plays supporting roles in multiple and continuous steps of male reproduction.

Inhibitory Effects of North American Wild Rice on Monocyte Adhesion and Inflammatory Modulators in Low-Density Lipoprotein Receptor-Knockout Mice.

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Moghadasian, Mohammed H; Zhao, Ruozhi; Ghazawwi, Nora; Le, Khuong; Apea-Bah, Franklin B; Beta, Trust; Shen, Garry X

2017-10-18

The present study examined the effects of wild rice on monocyte adhesion, inflammatory and fibrinolytic mediators in low-density lipoprotein receptor-knockout (LDLr-KO) mice. Male LDLr-KO mice received a cholesterol (0.06%, w/w)-supplemented diet with or without white or wild rice (60%, w/w) for 20 weeks. White rice significantly increased monocyte adhesion and abundances of monocyte chemoattractant protein-1, tissue necrosis factor-α, intracellular cell adhesion molecule-1, plasminogen activator inhibitor-1, urokinase plasminogen activator (uPA), and uPA receptor in aortae and hearts of LDLr-KO mice compared to the control diet. Wild rice inhibited monocyte adhesion to the aorta, atherosclerosis, and abundances of the inflammatory and fibrinolytic regulators in the cardiovascular tissue of LDLr-KO mice compared to white rice. White or wild rice did not significantly alter the levels of cholesterol, triglycerides, or antioxidant enzymes in plasma. The anti-atherosclerotic effect of wild rice may result from its inhibition on monocyte adhesion and inflammatory modulators in LDLr-KO mice.

Knockout of Murine Mamld1 Impairs Testicular Growth and Daily Sperm Production but Permits Normal Postnatal Androgen Production and Fertility

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Mami Miyado

2017-06-01

Full Text Available MAMLD1 has been implicated in testicular function in both human and mouse fetuses. Although three patients with MAMLD1 mutations were reported to have hypergonadotropic hypogonadism in their teens, the functional significance of MAMLD1 in the postnatal testis remains unclear. Here, we analyzed the phenotype of Mamld1 knockout (KO male mice at reproductive ages. The reproductive organs of KO male mice were morphologically unremarkable, except for relatively small testes. Seminiferous tubule size and number of proliferating spermatogonia/spermatocytes were reduced in the KO testis. Daily sperm production of KO mice was mildly attenuated, whereas total sperm counts in epididymal semen remained normal. Sperm motility and morphology, as well as androgen levels in serum and testicular tissues and the number of pups born from cross-mated wildtype (WT female mice, were comparable between WT and KO male mice. These results indicate that MAMLD1 contributes to the maintenance of postnatal testicular growth and daily sperm production but is dispensable for androgen biosynthesis and fertility. MAMLD1 likely plays supporting roles in multiple and continuous steps of male reproduction.

Dgroup: DG01062 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available ceptor antagonist, Phosphodiesterase (PDE) inhibitor, Xanthine cardiodiuretics; X...anthine bronchodilator; Cardiac diuretics ADORA1 [HSA:134] [KO:K04265] ADORA2A [HSA:135] [KO:K04266] PDE [HS

Drastic anthocyanin increase in response to PAP1 overexpression in fls1 knockout mutant confers enhanced osmotic stress tolerance in Arabidopsis thaliana.

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Lee, Won Je; Jeong, Chan Young; Kwon, Jaeyoung; Van Kien, Vu; Lee, Dongho; Hong, Suk-Whan; Lee, Hojoung

2016-11-01

KEY MESSAGE : pap1 - D/fls1ko double mutant plants that produce substantial amounts of anthocyanin show tolerance to abiotic stress. Anthocyanins are flavonoids that are abundant in various plants and have beneficial effects on both plants and humans. Many genes in flavonoid biosynthetic pathways have been identified, including those in the MYB-bHLH-WD40 (MBW) complex. The MYB gene Production of Anthocyanin Pigment 1 (PAP1) plays a particularly important role in anthocyanin accumulation. PAP1 expression in many plant systems strongly increases anthocyanin levels, resulting in a dark purple color in many plant organs. In this study, we generated double mutant plants that harbor fls1ko in the pap1-D background (i.e., pap1-D/fls1ko plants), to examine whether anthocyanins can be further enhanced by blocking flavonol biosynthesis under PAP1 overexpression. We also wanted to examine whether the increased anthocyanin levels contribute to defense against osmotic stresses. The pap1-D/fls1ko mutants accumulated higher anthocyanin levels than pap1-D plants in both control and sucrose-treated conditions. However, flavonoid biosynthesis genes were slightly down-regulated in the pap1-D/fls1ko seedlings as compared to their expression in pap1-D seedlings. We also report the performance of pap1-D/fls1ko seedlings in response to plant osmotic stresses.

Mucin deficiency causes functional and structural changes of the ocular surface.

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Floyd, Anne M; Zhou, Xu; Evans, Christopher; Rompala, Olivia J; Zhu, Lingxiang; Wang, Mingwu; Chen, Yin

2012-01-01

MUC5AC is the most abundant gel-forming mucin in the ocular system. However, the specific function is unknown. In the present study, a Muc5ac knockout (KO) mouse model was subject to various physiological measurements as compared to its wide-type (WT) control. Interestingly, when KO mice were compared to WT mice, the mean tear break up time (TBUT) values were significantly lower and corneal fluorescein staining scores were significantly higher. But the tear volume was not changed. Despite the lack of Muc5ac expression in the conjunctiva of KO mice, Muc5b expression was significantly increased in these mice. Corneal opacification, varying in location and severity, was found in a few KO mice but not in WT mice. The present results suggest a significant difference in the quality, but not the quantity, of tear fluid in the KO mice compared to WT mice. Dry eye disease is multifactorial and therefore further evaluation of the varying components of the tear film, lacrimal unit and corneal structure of these KO mice may help elucidate the role of mucins in dry eye disease. Because Muc5ac knockout mice have clinical features of dry eye, this mouse model will be extremely useful for further studies regarding the pathophysiology of the ocular surface in dry eye in humans.

Mucin deficiency causes functional and structural changes of the ocular surface.

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Anne M Floyd

Full Text Available MUC5AC is the most abundant gel-forming mucin in the ocular system. However, the specific function is unknown. In the present study, a Muc5ac knockout (KO mouse model was subject to various physiological measurements as compared to its wide-type (WT control. Interestingly, when KO mice were compared to WT mice, the mean tear break up time (TBUT values were significantly lower and corneal fluorescein staining scores were significantly higher. But the tear volume was not changed. Despite the lack of Muc5ac expression in the conjunctiva of KO mice, Muc5b expression was significantly increased in these mice. Corneal opacification, varying in location and severity, was found in a few KO mice but not in WT mice. The present results suggest a significant difference in the quality, but not the quantity, of tear fluid in the KO mice compared to WT mice. Dry eye disease is multifactorial and therefore further evaluation of the varying components of the tear film, lacrimal unit and corneal structure of these KO mice may help elucidate the role of mucins in dry eye disease. Because Muc5ac knockout mice have clinical features of dry eye, this mouse model will be extremely useful for further studies regarding the pathophysiology of the ocular surface in dry eye in humans.

Nfatc2 and Tob1 have non-overlapping function in T cell negative regulation and tumorigenesis.

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Sarah L May

Full Text Available Nfatc2 and Tob1 are intrinsic negative regulators of T cell activation. Nfatc2-deficient and Tob1-deficient T cells show reduced thresholds of activation; however, whether these factors have independent or overlapping roles in negative regulation of T cell responses has not been previously examined. Here, we show that Nfatc2 knockout (KO but not Tob1 KO mice have age-associated accumulation of persistently activated T cells in vivo and expansion of the CD44+ memory cell compartment and age-associated lymphocytic infiltrates in visceral organs, without significant changes in numbers of CD4+CD25+Foxp3+ regulatory T cells (Treg. In vitro, CD4+CD25- "conventional" T cells (Tconvs from both KO strains showed greater proliferation than wild type (WT Tconvs. However, while Tregs from Nfatc2 KO mice retained normal suppressive function, Tregs from Tob1 KOs had enhanced suppressive activity. Nfatc2 KO Tconvs expanded somewhat more rapidly than WT Tconvs under conditions of homeostatic proliferation, but their accelerated growth capacity was negated, at least acutely, in a lymphoreplete environment. Finally, Nfatc2 KO mice developed a previously uncharacterized increase in B-cell malignancies, which was not accelerated by the absence of Tob1. The data thus support the prevailing hypothesis that Nfatc2 and Tob1 are non-redundant regulators of lymphocyte homeostasis.

Role of METTL20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions.

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Shimazu, Tadahiro; Furuse, Tamio; Balan, Shabeesh; Yamada, Ikuko; Okuno, Shuzo; Iwanari, Hiroko; Suzuki, Takehiro; Hamakubo, Takao; Dohmae, Naoshi; Yoshikawa, Takeo; Wakana, Shigeharu; Shinkai, Yoichi

2018-01-19

METTL20 is a seven-β-strand methyltransferase that is localised to the mitochondria and tri-methylates the electron transfer flavoprotein (ETF) β subunit (ETFB) at lysines 200 and 203. It has been shown that METTL20 decreases the ability of ETF to extract electrons from medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) and glutaryl-CoA dehydrogenase in vitro. METTL20-mediated methylation of ETFB influences the oxygen consumption rate in permeabilised mitochondria, suggesting that METTL20-mediated ETFB methylation may also play a regulatory role in mitochondrial metabolism. In this study, we generated Mettl20 knockout (KO) mice to uncover the in vivo functions of METTL20. The KO mice were viable, and a loss of ETFB methylation was confirmed. In vitro enzymatic assays revealed that mitochondrial ETF activity was higher in the KO mice than in wild-type mice, suggesting that the KO mice had higher β-oxidation capacity. Calorimetric analysis showed that the KO mice fed a ketogenic diet had higher oxygen consumption and heat production. A subsequent cold tolerance test conducted after 24 h of fasting indicated that the KO mice had a better ability to maintain their body temperature in cold environments. Thus, METTL20 regulates ETF activity and heat production through lysine methylation when β-oxidation is highly activated.

GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior

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Fuka Aizawa

2016-12-01

Full Text Available The free fatty acid receptor 1 (GPR40/FFAR1 is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO mice. The emotional behavior in wild and KO male mice was evaluated at 9–10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC–MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain.

Cyclophilin B Deficiency Causes Abnormal Dentin Collagen Matrix.

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Terajima, Masahiko; Taga, Yuki; Cabral, Wayne A; Nagasawa, Masako; Sumida, Noriko; Hattori, Shunji; Marini, Joan C; Yamauchi, Mitsuo

2017-08-04

Cyclophilin B (CypB) is an endoplasmic reticulum-resident protein that regulates collagen folding, and also contributes to prolyl 3-hydroxylation (P3H) and lysine (Lys) hydroxylation of collagen. In this study, we characterized dentin type I collagen in CypB null (KO) mice, a model of recessive osteogenesis imperfecta type IX, and compared to those of wild-type (WT) and heterozygous (Het) mice. Mass spectrometric analysis demonstrated that the extent of P3H in KO collagen was significantly diminished compared to WT/Het. Lys hydroxylation in KO was significantly diminished at the helical cross-linking sites, α1/α2(I) Lys-87 and α1(I) Lys-930, leading to a significant increase in the under-hydroxylated cross-links and a decrease in fully hydroxylated cross-links. The extent of glycosylation of hydroxylysine residues was, except α1(I) Lys-87, generally higher in KO than WT/Het. Some of these molecular phenotypes were distinct from other KO tissues reported previously, indicating the dentin-specific control mechanism through CypB. Histological analysis revealed that the width of predentin was greater and irregular, and collagen fibrils were sparse and significantly smaller in KO than WT/Het. These results indicate a critical role of CypB in dentin matrix formation, suggesting a possible association between recessive osteogenesis imperfecta and dentin defects that have not been clinically detected.

A comparison of patterns of disease extension in keratosis obturans and external auditory canal cholesteatoma.

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Shinnabe, Akihiro; Hara, Mariko; Hasegawa, Masayo; Matsuzawa, Shingo; Kanazawa, Hiromi; Yoshida, Naohiro; Iino, Yukiko

2013-01-01

To investigate the different pathways of progression to the middle ear in keratosis obturans (KO) and external auditory canal cholesteatoma (EACC). Retrospective case review. Referral hospital otolaryngology department. Patients with KO or EACC and middle ear disease who underwent surgical management were included. Four ears of 4 patients (mean age, 41.25 yr) were the KO group, and 5 ears of 4 patients (mean age, 49.5 yr) were the EACC group. Intraoperative findings of the middle ear cavity were investigated in KO and EACC groups. In the KO group, 3 patients had a perforated tympanic membrane and cholesteatoma in the tympanic cavity. The other patient had preoperative right facial palsy. Removal of the keratin plug revealed an adherent tympanic membrane. In intraoperative findings, the tympanic segment of the fallopian canal was found to be eroded because of inflammation. No case initially progressed to the mastoid cavity. Four patients had external auditory canal cholesteatoma with middle ear disease. In EACC group, all patients had initial progression to the mastoid cavity. KO tends to progress initially to the tympanic cavity via a diseased tympanic membrane. EACC tends to progress to the mastoid cavity via destruction of the posterior bony canal. This is the first report to investigate differences in pathway of progression to the middle ear cavity in these 2 diseases.

A mental retardation gene, motopsin/neurotrypsin/prss12, modulates hippocampal function and social interaction.

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Mitsui, Shinichi; Osako, Yoji; Yokoi, Fumiaki; Dang, Mai T; Yuri, Kazunari; Li, Yuqing; Yamaguchi, Nozomi

2009-12-01

Motopsin is a mosaic serine protease secreted from neuronal cells in various brain regions, including the hippocampus. The loss of motopsin function causes nonsyndromic mental retardation in humans and impairs long-term memory formation in Drosophila. To understand motopsin's function in the mammalian brain, motopsin knockout (KO) mice were generated. Motopsin KO mice did not have significant deficits in memory formation, as tested using the Morris water maze, passive avoidance and Y-maze tests. A social recognition test showed that the motopsin KO mice had the ability to recognize two stimulator mice, suggesting normal social memory. In a social novelty test, motopsin KO mice spent a longer time investigating a familiar mouse than wild-type (WT) mice did. In a resident-intruder test, motopsin KO mice showed prolonged social interaction as compared with WT mice. Consistent with the behavioral deficit, spine density was significantly decreased on apical dendrites, but not on basal dendrites, of hippocampal pyramidal neurons of motopsin KO mice. In contrast, pyramidal neurons at the cingulate cortex showed normal spine density. Spatial learning and social interaction induced the phosphorylation of cAMP-responsive element-binding protein (CREB) in hippocampal neurons of WT mice, whereas the phosphorylation of CREB was markedly decreased in mutant mouse brains. Our results indicate that an extracellular protease, motopsin, preferentially affects social behaviors, and modulates the functions of hippocampal neurons.

Effect of dentate gyrus disruption on remembering what happened where

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Min W Jung

2015-06-01

Full Text Available Our previous studies using Bax knockout (Bax-KO mice, in which newly generated granule cells continue to accumulate, disrupting neural circuitry specifically in the dentate gyrus (DG, suggest the involvement of the DG in binding the internally-generated spatial map with sensory information on external landmarks (spatial map-object association in forming a distinct spatial context for each environment. In order to test whether the DG is also involved in binding the internal spatial map with sensory information on external events (spatial map-event association, we tested the behavior of Bax-KO mice in a delayed-non-match-to-place task. Performance of Bax-KO mice was indistinguishable from that of wild-type mice as long as there was no interruption during the delay period (tested up to 5 min, suggesting that on-line maintenance of working memory is intact in Bax-KO mice. However, Bax-KO mice showed profound performance deficits when they were removed from the maze during the delay period (interruption condition with a sufficiently long (65 s delay, suggesting that episodic memory was impaired in Bax-KO mice. Together with previous findings, these results suggest the role of the DG in binding spatial information derived from dead reckoning and nonspatial information, such as external objects and events, in the process of encoding episodic memory.

Glial degeneration with oxidative damage drives neuronal demise in MPSII disease.

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Zalfa, Cristina; Verpelli, Chiara; D'Avanzo, Francesca; Tomanin, Rosella; Vicidomini, Cinzia; Cajola, Laura; Manara, Renzo; Sala, Carlo; Scarpa, Maurizio; Vescovi, Angelo Luigi; De Filippis, Lidia

2016-08-11

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression.

Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water.

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Chen, Baowei; Arnold, Lora L; Cohen, Samuel M; Thomas, David J; Le, X Chris

2011-12-01

Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic (iAs) producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated arsenicals may contribute to toxicity associated with exposure to inorganic arsenic. Here, adult female wild-type (WT) C57BL/6 mice and female As3mt knockout (KO) mice received drinking water that contained 1, 10, or 25 ppm (mg/l) of arsenite for 33 days and blood, liver, kidney, and lung were taken for arsenic speciation. Genotype markedly affected concentrations of arsenicals in tissues. Summed concentrations of arsenicals in plasma were higher in WT than in KO mice; in red blood cells, summed concentrations of arsenicals were higher in KO than in WT mice. In liver, kidney, and lung, summed concentrations of arsenicals were greater in KO than in WT mice. Although capacity for arsenic methylation is much reduced in KO mice, some mono-, di-, and tri-methylated arsenicals were found in tissues of KO mice, likely reflecting the activity of other tissue methyltransferases or preabsorptive metabolism by the microbiota of the gastrointestinal tract. These results show that the genotype for arsenic methylation determines the phenotypes of arsenic retention and distribution and affects the dose- and organ-dependent toxicity associated with exposure to inorganic arsenic.

AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons.

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Claret, Marc; Smith, Mark A; Batterham, Rachel L; Selman, Colin; Choudhury, Agharul I; Fryer, Lee G D; Clements, Melanie; Al-Qassab, Hind; Heffron, Helen; Xu, Allison W; Speakman, John R; Barsh, Gregory S; Viollet, Benoit; Vaulont, Sophie; Ashford, Michael L J; Carling, David; Withers, Dominic J

2007-08-01

Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. In contrast, AgRP alpha 2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus.

Disease: H01431 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available lethora. Endocrine disease GNAS [HSA:2778] [KO:K04632] AIP [HSA:9049] [KO:K17767] ... Trans-sphenoidal pituitary surgery... Pituitary irradiation (gamma Knife surgery) Medical treatments towards the pituitary: Cabergoli

Diacylglycerol kinase β knockout mice exhibit attention-deficit behavior and an abnormal response on methylphenidate-induced hyperactivity.

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Mitsue Ishisaka

Full Text Available BACKGROUND: Diacylglycerol kinase (DGK is an enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. DGKβ is one of the subtypes of the DGK family and regulates many intracellular signaling pathways in the central nervous system. Previously, we demonstrated that DGKβ knockout (KO mice showed various dysfunctions of higher brain function, such as cognitive impairment (with lower spine density, hyperactivity, reduced anxiety, and careless behavior. In the present study, we conducted further tests on DGKβ KO mice in order to investigate the function of DGKβ in the central nervous system, especially in the pathophysiology of attention deficit hyperactivity disorder (ADHD. METHODOLOGY/PRINCIPAL FINDINGS: DGKβ KO mice showed attention-deficit behavior in the object-based attention test and it was ameliorated by methylphenidate (MPH, 30 mg/kg, i.p.. In the open field test, DGKβ KO mice displayed a decreased response to the locomotor stimulating effects of MPH (30 mg/kg, i.p., but showed a similar response to an N-methyl-d-aspartate (NMDA receptor antagonist, MK-801 (0.3 mg/kg, i.p., when compared to WT mice. Examination of the phosphorylation of extracellular signal-regulated kinase (ERK, which is involved in regulation of locomotor activity, indicated that ERK1/2 activation induced by MPH treatment was defective in the striatum of DGKβ KO mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest that DGKβ KO mice showed attention-deficit and hyperactive phenotype, similar to ADHD. Furthermore, the hyporesponsiveness of DGKβ KO mice to MPH was due to dysregulation of ERK phosphorylation, and that DGKβ has a pivotal involvement in ERK regulation in the striatum.

Tissue inhibitor of metalloproteinase-3 knockout mice exhibit enhanced energy expenditure through thermogenesis.

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Yohsuke Hanaoka

Full Text Available Tissue inhibitors of metalloproteinases (TIMPs regulate matrix metalloproteinase activity and maintain extracellular matrix homeostasis. Although TIMP-3 has multiple functions (e.g., apoptosis, inhibition of VEGF binding to VEGF receptor, and inhibition of TNFα converting enzyme, its roles in thermogenesis and metabolism, which influence energy expenditure and can lead to the development of metabolic disorders when dysregulated, are poorly understood. This study aimed to determine whether TIMP-3 is implicated in metabolism by analyzing TIMP-3 knockout (KO mice. TIMP-3 KO mice had higher body temperature, oxygen consumption, and carbon dioxide production than wild-type (WT mice, although there were no differences in food intake and locomotor activity. These results suggest that metabolism is enhanced in TIMP-3 KO mice. Real-time PCR analysis showed that the expression of PPAR-δ, UCP-2, NRF-1 and NRF-2 in soleus muscle, and PGC-1α and UCP-2 in gastrocnemius muscle, was higher in TIMP-3 KO mice than in WT mice, suggesting that TIMP-3 deficiency may increase mitochondrial activity. When exposed to cold for 8 hours to induce thermogenesis, TIMP-3 KO mice had a higher body temperature than WT mice. In the treadmill test, oxygen consumption and carbon dioxide production were higher in TIMP-3 KO mice both before and after starting exercise, and the difference was more pronounced after starting exercise. Our findings suggest that TIMP-3 KO mice exhibit enhanced metabolism, as reflected by a higher body temperature than WT mice, possibly due to increased mitochondrial activity. Given that TIMP-3 deficiency increases energy expenditure, TIMP-3 may present a novel therapeutic target for preventing metabolic disorders.

Ethics in Knowledge Organization: Two Conferences Point to a New Core in the Domain

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Richard P. Smiraglia

2015-01-01

Full Text Available http://dx.doi.org/10.5007/1518-2924.2015v20nesp1p1 Two conferences called "Ethics in Information Organization (EIO," held in 2009 and 2013, brought together practitioners and scholars in knowledge organization (KO to discuss ethical decision-making for the organization of knowledge. Traditionally the notion of ethics as a component of knowledge organization has occupied a sort of background position. Concepts of cultural warrant clash with concepts of literary warrant to produce harmful knowledge organization systems. Here tools of domain analytical visualization are applied to the two EIO conferences to demonstrate the potential intension of ethics for KO. Co-word analysis helps to visualize the thematic core in the most frequently used terms: user, ethical, knowledge, national, description, and access. There clearly is a meta-level trajectory incorporating ethics and the user, while the intension includes all applied approaches to KO as well as strong recognition of national, regional, and social cultural identities. Another approach to domain analysis is to examine the social semantics (by analyzing the public record of discourse through citation patterns. Author co-citation analysis shows work anchored in the basic theoretical premises of KO, but also bringing ideas from outside the domain to bear on the problems of objective violence. A network visualization shows how the work on ethics in KO is based on the core principles of KO, but relies also on evidence from librarianship and philosophical guidance to bring forward the issues surrounding objective violence in KOS. The authors contributing to this small pair of conferences have laid out a pathway for expanding understanding of the role of ethics in KO.

Generation and characterization of mice carrying a conditional allele of the Wwox tumor suppressor gene.

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John H Ludes-Meyers

2009-11-01

Full Text Available WWOX, the gene that spans the second most common human chromosomal fragile site, FRA16D, is inactivated in multiple human cancers and behaves as a suppressor of tumor growth. Since we are interested in understanding WWOX function in both normal and cancer tissues we generated mice harboring a conditional Wwox allele by flanking Exon 1 of the Wwox gene with LoxP sites. Wwox knockout (KO mice were developed by breeding with transgenic mice carrying the Cre-recombinase gene under the control of the adenovirus EIIA promoter. We found that Wwox KO mice suffered from severe metabolic defect(s resulting in growth retardation and all mice died by 3 wk of age. All Wwox KO mice displayed significant hypocapnia suggesting a state of metabolic acidosis. This finding and the known high expression of Wwox in kidney tubules suggest a role for Wwox in acid/base balance. Importantly, Wwox KO mice displayed histopathological and hematological signs of impaired hematopoiesis, leukopenia, and splenic atrophy. Impaired hematopoiesis can also be a contributing factor to metabolic acidosis and death. Hypoglycemia and hypocalcemia was also observed affecting the KO mice. In addition, bone metabolic defects were evident in Wwox KO mice. Bones were smaller and thinner having reduced bone volume as a consequence of a defect in mineralization. No evidence of spontaneous neoplasia was observed in Wwox KO mice. We have generated a new mouse model to inactivate the Wwox tumor suppressor gene conditionally. This will greatly facilitate the functional analysis of Wwox in adult mice and will allow investigating neoplastic transformation in specific target tissues.

Deletion of interleukin 1 receptor-associated kinase 1 (Irak1) improves glucose tolerance primarily by increasing insulin sensitivity in skeletal muscle.

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Sun, Xiao-Jian; Kim, Soohyun Park; Zhang, Dongming; Sun, Helen; Cao, Qi; Lu, Xin; Ying, Zhekang; Li, Liwu; Henry, Robert R; Ciaraldi, Theodore P; Taylor, Simeon I; Quon, Michael J

2017-07-21

Chronic inflammation may contribute to insulin resistance via molecular cross-talk between pathways for pro-inflammatory and insulin signaling. Interleukin 1 receptor-associated kinase 1 (IRAK-1) mediates pro-inflammatory signaling via IL-1 receptor/Toll-like receptors, which may contribute to insulin resistance, but this hypothesis is untested. Here, we used male Irak1 null (k/o) mice to investigate the metabolic role of IRAK-1. C57BL/6 wild-type (WT) and k/o mice had comparable body weights on low-fat and high-fat diets (LFD and HFD, respectively). After 12 weeks on LFD (but not HFD), k/o mice ( versus WT) had substantially improved glucose tolerance (assessed by the intraperitoneal glucose tolerance test (IPGTT)). As assessed with the hyperinsulinemic euglycemic glucose clamp technique, insulin sensitivity was 30% higher in the Irak1 k/o mice on chow diet, but the Irak1 deletion did not affect IPGTT outcomes in mice on HFD, suggesting that the deletion did not overcome the impact of obesity on glucose tolerance. Moreover, insulin-stimulated glucose-disposal rates were higher in the k/o mice, but we detected no significant difference in hepatic glucose production rates (± insulin infusion). Positron emission/computed tomography scans indicated higher insulin-stimulated glucose uptake in muscle, but not liver, in Irak1 k/o mice in vivo Moreover, insulin-stimulated phosphorylation of Akt was higher in muscle, but not in liver, from Irak1 k/o mice ex vivo In conclusion, Irak1 deletion improved muscle insulin sensitivity, with the effect being most apparent in LFD mice. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Kynurenine 3-monooxygenase is implicated in antidepressants-responsive depressive-like behaviors and monoaminergic dysfunctions.

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Tashiro, Tomoyuki; Murakami, Yuki; Mouri, Akihiro; Imamura, Yukio; Nabeshima, Toshitaka; Yamamoto, Yasuko; Saito, Kuniaki

2017-01-15

l-Tryptophan (TRP) is metabolized via serotonin and kynurenine pathways (KP). Several studies have demonstrated that abnormality of both pathways is involved in the pathogenesis of major depressive disorder (MDD). Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the KP, has been suggested to play major roles in physiological and pathological events mediated by bioactive kynurenine metabolites. In this study, we investigated the role of KMO in the emotional and cognitive functions by using KMO knockout (KO) mice. We measured contents of TRP and monoamines and their metabolites in the serum and hippocampus of KMO KO mice. Further, we investigated whether antidepressants improved the depressive-like behaviors in KMO KO mice. KMO KO mice showed depressive-like behaviors such as decreased sucrose preference and increased immobility in the forced swimming test and high anxiety by decreased time spent in the center area of open field. But, there was no difference in spontaneous alternation in Y-maze test, counts of rearing or locomotor activity. Higher contents of TRP metabolites such as kynurenine (KYN), kynurenic acid (KA), anthranilic acid (AA), and 3-hydroxykynurenine (3-HK) in the serum and hippocampus and decreased serotonin turnover and higher content of normetanephrine (NM) in the hippocampus were observed in the KMO KO mice. Although both antidepressant attenuated increase of immobility, sertraline but not imipramine improved decrease of sucrose preference in the KMO KO mice. These findings suggested that KMO KO mice show antidepressants-responsive depressive-like behaviors and monoaminergic dysfunctions via abnormality of kynurenine metabolism with good validities as MDD model. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice

International Nuclear Information System (INIS)

Haque, Rizwanul; Umstead, Todd M.; Ponnuru, Padmavathi; Guo Xiaoxuan; Hawgood, Samuel; Phelps, David S.; Floros, Joanna

2007-01-01

Millions are exposed to ozone levels above recommended limits, impairing lung function, causing epithelial damage and inflammation, and predisposing some individuals to pneumonia, asthma, and other lung conditions. Surfactant protein-A (SP-A) plays a role in host defense, the regulation of inflammation, and repair of tissue damage. We tested the hypothesis that the lungs of SP-A(-/-) (KO) mice are more susceptible to ozone-induced damage. We compared the effects of ozone on KO and wild type (WT) mice on the C57BL/6 genetic background by exposing them to 2 parts/million of ozone for 3 or 6 h and sacrificing them 0, 4, and 24 h later. Lungs were subject to bronchoalveolar lavage (BAL) or used to measure endpoints of oxidative stress and inflammation. Despite more total protein in BAL of KO mice after a 3 h ozone exposure, WT mice had increased oxidation of protein and had oxidized SP-A dimers. In KO mice there was epithelial damage as assessed by increased LDH activity and there was increased phospholipid content. In WT mice there were more BAL PMNs and elevated macrophage inflammatory protein (MIP)-2 and monocyte chemoattractant protein (MCP)-1. Changes in MIP-2 and MCP-1 were observed in both KO and WT, however mRNA levels differed. In KO mice MIP-2 mRNA levels changed little with ozone, but in WT levels they were significantly increased. In summary, several aspects of the inflammatory response differ between WT and KO mice. These in vivo findings appear to implicate SP-A in regulating inflammation and limiting epithelial damage in response to ozone exposure

Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration.

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Hatazawa, Yukino; Ono, Yusuke; Hirose, Yuma; Kanai, Sayaka; Fujii, Nobuharu L; Machida, Shuichi; Nishino, Ichizo; Shimizu, Takahiko; Okano, Masaki; Kamei, Yasutomi; Ogawa, Yoshihiro

2018-03-01

DNA methylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNA methyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy. We made skeletal muscle-specific Dnmt3a-knockout (Dnmt3a-KO) mice. The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KO mice. Diminished mRNA and protein expression of Dnmt3a were observed in skeletal muscles as well as in satellite cells, which are important for muscle regeneration, in Dnmt3a-KO mice. Dnmt3a-KO satellite cell showed smaller in size (length/area), suggesting suppressed myotube differentiation. Microarray analysis of satellite cells showed that expression of growth differentiation factor 5 (Gdf5) mRNA was markedly increased in Dnmt3a-KO mice. The DNA methylation level of the Gdf5 promoter was markedly decreased in Dnmt3a-KO satellite cells. In addition, DNA methylation inhibitor azacytidine treatment increased Gdf5 expression in wild-type satellite cells, suggesting Gdf5 expression is regulated by DNA methylation. Also, we observed increased inhibitor of differentiation (a target of Gdf5) mRNA expression in Dnmt3a-KO satellite cells. Thus, Dnmt3a appears to regulate satellite cell differentiation via DNA methylation. This mechanism may play a role in the decreased regeneration capacity during atrophy such as in aged sarcopenia.-Hatazawa, Y., Ono, Y., Hirose, Y., Kanai, S., Fujii, N. L., Machida, S., Nishino, I., Shimizu, T., Okano, M., Kamei, Y., Ogawa, Y. Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration.

Impact of chronic low to moderate alcohol consumption on blood lipid and heart energy profile in acetaldehyde dehydrogenase 2-deficient mice.

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Fan, Fan; Cao, Quan; Wang, Cong; Ma, Xin; Shen, Cheng; Liu, Xiang-wei; Bu, Li-ping; Zou, Yun-zeng; Hu, Kai; Sun, Ai-jun; Ge, Jun-bo

2014-08-01

To investigate the roles of acetaldehyde dehydrogenase 2 (ALDH2), the key enzyme of ethanol metabolism, in chronic low to moderate alcohol consumption-induced heart protective effects in mice. Twenty-one male wild-type (WT) or ALDH2-knockout (KO) mice were used in this study. In each genotype, 14 animals received alcohol (2.5%, 5% and 10% in week 1-3, respectively, and 18% in week 4-7), and 7 received water for 7 weeks. After the treatments, survival rate and general characteristics of the animals were evaluated. Serum ethanol and acetaldehyde levels and blood lipids were measured. Metabolomics was used to characterize the heart and serum metabolism profiles. Chronic alcohol intake decreased the survival rate of KO mice by 50%, and significantly decreased their body weight, but did not affect those of WT mice. Chronic alcohol intake significantly increased the serum ethanol levels in both WT and KO mice, but KO mice had significantly higher serum acetaldehyde levels than WT mice. Chronic alcohol intake significantly increased the serum HDL cholesterol levels in WT mice, and did not change the serum HDL cholesterol levels in KO mice. After chronic alcohol intake, WT and KO mice showed differential heart and serum metabolism profiles, including the 3 main energy substrate types (lipids, glucose and amino acids) and three carboxylic acid cycles. Low to moderate alcohol consumption increases HDL cholesterol levels and improves heart energy metabolism profile in WT mice but not in ALDH2-KO mice. Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.

Die saalsuster as koördineerder

OpenAIRE

A. Bruwer

1980-01-01

The hospital as unique organisational unit is proposed, based on the theory of the existence o f a dual authority system within the hospital. The place of the ward sister in the hospital is explored with emphasis on her co-ordinating function. This function of the nurse is not limited to nursing activities alone but refers in particular to her role as co-ordinator of patient care. If the nurse is to retain this special position in the hospital organisation a more structured approach towards t...

Die saalsuster as koördineerder

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A. Bruwer

1980-09-01

Full Text Available The hospital as unique organisational unit is proposed, based on the theory of the existence o f a dual authority system within the hospital. The place of the ward sister in the hospital is explored with emphasis on her co-ordinating function. This function of the nurse is not limited to nursing activities alone but refers in particular to her role as co-ordinator of patient care. If the nurse is to retain this special position in the hospital organisation a more structured approach towards teaching of administrative skills is advocated to enable the nurse to create a therapeutic milieu in the ward.

Naukowa filozofia Koła Krakowskiego

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Zbigniew Wolak

2005-06-01

Full Text Available The Cracow Circle was a group of four Polish philosophers and logicians (Salamucha, Bocheński, Drewnowski, Sobociński connected with Lvov-Warsaw School. They tried to apply the modern logic to a Christian thought. This application first needed explication what the mathematical logic really is—not a science connected with the Aristotelian abstraction of the second degree but formal science unnecessary in a strict reasoning and defining. Then they showed how important was always exactness in Christian thought and wrote some papers in which the modern logic was used in different issues (maybe the most famous was Salamucha’s analysis of Thomas’ proof ex motu of the existence of God. Cracow Circle was also strongly interested in relations between science and religion, they tried to show and explore new ways to develop Christian, especially catholic, views of the world, philosophy and theology. Very interesting was Drewnowski’s philosophical program and its applications in various problems in philosophy, theology, sociology etc.

Meteorološko osiguranje kopnenog prometa

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Branko Gelo

2012-10-01

Full Text Available The paper deals with some basic aspects of meteorological service management as related to safety and smooth operation of surface transport (road, rail, postal, telecommunications, internal circulation, pipelines, funiculars, pavements and pathways with reference to different problems regarding safety hazards, environmental protection, economy problems, time-tables and frequencies and transport industry. A review has been made of respective presentation and methods of forwarding given meteorological elements and aspects (reports, forecasts, maps as required for surface transport with reference to traffic routes (climatological, synoptic-weather.

OeKO 3: Jobs versus environment

International Nuclear Information System (INIS)

Mueller-Witt, H.

1980-01-01

The book tries to gather the representatives of different political directions and groups such as socialist, ecogolists and trade unionists presently moving apart in a discussion concerning the popular question: How can we combine the necessary protection of our threatened environment with the legitimate interest in the guaranteiing of the prosperity, how can we harmonic the contradictory interest of ecology and economy. In the first part, especially ecologically oriented economists give their opinions in order to make a contribution to reduce the big deficit of economically well-grounded analyses in the ecological movement. In the second part, questions of the conversion of ecological basic positions in policy are dealt with. The book closes with a documentation of ecological programmes. (orig.) [de

Nyhedsbrev for KoBra no 6

DEFF Research Database (Denmark)

Mygind, Ole

2012-01-01

Indholdsfortegnelse Fra vores egen verden • Nyt fokus og nyt navn til videncenteret? • Ny videncenterleder • Nye ansatte i videncenteret • Britta Kusk Nørgaard goes Ph.d • Formidling i nyhedsbrevet • Udvikling af tværprofessionelle kompetencer • Hvordan kan man som bachelorstuderende være med til...

To investigate the necessity of STRA6 upregulation in T cells during T cell immune responses.

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Rafik Terra

Full Text Available Our earlier study revealed that STRA6 (stimulated by retinoic acid gene 6 was up-regulated within 3 h of TCR stimulation. STRA6 is the high-affinity receptor for plasma retinol-binding protein (RBP and mediates cellular vitamin A uptake. We generated STRA6 knockout (KO mice to assess whether such up-regulation was critical for T-cell activation, differentiation and function. STRA6 KO mice under vitamin A sufficient conditions were fertile without apparent anomalies upon visual inspection. The size, cellularity and lymphocyte subpopulations of STRA6 KO thymus and spleen were comparable to those of their wild type (WT controls. KO and WT T cells were similar in terms of TCR-stimulated proliferation in vitro and homeostatic expansion in vivo. Naive KO CD4 cells differentiated in vitro into Th1, Th2, Th17 as well as regulatory T cells in an analogous manner as their WT counterparts. In vivo experiments revealed that anti-viral immune responses to lymphocytic choriomeningitis virus in KO mice were comparable to those of WT controls. We also demonstrated that STRA6 KO and WT mice had similar glucose tolerance. Total vitamin A levels are dramatically lower in the eyes of KO mice as compared to those of WT mice, but the levels in other organs were not significantly affected after STRA6 deletion under vitamin A sufficient conditions, indicating that the eye is the mouse organ most sensitive to the loss of STRA6. Our results demonstrate that 1 in vitamin A sufficiency, the deletion of STRA6 in T cells does no affect the T-cell immune responses so-far tested, including those depend on STAT5 signaling; 2 STRA6-independent vitamin A uptake compensated the lack of STRA6 in lymphoid organs under vitamin A sufficient conditions in mice; 3 STRA6 is critical for vitamin A uptake in the eyes even in vitamin A sufficiency.

Comprehensive behavioral analysis of pituitary adenylate cyclase-activating polypeptide (PACAP knockout mice

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Satoko eHattori

2012-10-01

Full Text Available Pituitary adenylate cyclase-activating polypeptide (PACAP is a neuropeptide acting as a neurotransmitter, neuromodulator, or neurotrophic factor. PACAP is widely expressed throughout the brain and exerts its functions through the PACAP-specific receptor (PAC1. Recent studies reveal that genetic variants of the PACAP and PAC1 genes are associated with mental disorders, and several behavioral abnormalities of PACAP knockout (KO mice are reported. However, an insufficient number of backcrosses was made using PACAP KO mice on the C57BL/6J background due to their postnatal mortality. To elucidate the effects of PACAP on neuropsychiatric function, the PACAP gene was knocked out in F1 hybrid mice (C57BL/6J x 129SvEv for appropriate control of the genetic background. The PACAP KO mice were then subjected to a behavioral test battery. PACAP deficiency had no significant effects on neurological screen. As shown previously, the mice exhibited significantly increased locomotor activity in a novel environment and abnormal anxiety-like behavior, while no obvious differences between genotypes were shown in home cage activity. In contrast to previous reports, the PACAP KO mice showed normal prepulse inhibition and slightly decreased depression-like behavior. Previous study demonstrates that the social interaction in a resident-intruder test was decreased in PACAP KO mice. On the other hand, we showed that PACAP KO mice exhibited increased social interaction in Crawley’s three-chamber social approach test, although PACAP KO had no significant impact on social interaction in a home cage. PACAP KO mice also exhibited mild performance deficit in working memory in an eight-arm radial maze and the T-maze, while they did not show any significant abnormalities in the left-right discrimination task in the T-maze. These results suggest that PACAP has an important role in the regulation of locomotor activity, social behavior, anxiety-like behavior and, potentially

Deletion of Gpr55 Results in Subtle Effects on Energy Metabolism, Motor Activity and Thermal Pain Sensation.

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Mikael Bjursell

Full Text Available The G-protein coupled receptor 55 (GPR55 is activated by cannabinoids and non-cannabinoid molecules and has been speculated to play a modulatory role in a large variety of physiological and pathological processes, including in metabolically perturbed states. We therefore generated male mice deficient in the gene coding for the cannabinoid/lysophosphatidylinositol (LPI receptor Gpr55 and characterized them under normal dietary conditions as well as during high energy dense diet feeding followed by challenge with the CB1 receptor antagonist/GPR55 agonist rimonabant. Gpr55 deficient male mice (Gpr55 KO were phenotypically indistinguishable from their wild type (WT siblings for the most part. However, Gpr55 KO animals displayed an intriguing nocturnal pattern of motor activity and energy expenditure (EE. During the initial 6 hours of the night, motor activity was significantly elevated without any significant effect observed in EE. Interestingly, during the last 6 hours of the night motor activity was similar but EE was significantly decreased in the Gpr55 KO mice. No significant difference in motor activity was detected during daytime, but EE was lower in the Gpr55 KO compared to WT mice. The aforementioned patterns were not associated with alterations in energy intake, daytime core body temperature, body weight (BW or composition, although a non-significant tendency to increased adiposity was seen in Gpr55 KO compared to WT mice. Detailed analyses of daytime activity in the Open Field paradigm unveiled lower horizontal activity and rearing time for the Gpr55 KO mice. Moreover, the Gpr55 KO mice displayed significantly faster reaction time in the tail flick test, indicative of thermal hyperalgesia. The BW-decreasing effect of rimonabant in mice on long-term cafeteria diet did not differ between Gpr55 KO and WT mice. In conclusion, Gpr55 deficiency is associated with subtle effects on diurnal/nocturnal EE and motor activity behaviours but does not

Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.

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Kashyap, Sonu; Warner, Gina; Hu, Zeng; Gao, Feng; Osman, Mazen; Al Saiegh, Yousif; Lien, Karen R; Nath, Karl; Grande, Joseph P

2017-01-01

Renovascular hypertension (RVH) has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C) model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO) protects the stenotic kidney (STK) from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS) was established in Wild-type (WT) and Smad3 KO mice (129 genetic background) by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.

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Sonu Kashyap

Full Text Available Renovascular hypertension (RVH has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO protects the stenotic kidney (STK from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS was established in Wild-type (WT and Smad3 KO mice (129 genetic background by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

Role of cellular FKBP52 protein in intracellular trafficking of recombinant adeno-associated virus 2 vectors

International Nuclear Information System (INIS)

Zhao Weihong; Zhong Li; Wu Jianqing; Chen Linyuan; Qing Keyun; Weigel-Kelley, Kirsten A.; Larsen, Steven H.; Shou Weinian; Warrington, Kenneth H.; Srivastava, Arun

2006-01-01

We have reported that tyrosine-phosphorylated forms of a cellular protein, FKBP52, inhibit the second-strand DNA synthesis of adeno-associated virus 2 (AAV), leading to inefficient transgene expression from recombinant AAV vectors. To further explore the role of FKBP52 in AAV-mediated transduction, we established murine embryo fibroblasts (MEFs) cultures from FKBP52 wild-type (WT), heterozygous (HE), and knockout (KO) mice. Conventional AAV vectors failed to transduce WT MEFs efficiently, and the transduction efficiency was not significantly increased in HE or KO MEFs. AAV vectors failed to traffic efficiently to the nucleus in these cells. Treatment with hydroxyurea (HU) increased the transduction efficiency of conventional AAV vectors by ∼25-fold in WT MEFs, but only by ∼4-fold in KO MEFs. The use of self-complementary AAV (scAAV) vectors, which bypass the requirement of viral second-strand DNA synthesis, revealed that HU treatment increased the transduction efficiency ∼23-fold in WT MEFs, but only ∼4-fold in KO MEFs, indicating that the lack of HU treatment-mediated increase in KO MEFs was not due to failure of AAV to undergo viral second-strand DNA synthesis. Following HU treatment, ∼59% of AAV genomes were present in the nuclear fraction from WT MEFs, but only ∼28% in KO MEFs, indicating that the pathway by which HU treatment mediates nuclear transport of AAV was impaired in KO MEFs. When KO MEFs were stably transfected with an FKBP52 expression plasmid, HU treatment-mediated increase in the transduction efficiency was restored in these cells, which correlated directly with improved intracellular trafficking. Intact AAV particles were also shown to interact with FKBP52 as well as with dynein, a known cellular protein involved in AAV trafficking. These studies suggest that FKBP52, being a cellular chaperone protein, facilitates intracellular trafficking of AAV, which has implications in the optimal use of recombinant AAV vectors in human gene

Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

Energy Technology Data Exchange (ETDEWEB)

Zhang, Pengpeng [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Shan, Tizhong; Liang, Xinrong [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Deng, Changyan [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Kuang, Shihuan, E-mail: skuang@purdue.edu [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States)

2014-09-12

Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor{sup flox/flox} mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor{sup flox/flox} mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function.

Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting.

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Manoocher Soleimani

Full Text Available Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2 and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2 in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of

Kültür Koşullarında Levrek (Dicentrarchus labrax L., 1758 Larvalarında Ağız Bölgesinin Osteolojik Gelişimi.

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Deniz Çoban

2015-12-01

Full Text Available Levrek larvalarında 0-42. günler arasında yoğun yetiştiricilik koşulları altında ağız boşluğunda çeneye ait elementlerin kıkırdak ve kemik gelişimleri incelenmiştir. Örnekler çalışma boyunca üç günde bir olacak şekilde elde edilmiş ve çalışma canlı yeminkesilmesi ile sonlanmıştır. Elde edilen örnekler formalinde sabitlendikten sonra alcian mavisi ve alizarin kırmızısı ile boyandı. Yumurtadan çıkan larvada ağza ait bir osteolojik oluşum tespit edilmemiştir. İlk oluşan element 3,8 mm total boyda (TB Meckel’s kıkırdağıdır. Bu oluşumu 4,6 mm TB’da trabecular bar, palato-quadrate ve hyosymplectic takip eder. 5,4 mm TB’da basibranchial, hyoid bar, maksillary ve branchial sepet oral boşluğun altında meydana gelmiştir. 7,9 mm TB’da dişe ait yapıların ilk işareti olan premaksillary oluşumu gözlenmiştir. 11,4 mm TB’da premaksillary ve dentary kıkırdak yapıda olup henüz kemikleşme başlamamış olup her ikisinde de bir sıra diş tespit edilmiştir. 15,8 mm TB’da premaksillary ve dentarynin uç bölgelerinde kemikleşme başlamıştır. Bu çalışmadan elde edilen sonuçlar diğer teleostlar ile karşılaştırılmış ve benzer bulgulara rastlanmıştır

What Are Asbestos-Related Lung Diseases?

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... asbestosis include: Fibrotic lung disease Pneumoconiosis (NOO-mo-ko-ne-O-sis) Interstitial (in-ter-STISH-al) ... tissue samples. One way is through bronchoscopy (bron-KOS-ko-pee). For this procedure, your doctor will ...

Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver.

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Hinrichs, Arne; Kessler, Barbara; Kurome, Mayuko; Blutke, Andreas; Kemter, Elisabeth; Bernau, Maren; Scholz, Armin M; Rathkolb, Birgit; Renner, Simone; Bultmann, Sebastian; Leonhardt, Heinrich; de Angelis, Martin Hrabĕ; Nagashima, Hiroshi; Hoeflich, Andreas; Blum, Werner F; Bidlingmaier, Martin; Wanke, Rüdiger; Dahlhoff, Maik; Wolf, Eckhard

2018-05-01

Laron syndrome (LS) is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR) gene. To establish a large animal model for LS, pigs with GHR knockout (KO) mutations were generated and characterized. CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs. Since the latter two groups were not significantly different in any parameter investigated, they were pooled as the GHR expressing control group. The characterization program included body and organ growth, body composition, endocrine and clinical-chemical parameters, as well as signaling studies in liver tissue. GHR-KO pigs lacked GHR and had markedly reduced serum insulin-like growth factor 1 (IGF1) levels and reduced IGF-binding protein 3 (IGFBP3) activity but increased IGFBP2 levels. Serum GH concentrations were significantly elevated compared with control pigs. GHR-KO pigs had a normal birth weight. Growth retardation became significant at the age of five weeks. At the age of six months, the body weight of GHR-KO pigs was reduced by 60% compared with controls. Most organ weights of GHR-KO pigs were reduced proportionally to body weight. However, the weights of liver, kidneys, and heart were disproportionately reduced, while the relative brain weight was almost doubled. GHR-KO pigs had a markedly increased percentage of total body fat relative to body weight and displayed transient juvenile hypoglycemia along with decreased serum triglyceride and cholesterol levels. Analysis of insulin receptor related signaling in the liver of adult fasted pigs revealed increased phosphorylation of IRS1 and PI3K. In agreement with the loss of GHR, phosphorylation of STAT5 was significantly reduced. In contrast, phosphorylation

Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver

Directory of Open Access Journals (Sweden)

Arne Hinrichs

2018-05-01

Full Text Available Objective: Laron syndrome (LS is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR gene. To establish a large animal model for LS, pigs with GHR knockout (KO mutations were generated and characterized. Methods: CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs. Since the latter two groups were not significantly different in any parameter investigated, they were pooled as the GHR expressing control group. The characterization program included body and organ growth, body composition, endocrine and clinical-chemical parameters, as well as signaling studies in liver tissue. Results: GHR-KO pigs lacked GHR and had markedly reduced serum insulin-like growth factor 1 (IGF1 levels and reduced IGF-binding protein 3 (IGFBP3 activity but increased IGFBP2 levels. Serum GH concentrations were significantly elevated compared with control pigs. GHR-KO pigs had a normal birth weight. Growth retardation became significant at the age of five weeks. At the age of six months, the body weight of GHR-KO pigs was reduced by 60% compared with controls. Most organ weights of GHR-KO pigs were reduced proportionally to body weight. However, the weights of liver, kidneys, and heart were disproportionately reduced, while the relative brain weight was almost doubled. GHR-KO pigs had a markedly increased percentage of total body fat relative to body weight and displayed transient juvenile hypoglycemia along with decreased serum triglyceride and cholesterol levels. Analysis of insulin receptor related signaling in the liver of adult fasted pigs revealed increased phosphorylation of IRS1 and PI3K. In agreement with the loss of GHR, phosphorylation of STAT5 was

Złamanie zmęczeniowe bliższej części piszczeli związane ze zmianami zwyrodnieniowymi kolana u chorej na reumatoidalne zapalenie stawów

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Aleksander Wielkopolski

2010-04-01

Full Text Available Zmęczeniowe złamania kości piszczelowej wtórne do zmian zwyrodnieniowychstawu kolanowego występują rzadko. Tego typuzłamania dotyczą głównie bliższego końca kości piszczelowej.Autorzy pracy opisują przypadek złamania zmęczeniowego piszczelize współistniejącymi zmianami zwyrodnieniowymi kolanau 57-letniej kobiety chorej na reumatoidalne zapalenie stawów.Chora była leczona operacyjnie z zastosowaniem tylnostabilizowanejendoprotezy stawu kolanowego z długim trzpieniem piszczelowym.To postępowanie pozwoliło osiągnąć redukcję dolegliwościbólowych, skorygować oś kończyny oraz uzyskać wygojeniezmęczeniowego złamania.

Drug: D10355 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available razine derivative Active form of prodrug: Aripiprazole [DR:D01164] Treatment of schizophrenia, bipolar disorder, and clinical depress...ion DRD2 [HSA:1813] [KO:K04145]; DRD3 [HSA:1814] [KO:K04

Koala retroviruses: characterization and impact on the life of koalas

OpenAIRE

Denner, Joachim; Young, Paul R

2013-01-01

Koala retroviruses (KoRV) have been isolated from wild and captive koalas in Australia as well as from koala populations held in zoos in other countries. They are members of the genus Gammaretrovirus, are most closely related to gibbon ape leukemia virus (GaLV), feline leukemia virus (FeLV) and porcine endogenous retrovirus (PERV) and are likely the result of a relatively recent trans-species transmission from rodents or bats. The first KoRV to be isolated, KoRV-A, is widely distributed in th...

Disease: H00431 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available (polymorphism) [HSA:1291] [KO:K06238] TGFB3 (polymorphism) [HSA:7043] [KO:K13377] ... machanical stress nutri...tion glucose intolerance high body mass index ... ICD-10: M48.8 MeSH: D017887 OMIM:

Disease: H01633 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available 555] SCNN1B [HSA:6338] [KO:K04825] SCNN1G [HSA:6340] [KO:K04827] ... Excess consumption of sodium [CPD:C01330] Excess consumption of cof...fee Excess consumption of alcohol ... Hydrochlorothiazide

ŠIMUN KOŽIČIĆ AND HIS PRINTING HOUSE IN PETAR KOLENDIĆ’S RESEARCH

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Anica Nazor

2012-01-01

Full Text Available Literary historian Petar Kolendić (1882–1969 published two tributes to Šimun Kožičić: Zadranin Šimun Kožičić i njegova štamparija na Reci (Šimun Kožičić from Zadar and his Printing House in Rijeka and Najstariji naš bukvar (Our Oldest Elementary Reader. Both were published in: Južni pregled (Southern Review, year IX, Skoplje 1934, pp 61¬71; 198¬201. In the first tribute, the author presented in brief Kožičić’s life. He recorded that Kožičić, with many bishops “from our parts”, arrived to Rome in 1512, when the (ecumenical Fifth Council of the Lateran was held “with the main aim to create a frame of mind against the Turks”, with the intention to offer necessary information in person. In the first session held on 10 May 1512, Kožičić had the opportunity to hear Bernardin Zane, the Archbishop of Split, address this matter; consequently, he held his own first speech at the Council on 27 April 1513. He held his second speech – according to Kolendić’s words – “probably in agreement with Prince Bernardin Frankopan” in the autumn, on 5 November 1516, outside the Council session, before Pope Leo X and his cardinals. Kolendić states that no typographic note accompanied the publications of both Kožičić’s speeches, but that they took place “with surety in Rome”. Well¬known facts are that Kožičić was forced to leave Modruš, that he barely managed to escape from the Turks, that he stayed in Vinodol, and that, around 1529, he withdrew to Rijeka where he opened his Glagolitic Printing House. He travelled to Venice to acquire printing inventory for his Printing House. Kolendić establishes which xylographs and letters Kožičić acquired there, and shows that Kožičić’s letters differ from the Glagolitic letters produced by Andrea Torresani or the Printing House Francesco Bindoni et Maffeo Pasini, who had before Kožičić published the Glagolitic Breviary (1493, Elementary Reader (1527 and

Experimental Demyelination and Axonal Loss Are Reduced in MicroRNA-146a Deficient Mice.

Science.gov (United States)

Martin, Nellie A; Molnar, Viktor; Szilagyi, Gabor T; Elkjaer, Maria L; Nawrocki, Arkadiusz; Okarmus, Justyna; Wlodarczyk, Agnieszka; Thygesen, Eva K; Palkovits, Miklos; Gallyas, Ferenc; Larsen, Martin R; Lassmann, Hans; Benedikz, Eirikur; Owens, Trevor; Svenningsen, Asa F; Illes, Zsolt

2018-01-01

The cuprizone (CPZ) model of multiple sclerosis (MS) was used to identify microRNAs (miRNAs) related to in vivo de- and remyelination. We further investigated the role of miR-146a in miR-146a-deficient (KO) mice: this miRNA is differentially expressed in MS lesions and promotes differentiation of oligodendrocyte precursor cells (OPCs) during remyelination, but its role has not been examined during demyelination. MicroRNAs were examined by Agilent Mouse miRNA Microarray in the corpus callosum during CPZ-induced demyelination and remyelination. Demyelination, axonal loss, changes in number of oligodendrocytes, OPCs, and macrophages/microglia was compared by histology/immunohistochemistry between KO and WT mice. Differential expression of target genes and proteins of miR-146a was analyzed in the transcriptome (4 × 44K Agilent Whole Mouse Genome Microarray) and proteome (liquid chromatography tandem mass spectrometry) of CPZ-induced de- and remyelination in WT mice. Levels of proinflammatory molecules in the corpus callosum were compared in WT versus KO mice by Meso Scale Discovery multiplex protein analysis. miR-146a was increasingly upregulated during CPZ-induced de- and remyelination. The absence of miR-146a in KO mice protected against demyelination, axonal loss, body weight loss, and atrophy of thymus and spleen. The number of CNP + oligodendrocytes was increased during demyelination in the miR-146a KO mice, while there was a trend of increased number of NG2 + OPCs in the WT mice. miR-146a target genes, SNAP25 and SMAD4, were downregulated in the proteome of demyelinating corpus callosum in WT mice. Higher levels of SNAP25 were measured by ELISA in the corpus callosum of miR-146a KO mice, but there was no difference between KO and WT mice during demyelination. Multiplex protein analysis of the corpus callosum lysate revealed upregulated TNF-RI, TNF-RII, and CCL2 in the WT mice in contrast to KO mice. The number of Mac3 + and Iba1 + macrophages/microglia was

Absence of DJ-1 causes age-related retinal abnormalities in association with increased oxidative stress.

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Bonilha, Vera L; Bell, Brent A; Rayborn, Mary E; Samuels, Ivy S; King, Anna; Hollyfield, Joe G; Xie, Chengsong; Cai, Huaibin

2017-03-01

Oxidative stress alters physiological function in most biological tissues and can lead to cell death. In the retina, oxidative stress initiates a cascade of events leading to focal loss of RPE and photoreceptors, which is thought to be a major contributing factor to geographic atrophy. Despite these implications, the molecular regulation of RPE oxidative stress under normal and pathological conditions remains largely unknown. A better understanding of the mechanisms involved in regulating RPE and photoreceptors oxidative stress response is greatly needed. To this end we evaluated photoreceptor and RPE changes in mice deficient in DJ-1, a protein that is thought to be important in protecting cells from oxidative stress. Young (3 months) and aged (18 months) DJ-1 knockout (DJ-1 KO) and age-matched wild-type mice were examined. In both group of aged mice, scanning laser ophthalmoscopy (SLO) showed the presence of a few autofluorescent foci. The 18 month-old DJ-1 KO retinas were also characterized by a noticeable increase in RPE fluorescence to wild-type. Optical coherence tomography (OCT) imaging demonstrated that all retinal layers were present in the eyes of both DJ-1 KO groups. ERG comparisons showed that older DJ-1 KO mice had reduced sensitivity under dark- and light-adapted conditions compared to age-matched control. Histologically, the RPE contained prominent vacuoles in young DJ-1 KO group with the appearance of enlarged irregularly shaped RPE cells in the older group. These were also evident in OCT and in whole mount RPE/choroid preparations labeled with phalloidin. Photoreceptors in the older DJ-1 KO mice displayed decreased immunoreactivity to rhodopsin and localized reduction in cone markers compared to the wild-type control group. Lower levels of activated Nrf2 were evident in retina/RPE lysates in both young and old DJ-1 KO mouse groups compared to wild-type control levels. Conversely, higher levels of protein carbonyl derivatives and i

Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome.

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Lovelace, Jonathan W; Wen, Teresa H; Reinhard, Sarah; Hsu, Mike S; Sidhu, Harpreet; Ethell, Iryna M; Binder, Devin K; Razak, Khaleel A

2016-05-01

Sensory processing deficits are common in autism spectrum disorders, but the underlying mechanisms are unclear. Fragile X Syndrome (FXS) is a leading genetic cause of intellectual disability and autism. Electrophysiological responses in humans with FXS show reduced habituation with sound repetition and this deficit may underlie auditory hypersensitivity in FXS. Our previous study in Fmr1 knockout (KO) mice revealed an unusually long state of increased sound-driven excitability in auditory cortical neurons suggesting that cortical responses to repeated sounds may exhibit abnormal habituation as in humans with FXS. Here, we tested this prediction by comparing cortical event related potentials (ERP) recorded from wildtype (WT) and Fmr1 KO mice. We report a repetition-rate dependent reduction in habituation of N1 amplitude in Fmr1 KO mice and show that matrix metalloproteinase-9 (MMP-9), one of the known FMRP targets, contributes to the reduced ERP habituation. Our studies demonstrate a significant up-regulation of MMP-9 levels in the auditory cortex of adult Fmr1 KO mice, whereas a genetic deletion of Mmp-9 reverses ERP habituation deficits in Fmr1 KO mice. Although the N1 amplitude of Mmp-9/Fmr1 DKO recordings was larger than WT and KO recordings, the habituation of ERPs in Mmp-9/Fmr1 DKO mice is similar to WT mice implicating MMP-9 as a potential target for reversing sensory processing deficits in FXS. Together these data establish ERP habituation as a translation relevant, physiological pre-clinical marker of auditory processing deficits in FXS and suggest that abnormal MMP-9 regulation is a mechanism underlying auditory hypersensitivity in FXS. Fragile X Syndrome (FXS) is the leading known genetic cause of autism spectrum disorders. Individuals with FXS show symptoms of auditory hypersensitivity. These symptoms may arise due to sustained neural responses to repeated sounds, but the underlying mechanisms remain unclear. For the first time, this study shows deficits

Sortilin 1 Loss-of-Function Protects Against Cholestatic Liver Injury by Attenuating Hepatic Bile Acid Accumulation in Bile Duct Ligated Mice.

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Li, Jibiao; Woolbright, Benjamin L; Zhao, Wen; Wang, Yifeng; Matye, David; Hagenbuch, Bruno; Jaeschke, Hartmut; Li, Tiangang

2018-01-01

Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein sorting in the endocytic or secretory pathways. Recent studies revealed a role of Sort1 in the regulation of cholesterol and bile acid (BA) metabolism. This study further investigated the role of Sort1 in modulating BA detoxification and cholestatic liver injury in bile duct ligated mice. We found that Sort1 knockout (KO) mice had attenuated liver injury 24 h after bile duct ligation (BDL), which was mainly attributed to less bile infarct formation. Sham-operated Sort1 KO mice had about 20% larger BA pool size than sham-operated wildtype (WT) mice, but 24 h after BDL Sort1 KO mice had significantly attenuated hepatic BA accumulation and smaller BA pool size. After 14 days BDL, Sort1 KO mice showed significantly lower hepatic BA concentration and reduced expression of inflammatory and fibrotic marker genes, but similar degree of liver fibrosis compared with WT mice. Unbiased quantitative proteomics revealed that Sort1 KO mice had increased hepatic BA sulfotransferase 2A1, but unaltered phase-I BA metabolizing cytochrome P450s or phase-III BA efflux transporters. Consistently, Sort1 KO mice showed elevated plasma sulfated taurocholate after BDL. Finally, we found that liver Sort1 was repressed after BDL, which may be due to BA activation of farnesoid x receptor. In conclusion, we report a role of Sort1 in the regulation of hepatic BA detoxification and cholestatic liver injury in mice. The mechanisms underlying increased hepatic BA elimination in Sort1 KO mice after BDL require further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors.

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Roopali Yadav

Full Text Available The delta family of ionotropic glutamate receptors consists of glutamate δ1 (GluD1 and glutamate δ2 (GluD2 receptors. While the role of GluD2 in the regulation of cerebellar physiology is well understood, the function of GluD1 in the central nervous system remains elusive. We demonstrate for the first time that deletion of GluD1 leads to abnormal emotional and social behaviors. We found that GluD1 knockout mice (GluD1 KO were hyperactive, manifested lower anxiety-like behavior, depression-like behavior in a forced swim test and robust aggression in the resident-intruder test. Chronic lithium rescued the depression-like behavior in GluD1 KO. GluD1 KO mice also manifested deficits in social interaction. In the sociability test, GluD1 KO mice spent more time interacting with an inanimate object compared to a conspecific mouse. D-Cycloserine (DCS administration was able to rescue social interaction deficits observed in GluD1 KO mice. At a molecular level synaptoneurosome preparations revealed lower GluA1 and GluA2 subunit expression in the prefrontal cortex and higher GluA1, GluK2 and PSD95 expression in the amygdala of GluD1 KO. Moreover, DCS normalized the lower GluA1 expression in prefrontal cortex of GluD1 KO. We propose that deletion of GluD1 leads to aberrant circuitry in prefrontal cortex and amygdala owing to its potential role in presynaptic differentiation and synapse formation. Furthermore, these findings are in agreement with the human genetic studies suggesting a strong association of GRID1 gene with several neuropsychiatric disorders including schizophrenia, bipolar disorder, autism spectrum disorders and major depressive disorder.

Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection

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Vidlak Debbie

2012-06-01

Full Text Available Abstract Although IL-17A (commonly referred to as IL-17 has been implicated in the pathogenesis of central nervous system (CNS autoimmune disease, its role during CNS bacterial infections remains unclear. To evaluate the broader impact of IL-17 family members in the context of CNS infection, we utilized IL-17 receptor (IL-17R knockout (KO mice that lack the ability to respond to IL-17, IL-17F and IL-17E (IL-25. In this article, we demonstrate that IL-17R signaling regulates bacterial clearance as well as natural killer T (NKT cell and gamma-delta (γδ T cell infiltrates during Staphylococcus aureus-induced brain abscess formation. Specifically, when compared with wild-type (WT animals, IL-17R KO mice exhibited elevated bacterial burdens at days 7 and 14 following S. aureus infection. Additionally, IL-17R KO animals displayed elevated neutrophil chemokine production, revealing the ability to compensate for the lack of IL-17R activity. Despite these differences, innate immune cell recruitment into brain abscesses was similar in IL-17R KO and WT mice, whereas IL-17R signaling exerted a greater influence on adaptive immune cell recruitment. In particular, γδ T cell influx was increased in IL-17R KO mice at day 7 post-infection. In addition, NK1.1high infiltrates were absent in brain abscesses of IL-17R KO animals and, surprisingly, were rarely detected in the livers of uninfected IL-17R KO mice. Although IL-17 is a key regulator of neutrophils in other infection models, our data implicate an important role for IL-17R signaling in regulating adaptive immunity during CNS bacterial infection.

Genetic deletion of afadin causes hydrocephalus by destruction of adherens junctions in radial glial and ependymal cells in the midbrain.

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Hideaki Yamamoto

Full Text Available Adherens junctions (AJs play a role in mechanically connecting adjacent cells to maintain tissue structure, particularly in epithelial cells. The major cell-cell adhesion molecules at AJs are cadherins and nectins. Afadin binds to both nectins and α-catenin and recruits the cadherin-β-catenin complex to the nectin-based cell-cell adhesion site to form AJs. To explore the role of afadin in radial glial and ependymal cells in the brain, we generated mice carrying a nestin-Cre-mediated conditional knockout (cKO of the afadin gene. Newborn afadin-cKO mice developed hydrocephalus and died neonatally. The afadin-cKO brain displayed enlarged lateral ventricles and cerebral aqueduct, resulting from stenosis of the caudal end of the cerebral aqueduct and obliteration of the ventral part of the third ventricle. Afadin deficiency further caused the loss of ependymal cells from the ventricular and aqueductal surfaces. During development, radial glial cells, which terminally differentiate into ependymal cells, scattered from the ventricular zone and were replaced by neurons that eventually covered the ventricular and aqueductal surfaces of the afadin-cKO midbrain. Moreover, the denuded ependymal cells were only occasionally observed in the third ventricle and the cerebral aqueduct of the afadin-cKO midbrain. Afadin was co-localized with nectin-1 and N-cadherin at AJs of radial glial and ependymal cells in the control midbrain, but these proteins were not concentrated at AJs in the afadin-cKO midbrain. Thus, the defects in the afadin-cKO midbrain most likely resulted from the destruction of AJs, because AJs in the midbrain were already established before afadin was genetically deleted. These results indicate that afadin is essential for the maintenance of AJs in radial glial and ependymal cells in the midbrain and is required for normal morphogenesis of the cerebral aqueduct and ventral third ventricle in the midbrain.

Comprehensive behavioral analysis of mice deficient in Rapgef2 and Rapgef6, a subfamily of guanine nucleotide exchange factors for Rap small GTPases possessing the Ras/Rap-associating domain.

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Maeta, Kazuhiro; Hattori, Satoko; Ikutomo, Junji; Edamatsu, Hironori; Bilasy, Shymaa E; Miyakawa, Tsuyoshi; Kataoka, Tohru

2018-05-10

Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap small GTPases, characterized by the possession of the Ras/Rap-associating domain. Previous genomic analyses suggested their possible involvement in the etiology of schizophrenia. We recently demonstrated the development of an ectopic cortical mass (ECM), which resembles the human subcortical band heterotopia, in the dorsal telencephalon-specific Rapgef2 conditional knockout (Rapgef2-cKO) brains. Additional knockout of Rapgef6 in Rapgef2-cKO mice resulted in gross enlargement of the ECM whereas knockout of Rapgef6 alone (Rapgef6-KO) had no discernible effect on the brain morphology. Here, we performed a battery of behavioral tests to examine the effects of Rapgef2 or Rapgef6 deficiency on higher brain functions. Rapgef2-cKO mice exhibited hyperlocomotion phenotypes. They showed decreased anxiety-like behavior in the elevated plus maze and the open-field tests as well as increased depression-like behavior in the Porsolt forced swim and tail suspension tests. They also exhibited increased sociability especially in novel environments. They showed defects in cognitive function as evidenced by reduced learning ability in the Barnes circular maze test and by impaired working memory in the T maze tests. In contrast, although Rapgef6 and Rapgef2 share similarities in biochemical roles, Rapgef6-KO mice exhibited mild behavioral abnormalities detected with a number of behavioral tests, such as hyperlocomotion phenotype in the open-field test and the social interaction test with a novel environment and working-memory defects in the T-maze test. In conclusion, although there were differences in their brain morphology and the magnitude of the behavioral abnormalities, Rapgef2-cKO mice and Rapgef6-KO mice exhibited hyperlocomotion phenotype and working-memory defect, both of which could be recognized as schizophrenia-like behavior.

Apolipoprotein E expression and behavioral toxicity of high charge, high energy (HZE) particle radiation

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Higuchi, Yoshinori; Nelson, Gregory A.; Vazquez, Marcelo; Laskowitz, Daniel T.; Slater, James M.; Pearlstein, Robert D.

2002-01-01

Apolipoprotein E (apoE) is a lipid binding protein that plays an important role in tissue repair following brain injury. In the present studies, we have investigated whether apoE affects the behavioral toxicity of high charge, high energy (HZE) particle radiation. METHODS: Sixteen male apoE knockout (KO) mice and sixteen genetically matched wild-type (WT) C57BL mice were used in this experiment. Half of the KO and half of the WT animals were irradiated with 600 MeV/amu iron particles (2 Gy whole body). The effect of irradiation on motor coordination and stamina (Rotarod test), exploratory behavior (open field test), and spatial working and reference memory (Morris water maze) was assessed. ROTAROD TEST: Performance was adversely affected by radiation exposure in both KO and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation effect was lost in WT, but still apparent in irradiated KO mice. OPEN FIELD TEST: Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after irradiation of KO mice, but had no effect on WT mice. MORRIS WATER MAZE: Radiation adversely affected spatial working memory in the KO mice, but had no discernible effect in the WT mice as assessed 180 d after irradiation. In contrast, irradiated WT mice showed marked impairment of spatial reference memory in comparison to non-irradiated mice, while no effect of radiation was observed in KO mice. CONCLUSIONS: These studies show that apoE expression influences the behavioral toxicity of HZE particle radiation and suggest that apoE plays a role in the repair/recovery from radiation injury of the CNS. ApoE deficiency may exacerbate the previously reported effects of HZE particle radiation in accelerating the brain aging process.

The role of endoplasmic reticulum stress in hippocampal insulin resistance.

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Sims-Robinson, Catrina; Bakeman, Anna; Glasser, Rebecca; Boggs, Janet; Pacut, Crystal; Feldman, Eva L

2016-03-01

Metabolic syndrome, which includes hypertension, hyperglycemia, obesity, insulin resistance, and dyslipidemia, has a negative impact on cognitive health. Endoplasmic reticulum (ER) stress is activated during metabolic syndrome, however it is not known which factor associated with metabolic syndrome contributes to this stress. ER stress has been reported to play a role in the development of insulin resistance in peripheral tissues. The role of ER stress in the development of insulin resistance in hippocampal neurons is not known. In the current study, we investigated ER stress in the hippocampus of 3 different mouse models of metabolic syndrome: the C57BL6 mouse on a high fat (HF) diet; apolipoprotein E, leptin, and apolipoprotein B-48 deficient (ApoE 3KO) mice; and the low density lipoprotein receptor, leptin, and apolipoprotein B-48 deficient (LDLR 3KO) mice. We demonstrate that ER stress is activated in the hippocampus of HF mice, and for the first time, in ApoE 3KO mice, but not LDLR 3KO mice. The HF and ApoE 3KO mice are hyperglycemic; however, the LDLR 3KO mice have normal glycemia. This suggests that hyperglycemia may play a role in the activation of ER stress in the hippocampus. Similarly, we also demonstrate that impaired insulin signaling is only present in the HF and ApoE 3KO mice, which suggests that ER stress may play a role in insulin resistance in the hippocampus. To confirm this we pharmacologically induced ER stress with thapsigargin in human hippocampal neurons. We demonstrate for the first time that thapsigargin leads to ER stress and impaired insulin signaling in human hippocampal neurons. Our results may provide a potential mechanism that links metabolic syndrome and cognitive health. Copyright © 2016 Elsevier Inc. All rights reserved.

Dopamine D₂-Like Receptors and Behavioral Economics of Food Reinforcement.

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Soto, Paul L; Hiranita, Takato; Xu, Ming; Hursh, Steven R; Grandy, David K; Katz, Jonathan L

2016-03-01

Previous studies suggest dopamine (DA) D2-like receptor involvement in the reinforcing effects of food. To determine contributions of the three D2-like receptor subtypes, knockout (KO) mice completely lacking DA D2, D3, or D4 receptors (D2R, D3R, or D4R KO mice) and their wild-type (WT) littermates were exposed to a series of fixed-ratio (FR) food-reinforcement schedules in two contexts: an open economy with additional food provided outside the experimental setting and a closed economy with all food earned within the experimental setting. A behavioral economic model was used to quantify reinforcer effectiveness with food pellets obtained as a function of price (FR schedule value) plotted to assess elasticity of demand. Under both economies, as price increased, food pellets obtained decreased more rapidly (ie, food demand was more elastic) in DA D2R KO mice compared with WT littermates. Extinction of responding was studied in two contexts: by eliminating food deliveries and by delivering food independently of responding. A hyperbolic model quantified rates of extinction. Extinction in DA D2R KO mice occurred less rapidly compared with WT mice in both contexts. Elasticity of food demand was higher in DA D4R KO than WT mice in the open, but not closed, economy. Extinction of responding in DA D4R KO mice was not different from that in WT littermates in either context. No differences in elasticity of food demand or extinction rate were obtained in D3R KO mice and WT littermates. These results indicate that the D2R is the primary DA D2-like receptor subtype mediating the reinforcing effectiveness of food.

Dopamine D2-Like Receptors and Behavioral Economics of Food Reinforcement

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Soto, Paul L; Hiranita, Takato; Xu, Ming; Hursh, Steven R; Grandy, David K; Katz, Jonathan L

2016-01-01

Previous studies suggest dopamine (DA) D2-like receptor involvement in the reinforcing effects of food. To determine contributions of the three D2-like receptor subtypes, knockout (KO) mice completely lacking DA D2, D3, or D4 receptors (D2R, D3R, or D4R KO mice) and their wild-type (WT) littermates were exposed to a series of fixed-ratio (FR) food-reinforcement schedules in two contexts: an open economy with additional food provided outside the experimental setting and a closed economy with all food earned within the experimental setting. A behavioral economic model was used to quantify reinforcer effectiveness with food pellets obtained as a function of price (FR schedule value) plotted to assess elasticity of demand. Under both economies, as price increased, food pellets obtained decreased more rapidly (ie, food demand was more elastic) in DA D2R KO mice compared with WT littermates. Extinction of responding was studied in two contexts: by eliminating food deliveries and by delivering food independently of responding. A hyperbolic model quantified rates of extinction. Extinction in DA D2R KO mice occurred less rapidly compared with WT mice in both contexts. Elasticity of food demand was higher in DA D4R KO than WT mice in the open, but not closed, economy. Extinction of responding in DA D4R KO mice was not different from that in WT littermates in either context. No differences in elasticity of food demand or extinction rate were obtained in D3R KO mice and WT littermates. These results indicate that the D2R is the primary DA D2-like receptor subtype mediating the reinforcing effectiveness of food. PMID:26205210

Synergistic effects of high fat feeding and apolipoprotein E deletion on enterocytic amyloid-beta abundance

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Dhaliwal Satvinder S

2008-04-01

Full Text Available Abstract Background Amyloid-β (Aβ, a key protein found in amyloid plaques of subjects with Alzheimer's disease is expressed in the absorptive epithelial cells of the small intestine. Ingestion of saturated fat significantly enhances enterocytic Aβ abundance whereas fasting abolishes expression. Apolipoprotein (apo E has been shown to directly modulate Aβ biogenesis in liver and neuronal cells but it's effect in enterocytes is not known. In addition, apo E modulates villi length, which may indirectly modulate Aβ as a consequence of differences in lipid absorption. This study compared Aβ abundance and villi length in wild-type (WT and apo E knockout (KO mice maintained on either a low-fat or high-fat diet. Wild-type C57BL/6J and apo E KO mice were randomised for six-months to a diet containing either 4% (w/w unsaturated fats, or chow comprising 16% saturated fats and 1% cholesterol. Quantitative immunohistochemistry was used to assess Aβ abundance in small intestinal enterocytes. Apo E KO mice given the low-fat diet had similar enterocytic Aβ abundance compared to WT controls. Results The saturated fat diet substantially increased enterocytic Aβ in WT and in apo E KO mice, however the effect was greater in the latter. Villi height was significantly greater in apo E KO mice than for WT controls when given the low-fat diet. However, WT mice had comparable villi length to apo E KO when fed the saturated fat and cholesterol enriched diet. There was no effect of the high-fat diet on villi length in apo E KO mice. Conclusion The findings of this study are consistent with the notion that lipid substrate availability modulates enterocytic Aβ. Apo E may influence enterocytic lipid availability by modulating absorptive capacity.

PTP1B deficiency improves hypothalamic insulin sensitivity resulting in the attenuation of AgRP mRNA expression under high-fat diet conditions.

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Sugiyama, Mariko; Banno, Ryoichi; Mizoguchi, Akira; Tominaga, Takashi; Tsunekawa, Taku; Onoue, Takeshi; Hagiwara, Daisuke; Ito, Yoshihiro; Morishita, Yoshiaki; Iwama, Shintaro; Goto, Motomitsu; Suga, Hidetaka; Arima, Hiroshi

2017-06-17

Hypothalamic insulin receptor signaling regulates energy balance and glucose homeostasis via agouti-related protein (AgRP). While protein tyrosine phosphatase 1B (PTP1B) is classically known to be a negative regulator of peripheral insulin signaling by dephosphorylating both insulin receptor β (IRβ) and insulin receptor substrate, the role of PTP1B in hypothalamic insulin signaling remains to be fully elucidated. In the present study, we investigated the role of PTP1B in hypothalamic insulin signaling using PTP1B deficient (KO) mice in vivo and ex vivo. For the in vivo study, hypothalamic insulin resistance induced by a high-fat diet (HFD) improved in KO mice compared to wild-type (WT) mice. Hypothalamic AgRP mRNA expression levels were also significantly decreased in KO mice independent of body weight changes. In an ex vivo study using hypothalamic organotypic cultures, insulin treatment significantly increased the phosphorylation of both IRβ and Akt in the hypothalamus of KO mice compared to WT mice, and also significantly decreased AgRP mRNA expression levels in KO mice. While incubation with inhibitors of phosphatidylinositol-3 kinase (PI3K) had no effect on basal levels of Akt phosphorylation, these suppressed insulin induction of Akt phosphorylation to almost basal levels in WT and KO mice. The inhibition of the PI3K-Akt pathway blocked the downregulation of AgRP mRNA expression in KO mice treated with insulin. These data suggest that PTP1B acts on the hypothalamic insulin signaling via the PI3K-Akt pathway. Together, our results suggest a deficiency of PTP1B improves hypothalamic insulin sensitivity resulting in the attenuation of AgRP mRNA expression under HFD conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired angiogenesis during fracture healing in GPCR kinase 2 interacting protein-1 (GIT1 knock out mice.

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Guoyong Yin

Full Text Available G protein coupled receptor kinase 2 (GRK2 interacting protein-1 (GIT1, is a scaffold protein that plays an important role in angiogenesis and osteoclast activity. We have previously demonstrated that GIT1 knockout (GIT1 KO mice have impaired angiogenesis and dysregulated osteoclast podosome formation leading to a reduction in the bone resorbing ability of these cells. Since both angiogenesis and osteoclast-mediated bone remodeling are involved in the fracture healing process, we hypothesized that GIT1 participates in the normal progression of repair following bone injury. In the present study, comparison of fracture healing in wild type (WT and GIT1 KO mice revealed altered healing in mice with loss of GIT1 function. Alcian blue staining of fracture callus indicated a persistence of cartilagenous matrix in day 21 callus samples from GIT1 KO mice which was temporally correlated with increased type 2 collagen immunostaining. GIT1 KO mice also showed a decrease in chondrocyte proliferation and apoptosis at days 7 and 14, as determined by PCNA and TUNEL staining. Vascular microcomputed tomography analysis of callus samples at days 7, 14 and 21 revealed decreased blood vessel volume, number, and connection density in GIT1 KO mice compared to WT controls. Correlating with this, VEGF-A, phospho-VEGFR2 and PECAM1 (CD31 were decreased in GIT1 KO mice, indicating reduced angiogenesis with loss of GIT1. Finally, calluses from GIT1 KO mice displayed a reduced number of tartrate resistant acid phosphatase-positive osteoclasts at days 14 and 21. Collectively, these results indicate that GIT1 is an important signaling participant in fracture healing, with gene ablation leading to reduced callus vascularity and reduced osteoclast number in the healing callus.

Dry Heathland Restoration in the Zlatnice Nature Reserve (Czech Republic: An Assessment of the Effectiveness of Grazing and Sod-Cutting

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Dostálek Jiří

2015-06-01

Full Text Available Vegetacija nižinskih suhih vresav v srednji Evropi (Euphorbio cyparissiae-Callunion vulgaris je v upadanju zaradi opuščanja tradicionalnega gospodarjenja in to se kaže v postopnem zaraščanju z lesnatimi rastlinami in spremenjenem vnosu hranil. Za obnovitev sestojev z vreso, ki so izginili, smo uporabili pašo z nizko intenzivnostjo in košnjo, ki sta tradicionalno priporočena načina za obnavljanje vegetacije z vreso (Calluna vulgaris iz semenske banke. Raziskavo smo opravili v naravnem rezervatu Zlatnice, ki se nahaja v severozahodnem delu Prage (Češka republika. Vzpostavili smo sistem stalnih 1 m2 ploskev. Za obnovitev vegetacije z vrsto Calluna vulgaris sta bila uspešna tako paša kot košnja. Pokrovnost vrese se je povečala dve leti po začetku poskusa s pašo, na površinah s košnjo pa se je značilno povečala tretje leto in vrednosti so bile primerljive s pašenimi površinami. Redna paša je ovirala povečanje pokrovnosti zelišč, medtem ko se je njihova pokrovnost povečala po posamezni košnji. Košnja je tudi vplivala na povečanje pokrovnosti mahov. Poizkus je pokazal, da je slabo intenzivna paša ovac in koz verjetno najbolj primeren način obnove suhih vresav na plitvih, s hranili revnih tleh, po več kot 20 let od uničenja vresave. Košnja je bolj zahtevna, pojavlja pa se tudi možnost razraščanja nezaželjenih zelišč in lesnatih rastlin, kar zopet vodi v degradacijo vegetacije z vrsto Calluna vulgaris.

Isoproterenol induces vascular oxidative stress and endothelial dysfunction via a Giα-coupled β2-adrenoceptor signaling pathway.

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Ana P Davel

Full Text Available OBJECTIVE: Sustained β-adrenergic stimulation is a hallmark of sympathetic hyperactivity in cardiovascular diseases. It is associated with oxidative stress and altered vasoconstrictor tone. This study investigated the β-adrenoceptor subtype and the signaling pathways implicated in the vascular effects of β-adrenoceptor overactivation. METHODS AND RESULTS: Mice lacking the β1- or β2-adrenoceptor subtype (β1KO, β2KO and wild-type (WT were treated with isoproterenol (ISO, 15 μg.g(-1 x day(-1, 7 days. ISO significantly enhanced the maximal vasoconstrictor response (Emax of the aorta to phenylephrine in WT (+34% and β1KO mice (+35% but not in β2KO mice. The nitric oxide synthase (NOS inhibitor L-NAME abolished the differences in phenylephrine response between the groups, suggesting that ISO impaired basal NO availability in the aorta of WT and β1KO mice. Superoxide dismutase (SOD, pertussis toxin (PTx or PD 98,059 (p-ERK 1/2 inhibitor incubation reversed the hypercontractility of aortic rings from ISO-treated WT mice; aortic contraction of ISO-treated β2KO mice was not altered. Immunoblotting revealed increased aortic expression of Giα-3 protein (+50% and phosphorylated ERK1/2 (+90% and decreased eNOS dimer/monomer ratio in ISO-treated WT mice. ISO enhanced the fluorescence response to dihydroethidium (+100% in aortas from WT mice, indicating oxidative stress that was normalized by SOD, PTx and L-NAME. The ISO effects were abolished in β2KO mice. CONCLUSIONS: The β2-adrenoceptor/Giα signaling pathway is implicated in the enhanced vasoconstrictor response and eNOS uncoupling-mediated oxidative stress due to ISO treatment. Thus, long-term β2-AR activation might results in endothelial dysfunction.

Apolipoprotein E expression and behavioral toxicity of high charge, high energy (HZE) particle radiation

International Nuclear Information System (INIS)

Higuchi, Yoshinori; Nelson, G.A.; Slater, J.M.; Pearlstein, R.D.; Laskowitz, D.T.

2002-01-01

Apolipoprotein E (apoE) is a lipid binding protein that plays an important role in tissue repair following brain injury. In the present studies, we have investigated whether apoE affects the behavioral toxicity of high charge, high energy (HZE) particle radiation. Sixteen male apoE knockout (KO) mice and sixteen genetically matched wild-type (WT) C57BL mice were used in this experiment. Half of the KO and half of the WT animals were irradiated with 600 MeV/amu iron particles (2 Gy whole body). The effect of irradiation on motor coordination and stamina (Rotarod test), exploratory behavior (open field test), and spatial working and reference memory (Morris water maze) was assessed. Rotarod test: Performance was adversely affected by radiation exposure in both KO and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation effect was lost in WT, but still apparent in irradiated KO mice. Open field test: Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after irradiation of KO mice, but had no effect on WT mice. Morris water maze: Radiation adversely affected spatial working memory in the KO mice, but had no discernible effect in the WT mice as assessed 180 d after irradiation. In contrast, irradiated WT mice showed marked impairment of spatial reference memory in comparison to non-irradiated mice, while no effect of radiation was observed in KO mice. These studies show that apoE expression influences the behavioral toxicity of HZE particle radiation and suggest that apoE plays a role in the repair/recovery from radiation injury of the central nervous system (CNS). ApoE deficiency may exacerbate the previously reported effects of HZE particle radiation in accelerating the brain aging process. (author)

Apolipoprotein E expression and behavioral toxicity of high charge, high energy (HZE) particle radiation

Energy Technology Data Exchange (ETDEWEB)

Higuchi, Yoshinori; Nelson, G.A.; Slater, J.M.; Pearlstein, R.D. [Loma Linda Univ., CA (United States). Medical Center; Vazquez, M. [Brookhaven National Lab., Upton, NY (United States); Laskowitz, D.T. [Duke Univ., Durham, NC (United States). Medical Center

2002-12-01

Apolipoprotein E (apoE) is a lipid binding protein that plays an important role in tissue repair following brain injury. In the present studies, we have investigated whether apoE affects the behavioral toxicity of high charge, high energy (HZE) particle radiation. Sixteen male apoE knockout (KO) mice and sixteen genetically matched wild-type (WT) C57BL mice were used in this experiment. Half of the KO and half of the WT animals were irradiated with 600 MeV/amu iron particles (2 Gy whole body). The effect of irradiation on motor coordination and stamina (Rotarod test), exploratory behavior (open field test), and spatial working and reference memory (Morris water maze) was assessed. Rotarod test: Performance was adversely affected by radiation exposure in both KO and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation effect was lost in WT, but still apparent in irradiated KO mice. Open field test: Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after irradiation of KO mice, but had no effect on WT mice. Morris water maze: Radiation adversely affected spatial working memory in the KO mice, but had no discernible effect in the WT mice as assessed 180 d after irradiation. In contrast, irradiated WT mice showed marked impairment of spatial reference memory in comparison to non-irradiated mice, while no effect of radiation was observed in KO mice. These studies show that apoE expression influences the behavioral toxicity of HZE particle radiation and suggest that apoE plays a role in the repair/recovery from radiation injury of the central nervous system (CNS). ApoE deficiency may exacerbate the previously reported effects of HZE particle radiation in accelerating the brain aging process. (author)

IDH2 Deficiency Aggravates Fructose-Induced NAFLD by Modulating Hepatic Fatty Acid Metabolism and Activating Inflammatory Signaling in Female Mice

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Jeong Hoon Pan

2018-05-01

Full Text Available Fructose is a strong risk factor for non-alcoholic fatty liver disease (NAFLD, resulting from the disruption of redox systems by excessive reactive oxygen species production in the liver cells. Of note, recent epidemiological studies indicated that women are more prone to developing metabolic syndrome in response to fructose-sweetened beverages. Hence, we examined whether disruption of the redox system through a deletion of NADPH supplying mitochondrial enzyme, NADP+-dependent isocitrate dehydrogenase (IDH2, exacerbates fructose-induced NAFLD conditions in C57BL/6 female mice. Wild-type (WT and IDH2 knockout (KO mice were treated with either water or 34% fructose water over six weeks. NAFLD phenotypes and key proteins and mRNAs involved in the inflammatory pathway (e.g., NF-κB p65 and IL-1β were assessed. Hepatic lipid accumulation was significantly increased in IDH2 KO mice fed fructose compared to the WT counterpart. Neutrophil infiltration was observed only in IDH2 KO mice fed fructose. Furthermore, phosphorylation of NF-κB p65 and expression of IL-1β was remarkably upregulated in IDH2 KO mice fed fructose, and expression of IκBα was decreased by fructose treatment in both WT and IDH2 KO groups. For the first time, we report our novel findings that IDH2 KO female mice may be more susceptible to fructose-induced NAFLD and the associated inflammatory response, suggesting a mechanistic role of IDH2 in metabolic diseases.

Ethanol self-administration in serotonin transporter knockout mice: unconstrained demand and elasticity.

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Lamb, R J; Daws, L C

2013-10-01

Low serotonin function is associated with alcoholism, leading to speculation that increasing serotonin function could decrease ethanol consumption. Mice with one or two deletions of the serotonin transporter (SERT) gene have increased extracellular serotonin. To examine the relationship between SERT genotype and motivation for alcohol, we compared ethanol self-administration in mice with zero (knockout, KO), one (HET) or two copies (WT) of the SERT gene. All three genotypes learned to self-administer ethanol. The SSRI, fluvoxamine, decreased responding for ethanol in the HET and WT, but not the KO mice. When tested under a progressive ratio schedule, KO mice had lower breakpoints than HET or WT. As work requirements were increased across sessions, behavioral economic analysis of ethanol self-administration indicated that the decreased breakpoint in KO as compared to HET or WT mice was a result of lower levels of unconstrained demand, rather than differences in elasticity, i.e. the proportional decreases in ethanol earned with increasing work requirements were similar across genotypes. The difference in unconstrained demand was unlikely to result from motor or general motivational factors, as both WT and KO mice responded at high levels for a 50% condensed milk solution. As elasticity is hypothesized to measure essential value, these results indicate that KO value ethanol similarly to WT or HET mice despite having lower break points for ethanol. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Desacyl Ghrelin Decreases Anxiety-like Behavior in Male Mice.

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Mahbod, Parinaz; Smith, Eric P; Fitzgerald, Maureen E; Morano, Rachel L; Packard, Benjamin A; Ghosal, Sriparna; Scheimann, Jessie R; Perez-Tilve, Diego; Herman, James P; Tong, Jenny

2018-01-01

Ghrelin is a 28-amino acid polypeptide that regulates feeding, glucose metabolism, and emotionality (stress, anxiety, and depression). Plasma ghrelin circulates as desacyl ghrelin (DAG) or, in an acylated form, acyl ghrelin (AG), through the actions of ghrelin O-acyltransferase (GOAT), exhibiting low or high affinity, respectively, for the growth hormone secretagogue receptor (GHSR) 1a. We investigated the role of endogenous AG, DAG, and GHSR1a signaling on anxiety and stress responses using ghrelin knockout (Ghr KO), GOAT KO, and Ghsr stop-floxed (Ghsr null) mice. Behavioral and hormonal responses were tested in the elevated plus maze and light/dark (LD) box. Mice lacking both AG and DAG (Ghr KO) increased anxiety-like behaviors across tests, whereas anxiety reactions were attenuated in DAG-treated Ghr KO mice and in mice lacking AG (GOAT KO). Notably, loss of GHSR1a (Ghsr null) did not affect anxiety-like behavior in any test. Administration of AG and DAG to Ghr KO mice with lifelong ghrelin deficiency reduced anxiety-like behavior and decreased phospho-extracellular signal-regulated kinase phosphorylation in the Edinger-Westphal nucleus in wild-type mice, a site normally expressing GHSR1a and involved in stress- and anxiety-related behavior. Collectively, our data demonstrate distinct roles for endogenous AG and DAG in regulation of anxiety responses and suggest that the behavioral impact of ghrelin may be context dependent. Copyright © 2018 Endocrine Society.

Effects of Eaf2 gene knockout on cataract induced by ultraviolet irradiation in mice

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Yan-Hua Jiang

2016-02-01

Full Text Available AIM:To evaluate the effects of Eaf2 gene knockout on cataract in mice induced by ultraviolet irradiation.METHODS:Fifteen wild type mice were used as the control group, and 10 Eaf2 KO mice were used as the experimental group. The 14-week mice were taken as the research objects in the two groups. So the subgroups were: WT -nonUV, WT -UV, Eaf2 KO-nonUV and Eaf2 KO-UV, a total of 4 groups. Observe the lens of mice in vivo with slit lamp microscope, grade the lens opacity with Lens Opacities Classification System II(LOCSII. Then the mice were sacrificed by breaking the neck, the lens were removed and were observed by dark field microscopy. According to the captured images, the proportion of cataract region was analyzed using Image J software. The data of the two groups were statistically analyzed.RESULTS: The results detected by the two methods were similar. In WT-UV group and Eaf2 KO-UV group, the degree of lens opacity was significantly higher than those of WT-nonUV group and Eaf2 KO-nonUV group. The lens opacity of WT-UV group was significantly higher than that in Eaf2 KO-UV group, and the difference was statistically significant(PCONCLUSION: Ultraviolet radiation can lead to the formation of cataract in mice. Eaf2 protein can promote the formation of cataract in mice caused by ultraviolet.

Cell-Specific Loss of SNAP25 from Cortical Projection Neurons Allows Normal Development but Causes Subsequent Neurodegeneration.

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Hoerder-Suabedissen, Anna; Korrell, Kim V; Hayashi, Shuichi; Jeans, Alexander; Ramirez, Denise M O; Grant, Eleanor; Christian, Helen C; Kavalali, Ege T; Wilson, Michael C; Molnár, Zoltán

2018-05-30

Synaptosomal associated protein 25 kDa (SNAP25) is an essential component of the SNARE complex regulating synaptic vesicle fusion. SNAP25 deficiency has been implicated in a variety of cognitive disorders. We ablated SNAP25 from selected neuronal populations by generating a transgenic mouse (B6-Snap25tm3mcw (Snap25-flox)) with LoxP sites flanking exon5a/5b. In the presence of Cre-recombinase, Snap25-flox is recombined to a truncated transcript. Evoked synaptic vesicle release is severely reduced in Snap25 conditional knockout (cKO) neurons as shown by live cell imaging of synaptic vesicle fusion and whole cell patch clamp recordings in cultured hippocampal neurons. We studied Snap25 cKO in subsets of cortical projection neurons in vivo (L5-Rbp4-Cre; L6-Ntsr1-Cre; L6b-Drd1a-Cre). cKO neurons develop normal axonal projections, but axons are not maintained appropriately, showing signs of swelling, fragmentation and eventually complete absence. Onset and progression of degeneration are dependent on the neuron type, with L5 cells showing the earliest and most severe axonal loss. Ultrastructural examination revealed that cKO neurites contain autophagosome/lysosome-like structures. Markers of inflammation such as Iba1 and lipofuscin are increased only in adult cKO cortex. Snap25 cKO can provide a model to study genetic interactions with environmental influences in several disorders.

Distinctive behavioral and cellular responses to fluoxetine in the mouse model for Fragile X syndrome

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Marko eUutela

2014-05-01

Full Text Available Fluoxetine is used as a therapeutic agent for autism spectrum disorder (ASD, including Fragile X syndrome (FXS. The treatment often associates with disruptive behaviors such as agitation and disinhibited behaviors in FXS. To identify mechanisms that increase the risk to poor treatment outcome, we investigated the behavioral and cellular effects of fluoxetine on adult Fmr1 knockout (KO mice, a mouse model for FXS. We found that fluoxetine reduced anxiety-like behavior of both wild type and Fmr1 KO mice seen as shortened latency to enter the center area in the open field test. In Fmr1 KO mice, fluoxetine normalized locomotor hyperactivity but abnormally increased exploratory activity. Reduced Brain-derived neurotrophic factor (BDNF and increased TrkB receptor expression levels in the hippocampus of Fmr1 KO mice associated with inappropriate coping responses under stressful condition and abolished antidepressant activity of fluoxetine. Fluoxetine response in the cell proliferation was also missing in the hippocampus of Fmr1 KO mice when compared with wild type controls. The postnatal expression of serotonin transporter was reduced in the thalamic nuclei of Fmr1 KO mice during the time of transient innervation of somatosensory neurons suggesting that developmental changes of serotonin transporter (SERT expression were involved in the differential cellular and behavioral responses to fluoxetine in wild type and Fmr1 mice. The results indicate that changes of BDNF/TrkB signaling contribute to differential behavioral responses to fluoxetine among individuals with ASD.

Negative Effects of Chronic Rapamycin Treatment on Behavior in a Mouse Model of Fragile X Syndrome

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Rachel M. Saré

2018-01-01

Full Text Available Fragile X syndrome (FXS, the most common form of inherited intellectual disability, is also highly associated with autism spectrum disorders (ASD. It is caused by expansion of a CGG repeat sequence on the X chromosome resulting in silencing of the FMR1 gene. This is modeled in the mouse by deletion of Fmr1 (Fmr1 KO. Fmr1 KO mice recapitulate many of the behavioral features of the disorder including seizure susceptibility, hyperactivity, impaired social behavior, sleep problems, and learning and memory deficits. The mammalian target of rapamycin pathway (mTORC1 is upregulated in Fmr1 KO mice and is thought to be important for the pathogenesis of this disorder. We treated Fmr1 KO mice chronically with an mTORC1 inhibitor, rapamycin, to determine if rapamycin treatment could reverse behavioral phenotypes. We performed open field, zero maze, social behavior, sleep, passive avoidance, and audiogenic seizure testing. We found that pS6 was upregulated in Fmr1 KO mice and normalized by rapamycin treatment, but, except for an anxiogenic effect, it did not reverse any of the behavioral phenotypes examined. In fact, rapamycin treatment had an adverse effect on sleep and social behavior in both control and Fmr1 KO mice. These results suggest that targeting the mTOR pathway in FXS is not a good treatment strategy and that other pathways should be considered.

Essential roles of GABA transporter-1 in controlling rapid eye movement sleep and in increased slow wave activity after sleep deprivation.

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Xin-Hong Xu

Full Text Available GABA is the major inhibitory neurotransmitter in the mammalian central nervous system that has been strongly implicated in the regulation of sleep. GABA transporter subtype 1 (GAT1 constructs high affinity reuptake sites for GABA and regulates GABAergic transmission in the brain. However, the role of GAT1 in sleep-wake regulation remains elusive. In the current study, we characterized the spontaneous sleep-wake cycle and responses to sleep deprivation in GAT1 knock-out (KO mice. GAT1 KO mice exhibited dominant theta-activity and a remarkable reduction of EEG power in low frequencies across all vigilance stages. Under baseline conditions, spontaneous rapid eye movement (REM sleep of KO mice was elevated both during the light and dark periods, and non-REM (NREM sleep was reduced during the light period only. KO mice also showed more state transitions from NREM to REM sleep and from REM sleep to wakefulness, as well as more number of REM and NREM sleep bouts than WT mice. During the dark period, KO mice exhibited more REM sleep bouts only. Six hours of sleep deprivation induced rebound increases in NREM and REM sleep in both genotypes. However, slow wave activity, the intensity component of NREM sleep was briefly elevated in WT mice but remained completely unchanged in KO mice, compared with their respective baselines. These results indicate that GAT1 plays a critical role in the regulation of REM sleep and homeostasis of NREM sleep.

Evidence for a role of srGAP3 in the positioning of commissural axons within the ventrolateral funiculus of the mouse spinal cord.

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Claire Bacon

Full Text Available Slit-Robo signaling guides commissural axons away from the floor-plate of the spinal cord and into the longitudinal axis after crossing the midline. In this study we have evaluated the role of the Slit-Robo GTPase activating protein 3 (srGAP3 in commissural axon guidance using a knockout (KO mouse model. Co-immunoprecipitation experiments confirmed that srGAP3 interacts with the Slit receptors Robo1 and Robo2 and immunohistochemistry studies showed that srGAP3 co-localises with Robo1 in the ventral and lateral funiculus and with Robo2 in the lateral funiculus. Stalling axons have been reported in the floor-plate of Slit and Robo mutant spinal cords but our axon tracing experiments revealed no dorsal commissural axon stalling in the floor plate of the srGAP3 KO mouse. Interestingly we observed a significant thickening of the ventral funiculus and a thinning of the lateral funiculus in the srGAP3 KO spinal cord, which has also recently been reported in the Robo2 KO. However, axons in the enlarged ventral funiculus of the srGAP3 KO are Robo1 positive but do not express Robo2, indicating that the thickening of the ventral funiculus in the srGAP3 KO is not a Robo2 mediated effect. We suggest a role for srGAP3 in the lateral positioning of post crossing axons within the ventrolateral funiculus.

Total hepatocellular disposition profiling of rosuvastatin and pitavastatin in sandwich-cultured human hepatocytes.

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Kanda, Katsuhiro; Takahashi, Ryosuke; Yoshikado, Takashi; Sugiyama, Yuichi

2018-04-09

This study describes the total disposition profiling of rosuvastatin (RSV) and pitavastatin (PTV) using a single systematic procedure called D-PREX (Disposition Profile Exploration) in sandwich-cultured human hepatocytes (SCHH). The biliary excretion fractions of both statins were clearly observed, which were significantly decreased dependent on the concentration of Ko143, an inhibitor for breast cancer resistance protein (BCRP). Ko143 also decreased the basolateral efflux fraction of RSV, whereas that of PTV was not significantly affected. To understand these phenomena, effects of Ko143 on biliary excretion (BCRP and multidrug resistance-associated protein (MRP) 2) and basolateral efflux (MRP3 and MRP4) transporters were examined using transporter-expressing membrane vesicles. BCRP, MRP3 and MRP4-mediated transport of RSV was observed, and Ko143 inhibited these transporters except MRP3. BCRP and MRP4 also mediated the transport of PTV, but the Ko143-mediated inhibition was only clear for BCRP. These results might explain the Ko143-mediated complete and partial inhibition of the biliary excretion and the basolateral efflux of RSV, respectively, in SCHH. In conclusion, D-PREX with sequential sampling of supernatants prior to cell lysis enables the evaluation of total drug disposition profiles resulting from complex interplays of intracellular pathways, which would provide high-throughput evaluation of drug disposition during drug discovery. Copyright © 2018 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

The therapeutic effect of memantine through the stimulation of synapse formation and dendritic spine maturation in autism and fragile X syndrome.

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Hongen Wei

Full Text Available Although the pathogenic mechanisms that underlie autism are not well understood, there is evidence showing that metabotropic and ionotropic glutamate receptors are hyper-stimulated and the GABAergic system is hypo-stimulated in autism. Memantine is an uncompetitive antagonist of NMDA receptors and is widely prescribed for treatment of Alzheimer's disease treatment. Recently, it has been shown to improve language function, social behavior, and self-stimulatory behaviors of some autistic subjects. However the mechanism by which memantine exerts its effect remains to be elucidated. In this study, we used cultured cerebellar granule cells (CGCs from Fmr1 knockout (KO mice, a mouse model for fragile X syndrome (FXS and syndromic autism, to examine the effects of memantine on dendritic spine development and synapse formation. Our results show that the maturation of dendritic spines is delayed in Fmr1-KO CGCs. We also detected reduced excitatory synapse formation in Fmr1-KO CGCs. Memantine treatment of Fmr1-KO CGCs promoted cell adhesion properties. Memantine also stimulated the development of mushroom-shaped mature dendritic spines and restored dendritic spine to normal levels in Fmr1-KO CGCs. Furthermore, we demonstrated that memantine treatment promoted synapse formation and restored the excitatory synapses to a normal range in Fmr1-KO CGCs. These findings suggest that memantine may exert its therapeutic capacity through a stimulatory effect on dendritic spine maturation and excitatory synapse formation, as well as promoting adhesion of CGCs.

GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

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Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Kurihara, Takashi; Hirasawa, Akira; Kasuya, Fumiyo; Miyata, Atsuro; Tokuyama, Shogo

2016-12-01

The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Divergent responses to thermogenic stimuli in BAT and subcutaneous adipose tissue from interleukin 18 and interleukin 18 receptor 1-deficient mice.

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Pazos, Patricia; Lima, Luis; Tovar, Sulay; González-Touceda, David; Diéguez, Carlos; García, María C

2015-12-10

Brown and beige adipocytes recruitment in brown (BAT) or white adipose tissue, mainly in the inguinal fat pad (iWAT), meet the need for temperature adaptation in cold-exposure conditions and protect against obesity in face of hypercaloric diets. Using interleukin18 (Il18) and Il18 receptor 1- knockout (Il18r1-KO) mice, this study aimed to investigate the role of IL18 signaling in BAT and iWAT activation and thermogenesis under both stimuli. Il18-KO, extremely dietary obesity-prone as previously described, failed to develop diet-induced thermogenesis as assessed by BAT and iWAT Ucp1 mRNA levels. Overweight when fed standard chow but not HFD, HFD-fed Il18r1-KO mice exhibited increased iWAT Ucp1 gene expression. Energy expenditure was reduced in pre-obese Il18r1-KO mice and restored upon HFD-challenge. Cold exposure lead to similar results; Il18r1-KO mice were protected against acute body temperature drop, displaying a more brown-like structure, alternative macrophage activation and thermogenic gene expression in iWAT than WT controls. Opposite effects were observed in Il18-KO mice. Thus, Il18 and Il18r1 genetic ablation disparate effects on energy homeostasis are likely mediated by divergent BAT responses to thermogenic stimuli as well as iWAT browning. These results suggest that a more complex receptor-signaling system mediates the IL18 adipose-tissue specific effects in energy expenditure.

Human stefin B role in cell's response to misfolded proteins and autophagy.

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Mira Polajnar

Full Text Available Alternative functions, apart from cathepsins inhibition, are being discovered for stefin B. Here, we investigate its role in vesicular trafficking and autophagy. Astrocytes isolated from stefin B knock-out (KO mice exhibited an increased level of protein aggregates scattered throughout the cytoplasm. Addition of stefin B monomers or small oligomers to the cell medium reverted this phenotype, as imaged by confocal microscopy. To monitor the identity of proteins embedded within aggregates in wild type (wt and KO cells, the insoluble cell lysate fractions were isolated and analyzed by mass spectrometry. Chaperones, tubulins, dyneins, and proteosomal components were detected in the insoluble fraction of wt cells but not in KO aggregates. In contrast, the insoluble fraction of KO cells exhibited increased levels of apolipoprotein E, fibronectin, clusterin, major prion protein, and serpins H1 and I2 and some proteins of lysosomal origin, such as cathepsin D and CD63, relative to wt astrocytes. Analysis of autophagy activity demonstrated that this pathway was less functional in KO astrocytes. In addition, synthetic dosage lethality (SDL gene interactions analysis in Saccharomyces cerevisiae expressing human stefin B suggests a role in transport of vesicles and vacuoles These activities would contribute, directly or indirectly to completion of autophagy in wt astrocytes and would account for the accumulation of protein aggregates in KO cells, since autophagy is a key pathway for the clearance of intracellular protein aggregates.

Reduced emotional and corticosterone responses to stress in μ-opioid receptor knockout mice

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Ide, Soichiro; Sora, Ichiro; Ikeda, Kazutaka; Minami, Masabumi; Uhl, George R.; Ishihara, Kumatoshi

2014-01-01

The detailed mechanisms of emotional modulation in the nervous system by opioids remain to be elucidated, although the opioid system is well known to play important roles in the mechanisms of analgesia and drug dependence. In the present study, we conducted behavioral tests of anxiety and depression and measured corticosterone concentrations in both male and female μ-opioid receptor knockout (MOP-KO) mice to reveal the involvement of μ-opioid receptors in stress-induced emotional responses. MOP-KO mice entered more and spent more time in the open arms of the elevated plus maze compared with wild-type mice. MOP-KO mice also displayed significantly decreased immobility in a 15 min tail-suspension test compared with wild-type mice. Similarly, MOP-KO mice exhibited significantly decreased immobility on days 2, 3, and 4 in a 6 min forced swim test conducted for 5 consecutive days. The increase in plasma corticosterone concentration induced by tail-suspension, repeated forced swim, or restraint stress was reduced in MOP-KO mice compared with wild-type mice. Corticosterone levels were not different between wild-type and MOP-KO mice before stress exposure. In contrast, although female mice tended to exhibit fewer anxiety-like responses in the tail-suspension test in both genotypes, no significant gender differences were observed in stress-induced emotional responses. These results suggest that MOPs play an important facilitatory role in emotional responses to stress, including anxiety- and depression-like behavior and corticosterone levels. PMID:19596019

Phosphodiesterase-1b (Pde1b) knockout mice are resistant to forced swim and tail suspension induced immobility and show upregulation of Pde10a.

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Hufgard, Jillian R; Williams, Michael T; Skelton, Matthew R; Grubisha, Olivera; Ferreira, Filipa M; Sanger, Helen; Wright, Mary E; Reed-Kessler, Tracy M; Rasmussen, Kurt; Duman, Ronald S; Vorhees, Charles V

2017-06-01

Major depressive disorder is a leading cause of suicide and disability. Despite this, current antidepressants provide insufficient efficacy in more than 60% of patients. Most current antidepressants are presynaptic reuptake inhibitors; postsynaptic signal regulation has not received as much attention as potential treatment targets. We examined the effects of disruption of the postsynaptic cyclic nucleotide hydrolyzing enzyme, phosphodiesterase (PDE) 1b, on depressive-like behavior and the effects on PDE1B protein in wild-type (WT) mice following stress. Littermate knockout (KO) and WT mice were tested in locomotor activity, tail suspension (TST), and forced swim tests (FST). FST was also used to compare the effects of two antidepressants, fluoxetine and bupropion, in KO versus WT mice. Messenger RNA (mRNA) expression changes were also determined. WT mice underwent acute or chronic stress and markers of stress and PDE1B expression were examined. Pde1b KO mice exhibited decreased TST and FST immobility. When treated with antidepressants, both WT and KO mice showed decreased FST immobility and the effect was additive in KO mice. Mice lacking Pde1b had increased striatal Pde10a mRNA expression. In WT mice, acute and chronic stress upregulated PDE1B expression while PDE10A expression was downregulated after chronic but not acute stress. PDE1B is a potential therapeutic target for depression treatment because of the antidepressant-like phenotype seen in Pde1b KO mice.

Impaired associative fear learning in mice with complete loss or haploinsufficiency of AMPA GluR1 receptors

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Michael Feyder

2007-12-01

Full Text Available There is compelling evidence that L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA glutamate receptors containing the GluR1 subunit contribute to the molecular mechanisms associated with learning. AMPA GluR1 glutamate receptor knockout mice (KO exhibit abnormal hippocampal and amygdala plasticity, and deficits on various assays for cognition including Pavlovian fear conditioning. Here we examined associative fear learning in mice with complete absence (KO or partial loss (heterozygous mutant, HET of GluR1 on multiple fear conditioning paradigms. After multi-trial delay or trace conditioning, KO displayed impaired tone and context fear recall relative to WT, whereas HET were normal. After one-trial delay conditioning, both KO and HET showed impaired tone and context recall. HET and KO showed normal nociceptive sensitivity in the hot plate and tail flick tests. These data demonstrate that the complete absence of GluR1 subunit-containing receptors prevents the formation of associative fear memories, while GluR1 haploinsufficiency is sufficient to impair one-trial fear learning. These findings support growing evidence of a major role for GluR1-containing AMPA receptors in amygdalamediated forms of learning and memory.

Elevated dopamine alters consummatory pattern generation and increases behavioral variability during learning

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Mark A. Rossi

2015-05-01

Full Text Available The role of dopamine in controlling behavior remains poorly understood. In this study we examined licking behavior in an established hyperdopaminergic mouse model—dopamine transporter knockout (DAT KO mice. DAT KO mice showed higher rates of licking, which is due to increased perseveration of licking in a bout. By contrast, they showed increased individual lick durations, and reduced inter-lick-intervals. During extinction, both KO and control mice transiently increased variability in lick pattern generation while reducing licking rate, yet they showed very different behavioral patterns. Control mice gradually increased lick duration as well as variability. By contrast, DAT KO mice exhibited more immediate (within 10 licks adjustments—an immediate increase in lick duration variability, as well as more rapid extinction. These results suggest that the level of dopamine can modulate the persistence and pattern generation of a highly stereotyped consummatory behavior like licking, as well as new learning in response to changes in environmental feedback. Increased dopamine in DAT KO mice not only increased perseveration of bouts and individual lick duration, but also increased the behavioral variability in response to the extinction contingency and the rate of extinction.

Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

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Xu, Minjun; Kitaura, Yasuyuki; Ishikawa, Takuya; Kadota, Yoshihiro; Terai, Chihaya; Shindo, Daichi; Morioka, Takashi; Ota, Miki; Morishita, Yukako; Ishihara, Kengo; Shimomura, Yoshiharu

2017-01-01

It is known that the catabolism of branched-chain amino acids (BCAAs) in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA) dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK). In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice) to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

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Minjun Xu

Full Text Available It is known that the catabolism of branched-chain amino acids (BCAAs in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK. In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

Deletion of the AcMNPV core gene ac109 results in budded virions that are non-infectious

International Nuclear Information System (INIS)

Fang Minggang; Nie, Yingchao; Theilmann, David A.

2009-01-01

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac109 is a core gene and its function in the virus life cycle is unknown. To determine its role in the baculovirus life cycle, we used the AcMNPV bacmid system to generate an ac109 deletion virus (vAc 109KO ). Fluorescence and light microscopy showed that transfection of vAc 109KO results in a single-cell infection phenotype. Viral DNA replication is unaffected and the development of occlusion bodies in vAc 109KO -transfected cells evidenced progression to the very late phases of viral infection. Western blot and confocal immunofluorescence analysis showed that AC109 is expressed in the cytoplasm and nucleus throughout infection. In addition, AC109 is a structural protein as it was detected in both budded virus (BV) and occlusion derived virus in both the envelope and nucleocapsid fractions. Titration assays by qPCR and TCID 50 showed that vAc 109KO produced BV but the virions are non-infectious. The vAc 109KO BV were indistinguishable from the BV of repaired and wild type control viruses as determined by negative staining and electron microscopy.

Male mice with deleted Wolframin (Wfs1 gene have reduced fertility

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Aunapuu Marina

2009-08-01

Full Text Available Abstract Background Wolfram Syndrome (WS is an autosomal recessive disorder characterised by non-autoimmune diabetes mellitus, optic atrophy, cranial diabetes insipidus and sensorineural deafness. Some reports have described hypogonadism in male WS patients. The aim of our study was to find out whether Wfs1 deficient (Wfs1KO male mice have reduced fertility and, if so, to examine possible causes. Methods Wfs1KO mice were generated by homologous recombination. Both Wfs1KO and wild type (wt male mice were mated with wt female mice. The number of litters and the number of pups were counted and pregnancy rates calculated. The motility and morphology of the sperm and the histology of testes were analysed. Serum testosterone and FSH concentrations were also measured. Results The pregnancy rate in wt females mated with Wfs1KO males was significantly lower than in the control group (15% vs. 32%; p Conclusion The impaired fertility of Wfs1KO male mice is most likely due to changes in sperm morphology and reduced number of spermatogenic cells. The exact mechanism through which the Wfs1 gene influences sperm morphology needs to be clarified in further studies.

Absence of Carbohydrate Response Element Binding Protein in Adipocytes Causes Systemic Insulin Resistance and Impairs Glucose Transport

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Archana Vijayakumar

2017-10-01

Full Text Available Lower adipose-ChREBP and de novo lipogenesis (DNL are associated with insulin resistance in humans. Here, we generated adipose-specific ChREBP knockout (AdChREBP KO mice with negligible sucrose-induced DNL in adipose tissue (AT. Chow-fed AdChREBP KO mice are insulin resistant with impaired insulin action in the liver, muscle, and AT and increased AT inflammation. HFD-fed AdChREBP KO mice are also more insulin resistant than controls. Surprisingly, adipocytes lacking ChREBP display a cell-autonomous reduction in insulin-stimulated glucose transport that is mediated by impaired Glut4 translocation and exocytosis, not lower Glut4 levels. AdChREBP KO mice have lower levels of palmitic acid esters of hydroxy stearic acids (PAHSAs in serum, and AT. 9-PAHSA supplementation completely rescues their insulin resistance and AT inflammation. 9-PAHSA also normalizes impaired glucose transport and Glut4 exocytosis in ChREBP KO adipocytes. Thus, loss of adipose-ChREBP is sufficient to cause insulin resistance, potentially by regulating AT glucose transport and flux through specific lipogenic pathways.

The Role of Fibroblast Growth Factor Binding Protein 1 in Skin Carcinogenesis and Inflammation

DEFF Research Database (Denmark)

Schmidt, Marcel Oliver; Garman, Khalid Ammar; Lee, Yong Gu

2018-01-01

, and is upregulated in various cancers. Here we evaluated the contribution of endogenous FGFBP1 to development and homeostasis as well as to skin pathologies utilizing Fgfbp1-knockout (KO) mice. Relative to wild-type (WT) littermates KO mice showed no gross pathologies. Still, in KO mice a significant thickening...... of the epidermis associated with a decreased transepidermal water loss and increased pro-inflammatory gene expression in the skin was detected. Also, skin carcinogen challenge by DMBA/TPA resulted in delayed and reduced papillomatosis in KO mice. This was paralleled by delayed healing of skin wounds and reduced...... angiogenic sprouting in subcutaneous matrigel plugs. Heterozygous GFP-knock-in mice revealed rapid induction of gene expression during papilloma induction and during wound healing. Examination of WT skin grafted onto Fgfbp1 GFP knockin reporter hosts and bone marrow transplants from the GFP reporter model...

Lack of caspase-3 attenuates immobilization-induced muscle atrophy and loss of tension generation along with mitigation of apoptosis and inflammation

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Zhu, Shimei; Nagashima, Michio; Khan, Mahammad A.S; Yasuhara, Shingo; Kaneki, Masao; Jeevendra Martyn, J. A.

2012-01-01

Introduction Immobilization by casting induces disuse muscle atrophy (DMA). Methods Using wild type (WT) and caspase-3 knockout (KO) mice, we evaluated the effect of caspase-3 on muscle mass, apoptosis and inflammation during DMA. Results Caspase-3 deficiency significantly attenuated muscle mass decrease [gastrocnemius: 28 ± 1% in KO vs. 41 ± 3% in WT; soleus: 47 ± 2% in KO vs. 56 ± 2% in WT; (P immobilized versus contralateral hindlimb. Lack of caspase-3 decreased immobilization-induced increased apoptotic myonuclei (3.2-fold) and macrophage infiltration (2.2-fold) in soleus muscle and attenuated increased monocyte chemoattractant protein-1 mRNA expression (2-fold in KO vs. 18-fold in WT) in gastrocnemius. Conclusion Caspase-3 plays a key role in DMA and associated decreased tension, presumably by acting on the apoptosis and inflammation pathways. PMID:23401051

Extension of car-to-X-communication by radiolocation techniques; Erweiterung der Fahrzeug-zu-Fahrzeug-Kommunikation mit Funkortungstechniken

Energy Technology Data Exchange (ETDEWEB)

Schwarz, Daniel [BMW Group, Muenchen (Germany). Bereich Konzepte ' ' Aktive und Integrale Sicherheit' '

2012-10-15

A transponder, carried by vulnerable road users, e.g. pedestrians or bicyclists, and integrated in a smartphone, enables localisation from the vehicle side. A connected driver assistant system can detect movements, predict a possible collision and take preventive actions like informing the driver, braking or steering. In the research project Ko-TAG (Cooperative Transponder) within the research initiative Ko-FAS (Cooperative Vehicle Safety) new sensor technologies are developed. BMW, as Ko-TAG project manager, explains the cooperative sensor technology and the automatic control technique of the preventive safety system. (orig.)

Karakteristik Kimiawi dan Mikrobiologi Kefir Susu Sapi dengan Penambahan Susu Kedelai

OpenAIRE

Julianto, Budi; Rossi, Evy; ', Yusmarini

2016-01-01

The purpose of this research was to observe chemical and microbiology characteristic of three kind of kefir, made from cow milk with addition of soymilk. Observed kefirs were kefir whey (KW), kefir optima (KO), and kefir prima (KP). A Completely Randomized Design (CRD) was used in this research with six treatments and three replications treatment consists of KW1 (100% cow milk), KW2 (50% cow milk: soymilk 50%), KO1 (100% cow milk), KO2 (50% cow milk: 50% soymilk), KP1 (100% cow milk), and KP2...

One-step triplex PCR/RT-PCR to detect canine distemper virus, canine parvovirus, and canine kobuvirus.

Science.gov (United States)

Liu, Dafei; Liu, Fei; Guo, Dongchun; Hu, Xiaoliang; Li, Zhijie; Li, Zhigang; Ma, Jianzhang; Liu, Chunguo

2018-01-23

To rapidly distinguish Canine distemper virus (CDV), canine parvovirus (CPV), and canine kobuvirus (CaKoV) in practice, a one-step multiplex PCR/RT-PCR assay was developed, with detection limits of 10 2.1 TCID 50 for CDV, 10 1.9 TCID 50 for CPV and 10 3 copies for CaKoV. This method did not amplify nonspecific DNA or RNA from other canine viruses. Therefore, the assay provides a sensitive tool for the rapid clinical detection and epidemiological surveillance of CDV, CPV and CaKoV in dogs.

Contributions of the Na⁺/K⁺-ATPase, NKCC1, and Kir4.1 to hippocampal K⁺ clearance and volume responses

DEFF Research Database (Denmark)

Larsen, Brian Roland; Assentoft, Mette; Cotrina, Maria L

2014-01-01

(+)/K(+)-ATPase activity. Their individual contribution to [K(+)]o management has been of extended controversy. This study aimed, by several complementary approaches, to delineate the transport characteristics of Kir4.1, NKCC1, and Na(+)/K(+)-ATPase and to resolve their involvement in clearance of extracellular K......(+) transients. Primary cultures of rat astrocytes displayed robust NKCC1 activity with [K(+)]o increases above basal levels. Increased [K(+)]o produced NKCC1-mediated swelling of cultured astrocytes and NKCC1 could thereby potentially act as a mechanism of K(+) clearance while concomitantly mediate...

Packaging material and aluminum. Hoso zairyo to aluminum

Energy Technology Data Exchange (ETDEWEB)

Itaya, T [Mitsubishi Aluminum Co. Ltd., Tokyo (Japan)

1992-02-01

The present paper introduces aluminum foil packaging materials among the relation between packing materials and aluminum. The characteristics of aluminum foil in the packaging area are in its barrier performance, non-toxicity, tastelessness and odorlessness. Its excellent functions and processibility suit best as functional materials for food, medicine and industrial material packaging. While an aluminum foil may be used as a single packing material as in foils used in homes, many of it as a packaging material are used in combination with adhesives, papers or plastic films, or coated or printed. It is used as composite materials laminated or coated with other materials according to their use for the purpose of complementing the aluminum foil as the base material. Representative method to laminate aluminum foils include the wet lamination, dry lamination, thermally dissolved lamination and extruded lamination. The most important quality requirement in lamination is the adhesion strength, which requires a close attention in selecting the kinds of adhesive, laminating conditions, and aging conditions. 8 figs., 6 tabs.

Drug: D08903 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available azole derivative See [DR:D00355] Non-erosive GERD, healing of erosive esophagitis, and maintenance of heal...ing of erosive esophagitis ATP4A [HSA:495] [KO:K01542]; ATP4B [HSA:496] [KO:K01543

Dgroup: DG00984 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available linesterase inhibitor ... DG01594 ... Butyrylcholinesterase inhibitor ... DG01968 ... Agents for Alzheimer-type dementi...a ATC code: N06DA03 Anti-Alzheimer's agent, Anticholinesterase agent ACHE [HSA:43] [KO:K01049] BCHE [HSA:590] [KO:K01050] ...

Sarcocystis jamaicensis n. sp., from Red-Tailed Hawks (Buteo jamaicensis) Definitive Host and IFN-γ Gene Knockout Mice as Experimental Intermediate Host.

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