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Sample records for active type ii

  1. Increased endocytotic and lysosomal activities in denervated type I and type II muscle fibres.

    PubMed

    Lawoko, G; Tågerud, S; Libelius, R

    1992-01-01

    Previous work has shown that increased endocytotic and lysosomal activities occur in the endplate region of denervated skeletal muscle fibres. This, however, does not engage all fibres of a muscle at a given time after denervation. The present study was carried out in order to determine if both type I (slow) and type II (fast) muscle fibres can react to denervation by increased endocytotic and lysosomal activities. Uptake of horseradish peroxidase as a marker for endocytosis was studied in conjunction with acid phosphatase staining for lysosomal activity in type I and type II fibres of the denervated mouse hemidiaphragm. Fibre typing was performed using a monoclonal antibody against fast skeletal myosin and by adenosine triphosphatase staining. The results show that increased endocytosis and lysosomal activation occur in both type I and type II fibres after denervation.

  2. 77 FR 60124 - Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-02

    ... Assessments for Type II Active Pharmaceutical Ingredient Drug Master Files Under the Generic Drug User Fee... Amendments of 2012 (GDUFA), holders of certain drug master files, namely, Type II active...

  3. Type I and type II fatty acid biosynthesis in Eimeria tenella: enoyl reductase activity and structure.

    PubMed

    Lu, J Z; Muench, S P; Allary, M; Campbell, S; Roberts, C W; Mui, E; McLeod, R L; Rice, D W; Prigge, S T

    2007-12-01

    Apicomplexan parasites of the genus Eimeria are the major causative agent of avian coccidiosis, leading to high economic losses in the poultry industry. Recent results show that Eimeria tenella harbours an apicoplast organelle, and that a key biosynthetic enzyme, enoyl reductase, is located in this organelle. In related parasites, enoyl reductase is one component of a type II fatty acid synthase (FAS) and has proven to be an attractive target for antimicrobial compounds. We cloned and expressed the mature form of E. tenella enoyl reductase (EtENR) for biochemical and structural studies. Recombinant EtENR exhibits NADH-dependent enoyl reductase activity and is inhibited by triclosan with an IC50 value of 60 nm. The crystal structure of EtENR reveals overall similarity with other ENR enzymes; however, the active site of EtENR is unoccupied, a state rarely observed in other ENR structures. Furthermore, the position of the central beta-sheet appears to block NADH binding and would require significant movement to allow NADH binding, a feature not previously seen in the ENR family. We analysed the E. tenella genomic database for orthologues of well-characterized bacterial and apicomplexan FAS enzymes and identified 6 additional genes, suggesting that E. tenella contains a type II FAS capable of synthesizing saturated, but not unsaturated, fatty acids. Interestingly, we also identified sequences that appear to encode multifunctional type I FAS enzymes, a feature also observed in Toxoplasma gondii, highlighting the similarity between these apicomplexan parasites.

  4. Phospholipid-transfer activities in cytosols from lung, isolated alveolar type II cells and alveolar type II cell-derived adenomas.

    PubMed Central

    Pool, G L; Bubacz, D G; Lumb, R H; Mason, R J

    1983-01-01

    We have examined phospholipid-transfer activities in cytosols from rat and mouse whole lung, isolated rat alveolar type II cells and alveolar type II cell-derived mouse pulmonary adenomas. We report an enrichment in phosphatidylcholine and phosphatidylglycerol (but not phosphatidylinositol) protein-catalysed transfer in the type II cell and adenoma cytosols compared with the whole-lung cytosols. The activities from these cytosols were resolved using column chromatofocusing, which clearly demonstrated the presence of a phosphatidylcholine-specific transfer protein in each of the four tissues. In addition, two proteins (rat) or three proteins (mouse) catalysing both phosphatidylcholine and phosphatidylglycerol transfer were resolved from whole lung, whereas in both the rat isolated alveolar type II cells and the mouse type II cell-derived adenomas one of these less specific proteins is not present. PMID:6661189

  5. Oligomeric State Regulated Trafficking of Human Platelet-Activating Factor Acetylhydrolase Type-II

    PubMed Central

    Monillas, Elizabeth S.; Caplan, Jeffrey L.; Thévenin, Anastasia F.; Bahnson, Brian J.

    2015-01-01

    The intracellular enzyme platelet-activating factor acetylhydrolase type-II (PAFAH-II) hydrolyzes platelet-activating factor and oxidatively fragmented phospholipids. PAFAH-II in its resting state is mainly cytoplasmic, and it responds to oxidative stress by becoming increasingly bound to endoplasmic reticulum and Golgi membranes. Numerous studies have indicated that this enzyme is essential for protecting cells from oxidative stress induced apoptosis. However, the regulatory mechanism of the oxidative stress response by PAFAH-II has not been fully resolved. Here, changes to the oligomeric state of human PAFAH-II were investigated as a potential regulatory mechanism toward enzyme trafficking. Native PAGE analysis in vitro and photon counting histogram within live cells showed that PAFAH-II is both monomeric and dimeric. A Gly-2-Ala site-directed mutation of PAFAH-II demonstrated that the N-terminal myristoyl group is required for homodimerization. Additionally, the distribution of oligomeric PAFAH-II is distinct within the cell; homodimers of PAFAH-II were localized to the cytoplasm while monomers were associated to the membranes of the endoplasmic reticulum and Golgi. We propose that the oligomeric state of PAFAH-II drives functional protein trafficking. PAFAH-II localization to the membrane is critical for substrate acquisition and effective oxidative stress protection. It is hypothesized that the balance between monomer and dimer serves as a regulatory mechanism of a PAFAH-II oxidative stress response. PMID:25707358

  6. Oligomeric state regulated trafficking of human platelet-activating factor acetylhydrolase type-II.

    PubMed

    Monillas, Elizabeth S; Caplan, Jeffrey L; Thévenin, Anastasia F; Bahnson, Brian J

    2015-05-01

    The intracellular enzyme platelet-activating factor acetylhydrolase type-II (PAFAH-II) hydrolyzes platelet-activating factor and oxidatively fragmented phospholipids. PAFAH-II in its resting state is mainly cytoplasmic, and it responds to oxidative stress by becoming increasingly bound to endoplasmic reticulum and Golgi membranes. Numerous studies have indicated that this enzyme is essential for protecting cells from oxidative stress induced apoptosis. However, the regulatory mechanism of the oxidative stress response by PAFAH-II has not been fully resolved. Here, changes to the oligomeric state of human PAFAH-II were investigated as a potential regulatory mechanism toward enzyme trafficking. Native PAGE analysis in vitro and photon counting histogram within live cells showed that PAFAH-II is both monomeric and dimeric. A Gly-2-Ala site-directed mutation of PAFAH-II demonstrated that the N-terminal myristoyl group is required for homodimerization. Additionally, the distribution of oligomeric PAFAH-II is distinct within the cell; homodimers of PAFAH-II were localized to the cytoplasm while monomers were associated to the membranes of the endoplasmic reticulum and Golgi. We propose that the oligomeric state of PAFAH-II drives functional protein trafficking. PAFAH-II localization to the membrane is critical for substrate acquisition and effective oxidative stress protection. It is hypothesized that the balance between monomer and dimer serves as a regulatory mechanism of a PAFAH-II oxidative stress response.

  7. Shaping of action potentials by type I and type II large-conductance Ca²+-activated K+ channels.

    PubMed

    Jaffe, D B; Wang, B; Brenner, R

    2011-09-29

    The BK channel is a Ca(2+) and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca(2+) was high (>20 μM) and the other where BK-activating Ca(2+) was low (∼0.4-1.2 μM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca(2+) channels due to electrogenic effects on spike duration. We also found that depending on Ca(2+) dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron.

  8. Biologic Activity of Type I and Type II Fusobacterium nucleatum Isolates from Clinically Characterized Sites,

    DTIC Science & Technology

    1984-07-26

    journal of choice is the Journal of Periodontology . 1 ncl JACK W. VINCENT as COL, DC Microbiology Branch SGRD-UDZ (19 Jul 84) TO COL Jack W. Vincent...Activitity of Type I and Type II Manuscript for Publication Fusobacterium nucleatum Isolates From Clinically Chatacterized Sites. 6. PERFORMING ONG...120) were obtained from subgingival plaque samples taken from 27 clinically characterized sites utilizing a selec- tive culture medium. All isolates

  9. Iron Kα emission in type-I and type-II active galactic nuclei

    NASA Astrophysics Data System (ADS)

    Ricci, C.; Ueda, Y.; Paltani, S.; Ichikawa, K.; Gandhi, P.; Awaki, H.

    2014-07-01

    The narrow Fe Kα line is one of the main signatures of the reprocessing of X-ray radiation from the material surrounding supermassive black holes, and it has been found to be omnipresent in the X-ray spectra of active galactic nuclei (AGN). In this work, we study the characteristics of the narrow Fe Kα line in different types of AGN. Using the results of a large Suzaku study, we find that Seyfert 2s have on average lower Fe Kα luminosities than Seyfert 1s for the same 10-50 keV continuum luminosity. Simulating dummy Seyfert 1s and Seyfert 2s populations using physical torus models of X-ray reflected emission, we find that this difference can be explained by means of different average inclination angles with respect to the torus, as predicted by the unified model. Alternative explanations include differences in the intensities of Compton humps, in the photon index distributions or in the average iron abundances. We show that the ratio between the flux of the broad and narrow Fe Kα line in the 6.35-6.45 keV range depends on the torus geometry considered, and is on average <25 per cent and <15 per cent for type-I and type-II AGN, respectively. We find evidence of absorption of the narrow Fe Kα line flux in Compton-thick AGN, which suggests that part of the reflecting material is obscured. We estimate that on average in obscured AGN the reflected radiation from neutral material is seen through a column density which is 1/4 of that absorbing the primary X-ray emission. This should be taken into account in synthesis models of the CXB and when studying the luminosity function of heavily obscured AGN. We detect the first evidence of the X-ray Baldwin effect in Seyfert 2s, with the same slope as that found for Seyfert 1s, which suggests that the mechanism responsible for the decrease of the equivalent width with the continuum luminosity is the same in the two classes of objects.

  10. Antimicrobial Activity of Pantothenol against Staphylococci Possessing a Prokaryotic Type II Pantothenate Kinase

    PubMed Central

    Chohnan, Shigeru; Murase, Misa; Kurikawa, Kota; Higashi, Kodai; Ogata, Yuta

    2014-01-01

    Pantothenol is a provitamin of pantothenic acid (vitamin B5) that is widely used in healthcare and cosmetic products. This analog of pantothenate has been shown to markedly inhibit the phosphorylation activity of the prokaryotic type II pantothenate kinase of Staphylococcus aureus, which catalyzes the first step of the coenzyme A biosynthetic pathway. Since type II enzymes are found exclusively in staphylococci, pantothenol suppresses the growth of S. aureus, S. epidermidis, and S. saprophyticus, which inhabit the skin of humans. Therefore, the addition of this provitamin to ointment and skincare products may be highly effective in preventing infections by opportunistic pathogens. PMID:24759689

  11. Activating types 1 and 2 angiotensin II receptors modulate the hypertrophic differentiation of chondrocytes☆

    PubMed Central

    Tsukamoto, Ichiro; Inoue, Shinji; Teramura, Takeshi; Takehara, Toshiyuki; Ohtani, Kazuhiro; Akagi, Masao

    2013-01-01

    A local tissue-specific renin–angiotensin system (local RAS) has been identified in many organs. However, no report has described the role of a local RAS in the hypertrophic differentiation of chondrocytes. To examine the role of a local RAS in the hypertrophic differentiation, we activated angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) separately in the cell line ATDC5, which involves differentiation from mesenchymal stem cells to hypertrophic chondrocytes. Activation of AT1R suppressed and activation of AT2R enhanced the expression of markers of hypertrophic differentiation, including type X collagen, matrix metalloproteinase 13 and runt-related transcription factor 2. PMID:23905010

  12. Substrate and Inhibitor Specificity of the Type II p21-Activated Kinase, PAK6

    PubMed Central

    Gao, Jia; Ha, Byung Hak; Lou, Hua Jane; Morse, Elizabeth M.; Zhang, Rong; Calderwood, David A.; Turk, Benjamin E.; Boggon, Titus J.

    2013-01-01

    The p21-activated kinases (PAKs) are important effectors of Rho-family small GTPases. The PAK family consists of two groups, type I and type II, which have different modes of regulation and signaling. PAK6, a type II PAK, influences behavior and locomotor function in mice and has an ascribed role in androgen receptor signaling. Here we show that PAK6 has a peptide substrate specificity very similar to the other type II PAKs, PAK4 and PAK5 (PAK7). We find that PAK6 catalytic activity is inhibited by a peptide corresponding to its N-terminal pseudosubstrate. Introduction of a melanoma-associated mutation, P52L, into this peptide reduces pseudosubstrate autoinhibition of PAK6, and increases phosphorylation of its substrate PACSIN1 (Syndapin I) in cells. Finally we determine two co-crystal structures of PAK6 catalytic domain in complex with ATP-competitive inhibitors. We determined the 1.4 Å co-crystal structure of PAK6 with the type II PAK inhibitor PF-3758309, and the 1.95 Å co-crystal structure of PAK6 with sunitinib. These findings provide new insights into the structure-function relationships of PAK6 and may facilitate development of PAK6 targeted therapies. PMID:24204982

  13. Signaling, Regulation, and Specificity of the Type II p21-activated Kinases*

    PubMed Central

    Ha, Byung Hak; Morse, Elizabeth M.; Turk, Benjamin E.; Boggon, Titus J.

    2015-01-01

    The p21-activated kinases (PAKs) are a family of six serine/threonine kinases that act as key effectors of RHO family GTPases in mammalian cells. PAKs are subdivided into two groups: type I PAKs (PAK1, PAK2, and PAK3) and type II PAKs (PAK4, PAK5, and PAK6). Although these groups are involved in common signaling pathways, recent work indicates that the two groups have distinct modes of regulation and have both unique and common substrates. Here, we review recent insights into the molecular level details that govern regulation of type II PAK signaling. We also consider mechanisms by which signal transduction is regulated at the level of substrate specificity. Finally, we discuss the implications of these studies for clinical targeting of these kinases. PMID:25855792

  14. [Impact of the activation of intention to perform physical activity in type II diabetics: a randomized clinical trial].

    PubMed

    da Silva, Marco Antonio Vieira; Gouvêa, Giovana Renata; Claro, Anielle Fabiane Buoso; Agondi, Rúbia de Freitas; Cortellazzi, Karine Laura; Pereira, Antonio Carlos; Meneghim, Marcelo de Castro; Mialhe, Fábio Luiz

    2015-03-01

    Type II diabetes mellitus is a highly prevalent disease among the adult Brazilian population, and one that can be controlled by interventions such as physical activity, among others. The aim of this randomized controlled study was to evaluate the impact of a traditional motivational strategy, associated with the activation of intention theory, on adherence to physical activity in patients with type II, diabetes mellitus who are part of the Unified Health System (SUS). Participants were divided into a control group (CG) and an intervention group (IG). In both groups, the traditional motivational strategy was applied, but the activation of intention strategy was only applied to the IG Group. After a two-month follow-up, statistically significant differences were verified between the groups, related to the practice of walking (p = 0.0050), number of days per week (p = 0.0076), minutes per day (p = 0.0050) and minutes walking per week (p = 0.0015). At the end of the intervention, statistically significant differences in abdominal circumference (p = 0.0048) between the groups were observed. The conclusion drawn is that the activation of intention strategy had greater impact on adherence to physical activity and reduction in abdominal circumference in type II diabetics, than traditional motivational strategy.

  15. ACTIVE IMMUNIZATION OF MICE WITH THE POLYSACCHARIDES OF PNEUMOCOCCI TYPES I, II AND III

    PubMed Central

    Zozaya, José; Clark, Janet

    1933-01-01

    1. Pneumococcus polysaccharides Types I, II and III adsorbed on collodion particles, and Types I and III adsorbed on carbon (norit) are antigenic in mice. 2. Unadsorbed pneumococcus polysaccharide of Type I is antigenic in mice in proper dilution. One preparation of Type II polysaccharide was not antigenic, while another one immunized against Types I and II. Type III polysaccharide was only slightly antigenic against Type III but immunized against Type I. 3. The antigenicity of pneumococcus polysaccharide in optimal dosage is tentatively explained by an adsorption phenomenon taking place in the body in instances in which the polysaccharides had not been adsorbed before injection. 4. The aggressin-like action of large doses of pneumococcus polysaccharides Types I, II and III is further established. PMID:19870119

  16. Exercise increases hexokinase II mRNA, but not activity in obesity and type 2 diabetes.

    PubMed

    Cusi, K J; Pratipanawatr, T; Koval, J; Printz, R; Ardehali, H; Granner, D K; Defronzo, R A; Mandarino, L J

    2001-05-01

    Glucose phosphorylation, catalyzed by hexokinase, is the first committed step in glucose uptake in skeletal muscle. Hexokinase II (HKII) is the isoform that is present in muscle and is regulated by insulin and muscle contraction. Glucose phosphorylation and HKII expression are both reduced in obese and type 2 diabetic subjects. A single bout of exercise increases HKII mRNA and activity in muscle from healthy subjects. The present study was performed to determine if a moderate exercise increases HKII mRNA expression and activity in patients with type 2 diabetes. Muscle biopsies were performed before and 3 hours after a single bout of cycle ergometer exercise in obese and type 2 diabetic patients. HKII mRNA and activity and glycogen synthase activity were determined in the muscle biopsies. Exercise increased HKII mRNA in obese and diabetic subjects by 1.67 +/- 0.34 and 1.87 +/- 0.26-fold, respectively (P <.05 for both). Exercise did not significantly increase HKI mRNA. When HKII mRNA increases were compared with the 2.26 +/- 0.36-fold increase in HKII mRNA previously reported for healthy lean subjects, no statistically significant differences were found. In contrast to the increase in HKII activity observed after exercise by lean healthy controls, exercise did not increase HKII activity in obese nondiabetic or diabetic subjects. Exercise increased glycogen synthase activity (GS(0.1) and GS(FV)) significantly in both obese nondiabetic and type 2 diabetic patients. The present results indicate that there is a posttranscriptional defect in the response of HKII expression to exercise in obese and type 2 diabetic subjects. This defect may contribute to reduced HKII activity and glucose uptake in these patients.

  17. [SERUM LEVEL OF ENDOTHELIAL MONOCYTE ACTIVATING POLYPEPTIDE-II IN CHILDHOOD-ONSET TYPE 1 DIABETIC PATIENTS AND OBESE ADOLESCENTS].

    PubMed

    Mogylnytska, L A

    2015-01-01

    The atherosclerotic process begins in adolescence, and its progression is determined by the same risk factors as in adults. Endothelial monocyte activating polypeptide-II (EMAP-II) is a multifunctional cytokine with proinflammatory and antiangiogenetic activity that may play a pathogenic role in the development of endothelial dysfunction and atherosclerosis. The aim of our study was to determine the serum level of EMAP-II in childhood-onset type 1 diabetic patients and obese adolescents. We found increased of serum level of EMAP-II in childhood-onset type 1 diabetic patients and in patients with obesity that do not suffer from diabetes. Also, the level of EMAP-II correlated with the serum level of glycosylated hemoglobin and blood glucose, and key markers of lipid metabolism, body mass index. Increased serum level of EMAP-II may be one of the pathway of endothelial dysfunction in type 1 diabetes.

  18. Biochemical evidence of key residues for the activation and autoprocessing of tomato type II metacaspase.

    PubMed

    Wen, Shuai; Ma, Qiu-Min; Zhang, Ya-Li; Yang, Ji-Ping; Zhao, Guang-Hua; Fu, Da-Qi; Luo, Yun-Bo; Qu, Gui-Qin

    2013-08-19

    To investigate the autolysis pattern and activation of metacaspase in higher plants, the biochemical characteristics of purified recombinant type II metacaspase (LeMCA1) from tomato were explored. Western blotting analysis indicated that four cleaved bands were formed; two N-terminal fragments and two C-terminal fragments. N-terminal sequencing confirmed that LeMCA1 cleaves at Lys223 and Arg332. Site mutants indicated that catalytic Cys139, cleaved Lys223, Arg332 and predicted calcium binding Asp116/Asp117 are the key residues that are responsible for its Ca²⁺ and pH dependent activation. The cleavage of the full-size fragment seemed crucial for the activation of LeMCA1 in vitro.

  19. A mutational analysis of the active site of human type II inosine 5'-monophosphate dehydrogenase.

    PubMed

    Futer, Olga; Sintchak, Michael D; Caron, Paul R; Nimmesgern, Elmar; DeCenzo, Maureen T; Livingston, David J; Raybuck, Scott A

    2002-01-31

    The oxidation of IMP to XMP is the rate-limiting step in the de novo synthesis of guanine ribonucleotides. This NAD-dependent reaction is catalyzed by the enzyme inosine monophosphate dehydrogenase (IMPDH). Based upon the recent structural determination of IMPDH complexed to oxidized IMP (XMP*) and the potent uncompetitive inhibitor mycophenolic acid (MPA), we have selected active site residues and prepared mutants of human type II IMPDH. The catalytic parameters of these mutants were determined. Mutations G326A, D364A, and the active site nucleophile C331A all abolish enzyme activity to less than 0.1% of wild type. These residues line the IMP binding pocket and are necessary for correct positioning of the substrate, Asp364 serving to anchor the ribose ring of the nucleotide. In the MPA/NAD binding site, significant loss of activity was seen by mutation of any residue of the triad Arg322, Asn303, Asp274 which form a hydrogen bonding network lining one side of this pocket. From a model of NAD bound to the active site consistent with the mutational data, we propose that these resides are important in binding the ribose ring of the nicotinamide substrate. Additionally, mutations in the pair Thr333, Gln441, which lies close to the xanthine ring, cause a significant drop in the catalytic activity of IMPDH. It is proposed that these residues serve to deliver the catalytic water molecule required for hydrolysis of the cysteine-bound XMP* intermediate formed after oxidation by NAD.

  20. Solar Type II Radio Bursts and IP Type II Events

    NASA Technical Reports Server (NTRS)

    Cane, H. V.; Erickson, W. C.

    2005-01-01

    We have examined radio data from the WAVES experiment on the Wind spacecraft in conjunction with ground-based data in order to investigate the relationship between the shocks responsible for metric type II radio bursts and the shocks in front of coronal mass ejections (CMEs). The bow shocks of fast, large CMEs are strong interplanetary (IP) shocks, and the associated radio emissions often consist of single broad bands starting below approx. 4 MHz; such emissions were previously called IP type II events. In contrast, metric type II bursts are usually narrowbanded and display two harmonically related bands. In addition to displaying complete dynamic spectra for a number of events, we also analyze the 135 WAVES 1 - 14 MHz slow-drift time periods in 2001-2003. We find that most of the periods contain multiple phenomena, which we divide into three groups: metric type II extensions, IP type II events, and blobs and bands. About half of the WAVES listings include probable extensions of metric type II radio bursts, but in more than half of these events, there were also other slow-drift features. In the 3 yr study period, there were 31 IP type II events; these were associated with the very fastest CMEs. The most common form of activity in the WAVES events, blobs and bands in the frequency range between 1 and 8 MHz, fall below an envelope consistent with the early signatures of an IP type II event. However, most of this activity lasts only a few tens of minutes, whereas IP type II events last for many hours. In this study we find many examples in the radio data of two shock-like phenomena with different characteristics that occur simultaneously in the metric and decametric/hectometric bands, and no clear example of a metric type II burst that extends continuously down in frequency to become an IP type II event. The simplest interpretation is that metric type II bursts, unlike IP type II events, are not caused by shocks driven in front of CMEs.

  1. Screening for catalytically active Type II restriction endonucleases using segregation-induced methylation deficiency

    PubMed Central

    Ukanis, Mindaugas; Sapranauskas, Rimantas; Lubys, Arvydas

    2012-01-01

    Type II restriction endonucleases (REases) are one of the basic tools of recombinant DNA technology. They also serve as models for elucidation of mechanisms for both site-specific DNA recognition and cleavage by proteins. However, isolation of catalytically active mutants from their libraries is challenging due to the toxicity of REases in the absence of protecting methylation, and techniques explored so far had limited success. Here, we present an improved SOS induction-based approach for in vivo screening of active REases, which we used to isolate a set of active variants of the catalytic mutant, Cfr10IE204Q. Detailed characterization of plasmids from 64 colonies screened from the library of ∼200 000 transformants revealed 29 variants of cfr10IR gene at the level of nucleotide sequence and 15 variants at the level of amino acid sequence, all of which were able to induce SOS response. Specific activity measurements of affinity-purified mutants revealed >200-fold variance among them, ranging from 100% (wild-type isolates) to 0.5% (S188C mutant), suggesting that the technique is equally suited for screening of mutants possessing high or low activity and confirming that it may be applied for identification of residues playing a role in catalysis. PMID:22753027

  2. High dispersion spectroscopy of solar-type superflare stars. II. Stellar rotation, starspots, and chromospheric activities

    NASA Astrophysics Data System (ADS)

    Notsu, Yuta; Honda, Satoshi; Maehara, Hiroyuki; Notsu, Shota; Shibayama, Takuya; Nogami, Daisaku; Shibata, Kazunari

    2015-06-01

    We conducted high dispersion spectroscopic observations of 50 superflare stars with Subaru/HDS. These 50 stars were selected from the solar-type superflare stars that we had discovered from the Kepler data. More than half (34 stars) of these 50 target superflare stars show no evidence of binarity, and we estimated stellar parameters of these 34 stars in our previous study (Notsu et al. 2015, PASJ, 67, 32). According to our previous studies using Kepler data, superflare stars show quasi-periodic brightness variations whose amplitude (0.1%-10%) is much larger than that of the solar brightness variations (0.01%-0.1%) caused by the existence of sunspots on the rotating solar surface. In this study, we investigated whether these quasi-periodic brightness variations of superflare stars are explained by the rotation of a star with fairly large starspots, by using stellar parameters derived in Paper I. First, we confirmed that the value of the projected rotational velocity, v sin i, is consistent with the rotational velocity estimated from the period of the brightness variation. Next, we measured the intensity of Ca II infrared triplet lines and Hα line, good indicators of the stellar chromospheric activity, and compared them with other stellar properties. The intensity of Ca II infrared triplet lines indicates that the mean magnetic field strength () of the target superflare stars can be higher than that of the Sun. A correlation between the amplitude of the brightness variation and the intensity of Ca II triplet line was found. All the targets expected to have large starspots because of their large amplitude of the brightness variation show high chromospheric activities compared to the Sun. These results support the idea that the brightness variation of superflare stars is due to the rotation with large starspots.

  3. [The effect of vitamin C on the lipolytic activity in type-II diabetics with angiopathy].

    PubMed

    Triana Mantilla, M E; Simón Carballo, R; Fernández Montequín, J I; Lima Santana, B; Cardona Alvarez, M E; Morejón Reinoso, O

    1991-01-01

    Effects produced by different doses of Vit C (2, 3 and 4 gr/day) on lipoprotein and hepatic lipase activities were studied between a group of 35 ambulatory patients, men and women, affected by diabetes mellitus type II with macroangiopathy at lower limbs and/or food. The medium age of patients was 62 years, ranging from 44 to 82 years. Patients were aleatory divided into four groups. One from those four groups was treated with placebo, the other three received Vit C. In the group treated with 3 gr./day of Vit C we found a significant reduction and increase (p less than 0.05) of lipoprotein and hepatic lipase activities, respectively, when we compared outcomes before and after eight weeks of treatment with Vit C. By other hand, when we compared the different groups, we found a significant increase in the hepatic lipase activity in the same group, particularly between the patients whose plasmatic Vit C levels before treatment were reduced. We didn't found any significant change in the rest of parameters.

  4. Cooperative activation of the T-type CaV3.2 channel: interaction between Domains II and III.

    PubMed

    Demers-Giroux, Pierre-Olivier; Bourdin, Benoîte; Sauvé, Rémy; Parent, Lucie

    2013-10-11

    T-type CaV3 channels are important mediators of Ca(2+) entry near the resting membrane potential. Little is known about the molecular mechanisms responsible for channel activation. Homology models based upon the high-resolution structure of bacterial NaV channels predict interaction between the S4-S5 helix of Domain II (IIS4-S5) and the distal S6 pore region of Domain II (IIS6) and Domain III (IIIS6). Functional intra- and inter-domain interactions were investigated with a double mutant cycle analysis. Activation gating and channel kinetics were measured for 47 single mutants and 20 pairs of mutants. Significant coupling energies (ΔΔG(interact) ≥ 1.5 kcal mol(-1)) were measured for 4 specific pairs of mutants introduced between IIS4-S5 and IIS6 and between IIS4-S5 and IIIS6. In agreement with the computer based models, Thr-911 in IIS4-S5 was functionally coupled with Ile-1013 in IIS6 during channel activation. The interaction energy was, however, found to be stronger between Val-907 in IIS4-S5 and Ile-1013 in IIS6. In addition Val-907 was significantly coupled with Asn-1548 in IIIS6 but not with Asn-1853 in IVS6. Altogether, our results demonstrate that the S4-S5 and S6 helices from adjacent domains are energetically coupled during the activation of a low voltage-gated T-type CaV3 channel.

  5. Activation of Type II Cells into Regenerative Stem Cell Antigen-1+ Cells during Alveolar Repair

    PubMed Central

    Kumar, Varsha Suresh; Zhang, Wei; Rehman, Jalees; Malik, Asrar B.

    2015-01-01

    The alveolar epithelium is composed of two cell types: type I cells comprise 95% of the gas exchange surface area, whereas type II cells secrete surfactant, while retaining the ability to convert into type I cells to induce alveolar repair. Using lineage-tracing analyses in the mouse model of Pseudomonas aeruginosa–induced lung injury, we identified a population of stem cell antigen (Sca)-1–expressing type II cells with progenitor cell properties that mediate alveolar repair. These cells were shown to be distinct from previously reported Sca-1–expressing bronchioalveolar stem cells. Microarray and Wnt reporter studies showed that surfactant protein (Sp)-C+Sca-1+ cells expressed Wnt signaling pathway genes, and inhibiting Wnt/β-catenin signaling prevented the regenerative function of Sp-C+Sca-1+ cells in vitro. Thus, P. aeruginosa–mediated lung injury induces the generation of a Sca-1+ subset of type II cells. The progenitor phenotype of the Sp-C+Sca-1+ cells that mediates alveolar epithelial repair might involve Wnt signaling. PMID:25474582

  6. Sulfatide-Mediated Activation of Type II Natural Killer T Cells Prevents Hepatic Ischemic Reperfusion Injury In Mice

    PubMed Central

    Arrenberg, Philomena; Maricic, Igor; Kumar, Vipin

    2011-01-01

    Background & Aims Hepatic ischemic reperfusion injury (IRI) is a major complication of liver transplantation and resectional hepatic surgeries. Natural killer T (NKT) cells predominate in liver, where they recognize lipid antigens bound to CD1d molecules. Type I NKT cells utilize a semi-invariant T-cell receptor and react with α-galactosylceramide; type II NKT cells use diverse T-cell receptors. Some type II NKT cells recognize the self-glycolipid sulfatide. It is not clear whether or how these distinct NKT cell subsets mediate hepatocellular damage following IRI. Methods We examined the roles of type I and type II NKT cells in mice with partial hepatic, warm ischemia and reperfusion injury. Results Mice that lack type I NKT cells (Jα18−/−) were protected from hepatic IRI, indicated by reduced hepatocellular necrosis and serum levels of alanine aminotransferase. Sulfatide-mediated activation of type II NKT cells reduced IFN-γ secretion by type I NKT cells and prevented IRI. Protection from hepatic IRI by sulfatide-mediated inactivation of type I NKT cells was associated with significant reductions in hepatic recruitment of myeloid cell subsets, especially the CD11b+Gr-1int, Gr-1−, and NK cells. Conclusion In mice, subsets of NKT cells have opposing roles in hepatic IRI: type I NKT cells promote injury whereas sulfatide-reactive type II NKT cells protect against injury. CD1d activation of NKT cells is conserved from mice to humans, so strategies to modify these processes might be developed to treat patients with hepatic reperfusion injury. PMID:20950612

  7. Structure-Function Basis of Attenuated Inverse Agonism of Angiotensin II Type 1 Receptor Blockers for Active-State Angiotensin II Type 1 Receptor.

    PubMed

    Takezako, Takanobu; Unal, Hamiyet; Karnik, Sadashiva S; Node, Koichi

    2015-09-01

    Ligand-independent signaling by the angiotensin II type 1 receptor (AT1R) can be activated in clinical settings by mechanical stretch and autoantibodies as well as receptor mutations. Transition of the AT1R to the activated state is known to lower inverse agonistic efficacy of clinically used AT1R blockers (ARBs). The structure-function basis for reduced efficacy of inverse agonists is a fundamental aspect that has been understudied not only in relation to the AT1R but also regarding other homologous receptors. Here, we demonstrate that the active-state transition in the AT1R indeed attenuates an inverse agonistic effect of four biphenyl-tetrazole ARBs through changes in specific ligand-receptor interactions. In the ground state, tight interactions of four ARBs with a set of residues (Ser109(TM3), Phe182(ECL2), Gln257(TM6), Tyr292(TM7), and Asn295(TM7)) results in potent inverse agonism. In the activated state, the ARB-AT1R interactions shift to a different set of residues (Val108(TM3), Ser109(TM3), Ala163(TM4), Phe182(ECL2), Lys199(TM5), Tyr292(TM7), and Asn295(TM7)), resulting in attenuated inverse agonism. Interestingly, V108I, A163T, N295A, and F182A mutations in the activated state of the AT1R shift the functional response to the ARB binding toward agonism, but in the ground state the same mutations cause inverse agonism. Our data show that the second extracellular loop is an important regulator of the functional states of the AT1R. Our findings suggest that the quest for discovering novel ARBs, and improving current ARBs, fundamentally depends on the knowledge of the unique sets of residues that mediate inverse agonistic potency in the two states of the AT1R.

  8. Structure-Function Basis of Attenuated Inverse Agonism of Angiotensin II Type 1 Receptor Blockers for Active-State Angiotensin II Type 1 Receptor

    PubMed Central

    Unal, Hamiyet; Karnik, Sadashiva S.; Node, Koichi

    2015-01-01

    Ligand-independent signaling by the angiotensin II type 1 receptor (AT1R) can be activated in clinical settings by mechanical stretch and autoantibodies as well as receptor mutations. Transition of the AT1R to the activated state is known to lower inverse agonistic efficacy of clinically used AT1R blockers (ARBs). The structure-function basis for reduced efficacy of inverse agonists is a fundamental aspect that has been understudied not only in relation to the AT1R but also regarding other homologous receptors. Here, we demonstrate that the active-state transition in the AT1R indeed attenuates an inverse agonistic effect of four biphenyl-tetrazole ARBs through changes in specific ligand-receptor interactions. In the ground state, tight interactions of four ARBs with a set of residues (Ser109TM3, Phe182ECL2, Gln257TM6, Tyr292TM7, and Asn295TM7) results in potent inverse agonism. In the activated state, the ARB-AT1R interactions shift to a different set of residues (Val108TM3, Ser109TM3, Ala163TM4, Phe182ECL2, Lys199TM5, Tyr292TM7, and Asn295TM7), resulting in attenuated inverse agonism. Interestingly, V108I, A163T, N295A, and F182A mutations in the activated state of the AT1R shift the functional response to the ARB binding toward agonism, but in the ground state the same mutations cause inverse agonism. Our data show that the second extracellular loop is an important regulator of the functional states of the AT1R. Our findings suggest that the quest for discovering novel ARBs, and improving current ARBs, fundamentally depends on the knowledge of the unique sets of residues that mediate inverse agonistic potency in the two states of the AT1R. PMID:26121982

  9. A dynamical model for FR II type radio sources with terminated jet activity

    NASA Astrophysics Data System (ADS)

    Kuligowska, Elżbieta

    2017-02-01

    Context. The extension of the KDA analytical model of FR II-type source evolution originally assuming a continuum injection process in the jet-IGM interaction towards a case of the jet's termination is presented and briefly discussed. Aims: The dynamical evolution of FR II-type sources predicted with this extended model, hereafter referred to as KDA EXT, and its application to the chosen radio sources. Methods: Following the classical approach based on the source's continuous injection and self-similarity, I propose the effective formulae describing the length and luminosity evolution of the lobes during an absence of the jet flow, and present the resulting diagrams for the characteristics mentioned. Results: Using an algorithm based on the numerical integration of a modified formula for jet power, the KDA EXT model is fitted to three radio galaxies. Their predicted spectra are then compared to the observed spectra, proving that these fits are better than the best spectral fit provided by the original KDA model of the FR II-type sources dynamical evolution.

  10. Signaling activity of transforming growth factor beta type II receptors lacking specific domains in the cytoplasmic region.

    PubMed Central

    Wieser, R; Attisano, L; Wrana, J L; Massagué, J

    1993-01-01

    The transforming growth factor beta (TGF-beta) type II receptor (T beta R-II) is a transmembrane serine/threonine kinase that contains two inserts in the kinase region and a serine/threonine-rich C-terminal extension. T beta R-II is required for TGF-beta binding to the type I receptor, with which it forms a heteromeric receptor complex, and its kinase activity is required for signaling by this complex. We investigated the role of various cytoplasmic regions in T beta R-II by altering or deleting these regions and determining the signaling activity of the resulting products in cell lines made resistant to TGF-beta by inactivation of the endogenous T beta R-II. TGF-beta binding to receptor I and responsiveness to TGF-beta in these cells can be restored by transfection of wild-type T beta R-II. Using this system, we show that the kinase insert 1 and the C-terminal tail of T beta R-II, in contrast to the corresponding regions in most tyrosine kinase receptors, are not essential to specify ligand-induced responses. Insert 2 is necessary to support the catalytic activity of the receptor kinase, and its deletion yields a receptor that is unable to mediate any of the responses tested. However, substitution of this insert with insert 2 from the activin receptor, ActR-IIB, does not diminish the ability of T beta R-II to elicit these responses. A truncated T beta R-II lacking the cytoplasmic domain still binds TGF-beta, supports ligand binding to receptor I, and forms a complex with this receptor. However, TGF-beta binding to receptor I facilitated by this truncated T beta R-II fails to inhibit cell proliferation, activate extracellular matrix protein production, or activate transcription from a promoter containing TGF-beta-responsive elements. We conclude that the transcriptional and antiproliferative responses to TGF-beta require both components of a heteromeric receptor complex that differs from tyrosine kinase receptors in its mode of signaling. Images PMID:8246946

  11. Occurrence and activity of a type II CRISPR-Cas system in Lactobacillus gasseri.

    PubMed

    Sanozky-Dawes, Rosemary; Selle, Kurt; O'Flaherty, Sarah; Klaenhammer, Todd; Barrangou, Rodolphe

    2015-09-01

    Bacteria encode clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated genes (cas), which collectively form an RNA-guided adaptive immune system against invasive genetic elements. In silico surveys have revealed that lactic acid bacteria harbour a prolific and diverse set of CRISPR-Cas systems. Thus, the natural evolutionary role of CRISPR-Cas systems may be investigated in these ecologically, industrially, scientifically and medically important microbes. In this study, 17 Lactobacillus gasseri strains were investigated and 6 harboured a type II-A CRISPR-Cas system, with considerable diversity in array size and spacer content. Several of the spacers showed similarity to phage and plasmid sequences, which are typical targets of CRISPR-Cas immune systems. Aligning the protospacers facilitated inference of the protospacer adjacent motif sequence, determined to be 5'-NTAA-3' flanking the 3' end of the protospacer. The system in L. gasseri JV-V03 and NCK 1342 interfered with transforming plasmids containing sequences matching the most recently acquired CRISPR spacers in each strain. We report the distribution and function of a native type II-A CRISPR-Cas system in the commensal species L. gasseri. Collectively, these results open avenues for applications for bacteriophage protection and genome modification in L. gasseri, and contribute to the fundamental understanding of CRISPR-Cas systems in bacteria.

  12. Nuclear Infrared Spectral Energy Distribution of Type II Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Videla, Liza; Lira, Paulina; Andrews, Heather; Alonso-Herrero, Almudena; Alexander, David M.; Ward, Martin

    2013-02-01

    We present near- and mid-IR observations of a sample of Seyfert II galaxies drawn from the 12 μm Galaxy sample. The sample was observed in the J, H, K, L, M and N bands. Galaxy surface brightness profiles are modeled using nuclear, bulge, bar (when necessary), and disk components. To check the reliability of our findings, the procedure was tested using Spitzer observations of M 31. Nuclear spectral energy distributions (SEDs) are determined for 34 objects, and optical spectra are presented for 38, including analysis of their stellar populations using the STARLIGHT spectral synthesis code. Emission line diagnostic diagrams are used to discriminate between genuine active galactic nuclei (AGNs) and H II nuclei. Combining our observations with those found in the literature, we have a total of 40 SEDs. It is found that about 40% of the SEDs are characterized by an upturn in the near-IR, which we have quantified as a NIR slope α < 1 for an SED characterized as λf λvpropλα. The three objects with an H II nucleus and two Seyfert nuclei with strong contamination from a circumnuclear also show an upturn. For genuine AGNs, this component could be explained as emission from the accretion disk, a jet, or from a very hot dust component leaking from the central region through a clumpy obscuring structure. The presence of a very compact nuclear starburst as the origin for this NIR excess emission is not favored by our spectroscopic data for these objects.

  13. Activity of quinolone CP-115,955 against bacterial and human type II topoisomerases is mediated by different interactions.

    PubMed

    Aldred, Katie J; Schwanz, Heidi A; Li, Gangqin; Williamson, Benjamin H; McPherson, Sylvia A; Turnbough, Charles L; Kerns, Robert J; Osheroff, Neil

    2015-02-10

    CP-115,955 is a quinolone with a 4-hydroxyphenyl at C7 that displays high activity against both bacterial and human type II topoisomerases. To determine the basis for quinolone cross-reactivity between bacterial and human enzymes, the activity of CP-115,955 and a series of related quinolones and quinazolinediones against Bacillus anthracis topoisomerase IV and human topoisomerase IIα was analyzed. Results indicate that the activity of CP-115,955 against the bacterial and human enzymes is mediated by different interactions. On the basis of the decreased activity of quinazolinediones against wild-type and resistant mutant topoisomerase IV and the low activity of quinolones against resistant mutant enzymes, it appears that the primary interaction of CP-115,955 with the bacterial system is mediated through the C3/C4 keto acid and the water-metal ion bridge. In contrast, the drug interacts with the human enzyme primarily through the C7 4-hydroxyphenyl ring and has no requirement for a substituent at C8 in order to attain high activity. Despite the fact that the human type II enzyme is unable to utilize the water-metal ion bridge, quinolones in the CP-115,955 series display higher activity against topoisomerase IIα in vitro and in cultured human cells than the corresponding quinazolinediones. Thus, quinolones may be a viable platform for the development of novel drugs with anticancer potential.

  14. The Activity of Quinolone CP-115,955 Against Bacterial and Human Type II Topoisomerases Is Mediated by Different Interactions

    PubMed Central

    Aldred, Katie J.; Schwanz, Heidi A.; Li, Gangqin; Williamson, Benjamin H.; McPherson, Sylvia A.; Turnbough, Charles L.; Kerns, Robert J.; Osheroff, Neil

    2015-01-01

    CP-115,955 is a quinolone with a 4-hydroxyphenyl at C7 that displays high activity against both bacterial and human type II topoisomerases. To determine the basis for quinolone cross-reactivity between bacterial and human enzymes, the activity of CP-115,955 and a series of related quinolones and quinazolinediones against Bacillus anthracis topoisomerase IV and human topoisomerase IIα was analyzed. Results indicate that the activity of CP-115,955 against the bacterial and human enzymes is mediated by different interactions. Based on the decreased activity of quinazolinediones against wild-type and resistant mutant topoisomerase IV and the low activity of quinolones against resistant mutant enzymes, it appears that the primary interaction of CP-115,955 with the bacterial system is mediated through the C3/C4 keto acid and the water-metal ion bridge. In contrast, the drug interacts with the human enzyme primarily through the C7 4-hydroxyphenyl ring and has no requirement for a substituent at C8 in order to attain high activity. Despite the fact that the human type II enzyme is unable to utilize the water-metal ion bridge, quinolones in the CP-115,955 series display higher activity against topoisomerase IIα in vitro and in cultured human cells than the corresponding quinazolinediones. Thus, quinolones may be a viable platform for the development of novel drugs with anticancer potential. PMID:25586498

  15. Histone acetyltransferase (HAT) activity of p300 modulates human T lymphotropic virus type 1 p30{sup II}-mediated repression of LTR transcriptional activity

    SciTech Connect

    Michael, Bindhu; Nair, Amrithraj M.; Datta, Antara; Hiraragi, Hajime; Ratner, Lee; Lairmore, Michael D. . E-mail: lairmore.1@osu.edu

    2006-10-25

    Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that causes adult T cell leukemia/lymphoma, and is implicated in a variety of lymphocyte-mediated inflammatory disorders. HTLV-1 provirus has regulatory and accessory genes in four pX open reading frames. HTLV-1 pX ORF-II encodes two proteins, p13{sup II} and p30{sup II}, which are incompletely defined in virus replication or pathogenesis. We have demonstrated that pX ORF-II mutations block virus replication in vivo and that ORF-II encoded p30{sup II}, a nuclear-localizing protein that binds with CREB-binding protein (CBP)/p300, represses CREB and Tax responsive element (TRE)-mediated transcription. Herein, we have identified p30{sup II} motifs important for p300 binding and in regulating TRE-mediated transcription in the absence and presence of HTLV-1 provirus. Within amino acids 100-179 of p30{sup II}, a region important for repression of LTR-mediated transcription, we identified a single lysine residue at amino acid 106 (K3) that significantly modulates the ability of p30{sup II} to repress TRE-mediated transcription. Exogenous p300, in a dose-responsive manner, reverses p30{sup II}-dependent repression of TRE-mediated transcription, in the absence or presence of the provirus, In contrast to wild type p300, p300 HAT mutants (defective in histone acetyltransferase activity) only partially rescued p30{sup II}-mediated LTR repression. Deacetylation by histone deacetylase-1 (HDAC-1) enhanced p30{sup II}-mediated LTR repression, while inhibition of deacetylation by trichostatin A decreases p30{sup II}-mediated LTR repression. Collectively, our data indicate that HTLV-1 p30{sup II} modulates viral gene expression in a cooperative manner with p300-mediated acetylation.

  16. Type II cyclic guanosine monophosphate-dependent protein kinase inhibits Rac1 activation in gastric cancer cells

    PubMed Central

    WANG, YING; CHEN, YONGCHANG; WU, MIN; LAN, TING; WU, YAN; LI, YUEYING; QIAN, HAI

    2015-01-01

    Enhanced motility of cancer cells is a critical step in promoting tumor metastasis, which remains the major cause of gastric cancer-associated mortality. The small GTPase Rac1 is a key signaling component in the regulation of cell migration. Previous studies have demonstrated that Rac1 activity may be regulated by protein kinase G (PKG); however, the underlying mechanism is not yet clear. The current study aimed to investigate the effect of type II cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG II) on Rac1 activity. The human gastric cancer cell line AGS was infected with adenoviral constructs encoding PKG II to increase the expression of this enzyme, and treated with a cGMP analog (8-pCPT-cGMP) to induce its activation. A Transwell assay was employed to measure cell migration, and the activity of Rac1 was assessed using a pull-down assay. Immunoprecipitation was used to isolate the Rac1 protein. Phosphorylation of phosphatidylinositol 4,5 bisphosphate 3 kinase (PI3K) and its downstream effecter protein kinase B (Akt) are associated with lysophosphatidic acid (LPA)-induced motility/migration of cancer cells. Extracellular signal regulated kinase (ERK) is the major signaling molecule of the Mitogen activated protein kinase (MAPK) mediated signaling pathway. ERK and its upstream activator MAPK kinase (MEK) are also involved in LPA-induced motility/migration of cancer cells. Phosphorylation of PI3K/Akt, MEK/ERK and enriched Rac1 were detected by western blotting. The results revealed that blocking the activation of Rac1 by ectopically expressing an inactive Rac1 mutant (T17N) impeded LPA-induced cell migration. Increased PKG II activity inhibited LPA-induced migration and LPA-induced activation of Rac1; however, it had no effect on the phosphorylation of Rac1. PKG II also inhibited the activation of PI3K/Akt and MEK/ERK mediated signaling, which is important for LPA-induced Rac1 activation. These results suggest that PKG II affects LPA

  17. Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1

    PubMed Central

    Otero, Miguel; Lago, Rocío; Lago, Francisca; Reino, Juan Jesús Gomez; Gualillo, Oreste

    2005-01-01

    The objective of the present study was to investigate the effect of leptin, alone or in combination with IL-1, on nitric oxide synthase (NOS) type II activity in vitro in human primary chondrocytes, in the mouse chondrogenic ATDC5 cell line, and in mature and hypertrophic ATDC5 differentiated chondrocytes. For completeness, we also investigated the signalling pathway of the putative synergism between leptin and IL-1. For this purpose, nitric oxide production was evaluated using the Griess colorimetric reaction in culture medium of cells stimulated over 48 hours with leptin (800 nmol/l) and IL-1 (0.025 ng/ml), alone or combined. Specific pharmacological inhibitors of NOS type II (aminoguanidine [1 mmol/l]), janus kinase (JAK)2 (tyrphostin AG490 and Tkip), phosphatidylinositol 3-kinase (PI3K; wortmannin [1, 2.5, 5 and 10 μmol/l] and LY294002 [1, 2.5, 5 and 10 μmol/l]), mitogen-activated protein kinase kinase (MEK)1 (PD098059 [1, 5, 10, 20 and 30 μmol/l]) and p38 kinase (SB203580 [1, 5, 10, 20 and 30 μmol/l]) were added 1 hour before stimulation. Nitric oxide synthase type II mRNA expression in ATDC5 chondrocytes was investigated by real-time PCR and NOS II protein expression was analyzed by western blot. Our results indicate that stimulation of chondrocytes with IL-1 results in dose-dependent nitric oxide production. In contrast, leptin alone was unable to induce nitric oxide production or expression of NOS type II mRNA or its protein. However, co-stimulation with leptin and IL-1 resulted in a net increase in nitric oxide concentration over IL-1 challenge that was eliminated by pretreatment with the NOS II specific inhibitor aminoguanidine. Pretreatment with tyrphostin AG490 and Tkip (a SOCS-1 mimetic peptide that inhibits JAK2) blocked nitric oxide production induced by leptin/IL-1. Finally, wortmannin, LY294002, PD098059 and SB203580 significantly decreased nitric oxide production. These findings were confirmed in mature and hypertrophic ATDC5 chondrocytes, and

  18. Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1.

    PubMed

    Otero, Miguel; Lago, Rocío; Lago, Francisca; Reino, Juan Jesús Gomez; Gualillo, Oreste

    2005-01-01

    The objective of the present study was to investigate the effect of leptin, alone or in combination with IL-1, on nitric oxide synthase (NOS) type II activity in vitro in human primary chondrocytes, in the mouse chondrogenic ATDC5 cell line, and in mature and hypertrophic ATDC5 differentiated chondrocytes. For completeness, we also investigated the signalling pathway of the putative synergism between leptin and IL-1. For this purpose, nitric oxide production was evaluated using the Griess colorimetric reaction in culture medium of cells stimulated over 48 hours with leptin (800 nmol/l) and IL-1 (0.025 ng/ml), alone or combined. Specific pharmacological inhibitors of NOS type II (aminoguanidine [1 mmol/l]), janus kinase (JAK)2 (tyrphostin AG490 and Tkip), phosphatidylinositol 3-kinase (PI3K; wortmannin [1, 2.5, 5 and 10 micromol/l] and LY294002 [1, 2.5, 5 and 10 micromol/l]), mitogen-activated protein kinase kinase (MEK)1 (PD098059 [1, 5, 10, 20 and 30 micromol/l]) and p38 kinase (SB203580 [1, 5, 10, 20 and 30 micromol/l]) were added 1 hour before stimulation. Nitric oxide synthase type II mRNA expression in ATDC5 chondrocytes was investigated by real-time PCR and NOS II protein expression was analyzed by western blot. Our results indicate that stimulation of chondrocytes with IL-1 results in dose-dependent nitric oxide production. In contrast, leptin alone was unable to induce nitric oxide production or expression of NOS type II mRNA or its protein. However, co-stimulation with leptin and IL-1 resulted in a net increase in nitric oxide concentration over IL-1 challenge that was eliminated by pretreatment with the NOS II specific inhibitor aminoguanidine. Pretreatment with tyrphostin AG490 and Tkip (a SOCS-1 mimetic peptide that inhibits JAK2) blocked nitric oxide production induced by leptin/IL-1. Finally, wortmannin, LY294002, PD098059 and SB203580 significantly decreased nitric oxide production. These findings were confirmed in mature and hypertrophic ATDC5

  19. Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors.

    PubMed

    Cooper, Ian R; McCarroll, Andrew J; McGarry, David; Kirkham, James; Pichowicz, Mark; Walker, Rolf; Warrilow, Catherine; Salisbury, Anne-Marie; Savage, Victoria J; Moyo, Emmanuel; Forward, Henry; Cheung, Jonathan; Metzger, Richard; Gault, Zoe; Nelson, Gary; Hughes, Diarmaid; Cao, Sha; Maclean, John; Charrier, Cédric; Craighead, Mark; Best, Stuart; Stokes, Neil R; Ratcliffe, Andrew J

    2016-09-01

    There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.

  20. Peptidoglycan-mediated IL-8 expression in human alveolar type II epithelial cells requires lipid raft formation and MAPK activation.

    PubMed

    Cheon, In Su; Woo, Sang Su; Kang, Seok-Seong; Im, Jintaek; Yun, Cheol-Heui; Chung, Dae Kyun; Park, Dong Ki; Han, Seung Hyun

    2008-03-01

    Staphylococcus aureus, a major sepsis-causing Gram-positive bacterium, invades pulmonary epithelial cells and causes lung diseases. In the lung, alveolar type II epithelial cells play an important role in innate immunity by secreting chemokines and antimicrobial peptides upon bacterial infection whereas type I cells mainly function in gas-exchange. In this study, we investigated the ability of S. aureus peptidoglycan (PGN) to induce expression of a chemokine, IL-8, in a human alveolar type II epithelial cell line, A549. PGN induces IL-8 mRNA and protein expression in a dose- and time-dependent manner. Supplementation of soluble CD14 further enhanced the PGN-induced IL-8 expression. Interestingly, PGN-induced IL-8 expression was inhibited by nystatin, a specific inhibitor for lipid rafts, but not by chlorpromazine, a specific inhibitor for clathrin-coated pits. Furthermore, PGN-induced IL-8 expression was attenuated by inhibitors for MAP kinases such as ERK, p38 kinase, and JNK/SAPK, whereas no inhibitory effect was observed by inhibitors for reactive oxygen species or protein kinase C. Electrophoretic mobility shift assay demonstrates that PGN increased the DNA binding of the transcription factors, AP-1 and NF-kappaB while minimally, NF-IL6, all of which are involved in the transcription of IL-8. Taken together, these results suggest that PGN induces IL-8 expression in a CD14-enhanced manner in human alveolar type II epithelial cells, through the formation of lipid rafts and the activation of MAP kinases, which ultimately leads to activation of AP-1, NF-kappaB, and NF-IL6.

  1. Role of type I & type II reactions in DNA damage and activation of caspase 3 via mitochondrial pathway induced by photosensitized benzophenone.

    PubMed

    Amar, Saroj Kumar; Goyal, Shruti; Mujtaba, Syed Faiz; Dwivedi, Ashish; Kushwaha, Hari Narayan; Verma, Ankit; Chopra, Deepti; Chaturvedi, Rajnish K; Ray, Ratan Singh

    2015-06-01

    Sunscreen users have been increased, since excessive sun exposure increased the risk of skin diseases. Benzophenone (BP) and its derivatives are commonly used in sunscreens as UV blocker. Its photosafety is concern for human health. Our study showed the role of type-I and type-II radicals in activation of caspase 3 and phototoxicity of BP under sunlight/UV radiation. BP photodegraded and formed two photoproducts. BP generates reactive oxygen species (ROS) singlet oxygen ((1)O2), superoxide anion (O2˙(-)) and hydroxyl radical (˙OH) through type-I and type-II photodynamic mechanisms. Photocytotoxicity significantly reduced cell viability under sunlight, UVB and UVA. DCF fluorescence confirmed intracellular ROS generation. BP showed single strand DNA breakage, further proved by cyclobutane pyrimidine dimmers (CPDs) formation. Lipid peroxidation and LDH leakage were enhanced by BP. P21 dependent cell cycle study showed sub G1 population which advocates apoptotic cell death, confirmed through AO/EB and annexin V/PI staining. BP decreased mitochondrial membrane potential, death protein released and activated caspase. We proposed cytochrome c regulated caspase 3 dependent apoptosis in HaCaT cell line through down regulation of Bcl2/Bax ratio. Phototoxicity potential of its photoproducts is essential to understand its total environmental fate. Hence, we conclude that BP may replace from cosmetics preparation of topical application.

  2. Preparation and Biological Activity of the Monoclonal Antibody against the Second Extracellular Loop of the Angiotensin II Type 1 Receptor

    PubMed Central

    Wei, Mingming; Zhao, Chengrui; Zhang, Suli; Wang, Li; Liu, Huirong; Ma, Xinliang

    2016-01-01

    The current study was to prepare a mouse-derived antibody against the angiotensin II type 1 receptor (AT1-mAb) based on monoclonal antibody technology, to provide a foundation for research on AT1-AA-positive diseases. Balb/C mice were actively immunized with the second extracellular loop of the angiotensin II type 1 receptor (AT1R-ECII). Then, mouse spleen lymphocytes were fused with myeloma cells and monoclonal hybridomas that secreted AT1-mAb were generated and cultured, after which those in logarithmic-phase were injected into the abdominal cavity of mice to retrieve the ascites. Highly purified AT1-mAb was isolated from mouse ascites after injection with 1 × 107 hybridomas. A greater amount of AT1-mAb was purified from mouse ascites compared to the cell supernatant of hybridomas. AT1-mAb purified from mouse ascites constricted the thoracic aorta of mice and increased the beat frequency of neonatal rat myocardial cells via the AT1R, identical to the effects of AT1-AA extracted from patients' sera. Murine blood pressure increased after intravenous injection of AT1-mAb via the tail vein. High purity and good biological activity of AT1-mAb can be obtained from mouse ascites after intraperitoneal injection of monoclonal hybridomas that secrete AT1-mAb. These data provide a simple tool for studying AT1-AA-positive diseases. PMID:27057554

  3. Healthy lifestyles in Europe: prevention of obesity and type II diabetes by diet and physical activity.

    PubMed

    Astrup, A

    2001-04-01

    The prevalence of obesity is increasing rapidly in all age groups in most EU-countries and is one of the fastest growing epidemics, now affecting 10-40% of the adult population. Obesity increases the risk of serious co-morbidities such as type 2 diabetes, cardiovascular disease, certain cancers and reduced life expectancy, and these complications may account for 5-10% of all health costs in EU countries. The risk of diabetes is particularly increased by obesity, and 80-95% of the increase in diabetes can be attributed to obesity and overweight with abdominal fat distribution. There is robust evidence from cross-sectional and longitudinal studies to support that an energy-dense, high fat diet and physical inactivity are independent risk factors for weight gain and obesity. Furthermore, interaction between dietary fat and physical fitness determine fat balance, so that the obesity promoting effect of a high fat diet is enhanced in susceptible subjects, particularly in sedentary individuals with a genetic predisposition to obesity. Ad libitum consumption of diets low in fat and high in protein and complex carbohydrates, with a low glycaemic index, contributes to the prevention of weight gain in normal weight subjects. It also causes a spontaneous weight loss of 3-4 kg in overweight subjects, and has beneficial effects on risk factors for diabetes and CVD. To prevent obesity and diabetes there are grounds for recommending the combination of increasing daily physical activity level to a PAL-value of at least 1.8 and reducing dietary fat content to 20-25 energy-% in sedentary subjects, and to 25-35% in more physically active individuals.

  4. Neuronal angiotensin II type 1 receptor upregulation in heart failure: activation of activator protein 1 and Jun N-terminal kinase.

    PubMed

    Liu, Dongmei; Gao, Lie; Roy, Shyamal K; Cornish, Kurtis G; Zucker, Irving H

    2006-10-27

    Chronic heart failure (CHF) is a leading cause of mortality in developed countries. Angiotensin II (Ang II) plays an important role in the development and progression of CHF. Many of the important functions of Ang II are mediated by the Ang II type 1 receptor (AT(1)R), including the increase in sympathetic nerve activity in CHF. However, the central regulation of the AT(1)R in the setting of CHF is not well understood. This study investigated the AT(1)R in the rostral ventrolateral medulla (RVLM) of rabbits with CHF, its downstream pathway, and its gene regulation by the transcription factor activator protein 1 (AP-1). Studies were performed in 5 groups of rabbits: sham (n=5), pacing-induced (3 to 4 weeks) CHF (n=5), CHF with intracerebroventricular (ICV) losartan treatment (n=5), normal with ICV Ang II treatment (n=5), and normal with ICV Ang II plus losartan treatment (n=5). AT(1)R mRNA and protein expressions, plasma Ang II, and AP-1-DNA binding activity were significantly higher in RVLM of CHF compared with Sham rabbits (240.4+/-30.2%, P<0.01; 206.6+/-25.8%, P<0.01; 280+/-36.5%, P<0.05; 207+/-16.4%, P<0.01, respectively). Analysis of the stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) pathway showed that phosphorylated c-Jun proteins, phosphorylated JNK proteins, and JNK activity increased significantly in RVLM of CHF compared with sham (262.9+/-48.1%, 213.8+/-27.7%, 148.2+/-10.1% of control, respectively). Importantly, ICV losartan in CHF rabbits attenuated these increases. ICV Ang II in normal rabbits simulated the molecular changes seen in CHF. This effect was blocked by concomitant ICV losartan. In addition, Ang II-induced AT(1)R expression was blocked by losartan and a JNK inhibitor, but not by extracellular signal-regulated kinase or p38 MAP kinase inhibitors in a neuronal cell culture. These data suggest that central Ang II activates the AT(1)R, SAPK/JNK pathway. AP-1 may further regulate gene expression in RVLM in the CHF state.

  5. Selective NO trapping in the pores of chain-type complex assemblies based on electronically activated paddlewheel-type [Ru2(II,II)]/[Rh2(II,II)] dimers.

    PubMed

    Kosaka, Wataru; Yamagishi, Kayo; Hori, Akihiro; Sato, Hiroshi; Matsuda, Ryotaro; Kitagawa, Susumu; Takata, Masaki; Miyasaka, Hitoshi

    2013-12-11

    The design of porous materials that undergo selective adsorption of a specific molecule is a critical issue in research on porous coordination polymers or metal-organic frameworks. For the purpose of the selective capture of molecules possessing an electron-acceptor character such as nitric oxide (NO), one-dimensional chain compounds possessing a high donor character have been synthesized using 4-chloroanisate-bridged paddlewheel-type dimetal(II, II) complexes with M = Ru and Rh and phenazine (phz) as the chain linker: [M2(4-Cl-2-OMePhCO2)4(phz)]·n(CH2Cl2) (M = Ru, 1; Rh, 2). These compounds are isostructural and are composed of chains with a [-{M2}-phz-] repeating unit and CH2Cl2 occupying the void space between the chains. Compounds 1 and 2 change to a new phase (1-dry and 2-dry) upon evacuating the crystallization solvent (CH2Cl2) and almost lose their pores in the drying process: no void space in 1-dry and 31.8 Å(3), corresponding to 2.9% of the cell volume, in 2-dry. Nevertheless, the compounds show a unique gas accommodation ability. Accompanied by a structural transformation (i.e., the first gate-opening) at low pressures of <10 kPa, both compounds show a typical physisorption isotherm for O2 (90 K) and CO2 (195 K), with the adsorption amount of ca. 2-4 gas molecules per [M2] unit. In addition, the adsorption isotherm for NO (121 K) involves the first gate-opening followed by a second gate-opening anomaly at NO pressures of ≈52 kPa for 1-dry and ≈21 kPa for 2-dry. At the first gate-opening, the absorbed amount of NO is ca. 4 molecules per [M2] unit, and then it reaches 8.4 and 6.3 for 1-dry and 2-dry, respectively, at 95 kPa. Only the isotherm for NO exhibits hysteresis in the desorption process, and some of the NO molecules are trapped in pores even after evacuating at 121 K, although it recovers to the original dried sample on heating to room temperature. The adsorbed NO molecules accrue a significant electron donation from the host framework even in

  6. Cu(II), Ni(II), and Zn(II) Complexes of Salan-Type Ligand Containing Ester Groups: Synthesis, Characterization, Electrochemical Properties, and In Vitro Biological Activities

    PubMed Central

    Jeslin Kanaga Inba, P.; Annaraj, B.; Thalamuthu, S.; Neelakantan, M. A.

    2013-01-01

    A salen ligand on reduction and N-alkylation affords a novel [N2O2] chelating ligand containing ester groups [L = diethyl-2,2′-(propane-1,3-diylbis((2-hydroxy-3-methoxy benzyl)azanediyl))diacetate]. The purity of the ligand was confirmed by NMR and HPLC chromatograms. Its Cu(II), Ni(II), and Zn(II) complexes were synthesized and characterized by a combination of elemental analysis, IR, NMR, UV-Vis, and mass spectral data, and thermogravimetric analysis (TG/DTA). The magnetic moments, UV-Vis, and EPR spectral studies support square planar geometry around the Cu(II) and Ni(II) ions. A tetrahedral geometry is observed in four-coordinate zinc with bulky N-alkylated salan ligand. The redox properties of the copper complex were examined in DMSO by cyclic voltammetry. The voltammograms show quasireversible process. The interaction of metal complexes with CT DNA was investigated by UV-Vis absorption titration, ethidium bromide displacement assay, cyclic voltammetry methods, and agarose gel electrophoresis. The apparent binding constant values suggest moderate intercalative binding modes between the complexes and DNA. The in vitro antioxidant and antimicrobial potentials of the synthesized compounds were also determined. PMID:23983672

  7. The type II secretion system (Xcp) of Pseudomonas putida is active and involved in the secretion of phosphatases.

    PubMed

    Putker, Florian; Tommassen-van Boxtel, Ria; Stork, Michiel; Rodríguez-Herva, José J; Koster, Margot; Tommassen, Jan

    2013-10-01

    The genome of the Gram-negative bacterium Pseudomonas putida harbours a complete set of xcp genes for a type II protein secretion system (T2SS). This study shows that expression of these genes is induced under inorganic phosphate (Pi ) limitation and that the system enables the utilization of various organic phosphate sources. A phosphatase of the PhoX family, previously designated UxpB, was identified, which was produced under low Pi conditions and transported across the cell envelope in an Xcp-dependent manner demonstrating that the xcp genes encode an active T2SS. The signal sequence of UxpB contains a twin-arginine translocation (Tat) motif as well as a lipobox, and both processing by leader peptidase II and Tat dependency were experimentally confirmed. Two different tat gene clusters were detected in the P. putida genome, of which one, named tat-1, is located adjacent to the uxpB and xcp genes. Both Tat systems appeared to be capable of transporting the UxpB protein. However, expression of the tat-1 genes was strongly induced by low Pi levels, indicating a function of this system in survival during Pi starvation.

  8. Valsartan ameliorates ageing-induced aorta degeneration via angiotensin II type 1 receptor-mediated ERK activity.

    PubMed

    Shan, HaiYan; Zhang, Siyang; Li, Xuelian; Yu, Kai; Zhao, Xin; Chen, Xinyue; Jin, Bo; Bai, XiaoJuan

    2014-06-01

    Angiotensin II (Ang II) plays important roles in ageing-related disorders through its type 1 receptor (AT1 R). However, the role and underlying mechanisms of AT1R in ageing-related vascular degeneration are not well understood. In this study, 40 ageing rats were randomly divided into two groups: ageing group which received no treatment (ageing control), and valsartan group which took valsartan (selective AT1R blocker) daily for 6 months. 20 young rats were used as adult control. The aorta structure were analysed by histological staining and electron microscopy. Bcl-2/Bax expression in aorta was analysed by immunohistochemical staining, RT-PCR and Western blotting. The expressions of AT1 R, AT2 R and mitogen-activated protein kinases (MAPKs) were detected. Significant structural degeneration of aorta in the ageing rats was observed, and the degeneration was remarkably ameliorated by long-term administration of valsartan. With ageing, the expression of AT1R was elevated, the ratio of Bcl-2/Bax was decreased and meanwhile, an important subgroup of MAPKs, extracellular signal-regulated kinase (ERK) activity was elevated. However, these changes in ageing rats could be reversed to some extent by valsartan. In vitro experiments observed consistent results as in vivo study. Furthermore, ERK inhibitor could also acquire partial effects as valsartan without affecting AT1R expression. The results indicated that AT1R involved in the ageing-related degeneration of aorta and AT1R-mediated ERK activity was an important mechanism underlying the process.

  9. Contractile properties and sarcoplasmic reticulum calcium content in type I and type II skeletal muscle fibres in active aged humans

    PubMed Central

    Lamboley, C R; Wyckelsma, V L; Dutka, T L; McKenna, M J; Murphy, R M; Lamb, G D

    2015-01-01

    This study examined the contractile properties and sarcoplasmic reticulum (SR) Ca2+ content in mechanically skinned vastus lateralis muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) humans to investigate whether changes in muscle fibre properties contribute to muscle weakness in old age. In type II fibres of Old subjects, specific force was reduced by ∼17% and Ca2+ sensitivity was also reduced (pCa50 decreased ∼0.05 pCa units) relative to that in Young. S-Glutathionylation of fast troponin I (TnIf) markedly increased Ca2+ sensitivity in type II fibres, but the increase was significantly smaller in Old versus Young (+0.136 and +0.164 pCa unit increases, respectively). Endogenous and maximal SR Ca2+ content were significantly smaller in both type I and type II fibres in Old subjects. In fibres of Young, the SR could be nearly fully depleted of Ca2+ by a combined caffeine and low Mg2+ stimulus, whereas in fibres of Old the amount of non-releasable Ca2+ was significantly increased (by > 12% of endogenous Ca2+ content). Western blotting showed an increased proportion of type I fibres in Old subjects, and increased amounts of calsequestrin-2 and calsequestrin-like protein. The findings suggest that muscle weakness in old age is probably attributable in part to (i) an increased proportion of type I fibres, (ii) a reduction in both maximum specific force and Ca2+ sensitivity in type II fibres, and also a decreased ability of S-glutathionylation of TnIf to counter the fatiguing effects of metabolites on Ca2+ sensitivity, and (iii) a reduction in the amount of releasable SR Ca2+ in both fibre types. Key points Muscle weakness in old age is due in large part to an overall loss of skeletal muscle tissue, but it remains uncertain how much also stems from alterations in the properties of the individual muscle fibres. This study examined the contractile properties and amount of stored intracellular calcium in single muscle fibres of Old (70

  10. Genes Involved in Interleukin-1 Receptor Type II Activities Are Associated With Asthmatic Phenotypes

    PubMed Central

    Madore, Anne-Marie; Vaillancourt, Vanessa T.; Bouzigon, Emmanuelle; Sarnowski, Chloé; Monier, Florent; Dizier, Marie-Hélène; Demenais, Florence

    2016-01-01

    Purpose Interleukin-1 (IL-1) plays a key role in inflammation and immunity and its decoy receptor, IL-1R2, has been implicated in transcriptomic and genetic studies of asthma. Methods Two large asthma family collections, the French-Canadian Saguenay—Lac-St-Jean (SLSJ) study and the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA), were used to investigate the association of SNPs in 10 genes that modulate IL-1R2 activities with asthma, allergic asthma, and atopy. Gene-gene interactions were also tested. Results One SNP in BACE2 was associated with allergic asthma in the SLSJ study and replicated in the EGEA study before statistical correction for multiple testing. Additionally, two SNPs in the MMP2 gene were replicated in both studies prior to statistical correction and reached significance in the combined analysis. Moreover, three gene-gene interactions also survived statistical correction in the combined analyses (BACE1-IL1RAP in asthma and allergic asthma and IL1R1-IL1RAP in atopy). Conclusions Our results highlight the relevance of genes involved in the IL-1R2 activity in the context of asthma and asthma-related traits. PMID:27334786

  11. Achondrogenesis type II with polydactyly.

    PubMed

    Rittler, M; Orioli, I M

    1995-11-06

    We report on a newborn male infant who presented the typical findings of achondrogenesis type II (Langer-Saldino), and who also showed postaxial polydactyly on both feet and bilateral microtia. Polydactyly is frequently part of the short-rib syndromes, but has not been reported in achondrogenesis. The hypothesis of polydactyly as part of a contiguous gene syndrome is discussed.

  12. Sirtuin 1 Activator SRT1720 Protects Against Lung Injury via Reduction of Type II Alveolar Epithelial Cells Apoptosis in Emphysema.

    PubMed

    Gu, Chao; Li, Yaqing; Xu, Wu-Lin; Yan, Jian-Ping; Xia, Ying-jie; Ma, Ying-Yu; Chen, Chun; Wang, Hui-Ju; Tao, Hou-quan

    2015-08-01

    In chronic obstructive pulmonary disease (COPD), two major pathological changes that occur are the loss of alveolar structure and airspace enlargement. Type II alveolar epithelial cells (AECII) play a vital role in maintaining alveolar homeostasis and lung tissue repair. Sirtuin 1 (SIRT1), a NAD(+)-dependent histone deacetylase, regulates many pathophysiological processes including inflammation, apoptosis, cellular senescence and stress resistance. The main aim of this study was to investigate whether SRT1720, a pharmacological SIRT1 activator, could protect against AECII apoptosis in rats with emphysema caused by cigarette smoke exposure and intratracheal lipopolysaccharide instillation in vivo. During the induction of emphysema in rats, administration of SRT1720 improved lung function including airway resistance and pulmonary dynamic compliance. SRT1720 treatment up-regulated the levels of surfactant protein (SP)A, SPC, SIRT1 and forkhead box O 3, increased SIRT1 activity, down-regulated the level of p53 and inhibited AECII apoptosis. Lung injury caused by emphysema was alleviated after SRT1720 treatment. SRT1720 could protect against AECII apoptosis in rats with emphysema and thus could be used in COPD treatment.

  13. Angiotensin II type I receptor (AT1R) is an independent prognosticator of esophageal squamous cell carcinoma and promotes cells proliferation via mTOR activation

    PubMed Central

    Li, Shau-Hsuan; Lu, Hung-I; Chang, Alice Y.W.; Huang, Wan-Ting; Lin, Wei-Che; Lee, Ching-Chang; Tien, Wan-Yu; Lan, Ya-Chun; Tsai, Hsin-Ting; Chen, Chang-Han

    2016-01-01

    Background The aim of this study was to investigate the effects of the angiotensin II/ angiotensin II type I receptor (AT1R) and angiotensin II type II receptor (AT2R) signaling pathway in esophageal squamous cell carcinoma (ESCC). Methods Immunohistochemistry was performed to evaluate the expression levels of AT1R and AT2R in tissues from 152 surgically resected ESCC patients, and those expression levels were then correlated with treatment outcomes. The angiotensin II/AT1R/AT2R signaling pathway and its biological effects in the context of ESCC were investigated in vitro and in vivo. Results In human samples, AT1R overexpression was univariately associated with inferior overall survival and remained multivariately independent (hazard ratio=1.812). In vitro, angiotensin II stimulated the growth of ESCC cells in a dose-dependent manner. Treatment with irbesartan or AT1R-RNAi knockdown but not treatment with PD123319 significantly decreased the level of angiotensin II-induced ESCC cell proliferation. Angiotensin II also caused mTOR activation in a dose-dependent manner, and everolimus or mTOR-RNAi knockdown significantly suppressed the level of angiotensin II-induced ESCC cell proliferation. Furthermore, AT1R-RNAi knockdown suppressed the activation of mTOR. Clinically, AT1R expression was also correlated with phosphorylated mTOR expression. In a xenograft model, local angiotensin II injection enhanced tumor growth, and this effect could be decreased by treatment with irbesartan or everolimus. In a 4-NQO-induced-ESCC murine model, irbesartan significantly decreased the incidence of esophageal tumor. Conclusions These findings suggest that AT1R overexpression is an independent adverse prognosticator for patients with ESCC and that angiotensin II/AT1R signaling stimulates ESCC growth, in part through mTOR activation. PMID:27564102

  14. Development and application of a new Silent reporter system to quantitate the activity of enhancer elements in the type II Collagen Gene.

    PubMed

    Ito, Kazuo; Shinomura, Tamayuki

    2016-07-01

    Type II collagen is a major component of cartilage, which provide structural stiffness to the tissue. As a sufficient amount of type II collagen is critical for maintaining the biomechanical properties of cartilage, its expression is tightly regulated in chondrocytes. Therefore, it is essential to elucidate in detail the transcriptional mechanism that controls expression of type II collagen, in particular by two enhancer elements we recently discovered. To systematically analyze and compare enhancer activities, we developed a novel reporter assay system that exploits site-specific integration of promoter and enhancer elements to activate a transcriptionally silent reporter gene. Using this system, we found that the enhancer elements have distinct characteristics, with one exhibiting additive effects and the other exhibiting synergistic effects when repeated in tandem.

  15. 11 beta-Hydroxysteroid dehydrogenase type II in the human endometrium: localization and activity during the menstrual cycle.

    PubMed

    Smith, R E; Salamonsen, L A; Komesaroff, P A; Li, K X; Myles, K M; Lawrence, M; Krozowski, Z

    1997-12-01

    The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) is a potent inactivator of glucocorticoids and is present in high amounts in the placental syncytiotrophoblast and sodium-transporting epithelia. Placental 11 beta HSD2 is thought to protect the fetus from high circulating levels of maternal glucocorticoids, whereas the renal enzyme is important in conferring aldosterone specificity on the mineralocorticoid receptor. An isoform of 11 beta HSD (11 beta HSD1) is also present in a wide range of tissues, but usually acts as an oxoreductase, converting the biologically inactive cortisone to cortisol. In the present study we have used an immunopurified antibody to the carboxy-terminus of human 11 beta HSD2 (HUH23) to demonstrate localization of the enzyme in luminal and glandular epithelia of human endometrium. In some specimens staining was uniformly distributed, but in others there was clear evidence of heterogeneity both between and within epithelia. Although 11 beta HSD2 was found mainly in the cytoplasm, some cells showed evidence of nuclear staining only. Western blot analysis showed a band at 41 kDa in endometrium and myometrium, confirming the presence of 11 beta HSD2. Measurement of activity throughout the menstrual cycle showed that mean levels (+/- SEM) of activity were 156 +/- 17 and 6.1 +/- 1.1 pmol product/min.g homogenate protein for 11 beta HSD2 and 11 beta HSD1, respectively. Patients taking combined estrogen/progesterone contraceptives had significantly lower activities of both enzymes (76 +/- 19 and 1.9 +/- 0.4; both P < 0.01) compared with the control group. 11 beta HSD2 activity was significantly higher in the secretory than in the proliferative phase of the cycle in controls (193 +/- 22 vs. 120 +/- 23; P < 0.05). All groups contained outliers with elevated enzyme activities, with some patients displaying 11 beta HSD2 levels comparable to those observed in human kidney (> 1000 pmol/min.g). Further analysis showed that there was a

  16. Light echoes - Type II supernovae

    NASA Technical Reports Server (NTRS)

    Schaefer, Bradley E.

    1987-01-01

    Type II supernovae (SNs) light curves show a remarkable range of shapes. Data have been collected for the 12 Type II SNs that have light curve information for more than four months past maximum. Contrary to previous reports, it is found that (1) the decay rate after 100 days past maximum varies by almost an order of magnitude and (2) the light curve shapes are not bimodally distributed, but actually form a continuum. In addition, it is found that the extinctions to the SNs are related to the light curve shapes. This implies that the absorbing dust is local to the SNs. The dust is likely to be part of a circumstellar shell emitted by the SN progenitor that Dwek (1983) has used to explain infrared echoes. The optical depth of the shell can get quite large. In such cases, it is found that the photons scattered and delayed by reflection off dust grains will dominate the light curve several months after peak brightness. This 'light echo' offers a straightforward explanation of the diversity of Type II SN light curves.

  17. P2Y2 receptor activation opens pannexin-1 channels in rat carotid body type II cells: potential role in amplifying the neurotransmitter ATP

    PubMed Central

    Zhang, Min; Piskuric, Nikol A; Vollmer, Cathy; Nurse, Colin A

    2012-01-01

    Signal processing in the carotid body (CB) is initiated at receptor glomus (or type I) cells which depolarize and release the excitatory neurotransmitter ATP during chemoexcitation by hypoxia and acid hypercapnia. Glomus cell clusters (GCs) occur in intimate association with glia-like type II cells which express purinergic P2Y2 receptors (P2Y2Rs) but their function is unclear. Here we immunolocalize the gap junction-like protein channel pannexin-1 (Panx-1) in type II cells and show Panx-1 mRNA expression in the rat CB. As expected, type II cell activation within or near isolated GCs by P2Y2R agonists, ATP and UTP (100 μm), induced a rise in intracellular [Ca2+]. Moreover in perforated-patch whole cell recordings from type II cells, these agonists caused a prolonged depolarization and a concentration-dependent, delayed opening of non-selective ion channels that was prevented by Panx-1 blockers, carbenoxolone (5 μm) and 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS; 10 μm). Because Panx-1 channels serve as conduits for ATP release, we hypothesized that paracrine, type II cell P2Y2R activation leads to ATP-induced ATP release. In proof-of-principle experiments we used co-cultured chemoafferent petrosal neurones (PNs), which express P2X2/3 purinoceptors, as sensitive biosensors of ATP released from type II cells. In several cases, UTP activation of type II cells within or near GCs led to depolarization or increased firing in nearby PNs, and the effect was reversibly abolished by the selective P2X2/3 receptor blocker, pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS; 10 μm). We propose that CB type II cells may function as ATP amplifiers during chemotransduction via paracrine activation of P2Y2Rs and Panx-1 channels. PMID:22733659

  18. Sulfoxide stimulation of chondrogenesis in limb mesenchyme is accompanied by an increase in type II collagen enhancer activity

    SciTech Connect

    Horton, W.E. Jr.; Higginbotham, J.D. )

    1991-05-01

    We have utilized a modification of the limb bud mesenchyme micromass culture system to screen compounds that might stimulate chondrogenesis. Two compounds in the sulfoxide family (methylphenylsulfoxide and p-chlorophenyl methyl sulfoxide) were stimulatory at 10(-2) M and 10(-3) M, respectively; whereas other sulfoxides and organic solvents were not active at these concentrations. In addition, specific growth factors (basic FGF, IGF-I, IGF-II) were not chondroinductive at concentrations that are active in other cell systems. Both sulfoxide compounds stimulated cartilage nodule formation, ({sup 35}S)sulfate incorporation, and activity of the regulatory sequences of the collagen II gene. In contrast, transforming growth factor beta-1 (10 ng/ml) stimulated sulfate incorporation but produced only a diffuse deposition of cartilage matrix and reduced the ability of the cells to utilize the regulatory sequences of the collagen II gene. The sulfoxides appear to promote the differentiation of limb bud cells to chondrocytes and thus exhibit chondroinductive activity.

  19. An unexpected Schiff base-type Ni(II) complex: synthesis, crystal structures, fluorescence, electrochemical property and SOD-like activities.

    PubMed

    Chai, Lan-Qin; Zhang, Hong-Song; Huang, Jiao-Jiao; Zhang, Yu-Li

    2015-02-25

    An unexpected Schiff base-type Ni(II) complex, [Ni(L(2))2]⋅CH3OH (HL(2) = 1-(2-{[(E)-3, 5-dibromo-2-hydroxybenzylidene]amino}phenyl)ethanone oxime), has been synthesized via complexation of Ni(II) acetate tetrahydrate with HL(1) (2-(3,5-dibromo-2-hydroxyphenyl)-4-methyl-1,2-dihydroquinazoline 3-oxide) originally. HL(1) and its corresponding Ni(II) complex were characterized by IR, (1)H NMR spectra, as well as by elemental analysis, UV-Vis and emission spectroscopy, respectively. Crystal structures of the ligand and complex have been determined by single-crystal X-ray diffraction. Each complex links two other molecules into an infinite 1-D chain via intermolecular hydrogen bonding interactions. Moreover, the electrochemical property of the nickle complex was studied by cyclic voltammetry. In addition, SOD-like activities of HL(1) and Ni(II) complex were also investigated.

  20. Ozone and aging up-regulate type II metacaspase gene expression and global metacaspase activity in the leaves of field-grown maize (Zea mays L.) plants.

    PubMed

    Ahmad, Rafiq; Zuily-Fodil, Yasmine; Passaquet, Chantal; Bethenod, Olivier; Roche, Romain; Repellin, Anne

    2012-05-01

    Maize plants (Zea mays L. cv. NK Perform) were exposed to O(3)-enriched air, using a new field fumigation system. Transcriptional changes for three type II-metacaspase genes were studied in the leaves (ranks 10 and 12), using quantitative real-time PCR. Global metacaspase activity was measured using metacaspase-specific synthetic tripeptide Boc-GRR-AMC. Aging had little effect on mRNA accumulation whereas four to six-fold increases were observed for the most O(3)-responsive type II metacaspase genes, in the older leaves 10. Global metacaspase activity increased by 257% and 333% in leaves 12 and 10, respectively, in response to the highest cumulated concentration. In non-fumigated plants, metacaspase activity progressively increased over the course of the experiment and always was higher in the older leaves 10. Together, these results suggest that metacaspase-mediated proteolysis is a crucial step in leaf responses to both O(3) and age-mediated senescence.

  1. [The functional activity and count of the natural killer cells in patients with recently diagnosed diabetes mellitus types I and II].

    PubMed

    Salozhin, K V; Sura, V V; Nasonov, E L; Korneeva, M N; Smirnova, O I

    1989-01-01

    Eight patients with type I diabetes mellitus (D-I), seven patients with type II diabetes mellitus (D-11) and 8 healthy donors were examined. The disease standing did not exceed 1 year since the moment of the diagnosis establishment. The patients with D-I manifested activation of natural killers (NK) as compared to their activity in the donors and patients with D-II (76.05 +/- 6.5%, 52.33 +/- 9.55% and 55.39 +/- 10.63%, respectively, p less than 0.01) in the presence of the attenuated response of NK to interleukin-2 and alpha-interferon, determined by NK prestimulation. The amount of NK (CD16-positive) in D-I was significantly less than in the donors and patients with D-II. The high activity of NK in D-I correlated with an increase of receptor expression for transferrin on the mononuclear cells of peripheral blood. At the same time 5 out of the 8 patients with D-I and 2 patients with D-II out of the 7 demonstrated the rise of serum alpha-interferon (in the titer 1:40 and over). Activation of NK and the rise of serum interferon may be due to viral etiology of the disease and may play a role in the autoimmune process in patients suffering from D-I.

  2. Angiotensin II type 2 receptor regulates ROMK-like K+ channel activity in the renal cortical collecting duct during high dietary K+ adaptation

    PubMed Central

    Liao, Yi; Zavilowitz, Beth; Ren, Jin; Liu, Wen; Chan, Pokman; Rohatgi, Rajeev; Estilo, Genevieve; Jackson, Edwin K.; Wang, Wen-Hui; Satlin, Lisa M.

    2014-01-01

    The kidney adjusts K+ excretion to match intake in part by regulation of the activity of apical K+ secretory channels, including renal outer medullary K+ (ROMK)-like K+ channels, in the cortical collecting duct (CCD). ANG II inhibits ROMK channels via the ANG II type 1 receptor (AT1R) during dietary K+ restriction. Because AT1Rs and ANG II type 2 receptors (AT2Rs) generally function in an antagonistic manner, we sought to characterize the regulation of ROMK channels by the AT2R. Patch-clamp experiments revealed that ANG II increased ROMK channel activity in CCDs isolated from high-K+ (HK)-fed but not normal K+ (NK)-fed rats. This response was blocked by PD-123319, an AT2R antagonist, but not by losartan, an AT1R antagonist, and was mimicked by the AT2R agonist CGP-42112. Nitric oxide (NO) synthase is present in CCD cells that express ROMK channels. Blockade of NO synthase with N-nitro-l-arginine methyl ester and free NO with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt completely abolished ANG II-stimulated ROMK channel activity. NO enhances the synthesis of cGMP, which inhibits phosphodiesterases (PDEs) that normally degrade cAMP; cAMP increases ROMK channel activity. Pretreatment of CCDs with IBMX, a broad-spectrum PDE inhibitor, or cilostamide, a PDE3 inhibitor, abolished the stimulatory effect of ANG II on ROMK channels. Furthermore, PKA inhibitor peptide, but not an activator of the exchange protein directly activated by cAMP (Epac), also prevented the stimulatory effect of ANG II. We conclude that ANG II acts at the AT2R to stimulate ROMK channel activity in CCDs from HK-fed rats, a response opposite to that mediated by the AT1R in dietary K+-restricted animals, via a NO/cGMP pathway linked to a cAMP-PKA pathway. PMID:25100281

  3. Angiotensin II type 2 receptor regulates ROMK-like K⁺ channel activity in the renal cortical collecting duct during high dietary K⁺ adaptation.

    PubMed

    Wei, Yuan; Liao, Yi; Zavilowitz, Beth; Ren, Jin; Liu, Wen; Chan, Pokman; Rohatgi, Rajeev; Estilo, Genevieve; Jackson, Edwin K; Wang, Wen-Hui; Satlin, Lisa M

    2014-10-01

    The kidney adjusts K⁺ excretion to match intake in part by regulation of the activity of apical K⁺ secretory channels, including renal outer medullary K⁺ (ROMK)-like K⁺ channels, in the cortical collecting duct (CCD). ANG II inhibits ROMK channels via the ANG II type 1 receptor (AT1R) during dietary K⁺ restriction. Because AT1Rs and ANG II type 2 receptors (AT2Rs) generally function in an antagonistic manner, we sought to characterize the regulation of ROMK channels by the AT2R. Patch-clamp experiments revealed that ANG II increased ROMK channel activity in CCDs isolated from high-K⁺ (HK)-fed but not normal K⁺ (NK)-fed rats. This response was blocked by PD-123319, an AT2R antagonist, but not by losartan, an AT1R antagonist, and was mimicked by the AT2R agonist CGP-42112. Nitric oxide (NO) synthase is present in CCD cells that express ROMK channels. Blockade of NO synthase with N-nitro-l-arginine methyl ester and free NO with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt completely abolished ANG II-stimulated ROMK channel activity. NO enhances the synthesis of cGMP, which inhibits phosphodiesterases (PDEs) that normally degrade cAMP; cAMP increases ROMK channel activity. Pretreatment of CCDs with IBMX, a broad-spectrum PDE inhibitor, or cilostamide, a PDE3 inhibitor, abolished the stimulatory effect of ANG II on ROMK channels. Furthermore, PKA inhibitor peptide, but not an activator of the exchange protein directly activated by cAMP (Epac), also prevented the stimulatory effect of ANG II. We conclude that ANG II acts at the AT2R to stimulate ROMK channel activity in CCDs from HK-fed rats, a response opposite to that mediated by the AT1R in dietary K⁺-restricted animals, via a NO/cGMP pathway linked to a cAMP-PKA pathway.

  4. Dietary sodium deprivation evokes activation of brain regional neurons and down-regulation of angiotensin II type 1 receptor and angiotensin-convertion enzyme mRNA expression.

    PubMed

    Lu, B; Yang, X J; Chen, K; Yang, D J; Yan, J Q

    2009-12-15

    Previous studies have indicated that the renin-angiotensin-aldosterone system (RAAS) is implicated in the induction of sodium appetite in rats and that different dietary sodium intakes influence the mRNA expression of central and peripheral RAAS components. To determine whether dietary sodium deprivation activates regional brain neurons related to sodium appetite, and changes their gene expression of RAAS components of rats, the present study examined the c-Fos expression after chronic exposure to low sodium diet, and determined the relationship between plasma and brain angiotensin I (ANG I), angiotensin II (ANG II) and aldosterone (ALD) levels and the sodium ingestive behavior variations, as well as the effects of prolonged dietary sodium deprivation on ANG II type 1 (AT1) and ANG II type 2 (AT2) receptors and angiotensin-convertion enzyme (ACE) mRNA levels in the involved brain regions using the method of real-time polymerase chain reaction (PCR). Results showed that the Fos immunoreactivity (Fos-ir) expression in forebrain areas such as subfornical organ (SFO), paraventricular hypothalamic nuclei (PVN), supraoptic nucleus (SON) and organum vasculosum laminae terminalis (OVLT) all increased significantly and that the levels of ANG I, ANG II and ALD also increased in plasma and forebrain in rats fed with low sodium diet. In contrast, AT1, ACE mRNA in PVN, SON and OVLT decreased significantly in dietary sodium depleted rats, while AT2 mRNA expression did not change in the examined areas. These results suggest that many brain areas are activated by increased levels of plasma and/or brain ANG II and ALD, which underlies the elevated preference for hypertonic salt solution after prolonged exposure to low sodium diet, and that the regional AT1 and ACE mRNA are down-regulated after dietary sodium deprivation, which may be mediated by increased ANG II in plasma and/or brain tissue.

  5. Moderately luminous Type II supernovae

    NASA Astrophysics Data System (ADS)

    Inserra, C.; Pastorello, A.; Turatto, M.; Pumo, M. L.; Benetti, S.; Cappellaro, E.; Botticella, M. T.; Bufano, F.; Elias-Rosa, N.; Harutyunyan, A.; Taubenberger, S.; Valenti, S.; Zampieri, L.

    2013-07-01

    Context. Core-collapse Supernovae (CC-SNe) descend from progenitors more massive than about 8 M⊙. Because of the young age of the progenitors, the ejecta may eventually interact with the circumstellar medium (CSM) via highly energetic processes detectable in the radio, X-ray, ultraviolet (UV) and, sometimes, in the optical domains. Aims: In this paper we present ultraviolet, optical and near infrared observations of five Type II SNe, namely SNe 2009dd, 2007pk, 2010aj, 1995ad, and 1996W. Together with few other SNe they form a group of moderately luminous Type II events. We investigate the photometric similarities and differences among these bright objects. We also attempt to characterise them by analysing the spectral evolutions, in order to find some traces of CSM-ejecta interaction. Methods: We collected photometry and spectroscopy with several telescopes in order to construct well-sampled light curves and spectral evolutions from the photospheric to the nebular phases. Both photometry and spectroscopy indicate a degree of heterogeneity in this sample. Modelling the data of SNe 2009dd, 2010aj and 1995ad allows us to constrain the explosion parameters and the properties of the progenitor stars. Results: The light curves have luminous peak magnitudes (-16.95 < MB < -18.70). The ejected masses of 56Ni for three SNe span a wide range of values (2.8 × 10-2 M⊙ < M(56Ni)< 1.4 × 10-1 M⊙), while for a fourth (SN 2010aj) we could determine a stringent upper limit (7 × 10-3 M⊙). Clues of interaction, such as the presence of high velocity (HV) features of the Balmer lines, are visible in the photospheric spectra of SNe 2009dd and 1996W. For SN 2007pk we observe a spectral transition from a Type IIn to a standard Type II SN. Modelling the observations of SNe 2009dd, 2010aj and 1995ad with radiation hydrodynamics codes, we infer kinetic plus thermal energies of about 0.2-0.5 foe, initial radii of 2-5 × 1013 cm and ejected masses of ~5.0-9.5 M⊙. Conclusions: These

  6. Angiotensin II Promotes the Development of Carotid Atherosclerosis in Type 2 Diabetes Patients via Regulating the T Cells Activities: A Cohort Study

    PubMed Central

    Wang, Kai; Jin, Feng; Zhang, Zhanpu; Sun, Xiaochuan

    2016-01-01

    Background Specific T cell phenotype has been reported to potentially contribute to the development of angiotensin II (Ang II)-induced several vascular disorders. Type 2 diabetes mellitus (T2DM) is intimately associated with cardiovascular disease. The present study aimed to investigate the relationship between T cell phenotypes and Ang II in T2DM patients combined with carotid atherosclerosis (CA). Material/Methods This study was performed on 50 patients with T2DM in our hospital. Based on the presence of CA, they were divided into CA group (presence of CA, n=30) or T2DM group (absence of CA, n=20). Additionally, 10 healthy participants were selected as controls. Basic characteristics of all participants were collected and recorded. Peripheral blood mononuclear cells (PBMCs) isolated from patients and controls with or without Ang II and Ang II receptor blocker (ARB) treatment were used to detect Th1, Th2, and Th17 cell proportions, mRNA levels of T-bet, GATA3, and RORγt as well as the expression of IFN-γ, IL-4, and IL-17 by flow cytometry, ELISA, and Real-Time PCR. Results Ang II levels were notably higher in patients in the CA group than those in the T2DM and control group (p<0.05). Th1 and Th17 positive cells, mRNA levels of T-bet and RORγt as well as the expression of IFN-γ and IL-17 were significantly increased in the CA group compared with the T2DM group and control group (p<0.05). Moreover, the activities of T cells and related cytokines were significantly increased of healthy controls after Ang II treatment (p<0.05), while these changes were notably weakened by ARB treatment (p<0.05). Conclusions Ang II promotes the development of CA in T2DM patients by regulating T cells activities. PMID:27782101

  7. Enteropeptidase, a type II transmembrane serine protease.

    PubMed

    Zheng, X Long; Kitamoto, Yasunori; Sadler, J Evan

    2009-06-01

    Enteropeptidase, a type II transmembrane serine protease, is localized to the brush border of the duodenal and jejunal mucosa. It is synthesized as a zymogen (proenteropeptidase) that requires activation by another protease, either trypsin or possibly duodenase. Active enteropeptidase then converts the pancreatic precursor, trypsinogen, to trypsin by cleavage of the specific trypsinogen activation peptide, Asp-Asp-Asp-Asp-Lys- Ile that is highly conserved in vertebrates. Trypsin, in turn, activates other digestive zymogens such as chymotrypsinogen, proelastase, procarboxypeptidase and prolipase in the lumen of the gut. The important biological function of enteropeptidase is highlighted by the manifestation of severe diarrhea, failure to thrive, hypoproteinemia and edema as a result of congenital deficiency of enteropeptidase activity in the gut. Conversely, duodenopancreatic reflux of proteolytically active enteropeptidase may cause acute and chronic pancreatitis.

  8. Clustering, cosmology and a new era of black hole demographics- II. The conditional luminosity functions of Type 2 and Type 1 active galactic nuclei

    NASA Astrophysics Data System (ADS)

    Ballantyne, D. R.

    2017-01-01

    The orientation-based unification model of active galactic nuclei (AGNs) posits that the principle difference between obscured (Type 2) and unobscured (Type 1) AGNs is the line of sight into the central engine. If this model is correct then there should be no difference in many of the properties of AGN host galaxies (e.g. the mass of the surrounding dark matter haloes). However, recent clustering analyses of Type 1 and Type 2 AGNs have provided some evidence for a difference in the halo mass, in conflict with the orientation-based unified model. In this work, a method to compute the conditional luminosity function (CLF) of Type 2 and Type 1 AGNs is presented. The CLF allows many fundamental halo properties to be computed as a function of AGN luminosity, which we apply to the question of the host halo masses of Type 1 and 2 AGNs. By making use of the total AGN CLF, the Type 1 X-ray luminosity function, and the luminosity-dependent Type 2 AGN fraction, the CLFs of Type 1 and 2 AGNs are calculated at z ≈ 0 and 0.9. At both z, there is no statistically significant difference in the mean halo mass of Type 2 and 1 AGNs at any luminosity. There is marginal evidence that Type 1 AGNs may have larger halo masses than Type 2s, which would be consistent with an evolutionary picture where quasars are initially obscured and then subsequently reveal themselves as Type 1s. As the Type 1 lifetime is longer, the host halo will increase somewhat in mass during the Type 1 phase. The CLF technique will be a powerful way to study the properties of many AGNs subsets (e.g. radio-loud, Compton-thick) as future wide-area X-ray and optical surveys substantially increase our ability to place AGNs in their cosmological context.

  9. CA150, a nuclear protein associated with the RNA polymerase II holoenzyme, is involved in Tat-activated human immunodeficiency virus type 1 transcription.

    PubMed Central

    Suñé, C; Hayashi, T; Liu, Y; Lane, W S; Young, R A; Garcia-Blanco, M A

    1997-01-01

    Maximal human immunodeficiency virus type 1 (HIV-1) gene expression requires specific cellular factors in addition to the virus-encoded trans-activator protein Tat and the RNA element TAR. We developed a functional assay, based on transcriptional activation in vitro, to identify these cellular factors. Here, we describe the purification and molecular cloning of CA150, a nuclear protein that is associated with the human RNA polymerase II holoenzyme and is involved in Tat-dependent HIV-1 transcriptional activation. The sequence of CA150 contains an extensive glutamine- and alanine-rich repeat that is found in transcriptional modulators such as GAL11 and SSN6 in Saccharomyces cerevisiae and Zeste in Drosophila melanogaster. Immunodepletion of CA150 abolished Tat trans activation in vitro. Moreover, overexpression of a mutant CA150 protein specifically and dramatically decreased Tat-mediated activation of the HIV-1 promoter in vivo, strongly suggesting a role for CA150 in HIV-1 gene regulation. Immunoprecipitation experiments demonstrated that both CA150 and Tat associate with the RNA polymerase II holoenzyme. Furthermore, we found that functional Tat associates with the holoenzyme whereas activation-deficient Tat mutants do not. Thus, we propose that Tat action is transduced via an RNA polymerase II holoenzyme that contains CA150. PMID:9315662

  10. Type II Diabetes Disparities in Diverse Women: The Potential Roles of Body Composition, Diet, and Physical Activity

    PubMed Central

    Crawford, Margaret A.; Mendoza-Vasconez, Andrea S.; Larsen, Britta A.

    2016-01-01

    The rates of diabetes in the U.S. are rapidly increasing, and vary widely across different racial/ethnic groups. This paper explores the potential contribution of body composition, diet, and physical activity in explaining diabetes disparities across women of different racial and ethnic backgrounds. For body composition, racial/ethnic groups differ widely by BMI, distribution of body mass, and quantity and type of adipose tissue. Dietary patterns that vary across race/ethnicity include consumption of meat, added sugars, high-glycemic carbohydrates, and fast food. Additionally, physical activity patterns of interest include aerobic vs. muscle-strengthening exercises, and the purpose of physical activity (leisure, occupation, or transportation). Overall, these variables provide a partial picture of the source of these widening disparities, and could help guide future research in addressing and reducing diabetes disparities. PMID:26648099

  11. Neurofibromatosis type II presenting as vertical diplopia.

    PubMed

    Sokwala, Ahmed; Knapp, Christopher; Gottlob, Irene

    2004-09-01

    Neurofibromatosis type II (NF II) is rare and most commonly presents with hearing loss, tinnitus and/or vestibular disturbance in the third decade of life. The authors describe a rare case presenting with NF II with vertical diplopia due to IV(th) nerve palsy. The patient was otherwise asymptomatic despite multiple extensive lesions on MRI.

  12. Resemblance and Dissemblance of Arabidopsis Type II Peroxiredoxins: Similar Sequences for Divergent Gene Expression, Protein Localization, and Activity1

    PubMed Central

    Bréhélin, Claire; Meyer, Etienne H.; de Souris, Jean-Paul; Bonnard, Géraldine; Meyer, Yves

    2003-01-01

    The Arabidopsis type II peroxiredoxin (PRXII) family is composed of six different genes, five of which are expressed. On the basis of the nucleotide and protein sequences, we were able to define three subgroups among the PRXII family. The first subgroup is composed of AtPRXII-B, -C, and -D, which are highly similar and localized in the cytosol. AtPRXII-B is ubiquitously expressed. More striking is the specific expression of AtPRXII-C and AtPRXII-D localized in pollen. The second subgroup comprises the mitochondrial AtPRXII-F, the corresponding gene of which is expressed constitutively. We show that AtPRXII-E, belonging to the last subgroup, is expressed mostly in reproductive tissues and that its product is addressed to the plastid. By in vitro enzymatic experiments, we demonstrate that glutaredoxin is the electron donor of recombinant AtPRXII-B for peroxidase reaction, but the donors of AtPRXII-E and AtPRXII-F have still to be identified. PMID:12913160

  13. Completeness assessment of type II active pharmaceutical ingredient drug master files under generic drug user fee amendment: review metrics and common incomplete items.

    PubMed

    Zhang, Huyi; Li, Haitao; Song, Wei; Shen, Diandian; Skanchy, David; Shen, Kun; Lionberger, Robert A; Rosencrance, Susan M; Yu, Lawrence X

    2014-09-01

    Under the Generic Drug User Fee Amendments (GDUFA) of 2012, Type II active pharmaceutical ingredient (API) drug master files (DMFs) must pay a user fee and pass a Completeness Assessment (CA) before they can be referenced in an Abbreviated New Drug Application (ANDA), ANDA amendment, or ANDA prior approval supplement (PAS). During the first year of GDUFA implementation, from October 1, 2012 to September 30, 2013, approximately 1,500 Type II API DMFs received at least one cycle of CA review and more than 1,100 Type II DMFs were deemed complete and published on FDA's "Available for Reference List". The data from CA reviews were analyzed for factors that influenced the CA review process and metrics, as well as the areas of DMF submissions which most frequently led to an incomplete CA status. The metrics analysis revealed that electronic DMFs appear to improve the completeness of submission and shorten both the review and response times. Utilizing the CA checklist to compile and proactively update the DMFs improves the chance for the DMFs to pass the CA in the first cycle. However, given that the majority of DMFs require at least two cycles of CA before being deemed complete, it is recommended that DMF fees are paid 6 months in advance of the ANDA submissions in order to avoid negatively impacting the filling status of the ANDAs.

  14. CHARACTERIZATION OF A SAMPLE OF INTERMEDIATE-TYPE ACTIVE GALACTIC NUCLEI. II. HOST BULGE PROPERTIES AND BLACK HOLE MASS ESTIMATES

    SciTech Connect

    Benitez, Erika; Cruz-Gonzalez, Irene; Martinez, Benoni; Jimenez-Bailon, Elena; Mendez-Abreu, Jairo; Lopez-Martin, Luis; Fuentes-Carrera, Isaura; Chavushyan, Vahram; Leon-Tavares, Jonathan

    2013-02-15

    We present a study of the host bulge properties and their relations with the black hole mass for a sample of 10 intermediate-type active galactic nuclei (AGNs). Our sample consists mainly of early-type spirals, four of them hosting a bar. For 70{sup +10} {sub -17}% of the galaxies, we have been able to determine the type of the bulge, and find that these objects probably harbor a pseudobulge or a combination of classical bulge/pseudobulge, suggesting that pseudobulges might be frequent in intermediate-type AGNs. In our sample, 50% {+-} 14% of the objects show double-peaked emission lines. Therefore, narrow double-peaked emission lines seem to be frequent in galaxies harboring a pseudobulge or a combination of classical bulge/pseudobulge. Depending on the bulge type, we estimated the black hole mass using the corresponding M {sub BH}-{sigma}* relation and found them within a range of 5.69 {+-} 0.21 < log M {sup {sigma}}*{sub BH} < 8.09 {+-} 0.24. Comparing these M {sup {sigma}}*{sub BH} values with masses derived from the FWHM of H{beta} and the continuum luminosity at 5100 A from their SDSS-DR7 spectra (M {sub BH}), we find that 8 out of 10 (80{sup +7} {sub -17}%) galaxies have black hole masses that are compatible within a factor of 3. This result would support that M {sub BH} and M {sup {sigma}}*{sub BH} are the same for intermediate-type AGNs, as has been found for type 1 AGNs. However, when the type of the bulge is taken into account, only three out of the seven (43{sup +18} {sub -15}%) objects of the sample have their M {sup {sigma}}*{sub BH} and M {sub BH} compatible within 3{sigma} errors. We also find that estimations based on the M {sub BH}-{sigma}* relation for pseudobulges are not compatible in 50% {+-} 20% of the objects.

  15. Fits, pyridoxine, and hyperprolinaemia type II.

    PubMed

    Walker, V; Mills, G A; Peters, S A; Merton, W L

    2000-03-01

    The rare inherited disorder hyperprolinaemia type II presents with fits in childhood, usually precipitated by infection. A diagnosis of hyperprolinaemia type II and vitamin B(6) deficiency was made in a well nourished child with fits. It is thought that pyridoxine deficiency was implicated in her fits and was the result of inactivation of the vitamin by the proline metabolite, pyrroline-5-carboxylate.

  16. Hearing Restoration in Neurofibromatosis Type II Patients

    PubMed Central

    Lee, Jeon Mi; Chang, Jin Woo; Choi, Jae Young

    2016-01-01

    Patients with neurofibromatosis type II will eventually succumb to bilateral deafness. For patients with hearing loss, modern medical science technology can provide efficient hearing restoration through a number of various methods. In this article, several hearing restoration methods for patients with neurofibromatosis type II are introduced. PMID:27189272

  17. Fine structure of the age-chromospheric activity relation in solar-type stars. I. The Ca II infrared triplet: Absolute flux calibration

    NASA Astrophysics Data System (ADS)

    Lorenzo-Oliveira, D.; Porto de Mello, G. F.; Dutra-Ferreira, L.; Ribas, I.

    2016-10-01

    Context. Strong spectral lines are useful indicators of stellar chromospheric activity. They are physically linked to the convection efficiency, differential rotation, and angular momentum evolution and are a potential indicator of age. However, for ages > 2 Gyr, the age-activity relationship remains poorly constrained thus hampering its full application. Aims: The Ca II infrared triplet (IRT lines, λλ 8498, 8542, and 8662) has been poorly studied compared to classical chromospheric indicators. We report in this paper absolute chromospheric fluxes in the three Ca II IRT lines, based on a new calibration tied to up-to-date model atmospheres. Methods: We obtain the Ca II IRT absolute fluxes for 113 FGK stars from high signal-to-noise ratio (S/N) and high-resolution spectra covering an extensive domain of chromospheric activity levels. We perform an absolute continuum flux calibration for the Ca II IRT lines anchored in atmospheric models calculated as an explicit function of effective temperatures (Teff), metallicity ([Fe/H]), and gravities (log g) avoiding the degeneracy usually present in photometric continuum calibrations based solely on color indices. Results: The internal uncertainties achieved for continuum absolute flux calculations are ≈2% of the solar chromospheric flux, one order of magnitude lower than for photometric calibrations. Using Monte Carlo simulations, we gauge the impact of observational errors on the final chromospheric fluxes due to the absolute continuum flux calibration and find that Teffuncertainties are properly mitigated by the photospheric correction leaving [Fe/H] as the dominating factor in the chromospheric flux uncertainty. Conclusions: Across the FGK spectral types, the Ca II IRT lines are sensitive to chromospheric activity. The reduced internal uncertainties reported here enable us to build a new chromospheric absolute flux scale and explore the age-activity relation from the active regime down to very low activity levels and

  18. Risk of type II diabetes and hypertension associated with chronic insomnia among active component, U.S. Armed Forces, 1998-2013.

    PubMed

    Lewis, Paul E; Emasealu, Oseizame V; Rohrbeck, Patricia; Hu, Zheng

    2014-10-01

    Chronic insomnia is a common clinical complaint and its incidence in both U.S. military and civilian populations has increased. Several studies have evaluated the association between chronic insomnia and the development of other chronic diseases. This study estimates the incidence of chronic insomnia. In addition, this report examines the association between both hypertension and type II diabetes and chronic insomnia in active component military members. The Defense Medical Surveillance System was used to identify a cohort of individuals with chronic insomnia between 1998 and 2013 and to match them by age and gender with a cohort without insomnia. During 1998-2013, there were 205,740 incident cases of chronic insomnia among active component service members with an overall rate of 90.3 per 10,000 person-years. Individuals in the chronic insomnia cohort were at higher risk for type II diabetes (adjusted hazard ratio [HR], 2.17 [95% CI, 1.75-2.69]) and hypertension (adjusted HR, 2.00 [95% CI, 1.85-2.16]). Sleep hygiene education along with evaluation and treatment of persistent symptoms are of public health importance in active duty service members.

  19. Stachybotrys chartarum alters surfactant-related phospholipid synthesis and CTP:cholinephosphate cytidylyltransferase activity in isolated fetal rat type II cells.

    PubMed

    Hastings, C; Rand, T; Bergen, H T; Thliveris, J A; Shaw, A R; Lombaert, G A; Mantsch, H H; Giles, B L; Dakshinamurti, S; Scott, J E

    2005-03-01

    Stachybotry chartarum, a fungal contaminant of water-damaged buildings commonly grows on damp cellulose-containing materials. It produces a complex array of mycotoxins. Their mechanisms of action on the pulmonary system are not entirely clear. Previous studies suggest spore products may depress formation of disaturated phosphatidylcholine (DSPC), the major surface-active component of pulmonary surfactant (PS). If S. chartarum can indeed affect formation of this phospholipid, then mold exposure may be a significant issue for pulmonary function in both mature lung and developing fetal lung. To address this possibility, fetal rat type II cells, the principal source of DSPC, were used to assess effects of S. chartarum extract on formation of DSPC. Isolated fetal rat lung type II cells prelabeled with 3H-choline and incubated with spore extract showed decreased incorporation of 3H-choline into DSPC. The activity of CTP:cholinephosphate cytidylyltransferase (CPCT), the rate-limiting enzyme in phosphatidylcholine synthesis was reduced by approximately 50% by a 1:10 dilution of spore extract. Two different S. chartarum extracts (isolates from S. chartarum (Cleveland) and S. chartarum (Hawaiian)) were used to compare activity of CPCT in the presence of phosphatidylglycerol (PG), a known activator. PG produced an approximate two-fold increase in CPCT activity. The spore isolate from Hawaii did not alter enzyme activity. S. chartarum (Cleveland) eliminated the PG-induced activation of CPCT. These results support previous observations that mold products alter PS metabolism and may pose a risk in developing lung, inhibiting surfactant synthesis. Different isolates of the same species of fungus are not equivalent in terms of potential exposure risks.

  20. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models.

    PubMed

    Herter, Sylvia; Herting, Frank; Mundigl, Olaf; Waldhauer, Inja; Weinzierl, Tina; Fauti, Tanja; Muth, Gunter; Ziegler-Landesberger, Doris; Van Puijenbroek, Erwin; Lang, Sabine; Duong, Minh Ngoc; Reslan, Lina; Gerdes, Christian A; Friess, Thomas; Baer, Ute; Burtscher, Helmut; Weidner, Michael; Dumontet, Charles; Umana, Pablo; Niederfellner, Gerhard; Bacac, Marina; Klein, Christian

    2013-10-01

    We report the first preclinical in vitro and in vivo comparison of GA101 (obinutuzumab), a novel glycoengineered type II CD20 monoclonal antibody, with rituximab and ofatumumab, the two currently approved type I CD20 antibodies. The three antibodies were compared in assays measuring direct cell death (AnnexinV/PI staining and time-lapse microscopy), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and internalization. The models used for the comparison of their activity in vivo were SU-DHL4 and RL xenografts. GA101 was found to be superior to rituximab and ofatumumab in the induction of direct cell death (independent of mechanical manipulation required for cell aggregate disruption formed by antibody treatment), whereas it was 10 to 1,000 times less potent in mediating CDC. GA101 showed superior activity to rituximab and ofatumumab in ADCC and whole-blood B-cell depletion assays, and was comparable with these two in ADCP. GA101 also showed slower internalization rate upon binding to CD20 than rituximab and ofatumumab. In vivo, GA101 induced a strong antitumor effect, including complete tumor remission in the SU-DHL4 model and overall superior efficacy compared with both rituximab and ofatumumab. When rituximab-pretreated animals were used, second-line treatment with GA101 was still able to control tumor progression, whereas tumors escaped rituximab treatment. Taken together, the preclinical data show that the glyoengineered type II CD20 antibody GA101 is differentiated from the two approved type I CD20 antibodies rituximab and ofatumumab by its overall preclinical activity, further supporting its clinical investigation.

  1. Genetic heterogeneity of Usher syndrome type II.

    PubMed Central

    Pieke Dahl, S; Kimberling, W J; Gorin, M B; Weston, M D; Furman, J M; Pikus, A; Möller, C

    1993-01-01

    Usher syndrome is an autosomal recessive disorder characterised by retinitis pigmentosa and congenital sensorineural hearing loss. A gene for Usher syndrome type II (USH2) has been localised to chromosome 1q32-q41. DNA from a family with four of seven sibs affected with clinical characteristics of Usher syndrome type II was genotyped using markers spanning the 1q32-1q41 region. These included D1S70 and D1S81, which are believed to flank USH2. Genotypic results and subsequent linkage analysis indicated non-linkage of this family to these markers. The A test analysis for heterogeneity with this family and 32 other Usher type II families was statistically significant at p < 0.05. Further clinical evaluation of this family was done in light of the linkage results to determine if any phenotypic characteristics would allow for clinical identification of the unlinked type. No clear phenotypic differences were observed; however, this unlinked family may represent a previously unreported subtype of Usher type II characterised by a milder form of retinitis pigmentosa and mild vestibular abnormalities. Heterogeneity of Usher syndrome type II complicates efforts to isolate and clone Usher syndrome genes using linkage analysis and limits the use of DNA markers in early detection of Usher type II. Images PMID:7901420

  2. Activation of the angiotensin II type 1 receptor leads to movement of the sixth transmembrane domain: analysis by the substituted cysteine accessibility method.

    PubMed

    Martin, Stéphane S; Holleran, Brian J; Escher, Emanuel; Guillemette, Gaétan; Leduc, Richard

    2007-07-01

    The role of transmembrane domain six (TMD6) of the angiotensin II type 1 receptor, which is predicted to undergo conformational changes after agonist binding, was investigated using the substituted-cysteine accessibility method. Each residue in the Lys240-Leu265 fragment was mutated, one at a time, to a cysteine. The resulting mutants were expressed in COS-7 cells, which were subsequently treated with the charged sulfhydryl-specific alkylating agent methanethiosulfonate-ethylammonium (MTSEA). This treatment led to a significant reduction in binding of (125)I-[Sar(1),Ile(8)]AngII to the F249C, H256C, T260C, and V264C mutant receptors, suggesting that these residues orient themselves within the water-accessible binding pocket of the AT(1) receptor. It is noteworthy that this pattern of acquired MTSEA sensitivity was altered for TMD6 cysteines engineered in a constitutively active AT(1) receptor. Indeed, mutant F249C was insensitive to MTSEA treatment, whereas the sensitivity of mutant V264C decreased. Under these conditions, one other mutant, F261C, was found to be sensitive to MTSEA treatment. Our results suggest that constitutive activation of the AT(1) receptor causes TMD6 to pivot. This movement moves the top (extracellular side) of TMD6 toward the binding pocket and simultaneously distances the bottom (intracellular side) away from the binding pocket. Using this approach, we identified key elements within TMD6 that contribute to the activation of class A GPCRs through structural rearrangements.

  3. Resistance domain in type II superconductors

    SciTech Connect

    Gurevich, A.V.; Mints, R.G.

    1980-01-05

    We show that traveling domains with a finite resistance can exist in type II superconductors in the presence of a transport current. An experiment in which this effect generates an alternating electric field and current is proposed.

  4. Achondrogenesis type II, abnormalities of extracellular matrix.

    PubMed

    Horton, W A; Machado, M A; Chou, J W; Campbell, D

    1987-09-01

    Immune and lectin histochemical and microchemical methods were employed to study growth cartilage from seven cases of achondrogenesis type II (Langer-Saldino). The normal architecture of the epiphyseal and growth plate cartilage was replaced by a morphologically heterogeneous tissue. Some areas were comprised of vascular canals surrounded by extensive fibrous tissue and enlarged cells that had the appearance and histochemical characteristics of hypertrophic chondrocytes. Other areas contained a mixture of cells ranging from small to the enlarged chondrocytes. The extracellular matrix in the latter areas was more abundant and had characteristics of both precartilage mesenchymal matrix and typical cartilage matrix; it contained types I and II collagen, cartilage proteoglycan, fibronectin, and peanut agglutinin binding glycoconjugate(s). Peptide mapping of cyanogen bromide cartilage collagen peptides revealed the presence of types I and II collagen. These observations could be explained by a defect in the biosynthesis of type II collagen or in chondrocyte differentiation.

  5. Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma

    PubMed Central

    Herting, Frank; Friess, Thomas; Bader, Sabine; Muth, Gunter; Hölzlwimmer, Gabriele; Rieder, Natascha; Umana, Pablo

    2014-01-01

    Obinutuzumab (GA101) is a novel glycoengineered type II CD20 antibody in development for non-Hodgkin lymphoma. We compared the anti-tumor activity of obinutuzumab and rituximab in preclinical studies using subcutaneous Z138 and WSU-DLCL2 xenograft mouse models. Obinutuzumab and rituximab were assessed alone and in combination with bendamustine, fludarabine, chlorambucil, doxorubicin and cyclophosphamide/vincristine. Owing to strong single-agent efficacy in these models, suboptimal doses of obinutuzumab were applied to demonstrate a combination effect. Obinutuzumab plus bendamustine achieved superior tumor growth inhibition versus rituximab plus bendamustine and showed a statistically significant effect versus the respective single treatments. Combinations of obinutuzumab with fludarabine, chlorambucil or cyclophosphamide/vincristine demonstrated significantly superior activity to rituximab-based treatment. Obinutuzumab monotherapy was at least as effective as rituximab plus chemotherapy in vivo, and obinutuzumab plus chemotherapy was superior to the respective monotherapies. These data support further clinical investigation of obinutuzumab plus chemotherapy. PMID:24304419

  6. Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma.

    PubMed

    Herting, Frank; Friess, Thomas; Bader, Sabine; Muth, Gunter; Hölzlwimmer, Gabriele; Rieder, Natascha; Umana, Pablo; Klein, Christian

    2014-09-01

    Obinutuzumab (GA101) is a novel glycoengineered type II CD20 antibody in development for non-Hodgkin lymphoma. We compared the anti-tumor activity of obinutuzumab and rituximab in preclinical studies using subcutaneous Z138 and WSU-DLCL2 xenograft mouse models. Obinutuzumab and rituximab were assessed alone and in combination with bendamustine, fludarabine, chlorambucil, doxorubicin and cyclophosphamide/vincristine. Owing to strong single-agent efficacy in these models, suboptimal doses of obinutuzumab were applied to demonstrate a combination effect. Obinutuzumab plus bendamustine achieved superior tumor growth inhibition versus rituximab plus bendamustine and showed a statistically significant effect versus the respective single treatments. Combinations of obinutuzumab with fludarabine, chlorambucil or cyclophosphamide/vincristine demonstrated significantly superior activity to rituximab-based treatment. Obinutuzumab monotherapy was at least as effective as rituximab plus chemotherapy in vivo, and obinutuzumab plus chemotherapy was superior to the respective monotherapies. These data support further clinical investigation of obinutuzumab plus chemotherapy.

  7. Antenatal diagnosis of achondrogenesis type II.

    PubMed

    Kodandapani, S; Ramkumar, V

    2009-01-01

    Achondrogenesis is a lethal congenital chondrodystrophy characterized by extreme micromelia, small thorax and polyhydramnios. We describe a case of achondrogenesis type II (Langer-Saldino achondrogenesis). Prenatal ultrasonography at 22-weeks gestation revealed a fetus with large head, short neck and chest, prominent abdomen and short limbs. Pregnancy was terminated. Radiologic examination of neonate revealed features of achondrogenesis type II. Routine ultrasound screening made early detection and timely management possible.

  8. Abnormal response to physical activity in femurs after heterozygous inactivation of one allele of the Col2a1 gene for type II collagen in mice.

    PubMed

    Nieminen, J; Sahlman, J; Hirvonen, T; Jämsä, T; Tuukkanen, J; Kovanen, V; Kröger, H; Jurvelin, J; Arita, M; Li, S W; Prockop, D J; Hyttinen, M M; Helminen, H J; Lapveteläinen, T; Puustjärvi, K

    2005-08-01

    The objective of this study was to evaluate the influence of heterozygous inactivation of one allele of the type II collagen gene (Col2a1) on biomechanical properties and mineral density of bone under physical loading conditions. C57BL/6-TGN mice with heterozygous knockout (HZK) inactivation of Col2a1 gene and their nontransgenic littermate controls were housed in individual cages with running wheels for 9 and 15 months. The running activity of each mouse was monitored continuously throughout the experiment. Bone mineral density (BMD) of mice femora was measured using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). Biomechanical properties were determined using three-point bending tests. Vertebral bone samples were prepared for quantitative polarized light microscopy and digital densitometry of proteoglycans. The concentration of total collagen and collagen cross-links were analyzed using high-performance liquid chromatograpy (HPLC). The average daily running distance was shorter for the HZK mice between the age of 4 and 15 months as compared with normal runners (P < 0.05). The ultimate breaking force was 14.8% and 23.6% (9 vs. 15 months) lower in HZK-runners than in wild-type runners. BMD of the femur was 6.1% lower in HZK-runners at the age of 9 months (P < 0.05). Physical activity increased cortical BMD in wild-type runners but not in the HZK runners at the age of 9 months. The collagen network of the HZK mice was less organized. There were only minor changes in BMD and mechanical and structural properties between sedentary HZK mice and their wild-type controls. Increased physical activity induced significantly lower bone density, mechanical properties, and organization of collagen fibers in male HZK mice. However, there were no major differences in biomechanical parameters between sedentary HZK and wild-type male mice. This suggests an important guiding role of collagen type II in bone remodelling and

  9. Type II endometrial cancers: A case series

    PubMed Central

    Lobo, Flora D.; Thomas, Eliz

    2016-01-01

    Introduction: Endometrial carcinoma ranks 3rd in India among gynecological malignancies. Endometrial cancer (EC) can be classified into two distinct groups – type I and type II, based on histology, which differs in molecular, clinical and histopathological profiles. Type II is nonestrogen dependent, nonendometrioid, more aggressive and carries poor prognosis. Although type II cancers contribute only about 10% of EC incidence, they present at advanced age and cause approximately 50% recurrence and deaths with a low 5-year, overall survival rate. Type II EC are also characterized by genetic alterations in p53, human epidermal growth factor-2/neu, p16 and E-cadherin. Materials and Methods: Endometrial carcinomas diagnosed from endometrial biopsies and hysterectomy specimens received in the Department of Pathology, Kasturba Medical College, Mangalore, from January 2007 to June 2012 were included in the study. Clinicopathological analysis of the 84 cases of EC was done with emphasis on morphology. p53 immunostaining was performed in two cases of serous carcinoma. Results: Out of a total of 84 cases of EC, ten cases were of type II (11.9%). Out of which, eight were serous carcinoma (9.5%) and two clear cell (2.4%). p53 immunostain was strongly positive in the serous papillary carcinomas. The age of the patients ranged from 45 to 75 years. Myometrial invasion was more than half. Treatment was hysterectomy followed by aggressive chemotherapy. Conclusion: Of the type II EC, serous carcinoma is the most common type. Clinical presentation and prognosis differs in comparison to type I EC, thus the recognition of this type of EC is pivotal. PMID:27499593

  10. Amount, type, and timing of recreational physical activity in relation to colon and rectal cancer in older adults: the Cancer Prevention Study II Nutrition Cohort.

    PubMed

    Chao, Ann; Connell, Cari J; Jacobs, Eric J; McCullough, Marjorie L; Patel, Alpa V; Calle, Eugenia E; Cokkinides, Vilma E; Thun, Michael J

    2004-12-01

    Physical activity has consistently been associated with lower risk of colon cancer, but information is limited on the amount, type, and timing of activities. The relationship between physical activity and rectal cancer is unclear. We examined characteristics of recreational physical activity in relation to colon and rectal cancer in the Cancer Prevention Study II Nutrition Cohort of 70,403 men and 80,771 women (median age, 63 years); 940 colon and 390 rectal cancers were identified from enrollment in 1992 to 1993 through August 1999. The multivariate-adjusted rate ratios (95% confidence intervals) associated with any recreational physical activity compared with none were 0.87 (0.71-1.06) for colon cancer and 0.70 (0.53-0.93) for rectal cancer. Colon cancer risk decreased significantly with increasing total hours (P for trend without reference group = 0.007) and metabolic equivalent hours (P for trend = 0.006) per week of activities. No clear decrease in rectal cancer risk was seen with increasing hours per week of physical activity. Rate ratios (95% confidence intervals) were 0.72 (0.52-0.98) for <2 hours, 0.68 (0.47-0.97) for 2 to 3 hours, 0.59 (0.41-0.83) for 4 to 6 hours, and 0.83 (0.59-1.16) for >/=7 hours per week of physical activity compared with none. Past exercise, as reported in 1982, was not associated with risk of either colon or rectal cancer. We conclude that increasing amounts of time spent at recreational physical activity are associated with substantially lower risk of colon cancer and that recreational physical activity is associated with lower risk of rectal cancer in older men and women.

  11. Prediction of Type II Burst Radiation for Large CME Events

    NASA Astrophysics Data System (ADS)

    Cairns, I. H.; Schmidt, J. M.

    2013-12-01

    Type IIs are associated with shocks in the corona and solar wind, either driven by CMEs or else blast waves. Recent quantitative theories for type II radiation show that the amount of radiation depends on the speed and spatial extent of the 3D shock, as well as on the background plasma, magnetic field configuration, and the number of superthermal electrons available for acceleration by the shock. In principle, then, Type II bursts may provide 1-3 day warnings of large and fast CMEs that might produce space weather at Earth. In this paper we couple the advanced 3D MHD BATS-R-US code of Toth, Gombosi, and colleagues with our new ``bolt-on'' theory for type II emission. The modeling includes initialization with coronal and active region magnetic fields reconstructed from solar magnetograms, coronal densities determined by 1 AU data, and CMEs modelled using STEREO coronagraph data. Two events with type IIs and strong CMEs are analyzed: 15 February 2011 and 7 March 2012. We demonstrate impressive accuracy in time, frequency, and intensity for both type II bursts. This strongly supports the type II theory, implies real understanding of the physics involved, and supports the near-term development of a capability to predict and track these events for space weather prediction.

  12. Methane monooxygenase from Methylosinus trichosporium OB3b. Purification and properties of a three-component system with high specific activity from a type II methanotroph.

    PubMed

    Fox, B G; Froland, W A; Dege, J E; Lipscomb, J D

    1989-06-15

    Methane monooxygenase has been purified from the Type II methanotroph Methylosinus trichosporium OB3b. As observed for methane monooxygenase isolated from Type I methanotrophs, three protein components are required: a 39.7-kDa NADH reductase containing 1 mol each of FAD and a [2Fe-2S] cluster, a 15.8-kDa protein factor termed component B that contains no metals or cofactors, and a 245-kDa hydroxylase which appears to contain an oxo- or hydroxo-bridged binuclear iron cluster. Through the use of stabilizing reagents, the hydroxylase is obtained in high yield and exhibits a specific activity 8-25-fold greater than reported for previous preparations. The component B and reductase exhibit 1.5- and 4-fold greater specific activity, respectively. Quantitation of the hydroxylase oxo-bridged cluster using EPR and Mössbauer spectroscopies reveals that the highest specific activity preparations (approximately 1700 nmol/min/mg) contain approximately 2 clusters/mol. In contrast, hydroxylase preparations exhibiting a wide range of specific activities below 500 nmol/min/mg contain approximately 1 cluster/mol on average. Efficient turnover coupled to NADH oxidation requires all three protein components. However, both alkanes and alkenes are hydroxylated by the chemically reduced hydroxylase under single turnover conditions in the absence of component B and the reductase. Neither of these components catalyzes hydroxylation individually nor do they significantly affect the yield of hydroxylated product from the chemically reduced hydroxylase. Hydroxylase reduced only to the mixed valent [Fe(II).Fe(III)] state is unreactive toward O2 and yields little hydroxylated product on single turnover. This suggests that the catalytically active species is the fully reduced form. The data presented here provide the first evidence based on catalysis that the site of the monooxygenation reaction is located on the hydroxylase. It thus appears likely that the oxo-bridged iron cluster is capable of

  13. Annotated compound data for modulators of detergent-solubilised or lipid-reconstituted respiratory type II NADH dehydrogenase activity obtained by compound library screening

    PubMed Central

    Dunn, Elyse A.; Cook, Gregory M.; Heikal, Adam

    2015-01-01

    The energy-generating membrane protein NADH dehydrogenase (NDH-2), a proposed antibacterial drug target (see “Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs” Weinstein et al. 2005 [1]), was screened for modulators of activity in either detergent-solublised or lipid reconstituted (proteolipsome) form. Here we present an annotated list of compounds identified in a small-scale screen against NDH-2. The dataset contains information regarding the libraries screened, the identities of hit compounds and the physicochemical properties governing solubility and permeability. The implications of these data for future antibiotic discovery are discussed in our associated report, “Comparison of lipid and detergent enzyme environments for identifying inhibitors of membrane-bound energy-transducing proteins” [2]. PMID:26862571

  14. Heterogeneously integrated III-V-on-silicon 2.3x μm distributed feedback lasers based on a type-II active region

    NASA Astrophysics Data System (ADS)

    Wang, Ruijun; Sprengel, Stephan; Malik, Aditya; Vasiliev, Anton; Boehm, Gerhard; Baets, Roel; Amann, Markus-Christian; Roelkens, Gunther

    2016-11-01

    We report on 2.3x μm wavelength InP-based type-II distributed feedback (DFB) lasers heterogeneously integrated on a silicon photonics integrated circuit. In the devices, a III-V epitaxial layer stack with a "W"-shaped InGaAs/GaAsSb multi-quantum-well active region is adhesively bonded to the first-order silicon DFB gratings. Single mode laser emission coupled to a single mode silicon waveguide with a side mode suppression ratio of 40 dB is obtained. In continuous-wave regime, the 2.32 μm laser operates close to room temperature (above 15 °C) and emits more than 1 mW output power with a threshold current density of 1.8 kA/cm2 at 5 °C. A tunable diode laser absorption measurement of CO is demonstrated using this source.

  15. Annotated compound data for modulators of detergent-solubilised or lipid-reconstituted respiratory type II NADH dehydrogenase activity obtained by compound library screening.

    PubMed

    Dunn, Elyse A; Cook, Gregory M; Heikal, Adam

    2016-03-01

    The energy-generating membrane protein NADH dehydrogenase (NDH-2), a proposed antibacterial drug target (see "Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs" Weinstein et al. 2005 [1]), was screened for modulators of activity in either detergent-solublised or lipid reconstituted (proteolipsome) form. Here we present an annotated list of compounds identified in a small-scale screen against NDH-2. The dataset contains information regarding the libraries screened, the identities of hit compounds and the physicochemical properties governing solubility and permeability. The implications of these data for future antibiotic discovery are discussed in our associated report, "Comparison of lipid and detergent enzyme environments for identifying inhibitors of membrane-bound energy-transducing proteins" [2].

  16. Genetics Home Reference: distal hereditary motor neuropathy, type II

    MedlinePlus

    ... distal hereditary motor neuropathy, type II distal hereditary motor neuropathy, type II Enable Javascript to view the ... PDF Open All Close All Description Distal hereditary motor neuropathy, type II is a progressive disorder that ...

  17. Type II achondrogenesis-hypochondrogenesis: identification of abnormal type II collagen.

    PubMed

    Godfrey, M; Hollister, D W

    1988-12-01

    We have extended the study of a mild case of type II achondrogenesis-hypochondrogenesis to include biochemical analyses of cartilage, bone, and the collagens produced by dermal fibroblasts. Type I collagen extracted from bone and types I and III collagen produced by dermal fibroblasts were normal, as was the hexosamine ratio of cartilage proteoglycans. Hyaline cartilage, however, contained approximately equal amounts of types I and II collagen and decreased amounts of type XI collagen. Unlike the normal SDS-PAGE mobility. Two-dimensional SDS-PAGE revealed extensive overmodification of all type II cyanogen bromide peptides in a pattern consistent with heterozygosity for an abnormal pro alpha 1(II) chain which impaired the assembly and/or folding of type II collagen. This interpretation implies that dominant mutations of the COL2A1 gene may cause type II achondrogenesis-hypochondrogenesis. More generally, emerging data implicating defects of type II collagen in the type II achondrogenesis-hypochondrogenesis-spondyloepiphyseal dysplasia congenita spectrum and in the Kniest-Stickler syndrome spectrum suggest that diverse mutations of this gene may be associated with widely differing phenotypic outcome.

  18. DO GIANT PLANETS SURVIVE TYPE II MIGRATION?

    SciTech Connect

    Hasegawa, Yasuhiro; Ida, Shigeru E-mail: ida@geo.titech.ac.jp

    2013-09-10

    Planetary migration is one of the most serious problems to systematically understand the observations of exoplanets. We clarify that the theoretically predicted type II, migration (like type I migration) is too fast, by developing detailed analytical arguments in which the timescale of type II migration is compared with the disk lifetime. In the disk-dominated regime, the type II migration timescale is characterized by a local viscous diffusion timescale, while the disk lifetime is characterized by a global diffusion timescale that is much longer than the local one. Even in the planet-dominated regime where the inertia of the planet mass reduces the migration speed, the timescale is still shorter than the disk lifetime except in the final disk evolution stage where the total disk mass decays below the planet mass. This suggests that most giant planets plunge into the central stars within the disk lifetime, and it contradicts the exoplanet observations that gas giants are piled up at r {approx}> 1 AU. We examine additional processes that may arise in protoplanetary disks: dead zones, photoevaporation of gas, and gas flow across a gap formed by a type II migrator. Although they make the type II migration timescale closer to the disk lifetime, we show that none of them can act as an effective barrier for rapid type II migration with the current knowledge of these processes. We point out that gas flow across a gap and the fraction of the flow accreted onto the planets are uncertain and they may have the potential to solve the problem. Much more detailed investigation for each process may be needed to explain the observed distribution of gas giants in extrasolar planetary systems.

  19. Type II seesaw dominance in SO(10)

    SciTech Connect

    Melfo, Alejandra; Ramirez, Alba; Senjanovic, Goran

    2010-10-01

    Grand unified theories where the neutrino mass is given by type II seesaw have the potential to provide interesting connections between the neutrino and charged fermion sectors. We explore the possibility of having a dominant type II seesaw contribution in supersymmetric SO(10). We show that this can be achieved in the model where symmetry breaking is triggered by 54 and 45 dimensional representations, without the need for additional fields other than those already required to have a realistic charged fermion mass spectrum. Physical consequences, such as the implementation of the Bajc, Senjanovic, and Vissani mechanism, the possibility of the fields responsible for type II seesaw dominance being messengers of supersymmetry breaking, and the realization of baryo and leptogenesis in these theories, are discussed.

  20. Anti-Müllerian hormone inhibits growth of AMH type II receptor-positive human ovarian granulosa cell tumor cells by activating apoptosis.

    PubMed

    Anttonen, Mikko; Färkkilä, Anniina; Tauriala, Hanna; Kauppinen, Marjut; Maclaughlin, David T; Unkila-Kallio, Leila; Bützow, Ralf; Heikinheimo, Markku

    2011-11-01

    Ovarian granulosa cell tumors (GCTs) are sex cord stromal tumors that constitute 3-5% of all ovarian cancers. GCTs usually present with an indolent course but there is a high risk of recurrence, which associates with increased mortality, and targeted treatments would be desirable. Anti-Müllerian hormone (AMH), a key factor regulating sexual differentiation of the reproductive organs, has been implicated as a growth inhibitor in ovarian cancer. GCTs and normal granulosa cells produce AMH, but its expression in large GCTs is usually downregulated. Further, as the lack of specific AMH-signaling pathway components leads to GCT development in mice, we hypothesized that AMH inhibits growth of GCTs. Utilizing a large panel of human GCT tissue samples, we found that AMH type I receptors (ALK2, ALK3 and ALK6) and type II receptor (AMHRII), as well as their downstream effectors Smad1/5, are expressed and active in GCTs. AMHRII expression was detected in the vast majority (96%) of GCTs and correlated with AMH mRNA and protein expression. AMH mRNA level was low in large GCTs, confirming previous findings on low-AMH protein expression in large human as well as mouse GCTs. To study the functional role of AMH in this peculiar ovarian cancer, we utilized a human GCT cell line (KGN) and 10 primary GCT cell cultures. We found that the AMH-Smad1/5-signaling pathway was active in these cells, and that exogenous AMH further activated Smad1/5 in KGN cells. Furthermore, AMH treatment reduced the number of KGN cells and primary GCT cells, with increasing amounts of AMH leading to augmented activation of caspase-3 and subsequent apoptosis. All in all, these data support the premise that AMH is a growth inhibitor of GCTs.

  1. Gliotoxin promotes Aspergillus fumigatus internalization into type II human pneumocyte A549 cells by inducing host phospholipase D activation.

    PubMed

    Jia, Xiaodong; Chen, Fangyan; Pan, Weihua; Yu, Rentao; Tian, Shuguang; Han, Gaige; Fang, Haiqin; Wang, Shuo; Zhao, Jingya; Li, Xianping; Zheng, Dongyu; Tao, Sha; Liao, Wanqing; Han, Xuelin; Han, Li

    2014-06-01

    The internalization of Aspergillus fumigatus into lung epithelial cells is critical for the infection process in the host. Gliotoxin is the most potent toxin produced by A. fumigatus. However, its role in A. fumigatus internalization into the lung epithelial cells is still largely unknown. In the present study, the deletion of the gliP gene regulating the production of gliotoxin in A. fumigatus suppressed the internalization of conidia into the A549 lung epithelial cells, and this suppression could be rescued by the exogenous addition of gliotoxin. At lower concentrations, gliotoxin enhanced the internalization of the conidia of A. fumigatus into A549 cells; in contrast, it inhibited the phagocytosis of J774 macrophages in a dose-dependent manner. Under a concentration of 100 ng/ml, gliotoxin had no effect on A549 cell viability but attenuated ROS production in a dose-dependent manner. Gliotoxin significantly stimulated the phospholipase D activity in the A549 cells at a concentration of 50 ng/ml. This stimulation was blocked by the pretreatment of host cells with PLD1- but not PLD2-specific inhibitor. Morphological cell changes induced by gliotoxin were observed in the A549 cells accompanying with obvious actin cytoskeleton rearrangement and a moderate alteration of phospholipase D distribution. Our data indicated that gliotoxin might be responsible for modulating the A. fumigatus internalization into epithelial cells through phospholipase D1 activation and actin cytoskeleton rearrangement.

  2. In vivo cough suppressive activity of pectic polysaccharide with arabinogalactan type II side chains of Piper nigrum fruits and its synergistic effect with piperine.

    PubMed

    Khawas, Sadhana; Nosáľová, Gabriela; Majee, Sujay Kumar; Ghosh, Kanika; Raja, Washim; Sivová, Veronika; Ray, Bimalendu

    2017-06-01

    Piper nigrum L. fruits are not only a prized spice, but also highly valued therapeutic agent that heals many ailments including asthma, cold and respiratory problems. Herein, we have investigated structural features and in vivo antitussive activity of three fractions isolated from Piper nigrum fruits. The water extract (PN-WE) upon fractionation with EtOH yielded two fractions: a soluble fraction (PN-eSf) and a precipitated (PN-ePf) one. The existence of a pectic polysaccharide with arabinogalactan type II side chains (147kDa) in PN-ePf and piperine in PN-eSf were revealed. Moreover, oligosaccharides providing fine structural details of side chains were generated from PN-ePf and then characterized. The parental water extract (PN-WE) that contained both pectic polysaccharide and piperine, after oral administration (50mgkg(-1) body weight) to guinea pigs, showed antitussive activity comparable to codeine phosphate (10mgkg(-1) body weight). The EtOH precipitated fraction (PN-ePf) containing pectic polysaccharide showed comparatively higher antitussive activity than EtOH soluble fraction (PN-eSf) that contained piperine, but their potencies are lower than the parental water extract. Significantly, the specific airway smooth muscle reactivity of all three fractions remained unchanged. Finally, pectic polysaccharide-piperine combination in parental extract synergistically enhances antitussive effect in guinea pigs.

  3. Program ACTIVE II: Design and Methods for a Multi-Center Community-Based Depression Treatment for Rural and Urban Adults with Type 2 Diabetes

    PubMed Central

    de Groot, Mary; Shubrook, Jay; Schwartz, Frank; Hornsby, W. Guyton; Pillay, Yegan; Saha, Chandan

    2015-01-01

    Objective Depression affects one in four adults with type 2 diabetes (T2DM) and is associated with worsened diabetes complications, increased health care costs and early mortality. Rural and low-income urban areas, including the Appalachian region, represent an epicenter of the T2DM epidemic. Program ACTIVE II is a comparative effectiveness treatment trial designed to test whether a combination of cognitive behavioral therapy (CBT) and community-based exercise (EXER) will offer greater improvements in diabetes and depression outcomes compared to individual treatment approaches and usual care (UC). The secondary aims are to assess changes in cardiovascular risk factors across groups and to conduct a cost-effectiveness analysis of predicted incidence of cardiovascular complications across groups. Methods The study is a 2-by-2 factorial randomized controlled trial consisting of 4 treatment groups: CBT alone, EXER alone, combination of CBT and EXER, and UC. Adults with T2DM for > 1 year and who meet DSM-IVTR criteria for Major Depressive Disorder (MDD) are eligible to participate at two rural Appalachian sites (southeastern Ohio and West Virginia) and one urban site (Indianapolis). This type II behavioral translation study uses a community-engaged research (CEnR) approach by incorporating community fitness centers and mental health practices as interventionists. Conclusions This is the first study to evaluate the comparative effectiveness of combined CBT and exercise in the treatment of depression using community-based intervention delivery. This approach may serve as a national model for expanding depression treatment for patients with T2DM. PMID:27500279

  4. Testing promoter activity in the trypanosome genome: isolation of a metacyclic-type VSG promoter, and unexpected insights into RNA polymerase II transcription.

    PubMed

    McAndrew, M; Graham, S; Hartmann, C; Clayton, C

    1998-09-01

    In trypanosomes, most genes are arranged in polycistronic transcription units. Individual mRNAs are generated by 5'-trans splicing and 3' polyadenylation. Remarkably, no regulation of RNA polymerase II transcription has been detected although many RNAs are differentially expressed during kinetoplastid life cycles. Demonstration of specific class II promoters is complicated by the difficulty in distinguishing between genuine promoter activity and stimulation of trans splicing. Using vectors that were designed to allow the detection of low promoter activities in a transcriptionally silent chromosomal context, we isolated a novel trypanosome RNA polymerase I promoter. We were however unable to detect class II promoter activity in any tested DNA fragment. We also integrated genes which were preceded by a T3 promoter into the genome of cells expressing bacteriophage T3 polymerase: surprisingly, transcription was alpha-amanitin sensitive. One possible interpretation of these results is that in trypanosomes, RNA polymerase II initiation is favored by genomic accessibility and double-strand melting.

  5. A Dibasic Amino Acid Pair Conserved in the Activation Loop Directs Plasma Membrane Localization and Is Necessary for Activity of Plant Type I/II Phosphatidylinositol Phosphate Kinase1[W

    PubMed Central

    Mikami, Koji; Saavedra, Laura; Hiwatashi, Yuji; Uji, Toshiki; Hasebe, Mitsuyasu; Sommarin, Marianne

    2010-01-01

    Phosphatidylinositol phosphate kinase (PIPK) is an enzyme involved in the regulation of cellular levels of phosphoinositides involved in various physiological processes, such as cytoskeletal organization, ion channel activation, and vesicle trafficking. In animals, research has focused on the modes of activation and function of PIPKs, providing an understanding of the importance of plasma membrane localization. However, it still remains unclear how this issue is regulated in plant PIPKs. Here, we demonstrate that the carboxyl-terminal catalytic domain, which contains the activation loop, is sufficient for plasma membrane localization of PpPIPK1, a type I/II B PIPK from the moss Physcomitrella patens. The importance of the carboxyl-terminal catalytic domain for plasma membrane localization was confirmed with Arabidopsis (Arabidopsis thaliana) AtPIP5K1. Our findings, in which substitution of a conserved dibasic amino acid pair in the activation loop of PpPIPK1 completely prevented plasma membrane targeting and abolished enzymatic activity, demonstrate its critical role in these processes. Placing our results in the context of studies of eukaryotic PIPKs led us to conclude that the function of the dibasic amino acid pair in the activation loop in type I/II PIPKs is plant specific. PMID:20427464

  6. [A case of type II achondrogenesis].

    PubMed

    Micheli, E; Perrone, C; Quarta Colosso, L; Vetrugno, M; Zecca, G; Indirli, G C; Greco, F; Elia, G; Ciancio, S

    1996-01-01

    We describe a rare case of type II achondrogenesis (gestational age = thirty-two weeks) dead forty-five minutes after birth. This congenital skeletal dysplasia is classified among the lethal osteochondrodysplasias. Clinical features were enough for diagnosis and autopsy added nothing to our clinical knowledges.

  7. Type II Technology Applications in Teacher Education:

    ERIC Educational Resources Information Center

    Chen Wang, Lih-Ching; Beasley, William

    2005-01-01

    The use of the Instant Messenger (IM) environment to carry out structured online class discussions in graduate teacher education courses is described. Properties of IM are delineated, and specific procedures in using IM as a vehicle for class discussions are discussed. Attributes of Type II technology applications are addressed directly, and the…

  8. Correction of Aberrant NADPH Oxidase Activity in Blood-Derived Mononuclear Cells from Type II Diabetes Mellitus Patients by a Naturally Fermented Papaya Preparation

    PubMed Central

    Dickerson, Ryan; Deshpande, Bhakthi; Gnyawali, Urmila; Lynch, Debbie; Gordillo, Gayle M.; Schuster, Dara; Osei, Kwame

    2012-01-01

    Abstract Supplementation of standardized fermented papaya preparation (FPP) to adult diabetic mice improves dermal wound healing outcomes. Peripheral blood mononuclear cells (PBMC) from type II diabetes mellitus (T2DM) patients elicit a compromised respiratory burst activity resulting in increased risk of infections for the diabetic patients. Aims: The objectives of the current study were to determine the effect of FPP supplementation on human diabetic PBMC respiratory burst activity and to understand underlying mechanisms of such action of FPP. Results: When stimulated with phorbol 12-myristate 13-acetate, the production of reactive oxygen species by T2DM PBMC was markedly compromised compared to that of the PBMC from non-DM donors. FPP treated ex vivo improved respiratory burst outcomes in T2DM PBMC. FPP treatment significantly increased phosphorylation of the p47phox subunit of NADPH oxidase. In addition, the protein and mRNA expression of Rac2 was potently upregulated after FPP supplemention. The proximal human Rac2 gene promoter is G–C rich and contains consensus binding sites for Sp1 and AP-1. While FPP had no significant effect on the AP-1 DNA binding activity, the Sp1 DNA binding activity was significantly upregulated in PBMC after treatment of the cells with FPP. Innovation: This work provided first evidence that compromised respiratory burst performance of T2DM PBMC may be corrected by a nutritional supplement. Conclusion: FPP can correct respiratory burst performance of T2DM PBMC via an Sp-1-dependant pathway. Studies testing the outcome of FPP supplementation in diabetic patients are warranted. Antioxid. Redox Signal. 17, 485–491. PMID:22369197

  9. Current Understanding of Usher Syndrome Type II

    PubMed Central

    Yang, Jun; Wang, Le; Song, Hongman; Sokolov, Maxim

    2012-01-01

    Usher syndrome is the most common deafness-blindness caused by genetic mutations. To date, three genes have been identified underlying the most prevalent form of Usher syndrome, the type II form (USH2). The proteins encoded by these genes are demonstrated to form a complex in vivo. This complex is localized mainly at the periciliary membrane complex in photoreceptors and the ankle-link of the stereocilia in hair cells. Many proteins have been found to interact with USH2 proteins in vitro, suggesting that they are potential additional components of this USH2 complex and that the genes encoding these proteins may be the candidate USH2 genes. However, further investigations are critical to establish their existence in the USH2 complex in vivo. Based on the predicted functional domains in USH2 proteins, their cellular localizations in photoreceptors and hair cells, the observed phenotypes in USH2 mutant mice, and the known knowledge about diseases similar to USH2, putative biological functions of the USH2 complex have been proposed. Finally, therapeutic approaches for this group of diseases are now being actively explored. PMID:22201796

  10. Cartilage collagen type II seromarker patterns in axial spondyloarthritis and psoriatic arthritis: associations with disease activity, smoking and HLA-B27.

    PubMed

    Munk, Heidi Lausten; Gudmann, Natasja Staehr; Christensen, Anne Friesgaard; Ejstrup, Leif; Sorensen, Grith Lykke; Loft, Anne Gitte; Bay-Jensen, Anne C; Siebuhr, Anne Sofie; Junker, Peter

    2016-04-01

    The aim of the study was to assess the possible association between type II collagen turnover seromarkers and disease profile in patients with axial spondyloarthritis (SpA) and psoriatic arthritis (PsA). Outpatients with axial SpA (n = 110) or PsA (n = 101) underwent clinical examination including disease activity measures and HLA-B27 typing. The procollagen IIA N-terminal peptide (PIIANP) and a matrix metalloproteinase-generated type II collagen fragment (C2M) were quantified in serum by ELISA. C2M was higher in SpA than in controls, 0.41 versus 0.36 ng/ml (p = 0.004), while PIIANP did not differ between patients and healthy subjects, 2252 versus 2142 ng/ml (p = 0.13). However, DMARD-naïve SpA patients had higher PIIANP, 2461 ng/ml (p = 0.01) and C2M, 0.44 ng/ml (p = 0.0007) levels than controls, and PIIANP correlated with CRP (ρ = 0.34). C2M was lower in SpA smokers, 0.36 ng/ml versus non-smokers, 0.43 ng/ml (p = 0.02), while PIIANP was higher in HLA-B27 positive, 2312 ng/ml versus negative patients, 2021 ng/ml (p = 0.03). In PsA, PIIANP and C2M did not differ between patients and controls, but PIIANP was elevated in patients not receiving DMARDs, 2726 ng/ml. In PsA, PIIANP and C2M did not differ according to smoking and HLA-B27. Cartilage degradation assessed by C2M is increased in SpA irrespective of treatment but not in PsA. Cartilage synthesis reflected by PIIANP is increased in untreated SpA and PsA. PIIANP correlates with CRP in SpA while not in PsA. In DMARD-naïve SpA but not in PsA, HLA-B27 positivity and smoking are associated with a chondro-proliferative metabolic pattern.

  11. The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases

    PubMed Central

    Kühn, Nora; Bergmann, Silke; Kösterke, Nadine; Lambertz, Ruth L. O.; Keppner, Anna; van den Brand, Judith M. A.; Weiß, Siegfried; Hummler, Edith; Hatesuer, Bastian

    2016-01-01

    ABSTRACT Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity. In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivity in vitro. Recently, we reported that inactivation of a single HA-activating protease gene, Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses. However, after infection of Tmprss2 knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight. In this study, we investigated an additional trypsin-like protease, TMPRSS4. Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung. Deletion of Tmprss4 alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus. In contrast, Tmprss2−/− Tmprss4−/− double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality. Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virus in vivo. IMPORTANCE Influenza epidemics and recurring pandemics are responsible for significant global morbidity and mortality. Due to high variability of the virus genome, resistance to available antiviral drugs is frequently observed, and new targets for treatment of influenza are needed. Host cell factors essential for processing of the virus hemagglutinin represent very suitable drug targets because the virus is dependent on these host factors for replication. We reported previously that Tmprss2-deficient mice are protected against H1N1 virus infections, but only marginal protection against H3N2 virus infections was observed. Here we show that deletion of two host protease genes, Tmprss2 and

  12. Competency Based Vocational Education Typing I and Typing II.

    ERIC Educational Resources Information Center

    Brown, G. Lee; Mahan, Louise

    Materials are provided for two competency-based educational courses in Typing I and II for the community college level. The first course covers the touch method operation of the typewriter; the second covers the extension of the touch method and develops such skills as production of business letters, manuscripts, carbon copies, tabulation, tables,…

  13. Discovery of a Series of Imidazo[4,5-b]pyridines with Dual Activity at Angiotensin II Type 1 Receptor and Peroxisome Proliferator-Activated Receptor-[gamma

    SciTech Connect

    Casimiro-Garcia, Agustin; Filzen, Gary F.; Flynn, Declan; Bigge, Christopher F.; Chen, Jing; Davis, Jo Ann; Dudley, Danette A.; Edmunds, Jeremy J.; Esmaeil, Nadia; Geyer, Andrew; Heemstra, Ronald J.; Jalaie, Mehran; Ohren, Jeffrey F.; Ostroski, Robert; Ellis, Teresa; Schaum, Robert P.; Stoner, Chad

    2013-03-07

    Mining of an in-house collection of angiotensin II type 1 receptor antagonists to identify compounds with activity at the peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) revealed a new series of imidazo[4,5-b]pyridines 2 possessing activity at these two receptors. Early availability of the crystal structure of the lead compound 2a bound to the ligand binding domain of human PPAR{gamma} confirmed the mode of interaction of this scaffold to the nuclear receptor and assisted in the optimization of PPAR{gamma} activity. Among the new compounds, (S)-3-(5-(2-(1H-tetrazol-5-yl)phenyl)-2,3-dihydro-1H-inden-1-yl)-2-ethyl-5-isobutyl-7-methyl-3H-imidazo[4,5-b]pyridine (2l) was identified as a potent angiotensin II type I receptor blocker (IC{sub 50} = 1.6 nM) with partial PPAR{gamma} agonism (EC{sub 50} = 212 nM, 31% max) and oral bioavailability in rat. The dual pharmacology of 2l was demonstrated in animal models of hypertension (SHR) and insulin resistance (ZDF rat). In the SHR, 2l was highly efficacious in lowering blood pressure, while robust lowering of glucose and triglycerides was observed in the male ZDF rat.

  14. Discovery of a series of imidazo[4,5-b]pyridines with dual activity at angiotensin II type 1 receptor and peroxisome proliferator-activated receptor-γ.

    PubMed

    Casimiro-Garcia, Agustin; Filzen, Gary F; Flynn, Declan; Bigge, Christopher F; Chen, Jing; Davis, Jo Ann; Dudley, Danette A; Edmunds, Jeremy J; Esmaeil, Nadia; Geyer, Andrew; Heemstra, Ronald J; Jalaie, Mehran; Ohren, Jeffrey F; Ostroski, Robert; Ellis, Teresa; Schaum, Robert P; Stoner, Chad

    2011-06-23

    Mining of an in-house collection of angiotensin II type 1 receptor antagonists to identify compounds with activity at the peroxisome proliferator-activated receptor-γ (PPARγ) revealed a new series of imidazo[4,5-b]pyridines 2 possessing activity at these two receptors. Early availability of the crystal structure of the lead compound 2a bound to the ligand binding domain of human PPARγ confirmed the mode of interaction of this scaffold to the nuclear receptor and assisted in the optimization of PPARγ activity. Among the new compounds, (S)-3-(5-(2-(1H-tetrazol-5-yl)phenyl)-2,3-dihydro-1H-inden-1-yl)-2-ethyl-5-isobutyl-7-methyl-3H-imidazo[4,5-b]pyridine (2l) was identified as a potent angiotensin II type I receptor blocker (IC(50) = 1.6 nM) with partial PPARγ agonism (EC(50) = 212 nM, 31% max) and oral bioavailability in rat. The dual pharmacology of 2l was demonstrated in animal models of hypertension (SHR) and insulin resistance (ZDF rat). In the SHR, 2l was highly efficacious in lowering blood pressure, while robust lowering of glucose and triglycerides was observed in the male ZDF rat.

  15. SHAPING OF ACTION POTENTIALS BY TYPE I AND TYPE II BK CHANNELS

    PubMed Central

    Jaffe, David B.; Wang, Bin; Brenner, Robert

    2011-01-01

    The BK channel is a Ca2+ and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca2+ was high (>20 µM) and the other where BK-activating Ca2+ was low (~0.4–1.2 µM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca2+ channels due to electrogenic effects on spike duration. We also found that depending on Ca2+ dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron. PMID:21723921

  16. Knowledge Is Power: Teaching Children about Type II Diabetes

    ERIC Educational Resources Information Center

    Feild-Berner, Natalie; Balgopal, Meena

    2011-01-01

    World Diabetes Day (November 14) offers a wonderful opportunity to educate elementary children about the power they have to control their health. First lady Michelle Obama has urged Americans to educate themselves about childhood obesity, which is often associated with the onset of type II diabetes (Rabin 2010). The authors developed activities to…

  17. Magnetization of anisotropic Type II superconductors

    SciTech Connect

    Mints, R.G.

    1989-04-10

    Peculiarities of magnetization of anisotropic type II superconductors are of considerable interest in view of the discovery of high-T/sub c/ superconductors characterized by strongly asymmetric layered structure. Specifics of the penetration of magnetic flux into an anisotropic type II superconductor were discussed in the literature. This analysis gave the distribution of induction in an isolated vortex, its energy, and critical magnetic field H/sub c1/. However, the magnetization curve of anisotropic superconductors was not considered. This paper deals with the magnetic moment of uniaxial London superconductor in the interval H/sub c1/ /le/ H/sub 0/ << H/sub c2/, where H/sub 0/ is the external magnetic field strength.

  18. Origin of wide-band IP type II bursts

    NASA Astrophysics Data System (ADS)

    Pohjolainen, S.; Allawi, H.; Valtonen, E.

    2013-10-01

    . Conclusions: We conclude that in most cases (in 18 out of 25 events) the wide-band IP type II bursts can be plasma emission, formed at or just above the CME leading edge. The results for the remaining seven events might suggest the possibility of a synchrotron source. These events, however, occurred during periods of high solar activity, and coronal conditions affecting the results of the burst height calculations cannot be ruled out. The observed wide and diffuse emission bands may also indicate specific CME leading edge structures and special shock conditions. Figures 2-26 and Table 4 are available in electronic form at http://www.aanda.org

  19. DMSO Enhances TGF-β Activity by Recruiting the Type II TGF-β Receptor From Intracellular Vesicles to the Plasma Membrane.

    PubMed

    Huang, Shuan Shian; Chen, Chun-Lin; Huang, Franklin W; Hou, Wei-Hsien; Huang, Jung San

    2016-07-01

    Dimethyl sulfoxide (DMSO) is used to treat many diseases/symptoms. The molecular basis of the pharmacological actions of DMSO has been unclear. We hypothesized that DMSO exerts some of these actions by enhancing TGF-β activity. Here we show that DMSO enhances TGF-β activity by ∼3-4-fold in Mv1Lu and NMuMG cells expressing Smad-dependent luciferase reporters. In Mv1Lu cells, DMSO enhances TGF-β-stimulated expression of P-Smad2 and PAI-1. It increases cell-surface expression of TGF-β receptors (TβR-I and/or TβR-II) by ∼3-4-fold without altering their cellular levels as determined by (125) I-labeled TGF-β-cross-linking/Western blot analysis, suggesting the presence of large intracellular pools in these cells. Sucrose density gradient ultracentrifugation/Western blot analysis reveals that DMSO induces recruitment of TβR-II (but not TβR-I) from its intracellular pool to plasma-membrane microdomains. It induces more recruitment of TβR-II to non-lipid raft microdomains than to lipid rafts/caveolae. Mv1Lu cells transiently transfected with TβR-II-HA plasmid were treated with DMSO and analyzed by indirect immunofluoresence staining using anti-HA antibody. In these cells, TβR-II-HA is present as a vesicle-like network in the cytoplasm as well as in the plasma membrane. DMSO causes depletion of TβR-II-HA-containing vesicles from the cytoplasm and co-localization of TβR-II-HA and cveolin-1 at the plasma membrane. These results suggest that DMSO, a fusogenic substance, enhances TGF-β activity presumably by inducing fusion of cytoplasmic vesicles (containing TβR-II) and the plasma membrane, resulting in increased localization of TβR-II to non-lipid raft microdomains where canonical signaling occurs. Fusogenic activity of DMSO may play a pivotal role in its pharmacological actions involving membrane proteins with large cytoplasmic pools. J. Cell. Biochem. 117: 1568-1579, 2016. © 2015 Wiley Periodicals, Inc.

  20. Superb hydroxyl radical-mediated biocidal effect induced antibacterial activity of tuned ZnO/chitosan type II heterostructure under dark

    NASA Astrophysics Data System (ADS)

    Podder, Soumik; Halder, Suman; Roychowdhury, Anirban; Das, Dipankar; Ghosh, Chandan Kr.

    2016-10-01

    hole transfer from CS for the first time, and a heterostructure of type II was proposed.

  1. TGF-β1 stimulates migration of type II endometrial cancer cells by down-regulating PTEN via activation of SMAD and ERK1/2 signaling pathways.

    PubMed

    Xiong, Siyuan; Cheng, Jung-Chien; Klausen, Christian; Zhao, Jianfang; Leung, Peter C K

    2016-09-20

    PTEN acts as a tumor suppressor primarily by antagonizing the PI3K/AKT signaling pathway. PTEN is frequently mutated in human cancers; however, in type II endometrial cancers its mutation rate is very low. Overexpression of TGF-β1 and its receptors has been reported to correlate with metastasis of human cancers and reduced survival rates. Although TGF-β1 has been shown to regulate PTEN expression through various mechanisms, it is not yet known if the same is true in type II endometrial cancer. In the present study, we show that treatment with TGF-β1 stimulates the migration of two type II endometrial cancer cell lines, KLE and HEC-50. In addition, TGF-β1 treatment down-regulates both mRNA and protein levels of PTEN. Overexpression of PTEN or inhibition of PI3K abolishes TGF-β1-stimulated cell migration. TGF-β1 induces SMAD2/3 phosphorylation and knockdown of common SMAD4 inhibits the suppressive effects of TGF-β1 on PTEN mRNA and protein. Interestingly, TGF-β1 induces ERK1/2 phosphorylation and pre-treatment with a MEK inhibitor attenuates the suppression of PTEN protein, but not mRNA, by TGF-β1. This study provides important insights into the molecular mechanisms mediating TGF-β1-induced down-regulation of PTEN and demonstrates an important role of PTEN in the regulation of type II endometrial cancer cell migration.

  2. TGF-β1 stimulates migration of type II endometrial cancer cells by down-regulating PTEN via activation of SMAD and ERK1/2 signaling pathways

    PubMed Central

    Xiong, Siyuan; Cheng, Jung-Chien; Klausen, Christian; Zhao, Jianfang; Leung, Peter C.K.

    2016-01-01

    PTEN acts as a tumor suppressor primarily by antagonizing the PI3K/AKT signaling pathway. PTEN is frequently mutated in human cancers; however, in type II endometrial cancers its mutation rate is very low. Overexpression of TGF-β1 and its receptors has been reported to correlate with metastasis of human cancers and reduced survival rates. Although TGF-β1 has been shown to regulate PTEN expression through various mechanisms, it is not yet known if the same is true in type II endometrial cancer. In the present study, we show that treatment with TGF-β1 stimulates the migration of two type II endometrial cancer cell lines, KLE and HEC-50. In addition, TGF-β1 treatment down-regulates both mRNA and protein levels of PTEN. Overexpression of PTEN or inhibition of PI3K abolishes TGF-β1-stimulated cell migration. TGF-β1 induces SMAD2/3 phosphorylation and knockdown of common SMAD4 inhibits the suppressive effects of TGF-β1 on PTEN mRNA and protein. Interestingly, TGF-β1 induces ERK1/2 phosphorylation and pre-treatment with a MEK inhibitor attenuates the suppression of PTEN protein, but not mRNA, by TGF-β1. This study provides important insights into the molecular mechanisms mediating TGF-β1-induced down-regulation of PTEN and demonstrates an important role of PTEN in the regulation of type II endometrial cancer cell migration. PMID:27542208

  3. Headache and Decompression Sickness: Type I or Type II?

    DTIC Science & Technology

    2001-06-01

    neurological exam was normal. Recompression with 100% oxygen produced relief within fifteen minutes. Follow up revealed no recurrence . Case 2 A twenty-seven...Follow up revealed no recurrence . Both cases pose an intriguing question. Should headache always be considered Type II DCS? DCS has a wide range of...with the supporting basis for this alternative view. The background for this paper is based on orthodontic and osteopathic medicine. For years

  4. UBIQUITOUS TORSIONAL MOTIONS IN TYPE II SPICULES

    SciTech Connect

    De Pontieu, B.; Hansteen, V. H.; Carlsson, M.; Rouppe van der Voort, L. H. M.; Rutten, R. J.; Watanabe, H.

    2012-06-10

    Spicules are long, thin, highly dynamic features that jut out ubiquitously from the solar limb. They dominate the interface between the chromosphere and corona and may provide significant mass and energy to the corona. We use high-quality observations with the Swedish 1 m Solar Telescope to establish that so-called type II spicules are characterized by the simultaneous action of three different types of motion: (1) field-aligned flows of order 50-100 km s{sup -1}, (2) swaying motions of order 15-20 km s{sup -1}, and (3) torsional motions of order 25-30 km s{sup -1}. The first two modes have been studied in detail before, but not the torsional motions. Our analysis of many near-limb and off-limb spectra and narrowband images using multiple spectral lines yields strong evidence that most, if not all, type II spicules undergo large torsional modulation and that these motions, like spicule swaying, represent Alfvenic waves propagating outward at several hundred km s{sup -1}. The combined action of the different motions explains the similar morphology of spicule bushes in the outer red and blue wings of chromospheric lines, and needs to be taken into account when interpreting Doppler motions to derive estimates for field-aligned flows in spicules and determining the Alfvenic wave energy in the solar atmosphere. Our results also suggest that large torsional motion is an ingredient in the production of type II spicules and that spicules play an important role in the transport of helicity through the solar atmosphere.

  5. Type II restriction endonuclease R.Hpy188I belongs to the GIY-YIG nuclease superfamily, but exhibits an unusual active site

    PubMed Central

    Kaminska, Katarzyna H; Kawai, Mikihiko; Boniecki, Michal; Kobayashi, Ichizo; Bujnicki, Janusz M

    2008-01-01

    Background Catalytic domains of Type II restriction endonucleases (REases) belong to a few unrelated three-dimensional folds. While the PD-(D/E)XK fold is most common among these enzymes, crystal structures have been also determined for single representatives of two other folds: PLD (R.BfiI) and half-pipe (R.PabI). Bioinformatics analyses supported by mutagenesis experiments suggested that some REases belong to the HNH fold (e.g. R.KpnI), and that a small group represented by R.Eco29kI belongs to the GIY-YIG fold. However, for a large fraction of REases with known sequences, the three-dimensional fold and the architecture of the active site remain unknown, mostly due to extreme sequence divergence that hampers detection of homology to enzymes with known folds. Results R.Hpy188I is a Type II REase with unknown structure. PSI-BLAST searches of the non-redundant protein sequence database reveal only 1 homolog (R.HpyF17I, with nearly identical amino acid sequence and the same DNA sequence specificity). Standard application of state-of-the-art protein fold-recognition methods failed to predict the relationship of R.Hpy188I to proteins with known structure or to other protein families. In order to increase the amount of evolutionary information in the multiple sequence alignment, we have expanded our sequence database searches to include sequences from metagenomics projects. This search resulted in identification of 23 further members of R.Hpy188I family, both from metagenomics and the non-redundant database. Moreover, fold-recognition analysis of the extended R.Hpy188I family revealed its relationship to the GIY-YIG domain and allowed for computational modeling of the R.Hpy188I structure. Analysis of the R.Hpy188I model in the light of sequence conservation among its homologs revealed an unusual variant of the active site, in which the typical Tyr residue of the YIG half-motif had been substituted by a Lys residue. Moreover, some of its homologs have the otherwise

  6. Transforming growth factor-β1 induces type II collagen and aggrecan expression via activation of extracellular signal-regulated kinase 1/2 and Smad2/3 signaling pathways.

    PubMed

    Zhu, Yanhui; Tao, Hairong; Jin, Chen; Liu, Yonzhang; Lu, Xiongwei; Hu, Xiaopeng; Wang, Xiang

    2015-10-01

    Transforming growth factor (TGF)‑β regulates the anabolic metabolism of articular cartilage and prevents cartilage degradation. TGF‑β1 influences cellular proliferation, differentiation and the extracellular matrix through activation of the extracellular signal‑regulated kinase (ERK)1/2 and Smad2/3 signaling pathways. However, it has remained to be fully elucidated precisely how the ERK1/2 and Smad2/3 signaling pathways mediate anabolic processes of articular cartilage. The present study investigated how ERK1/2 and Smad2/3 signaling mediate TGF‑β1‑stimulated type II collagen and aggrecan expression in rat chondrocytes. The results confirmed that TGF‑β1 stimulates type II collagen and aggrecan expression in rat chondrocytes, and furthermore, that the ERK1/2 and Smad2/3 signaling pathways were activated by TGF‑β1. Conversely, the TGF‑β receptor I (ALK5) kinase inhibitor SB525334 significantly impaired TGF‑β1‑induced type II collagen and aggrecan expression, coinciding with a reduction of ERK1/2 and Smad3 phosphorylation. In addition, TGF‑β1‑induced type II collagen and aggrecan expression were significantly suppressed by ERK1/2 inhibitor PD98059. Similarly, TGF‑β1‑stimulated type II collagen and aggrecan expression were decreased in the presence of a Smad3 phosphorylation inhibitor SIS3. Therefore, the present study demonstrated that the ERK1/2 and Smad2/3 signaling pathways regulate type II collagen and aggrecan expression in rat chondrocytes.

  7. A TYPE II RADIO BURST WITHOUT A CORONAL MASS EJECTION

    SciTech Connect

    Su, W.; Cheng, X.; Ding, M. D.; Chen, P. F.; Sun, J. Q. E-mail: dmd@nju.edu.cn

    2015-05-10

    Type II radio bursts are thought to be a signature of coronal shocks. In this paper, we analyze a short-lived type II burst that started at 07:40 UT on 2011 February 28. By carefully checking white-light images, we find that the type II radio burst is not accompanied by a coronal mass ejection, only by a C2.4 class flare and narrow jet. However, in the EUV images provided by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory, we find a wave-like structure that propagated at a speed of ∼600 km s{sup −1} during the burst. The relationship between the type II radio burst and the wave-like structure is, in particular, explored. For this purpose, we first derive the density distribution under the wave by the differential emission measure method, which is used to restrict the empirical density model. We then use the restricted density model to invert the speed of the shock that produces the observed frequency drift rate in the dynamic spectrum. The inverted shock speed is similar to the speed of the wave-like structure. This implies that the wave-like structure is most likely a coronal shock that produces the type II radio burst. We also examine the evolution of the magnetic field in the flare-associated active region and find continuous flux emergence and cancellation taking place near the flare site. Based on these facts, we propose a new mechanism for the formation of the type II radio burst, i.e., the expansion of the strongly inclined magnetic loops after reconnecting with a nearby emerging flux acts as a piston to generate the shock wave.

  8. Spectral modeling of Type II SNe

    NASA Astrophysics Data System (ADS)

    Dessart, Luc

    2015-08-01

    The red supergiant phase represents the final stage of evolution in the life of moderate mass (8-25Msun) massive stars. Hidden from view, the core changes considerably its structure, progressing through the advanced stages of nuclear burning, and eventually becomes degenerate. Upon reaching the Chandrasekhar mass, this Fe or ONeMg core collapses, leading to the formation of a proto neutron star. A type II supernova results if the shock that forms at core bounce, eventually wins over the envelope accretion and reaches the progenitor surface.The electromagnetic display of such core-collapse SNe starts with this shock breakout, and persists for months as the ejecta releases the energy deposited initially by the shock or continuously through radioactive decay. Over a timescale of weeks to months, the originally optically-thick ejecta thins out and turns nebular. SN radiation contains a wealth of information about the explosion physics (energy, explosive nucleosynthesis), the progenitor properties (structure and composition). Polarised radiation also offers signatures that can help constrain the morphology of the ejecta.In this talk, I will review the current status of type II SN spectral modelling, and emphasise that a proper solution requires a time dependent treatment of the radiative transfer problem. I will discuss the wealth of information that can be gleaned from spectra as well as light curves, from both the early times (photospheric phase) and late times (nebular phase). I will discuss the diversity of Type SNe properties and how they are related to the diversity of red supergiant stars from which they originate.SN radiation offers an alternate means of constraining the properties of red-supergiant stars. To wrap up, I will illustrate how SNe II-P can also be used as probes, for example to constrain the metallicity of their environment.

  9. INTERPLANETARY SHOCKS LACKING TYPE II RADIO BURSTS

    SciTech Connect

    Gopalswamy, N.; Kaiser, M. L.; Xie, H.; Maekelae, P.; Akiyama, S.; Yashiro, S.; Howard, R. A.; Bougeret, J.-L.

    2010-02-20

    We report on the radio-emission characteristics of 222 interplanetary (IP) shocks detected by spacecraft at Sun-Earth L1 during solar cycle 23 (1996 to 2006, inclusive). A surprisingly large fraction of the IP shocks ({approx}34%) was radio quiet (RQ; i.e., the shocks lacked type II radio bursts). We examined the properties of coronal mass ejections (CMEs) and soft X-ray flares associated with such RQ shocks and compared them with those of the radio-loud (RL) shocks. The CMEs associated with the RQ shocks were generally slow (average speed {approx}535 km s{sup -1}) and only {approx}40% of the CMEs were halos. The corresponding numbers for CMEs associated with RL shocks were 1237 km s{sup -1} and 72%, respectively. Thus, the CME kinetic energy seems to be the deciding factor in the radio-emission properties of shocks. The lower kinetic energy of CMEs associated with RQ shocks is also suggested by the lower peak soft X-ray flux of the associated flares (C3.4 versus M4.7 for RL shocks). CMEs associated with RQ CMEs were generally accelerating within the coronagraph field of view (average acceleration {approx}+6.8 m s{sup -2}), while those associated with RL shocks were decelerating (average acceleration {approx}-3.5 m s{sup -2}). This suggests that many of the RQ shocks formed at large distances from the Sun, typically beyond 10 Rs, consistent with the absence of metric and decameter-hectometric (DH) type II radio bursts. A small fraction of RL shocks had type II radio emission solely in the kilometric (km) wavelength domain. Interestingly, the kinematics of the CMEs associated with the km type II bursts is similar to those of RQ shocks, except that the former are slightly more energetic. Comparison of the shock Mach numbers at 1 AU shows that the RQ shocks are mostly subcritical, suggesting that they were not efficient in accelerating electrons. The Mach number values also indicate that most of these are quasi-perpendicular shocks. The radio-quietness is predominant

  10. Minkowski Flux Vacua of Type II Supergravities

    NASA Astrophysics Data System (ADS)

    Andriot, David; Blâbäck, Johan; Van Riet, Thomas

    2017-01-01

    We study flux compactifications of 10D type II supergravities to 4D Minkowski space-time, supported by parallel orientifold Op planes with 3 ≤p ≤8 . With some geometric restrictions, the 4D Ricci scalar can be written as a negative sum of squares involving Bogomol'nyi-Prasad-Sommerfield-like conditions. Setting all squares to zero provides automatically a solution to 10D equations of motion. This way we characterize a broad class, if not the complete set, of Minkowski flux vacua with parallel orientifolds. We conjecture an extension with nongeometric fluxes. None of our results rely on supersymmetry.

  11. Type II alveolar epithelial cell in vitro culture in aerobiosis.

    PubMed

    Aerts, C; Voisin, C; Wallaert, B

    1988-08-01

    A method of Type II alveolar epithelial cell culture in aerobiosis has been developed. Isolation of Type II cells was performed by digesting guinea-pig lung tissue with crude trypsin and elastase and using discontinuous Percoll density gradients. The Type II cells, as identified by light and electron microscopy, were cultured in aerobiosis for up to six days, in direct contact with the atmosphere in conditions mimicking those present in the lower respiratory tract. Significant activities of cellular superoxide dismutase (SOD), manganese dependent superoxide dismutase (Mn-SOD), catalase and glutathione peroxidase (GSH-Px) were found at the time of isolation. In contrast, cell glutathione content varied widely from one experiment to another. Changes of antioxidant enzymes were evaluated during cell culture in aerobiosis. SOD, Mn-SOD and catalase were significantly decreased after three days but were not significantly different between a three day and six day culture. Antioxidant changes did not influence the cell culture. In marked contrast, decrease in cell glutathione was associated with rapid cell death, whereas good cell survival was obtained at high levels of cell glutathione. Cell culture in aerobiosis will permit a precise evaluation of the effects of gases, particularly oxidant gases, on a primary culture of Type II alveolar epithelial cells.

  12. Gain spectroscopy of a type-II VECSEL chip

    NASA Astrophysics Data System (ADS)

    Lammers, C.; Stein, M.; Berger, C.; Möller, C.; Fuchs, C.; Ruiz Perez, A.; Rahimi-Iman, A.; Hader, J.; Moloney, J. V.; Stolz, W.; Koch, S. W.; Koch, M.

    2016-12-01

    Using optical pump-white light probe spectroscopy, the gain dynamics is investigated for a vertical-external-cavity surface-emitting laser chip, which is based on a type-II heterostructure. The active region of the chip consists of a GaAs/(GaIn)As/Ga(AsSb)/(GaIn)As/GaAs multiple quantum well. For this structure, a fully microscopic theory predicts a modal room temperature gain at a wavelength of 1170 nm, which is confirmed by the experimental spectra. The results show a gain buildup on the type-II chip that is delayed relative to that of a type-I chip. This slower gain dynamics is attributed to a diminished cooling rate arising from the reduced electron-hole scattering.

  13. SPECTRA OF TYPE II CEPHEID CANDIDATES AND RELATED STARS

    SciTech Connect

    Schmidt, E. G.; Rogalla, Danielle; Thacker-Lynn, Lauren E-mail: drogall1@bigred.unl.edu

    2011-02-15

    We present low-resolution spectra for variable stars in the Cepheid period range from the ROTSE-I Demonstration Project and the All Sky Automated Survey, some of which were previously identified as type II Cepheid candidates. We have derived effective temperatures, gravities, and metallicities from the spectra. Based on this, three types of variables were identified: Cepheid strip stars, cool stars that lie along the red subgiant and giant branch, and cool main-sequence stars. Many fewer type II Cepheids were found than expected and most have amplitudes less than 0.4 mag. The cool variables include many likely binaries as well as intrinsic variables. Variation among the main-sequence stars is likely to be mostly due to binarity or stellar activity.

  14. HADES RV Programme with HARPS-N at TNG. IV. Time resolved analysis of the Ca ii H&K and Hα chromospheric emission of low-activity early-type M dwarfs

    NASA Astrophysics Data System (ADS)

    Scandariato, G.; Maldonado, J.; Affer, L.; Biazzo, K.; Leto, G.; Stelzer, B.; Zanmar Sanchez, R.; Claudi, R.; Cosentino, R.; Damasso, M.; Desidera, S.; González Álvarez, E.; González Hernández, J. I.; Gratton, R.; Lanza, A. F.; Maggio, A.; Messina, S.; Micela, G.; Pagano, I.; Perger, M.; Piotto, G.; Rebolo, R.; Ribas, I.; Rosich, A.; Sozzetti, A.; Suárez Mascareño, A.

    2017-01-01

    Context. M dwarfs are prime targets for current and future planet search programs, particularly those focused on the detection and characterization of rocky planets in the habitable zone. In this context, understanding their magnetic activity is important for two main reasons: it affects our ability to detect small planets and it plays a key role in the characterization of the stellar environment. Aims: We analyze observations of the Ca ii H&K and Hα lines as diagnostics of chromospheric activity for low-activity early-type M dwarfs. Methods: We analyze the time series of spectra of 71 early-type M dwarfs collected in the framework of the HADES project for planet search purposes. The HARPS-N spectra simultaneously provide the Ca ii H&K doublet and the Hα line. We develop a reduction scheme able to correct the HARPS-N spectra for instrumental and atmospheric effects, and also to provide flux-calibrated spectra in units of flux at the stellar surface. The Ca ii H&K and Hα fluxes are then compared with each other, and their time variability is analyzed. Results: We find that the Ca ii H and K flux excesses are strongly correlated with each other, while the Hα flux excess is generally less correlated with the Ca ii H&K doublet. We also find that Hα emission does not increase monotonically with the Ca ii H&K line flux, showing some absorption before being filled in by chromospheric emission when Ca ii H&K activity increases. Analyzing the time variability of the emission fluxes, we derive a tentative estimate of the rotation period (on the order of a few tens of days) for some of the program stars, and the typical lifetime of chromospheric active regions (on the order of a few stellar rotations). Conclusions: Our results are in good agreement with similar previous studies. In particular, we find evidence that the chromospheres of early-type M dwarfs could be characterized by different filament coverage, affecting the formation mechanism of the Hα line. We also

  15. Prenatal diagnosis of Pfeiffer syndrome type II.

    PubMed

    Blaumeiser, Bettina; Loquet, Philip; Wuyts, Wim; Nöthen, Markus M

    2004-08-01

    Pfeiffer syndrome is an autosomal dominant disorder characterized by coronal craniosynostosis, midface hypoplasia, broad thumbs and great toes. On the basis of clinical findings, three subtypes have been delineated. The clinical variability of Pfeiffer syndrome as well as other causes of craniosynostosis can make a prenatal diagnosis based on sonography alone difficult. We describe a fetus in whom sonographic findings (including 3D ultrasound) suggested a Pfeiffer syndrome type II and in which subsequent molecular analysis verified the diagnosis by identifying a de novo mutation in the FGFR2 gene. To the best of our knowledge, this is the first report of a prenatal molecular diagnosis of Pfeiffer syndrome in a patient without family history.

  16. Ordering dynamics in type-II superconductors.

    PubMed

    Guttenberg, Nicholas; Goldenfeld, Nigel

    2006-12-01

    We use analytic and numerical methods to analyze the dynamics of vortices following the quench of a type-II superconductor under the application of an external magnetic field. In three dimensions, in the absence of a field, the spacing between vortices scales with time t with an exponent phi=0.414+/-0.01, in a thin sheet of a superconductor, the scaling exponent is phi=0.294+/-0.01. When an external magnetic field h is applied, the vortices are confined with respect to the length scale of the Abrikosov lattice, leading to a crossover between the power-law scaling length scale and the lattice length scale. From this we suggest a one-parameter scaling of r with h and r that is consistent with numerical data.

  17. EARLY-TYPE HOST GALAXIES OF TYPE II AND Ib SUPERNOVAE

    SciTech Connect

    Suh, Hyewon; Jeong, Hyunjin; Yi, Sukyoung K.; Yoon, Sung-chul

    2011-04-01

    Recent studies find that some early-type galaxies host Type II or Ibc supernovae (SNe II, Ibc). This may imply recent star formation activities in these SNe host galaxies, but a massive star origin of the SNe Ib so far observed in early-type galaxies has been questioned because of their intrinsic faintness and unusually strong Ca lines shown in the nebular phase. To address the issue, we investigate the properties of early-type SNe host galaxies using the data with Galaxy Evolution Explorer (GALEX) ultraviolet photometry and the Sloan Digital Sky Survey optical data. Our sample includes eight SNe II and one peculiar SN Ib (SN 2000ds) host galaxies as well as 32 SN Ia host galaxies. The host galaxy of SN 2005cz, another peculiar SN Ib, is also analyzed using the GALEX data and the NASA/IPAC Extragalactic Database optical data. We find that the NUV-optical colors of SN II/Ib host galaxies are systematically bluer than those of SN Ia host galaxies, and some SN II/Ib host galaxies with NUV - r colors markedly bluer than the others exhibit strong radio emission. We perform a stellar population synthesis analysis and find a clear signature of recent star formation activities in most of the SN II/Ib host galaxies. Our results generally support the association of the SNe II/Ib hosted in early-type galaxies with core collapse of massive stars. We briefly discuss implications for the progenitors of the peculiar SNe Ib 2000ds and 2005cz.

  18. T lymphocytes and dendritic cells are activated by the deletion of peroxiredoxin II (Prx II) gene.

    PubMed

    Moon, Eun-Yi; Noh, Young-Wook; Han, Ying-Hao; Kim, Sun-Uk; Kim, Jin-Man; Yu, Dae-Yeul; Lim, Jong-Seok

    2006-02-15

    Peroxiredoxin II (Prx II) is a member of antioxidant enzyme family and it plays a protective role against oxidative damage. Constitutive production of endogenous reactive oxygen species was detected in spleen and bone marrow cells lacking Prx II. Here, we investigated the role of Prx II in immune responses. The total number of splenocytes (especially, the population of S-phase cells and CD3(+) T cells) was significantly higher in Prx II(-/-) mice than in wild type. Number of peripheral blood mononuclear cells (PBMCs) in Prx II(-/-) mice was also higher than wild type. Differentiation of Prx II(-/-) mouse bone marrow cells into CD11c-positive dendritic cells was greater than that of wild type. Transplantation of Prx II(-/-) bone marrow cells into wild type mice increased PBMCs in blood and bone marrow-derived dendritic cells. Prx II deletion enhances concanavalin A (ConA)-induced splenocyte proliferation and mixed lymphocyte reaction (MLR) activity of bone marrow-derived CD11c-positive dendritic cells to stimulate recipient splenocytes. Collectively, these data suggest that Prx II inhibits the immune cell responsiveness, which may be regulated by scavenging the low amount of reactive oxygen species (ROS).

  19. Angiotensin II, sympathetic nerve activity and chronic heart failure.

    PubMed

    Wang, Yutang; Seto, Sai-Wang; Golledge, Jonathan

    2014-03-01

    Sympathetic nerve activity has been reported to be increased in both humans and animals with chronic heart failure. One of the mechanisms believed to be responsible for this phenomenon is increased systemic and cerebral angiotensin II signaling. Plasma angiotensin II is increased in humans and animals with chronic heart failure. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites during chronic heart failure. Angiotensin II signaling is enhanced in different brain sites such as the paraventricular nucleus, the rostral ventrolateral medulla and the area postrema. Blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the paraventricular nucleus. Injection of an angiotensin receptor blocker into the area postrema activates the sympathoinhibitory baroreflex. In peripheral regions, angiotensin II elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings, which may contribute to the increase in sympathetic nerve activity seen in chronic heart failure. Increased circulating angiotensin II during chronic heart failure may enhance the sympathoexcitatory chemoreflex and inhibit the sympathoinhibitory baroreflex. In addition, increased circulating angiotensin II can directly act on the central nervous system via the subfornical organ and the area postrema to increase sympathetic outflow. Inhibition of angiotensin II formation and its type 1 receptor has been shown to have beneficial effects in chronic heart failure patients.

  20. Waardenburg syndrome type II: phenotypic findings and diagnostic criteria.

    PubMed

    Liu, X Z; Newton, V E; Read, A P

    1995-01-02

    The Waardenburg syndrome (WS) consists of at least two distinct autosomal dominant hereditary disorders. WS Type I has been mapped to the distal part of chromosome 2q and the gene identified as PAX3. Other gene(s) are responsible for WS Type II. Mapping WS Type II requires accurate diagnosis within affected families. To establish diagnostic criteria for WS Type II, 81 individuals from 21 families with Type II WS were personally studied, and compared with 60 personally studied patients from 8 families with Type I and 253 cases of WS (Type I or II) from the literature. Sensorineural hearing loss (77%) and heterochromia iridum (47%) were the two most important diagnostic indicators for WS Type II. Both were more common in Type II than in Type I. Other clinical manifestations, such as white forelock and skin patches, were more frequent in Type I. We estimate the frequency of phenotypic traits and propose diagnostic criteria for WS Type II. In practice, a diagnosis of WS Type II can be made with confidence given a family history of congenital hearing loss and pigmentary disorders, where individuals have been accurately measured for ocular distances to exclude dystopia canthorum.

  1. Restricted growth of U-type infectious haematopoietic necrosis virus (IHNV) in rainbow trout cells may be linked to casein kinase II activity

    USGS Publications Warehouse

    Park, J.-W.; Moon, C.H.; Harmache, A.; Wargo, A.R.; Purcell, M.K.; Bremont, M.; Kurath, G.

    2011-01-01

    casein kinase II (CKII) inhibitor, 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB), reduced the titre of the U type 8.3-fold at 24 h post-infection. In contrast, 100 μm of the CKII inhibitor reduced the titre of the M type only 1.3-fold at 48 h post-infection. Our data suggest that the different growth of U- and M-type IHNV in RTG-2 cells may be linked to a differential requirement for cellular protein kinases such as CKII for their growth.

  2. Restricted growth of U-type infectious haematopoietic necrosis virus (IHNV) in rainbow trout cells may be linked to casein kinase II activity.

    PubMed

    Park, J W; Moon, C H; Harmache, A; Wargo, A R; Purcell, M K; Bremont, M; Kurath, G

    2011-02-01

    casein kinase II (CKII) inhibitor, 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB), reduced the titre of the U type 8.3-fold at 24 h post-infection. In contrast, 100 μm of the CKII inhibitor reduced the titre of the M type only 1.3-fold at 48 h post-infection. Our data suggest that the different growth of U- and M-type IHNV in RTG-2 cells may be linked to a differential requirement for cellular protein kinases such as CKII for their growth.

  3. The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm.

    PubMed Central

    Bhushan, A; Lin, H Y; Lodish, H F; Kintner, C R

    1994-01-01

    The type II receptors for the polypeptide growth factors transforming growth factor beta (TGF-beta) and activin belong to a new family of predicted serine/threonine protein kinases. In Xenopus embryos, the biological effects of activin and TGF-beta 1 are strikingly different; activin induces a full range of mesodermal cell types in the animal cap assay, while TGF-beta 1 has no effects, presumably because of the lack of functional TGF-beta receptors. In order to assess the biological activities of exogenously added TGF-beta 1, RNA encoding the TGF-beta type II receptor was introduced into Xenopus embryos. In animal caps from these embryos, TGF-beta 1 and activin show similar potencies for induction of mesoderm-specific mRNAs, and both elicit the same types of mesodermal tissues. In addition, the response of animal caps to TGF-beta 1, as well as to activin, is blocked by a dominant inhibitory ras mutant, p21(Asn-17)Ha-ras. These results indicate that the activin and TGF-beta type II receptors can couple to similar signalling pathways and that the biological specificities of these growth factors lie in their different ligand-binding domains and in different competences of the responding cells. Images PMID:8196664

  4. New insights into bacterial type II polyketide biosynthesis

    PubMed Central

    Zhang, Zhuan; Pan, Hai-Xue; Tang, Gong-Li

    2017-01-01

    Bacterial aromatic polyketides, exemplified by anthracyclines, angucyclines, tetracyclines, and pentangular polyphenols, are a large family of natural products with diverse structures and biological activities and are usually biosynthesized by type II polyketide synthases (PKSs). Since the starting point of biosynthesis and combinatorial biosynthesis in 1984–1985, there has been a continuous effort to investigate the biosynthetic logic of aromatic polyketides owing to the urgent need of developing promising therapeutic candidates from these compounds. Recently, significant advances in the structural and mechanistic identification of enzymes involved in aromatic polyketide biosynthesis have been made on the basis of novel genetic, biochemical, and chemical technologies. This review highlights the progress in bacterial type II PKSs in the past three years (2013–2016). Moreover, novel compounds discovered or created by genome mining and biosynthetic engineering are also included. PMID:28299197

  5. A combined optical and X-ray study of unobscured type 1 active galactic nuclei - II. Relation between X-ray emission and optical spectra

    NASA Astrophysics Data System (ADS)

    Jin, Chichuan; Ward, Martin; Done, Chris

    2012-06-01

    In this second paper in a series of three, we study the properties of the various emission features and underlying continuum in the optical spectra of type 1 active galactic nuclei (AGNs) by using the unobscured hard X-ray emission as a diagnostic. We introduce the use of the 'correlation spectrum technique' (CST) for the first time. We use this to show the strength of the correlation between the hard X-ray luminosity and each wavelength of the optical spectrum. This shows that for broad-line Seyfert 1 galaxies all the strong emission lines (the broad component of Hα and Hβ, [Ne III] λλ3869/3967, [O I] λλ6300/6364, [O II] λλ3726/3729 and [O III] λλ4959/5007) and the optical underlying continuum all strongly correlate with the hard X-ray emission. In contrast, the narrow-line Seyfert 1 galaxies show a stronger correlation in the optical continuum but a weaker correlation in the lines. A cross-correlation with luminosity between the various Balmer line components and the broad-band spectral energy distribution (SED) components shows that the best correlation exists between the hard X-ray component and the broad component (BC) of the Balmer lines. Such a correlation is weaker for the intermediate (IC) and narrow components, which supports the view that the broad-line region (BLR) has the closest link with the AGN's compact X-ray emission. The equivalent widths of the Balmer line IC and BC are found to correlate with ?, ?, Balmer line full width at half-maximum (FWHM) and black hole mass. There is a non-linear dependence of the Balmer line IC and BC luminosities with ? and L5100, which suggests that a second-order factor such as the intermediate-line region (ILR) and BLR covering factors affect the Balmer line component luminosities. The Balmer decrement is found to decrease from ˜5 in the line core to ˜2 in the extended wings, with mean decrements of 2.1 in the BLR and 4.8 in the ILR. This suggests different physical conditions in these regions, such as

  6. Synthesis, characterization and anti-proliferative activity of Cd(II) complexes with NNN type pyrazole-based ligand and pseudohalide ligands as coligand.

    PubMed

    Hopa, Cigdem; Yildirim, Hatice; Kara, Hulya; Kurtaran, Raif; Alkan, Mahir

    2014-01-01

    Cd(II) complexes of tridentate nitrogen donor ligand, 2,6-bis(3,4,5-trimethylpyrazolyl)pyridine (btmpp), Cd(btmpp)X2 (X:Cl, ONO or N(CN)2) have been synthesized and characterized by elemental and spectral (FT-IR, (1)H NMR, (13)C NMR, UV-Vis) analyses, differential thermal analysis and single crystal X-ray diffraction studies. The molecular structure of reported complex 1, revealed distorted square-pyramidal geometry around Cadmium. Complexes 1-3 and corresponding ligand were tested for cytotoxic activity against the human carcinoma cell lines HEP3B (hepatocellular carcinoma), PC3 (prostate adenocarcinoma), MCF7 (breast adenocarcinoma) and Saos2 (osteosarcoma). The results show that, complexes are more cytotoxic than the free ligand and complex 2 is the most cytotoxic complex for PC3.

  7. Synthesis, characterization and anti-proliferative activity of Cd(II) complexes with NNN type pyrazole-based ligand and pseudohalide ligands as coligand

    NASA Astrophysics Data System (ADS)

    Hopa, Cigdem; Yildirim, Hatice; Kara, Hulya; Kurtaran, Raif; Alkan, Mahir

    2014-03-01

    Cd(II) complexes of tridentate nitrogen donor ligand, 2,6-bis(3,4,5-trimethylpyrazolyl)pyridine (btmpp), Cd(btmpp)X2 (X:Cl, ONO or N(CN)2) have been synthesized and characterized by elemental and spectral (FT-IR, 1H NMR, 13C NMR, UV-Vis) analyses, differential thermal analysis and single crystal X-ray diffraction studies. The molecular structure of reported complex 1, revealed distorted square-pyramidal geometry around Cadmium. Complexes 1-3 and corresponding ligand were tested for cytotoxic activity against the human carcinoma cell lines HEP3B (hepatocellular carcinoma), PC3 (prostate adenocarcinoma), MCF7 (breast adenocarcinoma) and Saos2 (osteosarcoma). The results show that, complexes are more cytotoxic than the free ligand and complex 2 is the most cytotoxic complex for PC3.

  8. Reduced surface expression of transforming growth factor beta receptor type II in mitogen-activated T cells from Sézary patients.

    PubMed Central

    Capocasale, R J; Lamb, R J; Vonderheid, E C; Fox, F E; Rook, A H; Nowell, P C; Moore, J S

    1995-01-01

    Sézary syndrome (SzS), the leukemic form of cutaneous T-cell lymphoma, is characterized by clonal proliferation of CD4+ T cells and immune dysfunctions, raising the possibility of cytokine-related abnormalities. We previously described a decreased response to the growth-inhibitory effects of transforming growth factor type beta (TGF-beta) in SzS T cells accompanied by apparent loss of surface type II TGF-beta receptor (TGF beta RII). To specifically determine if defects exist in TGF beta RII protein expression and/or transport in SzS patients, we developed a sensitive flow cytometric method to detect TGF beta RII on the surface and intracellularly in the CD4+ T cells. Our results indicate that unlike normal CD4+ T cells, CD4+ T cells from 9 of 12 SzS patients expressed little, if any, surface TGF beta RII in response to mitogen stimulation. At the intracellular level, however, pools of TGF beta RII were comparable to those in normal CD4+ T cells. This indicates that defective trafficking of this inhibitory cytokine receptor may contribute significantly to the development of this disease. Images Fig. 2 PMID:7777538

  9. Types of Physical Activity

    MedlinePlus

    ... the exercises even count in all three categories! Fitness types and tips Confused about the types of ... injuries. Some ways to increase flexibility are ballet, yoga, martial arts, or pilates (say: puh-LAH-teez) . ...

  10. Coronal magnetic fields from multiple type II bursts

    NASA Astrophysics Data System (ADS)

    Honnappa, Vijayakumar; Raveesha, K. H.; Subramanian, K. R.

    Coronal magnetic fields from multiple type II bursts Vijayakumar H Doddamani1*, Raveesha K H2 and Subramanian3 1Bangalore University, Bangalore, Karnataka state, India 2CMR Institute of Technology, Bangalore, Karnataka state, India 3 Retd, Indian Institute of Astrophysics, Bangalore, Karnataka state, India Abstract Magnetic fields play an important role in the astrophysical processes occurring in solar corona. In the solar atmosphere, magnetic field interacts with the plasma, producing abundant eruptive activities. They are considered to be the main factors for coronal heating, particle acceleration and the formation of structures like prominences, flares and Coronal Mass Ejections. The magnetic field in solar atmosphere in the range of 1.1-3 Rsun is especially important as an interface between the photospheric magnetic field and the solar wind. Its structure and time dependent change affects space weather by modifying solar wind conditions, Cho (2000). Type II doublet bursts can be used for the estimation of the strength of the magnetic field at two different heights. Two type II bursts occur sometimes in sequence. By relating the speed of the type II radio burst to Alfven Mach Number, the Alfven speed of the shock wave generating type II radio burst can be calculated. Using the relation between the Alfven speed and the mean frequency of emission, the magnetic field strength can be determined at a particular height. We have used the relative bandwidth and drift rate properties of multiple type II radio bursts to derive magnetic field strengths at two different heights and also the gradient of the magnetic field in the outer corona. The magnetic field strength has been derived for different density factors. It varied from 1.2 to 2.5 gauss at a solar height of 1.4 Rsun. The empirical relation of the variation of the magnetic field with height is found to be of the form B(R) = In the present case the power law index ‘γ’ varied from -3 to -2 for variation of

  11. Type II Migration and Giant Planet Survival

    NASA Technical Reports Server (NTRS)

    Ward, William R.

    2003-01-01

    Type II migration, in which a newly formed large planet opens a gap in its precursor circumstellar nebula and subsequently evolves with it, has been implicated as a delivery mechanism responsible for close stellar companions. Large scale migration is possible in a viscously spreading disk of surface density sigma (r,t) when most of it is sacrificed to the primary in order to promote a small portion of the disk to much higher angular momentum orbits. Embedded planets generally follow its evolution unless their own angular momentum is comparable to that of the disk. The fraction of the starting disk mass, M (sub d) = 2pi integral rsigma(r,0)dr, that is consumed by the star depends on the distance at which material escapes the disk's outer boundary. If the disk is allowed to expand indefinitely, virtually all of the disk will fall into the primary in order to send a vanishingly small portion to infinity. For such a case, it is difficult to explain the survival of any giant planets, including Jupiter and Saturn. Realistically, however, there are processes that could truncate a disk at a finite distance, r(sub d). Recent numerical modeling has illustrated that planets can survive in this case. We show here that much of these results can be understood by simple conservation arguments.

  12. Monoclonal antibodies against type II rat brain protein kinase

    SciTech Connect

    Nakabayashi, C.H.; Huang, K.P.

    1987-05-01

    Three monoclonal antibodies (8/1, 10/10, and 25/3) against rat brain type II protein kinase C (PKC) were used to carry out the immunochemical characterization of this kinase. These antibodies immunoprecipitated the type II PKC in a dose-dependent manner but did neither to type I nor type III isozyme. Purified type II PKC has a molecular weight of 82,000 and consists of heterogeneous isoelectric point species, all of which are cross reactive with these antibodies. Immunoblot analysis of the tryptic fragments from PKC revealed that all three antibodies recognized the 33-38-KDa fragments, the phospholipid/phorbol ester-binding domain, but not the 45-48-KDa fragments, the kinase catalytic domain. The immune complexes of the kinase and the antibodies retained the kinase activity which was dependent on Ca/sup 2 +/ and phosphatidylserine (PS) and further activated by diacylglycerol. With antibody 8/1, the apparent Km values of the kinase for Ca/sup 2 +/ and PS were not influenced. The initial rate and final extent of autophosphorylation were reduced. The concentration of PS required for half-maximal (/sup 3/H)phorbol 12,13-dibutyrate (PDBu) binding was increased and the total PDBu binding was reduced. In the presence of optimum concentrations of Ca/sup 2 +/ and PS, the Kd of PDBu was unaffected by the antibody but the total binding was reduced. These results demonstrate that the PS/PDBu-binding domain contains the major epitope for the antibodies and the antibody mainly influences the PS/PDBu binding to the kinase.

  13. Subcellular dynamics of type II PKA in neurons

    PubMed Central

    Zhong, Haining; Sia, Gek-Ming; Sato, Takashi R.; Gray, Noah W.; Mao, Tianyi; Khuchua, Zaza; Huganir, Richard L.; Svoboda, Karel

    2009-01-01

    SUMMARY Protein kinase A (PKA) plays multiple roles in neurons. The localization and specificity of PKA are largely controlled by A-kinase anchoring proteins (AKAPs). However, the dynamics of PKA in neurons, and the roles of specific AKAPs, are poorly understood. We imaged the distribution of type II PKA in hippocampal and cortical layer 2/3 pyramidal neurons in vitro and in vivo. PKA was concentrated in dendritic shafts compared to the soma, axons and dendritic spines. This spatial distribution was imposed by the microtubule-binding protein MAP2, indicating that MAP2 is the dominant AKAP in neurons. Following cAMP elevation, catalytic subunits dissociated from the MAP2-tethered regulatory subunits and rapidly moved to become enriched in nearby spines. The spatial gradient of type II PKA between dendritic shafts and spines was critical for the regulation of synaptic strength and long-term potentiation. The localization and activity-dependent translocation of type II PKA are therefore important determinants of PKA function. PMID:19447092

  14. [Achondrogenesis type I and II and hypochondrogenesis (author's transl)].

    PubMed

    Bueno, M; Toledo, F; Toledo, J; Villegas, T; López, S; Remírez, J; García-Julián, G

    1980-10-01

    A study is made of achondrogenesis in relation to four observations of early fatal development. One case corresponds to type I (Parenti-Fraccaro); another to type II (Langer-Saldino); the final two, brothers, seem to come under the variation of hypochondrogenesis. In this study, authors stress the heterogenous nature of lethal, neonatal (short-limb) nanisms of which currently include: Type I and II achondrogenesis, hypochondrogenesis, homozygote achondroplasia, classical Torrance-type and San Diego-type thanatophoric dysplasia.

  15. Comparing the host galaxies of type Ia, type II, and type Ibc supernovae

    SciTech Connect

    Shao, X.; Liang, Y. C.; Chen, X. Y.; Zhong, G. H.; Deng, L. C.; Zhang, B.; Shi, W. B.; Zhou, L.; Dennefeld, M.; Hammer, F.; Flores, H. E-mail: ycliang@bao.ac.cn

    2014-08-10

    We compare the host galaxies of 902 supernovae (SNe), including SNe Ia, SNe II, and SNe Ibc, which are selected by cross-matching the Asiago Supernova Catalog with the Sloan Digital Sky Survey (SDSS) Data Release 7. We selected an additional 213 galaxies by requiring the light fraction of spectral observations to be >15%, which could represent well the global properties of the galaxies. Among these 213 galaxies, 135 appear on the Baldwin-Phillips-Terlevich diagram, which allows us to compare the hosts in terms of whether they are star-forming (SF) galaxies, active galactic nuclei (AGNs; including composites, LINERs, and Seyfert 2s) or absorption-line galaxies (Absorps; i.e., their related emission lines are weak or non-existent). The diagrams related to the parameters D{sub n}(4000), Hδ{sub A}, stellar masses, star formation rates (SFRs), and specific SFRs for the SNe hosts show that almost all SNe II and most of the SNe Ibc occur in SF galaxies, which have a wide range of stellar masses and low D{sub n}(4000). The SNe Ia hosts as SF galaxies following similar trends. A significant fraction of SNe Ia occurs in AGNs and absorption-line galaxies, which are massive and have high D{sub n}(4000). The stellar population analysis from spectral synthesis fitting shows that the hosts of SNe II have a younger stellar population than hosts of SNe Ia. These results are compared with those of the 689 comparison galaxies where the SDSS fiber captures less than 15% of the total light. These comparison galaxies appear biased toward higher 12+log(O/H) (∼0.1 dex) at a given stellar mass. Therefore, we believe the aperture effect should be kept in mind when the properties of the hosts for different types of SNe are discussed.

  16. Preferential Type II Muscle Fiber Damage From Plyometric Exercise

    PubMed Central

    Macaluso, Filippo; Isaacs, Ashwin W.; Myburgh, Kathryn H.

    2012-01-01

    Context Plyometric training has been successfully used in different sporting contexts. Studies that investigated the effect of plyometric training on muscle morphology are limited, and results are controversial with regard to which muscle fiber type is mainly affected. Objective To analyze the skeletal muscle structural and ultrastructural change induced by an acute bout of plyometric exercise to determine which type of muscle fibers is predominantly damaged. Design Descriptive laboratory study. Setting Research laboratory. Patients or Other Participants Eight healthy, untrained individuals (age = 22 ± 1 years, height = 179.2 ± 6.4 cm, weight = 78.9 ± 5.9 kg). Intervention(s) Participants completed an acute bout of plyometric exercise (10 sets of 10 squat-jumps with a 1-minute rest between sets). Main Outcome Measure(s) Blood samples were collected 9 days and immediately before and 6 hours and 1, 2, and 3 days after the acute intervention. Muscle samples were collected 9 days before and 3 days after the exercise intervention. Blood samples were analyzed for creatine kinase activity. Muscle biopsies were analyzed for damage using fluorescent and electron transmission microscopy. Results Creatine kinase activity peaked 1 day after the exercise bout (529.0 ± 317.8 U/L). Immunofluorescence revealed sarcolemmal damage in 155 of 1616 fibers analyzed. Mainly fast-twitch fibers were damaged. Within subgroups, 7.6% of type I fibers, 10.3% of type IIa fibers, and 14.3% of type IIx fibers were damaged as assessed by losses in dystrophin staining. Similar damage was prevalent in IIx and IIa fibers. Electron microscopy revealed clearly distinguishable moderate and severe sarcomere damage, with damage quantifiably predominant in type II muscle fibers of both the glycolytic and oxidative subtypes (86% and 84%, respectively, versus only 27% of slow-twitch fibers). Conclusions We provide direct evidence that a single bout of plyometric exercise affected mainly type II muscle

  17. Photovoltaic detector based on type II heterostructure with deep AlSb/InAsSb/AlSb quantum well in the active region for the midinfrared spectral range

    SciTech Connect

    Mikhailova, M. P. Andreev, I. A.; Moiseev, K. D.; Ivanov, E. V.; Konovalov, G. G.; Mikhailov, M. Yu.; Yakovlev, Yu. P.

    2011-02-15

    Photodetectors for the spectral range 2-4 {mu}m, based on an asymmetric type-II heterostructure p-InAs/AlSb/InAsSb/AlSb/(p, n)GaSb with a single deep quantum well (QW) or three deep QWs at the heterointerface, have been grown by metal-organic vapor phase epitaxy and analyzed. The transport, luminescent, photoelectric, current-voltage, and capacitance-voltage characteristics of these structures have been examined. A high-intensity positive and negative luminescence was observed in the spectral range 3-4 {mu}m at high temperatures (300-400 K). The photosensitivity spectra were in the range 1.2-3.6 {mu}m (T = 77 K). Large values of the quantum yield ({eta} = 0.6-0.7), responsivity (S{sub {lambda}} = 0.9-1.4 A W{sup -1}), and detectivity (D*{sub {lambda}} = 3.5 Multiplication-Sign 10{sup 11} to 10{sup 10} cm Hz{sup 1/2} W{sup -1}) were obtained at T = 77-200 K. The small capacitance of the structures (C = 7.5 pF at V = -1 V and T = 300 K) enabled an estimate of the response time of the photodetector at {tau} = 75 ps, which corresponds to a bandwidth of about 6 GHz. Photodetectors of this kind are promising for heterodyne detection of the emission of quantum-cascade lasers and IR spectroscopy.

  18. Type-II Dirac surface states in topological crystalline insulators

    NASA Astrophysics Data System (ADS)

    Chiu, Ching-Kai; Chan, Y.-H.; Li, Xiao; Nohara, Y.; Schnyder, A. P.

    2017-01-01

    Recently, it has been realized that topological Weyl semimetals come in two different varieties: (i) with standard Weyl cones with pointlike Fermi surfaces (type I) and (ii) with tilted Weyl cones that appear at the contact of electron and hole pockets (type II). These two types of Weyl semimetals have very different physical properties, in particular, in their thermodynamics and magnetotransport. Here, we show that Dirac cone surface states of topological crystalline insulators can be distinguished in a similar way. We demonstrate this in terms of a general surface theory and then apply this knowledge to a family of antiperovskites of the form A3E O , where A denotes an alkaline earth metal, while E stands for Pb or Sn. Using ab initio DFT calculations, we investigate the bulk and surface topology of these antiperovskites and show that they exhibit type-I as well as type-II Dirac surface states protected by reflection symmetry. We find that the type-II Dirac states, as opposed to the type-I Dirac states, exhibit characteristic van Hove singularities in their dispersion, which lead to different thermodynamic properties, and which can serve as an experimental fingerprint of type-II surface states. The different magnetotransport characteristics between type-I and type-II surface states are discussed. In addition, we show that both type-I and type-II surface states exhibit an unusual helical spin polarization, which could lead to topological surface superconductivity.

  19. Surgical Treatment of Tubular Breast Type II

    PubMed Central

    Dabizha, Oleksii Y.; Kostenko, Alona A.; Gomolyako, Irina V.; Samko, Kristina A.; Borovyk, Denys V.

    2016-01-01

    Background: Tubular breasts are caused by connective tissue malformation and occur in puberty. The main clinical characteristics of the tubular breast are breast asymmetry, dense fibrous ring around the areola, hernia bulging of the areola, megaareola, and hypoplasia of quadrants of the breast. Pathology causes great psychological discomfort to patients. Methods: This study included 17 patients, aged 18 to 34 years, with tubular breast type II who had bilateral pathology and were treated from 2013 to 2016. They had surgical treatment by method of the clinic. Correction technique consisted of mobilization of the central part of the gland and formation of a glandular flap with vertical and horizontal scorings, which looks like a “chessboard,” that was sufficient to cover the lower pole of the implant. The flap was fixed to the submammary folds with stitches that prevented its reduction and accented a new submammary fold. To underscore the importance of the method and to study the structural features of the vascular bed of tubular breast tissue, a morphological study was conducted. Results: Mean follow-up time was 25 months (range between 13 and 37 mo). The proposed technique achieved good results. Complications (hematoma, circumareolar scarring, and “double-bubble” deformity) were identified in 4 patients. Conclusions: Our morphological study confirmed that tubular breast tissue has increased vascularity due to the vessels with characteristic minor malformation and due to the high restorative potential of the vascular bed. Therefore, an extended glandular flap could be freely mobilized without damaging its blood supply; thus, the flap in most cases covered the implant completely and good aesthetic results were achieved. PMID:27826461

  20. Type II superlattice technology for LWIR detectors

    NASA Astrophysics Data System (ADS)

    Klipstein, P. C.; Avnon, E.; Azulai, D.; Benny, Y.; Fraenkel, R.; Glozman, A.; Hojman, E.; Klin, O.; Krasovitsky, L.; Langof, L.; Lukomsky, I.; Nitzani, M.; Shtrichman, I.; Rappaport, N.; Snapi, N.; Weiss, E.; Tuito, A.

    2016-05-01

    SCD has developed a range of advanced infrared detectors based on III-V semiconductor heterostructures grown on GaSb. The XBn/XBp family of barrier detectors enables diffusion limited dark currents, comparable with MCT Rule-07, and high quantum efficiencies. This work describes some of the technical challenges that were overcome, and the ultimate performance that was finally achieved, for SCD's new 15 μm pitch "Pelican-D LW" type II superlattice (T2SL) XBp array detector. This detector is the first of SCD's line of high performance two dimensional arrays working in the LWIR spectral range, and was designed with a ~9.3 micron cut-off wavelength and a format of 640 x 512 pixels. It contains InAs/GaSb and InAs/AlSb T2SLs, engineered using k • p modeling of the energy bands and photo-response. The wafers are grown by molecular beam epitaxy and are fabricated into Focal Plane Array (FPA) detectors using standard FPA processes, including wet and dry etching, indium bump hybridization, under-fill, and back-side polishing. The FPA has a quantum efficiency of nearly 50%, and operates at 77 K and F/2.7 with background limited performance. The pixel operability of the FPA is above 99% and it exhibits a stable residual non uniformity (RNU) of better than 0.04% of the dynamic range. The FPA uses a new digital read-out integrated circuit (ROIC), and the complete detector closely follows the interfaces of SCD's MWIR Pelican-D detector. The Pelican- D LW detector is now in the final stages of qualification and transfer to production, with first prototypes already integrated into new electro-optical systems.

  1. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    SciTech Connect

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  2. Type II collagenopathies: Are there additional family members?

    SciTech Connect

    Freisinger, P.; Pontz, B.F.; Emmrich, P.; Stoess, H.; Bonaventure, J.

    1996-05-03

    The type II collagenopathies represent a group of chondrodysplasia sharing clinical and radiological manifestations which are expressed as a continuous spectrum of phenotypes, ranging from perinatally lethal to very mild conditions. Their common molecular bases are mutations in the type II collagen gene (COL2A1). We describe one case of lethal platyspondylic dysplasia, Torrance type, and a variant of lethal Kniest dysplasia, neither of which has been reported as a type II collagenopathy. Biochemical studies of cartilage collagens and morphological analysis of cartilage sections suggest that abnormalities of type II collagen structure and biosynthesis are the main pathogenetic factors in both cases. Thus, the phenotypic spectrum of type II collagenopathies might be greater than hitherto suspected. 20 refs., 6 figs.

  3. XIAP acts as a switch between type I and type II FAS-induced apoptosis signalling

    PubMed Central

    Jost, Philipp J.; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D.; Nachbur, Ueli; Huang, David C.S.; Bouillet, Philippe; Thomas, Helen E.; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2010-01-01

    FAS (APO-1/CD95) and its physiological ligand, FASL, regulate apoptotic death of unwanted or dangerous cells in many tissues, functioning as a guardian against autoimmunity and cancer development1-4. Distinct cell types differ in the mechanisms by which the ‘death receptor’ FAS triggers their apoptosis1-4. In type I cells, such as lymphocytes, activation of ‘effector caspases’ by FAS-induced activation of caspase-8 suffices for cell killing whereas in type II cells, including hepatocytes and pancreatic β-cells, amplification of the caspase cascade through caspase-8 mediated activation of the pro-apoptotic BCL-2 family member BID5 is essential6-8. Here we show, that loss of X-chromosome linked inhibitor of apoptosis (XIAP)9,10 function by gene-targeting or treatment with a second mitochondria-derived activator of caspases (SMAC11, also called DIABLO12: direct IAP binding protein with low pI) mimetic drug rendered hepatocytes independent of BID for FAS-induced apoptosis signalling. These results show that XIAP is the critical discriminator between type I versus type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions. PMID:19626005

  4. XIAP discriminates between type I and type II FAS-induced apoptosis.

    PubMed

    Jost, Philipp J; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D; Nachbur, Ueli; Huang, David C S; Bouillet, Philippe; Thomas, Helen E; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2009-08-20

    FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.

  5. Fermentation with Aquilariae Lignum Enhances the Anti-Diabetic Activity of Green Tea in Type II Diabetic db/db Mouse

    PubMed Central

    Kang, Su Jin; Lee, Ji Eun; Lee, Eun Kyung; Jung, Dae Hwa; Song, Chang Hyun; Park, Soo Jin; Choi, Seong Hun; Han, Chang Hyun; Ku, Sae Kwang; Lee, Young Joon

    2014-01-01

    The major components of tea may be significantly influenced according to the type of fermentation, and consequently the effects of different teas will differ. We examined whether green tea fermented with Aquilariae Lignum (fGT) shows a stronger anti-diabetic effect than unfermented green tea (GT) on mice with type 2 diabetes. To evaluate the anti-obesity effect of fGT, we assessed body weight, fecal excretion, serum leptin levels, exocrine pancreatic zymogen granule contents, and periovarian fat weight and adiponectin contents. Blood glucose levels, pancreatic weight, and numbers of pancreatic islet insulin- and glucagon-producing cells were determined to evaluate anti-hypoglycemic effects, while total cholesterol, triglyceride, and low- and high-density lipoprotein levels were determined to evaluate anti-hyperlipidemic effects. The antioxidant effect of fGT was detected by measuring malondialdehyde and glutathione contents and the activities of catalase and superoxide dismutase. fGT showed anti-obesity, anti-hypoglycemic, anti-hyperlipidemia, and antioxidant effects. Additionally, fGT exerted stronger anti-diabetic effects compared with GT. Collectively, these results suggested that fGT fermented with the appropriate amounts of Aquilariae Lignum (49:1) has a stronger effect compared with GT. Thus, fGT is a promising and potent new therapeutic agent for type 2 diabetes. PMID:25207824

  6. [Coordination compounds of Pd(II) with potential antitumor activity].

    PubMed

    González Vílchez, F; García Basallote, M; Benítez Ordóñez, J; Vilaplana Serrano, R

    1982-01-01

    The first results about the anti-neoplastic activity of Pd(II) ion coordinative compounds with complexones of the ethylenediamine-tetraacetic acid type are described. The assays employing Ehrlich ascites cancer of the mouse show that the presence of substitutes in the ethylenediamine skeleton originates important changes of the activity of such compounds.

  7. Diosgenin from Dioscorea bulbifera: novel hit for treatment of type II diabetes mellitus with inhibitory activity against α-amylase and α-glucosidase.

    PubMed

    Ghosh, Sougata; More, Piyush; Derle, Abhishek; Patil, Ajay B; Markad, Pramod; Asok, Adersh; Kumbhar, Navanath; Shaikh, Mahemud L; Ramanamurthy, Boppana; Shinde, Vaishali S; Dhavale, Dilip D; Chopade, Balu A

    2014-01-01

    Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, 1H NMR and 13C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus.

  8. Generating controllable type-II Weyl points via periodic driving

    NASA Astrophysics Data System (ADS)

    Bomantara, Raditya Weda; Gong, Jiangbin

    2016-12-01

    Type-II Weyl semimetals are a novel gapless topological phase of matter discovered recently in 2015. Similar to normal (type-I) Weyl semimetals, type-II Weyl semimetals consist of isolated band touching points. However, unlike type-I Weyl semimetals which have a linear energy dispersion around the band touching points forming a three-dimensional (3D) Dirac cone, type-II Weyl semimetals have a tilted conelike structure around the band touching points. This leads to various novel physical properties that are different from type-I Weyl semimetals. In order to study further the properties of type-II Weyl semimetals and perhaps realize them for future applications, generating controllable type-II Weyl semimetals is desirable. In this paper, we propose a way to generate a type-II Weyl semimetal via a generalized Harper model interacting with a harmonic driving field. When the field is treated classically, we find that only type-I Weyl points emerge. However, by treating the field quantum mechanically, some of these type-I Weyl points may turn into type-II Weyl points. Moreover, by tuning the coupling strength, it is possible to control the tilt of the Weyl points and the energy difference between two Weyl points, which makes it possible to generate a pair of mixed Weyl points of type-I and type-II. We also discuss how to physically distinguish these two types of Weyl points in the framework of our model via the Landau level structures in the presence of an artificial magnetic field. The results are of general interest to quantum optics as well as ongoing studies of Floquet topological phases.

  9. World War II Memorial Learning Activities.

    ERIC Educational Resources Information Center

    Tennessee State Dept. of Education, Nashville.

    These learning activities can help students get the most out of a visit to the Tennessee World War II Memorial, a group of ten pylons located in Nashville (Tennessee). Each pylon contains informational text about the events of World War II. The ten pylons are listed as: (1) "Pylon E-1--Terror: America Enters the War against Fascism, June…

  10. The effect of type II collagen on MSC osteogenic differentiation and bone defect repair.

    PubMed

    Chiu, Li-Hsuan; Lai, Wen-Fu T; Chang, Shwu-Fen; Wong, Chin-Chean; Fan, Cheng-Yu; Fang, Chia-Lang; Tsai, Yu-Hui

    2014-03-01

    The function of type II collagen in cartilage is well documented and its importance for long bone development has been implicated. However, the involvement of type II collagen in bone marrow derived mesenchymal stem cell (BMSC) osteogenesis has not been well investigated. This study elucidated the pivotal role of type II collagen in BMSC osteogenesis and its potential application to bone healing. Type II collagen-coated surface was found to accelerate calcium deposition, and the interaction of osteogenic medium-induced BMSCs with type II collagen-coated surface was mainly mediated through integrin α2β1. Exogenous type II collagen directly activated FAK-JNK signaling and resulted in the phosphorylation of RUNX2. In a segmental defect model in rats, type II collagen-HA/TCP-implanted rats showed significant callus formation at the reunion site, and a higher SFI (sciatic function index) scoring as comparing to other groups were also observed at 7, 14, and 21 day post-surgery. Collectively, type II collagen serves as a better modulator during early osteogenic differentiation of BMSCs by facilitating RUNX2 activation through integrin α2β1-FAK-JNK signaling axis, and enhance bone defect repair through an endochondral ossification-like process. These results advance our understanding about the cartilaginous ECM-BMSC interaction, and provide perspective for bone defect repair strategies.

  11. Ring A of nukacin ISK-1: a lipid II-binding motif for type-A(II) lantibiotic.

    PubMed

    Islam, Mohammad R; Nishie, Mami; Nagao, Jun-ichi; Zendo, Takeshi; Keller, Sandro; Nakayama, Jiro; Kohda, Daisuke; Sahl, Hans-Georg; Sonomoto, Kenji

    2012-02-29

    Ring A of nukacin ISK-1, which is also present in different type-A(II) lantibiotics, resembles a lipid II-binding motif (TxS/TxD/EC, x denotes undefined residues) similar to that present in mersacidin (type-B lantibiotics), which suggests that nukacin ISK-1 binds to lipid II as a docking molecule. Results from our experiments on peptidoglycan precursor (UDP-MurNAc-pp) accumulation and peptide antagonism assays clearly indicated that nukacin ISK-1 inhibits cell-wall biosynthesis, accumulating lipid II precursor inside the cell, and the peptide activity can be repressed by lipid I and lipid II. Interaction analysis of nukacin ISK-1 and different ring A variants with lipid II revealed that nukacin ISK-1 and nukacin D13E (a more active variant) have a high affinity (K(D) = 0.17 and 0.19 μM, respectively) for lipid II, whereas nukacin D13A (a less active variant) showed a lower affinity, and nukacin C14S (a negative variant lacking the ring A structure) exhibited no interaction. Therefore, on the basis of the structural similarity and positional significance of the amino acids in this region, we concluded that nukacin ISK-1 binds lipid II via its ring A region and may lead to the inhibition of cell-wall biosynthesis.

  12. Degree of polarization of type-II unpolarized light

    SciTech Connect

    Luis, Alfredo

    2007-05-15

    We address a quantitative determination of the degree of polarization of type-II unpolarized light via the computation of the distance between the polarization distribution and the uniform distribution associated with fully unpolarized light (i.e., type-I unpolarized light or natural light). We determine the maximum degree of polarization for type-II unpolarized light and the states reaching it. We show that the degree of polarization can be arbitrarily large, approaching complete polarization for increasing mean photon numbers.

  13. Use of Enterally Delivered Angiotensin II Type Ia Receptor Antagonists to Reduce the Severity of Colitis

    PubMed Central

    Okawada, Manabu; Koga, Hiroyuki; Larsen, Scott D.; Showalter, Hollis D.; Turbiak, Anjanette J.; Jin, Xiaohong; Lucas, Peter C.; Lipka, Elke; Hillfinger, John; Kim, Jae Seung

    2011-01-01

    Background Renin-angiotensin system blockade reduces inflammation in several organ systems. Having found a fourfold increase in angiotensin II type Ia receptor expression in a dextran sodium sulfate colitis model, we targeted blockade with angiotensin II type Ia receptor antagonists to prevent colitis development. Because hypotension is a major complication of angiotensin II type Ia receptor antagonists use, we hypothesized that use of angiotensin II type Ia receptor antagonists compounds which lack cell membrane permeability, and thus enteric absorption, would allow for direct enteral delivery at far higher concentrations than would be tolerated systemically, yet retain efficacy. Methods Based on the structure of the angiotensin II type Ia receptor antagonist losartan, deschloro-losartan was synthesized, which has extremely poor cell membrane permeability. Angiotensin II type Ia receptor antagonist efficacy was evaluated by determining the ability to block NF-κB activation in vitro. Dextran sodium sulfate colitis was induced in mice and angiotensin II type Ia receptor antagonist efficacy delivered transanally was assessed. Results In vitro, deschloro-losartan demonstrated near equal angiotensin II type Ia receptor blockade compared to losartan as well as another angiotensin II type Ia receptor antagonist, candesartan. In the dextran sodium sulfate model, each compound significantly improved clinical and histologic scores and epithelial cell apoptosis. Abundance of TNF-α, IL-1β, and IL6 mRNA were significantly decreased with each compound. In vitro and in vivo intestinal drug absorption, as well as measures of blood pressure and mucosal and colonic blood flow, showed significantly lower uptake of deschloro-losartan compared to losartan and candesartan. Conclusions This study demonstrated efficacy of high-dose angiotensin II type Ia receptor antagonists in this colitis model. We postulate that a specially designed angiotensin II type Ia receptor antagonist with

  14. Herringbone bursts associated with type II solar radio emission

    NASA Technical Reports Server (NTRS)

    Cairns, I. H.; Robinson, R. D.

    1987-01-01

    Detailed observations of the herringbone (HB) fine structure on type II solar radio bursts are presented. Data from the Culgoora radiospectrograph, radiometer and radioheliograph are analyzed. The characteristic spectral profiles, frequency drift rates and exciter velocities, fluxes, source sizes, brightness temperatures, and polarizations of individual HB bursts are determined. Correlations between individual bursts within the characteristic groups of bursts and the properties of the associated type II bursts are examined. These data are compatible with HB bursts being radiation at multiples of the plasma frequency generated by electron streams accelerated by the type II shock. HB bursts are physically distinct phenomena from type II and type III bursts, differing significantly in emission processes and/or source conditions; this conclusion indicates that many of the presently available theoretical ideas for HB bursts are incorrect.

  15. Type II oestrogen binding sites in human colorectal carcinoma.

    PubMed Central

    Piantelli, M; Ricci, R; Larocca, L M; Rinelli, A; Capelli, A; Rizzo, S; Scambia, G; Ranelletti, F O

    1990-01-01

    Seven cases of colorectal adenocarcinomas were investigated for the presence of oestrogen receptors and progesterone receptors. The tumours specifically bound oestradiol. This binding almost exclusively resulted from the presence of high numbers of type II oestrogen binding sites. Oestrogen receptors were absent or present at very low concentrations. Immunohistochemical investigation of nuclear oestrogen receptors gave negative results. This indicates that antioestrogen receptor antibodies recognise oestrogen receptors but not type II oestrogen binding sites. The presence of specific type II oestrogen binding sites and progesterone binding offers further evidence for a potential role for these steroids and their receptors in colorectal carcinoma. PMID:2266171

  16. Type II achondrogenesis-hypochondrogenesis: morphologic and immunohistopathologic studies.

    PubMed

    Godfrey, M; Keene, D R; Blank, E; Hori, H; Sakai, L Y; Sherwin, L A; Hollister, D W

    1988-12-01

    A 32-wk-gestation female with type II achondrogenesis-hypochondrogenesis has been studied. The clinical features were typical, and radiographs revealed short ribs, hypoplastic ilia, absence of ossification of sacrum, pubis, ischia, tali, calcanei, and many vertebral bodies; the long bones were short with mild metaphyseal flaring. The femoral cylinder index was 6.3. Comparison with previous cases placed the patient toward the mild end of the achondrogenesis-hypochondrogenesis spectrum (Whitley-Gorlin prototype IV). Light microscopy revealed hypercellular cartilage with decreased matrix traversed by numerous fibrous vascular canals. The growth plate was markedly abnormal. Ultrastructural studies revealed prominently dilated rough endoplasmic reticulum containing a fine granular material with occasional fibrils in all chondrocytes. Immunohistologic studies indicated irregular large areas of cartilage matrix staining with monoclonal antibody to human type III collagen. The relative intensity of matrix staining for type II collagen appeared diminished. More striking, however, were intense focal accumulations of type II collagen within small rounded perinuclear structures of most chondrocytes but not other cell types. These results strongly suggest intracellular retention of type II collagen within vacuolar structures, probably within the dilated rough endoplasmic reticulum observed in all chondrocytes by electron microscopy (EM), and imply the presence of an abnormal, poorly secreted type II collagen molecule. Biochemical studies (see companion paper) suggest that this patient had a new dominant lethal disorder caused by a structural abnormality of type II collagen.

  17. Serum markers for type II diabetes mellitus

    DOEpatents

    Metz, Thomas O; Qian, Wei-Jun; Jacobs, Jon M; Polpitiya, Ashoka D; Camp, II, David G; Smith, Richard D

    2014-03-18

    A method for identifying persons with increased risk of developing type 2 diabetes mellitus utilizing selected biomarkers described hereafter either alone or in combination. The present invention allows for broad based, reliable, screening of large population bases and provides other advantages, including the formulation of effective strategies for characterizing, archiving, and contrasting data from multiple sample types under varying conditions.

  18. A COL2A1 mutation in achondrogenesis type II results in the replacement of type II collagen by type I and III collagens in cartilage.

    PubMed

    Chan, D; Cole, W G; Chow, C W; Mundlos, S; Bateman, J F

    1995-01-27

    An autosomal dominant mutation in the COL2A1 gene was identified in a fetus with achondrogenesis type II. A transition of G2853 to A in exon 41 produced a substitution of Gly769 by Ser within the triple helical domain of the alpha 1(II) chain of type II collagen, interrupting the mandatory Gly-X-Y triplet sequence required for the normal formation of stable triple helical type II collagen molecules, resulting in the complete absence of type II collagen in the cartilage, which had a gelatinous composition. Type I and III collagens were the major species found in cartilage tissue and synthesized by cultured chondrocytes along with cartilage type XI collagen. However, cultured chondrocytes produced a trace amount of type II collagen, which was retained within the cells and not secreted. In situ hybridization of cartilage sections showed that the chondrocytes produced both type II and type I collagen mRNA. As a result, it is likely that the chondrocytes produced type II collagen molecules, which were then degraded. The close proximity of the Gly769 substitution by Ser to the mammalian collagenase cleavage site at Gly775-Leu776 may have produced an unstable domain that was highly susceptible to proteolysis. The type I and III collagens that replaced type II collagen were unable to maintain the normal structure of the hyaline cartilage but did support chondrocyte maturation, evidenced by the expression of type X collagen in the hypertrophic zone of the growth plate cartilage.

  19. Type II intermediate-luminosity optical transients (ILOTs)

    NASA Astrophysics Data System (ADS)

    Kashi, Amit; Soker, Noam

    2017-01-01

    We propose that in a small fraction of intermediate luminosity optical transients (ILOTs) powered by a strongly interacting binary system, the ejected mass in the equatorial plane can block the central source from our line of sight. We can therefore observe only radiation that is reprocessed by polar outflow, much as in type II active galactic nuclei (AGN). An ejection of M_ej,e=10^{-4} M_⊙ (1 M_⊙) at 30 degrees from the equatorial plane and at a velocity of v_e = 100 {km} {s}^{-1} will block the central source in the NIR for about 5 years (500 years). During that period of time the object might disappear in the visible band, and be detected only in the IR band due to polar dust. We raise the possibility that the recently observed disappearance of a red giant in the visible, designated N6946-BH1, is a type II ILOT rather than a failed supernova. For this case we estimate that the ejected mass in the polar direction was M_ej,p≈ 10^{-3} M_⊙. Our scenario predicts that this event should reinstate its visible emission in several decades.

  20. Prenylation of Rab8 GTPase by type I and type II geranylgeranyl transferases.

    PubMed Central

    Wilson, A L; Erdman, R A; Castellano, F; Maltese, W A

    1998-01-01

    Rab GTPases are post-translationally modified by addition of geranylgeranyl moieties to carboxyl-terminal cysteine residues. For Rab proteins ending with xxCC xCxC and CCxx motifs this modification is catalysed by geranylgeranyltransferase type II (GGTaseII), and is entirely dependent on the Rab substrate being bound to Rab escort protein (REP). Several Rab proteins contain carboxyl-terminal CaaL prenylation motifs typical of members of the Rho family, which are modified in a REP-independent manner by geranylgeranyltransferase type I (GGTaseI). The present studies show that one such Rab protein (Rab8), which ends with a CVLL motif, is uniquely able to serve as a substrate for either REP/GGTaseII or GGTaseI in cell-free assays. The modification of Rab8 by GGTaseI did not require REP, indicating that a REP-induced conformational change is not essential for exposure of the Rab carboxyl-terminal cysteine prenylation site. To determine whether one enzyme plays a predominant role in Rab8 prenylation in vivo, the incorporation of [3H]mevalonate into Rab8 was measured in human embryonal kidney 293 cells under conditions where the activity of GGTaseI, but not GGTaseII, was blocked by the peptidomimetic inhibitor GGTI-298. The GGTaseI inhibitor did not prevent prenylation of either overexpressed Myc-tagged Rab8 or endogenous Rab8, whereas prenylation of a known GGTaseI substrate with the same carboxyl-terminal motif, Cdc42Hs, was completely blocked. To rule out the possibility that the apparent prenylation of Rab8 by GGTaseII occurs only when GGTaseI activity is eliminated, metabolic labelling studies were carried out in the absence of the GGTaseI inhibitor, using a REP-binding-deficient Rab8 construct (Y78D) that cannot serve as a substrate for GGTaseII, but is indistinguishable from wild-type Rab8 as a substrate for GGTaseI. Prenylation of the Y78D mutant was reduced by 60-70% in intact cells, consistent with the conclusion that the majority of Rab8 is prenylated by the

  1. Tyrosine Hydroxylase Expression in Type II Cochlear Afferents in Mice.

    PubMed

    Vyas, Pankhuri; Wu, Jingjing Sherry; Zimmerman, Amanda; Fuchs, Paul; Glowatzki, Elisabeth

    2017-02-01

    Acoustic information propagates from the ear to the brain via spiral ganglion neurons that innervate hair cells in the cochlea. These afferents include unmyelinated type II fibers that constitute 5 % of the total, the majority being myelinated type I neurons. Lack of specific genetic markers of type II afferents in the cochlea has been a roadblock in studying their functional role. Unexpectedly, type II afferents were visualized by reporter proteins induced by tyrosine hydroxylase (TH)-driven Cre recombinase. The present study was designed to determine whether TH-driven Cre recombinase (TH-2A-CreER) provides a selective and reliable tool for identification and genetic manipulation of type II rather than type I cochlear afferents. The "TH-2A-CreER neurons" radiated from the spiral lamina, crossed the tunnel of Corti, turned towards the base of the cochlea, and traveled beneath the rows of outer hair cells. Neither the processes nor the somata of TH-2A-CreER neurons were labeled by antibodies that specifically labeled type I afferents and medial efferents. TH-2A-CreER-positive processes partially co-labeled with antibodies to peripherin, a known marker of type II afferents. Individual TH-2A-CreER neurons gave off short branches contacting 7-25 outer hair cells (OHCs). Only a fraction of TH-2A-CreER boutons were associated with CtBP2-immunopositive ribbons. These results show that TH-2A-CreER provides a selective marker for type II versus type I afferents and can be used to describe the morphology and arborization pattern of type II cochlear afferents in the mouse cochlea.

  2. Notch maintains Drosophila type II neuroblasts by suppressing expression of the Fez transcription factor Earmuff.

    PubMed

    Li, Xiaosu; Xie, Yonggang; Zhu, Sijun

    2016-07-15

    Notch signaling is crucial for maintaining neural stem cell (NSC) self-renewal and heterogeneity; however, the underlying mechanism is not well understood. In Drosophila, loss of Notch prematurely terminates the self-renewal of larval type II neuroblasts (NBs, the Drosophila NSCs) and transforms type II NBs into type I NBs. Here, we demonstrate that Notch maintains type II NBs by suppressing the activation of earmuff (erm) by Pointed P1 (PntP1). We show that loss of Notch or components of its canonical pathway leads to PntP1-dependent ectopic Erm expression in type II NBs. Knockdown of Erm significantly rescues the loss-of-Notch phenotypes, and misexpression of Erm phenocopies the loss of Notch. Ectopically expressed Erm promotes the transformation of type II NBs into type I NBs by inhibiting PntP1 function and expression in type II NBs. Our work not only elucidates a key mechanism of Notch-mediated maintenance of type II NB self-renewal and identity, but also reveals a novel function of Erm.

  3. The multiple acyl-coenzyme A dehydrogenation disorders, glutaric aciduria type II and ethylmalonic-adipic aciduria. Mitochondrial fatty acid oxidation, acyl-coenzyme A dehydrogenase, and electron transfer flavoprotein activities in fibroblasts.

    PubMed Central

    Amendt, B A; Rhead, W J

    1986-01-01

    The multiple acyl-coenzyme A (CoA) dehydrogenation disorders (MAD) include severe (S) and mild (M) variants, glutaric aciduria type II (MAD:S) and ethylmalonic-adipic aciduria (MAD:M). Intact MAD:M mitochondria oxidized [1-14C]octanoate, [1-14C]palmityl-CoA, and [1,5-14C]glutarate at 20-46% of control levels; MAD:S mitochondria oxidized these three substrates at 0.4-18% of control levels. In MAD:M mitochondria, acyl-CoA dehydrogenase (ADH) activities were similar to control, whereas MAD:S ADH activities ranged from 38% to 73% of control. Electron transfer flavoprotein (ETF) activities in five MAD:M cell lines ranged from 29 to 51% of control (P less than 0.01); ETF deficiency was the primary enzymatic defect in two MAD:M lines. In four MAD:S patients, ETF activities ranged from 3% to 6% of control (P less than 0.001); flavin adenine dinucleotide addition increased residual ETF activity from 4% to 21% of control in a single MAD:S line (P less than 0.01). Three MAD:S patients had ETF activities ranging from 33 to 53% of control; other investigators found deficient ETF-dehydrogenase activity in these MAD:S and three of our MAD:M cell lines. PMID:3722376

  4. Health Activities Project (HAP), Trial Edition II.

    ERIC Educational Resources Information Center

    Buller, Dave; And Others

    Contained within this Health Activities Project (HAP) trial edition (set II) are a teacher information folio and numerous student activity folios which center around the idea that students in grades 5-8 can control their own health and safety. Each student folio is organized into a Synopsis, Health Background, Materials, Setting Up, and Activities…

  5. Proteolysis of synaptobrevin, syntaxin, and SNAP-25 in alveolar epithelial type II cells.

    PubMed

    Zimmerman, U J; Malek, S K; Liu, L; Li, H L

    1999-10-01

    Synaptobrevin-2, syntaxin-1, and SNAP-25 were identified in rat alveolar epithelial type II cells by Western blot analysis. Synaptobrevin-2 was localized in the lamellar bodies, and syntaxin-1 and SNAP-25 were found in 0.4% Nonidet P40-soluble and -insoluble fractions, respectively, of the type II cells. When the isolated type II cells were stimulated for secretion with calcium ionophore A23187 or with phorbol 12-myristate 13-acetate, these proteins were found to have been proteolyzed. Preincubation of cells with calpain inhibitor II (N-acetylleucylleucylmethionine), however, prevented the proteolysis. Treatment of the cell lysate with exogenous calpain resulted in a time-dependent decrease of these proteins. The data suggest that synaptobrevin, syntaxin, and SNAP-25 are subject to proteolytic modification by activated calpain in intact type II cells stimulated for secretion.

  6. Achondrogenesis type II (Langer-Saldino)--a case report.

    PubMed

    Swar, M O; Srikrishna, B V

    1995-09-01

    Achondrogenesis is a lethal form of congenital chondrodystophy characterised by extreme micromelia. Definitive clinical and radiographic criteria have been established to differentiate Type II Achondrogenesis (Langer-Saldino) from type I Achondrogenesis (Parenti-Fraccaro). The mode of inheritance is autosomal recessive for both types. We are presenting a case of Type II Achondrogenesis, a still born male to consanguinous parents. The clinical features included an enlarged head, protuberant abdomen and short stubby limbs. The mother had earlier delivered two still born males presumably with similar features. Radiographic characteristics of absence of rib fractures and well ossified iliac bones with concave medial margins and absent or deficient ossification of the sacrum, ischiae, and pubic bones differentiated Type II Achondrogenesis from Type I Achondrogenesis.

  7. Achondrogenesis type II with normally developed extremities: a case report.

    PubMed

    Kocakoc, Ercan; Kiris, Adem

    2002-07-01

    We present a case of achondrogenesis type II with normally developed extremities that was confirmed with postmortem ultrasonographic and radiographic examination. The length of the long bones may vary and the diagnosis of achondrogenesis should not be ruled out with normally developed extremities. Intrauterine sonographic examination of the vertebrae is very important and the absence of vertebral body ossification may be the unique finding of achondrogenesis type II. Axial ultrasonographic images and postmortem plain radiographs are useful to clarify the pathology.

  8. Unsupervised Clustering of Type II Supernova Light Curves

    NASA Astrophysics Data System (ADS)

    Rubin, Adam; Gal-Yam, Avishay

    2016-09-01

    As new facilities come online, the astronomical community will be provided with extremely large data sets of well-sampled light curves (LCs) of transients. This motivates systematic studies of the LCs of supernovae (SNe) of all types, including the early rising phase. We performed unsupervised k-means clustering on a sample of 59 R-band SN II LCs and find that the rise to peak plays an important role in classifying LCs. Our sample can be divided into three classes: slowly rising (II-S), fast rise/slow decline (II-FS), and fast rise/fast decline (II-FF). We also identify three outliers based on the algorithm. The II-FF and II-FS classes are disjoint in their decline rates, while the II-S class is intermediate and “bridges the gap.” This may explain recent conflicting results regarding II-P/II-L populations. The II-FS class is also significantly less luminous than the other two classes. Performing clustering on the first two principal component analysis components gives equivalent results to using the full LC morphologies. This indicates that Type II LCs could possibly be reduced to two parameters. We present several important caveats to the technique, and find that the division into these classes is not fully robust. Moreover, these classes have some overlap, and are defined in the R band only. It is currently unclear if they represent distinct physical classes, and more data is needed to study these issues. However, we show that the outliers are actually composed of slowly evolving SN IIb, demonstrating the potential of such methods. The slowly evolving SNe IIb may arise from single massive progenitors.

  9. Angiotensin-II mediates ACE2 Internalization and Degradation through an Angiotensin-II type I receptor-dependent mechanism

    PubMed Central

    Lazartigues, Eric; Filipeanu, Catalin M.

    2014-01-01

    Angiotensin Converting Enzyme type 2 (ACE2) is a pivotal component of the renin-angiotensin system, promoting the conversion of Angiotensin (Ang)-II to Ang-(1-7). We previously reported that decreased ACE2 expression and activity contribute to the development of Ang-II-mediated hypertension in mice. The present study aimed to investigate the mechanisms involved in ACE2 down-regulation during neurogenic hypertension. In ACE2-transfected Neuro-2A cells, Ang-II treatment resulted in a significant attenuation of ACE2 enzymatic activity. Examination of the subcellular localization of ACE2 revealed that Ang-II treatment leads to ACE2 internalization and degradation into lysosomes. These effects were prevented by both the Ang-II type 1 receptor (AT1R) blocker losartan and the lysosomal inhibitor leupeptin. In contrast, in HEK293T cells, which lack endogenous AT1R, Ang-II failed to promote ACE2 internalization. Moreover, this effect could be induced after AT1R transfection. Further, co-immunoprecipitation experiments demonstrated that AT1R and ACE2 form complexes and these interactions were decreased by Ang-II treatment, which also enhanced ACE2 ubiquitination. In contrast, ACE2 activity was not changed by transfection of AT2 or Mas receptors. In vivo, Ang-II-mediated hypertension was blunted by chronic infusion of leupeptin in wildtype C57Bl/6, but not in ACE2 knockout mice. Overall, this is the first demonstration that elevated Ang-II levels reduce ACE2 expression and activity by stimulation of lysosomal degradation through an AT1R-dependent mechanism. PMID:25225202

  10. Characterization of the Type III restriction endonuclease PstII from Providencia stuartii.

    PubMed

    Sears, Alice; Peakman, Luke J; Wilson, Geoffrey G; Szczelkun, Mark D

    2005-01-01

    A new Type III restriction endonuclease designated PstII has been purified from Providencia stuartii. PstII recognizes the hexanucleotide sequence 5'-CTGATG(N)(25-26/27-28)-3'. Endonuclease activity requires a substrate with two copies of the recognition site in head-to-head repeat and is dependent on a low level of ATP hydrolysis ( approximately 40 ATP/site/min). Cleavage occurs at just one of the two sites and results in a staggered cut 25-26 nt downstream of the top strand sequence to generate a two base 5'-protruding end. Methylation of the site occurs on one strand only at the first adenine of 5'-CATCAG-3'. Therefore, PstII has characteristic Type III restriction enzyme activity as exemplified by EcoPI or EcoP15I. Moreover, sequence asymmetry of the PstII recognition site in the T7 genome acts as an historical imprint of Type III restriction activity in vivo. In contrast to other Type I and III enzymes, PstII has a more relaxed nucleotide specificity and can cut DNA with GTP and CTP (but not UTP). We also demonstrate that PstII and EcoP15I cannot interact and cleave a DNA substrate suggesting that Type III enzymes must make specific protein-protein contacts to activate endonuclease activity.

  11. Uterine type II estrogen-binding sites are not of eosinophil origin

    SciTech Connect

    Not Available

    1986-01-05

    A recent report suggested that nuclear type II sites in the rat uterus are of eosinophil origin and may represent (/sup 3/H)estradiol binding to eosinophil peroxidase. To further evaluate this hypothesis the authors examined the response of nuclear type II sites to estrogen under conditions where eosinophils are not present. Results of the experiments show that physiological levels of estradiol-17..beta.. (10 nM for 72 h) will stimulate nuclear type II sites in highly purified cultures of rat uterine stromal and myometrial cells. The magnitude of the response of type II sites to estradiol in these stromal (4-fold) and myometrial (80-fold) cell cultures was essentially identical to that observed in the uterine cell types following in vivo estrogen treatment. Since these highly purified cultures of uterine cells were prepared from the uterus of a 21-day ovariectomized rat which is devoid of eosinophils, it was concluded that estradiol stimulation of nuclear type II sites is a direct intracellular response to estrogen which occurs independent of eosinophil accumulation. Furthermore, it was found that type II sites in the rat uterus are not peroxidase. Stimulation of cytosol and nuclear type II sites by estrogen in the rat uterus is a direct intracellular response to the hormone unrelated to eosinophil accumulation and/or peroxidase activity.

  12. THE CONNECTIONS BETWEEN THE UV AND OPTICAL Fe ii EMISSION LINES IN TYPE 1 AGNs

    SciTech Connect

    Kovacević-Dojcinović, Jelena; Popović, Luka Č. E-mail: lpopovic@aob.bg.ac.rs

    2015-12-15

    We investigate the spectral properties of the UV (λλ2650–3050 Å) and optical (λλ4000–5500 Å) Fe ii emission features in a sample of 293 Type 1 active galactic nuclei (AGNs) from the Sloan Digital Sky Survey database. We explore different correlations between their emission line properties, as well as the correlations with other emission lines from the spectral range. We find several interesting correlations and outline the most interesting results as follows. (i) There is a kinematical connection between the UV and optical Fe ii lines, indicating that the UV and optical Fe ii lines originate from the outer part of the broad line region, the so-called intermediate line region. (ii) The unexplained anticorrelations of the optical Fe ii equivalent width (EW Fe ii{sub opt}) versus EW [O iii] 5007 Å and EW Fe ii{sub opt} versus FWHM Hβ have not been detected for the UV Fe ii lines. (iii) The significant averaged redshift in the UV Fe ii lines, which is not present in optical Fe ii, indicates an inflow in the UV Fe ii emitting clouds, and probably their asymmetric distribution. (iv) Also, we confirm the anticorrelation between the intensity ratio of the optical and UV Fe ii lines and the FWHM of Hβ, and we find the anticorrelations of this ratio with the widths of Mg ii 2800 Å, optical Fe ii, and UV Fe ii. This indicates a very important role for the column density and microturbulence in the emitting gas. We discuss the starburst activity in high-density regions of young AGNs as a possible explanation of the detected optical Fe ii correlations and intensity line ratios of the UV and optical Fe ii lines.

  13. Acoustic Type-II Weyl Nodes from Stacking Dimerized Chains

    NASA Astrophysics Data System (ADS)

    Yang, Zhaoju; Zhang, Baile

    2016-11-01

    Lorentz-violating type-II Weyl fermions, which were missed in Weyl's prediction of nowadays classified type-I Weyl fermions in quantum field theory, have recently been proposed in condensed matter systems. The semimetals hosting type-II Weyl fermions offer a rare platform for realizing many exotic physical phenomena that are different from type-I Weyl systems. Here we construct the acoustic version of a type-II Weyl Hamiltonian by stacking one-dimensional dimerized chains of acoustic resonators. This acoustic type-II Weyl system exhibits distinct features in a finite density of states and unique transport properties of Fermi-arc-like surface states. In a certain momentum space direction, the velocity of these surface states is determined by the tilting direction of the type-II Weyl nodes rather than the chirality dictated by the Chern number. Our study also provides an approach of constructing acoustic topological phases at different dimensions with the same building blocks.

  14. Quantum cascade light emitting diodes based on type-II quantum wells

    SciTech Connect

    Lin, C.H.; Yang, R.Q.; Zhang, D.; Murry, S.J.; Pei, S.S.; Allerman, A.A.; Kurtz, S.R.

    1997-01-21

    The authors have demonstrated room-temperature CW operation of type-II quantum cascade (QC) light emitting diodes at 4.2 {micro}m using InAs/InGaSb/InAlSb type-II quantum wells. The type-II QC configuration utilizes sequential multiple photon emissions in a staircase of coupled type-II quantum wells. The device was grown by molecular beam epitaxy on a p-type GaSb substrate and was compared of 20 periods of active regions separated by digitally graded quantum well injection regions. The maximum average output power is about 250 {micro}W at 80 K, and 140 {micro}W at 300 K at a repetition rate of 1 kHz with a duty cycle of 50%.

  15. CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms

    PubMed Central

    Meyer, Sara C.; Keller, Matthew D.; Chiu, Sophia; Koppikar, Priya; Guryanova, Olga A.; Rapaport, Franck; Xu, Ke; Manova, Katia; Pankov, Dmitry; O’Reilly, Richard J.; Kleppe, Maria; McKenney, Anna Sophia; Shih, Alan H.; Shank, Kaitlyn; Ahn, Jihae; Papalexi, Eftymia; Spitzer, Barbara; Socci, Nick; Viale, Agnes; Mandon, Emeline; Ebel, Nicolas; Andraos, Rita; Rubert, Joëlle; Dammassa, Ernesta; Romanet, Vincent; Dölemeyer, Arno; Zender, Michael; Heinlein, Melanie; Rampal, Rajit; Weinberg, Rona Singer; Hoffman, Ron; Sellers, William R.; Hofmann, Francesco; Murakami, Masato; Baffert, Fabienne; Gaul, Christoph; Radimerski, Thomas; Levine, Ross L.

    2015-01-01

    Summary Although clinically tested JAK inhibitors reduce splenomegaly and systemic symptoms, molecular responses are not observed in most myeloproliferative neoplasms (MPN) patients. We previously demonstrated that MPN cells become persistent to type I JAK inhibitors that bind the active conformation of JAK2. We investigated if CHZ868, a type II JAK inhibitor, would demonstrate activity in JAK inhibitor persistent cells, murine MPN models, and MPN patient samples. JAK2- and MPL-mutant cell lines were sensitive to CHZ868, including type I JAK inhibitor persistent cells. CHZ868 showed significant activity in murine MPN models and induced reductions in mutant allele burden not observed with type I JAK inhibitors. These data demonstrate that type II JAK inhibition is a viable therapeutic approach for MPN patients. PMID:26175413

  16. Immunohistochemical analysis of lattice corneal dystrophies types I and II.

    PubMed Central

    Kivelä, T; Tarkkanen, A; McLean, I; Ghiso, J; Frangione, B; Haltia, M

    1993-01-01

    Corneal buttons from four patients with lattice corneal dystrophy (LD) type I, thought to be an isolated corneal amyloidosis, and from six patients with LD type II, part of systemic familial amyloidosis, Finnish type (FAF; Meretoja's syndrome), were studied by immunohistochemistry to determine the differential distribution in the amyloid deposits of amyloid P component (AP), mutated gelsolin specific for FAF, and native gelsolin. In both types of LD, antibodies to AP labelled lattice lines and a discontinuous layer of amyloid deposits under Bowman's layer. In LD type II, particularly, they also reacted with streak-like amyloid deposits between corneal almellae, especially in the limbal region. While the anti-FAF antiserum strongly labelled all amyloid deposits in LD type II, it failed to react unequivocally with them in LD type I. Both in LD type I and in two control specimens representing granular dystrophy, the monoclonal antibody (MAb) GS-2C4 to gelsolin faintly labelled some deposits, while in LD type II it reacted non-homogeneously with most amyloid deposits. In all specimens, MAb GS-2C4 labelled corneal epithelial cells and occasional stromal keratocytes and endothelial cells. The results suggest that Meretoja's syndrome, a systemic disease, can be diagnosed even retrospectively from corneal buttons subjected to histopathological study. Images PMID:8110676

  17. Genetics Home Reference: mucopolysaccharidosis type II

    MedlinePlus

    ... function of the I2S enzyme. Lack of I2S enzyme activity leads to the accumulation of GAGs within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different ... a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008 Mar;167( ...

  18. Complex Type-II Interband Cascade MQW Photodetectors

    NASA Technical Reports Server (NTRS)

    Yang, Rui

    2007-01-01

    Multiple-quantum-well (MQW) photodetectors of a proposed type would contain active regions comprising multiple superlattice subregions. These devices would have complex structures: The superlattice of each subregion would be designed for enhanced absorption of photons in a desired wavelength band (typically in the infrared) and multiple subregions of different design would be cascaded for multicolor operation. The designs of these photodetectors would take advantage of the characteristic alignment of the edges of the electron-energy bands in type-II quantum-well structures: Within each finite superlattice, interband transitions would be used for detecting photons, and between finite superlattices, intraband relaxation and interband tunneling would be used for transport of charge carriers, all such as to enable detection of normally incident photons. Absorption of photons in the active region of a photodetector according to the proposal could be significantly enhanced by designing the superlattice/MQW structures to contain closely spaced energy states. The photodetector could be operated with a small bias to facilitate transport of charge carriers. The superlattices could be somewhat chirped, with a preferred transport direction.

  19. Alveolar type II cell-fibroblast interactions, synthesis and secretion of surfactant and type I collagen.

    PubMed

    Griffin, M; Bhandari, R; Hamilton, G; Chan, Y C; Powell, J T

    1993-06-01

    During alveolar development and alveolar repair close contacts are established between fibroblasts and lung epithelial cells through gaps in the basement membrane. Using co-culture systems we have investigated whether these close contacts influence synthesis and secretion of the principal surfactant apoprotein (SP-A) by cultured rat lung alveolar type II cells and the synthesis and secretion of type I collagen by fibroblasts. The alveolar type II cells remained cuboidal and grew in colonies on fibroblast feeder layers and on Matrigel-coated cell culture inserts but were progressively more flattened on fixed fibroblast monolayers and plastic. Alveolar type II cells cultured on plastic released almost all their SP-A into the medium by 4 days. Alveolar type II cells cultured on viable fibroblasts or Matrigel-coated inserts above fibroblasts accumulated SP-A in the medium at a constant rate for the first 4 days, and probably recycle SP-A by endocytosis. The amount of mRNA for SP-A was very low after 4 days of culture of alveolar type II cells on plastic, Matrigel-coated inserts or fixed fibroblast monolayers: relatively, the amount of mRNA for SP-A was increased 4-fold after culture of alveolar type II cells on viable fibroblasts. Co-culture of alveolar type II cells with confluent human dermal fibroblasts stimulated by 2- to 3-fold the secretion of collagen type I into the culture medium, even after the fibroblasts' growth had been arrested with mitomycin C. Collagen secretion, by fibroblasts, also was stimulated 2-fold by conditioned medium from alveolar type II cells cultured on Matrigel. The amount of mRNA for type I collagen increased only modestly when fibroblasts were cultured in this conditioned medium. This stimulation of type I collagen secretion diminished as the conditioned medium was diluted out, but at high dilutions further stimulation occurred, indicating that a factor that inhibited collagen secretion also was being diluted out. The conditioned medium

  20. A sample of Type II-L supernovae

    NASA Astrophysics Data System (ADS)

    Faran, T.; Poznanski, D.; Filippenko, A. V.; Chornock, R.; Foley, R. J.; Ganeshalingam, M.; Leonard, D. C.; Li, W.; Modjaz, M.; Serduke, F. J. D.; Silverman, J. M.

    2014-11-01

    What are Type II-Linear supernovae (SNe II-L)? This class, which has been ill defined for decades, now receives significant attention - both theoretically, in order to understand what happens to stars in the ˜15-25 M⊙ range, and observationally, with two independent studies suggesting that they cannot be cleanly separated photometrically from the regular hydrogen-rich SNe II-P characterized by a marked plateau in their light curve. Here, we analyse the multiband light curves and extensive spectroscopic coverage of a sample of 35 SNe II and find that 11 of them could be SNe II-L. The spectra of these SNe are hydrogen deficient, typically have shallow Hα absorption, may show indirect signs of helium via strong O I λ7774 absorption, and have faster line velocities consistent with a thin hydrogen shell. The light curves can be mostly differentiated from those of the regular, hydrogen-rich SNe II-P by their steeper decline rates and higher luminosity, and we propose to define them based on their decline in the V band: SNe II-L decline by more than 0.5 mag from peak brightness by day 50 after explosion. Using our sample we provide template light curves for SNe II-L and II-P in four photometric bands.

  1. Division II: Commission 10: Solar Activity

    NASA Astrophysics Data System (ADS)

    van Driel-Gesztelyi, Lidia; Scrijver, Karel J.; Klimchuk, James A.; Charbonneau, Paul; Fletcher, Lyndsay; Hasan, S. Sirajul; Hudson, Hugh S.; Kusano, Kanya; Mandrini, Cristina H.; Peter, Hardi; Vršnak, Bojan; Yan, Yihua

    2015-08-01

    The Business Meeting of Commission 10 was held as part of the Business Meeting of Division II (Sun and Heliosphere), chaired by Valentin Martínez-Pillet, the President of the Division. The President of Commission 10 (C10; Solar activity), Lidia van Driel-Gesztelyi, took the chair for the business meeting of C10. She summarised the activities of C10 over the triennium and the election of the incoming OC.

  2. Activation of store-mediated calcium entry by secretion-like coupling between the inositol 1,4,5-trisphosphate receptor type II and human transient receptor potential (hTrp1) channels in human platelets.

    PubMed Central

    Rosado, J A; Sage, S O

    2001-01-01

    Physical coupling between inositol 1,4,5-trisphosphate (IP(3)) receptors and transient receptor potential (Trp) channels has been demonstrated in both transfected and normal cells as a candidate mechanism for the activation of store-mediated Ca(2+) entry (SMCE). We have investigated the properties of the coupling between the type II IP(3) receptor and naturally expressed human Trp1 (hTrp1) in human platelets. Treatment with xestospongin C, an inhibitor of IP(3) receptor function, abolished SMCE and coupling between the IP(3) receptor and hTrp1. The coupling was activated by depletion of the intracellular Ca(2+) stores, and was reversed by refilling of the stores. We have also examined the role of actin filaments in the activation and maintenance of the coupling. Stabilization of the cortical actin network with jasplakinolide prevented the coupling, indicating that, as with secretion, the actin filaments at the cell periphery act as a negative clamp which prevents constitutive coupling. In addition, the actin cytoskeleton plays a positive role, since disruption of the actin network inhibited the coupling when the Ca(2+) stores were depleted. These results provide strong evidence for the activation of SMCE by a secretion-like coupling mechanism involving a reversible association between IP(3) receptors and hTrp1 in normal human cells. PMID:11336651

  3. Depression among patients with type-II diabetes mellitus.

    PubMed

    Khan, Mohammad Akmal; Sultan, Sayed Mohammad; Nazli, Rubina; Akhtar, Tasleem; Khan, Mudasar Ahmad; Sher, Nabila; Aslam, Hina

    2014-10-01

    This study aimed to determine the frequency of depression among patients with type-II diabetes mellitus in Peshawar at Khyber Teaching Hospital, Peshawar, from March to September 2010. Depression was assessed by using Beck Depressive Inventory-II (BDI-II). Out of 140 patients with type-II diabetes, 85 (61%) were women and 55 (39%) were men. Mean age was 45±7.45 years. Eighty four (60%) patients presented with severe depression. Depression was higher in females than males and widows. Depression was high in diabetic patients, especially in females and widows. It is of essence that psychiatric attention may be necessary to be incorporated in diabetes care both for prevention and treatment.

  4. Balneotherapy and platelet glutathione metabolism in type II diabetic patients

    NASA Astrophysics Data System (ADS)

    Ohtsuka, Yoshinori; Yabunaka, Noriyuki; Watanabe, Ichiro; Noro, Hiroshi; Agishi, Yuko

    1996-09-01

    Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r=0.692, P<0.02). After 4 weeks of balneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG <150 mg/dl), the level increased ( P<0.01) and in poorly controlled patients (FPG >150 mg/dl), the value decreased ( P<0.05). There was a negative correlation between glutathione peroxidase (GPX) activities and the levels of FPG ( r=-0.430, P<0.05). After balneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within ±3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

  5. Enhanced proliferation of primary rat type II pneumocytes by Jaagsiekte sheep retrovirus envelope protein

    SciTech Connect

    Johnson, Chassidy; Jahid, Sohail; Voelker, Dennis R.; Fan Hung

    2011-04-10

    Jaagsiekte sheep retrovirus (JSRV) is the causative agent of a contagious lung cancer in sheep. The envelope protein (Env) is the oncogene, as it can transform cell lines in culture and induce tumors in animals, although the mechanisms for transformation are not yet clear because a system to perform transformation assays in differentiated type II pneumocytes does not exist. In this study we report culture of primary rat type II pneumocytes in conditions that favor prolonged expression of markers for type II pneumocytes. Env-expressing cultures formed more colonies that were larger in size and were viable for longer periods of time compared to vector control samples. The cells that remained in culture longer were confirmed to be derived from type II pneumocytes because they expressed surfactant protein C, cytokeratin, displayed alkaline phosphatase activity and were positive for Nile red. This system will be useful to study JSRV Env in the targets of transformation.

  6. Type II supernovae as probes of environment metallicity: observations of host H II regions

    NASA Astrophysics Data System (ADS)

    Anderson, J. P.; Gutiérrez, C. P.; Dessart, L.; Hamuy, M.; Galbany, L.; Morrell, N. I.; Stritzinger, M. D.; Phillips, M. M.; Folatelli, G.; Boffin, H. M. J.; de Jaeger, T.; Kuncarayakti, H.; Prieto, J. L.

    2016-05-01

    Context. Spectral modelling of type II supernova atmospheres indicates a clear dependence of metal line strengths on progenitor metallicity. This dependence motivates further work to evaluate the accuracy with which these supernovae can be used as environment metallicity indicators. Aims: To assess this accuracy we present a sample of type II supernova host H ii-region spectroscopy, from which environment oxygen abundances have been derived. These environment abundances are compared to the observed strength of metal lines in supernova spectra. Methods: Combining our sample with measurements from the literature, we present oxygen abundances of 119 host H ii regions by extracting emission line fluxes and using abundance diagnostics. These abundances are then compared to equivalent widths of Fe ii 5018 Å at various time and colour epochs. Results: Our distribution of inferred type II supernova host H ii-region abundances has a range of ~0.6 dex. We confirm the dearth of type II supernovae exploding at metallicities lower than those found (on average) in the Large Magellanic Cloud. The equivalent width of Fe ii 5018 Å at 50 days post-explosion shows a statistically significant correlation with host H ii-region oxygen abundance. The strength of this correlation increases if one excludes abundance measurements derived far from supernova explosion sites. The correlation significance also increases if we only analyse a "gold" IIP sample, and if a colour epoch is used in place of time. In addition, no evidence is found of a correlation between progenitor metallicity and supernova light-curve or spectral properties - except for that stated above with respect to Fe ii 5018 Å equivalent widths - suggesting progenitor metallicity is not a driving factor in producing the diversity that is observed in our sample. Conclusions: This study provides observational evidence of the usefulness of type II supernovae as metallicity indicators. We finish with a discussion of the

  7. Production of human type II collagen using an efficient baculovirus-silkworm multigene expression system.

    PubMed

    Qi, Qi; Yao, Lunguang; Liang, Zhisheng; Yan, Donghua; Li, Zhuo; Huang, Yadong; Sun, Jingchen

    2016-12-01

    Human type II collagen is a macromolecular protein found throughout the human body. The baculovirus expression vector system is one of the most ideal systems for the routine production and display of recombinant eukaryotic proteins in insect, larvae, and mammalian cells. We use this system to express a full-length gene, human type II collagen cDNA (4257 bp), in cultured Spodoptera frugiperda 9 cells (Sf9), Bombyx mori cells, and silkworm larvae. In this study, the expression of human type II collagen gene in both insect cells and silkworm larvae was purified by nickel column chromatography, leading to 300-kDa bands in SDS-PAGE and western blotting indicative of collagen α-chains organized in a triple-helical structure. About 1 mg/larva human type II collagen is purified from silkworm skin, which shows a putative large scale of collagen production way. An activity assay of recombinant human type II collagen expressed by silkworm larvae demonstrated that the recombinant protein has considerable bioactive properties. Scanning electron microscopy of purified proteins clearly reveals randomly distributed and pitted structures. We conclude that the baculovirus-silkworm multigene expression system can be used as an efficient platform for express active human type II collagen and other complicated eukaryotic proteins.

  8. Comparison of type I and type II bovine viral diarrhea virus infection in swine.

    PubMed Central

    Walz, P H; Baker, J C; Mullaney, T P; Kaneene, J B; Maes, R K

    1999-01-01

    Some isolates of type II bovine viral diarrhea virus (BVDV) are capable of causing severe clinical disease in cattle. Bovine viral diarrhea virus infection has been reported in pigs, but the ability of these more virulent isolates of type II BVDV to induce severe clinical disease in pigs is unknown. It was our objective to compare clinical, virologic, and pathologic findings between type I and type II BVDV infection in pigs. Noninfected control and BVDV-infected 2-month-old pigs were used. A noncytopathic type I and a noncytopathic type II BVDV isolate were chosen for evaluation in feeder age swine based upon preliminary in vitro and in vivo experiments. A dose titration study was performed using 4 groups of 4 pigs for each viral isolate. The groups were inoculated intranasally with either sham (control), 10(3), 10(5), or 10(7) TCID50 of virus. The pigs were examined daily and clinical findings were recorded. Antemortem and postmortem samples were collected for virus isolation. Neither the type I nor type II BVDV isolates resulted in clinical signs of disease in pigs. Bovine viral diarrhea virus was isolated from antemortem and postmortem samples from groups of pigs receiving the 10(5) and the 10(7) TCID50 dose of the type I BVDV isolate. In contrast, BVDV was only isolated from postmortem samples in the group of pigs receiving the 10(7) TCID50 dose of the type II BVDV isolate. Type I BVDV was able to establish infection in pigs at lower doses by intranasal instillation than type II BVDV. Infection of pigs with a type II isolate of BVDV known to cause severe disease in calves did not result in clinically apparent disease in pigs. PMID:10369569

  9. A new long form of Sox5 (L-Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene.

    PubMed Central

    Lefebvre, V; Li, P; de Crombrugghe, B

    1998-01-01

    Transcripts for a new form of Sox5, called L-Sox5, and Sox6 are coexpressed with Sox9 in all chondrogenic sites of mouse embryos. A coiled-coil domain located in the N-terminal part of L-Sox5, and absent in Sox5, showed >90% identity with a similar domain in Sox6 and mediated homodimerization and heterodimerization with Sox6. Dimerization of L-Sox5/Sox6 greatly increased efficiency of binding of the two Sox proteins to DNA containing adjacent HMG sites. L-Sox5, Sox6 and Sox9 cooperatively activated expression of the chondrocyte differentiation marker Col2a1 in 10T1/2 and MC615 cells. A 48 bp chondrocyte-specific enhancer in this gene, which contains several HMG-like sites that are necessary for enhancer activity, bound the three Sox proteins and was cooperatively activated by the three Sox proteins in non-chondrogenic cells. Our data suggest that L-Sox5/Sox6 and Sox9, which belong to two different classes of Sox transcription factors, cooperate with each other in expression of Col2a1 and possibly other genes of the chondrocytic program. PMID:9755172

  10. Asymptomatic type II hyperprolinaemia associated with hyperglycinaemia in three sibs.

    PubMed Central

    Pavone, L; Mollica, F; Levy, H L

    1975-01-01

    Three clinically normal sibs were discovered to have type II hyperprolinaemia in a routine serum amino acid screening programme in Sicily. In addition to the basic biochemical features of type II hyperprolinaemia, all 3 children had marked hyperglycinaemia, whereas their parents had both normal blood proline and glycine concentrations. Clinical normality in individuals with hyperprolinaemia may suggest that these two metabolic disorders (types I and II) are benign entities. Furthermore, the absence of clinical abnormality in these sibs, despite the presence of marked hyperprolinaemia and hyperglycinaemia, may suggest that neither of these findings alone causes brain damage. The hyperglycinaemia in these sibs is unexplained and is an unusual if not unique finding in association with hyperprolinaemia. PMID:1200680

  11. Realizing type-II Weyl points in an optical lattice

    NASA Astrophysics Data System (ADS)

    Shastri, Kunal; Yang, Zhaoju; Zhang, Baile

    2017-01-01

    The recent discovery of the Lorentz symmetry-violating "type-II" Weyl semimetal phase has renewed interest in the study of Weyl physics in condensed-matter systems. However, tuning the exceptional properties of this novel state has remained a challenge. Optical lattices, created using standing laser beams, provide a convenient platform to tune tunneling parameters continuously in time. In this paper, we propose a generalized two level system exhibiting type-II Weyl points that can be realized using ultracold atoms in an optical lattice. The system is engineered using a three-dimensional lattice with complex π phase tunneling amplitudes. Various unique properties of the type-II Weyl semimetal such as open Fermi surface, anomalous chirality, and topological Fermi arcs can be probed using the proposed optical lattice scheme.

  12. Vortex liquid crystals in anisotropic type II superconductors.

    PubMed

    Carlson, E W; Castro Neto, A H; Campbell, D K

    2003-02-28

    In an isotropic type II superconductor in a moderate magnetic field, the transition to the normal state occurs by vortex lattice melting. In certain anisotropic cases, the vortices acquire elongated cross sections and interactions. Systems of anisotropic, interacting constituents generally exhibit liquid crystalline phases. We examine the possibility of a two step melting in homogeneous type II superconductors with anisotropic superfluid stiffness from a vortex lattice into first a vortex smectic and then a vortex nematic at high temperature and magnetic field. We find that fluctuations of the ordered phase favor an instability to an intermediate smectic-A in the absence of intrinsic pinning.

  13. Achondrogenesis type II (Langer-Saldino achondrogenesis): a case report.

    PubMed

    Lee, H S; Doh, J W; Kim, C J; Chi, J G

    2000-10-01

    Achondrogenesis is a lethal form of congenital chondrodystrophy characterized by extreme micromelia. We describe a case of achondrogenesis type II (Langer-Saldino achondrogenesis) detected by prenatal ultrasonography at 20-week gestation. A dwarfed fetus with large head, short neck and chest, prominent abdomen and short limbs was terminated transvaginally. Radiologic and histopathologic examination revealed features of mild form of achondrogenesis type II. Although the case had no known risk factor and the phenotypic abnormality was mild, modern development in prenatal screening made the early detection possible.

  14. Clinical and morphological features of Waardenburg syndrome type II.

    PubMed

    Mullaney, P B; Parsons, M A; Weatherhead, R G; Karcioglu, Z A

    1998-01-01

    Evaluation of 4-month-old girl who presented with congenital cataracts revealed heterochromia iridis, fundus hypopigmentation, residual white forelock and sensory neural hearing loss--findings consistent with Waardenburg syndrome type II. Bilateral peripheral iridectomies performed at lensectomy provided tissue for evaluation. Light microscopy revealed fewer melanocytes in the blue iris than in the brown. Electron microscopic examination showed a significant (p = 0.0001) reduction in melanosome size in the blue iris, and the nerve endings contained fewer vesicles. A defect in neural crest cell migration and melanin synthesis may be responsible for the heterochromia iridis seen in Waardenburg syndrome type II.

  15. Virtual screening and optimization of Type II inhibitors of JAK2 from a natural product library.

    PubMed

    Ma, Dik-Lung; Chan, Daniel Shiu-Hin; Wei, Guo; Zhong, Hai-Jing; Yang, Hui; Leung, Lai To; Gullen, Elizabeth A; Chiu, Pauline; Cheng, Yung-Chi; Leung, Chung-Hang

    2014-11-21

    Amentoflavone has been identified as a JAK2 inhibitor by structure-based virtual screening of a natural product library. In silico optimization using the DOLPHIN model yielded analogues with enhanced potency against JAK2 activity and HCV activity in cellulo. Molecular modeling and kinetic experiments suggested that the analogues may function as Type II inhibitors of JAK2.

  16. Identification of type II and III DDR2 inhibitors.

    PubMed

    Richters, André; Nguyen, Hoang D; Phan, Trang; Simard, Jeffrey R; Grütter, Christian; Engel, Julian; Rauh, Daniel

    2014-05-22

    Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.

  17. Sensory effects of capsaicin congeners. Part II: Importance of chemical structure and pungency in desensitizing activity of capsaicin-type compounds.

    PubMed

    Szolcsányi, J; Jancsó-Gábor, A

    1976-01-01

    The characteristic insensitivity of sensory nerve endings to chemically induced pain brought about by capsaicin could be reproduced on the rat's eye by pungent vanillylamides, homovanilloyl-alkylamides and piperine, while homovanilloyl-cycloalkylamides, -azacycloalkylamides, - alkylesters, -alkyl-homovanillylamides, undecenoyl-3-aminopropranololand zingerone were practically ineffective in this respect. Desensitizing potency was not parallel with the stimulating effect of the compounds, e.g. the strongly pungent homovanilloyl-octylester failed to desensitize the receptors, while the less pungent homovanilloyl-dodecylamide proved to be a more potent desensitizing agent than capsaicin itself. It is concluded that the inverse position of the acylamide linkage does not modify, while its replacement by an esteric group completely abolishes the desensitizing activity. In contrast to the stimulating effect, in desensitizing action the presence of an alkyl chain is essential and its optimal length corresponds to 10-12 C atoms. On the basis of these results the possible molecular interactions at the site of action are discussed.

  18. Towards a Cosmological Hubble Diagram for Type II-PSupernovae

    SciTech Connect

    Nugent, Peter; Sullivan, Mark; Ellis, Richard; Gal-Yam, Avishay; Leonard, Douglas C.; Howell, D. Andrew; Astier, Pierre; Carlberg, RaymondG.; Conley, Alex; Fabbro, Sebastien; Fouchez, Dominique; Neill, James D.; Pain, Reynald; Perrett, Kathy; Pritchet, Chris J; Regnault, Nicolas

    2006-03-20

    We present the first high-redshift Hubble diagram for Type II-P supernovae (SNe II-P) based upon five events at redshift upto z {approx}0.3. This diagram was constructed using photometry from the Canada-France-Hawaii Telescope Supernova Legacy Survey and absorption line spectroscopy from the Keck observatory. The method used to measure distances to these supernovae is based on recent work by Hamuy&Pinto (2002) and exploits a correlation between the absolute brightness of SNeII-P and the expansion velocities derived from the minimum of the Fe II 516.9 nm P-Cygni feature observed during the plateau phases. We present three refinements to this method which significantly improve the practicality of measuring the distances of SNe II-P at cosmologically interesting redshifts. These are an extinction correction measurement based on the V-I colors at day 50, across-correlation measurement for the expansion velocity and the ability to extrapolate such velocities accurately over almost the entire plateau phase. We apply this revised method to our dataset of high-redshift SNe II-P and find that the resulting Hubble diagram has a scatter of only 0.26 magnitudes, thus demonstrating the feasibility of measuring the expansion history, with present facilities, using a method independent of that based upon supernovae of Type Ia.

  19. Reduced DNA topoisomerase II activity in ataxia-telangiectasia cells.

    PubMed Central

    Singh, S P; Mohamed, R; Salmond, C; Lavin, M F

    1988-01-01

    Considerable evidence supports a defect at the level of chromatin structure or recognition of that structure in cells from patients with the human genetic disorder ataxia-telangiectasia. Accordingly, we have investigated the activities of enzymes that alter the topology of DNA in Epstein Barr Virus-transformed lymphoblastoid cells from patients with this syndrome. Reduced activity of DNA topoisomerase II, determined by unknotting of P4 phage DNA, was observed in partially purified extracts from 5 ataxia-telangiectasia cell lines. The levels of enzyme activity was reduced substantially in 4 of these cell lines and to a lesser extent in the other cell line compared to controls. DNA topoisomerase I, assayed by relaxation of supercoiled DNA, was found to be present at comparable levels in both cell types. Reduced activity of topoisomerase II in ataxia-telangiectasia is compatible with the molecular, cellular and clinical changes described in this syndrome. Images PMID:2836804

  20. Structure–activity correlations of variant forms of the B pentamer of Escherichia coli type II heat-labile enterotoxin LT-IIb with Toll-like receptor 2 binding

    SciTech Connect

    Cody, Vivian; Pace, Jim; Nawar, Hesham F.; King-Lyons, Natalie; Liang, Shuang; Connell, Terry D.; Hajishengallis, George

    2012-12-01

    Structural data for the S74D variant of the pentameric B subunit of type II heat-labile enterotoxin of Escherichia coli reveal a smaller pore opening that may explain its reduced Toll-like receptor binding affinity compared to that of the wild type enterotoxin. The explanation for the enhanced Toll-like receptor binding affinity of the S74A variant is more complex than simply being attributed to the pore opening. The pentameric B subunit of the type II heat-labile enterotoxin of Escherichia coli (LT-IIb-B{sub 5}) is a potent signaling molecule capable of modulating innate immune responses. It has previously been shown that LT-IIb-B{sub 5}, but not the LT-IIb-B{sub 5} Ser74Asp variant [LT-IIb-B{sub 5}(S74D)], activates Toll-like receptor (TLR2) signaling in macrophages. Consistent with this, the LT-IIb-B{sub 5}(S74D) variant failed to bind TLR2, in contrast to LT-IIb-B{sub 5} and the LT-IIb-B{sub 5} Thr13Ile [LT-IIb-B{sub 5}(T13I)] and LT-IIb-B{sub 5} Ser74Ala [LT-IIb-B{sub 5}(S74A)] variants, which displayed the highest binding activity to TLR2. Crystal structures of the Ser74Asp, Ser74Ala and Thr13Ile variants of LT-IIb-B{sub 5} have been determined to 1.90, 1.40 and 1.90 Å resolution, respectively. The structural data for the Ser74Asp variant reveal that the carboxylate side chain points into the pore, thereby reducing the pore size compared with that of the wild-type or the Ser74Ala variant B pentamer. On the basis of these crystallographic data, the reduced TLR2-binding affinity of the LT-IIb-B{sub 5}(S74D) variant may be the result of the pore of the pentamer being closed. On the other hand, the explanation for the enhanced TLR2-binding activity of the LT-IIb-B{sub 5}(S74A) variant is more complex as its activity is greater than that of the wild-type B pentamer, which also has an open pore as the Ser74 side chain points away from the pore opening. Data for the LT-IIb-B{sub 5}(T13I) variant show that four of the five variant side chains point to the outside

  1. Glycogen storage disease types I and II: Treatment updates

    PubMed Central

    Kishnani, P. S.; Chen, Y. T.

    2009-01-01

    Summary Prior to 2006 therapy for glycogen storage diseases consisted primarily of dietary interventions, which in the case of glycogen storage disease (GSD) type II (GSD II; Pompe disease) remained essentially palliative. Despite improved survival and growth, long-term complications of GSD type I (GSD I) have not responded to dietary therapy with uncooked cornstarch or continuous gastric feeding. The recognized significant risk of renal disease and liver malignancy in GSD I has prompted efforts towards curative therapy, including organ transplantation, in those deemed at risk. Results of clinical trials in infantile Pompe disease with alglucosidase alfa (Myozyme) showed prolonged survival reversal of cardiomyopathy, and motor gains. This resulted in broad label approval of Myozyme for Pompe disease in 2006. Furthermore, the development of experimental therapies, such as adeno-associated virus (AAV) vector-mediated gene therapy, holds promise for the availability of curative therapy in GSD I and GSD II/Pompe disease in the future. PMID:17308886

  2. Glycogen storage disease types I and II: treatment updates.

    PubMed

    Koeberl, D D; Kishnani, P S; Chen, Y T

    2007-04-01

    Prior to 2006 therapy for glycogen storage diseases consisted primarily of dietary interventions, which in the case of glycogen storage disease (GSD) type II (GSD II; Pompe disease) remained essentially palliative. Despite improved survival and growth, long-term complications of GSD type I (GSD I) have not responded to dietary therapy with uncooked cornstarch or continuous gastric feeding. The recognized significant risk of renal disease and liver malignancy in GSD I has prompted efforts towards curative therapy, including organ transplantation, in those deemed at risk. Results of clinical trials in infantile Pompe disease with alglucosidase alfa (Myozyme) showed prolonged survival reversal of cardiomyopathy, and motor gains. This resulted in broad label approval of Myozyme for Pompe disease in 2006. Furthermore, the development of experimental therapies, such as adeno-associated virus (AAV) vector-mediated gene therapy, holds promise for the availability of curative therapy in GSD I and GSD II/Pompe disease in the future.

  3. INSERTION DEVICE ACTIVITIES FOR NSLS-II.

    SciTech Connect

    TANABE,T.; HARDER, D.A.; HULBERT, S.; RAKOWSKI, G.; SKARITKA, J.

    2007-06-25

    National Synchrotron Light Source-II (NSLS-II) will be a medium energy storage ring of 3GeV electron beam energy with sub-nm.rad horizontal emittance and top-off capability at 500mA. Damping wigglers will be used not only to reduce the beam emittance but also used as broadband sources for users. Cryo-Permanent Magnet Undulators (CPMUs) are considered for hard X-ray linear device, and permanent magnet based elliptically polarized undulators (EPUs) for variable polarization devices for soft X-ray. 6T superconducting wiggler with minimal fan angle will be installed in the second phase as well as quasi-periodic EPU for VUV and possibly high-temperature superconducting undulator. R&D plans have been established to pursue the performance enhancement of the baseline devices and to design new types of insertion devices. A new insertion device development laboratory will also be established.

  4. Antidepressants in type II versus type I bipolar depression: A randomized discontinuation trial

    PubMed Central

    Vöhringer, Paul A.; Ostacher, Michael J.; El-Mallakh, Rif S.; Holtzman, Niki S.; Thommi, Sairah B.; Whitham, Elizabeth A.; Sullivan, Matthew C.; Baldassano, Claudia F.; Goodwin, Fredrick K.; Baldessarini, Ross J.; Ghaemi, S. Nassir

    2015-01-01

    Background We sought to test the hypothesis that antidepressants (ADs) may show preferential efficacy and safety among type-II over type-I bipolar disorder (BD) patients. Methods DSM-IV BD-I (n=21) and -II patients (n=49) in acute major depressive episodes were treated with ADs plus mood-stabilizers to euthymia sustained for two months, and then randomized openly to continue or discontinue ADs for up to three years. Outcomes were episode-recurrences and changes in standardized symptom-ratings. Results In follow-up averaging 1.64±0.98 years, both subgroups showed improvement in depressive episode frequency with AD continuation, but contrary to the hypothesis, more improvement was seen in type I than in type II bipolar depression (for type II, mean decrease in depressive episodes per year 0.21 ± 0.26 [CI:0.05, 0.37]; for type I: mean decrease 0.35 ± 0.15 [CI:0.30, 0.41]). Type II subjects continued on ADs had slightly more depressive, but fewer manic/hypomanic, episodes than BD-I subjects. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission. Conclusions The findings do not confirm the hypothesis that long-term AD treatment in BP-II has better outcomes than in BD-I patients, except somewhat lower risk of manic/hypomanic episodes. PMID:26267418

  5. Oro-facial-digital syndrome type II with otolaryngological manifestations.

    PubMed

    Havle, A; Shedge, S; Malashetti, S; Jain, V

    2015-01-01

    We present a case of oro-facial-digital syndrome type II (Mohr's syndrome) which is characterized by malformations of the oral cavity, face and digits. The facial and oral features include tongue nodules, cleft or high-arched palate, missing teeth, broad nose; cleft lip. The digital features include clinodactyly, polydactyly, syndactyly, brachydactyly and duplication of the hallux.

  6. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Coliform test: Type II devices. 159.126 Section 159.126 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.126 Coliform...

  7. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Coliform test: Type II devices. 159.126 Section 159.126 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.126 Coliform...

  8. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Coliform test: Type II devices. 159.126 Section 159.126 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.126 Coliform...

  9. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Coliform test: Type II devices. 159.126 Section 159.126 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.126 Coliform...

  10. Subcellular localization of mammalian type II membrane proteins.

    PubMed

    Aturaliya, Rajith N; Fink, J Lynn; Davis, Melissa J; Teasdale, Melvena S; Hanson, Kelly A; Miranda, Kevin C; Forrest, Alistair R R; Grimmond, Sean M; Suzuki, Harukazu; Kanamori, Mutsumi; Kai, Chikatoshi; Kawai, Jun; Carninci, Piero; Hayashizaki, Yoshihide; Teasdale, Rohan D

    2006-05-01

    Application of a computational membrane organization prediction pipeline, MemO, identified putative type II membrane proteins as proteins predicted to encode a single alpha-helical transmembrane domain (TMD) and no signal peptides. MemO was applied to RIKEN's mouse isoform protein set to identify 1436 non-overlapping genomic regions or transcriptional units (TUs), which encode exclusively type II membrane proteins. Proteins with overlapping predicted InterPro and TMDs were reviewed to discard false positive predictions resulting in a dataset comprised of 1831 transcripts in 1408 TUs. This dataset was used to develop a systematic protocol to document subcellular localization of type II membrane proteins. This approach combines mining of published literature to identify subcellular localization data and a high-throughput, polymerase chain reaction (PCR)-based approach to experimentally characterize subcellular localization. These approaches have provided localization data for 244 and 169 proteins. Type II membrane proteins are localized to all major organelle compartments; however, some biases were observed towards the early secretory pathway and punctate structures. Collectively, this study reports the subcellular localization of 26% of the defined dataset. All reported localization data are presented in the LOCATE database (http://www.locate.imb.uq.edu.au).

  11. Free flap transfer for complex regional pain syndrome type II

    PubMed Central

    Matsuda, Ken; Kikuchi, Mamoru; Murase, Tsuyoshi; Hosokawa, Ko; Shibata, Minoru

    2014-01-01

    Abstract A patient with complex regional pain syndrome type II was successfully treated using free anterolateral thigh flap transfer with digital nerve coaptation to the cutaneous nerve of the flap. Release of the scarred tissue and soft tissue coverage with targeted sensory nerve coaptation were useful in relieving severe pain. PMID:27252946

  12. 33 CFR 159.126 - Coliform test: Type II devices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... follows: During each of the 10 test days, one sample must be taken at the beginning, middle and end of an 8-consecutive hour period with one additional sample taken immediately following the peak capacity... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Coliform test: Type II...

  13. Carbon and Silicate Dust Condensation in Type II Supernovae

    NASA Astrophysics Data System (ADS)

    Deneault, Ethan A.-N.; Morales, B.

    2012-01-01

    We investigate the chemistry of formation and destruction processes of molecules in the expanding and cooling ejecta of Type II Supernovae. In this work, we use a kinetic chemistry network to explore the parameters and conditions of the ejecta which are required for the condensation of graphite and silicon carbide grains.

  14. Type II (noninsulin-dependent) diabetes: new treatment options.

    PubMed

    Bodzin, B J

    1997-01-01

    Type II diabetes (noninsulin-dependent diabetes mellitus [NIDDM]) is a common primary and secondary diagnosis in home care patients. This article describes the pathophysiology of NIDDM, the new drugs that have been released for treatment, and the nursing implications inherent in using these new medications.

  15. Type II restriction endonucleases--a historical perspective and more.

    PubMed

    Pingoud, Alfred; Wilson, Geoffrey G; Wende, Wolfgang

    2014-07-01

    This article continues the series of Surveys and Summaries on restriction endonucleases (REases) begun this year in Nucleic Acids Research. Here we discuss 'Type II' REases, the kind used for DNA analysis and cloning. We focus on their biochemistry: what they are, what they do, and how they do it. Type II REases are produced by prokaryotes to combat bacteriophages. With extreme accuracy, each recognizes a particular sequence in double-stranded DNA and cleaves at a fixed position within or nearby. The discoveries of these enzymes in the 1970s, and of the uses to which they could be put, have since impacted every corner of the life sciences. They became the enabling tools of molecular biology, genetics and biotechnology, and made analysis at the most fundamental levels routine. Hundreds of different REases have been discovered and are available commercially. Their genes have been cloned, sequenced and overexpressed. Most have been characterized to some extent, but few have been studied in depth. Here, we describe the original discoveries in this field, and the properties of the first Type II REases investigated. We discuss the mechanisms of sequence recognition and catalysis, and the varied oligomeric modes in which Type II REases act. We describe the surprising heterogeneity revealed by comparisons of their sequences and structures.

  16. Selective expression of latency-associated peptide (LAP) and IL-1 receptor type I/II (CD121a/CD121b) on activated human FOXP3+ regulatory T cells allows for their purification from expansion cultures

    PubMed Central

    Andersson, John; Hardwick, Donna; Bebris, Lolita; Illei, Gabor G.

    2009-01-01

    Although adoptive transfer of regulatory T cells (Foxp3+ Tregs) has proven to be efficacious in the prevention and treatment of autoimmune diseases and graft-versus-host disease in rodents, a major obstacle for the use of Treg immunotherapy in humans is the difficulty of obtaining a highly purified preparation after ex vivo expansion. We have identified latency-associated peptide (LAP) and IL-1 receptor type I and II (CD121a/CD121b) as unique cell-surface markers that distinguish activated Tregs from activated FOXP3− and FOXP3+ non-Tregs. We show that it is feasible to sort expanded FOXP3+ Tregs from non-Tregs with the use of techniques for magnetic bead cell separation based on expression of these 3 markers. After separation, the final product contains greater than 90% fully functional FOXP3+ Tregs. This novel protocol should facilitate the purification of Tregs for both cell-based therapies as well as detailed studies of human Treg function in health and disease. PMID:19299332

  17. Reproducible isolation of type II pneumocytes from fetal and adult rat lung using nycodenz density gradients.

    PubMed

    Viscardi, R M; Ullsperger, S; Resau, J H

    1992-01-01

    Isolating fresh, relatively pure type II pneumocytes from the lung, particularly of fetal origin, is a difficult process. Separation by buoyant density gradient centrifugation has been used successfully to isolate adult type II cells. There is concern, however, that Percoll, a gradient medium that is commonly used for type II cell isolation, may be toxic to cells. We evaluated a new gradient medium, Nycodenz, that is (1) a true solution, (2) transparent, (3) not metabolized by cells, and (4) nontoxic to cells. Type II pneumocytes were isolated from 19- and 21-day gestation fetal and adult rat lung by elastase digestion and separated on preformed isotonic Nycodenz gradients (2 mL each of 27.6, 20.7, 13.8, and 4.6 (w/v) solutions). Type II pneumocytes were recovered from the density range 1.057-1.061 and identified by binding of FITC-conjugated and gold-complexed Maclura pomifera lectin. Cells derived from 19-day fetal lung contained abundant glycogen and reacted with a monoclonal antibody to the cytokeratins 8 and 18, which are markers of the fetal type II cell. Adult type II cells reacted with antibodies to cytokeratins 8, 18, and 19. Type II cell purity was 79.7 +/- 2.4%, 83.8 +/- 2.8%, and 82.6 +/- 1.8% (means +/- SEM) for 19- and 21-day gestation fetal and adult lung preparations, respectively. Cell viability was greater than 95%. The final cell yield for adult preparations was 17.8 +/- 2.7 x 10(6)/rat (means +/- SEM). To determine if the freshly isolated type II pneumocytes were functionally active, the incorporation of [3H]choline into phosphatidylcholine was measured. The percent saturation of phosphatidylcholine was high for both populations of freshly isolated cells. However, adult type II pneumocytes incorporated [3H]choline into phosphatidylcholine more rapidly than 21-day gestation fetal cells (5.97 x 10(-3) dpm/10(6) cells/h vs. 0.32 x 10(-3) dpm/10(6) cells/h, P less than .005). We have demonstrated that, using the Nycodenz isolation method, it is

  18. Myosin II Activity Softens Cells in Suspension

    PubMed Central

    Chan, Chii J.; Ekpenyong, Andrew E.; Golfier, Stefan; Li, Wenhong; Chalut, Kevin J.; Otto, Oliver; Elgeti, Jens; Guck, Jochen; Lautenschläger, Franziska

    2015-01-01

    The cellular cytoskeleton is crucial for many cellular functions such as cell motility and wound healing, as well as other processes that require shape change or force generation. Actin is one cytoskeleton component that regulates cell mechanics. Important properties driving this regulation include the amount of actin, its level of cross-linking, and its coordination with the activity of specific molecular motors like myosin. While studies investigating the contribution of myosin activity to cell mechanics have been performed on cells attached to a substrate, we investigated mechanical properties of cells in suspension. To do this, we used multiple probes for cell mechanics including a microfluidic optical stretcher, a microfluidic microcirculation mimetic, and real-time deformability cytometry. We found that nonadherent blood cells, cells arrested in mitosis, and naturally adherent cells brought into suspension, stiffen and become more solidlike upon myosin inhibition across multiple timescales (milliseconds to minutes). Our results hold across several pharmacological and genetic perturbations targeting myosin. Our findings suggest that myosin II activity contributes to increased whole-cell compliance and fluidity. This finding is contrary to what has been reported for cells attached to a substrate, which stiffen via active myosin driven prestress. Our results establish the importance of myosin II as an active component in modulating suspended cell mechanics, with a functional role distinctly different from that for substrate-adhered cells. PMID:25902426

  19. A universal characteristic of type II radio bursts

    NASA Astrophysics Data System (ADS)

    Aguilar-Rodriguez, E.; Gopalswamy, N.; MacDowall, R.; Yashiro, S.; Kaiser, M. L.

    2005-12-01

    We present a study on the spectral properties of interplanetary type II radio bursts observed by the Radio and Plasma Wave (WAVES) experiment on board the Wind spacecraft. We investigated the relative bandwidth of the type II radio bursts observed by WAVES from 1997 up to 2003. We obtained three sets of events, based on the frequency domain of occurrence: 109 events in the low-frequency domain (30 KHz to 1000 kHz, detected by the RAD1 receiver), 216 events in the high-frequency domain (1-14 MHz, observed by the RAD2 receiver), and 73 events that spanned both domains (RAD1 and RAD2). Statistical results show that the average bandwidth-to-frequency ratio (BFR) was 0.28 ± 0.15, 0.26 ± 0.16, and 0.32 ± 0.15 for RAD1, RAD2, and RAD1 + RAD2, respectively. We compared our results with those obtained for ISEE-3 type II bursts and found a difference in the average BFR, which seems to be due to a selection effect. The BFR of the WAVES type II bursts is similar to that of metric type II bursts reported in published works. This suggests that the BFR is a universal characteristic, irrespective of the spectral domain. Finally, we also studied the BFR evolution with heliocentric distance using white-light observation of the associated coronal mass ejections. We found that the BFR remains roughly constant in the SOHO/LASCO field of view (i.e., from 2.1 to 32 solar radii), while the bandwidth itself decreases.

  20. Water-soluble undenatured type II collagen ameliorates collagen-induced arthritis in mice.

    PubMed

    Yoshinari, Orie; Shiojima, Yoshiaki; Moriyama, Hiroyoshi; Shinozaki, Junichi; Nakane, Takahisa; Masuda, Kazuo; Bagchi, Manashi

    2013-11-01

    Earlier studies have reported the efficacy of type II collagen (C II) in treating rheumatoid arthritis (RA). However, a few studies have investigated the ability of the antigenic collagen to induce oral tolerance, which is defined as active nonresponse to an orally administered antigen. We hypothesized that water-soluble undenatured C II had a similar effect as C II in RA. The present study was designed to examine the oral administration of a novel, water-soluble, undenatured C II (commercially known as NEXT-II) on collagen-induced arthritis (CIA) in mice. In addition, the underlying mechanism of NEXT-II was also identified. After a booster dose (collagen-Freund's complete adjuvant), mice were assigned to control CIA group, or NEXT-II treatment group, to which saline and NEXT-II were administered, respectively. The arthritis index in the NEXT-II group was significantly lower compared with the CIA group. Serum IL-6 levels in the NEXT-II group were significantly lower compared with the CIA group, while serum IL-2 level was higher. Furthermore, oral administration of NEXT-II enhanced the proportion of CD4+CD25+T (Treg) cells, and gene expressions of stimulated dendritic cells induced markers for regulatory T cells such as forkhead box p3 (Foxp3), transforming growth factor (TGF)-β1, and CD25. These results demonstrated that orally administered water-soluble undenatured C II (NEXT-II) is highly efficacious in the suppression of CIA by inducing CD4+CD25+ Treg cells.

  1. Simvastatin enhances bone morphogenetic protein receptor type II expression

    SciTech Connect

    Hu Hong; Sung, Arthur; Zhao, Guohua; Shi, Lingfang; Qiu Daoming; Nishimura, Toshihiko; Kao, Peter N. . E-mail: peterkao@stanford.edu

    2006-01-06

    Statins confer therapeutic benefits in systemic and pulmonary vascular diseases. Bone morphogenetic protein (BMP) receptors serve essential signaling functions in cardiovascular development and skeletal morphogenesis. Mutations in BMP receptor type II (BMPR2) are associated with human familial and idiopathic pulmonary arterial hypertension, and pathologic neointimal proliferation of vascular endothelial and smooth muscle cells within small pulmonary arteries. In severe experimental pulmonary hypertension, simvastatin reversed disease and conferred a 100% survival advantage. Here, modulation of BMPR2 gene expression by simvastatin is characterized in human embryonic kidney (HEK) 293T, pulmonary artery smooth muscle, and lung microvascular endothelial cells (HLMVECs). A 1.4 kb BMPR2 promoter containing Egr-1 binding sites confers reporter gene activation in 293T cells which is partially inhibited by simvastatin. Simvastatin enhances steady-state BMPR2 mRNA and protein expression in HLMVEC, through posttranscriptional mRNA stabilization. Simvastatin induction of BMPR2 expression may improve BMP-BMPR2 signaling thereby enhancing endothelial differentiation and function.

  2. Intrafibrillar Mineral May be Absent in Dentinogenesis Imperfecta Type II (DI-II)

    SciTech Connect

    Pople, John A.

    2001-03-29

    High-resolution synchrotron radiation computed tomography (SRCT) and small angle x-ray scattering (SAXS) were performed on normal and dentinogenesis imperfecta type II (DI-II) teeth. Three normal and three DI-II human third molars were used in this study. The normal molars were unerupted and had intact enamel; donors were female and ranged in age from 18-21y. The DI-II specimens, which were also unerupted with intact enamel, came from a single female donor age 20y. SRCT showed that the mineral concentration was 33% lower on average in the DI-II dentin with respect to normal dentin. The SAXS spectra from normal dentin exhibited low-angle diffraction peaks at harmonics of 67.6 nm, consistent with nucleation and growth of the apatite phase within gaps in the collagen fibrils (intrafibrillar mineralization). In contrast, the low-angle peaks were almost nonexistent in the DI-II dentin. Crystallite thickness was independent of location in both DI-II and normal dentin, although the crystallites were significantly thicker in DI-II dentin (6.8 nm (s.d. = 0.5) vs 5.1 nm (s.d. = 0.6)). The shape factor of the crystallites, as determined by SAXS, showed a continuous progression in normal dentin from roughly one-dimensional (needle-like) near the pulp to two-dimensional (plate-like) near the dentin-enamel junction. The crystallites in DI-II dentin, on the other hand, remained needle-like throughout. The above observations are consistent with an absence of intrafibrillar mineral in DI-II dentin.

  3. Adsorbent-adsorbate interactions in the adsorption of Cd(II) and Hg(II) on ozonized activated carbons.

    PubMed

    Sánchez-Polo, M; Rivera-Utrilla, J

    2002-09-01

    The present work investigated the effect of surface oxygenated groups on the adsorption of Cd(II) and Hg(II) by activated carbon. A study was undertaken to determine the adsorption isotherms and the influence of the pH on the adsorption of each metallic ion by a series of ozonized activated carbons. In the case of Cd(II), the adsorption capacity and the affinity of the adsorbent augmented with the increase in acid-oxygenated groups on the activated carbon surface. These results imply that electrostatic-type interactions predominate in this adsorption process. The adsorption observed at solution pH values below the pH(PZC) of the carbon indicates that other forces also participate in this process. Ionic exchange between -C pi-H3O+ interaction protons and Cd(II) ions would account for these findings. In the case of Hg(II), the adsorption diminished with an increase in the degree of oxidation of the activated carbon. The presence of electron-withdrawing groups on oxidized carbons decreases the electronic density of their surface, producing a reduction in the adsorbent-adsorbate dispersion interactions and in their reductive capacity, thus decreasing the adsorption of Hg(II) on the activated carbon. At pH values above 3, the pH had no influence on the adsorption of Hg(II) by the activated carbon, confirming that electrostatic interactions do not have a determinant influence on Hg(II) adsorption.

  4. Differential properties of type I and type II benzodiazepine receptors in mammalian CNS neurones.

    PubMed Central

    Yakushiji, T.; Shirasaki, T.; Munakata, M.; Hirata, A.; Akaike, N.

    1993-01-01

    1. The effects of benzodiazepine receptor (BZR) partial agonists, Y-23684 and CL218,872, were compared with its full agonist, diazepam, on gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) in acutely dissociated rat cerebral cortex (CTX), cerebellar Purkinje (CPJ) and spinal ventral horn (SVH) neurones, by the whole-cell mode patch-clamp technique. 2. The GABA-induced responses were essentially the same in both SVH and CPJ neurones, but the KD value of the GABA response in CTX neurone was lower than those in the other two brain regions. 3. Enhancement of the GABA response by the two partial agonists was about one-third of that by diazepam in the SVH neurones (where type II subtype of BZR, BZ2, is predominant), whereas these partial agonists potentiated the GABA response as much as diazepam in CPJ neurones (where the type I subtype of BZR, BZ1, is predominant). In CTX neurones where both type I and II variants are expressed, the augmentation ratio of the GABA response by diazepam was between the values in CPJ and SVH neurones. 4. In concentration-response relationships of BZR partial agonists, the threshold concentrations, KD values and maximal augmentation ratio of the GABA response were similar in all CTX, CPJ and SVH neurones. Also, in all preparations, the threshold concentration and KD values of diazepam action were 10 fold less than those induced by partial agonists. 5. All BZR agonists shifted the concentration-response relationship for GABA to the left without changing the maximum current amplitude, indicating that activation of both BZ1 and BZ2 increase the affinity of the GABAA receptor for GABA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8395299

  5. Differential properties of type I and type II benzodiazepine receptors in mammalian CNS neurones.

    PubMed

    Yakushiji, T; Shirasaki, T; Munakata, M; Hirata, A; Akaike, N

    1993-07-01

    1. The effects of benzodiazepine receptor (BZR) partial agonists, Y-23684 and CL218,872, were compared with its full agonist, diazepam, on gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) in acutely dissociated rat cerebral cortex (CTX), cerebellar Purkinje (CPJ) and spinal ventral horn (SVH) neurones, by the whole-cell mode patch-clamp technique. 2. The GABA-induced responses were essentially the same in both SVH and CPJ neurones, but the KD value of the GABA response in CTX neurone was lower than those in the other two brain regions. 3. Enhancement of the GABA response by the two partial agonists was about one-third of that by diazepam in the SVH neurones (where type II subtype of BZR, BZ2, is predominant), whereas these partial agonists potentiated the GABA response as much as diazepam in CPJ neurones (where the type I subtype of BZR, BZ1, is predominant). In CTX neurones where both type I and II variants are expressed, the augmentation ratio of the GABA response by diazepam was between the values in CPJ and SVH neurones. 4. In concentration-response relationships of BZR partial agonists, the threshold concentrations, KD values and maximal augmentation ratio of the GABA response were similar in all CTX, CPJ and SVH neurones. Also, in all preparations, the threshold concentration and KD values of diazepam action were 10 fold less than those induced by partial agonists. 5. All BZR agonists shifted the concentration-response relationship for GABA to the left without changing the maximum current amplitude, indicating that activation of both BZ1 and BZ2 increase the affinity of the GABAA receptor for GABA. 6. The results are important in clarifying the mechanism of anxiety and might explain the anxioselectivity of BZR partial agonists.

  6. Repression of host RNA polymerase II transcription by herpes simplex virus type 1.

    PubMed Central

    Spencer, C A; Dahmus, M E; Rice, S A

    1997-01-01

    Lytic infection of mammalian cells with herpes simplex virus type 1 (HSV-1) results in rapid repression of host gene expression and selective activation of the viral genome. This transformation in gene expression is thought to involve repression of host transcription and diversion of the host RNA polymerase (RNAP II) transcription machinery to the viral genome. However, the extent of virus-induced host transcription repression and the mechanisms responsible for these major shifts in transcription specificities have not been examined. To determine how HSV-1 accomplishes repression of host RNAP II transcription, we assayed transcription patterns on several cellular genes in cells infected with mutant and wild-type HSV-1. Our results suggest that HSV-1 represses RNAP II transcription on most cellular genes. However, each cellular gene we examined responds differently to the transcription repressive effects of virus infection, both quantitatively and with respect to the involvement of viral gene products. Virus-induced shutoff of host RNAP II transcription requires expression of multiple immediate-early genes. In contrast, expression of delayed-early and late genes and viral DNA replication appear to contribute little to repression of host cell RNAP II transcription. Modification of RNAP II to the intermediately phosphorylated (II(I)) form appears unlinked to virus-induced repression of host cell transcription. However, full repression of host transcription is correlated with depletion of the hyperphosphorylated (IIO) form of RNAP II. PMID:9032335

  7. The Three-Dimensional Structural Basis of Type II Hyperprolinemia

    SciTech Connect

    Srivastava, Dhiraj; Singh, Ranjan K.; Moxley, Michael A.; Henzl, Michael T.; Becker, Donald F.; Tanner, John J.

    2012-08-31

    Type II hyperprolinemia is an autosomal recessive disorder caused by a deficiency in {Delta}{sup 1}-pyrroline-5-carboxylate dehydrogenase (P5CDH; also known as ALDH4A1), the aldehyde dehydrogenase that catalyzes the oxidation of glutamate semialdehyde to glutamate. Here, we report the first structure of human P5CDH (HsP5CDH) and investigate the impact of the hyperprolinemia-associated mutation of Ser352 to Leu on the structure and catalytic properties of the enzyme. The 2. 5-{angstrom}-resolution crystal structure of HsP5CDH was determined using experimental phasing. Structures of the mutant enzymes S352A (2.4 {angstrom}) and S352L (2.85 {angstrom}) were determined to elucidate the structural consequences of altering Ser352. Structures of the 93% identical mouse P5CDH complexed with sulfate ion (1.3 {angstrom} resolution), glutamate (1.5 {angstrom}), and NAD{sup +} (1.5 {angstrom}) were determined to obtain high-resolution views of the active site. Together, the structures show that Ser352 occupies a hydrophilic pocket and is connected via water-mediated hydrogen bonds to catalytic Cys348. Mutation of Ser352 to Leu is shown to abolish catalytic activity and eliminate NAD{sup +} binding. Analysis of the S352A mutant shows that these functional defects are caused by the introduction of the nonpolar Leu352 side chain rather than the removal of the Ser352 hydroxyl. The S352L structure shows that the mutation induces a dramatic 8-{angstrom} rearrangement of the catalytic loop. Because of this conformational change, Ser349 is not positioned to interact with the aldehyde substrate, conserved Glu447 is no longer poised to bind NAD{sup +}, and Cys348 faces the wrong direction for nucleophilic attack. These structural alterations render the enzyme inactive.

  8. The three-dimensional structural basis of type II hyperprolinemia.

    PubMed

    Srivastava, Dhiraj; Singh, Ranjan K; Moxley, Michael A; Henzl, Michael T; Becker, Donald F; Tanner, John J

    2012-07-13

    Type II hyperprolinemia is an autosomal recessive disorder caused by a deficiency in Δ(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH; also known as ALDH4A1), the aldehyde dehydrogenase that catalyzes the oxidation of glutamate semialdehyde to glutamate. Here, we report the first structure of human P5CDH (HsP5CDH) and investigate the impact of the hyperprolinemia-associated mutation of Ser352 to Leu on the structure and catalytic properties of the enzyme. The 2. 5-Å-resolution crystal structure of HsP5CDH was determined using experimental phasing. Structures of the mutant enzymes S352A (2.4 Å) and S352L (2.85 Å) were determined to elucidate the structural consequences of altering Ser352. Structures of the 93% identical mouse P5CDH complexed with sulfate ion (1.3 Å resolution), glutamate (1.5 Å), and NAD(+) (1.5 Å) were determined to obtain high-resolution views of the active site. Together, the structures show that Ser352 occupies a hydrophilic pocket and is connected via water-mediated hydrogen bonds to catalytic Cys348. Mutation of Ser352 to Leu is shown to abolish catalytic activity and eliminate NAD(+) binding. Analysis of the S352A mutant shows that these functional defects are caused by the introduction of the nonpolar Leu352 side chain rather than the removal of the Ser352 hydroxyl. The S352L structure shows that the mutation induces a dramatic 8-Å rearrangement of the catalytic loop. Because of this conformational change, Ser349 is not positioned to interact with the aldehyde substrate, conserved Glu447 is no longer poised to bind NAD(+), and Cys348 faces the wrong direction for nucleophilic attack. These structural alterations render the enzyme inactive.

  9. Refined genetic and physical mapping of BPES type II.

    PubMed

    Messiaen, L; Leroy, B P; De Bie, S; De Pauw, K; Van Roy, N; Speleman, F; Van Camp, G; De Paepe, A

    1996-01-01

    BPES is a genetic disorder including blepharophimosis, ptosis of the eyelids, epicanthus inversus and telecanthus. Type I is associated with female infertility, whereas type II presents without other symptoms. Both types I and II occur sporadically or are inherited as an autosomal dominant trait. We present a molecular genetic and cytogenetic study in a large four-generation Belgian family with BPES type II. Karyotype analysis on high-resolution banded chromosomes yielded normal results. Fluorescence in situ hybridization (FISH) with cosmid probes spanning 3q22-q24 revealed normal hybridization patterns. Sixteen polymorphic CA repeats encompassing region 3q13-q25 were analysed. Linkage analysis in this large four-generation family provides conclusive evidence for the presence of a BPES gene in this region. Two-point lod scores greater than 3.0 between the disease and the following markers were seen: D3S1589 (4.67), D3S1292 (3.52), D3S1290 (3.59) and D3S1549 (3.65). By FISH, D3S1290, D3S1292 and D3S1549 were assigned to chromosome 3q23 using YACs positive for these markers.

  10. Type II restriction endonucleases—a historical perspective and more

    PubMed Central

    Pingoud, Alfred; Wilson, Geoffrey G.; Wende, Wolfgang

    2014-01-01

    This article continues the series of Surveys and Summaries on restriction endonucleases (REases) begun this year in Nucleic Acids Research. Here we discuss ‘Type II’ REases, the kind used for DNA analysis and cloning. We focus on their biochemistry: what they are, what they do, and how they do it. Type II REases are produced by prokaryotes to combat bacteriophages. With extreme accuracy, each recognizes a particular sequence in double-stranded DNA and cleaves at a fixed position within or nearby. The discoveries of these enzymes in the 1970s, and of the uses to which they could be put, have since impacted every corner of the life sciences. They became the enabling tools of molecular biology, genetics and biotechnology, and made analysis at the most fundamental levels routine. Hundreds of different REases have been discovered and are available commercially. Their genes have been cloned, sequenced and overexpressed. Most have been characterized to some extent, but few have been studied in depth. Here, we describe the original discoveries in this field, and the properties of the first Type II REases investigated. We discuss the mechanisms of sequence recognition and catalysis, and the varied oligomeric modes in which Type II REases act. We describe the surprising heterogeneity revealed by comparisons of their sequences and structures. PMID:24878924

  11. On the nature of rapidly fading Type II supernovae

    NASA Astrophysics Data System (ADS)

    Moriya, Takashi J.; Pruzhinskaya, Maria V.; Ergon, Mattias; Blinnikov, Sergei I.

    2016-01-01

    It has been suggested that Type II supernovae with rapidly fading light curves (a.k.a. Type IIL supernovae) are explosions of progenitors with low-mass hydrogen-rich envelopes which are of the order of 1 M⊙. We investigate light-curve properties of supernovae from such progenitors. We confirm that such progenitors lead to rapidly fading Type II supernovae. We find that the luminosity of supernovae from such progenitors with the canonical explosion energy of 1051 erg and 56Ni mass of 0.05 M⊙ can increase temporarily shortly before all the hydrogen in the envelope recombines. As a result, a bump appears in their light curves. The bump appears because the heating from the nuclear decay of 56Ni can keep the bottom of hydrogen-rich layers in the ejecta ionized, and thus the photosphere can stay there for a while. We find that the light-curve bump becomes less significant when we make explosion energy larger (≳2 × 1051 erg), 56Ni mass smaller (≲0.01 M⊙), 56Ni mixed in the ejecta, or the progenitor radius larger. Helium mixing in hydrogen-rich layers makes the light-curve decline rates large but does not help reducing the light-curve bump. Because the light-curve bump we found in our light-curve models has not been observed in rapidly fading Type II supernovae, they may be characterized by not only low-mass hydrogen-rich envelopes but also higher explosion energy, larger degrees of 56Ni mixing, and/or larger progenitor radii than slowly fading Type II supernovae, so that the light-curve bump does not become significant.

  12. Combination of MTX and LEF attenuates inflammatory bone erosion by down-regulation of receptor activator of NF-kB ligand and interleukin-17 in type II collagen-induced arthritis rats.

    PubMed

    Yao, Yao; Ding, Cong-zhu; Fang, Yun

    2013-07-01

    The objectives of this study were to determine the effect of combination of methotrexate (MTX) and leflunomide (LEF) on type II collagen-induced arthritis rats and its mechanism. Curative effect was confirmed on CIA rats, which were randomized and divided into model, MTX, LEF and MTX + LEF group. Weights and joint swelling scores of rats were recorded. Interleukin (IL)-17, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) concentration in serum were determined by ELISA. H&E dyeing of joint was used to estimate the inflammation and osteoclasia extent. The mechanism was investigated through fibroblast-like synoviocytes isolated from RA patients. The effect of MTX and LEF on cell viability, and RANKL and OPG expression were indicated through MTT and RT-PCR analysis, respectively. Combination therapy would be effective in treating CIA rats. Joint swelling scores and IL-17 and RANKL level in serum were decreased obviously (P < 0.05), while OPG level was elevated (P < 0.05). Anti-inflammatory and anti-osteoclasia effect would be indicated by H&E dyeing results. Moreover, FLS cell viability was inhibited by combination treatment in vitro (P < 0.05), and expression of osteoclasia-related genes (RANKL and OPG) was modified (P < 0.05). Combination therapy would relive the synovium hypertrophy through depressing cell viability and osteoclasia through decreasing RANKL and increasing OPG expression. Otherwise, combination was superior to monotherapy.

  13. Chromospheric Activity in Population II Giants

    NASA Technical Reports Server (NTRS)

    Harper, Graham M.

    2004-01-01

    One of the mysteries of Population II giants is that they still show chromospheric emission despite their great age. The global dynamo which was active during their main-sequence lifetimes is expected to become extremely weak through magnetic rotational braking. The nature of the observed emission is not understood; although acoustic shock waves might provide the heating, acoustic waves are not predicted to drive the observed mass loss - which in turn requires the dissipation of magneto-hydrodynamic waves. This program was designed to search for the faint stellar H Ly beta emission wings and the fluorescent Fe II and H2 emission from one of the brightest, metal poor, Population II stars. These FUSE diagnostics, when combined with existing UV and optical spectra, help determine the major radiative cooling channels for the chromosphere. This observation was to complement that previously planned for the mildly metal deficient giant alpha Boo (K2 III). However, alpha Boo has yet to be observed with FUSE.

  14. Rules for distinguishing toxicants that cause type I and type II narcosis syndromes

    SciTech Connect

    Veith, G.D.; Broderius, S.J. )

    1990-07-01

    Narcosis is a nonspecific reversible state of arrested activity of protoplasmic structures caused by a wide variety of organic chemicals. The vast majority of industrial organic chemicals can be characterized by a baseline structure-toxicity relationship as developed for diverse aquatic organisms, using only the n-octanol/water partition coefficient as a descriptor. There are, however, many apparent narcotic chemicals that are more toxic than baseline narcosis predicts. Some of these chemicals have been distinguished as polar narcotics. Joint toxic theory and isobole diagrams were used to show that chemicals strictly additive with phenol were generally more toxic than predicted by narcosis I models and characterized by a different mode of action called narcosis II syndrome. This type of toxicity is exemplified by certain amides, amines, phenols, and nitrogen heterocycles. Evidence is provided that suggests that narcosis II syndrome may result from the presence of a strong hydrogen bonding group on the molecule, and narcosis I syndrome results from hydrophobic bonding of the chemical to enzymes and/or membranes. This shift in toxic action is apparently indistinguishable for narcotic chemicals with log P greater than about 2.7. General rules for selecting the appropriate models are proposed.

  15. Characteristics of Type-II Radio Bursts Associated with Flares and CMEs

    NASA Astrophysics Data System (ADS)

    Vasanth, V.; Umapathy, S.; Vršnak, Bojan; Anna Lakshmi, M.

    2011-10-01

    We present a statistical study of the characteristics of type-II radio bursts observed in the metric (m) and deca-hectometer (DH) wavelength range during 1997-2008. The collected events are divided into two groups: Group I contains the events of m-type-II bursts with starting frequency ≥ 100 MHz, and group II contains the events with starting frequency of m-type-II radio bursts < 100 MHz. We have analyzed both samples considering three different aspects: i) statistical properties of type-II bursts, ii) statistical properties of flares and CMEs associated with type-II bursts, and iii) time delays between type-II bursts, flares, and CMEs. We find significant differences in the properties of m-type-II bursts in duration, bandwidth, drift rate, shock speed and delay between m- and DH-type-II bursts. From the timing analysis we found that the majority of m-type-II bursts in both groups occur during the flare impulsive phase. On the other hand, the DH-type-II bursts in both groups occur during the decaying phase of the associated flares. Almost all m-DH-type-II bursts are found to be associated with CMEs. Our results indicate that there are two kinds of shock in which group I (high frequency) m-type-II bursts seem to be ignited by flares whereas group II (low frequency) m-type-II bursts are CME-driven.

  16. Exploring Type I and Type II Errors Using Rhizopus Sporangia Diameter Measurements.

    ERIC Educational Resources Information Center

    Smith, Robert A.; Burns, Gerard; Freud, Brian; Fenning, Stacy; Hoffman, Rosemary; Sabapathi, Durai

    2000-01-01

    Presents exercises in which students can explore Type I and Type II errors using sporangia diameter measurements as a means of differentiating between two species. Examines the influence of sample size and significance level on the outcome of the analysis. (SAH)

  17. Prediction of Type II Radio Bursts Associated with Large CME Events

    NASA Astrophysics Data System (ADS)

    Cairns, Iver; Schmidt, Joachim

    Type II radio bursts are associated with shocks in the corona and solar wind, either driven by CMEs or else by blast waves. Recently we coupled the advanced 3D MHD BATS-R-US code of Toth, Gombosi, and colleagues with our kinetic ``bolt-on'' theory for type II emission. Initialising the simulation code with event specific coronal and CME data, the combined code can be used to predict the dynamic spectrum of type II emission for a specific radio event. We demonstrate very good agreement with Wind spacecraft observations for three type II bursts, one on 15 February 2011 and two on 7 March 2012 (associated with successive CMEs from different sides of the same active region). The intensities, frequencies, and times of fundamental and harmonic type II emission are predicted very well from the high corona to 1 AU (frequencies ~ 20 MHz - 30 kHz). The islands of increased emission correspond to different regions of the shock interacting with coronal structures, with streamers typically corresponding to reduced emission. The results provide strong evidence that both the type II theory and the BATS-R-US (driven with event-specific data) are accurate. They also provide strong evidence that the observation and detailed theoretical modelling of type II bursts can in principle provide warnings with lead-times of over a day for large and fast CMEs that might produce space weather at Earth. The MHD code can also predict whether the CME will hit Earth's magnetopause and the magnetic field direction at the magnetopause as the shock, sheath, and CME, vital quantities for predicting space weather at Earth.

  18. Multicolor Oservations of the Type II Cepheid Prototype W Virginis

    NASA Astrophysics Data System (ADS)

    Templeton, Matthew R.; Henden, A. A.; Crawford, T.; James, R.; Bonnardeau, M.; Wells, D.

    2006-12-01

    We present preliminary results of the AAVSO's six-month photometric campaign on the bright, pulsating variable star W Virginis, class prototype of the Type II Cepheid variables. This campaign was organized in support of separate spectroscopic observations (Wallerstein et al., in preparation), but these photometric data also stand alone as a valuable, recent, multicolor light curve of this object. Observations were obtained by several amateur and professional observers using a variety of equipment; data are primarily in the V filter, but include two complete pulsation cycles in the BVRcIc filters. We present lightand color-curves of this star, and compare our results to previous observational and theoretical results on W Vir and the Type II Cepheids.

  19. THE CONNECTION OF TYPE II SPICULES TO THE CORONA

    SciTech Connect

    Judge, Philip G.; McIntosh, Scott W.; De Pontieu, Bart; Olluri, Kosovare

    2012-02-20

    We examine the hypothesis that plasma associated with 'Type II' spicules is heated to coronal temperatures, and that the upward moving hot plasma constitutes a significant mass supply to the solar corona. One-dimensional hydrodynamical models including time-dependent ionization are brought to bear on the problem. These calculations indicate that heating of field-aligned spicule flows should produce significant differential Doppler shifts between emission lines formed in the chromosphere, transition region, and corona. At present, observational evidence for the computed 60-90 km s{sup -1} differential shifts is weak, but the data are limited by difficulties in comparing the proper motion of Type II spicules with spectral and kinematic properties of an associated transition region and coronal emission lines. Future observations with the upcoming infrared interferometer spectrometer instrument should clarify if Doppler shifts are consistent with the dynamics modeled here.

  20. UBVRIz Light Curves of 51 Type II Supernovae

    NASA Astrophysics Data System (ADS)

    Galbany, Lluís; Hamuy, Mario; Phillips, Mark M.; Suntzeff, Nicholas B.; Maza, José; de Jaeger, Thomas; Moraga, Tania; González-Gaitán, Santiago; Krisciunas, Kevin; Morrell, Nidia I.; Thomas-Osip, Joanna; Krzeminski, Wojtek; González, Luis; Antezana, Roberto; Wishnjewski, Marina; McCarthy, Patrick; Anderson, Joseph P.; Gutiérrez, Claudia P.; Stritzinger, Maximilian; Folatelli, Gastón; Anguita, Claudio; Galaz, Gaspar; Green, Elisabeth M.; Impey, Chris; Kim, Yong-Cheol; Kirhakos, Sofia; Malkan, Mathew A.; Mulchaey, John S.; Phillips, Andrew C.; Pizzella, Alessandro; Prosser, Charles F.; Schmidt, Brian P.; Schommer, Robert A.; Sherry, William; Strolger, Louis-Gregory; Wells, Lisa A.; Williger, Gerard M.

    2016-02-01

    We present a compilation of UBVRIz light curves of 51 type II supernovae discovered during the course of four different surveys during 1986-2003: the Cerro Tololo Supernova Survey, the Calán/Tololo Supernova Program (C&T), the Supernova Optical and Infrared Survey (SOIRS), and the Carnegie Type II Supernova Survey (CATS). The photometry is based on template-subtracted images to eliminate any potential host galaxy light contamination, and calibrated from foreground stars. This work presents these photometric data, studies the color evolution using different bands, and explores the relation between the magnitude at maximum brightness and the brightness decline parameter (s) from maximum light through the end of the recombination phase. This parameter is found to be shallower for redder bands and appears to have the best correlation in the B band. In addition, it also correlates with the plateau duration, being shorter (longer) for larger (smaller) s values.

  1. Progression of Jackhammer Esophagus to Type II Achalasia

    PubMed Central

    Abdallah, Jason; Fass, Ronnie

    2016-01-01

    It has been suggested that patients with certain motility disorders may progress overtime to develop achalasia. We describe a 66 year-old woman who presented with dysphagia for solids and liquids for a period of 18 months. Her initial workup showed normal endoscopy and non-specific esophageal motility disorder on conventional manometry. Six months later, due to persistence of symptoms, the patient underwent a high resolution esophageal manometry (HREM) demonstrating jackhammer esophagus. The patient was treated with a high dose proton pump inhibitor but without resolution of her symptoms. During the last year, the patient reported repeated episodes of food regurgitation and a significant weight loss. A repeat HREM revealed type II achalasia. Multiple case reports, and only a few prospective studies have demonstrated progression from certain esophageal motility disorders to achalasia. However, this report is the first to describe a case of jackhammer esophagus progressing to type II achalasia. PMID:26717932

  2. On the Covariant Quantization of Type II Superstrings

    NASA Astrophysics Data System (ADS)

    Guttenberg, Sebastian; Knapp, Johanna; Kreuzer, Maximilian

    2004-06-01

    In a series of papers Grassi, Policastro, Porrati and van Nieuwenhuizen have introduced a new method to covariantly quantize the GS-superstring by constructing a resolution of the pure spinor constraint of Berkovits' approach. Their latest version is based on a gauged WZNW model and a definition of physical states in terms of relative cohomology groups. We first put the off-shell formulation of the type-II version of their ideas into a chirally split form and directly construct the free action of the gauged WZNW model, thus circumventing some complications of the super group manifold approach to type-II. Then we discuss the BRST charges that define the relative cohomology and the N=2 superconformal algebra. A surprising result is that nilpotency of the BRST charge requires the introduction of another quartet of ghosts.

  3. UBVRIz LIGHT CURVES OF 51 TYPE II SUPERNOVAE

    SciTech Connect

    Galbany, Lluis; Hamuy, Mario; Jaeger, Thomas de; Moraga, Tania; González-Gaitán, Santiago; Gutiérrez, Claudia P.; Phillips, Mark M.; Morrell, Nidia I.; Thomas-Osip, Joanna; Suntzeff, Nicholas B.; Maza, José; González, Luis; Antezana, Roberto; Wishnjewski, Marina; Krisciunas, Kevin; Krzeminski, Wojtek; McCarthy, Patrick; Anderson, Joseph P.; Stritzinger, Maximilian; Folatelli, Gastón; and others

    2016-02-15

    We present a compilation of UBVRIz light curves of 51 type II supernovae discovered during the course of four different surveys during 1986–2003: the Cerro Tololo Supernova Survey, the Calán/Tololo Supernova Program (C and T), the Supernova Optical and Infrared Survey (SOIRS), and the Carnegie Type II Supernova Survey (CATS). The photometry is based on template-subtracted images to eliminate any potential host galaxy light contamination, and calibrated from foreground stars. This work presents these photometric data, studies the color evolution using different bands, and explores the relation between the magnitude at maximum brightness and the brightness decline parameter (s) from maximum light through the end of the recombination phase. This parameter is found to be shallower for redder bands and appears to have the best correlation in the B band. In addition, it also correlates with the plateau duration, being shorter (longer) for larger (smaller) s values.

  4. Shock waves and nucleosynthesis in type II supernovae

    NASA Technical Reports Server (NTRS)

    Aufderheide, M. B.; Baron, E.; Thielemann, F.-K.

    1991-01-01

    In the study of nucleosynthesis in type II SN, shock waves are initiated artificially, since collapse calculations do not, as yet, give self-consistent shock waves strong enough to produce the SN explosion. The two initiation methods currently used by light-curve modelers are studied, with a focus on the peak temperatures and the nucleosynthetic yields in each method. The various parameters involved in artificially initiating a shock wave and the effects of varying these parameters are discussed.

  5. Study of interacting CMEs and DH type II radio bursts

    NASA Astrophysics Data System (ADS)

    Prasanna Subramanian, S.; Shanmugaraju, A.

    2013-04-01

    The subject of interaction between the Corona Mass Ejections (CMEs) is important in the concept of space-weather studies. In this paper, we analyzed a set of 15 interacting events taken from the list compiled by Manoharan et al. (in J. Geophys. Res. 109:A06109, 2004) and their associated DH type II radio bursts. The pre and primary CMEs, and their associated DH type II bursts are identified using the SOHO/LASCO catalog and Wind/WAVES catalog, respectively. All the primary CMEs are associated with shocks and interplanetary CMEs. These CMEs are found to be preceded by secondary slow CMEs. Most of primary CMEs are halo type CME and much faster (Mean speed = 1205 km s-1) than the pre CME (Mean speed = 450 km s-1). The average delay between the pre and primary CMEs, drift rate of DH type IIs and interaction height are found to be 211 min, 0.878 kHz/s and 17.87 Ro, respectively. The final observed distance (FOD) of all pre CMEs are found to be less than 15 Ro and it is seen that many of the pre CMEs got merged with the primary CMEs, and, they were not traced as separate CMEs in the LASCO field of view. Some radio signatures are identified for these events in the DH spectrum around the time of interaction. The interaction height obtained from the height-time plots of pre and primary CMEs is found to have correlations with (i) the time delay between the two CMEs and (ii) the central frequency of emission in the radio signatures in the DH spectrum around the time of interaction. The centre frequency of emission in the DH spectrum around the time of interaction seems to decrease when the interaction height increases. This result is compared with an interplanetary density model of Saito et al. (in Solar Phys. 55:121, 1977).

  6. Closed Timelike Curves in Type II Non-Vacuum Spacetime

    NASA Astrophysics Data System (ADS)

    Ahmed, Faizuddin

    2017-02-01

    Here we present a cyclicly symmetric non-vacuum spacetime, admitting closed timelike curves (CTCs) which appear after a certain instant of time, i.e., a time-machine spacetime. The spacetime is asymptotically flat, free-from curvature singularities and a four-dimensional extension of the Misner space in curved spacetime. The spacetime is of type II in the Petrov classification scheme and the matter field pure radiation satisfy the energy condition.

  7. Classification of SN2005dj, a Type II Supernova

    NASA Astrophysics Data System (ADS)

    Blanc, N.; Bongard, S.; Copin, Y.; Gangler, E.; Sauge, L.; Smadja, G.; Antilogus, P.; Garavini, G.; Gilles, S.; Pain, R.; Aldering, G.; Bailey, S.; Lee, B. C.; Loken, S.; Nugent, P.; Perlmutter, S.; Scalzo, R.; Thomas, R. C.; Wang, L.; Weaver, B. A.; Bonnaud, C.; Pecontal, E.; Kessler, R.; Baltay, C.; Rabinowitz, D.; Bauer, A.

    2005-08-01

    The Nearby Supernova Factory reports that a spectrum (range 320-1000 nm) of SN 2005dj (IAUC#8585), obtained August 19.6 UT with the Supernova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope, reveals P-Cygni H-alpha and H-beta, indicative of a Type II supernova. The observed redshift is consistent with that of the host UGC 3545 (z = 0.011508, Huchtmeier & Skillman 1998 via NED).

  8. Evaluation of nanoarchitectured collagen type II molecules on cartilage engineering.

    PubMed

    Kuo, Shyh Ming; Chiang, Ming Yu; Lan, Cheng Wen; Niu, Gregory Cheng-Chie; Chang, Shwu Jen

    2013-02-01

    Scaffold architecture, including the geometry and dimension of scaffolds, is an important parameter in cell adhesion, migration, proliferation, and differentiation. Following the characterization of collagen type II nanoarchitectured molecules, collagen fibrils (CNFs) and collagen spheres (CNPs) prepared using a high-voltage electric field in our laboratory, we proposed to use these nanoarchitectured molecules to assess their influence on the culturing of chondrocytes in stirred bioreactors. The results demonstrate that chondrocytes rapidly formed more and larger chondrocyte pellets (spheroids) after the addition of nanoarchitectured molecules into the culture medium. The maintenance of chondrocytes with round morphology and increased glycosaminoglycan secretion indicated that these spheroids contained viable and un-dedifferentiated chondrocytes. No significant increases in DNA content were detected. These results show that the introduction of these molecules did not affect chondrocyte proliferation during a 3-day culture period. After the addition of CNPs and CNFs into the culture medium, the expression levels of collagen type II and aggrecan genes in chondrocytes increased significantly as demonstrated by real-time PCR analysis. Interestingly, chondrocytes exhibited distinct collagen type II and aggrecan gene expression profiles in culture with CNPs and CNFs. The aggrecan gene expression level of the chondrocytes was 2.5-fold greater following CFN addition than following the addition of CNPs. In contrast, the collagen type II expression level of the chondrocytes was 2.2-fold greater following the addition of CNPs than following the addition of CNFs. The chondrocyte pellets rapidly restored defects in articular cartilage during a 1-month implantation period in a rabbit model.

  9. ACCELERATION OF TYPE II SPICULES IN THE SOLAR CHROMOSPHERE

    SciTech Connect

    Goodman, Michael L.

    2012-10-01

    A 2.5D, time-dependent magnetohydrodynamic model is used to test the proposition that observed type II spicule velocities can be generated by a Lorentz force under chromospheric conditions. It is found that current densities localized on observed space and time scales of type II spicules and that generate maximum magnetic field strengths {<=}50 G can generate a Lorentz force that accelerates plasma to terminal velocities similar to those of type II spicules. Maximum vertical flow speeds are {approx}150-460 km s{sup -1}, horizontally localized within {approx}2.5-10 km from the vertical axis of the spicule, and comparable to slow solar wind speeds, suggesting that significant solar wind acceleration occurs in type II spicules. Horizontal speeds are {approx}20 times smaller than vertical speeds. Terminal velocity is reached {approx}100 s after acceleration begins. The increase in the mechanical and thermal energy of the plasma during acceleration is (2-3) Multiplication-Sign 10{sup 22} ergs. The radial component of the Lorentz force compresses the plasma during the acceleration process by factors as large as {approx}100. The Joule heating flux generated during this process is essentially due to proton Pedersen current dissipation and can be {approx}0.1-3.7 times the heating flux of {approx}10{sup 6} ergs cm{sup -2} s{sup -1} associated with middle-upper chromospheric emission. About 84%-94% of the magnetic energy that accelerates and heats the spicules is converted into bulk flow kinetic energy.

  10. Cardiopulmonary bypass with bivalirudin in type II heparin-induced thrombocytopenia.

    PubMed

    Clayton, Stephanie B; Acsell, Jeffrey R; Crumbley, Arthur J; Uber, Walter E

    2004-12-01

    Cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia poses significant challenges. Inadequate pharmacokinetic profiles, monitoring, reversibility, and availability often limit alternative anticoagulation strategies. Bivalirudin, a semisynthetic direct thrombin inhibitor, was recently approved for use in patients undergoing percutaneous coronary interventions. Its unique properties, including a relatively short half-life, an anticoagulation effect that closely correlates with activated clotting time, and an alternate metabolic pathway for elimination, make bivalirudin an attractive agent for cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia. We report our experience using bivalirudin in 2 patients undergoing coronary artery bypass grafting.

  11. Type III intermediate filament peripherin inhibits neuritogenesis in type II spiral ganglion neurons in vitro

    PubMed Central

    Barclay, Meagan; Julien, Jean-Pierre; Ryan, Allen F.; Housley, Gary D.

    2010-01-01

    Peripherin, a type III intermediate filament protein, forms part of the cytoskeleton in a subset of neurons, most of which have peripheral fibre projections. Studies suggest a role for peripherin in axon outgrowth and regeneration, but evidence for this in sensory and brain tissues is limited. The exclusive expression of peripherin in a sub-population of primary auditory neurons, the type II spiral ganglion neurons (SGN) prompted our investigation of the effect of peripherin gene deletion (pphKO) on these neurons. We used confocal immunofluorescence to examine the establishment of the innervation of the cochlear outer hair cells by the type II SGN neurites in vivo and in vitro, in wildtype (WT) and pphKO mice, in the first postnatal week. The distribution of the type II SGN nerve fibres was normal in pphKO cochleae. However, using P1 spiral ganglion explants under culture conditions where the majority of neurites were derived from type II SGN, pphKO resulted in increased numbers of neurites/explant compared WT controls. Type II SGN neurites from pphKO explants extended ~ double the distance of WT neurites, and had reduced complexity based on greater distance between turning points. Addition of brain-derived neurotrophic factor (BDNF) to the culture media increased neurite number in WT and KO explants ~30-fold, but did not affect neurite length or distance between turning. These results indicate that peripherin may interact with other cytoskeletal elements to regulate outgrowth of the peripheral neurites of type II SGN, distinguishing these neurons from the type I SGN innervating the inner hair cells. PMID:20132868

  12. Type-II superlattice infrared detector technology at Fraunhofer IAF

    NASA Astrophysics Data System (ADS)

    Rehm, Robert; Daumer, Volker; Hugger, Tsvetelina; Kohn, Norbert; Luppold, Wolfgang; Müller, Raphael; Niemasz, Jasmin; Schmidt, Johannes; Rutz, Frank; Stadelmann, Tim; Wauro, Matthias; Wörl, Andreas

    2016-05-01

    For more than two decades, Antimony-based type-II superlattice photodetectors for the infrared spectral range between 3-15 μm are under development at the Fraunhofer Institute for Applied Solid State Physics (IAF). Today, Fraunhofer IAF is Germany's only national foundry for InAs/GaSb type-II superlattice detectors and we cover a wide range of aspects from basic materials research to small series production in this field. We develop single-element photodetectors for sensing systems as well as two-dimensional detector arrays for high-performance imaging and threat warning systems in the mid-wavelength and long-wavelength region of the thermal infrared. We continuously enhance our production capabilities by extending our in-line process control facilities. As a recent example, we present a semiautomatic wafer probe station that has developed into an important tool for electrooptical characterization. A large amount of the basic materials research focuses on the reduction of the dark current by the development of bandgap engineered device designs on the basis of heterojunction concepts. Recently, we have successfully demonstrated Europe's first LWIR InAs/GaSb type-II superlattice imager with 640x512 pixels with 15 μm pitch. The demonstrator camera already delivers a good image quality and achieves a thermal resolution better than 30 mK.

  13. Coronas Mass Ejections, Shocks, and Type II Radio Bursts

    NASA Technical Reports Server (NTRS)

    Gopalswamy, Natchimuthuk

    2010-01-01

    Coronal mass ejections (CMEs) are the most energetic phenomena in the interplanetary medium. Type II radio bursts are the earliest indicators of particle acceleration by CME-driven shocks. There is one-to-one correspondence between large solar energetic particle (SEP) events and long wavelength type II bursts because the same CME-driven shock is supposed to accelerate electrons and ions. However, there are some significant deviations: some CMEs lacking type II bursts (radio-quiet or RQ CMEs) are associated with small SEP events while some radioloud (RL) CMEs are not associated with SEP events, suggesting subtle differences in the acceleration of electrons and protons. Not all CME-driven shocks are radio loud: more than one third of the interplanetary shocks during solar cycle 23 were radio quiet. Some RQ shocks were associated with energetic storm particle (ESP) events, which are detected when the shocks arrive at the observing spacecraft. This paper attempts to explain these contradictory results in terms of the properties of CMEs, shocks, and the ambient medium.

  14. Perinatal lethal type II osteogenesis imperfecta: a case report.

    PubMed

    Ayadi, Imene Dahmane; Hamida, Emira Ben; Rebeh, Rania Ben; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    We report a new case of osteogenesis imperfecta (OI) type II which is a perinatal lethal form. First trimester ultrasound didn't identified abnormalities. Second trimester ultrasound showed incurved limbs, narrow chest, with hypomineralization and multiple fractures of ribs and long bones. Parents refused pregnancy termination; they felt that the diagnosis was late. At birth, the newborn presented immediate respiratory distress. Postnatal examination and bone radiography confirmed the diagnosis of OI type IIA. Death occurred on day 25 of life related to respiratory failure.

  15. Oxidative inactivation of alpha 1-proteinase inhibitor by alveolar epithelial type II cells.

    PubMed

    Wallaert, B; Aerts, C; Gressier, B; Gosset, P; Voisin, C

    1993-12-01

    The aim of this work was to evaluate the ability of guinea pig alveolar epithelial type II cells to generate significant amounts of reactive oxygen species to inactivate alpha 1-proteinase inhibitor (alpha 1-PI). Inactivation of alpha 1-PI was evaluated by its inhibitory activity against porcine pancreatic elastase and was expressed as a percentage. The same experiments were performed in parallel with alveolar macrophages (AM) obtained from the same animals and with MRC-5 fibroblasts. Both type II cells and AM released significant amounts of hydrogen peroxide and superoxide, whereas the fibroblasts did not. Unstimulated type II cells (0.5 +/- 2%), AM (1.2 +/- 1.5%), and fibroblasts (0.5 +/- 0.5%) were unable to inactivate alpha 1-PI. Addition of phorbol myristate acetate did not increase their ability to inactivate alpha 1-PI. In contrast, type II cells (79.7 +/- 7%) and AM (80.1 +/- 8%) dramatically inactivated alpha 1-PI in the presence of myeloperoxidase (25 mU/ml), whereas fibroblasts did not. Addition of catalase to the reaction significantly prevented the inactivation of alpha 1-PI. Western blot analysis of alpha 1-PI did not reveal a significant proteolysis of alpha 1-PI, which supports the hypothesis that, in the presence of neutrophil-derived myeloperoxidase, type II cells may oxidatively inactivate alpha 1-PI.

  16. THE IMMUNOLOGICAL SPECIFICITY OF TYPE II PNEUMOCOCCUS AND ITS SEPARATION INTO PARTIAL SPECIFICITIES. II

    PubMed Central

    Heidelberger, Michael

    1960-01-01

    Quantitative data are given on the cross reactions in Type II antipneumococcal horse sera of plant gums and hemicelluloses containing multiple terminal groupings of glucuronic acid and/or 4-O-methylglucuronic acid. Great variability is shown both in the reactivities of the polysaccharides and in the antibodies in the sera of different animals immunized with the same antigen. The 4-O-methyl substituent on the glucuronic acid residues in a gum often appears to diminish cross-precipitation with antibodies to S II. PMID:13852209

  17. A study of low-energy type II supernovae

    NASA Astrophysics Data System (ADS)

    Lisakov, Sergey M.; Dessart, Luc; Hillier, D. John; Waldman, Roni; Livne, Eli

    2015-08-01

    All stars with an initial mass greater than 8Msun, but not massive enough to encounter the pair-production instability, eventually form a degenerate core and collapse to form a compact object, either a neutron star or a black hole.At the lower mass end, these massive stars die as red-supergiant stars and give rise to Type II supernovae (SNe). The diversity of observed properties of SNe II suggests a range of progenitor mass, radii, but also explosion energy.We have performed a large grid simulations designed to cover this range of progenitor and explosion properties. Using MESA STAR, we compute a set of massive star models (12-30Msun) from the main sequence until core collapse. We then generate explosions with V1D to produce ejecta with a range of explosion energies and yields. Finally, all ejecta are evolved with CMFGEN to generate multi-band light curves and spectra.In this poster, we focus our attention on the properties of low-energy explosions that give rise to low-luminosity Type II Plateau (II-P) SNe. In particular, we present a detailed study of SN 2008bk, but also include other notorious low-energy SNe II-P like 2005cs, emphasising their non-standard properties by comparing to models that match well events like SN 1999em. Such low-energy explosions, characterised by low ejecta expansion rates, are more suitable for reliable spectral line identifications.Based on our models, we discuss the distinct signatures of low-energy explosions in lower and higher mass models. One important goal is to identify whether there is a progenitor-mass bias leading to such events.

  18. Effect of a misspecification of response rates on type I and type II errors, in a phase II Simon design.

    PubMed

    Baey, Charlotte; Le Deley, Marie-Cécile

    2011-07-01

    Phase-II trials are a key stage in the clinical development of a new treatment. Their main objective is to provide the required information for a go/no-go decision regarding a subsequent phase-III trial. In single arm phase-II trials, widely used in oncology, this decision relies on the comparison of efficacy outcomes observed in the trial to historical controls. The false positive rate generally accepted in phase-II trials, around 10%, contrasts with the very high attrition rate of new compounds tested in phase-III trials, estimated at about 60%. We assumed that this gap could partly be explained by the misspecification of the response rate expected with standard treatment, leading to erroneous hypotheses tested in the phase-II trial. We computed the false positive probability of a defined design under various hypotheses of expected efficacy probability. Similarly we calculated the power of the trial to detect the efficacy of a new compound for different expected efficacy rates. Calculations were done considering a binary outcome, such as the response rate, with a decision rule based on a Simon two-stage design. When analysing a single-arm phase-II trial, based on a design with a pre-specified null hypothesis, a 5% absolute error in the expected response rate leads to a false positive rate of about 30% when it is supposed to be 10%. This inflation of type-I error varies only slightly according to the hypotheses of the initial design. Single-arm phase-II trials poorly control for the false positive rate. Randomised phase-II trials should, therefore, be more often considered.

  19. Non-insulin-dependent (type II) diabetes mellitus.

    PubMed Central

    Rodger, W

    1991-01-01

    Non-insulin-dependent (type II) diabetes mellitus is an inherited metabolic disorder characterized by hyperglycemia with resistance to ketosis. The onset is usually after age 40 years. Patients are variably symptomatic and frequently obese, hyperlipidemic and hypertensive. Clinical, pathological and biochemical evidence suggests that the disease is caused by a combined defect of insulin secretion and insulin resistance. Goals in the treatment of hyperglycemia, dyslipidemia and hypertension should be appropriate to the patient's age, the status of diabetic complications and the safety of the regimen. Nonpharmacologic management includes meal planning to achieve a suitable weight, such that carbohydrates supply 50% to 60% of the daily energy intake, with limitation of saturated fats, cholesterol and salt when indicated, and physical activity appropriate to the patient's age and cardiovascular status. Follow-up should include regular visits with the physician, access to diabetes education, self-monitoring of the blood or urine glucose level and laboratory-based measurement of the plasma levels of glucose and glycated hemoglobin. If unacceptably high plasma glucose levels (e.g., 8 mmol/L or more before meals) persist the use of orally given hypoglycemic agents (a sulfonylurea agent or metformin or both) is indicated. Temporary insulin therapy may be needed during intercurrent illness, surgery or pregnancy. Long-term insulin therapy is recommended in patients with continuing symptoms or hyperglycemia despite treatment with diet modification and orally given hypoglycemic agents. The risk of pancreatitis may be reduced by treating severe hypertriglyceridemia (fasting serum level greater than 10 mmol/L) and atherosclerotic disease through dietary and, if necessary, pharmacologic management of dyslipidemia. Antihypertensive agents are available that have fewer adverse metabolic effects than thiazides and beta-adrenergic receptor blockers. New drugs are being developed that

  20. Comparison of the relative toxicities of Shiga-like toxins type I and type II for mice.

    PubMed Central

    Tesh, V L; Burris, J A; Owens, J W; Gordon, V M; Wadolkowski, E A; O'Brien, A D; Samuel, J E

    1993-01-01

    In earlier studies using a streptomycin-treated mouse model of infection caused by enterohemorrhagic Escherichia coli (EHEC), animals fed Shiga-like toxin type II (SLT-II)-producing strains developed acute renal cortical necrosis and died, while mice fed Shiga-like toxin type I (SLT-I)-producing clones did not die (E. A. Wadolkowski, L. M. Sung, J. A. Burris, J. E. Samuel, and A. D. O'Brien, Infect. Immun. 58:3959-3965, 1990). To examine the bases for the differences we noted between the two toxins in the murine infection model, we injected mice with purified toxins and carried out histopathological examinations. Despite the genetic and structural similarities between the two toxins, SLT-II had a 50% lethal dose (LD50) which was approximately 400 times lower than that of SLT-I when injected intravenously or intraperitoneally into mice. Histopathologic examination of toxin-injected mice revealed that detectable damage was limited to renal cortical tubule epithelial cells. Passive administration of anti-SLT-II antibodies protected mice from SLT-II-mediated kidney damage and death. Immunofluorescence staining of normal murine kidney sections incubated with purified SLT-I or SLT-II demonstrated that both toxins bound to cortical tubule and medullary duct epithelial cells. Compared with SLT-I, SLT-II was more heat and pH stable, suggesting that SLT-II is a relatively more stable macromolecule. Although both toxins bound to globotriaosylceramide, SLT-I bound with a higher affinity in a solid-phase binding assay. Differences in enzymatic activity between the two toxins were not detected. These data suggest that structural/functional differences between the two toxins, possibly involving holotoxin stability and/or receptor affinity, may contribute to the differential LD50s in mice. Images PMID:8335369

  1. Synthesis, physico-chemical studies of manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II) complexes with some p-substituted acetophenone benzoylhydrazones and their antimicrobial activity.

    PubMed

    Singh, Vinod P; Singh, Shweta; Katiyar, Anshu

    2009-04-01

    Complexes of the type [M(pabh)(H2O)Cl], [M(pcbh)(H2O)Cl] and [M(Hpabh)(H2O)2 (SO4)] where, M = Mn(II), Co(II), Ni(II), Cu(II) and Zn(II); Hpabh = p-amino acetophenone benzoyl hydrazone and Hpcbh = p-chloro acetophenone benzoyl hydrazone have been synthesized and characterized with the help of elemental analyses, electrical conductance, magnetic susceptibility measurements, electronic, ESR and IR spectra, thermal (TGA & DTA) and X-ray diffraction studies. Co(II), Ni(II) and Cu(II) chloride complexes are square planar, whereas their sulfate complexes have spin-free octahedral geometry. ESR spectra of Cu(II) complexes with Hpabh are axial and suggest d(x(2)-y(2) as the ground state. The ligand is bidentate bonding through > C = N--and deprotonated enolate group in all the chloro complexes, whereas, >C = N and >C = O groups in all the sulfato complexes. Thermal studies (TGA & DTA) on [Cu(Hpabh)(H2O)2(SO4)] indicate a multistep decomposition pattern, which are both exothermic and endothermic in nature. X-ray powder diffraction parameters for [Co(pabh)(H2O)Cl] and [Ni(Hpabh)(H2O)2(SO4)] correspond to tetragonal and orthorhombic crystal lattices, respectively. The ligands as well as their complexes show a significant antifungal and antibacterial activity. The metal complexes are more active than the ligand.

  2. Deciphering the role of the type II glyoxalase isoenzyme YcbL (GlxII-2) in Escherichia coli.

    PubMed

    Reiger, Matthias; Lassak, Jürgen; Jung, Kirsten

    2015-01-01

    In Escherichia coli, detoxification of methylglyoxal (MG) requires glyoxalases I and II. Glyoxalase I (gloA/GlxI) isomerizes the hemithioacetal, formed spontaneously from MG and glutathione (GSH) to S-lactoylglutathione (SLG), which is hydrolyzed by glyoxalase II (gloB/GlxII) to lactate and GSH. YcbL from Salmonella enterica serovar Typhimurium is an unusual type II glyoxalase whose role in MG detoxification has remained enigmatic. Here we show that YcbL (gloC/GlxII-2) acts as an accessory type II glyoxylase in E. coli. The two isoenzymes have additive effects and ensure maximal MG degradation.

  3. The Rho pathway mediates transition to an alveolar type I cell phenotype during static stretch of alveolar type II cells

    PubMed Central

    Foster, Cherie D; Varghese, Linda S; Gonzales, Linda W.; Margulies, Susan S.; Guttentag, Susan H.

    2011-01-01

    Stretch is an essential mechanism for lung growth and development. Animal models in which fetal lungs have been chronically over- or under-distended demonstrate a disrupted mix of type II and type I cells, with static overdistention typically promoting a type I cell phenotype. The Rho GTPase family, key regulators of cytoskeletal signaling, are known to mediate cellular differentiation in response to stretch in other organs. Using a well-described model of alveolar epithelial cell differentiation and a validated stretch device, we investigated the effects of supraphysiologic stretch on human fetal lung (HFL) alveolar epithelial cell phenotype. Static stretch applied to epithelial cells suppressed type II cell markers (SP-B and Pepsinogen C, PGC), and induced type I cell markers (Caveolin-1, Claudin 7 and Plasminogen Activator Inhibitor-1, PAI-1) as predicted. Static stretch was also associated with Rho A activation. Furthermore, the Rho kinase (ROCK) inhibitor Y27632 decreased Rho A activation, and blunted the stretch-induced changes in alveolar epithelial cell marker expression. Together these data provide further evidence that mechanical stimulation of the cytoskeleton and Rho activation are key upstream events in mechanotransduction-associated alveolar epithelial cell differentiation. PMID:20220547

  4. Functionalized fullerenes mediate photodynamic killing of cancer cells: Type I versus Type II photochemical mechanism

    PubMed Central

    Mroz, Pawel; Pawlak, Anna; Satti, Minahil; Lee, Haeryeon; Wharton, Tim; Gali, Hariprasad; Sarna, Tadeusz; Hamblin, Michael R.

    2007-01-01

    Photodynamic therapy (PDT) employs the combination of non-toxic photosensitizers (PS) and harmless visible light to generate reactive oxygen species (ROS) and kill cells. Most clinically studied PS are based on the tetrapyrrole structure of porphyrins, chlorins and related molecules, but new non-tetrapyrrole PS are being sought. Fullerenes are soccer-ball shaped molecules composed of sixty or seventy carbon atoms and have attracted interest in connection with the search for biomedical applications of nanotechnology. Fullerenes are biologically inert unless derivatized with functional groups, whereupon they become soluble and can act as PS. We have compared the photodynamic activity of six functionalized fullerenes with 1, 2, or 3 hydrophilic or 1, 2, or 3 cationic groups. The octanol-water partition coefficients were determined and the relative contributions of Type I photochemistry (photogeneration of superoxide in the presence of NADH) and Type II photochemistry (photogeneration of singlet oxygen) were studied by measurement of oxygen consumption, 1270-nm luminescence and EPR spin-trapping of the superoxide product. We studied three mouse cancer cell lines: (J774, LLC and CT26) incubated for 24 h with fullerenes and illuminated with white light. The order of effectiveness as PS was inversely proportional to the degree of substitution of the fullerene nucleus for both the neutral and cationic series. The mono-pyrrolidinium fullerene was the most active PS against all cell lines and induced apoptosis 4–6 hours after illumination. It produced diffuse intracellular fluorescence when dichlorodihydrofluorescein was added as an ROS probe suggesting a Type I mechanism for phototoxicity. We conclude that certain functionalized fullerenes have potential as novel PDT agents and phototoxicity may be mediated both by superoxide and by singlet oxygen. PMID:17664135

  5. Angiotensin II-induced angiotensin II type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy

    NASA Astrophysics Data System (ADS)

    Li, Hewang; Yu, Peiying; Felder, Robin A.; Periasamy, Ammasi; Jose, Pedro A.

    2009-02-01

    Upon activation, the angiotensin (Ang) II type 1 receptor (AT1Rs) rapidly undergoes endocytosis. After a series of intracellular processes, the internalized AT1Rs recycle back to the plasma membrane or are trafficked to proteasomes or lysosomes for degradation. We recently reported that AT1Rs degrades in proteasomes upon stimulation of the D5 dopamine receptor (D5R) in human renal proximal tubule and HEK-293 cells. This is in contrast to the degradation of AT1R in lysosomes upon binding Ang II. However, the dynamic regulation of the AT1Rs in lysosomes is not well understood. Here we investigated the AT1Rs lysosomal degradation using FRET-FLIM in HEK 293 cells heterologously expressing the human AT1R tagged with EGFP as the donor fluorophore. Compared to its basal state, the lifetime of AT1Rs decreased after a 5-minute treatment with Ang II treatment and colocalized with Rab5 but not Rab7 and LAMP1. With longer Ang II treatment (30 min), the AT1Rs lifetime decreased and co-localized with Rab5, as well as Rab7 and LAMP1. The FLIM data are corroborated with morphological and biochemical co-immunoprecipitation studies. These data demonstrate that Ang II induces the internalization of AT1Rs into early sorting endosomes prior to trafficking to late endosomes and subsequent degradation in lysosomes.

  6. Dynamics of keratin assembly: exogenous type I keratin rapidly associates with type II keratin in vivo

    PubMed Central

    1993-01-01

    Keratin intermediate filaments (IF) are obligate heteropolymers containing equal amounts of type I and type II keratin. We have previously shown that microinjected biotinylated type I keratin is rapidly incorporated into endogenous bundles of keratin IF (tonofilaments) of PtK2 cells. In this study we show that the earliest steps in the assembly of keratin subunits into tonofilaments involve the extremely rapid formation of discrete aggregates of microinjected keratin. These are seen as fluorescent spots containing both type I and type II keratins within 1 min post-injection as determined by double label immunofluorescence. These observations suggest that endogenous type II keratin subunits can be rapidly mobilized from their endogenous state to form complexes with the injected type I protein. Furthermore, confocal microscopy and immunogold electron microscopy suggest that the type I-type II keratin spots from in close association with the endogenous keratin IF network. When the biotinylated protein is injected at concentrations of 0.3-0.5 mg/ml, the organization of the endogenous network of tonofilaments remains undisturbed during incorporation into tonofilaments. However, microinjection of 1.5-2.0 mg/ml of biotinylated type I results in significant alterations in the organization and assembly state of the endogenous keratin IF network soon after microinjection. The results of this study are consistent with the existence of a state of equilibrium between keratin subunits and polymerized keratin IF in epithelial cells, and provide further proof that IF are dynamic elements of the cytoskeleton of mammalian cells. PMID:7686161

  7. [Effect of melatonin on antioxidant state under type ii diabetes at rat].

    PubMed

    Agarkov, A A; Popova, T N; Matasova, L V

    2013-01-01

    The effect of melatonin on the intensity of free radical processes and activities of superoxide dismutase (SOD, EC 1.15.1.1.) and catalase (EC 1.11.1.6) has been investigated in liver and blood serum of rats with diabetes mellitus type II. The development of diabetes was accompanied by the increase in biochemiluminescence parameters and the enzyme activities studied. Melatonin administration changed the parameters studied towards control values.

  8. "Addition" and "Subtraction": Selectivity Design for Type II Maternal Embryonic Leucine Zipper Kinase Inhibitors.

    PubMed

    Chen, Xin; Giraldes, John; Sprague, Elizabeth R; Shakya, Subarna; Chen, Zhuoliang; Wang, Yaping; Joud, Carol; Mathieu, Simon; Chen, Christine Hiu-Tung; Straub, Christopher; Duca, Jose; Hurov, Kristen; Yuan, Yanqiu; Shao, Wenlin; Touré, B Barry

    2017-03-09

    While adding the structural features that are more favored by on-target activity is the more common strategy in selectivity optimization, the opposite strategy of subtracting the structural features that contribute more to off-target activity can also be very effective. Reported here is our successful effort of improving the kinase selectivity of type II maternal embryonic leucine zipper kinase inhibitors by applying these two complementary approaches together, which clearly demonstrates the powerful synergy between them.

  9. Geochemistry of the alginite and amorphous organic matter from type II-S kerogens

    USGS Publications Warehouse

    Stankiewicz, B.A.; Kruge, M.A.; Mastalerz, Maria; Salmon, G.L.

    1996-01-01

    Maceral fractions of the Type II-S kerogens from the Monterey Formation (Miocene. California. U.S.A.) and Duwi Formation (Campanian/Maastrichtian, Egypt) were separated by density gradient centrifugation. The Monterey Fm. kerogen sample was comprised chiefly of light red-fluorescing amorphous organic matter (AOM), the flash pyrolyzate of which was characterized by a predominance of alkylbenzenes, alkylthiophenes and alkylpyrroles. In contrast, the pyrolyzates of its alginite concentrate showed a highly aliphatic character, typical of this maceral, with the series of n-alkenes and n-alkanes (C6- C26) predominating. The pyrolyzate of the dominant light brown-fluorescing AOM of the Duwi Fm. kerogen had a relatively high concentration of alkylbenzenes and alkylthiophenes, while its elginite concentrate showed a more aliphatic character upon pyrolysis. There was a marked enrichment of thiophenic sulfur in the light-colored AOM of both samples (and also pyrrolic nitrogen in the case of the Monterey) relative to the alginite. The results support a bacterially-mediated, degradative origin for Type II-S amorphous organic matter, with algal remains as the primary source of the kerogen.

  10. Early photocoagulation in patients with either type I or type II diabetes.

    PubMed Central

    Ferris, F

    1996-01-01

    OBJECTIVE: To determine the benefits of early photocoagulation in patients with type I versus type II diabetes. DESIGN: One eye of each of 3,711 patients was randomly assigned to early photocoagulation; the other was assigned to deferral of photocoagulation, with follow-up visits scheduled every 4 months and photocoagulation to be carried out promptly if high-risk proliferative retinopathy developed. Patients were categorized by age and type of diabetes. MAIN OUTCOME MEASURES: Best corrected visual acuity was measured at each study visit scheduled at 4-month intervals. Stereoscopic fundus photographs were taken and evaluated at baseline, 4 months, and yearly thereafter. Retinopathy severity was assessed from fundus photographs. Severe visual loss was defined as visual acuity of worse than 5/200 for at least two consecutive study visits. RESULTS: Previously published results of the Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated a statistically significant benefit of early photocoagulation in preventing severe vision loss. Further analyses demonstrate that this benefit of early photocoagulation is greater in patients with type II diabetes than in those with type I. The relative benefit of early photocoagulation in patients with type II diabetes is also seen for other outcomes (development of high-risk proliferative retinopathy, development of the combined end point [severe visual loss or vitrectomy], development of moderate visual loss, or development of legal blindness). The patients most likely to benefit from early photocoagulation had severe nonproliferative retinopathy or early proliferative retinopathy. Analyses from the Diabetic Retinopathy Study confirm the relative benefit of scatter photocoagulation for type II patients. Because of the high correlation between age and type of diabetes, analyses sub-grouped by age show similar results. CONCLUSION: These analyses suggest that patients with type II diabetes, or older patients with diabetes

  11. Action Potentials and Ion Conductances in Wild-type and CALHM1-knockout Type II Taste Cells.

    PubMed

    Ma, Zhongming; Saung, Wint Thu; Foskett, J Kevin

    2017-02-15

    Taste bud type II cells fire action potentials in response to tastants, triggering non-vesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. Here, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1-knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1-KO mice, and their associated non-selective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1-KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na(+) currents either estimated from action potentials or recorded from steady-state voltage-pulses, or action potential threshold, overshoot peak, after-hyperpolarization and firing frequency. However, Calhm1-deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials.

  12. Safety and toxicological evaluation of a novel, water-soluble undenatured type II collagen.

    PubMed

    Yoshinari, Orie; Marone, Palma Ann; Moriyama, Hiroyoshi; Bagchi, Manashi; Shiojima, Yoshiaki

    2013-09-01

    This study was conducted to determine the broad-spectrum safety of a novel, water-soluble undenatured type II collagen (NEXT-II) derived from chicken sternum cartilage. The presence of epitope in NEXT-II was confirmed by using a commercial kit. The acute oral LD₅₀ of NEXT-II was found to be greater than 5000 mg/kg bw in rats, while the single-dose acute dermal LD₅₀ was greater than 2000 mg/kg bw. The primary dermal irritation index (PDII) of NEXT-II was found to be 1.8 and classified as slightly irritating to the skin. In primary eye irritation studies, the maximum mean total score (MMTS) of NEXT-II was observed to be 7.3 and classified as minimally irritating to the eye. Long-term safety studies were conducted in dogs over a period of 150 d, and no significant changes were observed in body weight, heart rate, respiration rate and blood chemistry. NEXT-II does not induce mutagenicity in the bacterial reverse mutation test in five Salmonella typhimurium strains either with or without metabolic activation. Furthermore, two experiments were conducted to assess the potential of NEXT-II to induce mutations with and without metabolic activation at the mouse lymphoma thymidine kinase locus using the cell line L5178Y. No biologically relevant increase of mutants was observed. Also, no dose-dependent toxicity was observed. Furthermore, colony sizing showed no clastogenic effects induced by NEXT-II under the experimental conditions. These studies demonstrated the broad spectrum of safety of NEXT-II.

  13. Activation-induced cell death of memory CD8+ T cells from pleural effusion of lung cancer patients is mediated by the type II Fas-induced apoptotic pathway.

    PubMed

    Prado-Garcia, Heriberto; Romero-Garcia, Susana; Morales-Fuentes, Jorge; Aguilar-Cazares, Dolores; Lopez-Gonzalez, Jose Sullivan

    2012-07-01

    Lung cancer is the second most common form of cancer and the leading cause of cancer death worldwide. Pleural effusions, containing high numbers of mononuclear and tumor cells, are frequent in patients with advanced stages of lung cancer. We reported that in pleural effusions from primary lung cancer, the CD8+ T cell subpopulation, and particularly the terminally differentiated subset, is reduced compared to that of non-malignant effusions. We analyzed the participation of activation-induced cell death (AICD) and extrinsic pathways (type I or II) as mechanisms for the decrease in pleural effusion CD8+ T cell subpopulation. Pleural effusion or peripheral blood CD4+ and CD8+ T cells, from lung cancer patients, were stimulated with anti-CD3 antibody and analyzed for (a) apoptosis by annexin-V-binding and TUNEL assay, (b) transcript levels of Fas ligand (FasL) and TRAIL by real-time RT-PCR, (c) expression of FasL and TRAIL, measured as integrated mean fluorescence intensities (iMFI) by flow cytometry, (d) expression of Bcl-2 and BIM molecules, measured as MFI, and (e) apoptosis inhibition using caspase-8 and -9 inhibitors. Pleural effusion CD8+ T cells, but not CD4+ T cells, from cancer patients underwent AICD. Blocking FasL/Fas pathway protected from AICD. Upregulation of FasL and TRAIL expressions was found in pleural effusion CD8+ T cells, which also showed a subset of Bcl-2 low cells. In memory CD8+ T cells, AICD depended on both extrinsic and intrinsic apoptotic pathways. Hence, in the pleural space of lung cancer patients, AICD might compromise the antitumor function of CD8+ T cells.

  14. Psycho-neuro-endocrine-immune mechanisms of action of yoga in type II diabetes

    PubMed Central

    Singh, Vijay Pratap; Khandelwal, Bidita; Sherpa, Namgyal T.

    2015-01-01

    Yoga has been found to benefit all the components of health viz. physical, mental, social and spiritual well being by incorporating a wide variety of practices. Pathophysiology of Type II DM and co-morbidities in Type II DM has been correlated with stress mechanisms. Stress suppresses body's immune system and neuro-humoral actions thereby aff ecting normal psychological state. It would not be wrong to state that correlation of diabetes with stress, anxiety and other psychological factors are bidirectional and lead to difficulty in understanding the interrelated mechanisms. Type II DM cannot be understood in isolation with psychological factors such as stress, anxiety and depression, neuro-endocrine and immunological factors. There is no review which tries to understand these mechanisms exclusively. The present literature review aims to understand interrelated Psycho-Neuro-Endocrine and Immunological mechanisms of action of Yoga in Type II Diabetes Mellitus. Published literature concerning mechanisms of action of Yoga in Type II DM emphasizing psycho-neuro-endocrine or immunological relations was retrieved from Pubmed using key words yoga, Type II diabetes mellitus, psychological, neural, endocrine, immune and mechanism of action. Those studies which explained the psycho-neuroendocrine and immune mechanisms of action of yoga were included and rest were excluded. Although primary aim of this study is to explain these mechanisms in Type II DM, some studies in non-diabetic population which had a similar pathway of stress mechanism was included because many insightful studies were available in that area. Search was conducted using terms yoga OR yogic AND diabetes OR diabetic IN title OR abstract for English articles. Of the 89 articles, we excluded non-English articles (22), editorials (20) and letters to editor (10). 37 studies were considered for this review. The postulated mechanism of action of yoga is through parasympathetic activation and the associated anti

  15. Psycho-neuro-endocrine-immune mechanisms of action of yoga in type II diabetes.

    PubMed

    Singh, Vijay Pratap; Khandelwal, Bidita; Sherpa, Namgyal T

    2015-01-01

    Yoga has been found to benefit all the components of health viz. physical, mental, social and spiritual well being by incorporating a wide variety of practices. Pathophysiology of Type II DM and co-morbidities in Type II DM has been correlated with stress mechanisms. Stress suppresses body's immune system and neuro-humoral actions thereby aff ecting normal psychological state. It would not be wrong to state that correlation of diabetes with stress, anxiety and other psychological factors are bidirectional and lead to difficulty in understanding the interrelated mechanisms. Type II DM cannot be understood in isolation with psychological factors such as stress, anxiety and depression, neuro-endocrine and immunological factors. There is no review which tries to understand these mechanisms exclusively. The present literature review aims to understand interrelated Psycho-Neuro-Endocrine and Immunological mechanisms of action of Yoga in Type II Diabetes Mellitus. Published literature concerning mechanisms of action of Yoga in Type II DM emphasizing psycho-neuro-endocrine or immunological relations was retrieved from Pubmed using key words yoga, Type II diabetes mellitus, psychological, neural, endocrine, immune and mechanism of action. Those studies which explained the psycho-neuroendocrine and immune mechanisms of action of yoga were included and rest were excluded. Although primary aim of this study is to explain these mechanisms in Type II DM, some studies in non-diabetic population which had a similar pathway of stress mechanism was included because many insightful studies were available in that area. Search was conducted using terms yoga OR yogic AND diabetes OR diabetic IN title OR abstract for English articles. Of the 89 articles, we excluded non-English articles (22), editorials (20) and letters to editor (10). 37 studies were considered for this review. The postulated mechanism of action of yoga is through parasympathetic activation and the associated anti

  16. Diagnostic Value of Adenosine Deaminase and Its Isoforms in Type II Diabetes Mellitus

    PubMed Central

    Larijani, Bagher; Heshmat, Ramin; Ebrahimi-Rad, Mina; Khatami, Shohreh; Valadbeigi, Shirin

    2016-01-01

    Background and Aims. In the present study, we have investigated the activity of adenosine deaminase (ADA) as a diagnostic marker in type 2 (or II) diabetes mellitus (T2DM). Design and Methods. The deaminase activity of ADA1 and ADA2 was determined in serum from 33 patients with type 2 (or II) diabetes mellitus and 35 healthy controls. We also determined the proportion of glycated hemoglobin (HbA1c). Results. Our results showed significant differences between total serum ADA (tADA) and ADA2 activities in the diabetic groups with HbA1c < 8 (%) and HbA1c ≥ 8 (%) with respect to the values in healthy individuals (p < 0.001). ADA2 activity in patients with high HbA1c was found to be much higher than that in patients with low HbA1c (p = 0.0001). In addition, total ADA activity showed a significant correlation with HbA1c (r = 0.6, p < 0.0001). Conclusions. Total serum ADA activity, specially that due to ADA2, could be useful test for the diagnosis of type 2 (or II) diabetes mellitus. PMID:28050278

  17. Bauhinia variegata (Caesalpiniaceae) leaf extract: An effective treatment option in type I and type II diabetes.

    PubMed

    Kulkarni, Yogesh A; Garud, Mayuresh S

    2016-10-01

    Among various metabolic disorders, diabetes mellitus is one of the most common disorder. Present study was designed to evaluate the effectiveness of aqueous extract of Bauhinia variegata leaves (AE) in animal models of type I and type II diabetes. Type I diabetes was induced by streptozotocin at the dose of 55mg/kg (i.p.) in male Sprague Dawley rats while type II diabetes was induced by high fat diet and streptozotocin at the dose of 35mg/kg (i.p.). Diabetic animals were treated with AE at the dose of 250, 500 and 1000mg/kg. Glipizide (5mg/kg) was used as standard treatment drug. Treatment was given for 28days. Parameters evaluated were body weight, plasma glucose, cholesterol, triglyceride, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, total proteins, albumin, creatinine and bun urea nitrogen. In type II diabetes, high density lipoprotein levels in plasma and plasma insulin level were also evaluated. Histopathological study of pancreases were carried out in type I study. AE showed significant decrease in plasma glucose significantly. AE was also found to decrease cholesterol, triglyceride, creatinine and blood urea nitrogen level in both types of diabetes. AE did not show any significant effect on plasma levels of aspartate aminotransferase, alanine transaminase, alkaline phosphatase. AE was found to increase the albumin and total protein levels. Histopathological study showed that AE decreases the necrotic changes in the pancreatic tissue. Aqueous extract of B. variegata leaves was found effective in treatment of both type I and type II diabetes.

  18. Angiotensin II activates endothelial constitutive nitric oxide synthase via AT1 receptors.

    PubMed

    Saito, S; Hirata, Y; Emori, T; Imai, T; Marumo, F

    1996-09-01

    To determine whether angiotensin (ANG) II, a vasoconstrictor hormone, activates constitutive nitric oxide synthase (cNOS) in endothelial cells (ECs), we investigated the cellular mechanism by which ANG II induces nitric oxide (NO) formation in cultured bovine ECs. ANG II rapidly (within 1 min) and dose-dependently (10(-9)-10(-6) M) increased nitrate/nitrite (NOx) production. This effect of ANG II was abolished by a NOS inhibitor, NG-monomethyl-L-arginine. An ANG II type 1 (AT1) receptor antagonist (DuP 753), but not an ANG II type 2 (AT2) receptor antagonist (PD 123177), dose-dependently inhibited ANG II-induced NOx production. A Ca(2+)-channel blocker (barnidipine) failed to affect ANG II-induced NOx production, whereas an intracellular Ca2+ chelator (BAPTA) and a calmodulin inhibitor (W-7) abolished NOx production induced by ANG II. A protein kinase C (PKC) inhibitor (H-7) and down-regulation of endogenous PKC after pretreatment with phorbol ester decreased NOx production stimulated by ANG II. ANG II transiently stimulated inositol 1,4,5-trisphosphate (IP3) formation, and increased cytosolic free Ca2+ concentrations; these effects were blocked by DuP 753. Our data demonstrate that ANG II stimulates NO release by activation of Ca2+/calmodulin-dependent cNOS via AT1 receptors in bovine ECs.

  19. A search for the primary abnormality in adult-onset type II citrullinemia

    SciTech Connect

    Kobayashi, Keiko; Shaheen, Nazma; Saheki, Takeyori ); Kumashiro, Ryukichi; Tanikawa, Kyuichi ); O'Brien, W.E.; Beaudet, A.L. )

    1993-11-01

    Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, the authors show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. The authors also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus. 29 refs., 1 fig., 3 tabs.

  20. Modeling fluid dynamics on type II quantum computers

    NASA Astrophysics Data System (ADS)

    Scoville, James; Weeks, David; Yepez, Jeffrey

    2006-03-01

    A quantum algorithm is presented for modeling the time evolution of density and flow fields governed by classical equations, such as the diffusion equation, the nonlinear Burgers equation, and the damped wave equation. The algorithm is intended to run on a type-II quantum computer, a parallel quantum computer consisting of a lattice of small type I quantum computers undergoing unitary evolution and interacting via information interchanges represented by an orthogonal matrices. Information is effectively transferred between adjacent quantum computers over classical communications channels because of controlled state demolition following local quantum mechanical qubit-qubit interactions within each quantum computer. The type-II quantum algorithm presented in this paper describes a methodology for generating quantum logic operations as a generalization of classical operations associated with finite-point group symmetries. The quantum mechanical evolution of multiple qubits within each node is described. Presented is a proof that the parallel quantum system obeys a finite-difference quantum Boltzman equation at the mesoscopic scale, leading in turn to various classical linear and nonlinear effective field theories at the macroscopic scale depending on the details of the local qubit-qubit interactions.

  1. Isolation and properties of type II alveolar cells from rat lung.

    PubMed

    Mason, R J; Williams, M C; Greenleaf, R D; Clements, J A

    1977-06-01

    Type II alveolar cells can be isolated and partially purified from adult rat lung by a series of steps that includes enzymatic digestion of the lung with trypsin and separation of cells on a discontinuous albumin density gradient. The yield of the isolated type II cells depends on the supplier and the housing of the rats used to prepare the cells. With specific pathogen-free rats housed in a laminar flow hood, the yield was 20.3 x 10(6) cells per rat, of which 50 per cent were type II cells. With rats from 2 other suppliers and no special housing, the yields were 8.8 and 8.3 x 10(6) cells per rat, of which 67 and 65 per cent were type II cells. The ultrastructural appearance of the isolated cells was similar to that of cells from intact lung, except for some dilatation of the endoplasmic reticulum and the perinuclear space. Most cells (92 +/- 5 per cent) excluded the vital dye, trypan blue. The cells consumed O2 at the rate of 76 +/- 12 nmole per 10(6) cells per hour and released only 5.7 +/- 2.0 per cent of their lactate dehydrogenase, a cytoplasmic enzyme, into the medium after 1 hour of incubation. The isolated type II cells contained disaturated phosphatidylcholine, a major component of purified surface-active material. The cells, however, had a low glucose utilization compared to their O2 consumption, which may indicate an abnormality in the metabolism of glucose. This population of cells could be further purified to 89 per cent type II cells by unit gravity velocity sedimentation.

  2. On the Intrinsic Diversity of Type II-Plateau Supernovae

    NASA Astrophysics Data System (ADS)

    Pejcha, Ondřej; Prieto, Jose L.

    2015-06-01

    Hydrogen-rich Type II-Plateau supernovae (SNe) exhibit correlations between the plateau luminosity {L}{pl}, the nickel mass {M}{Ni}, the explosion energy {E}{exp}, and the ejecta mass {M}{ej}. Using our global, self-consistent, multi-band model of nearby well-observed SNe, we find that the covariances of these quantities are strong and that the confidence ellipsoids are oriented in the direction of the correlations, which reduces their significance. By proper treatment of the covariance matrix of the model, we discover a significant intrinsic width to the correlations between {L}{pl}, {E}{exp} and {M}{Ni}, where the uncertainties due to the distance and the extinction dominate. For fixed {E}{exp}, the spread in {M}{Ni} is about 0.25 dex, which we attribute to the differences in the progenitor internal structure. We argue that the effects of incomplete γ-ray trapping are not important in our sample. Similarly, the physics of the Type II-Plateau SN light curves leads to inherently degenerate estimates of {E}{exp} and {M}{ej}, which makes their observed correlation weak. Ignoring the covariances of SN parameters or the intrinsic width of the correlations causes significant biases in the slopes of the fitted relations. Our results imply that Type II-Plateau SN explosions are not described by a single physical parameter or a simple one-dimensional trajectory through the parameter space, but instead reflect the diversity of the core and surface properties of their progenitors. We discuss the implications for the physics of the explosion mechanism and possible future observational constraints.

  3. Effect of the type-I to type-II Weyl semimetal topological transition on superconductivity

    NASA Astrophysics Data System (ADS)

    Li, Dingping; Rosenstein, Baruch; Shapiro, B. Ya.; Shapiro, I.

    2017-03-01

    The influence of recently discovered topological transition between type-I and type-II Weyl semimetals on superconductivity is considered. A set of Gorkov equations for weak superconductivity in Weyl semimetal under topological phase transition is derived and solved. The critical temperature and superconducting gap both have spikes in the transition point as functions of the tilt parameter of the Dirac cone determined, in turn, by the material parameters like pressure. The spectrum of superconducting excitations is different in two phases: The sharp cone pinnacle is characteristic for type I, while two parallel almost flat bands, are formed in type II. Spectral density is calculated on both sides of transition to demonstrate the different weights of the bands. The superconductivity thus can be used as a clear indicator for the topological transformation. Results are discussed in the light of recent experiments.

  4. Predicted continuum spectra of type II supernovae - LTE results

    NASA Technical Reports Server (NTRS)

    Shaviv, G.; Wehrse, R.; Wagoner, R. V.

    1985-01-01

    The continuum spectral energy distribution of the flux emerging from type II supernovae is calculated from quasi-static radiative transfer through a power-law density gradient, assuming radiative equilibrium and LTE. It is found that the Balmer jump disappears at high effective temperatures and low densities, while the spectrum resembles that of a dilute blackbody but is flatter with a sharper cutoff at the short-wavelength end. A significant UV excess is found in all models calculated. The calculation should be considered exploratory because of significant effects which are anticipated to arise from departure from LTE.

  5. Predictive data modeling of human type II diabetes related statistics

    NASA Astrophysics Data System (ADS)

    Jaenisch, Kristina L.; Jaenisch, Holger M.; Handley, James W.; Albritton, Nathaniel G.

    2009-04-01

    During the course of routine Type II treatment of one of the authors, it was decided to derive predictive analytical Data Models of the daily sampled vital statistics: namely weight, blood pressure, and blood sugar, to determine if the covariance among the observed variables could yield a descriptive equation based model, or better still, a predictive analytical model that could forecast the expected future trend of the variables and possibly eliminate the number of finger stickings required to montior blood sugar levels. The personal history and analysis with resulting models are presented.

  6. Interaction of ultrasound with vortices in type-II superconductors

    SciTech Connect

    Sonin, E.B.

    1996-04-01

    The theory of ultrasound in the mixed state of type-II superconductors is suggested which takes into account the Magnus force on vortices, the anti-Magnus force on ions, and diamagnetism of the mixed state. The acoustic Faraday effect (rotation of polarization of the transverse ultrasonic wave propagating along vortices) is linear in the Magnus force in any regime of the flux flow for wavelengths now used in the ultrasound experiments. Therefore, in contrast to previous predictions, the Faraday effect should be looked for only in clean superconductors with a strong Magnus force. {copyright} {ital 1996 The American Physical Society.}

  7. Type II strained layer superlattice: A potential future IR solution

    NASA Astrophysics Data System (ADS)

    Tidrow, Meimei Z.

    2009-11-01

    Type II strained layer superlattice (SLS) has been making tremendous progress in the past few years funded by the Missile Defense Agency Advanced Technology Directorate (MDA/DV) under the Passive EO/IR Program. SLS has shown great potential as a future solution for infrared military systems. In this presentation, the most recent progress in SLS development will be presented. The presentation will also discuss the comparison of SLS with mercury-cadmium-telluride (HgCdTe) using Rule 07, SLS minority carrier lifetime issues, and future directions.

  8. Biochemical and Bioinformatic Characterization of Type II Metacaspase Protein (TaeMCAII) from Wheat.

    PubMed

    Piszczek, E; Dudkiewicz, M; Mielecki, M

    2012-01-01

    The biochemical analysis and homology modeling of a tertiary structure of a cereal type II metacaspase protein from wheat (Triticum aestivum), TaeMCAII, are presented. The biochemical characterization of synthetic oligopeptides and protease inhibitors of Escherichia coli-produced and purified recombinant TaeMCAII revealed that this metacaspase protein, similar to other known plant metacaspases, is an arginine/lysine-specific cysteine protease. Thus, a model of a plant type II metacaspase structure based on newly identified putative metacaspase-like template was proposed. Homology modeling of the TaeMCAII active site tertiary structure showed two cysteine residues, Cys140 and 23, in close proximity to the catalytic histidine, most likely participating in proton exchange during the catalytic process. The autoprocessing that leads to activation of TaeMCAII was highly dependent on Cys140. TaeMCAII required high levels of calcium ions for activity, which could indicate its involvement in stress signaling pathways connected to programmed cell death.

  9. Effect of hole transport on performance of infrared type-II superlattice light emitting diodes

    SciTech Connect

    Lin, Youxi; Suchalkin, Sergey; Kipshidze, Gela; Hosoda, Takashi; Westerfeld, David; Shterengas, Leon; Belenky, Gregory; Laikhtman, Boris

    2015-04-28

    The effect of hole transport on the performance of infrared light emitting diodes (LED) was investigated. The active area of the LEDs comprised two type-II superlattices with different periods and widths connected in series. Electroluminescence spectra of the devices with different positions of long wave and mid wave superlattice sections were mostly contributed by the superlattice closest to the p-contact. The experimental results indicate that due to suppressed vertical hole transport, the recombination of electrically injected electrons and holes in a type II superlattice LED active region takes place within a few superlattice periods near p-barrier. Possible reason for the effect is reduction of hole diffusion coefficient in an active area of a superlattice LED under bias.

  10. Cognitive Dysfunction Is Worse among Pediatric Patients with Bipolar Disorder Type I than Type II

    ERIC Educational Resources Information Center

    Schenkel, Lindsay S.; West, Amy E.; Jacobs, Rachel; Sweeney, John A.; Pavuluri, Mani N.

    2012-01-01

    Background: Impaired profiles of neurocognitive function have been consistently demonstrated among pediatric patients with bipolar disorder (BD), and may aid in the identification of endophenotypes across subtypes of the disorder. This study aims to determine phenotypic cognitive profiles of patients with BD Type I and II. Methods: Subjects (N =…

  11. [Achondrogenesis type II-hypochondrogenesis: radiological features.Case report].

    PubMed

    Delgado Carrasco, J; Casanova Morcillo, A; Zabalza Alvillos, M; Ayala Garcés, A

    2001-12-01

    We present a case of lethal dysplasia in the neonatal period. The abnormality was suspected after ultrasonography of a pregnant woman presenting weak fetal movements revealed shortening of the extremities, voluminous cranium and polyhydramnios. Clinical and radiological findings showed platyspondylic dwarfism with short extremities, narrow thorax and hydropic appearance. The infant died on the third day of life from progressive respiratory distress. In the absence of histological, chondro-osseus and molecular studies, detailed clinical and radiological studies, as well as the lethal evolution during the neonatal period, guided the diagnosis of hypochondrogenesis. This entity, together with achondrogenesis II (and other dysplasias), forms part of the same spectrum of collagen type II abnormalities produced by a defect in the gene (COL2A1) that codifies collagen II, located in chromosome 12 I(12q13.1-13.2). When a heterozygote is produced, transmission is dominant autosomal. The phenotype shows wide variation and severity depends on the mechanism and location of the mutation. The definitive diagnosis is given by cytomolecular studies, while individualization of the different entities is based on histological data from the cartilage; clinical findings and skeletal radiology serve as a guide.

  12. Clinical and immunohistochemical characteristics of type II and type I focal cortical dysplasia

    PubMed Central

    Yao, Kun; Duan, Zejun; Zhou, Jian; Li, Lin; Zhai, Feng; Dong, Yanting; Wang, Xiaoyan; Ma, Zhong; Bian, Yu; Qi, Xueling; Li, Liang

    2016-01-01

    Focal cortical dysplasia (FCD) II and I are major causes for drug-resistant epilepsy. In order to gain insight into the possible correlations between FCD II and FCD I, different clinical characteristics and immunohistochemical expression characteristics in FCD I and II were analyzed. The median age of onset and duration of epilepsy in FCD I and FCD II patients were 2.1 years and 5.3 years vs 2.4 years and 4.5 years. Therefore, the median age of onset and duration of epilepsy were similar in the two groups. Pathological lesions were predominantly located in frontal lobe in FCD II and temporal in FCD I. Significantly more signal abnormalities in FLAIR and T2 images were demonstrated in FCD II than FCD I. The rate of satisfied seizure outcome was relative higher in FCDII patients (95.12%) than that in FCDI group (84.6%). Furthermore, we detected expressions of progenitor cell proteins and the mammalian target of rapamycin (mTOR) cascade activation protein in FCDs. Results showed that sex-determiningregion Y-box 2(SOX2), Kruppel-likefactor 4 (KLF4) and phospho-S6 ribosomal proteins (ser240/244 or ser235/236) were expressed in FCDII group but not in FCD I. Overall, this study unveils FCD I and II exhibit distinct clinical and immunohistochemical expression characteristics, revealing different pathogenic mechanisms. PMID:27811355

  13. Type-II Bursts in Meter and Deca - Hectometer Wavelengths and Their Relation to Flares and CMEs: II

    NASA Astrophysics Data System (ADS)

    Prakash, O.; Umapathy, S.; Shanmugaraju, A.; Pappa Kalaivani, P.; Vršnak, Bojan

    2010-09-01

    A study of the relationship between 38 type-II bursts recorded in meter and deca-hectometer (hereinafter m and DH) wavelength range and the associated flares and CMEs observed during the years 2000 - 2005 was carried out by Prakash et al. (2009). These events were divided into two classes: i) Class I, representing events where DH-type-II bursts are not a continuation of m-type-II bursts and ii) Class II, where DH-type-II bursts are a continuation of m-type-II bursts. In the present work, we extend the analysis of this sample of 38 events in three different steps: i) statistical properties of m- and DH-type-II bursts; ii) analysis of time lags between onsets of flares and CMEs associated with type-II bursts; and iii) statistical properties and relation between flares and CMEs of Class I and Class II events. We found a significant difference between the properties of m- and DH-type-II bursts of Class I and Class II events. For example, there are significant differences in starting and ending frequencies, bandwidth and speed. From the time delay analysis, we found the following. i) In 64% of Class I events, flares start after the onset of CMEs and the remaining 36% of flares start before the onset of CMEs. On the other hand, in the case of Class II events, the values are 83% and 17%, respectively. ii) The difference between the mean values of delay between flare start and DH start has high statistical significance (probability P of null hypothesis <1%). The time delays between the start of m-type-II burst and the CME onset are considerably larger for Class I events ( P=7%) than Class II events. iii) There are notable differences in: (a) delay between the flare and CME onset times ( P<1%); (b) flare rise time of Class I and Class II events ( P<5%). iv) While the flare rise time is well correlated with the lag between the flare start and the CME onset in Class I events, there is no such correlation for Class II events.

  14. A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a KLHL3 mutation

    PubMed Central

    Mitani, Marie; Furuichi, Munehiro; Narumi, Satoshi; Hasegawa, Tomonobu; Chiga, Motoko; Uchida, Shinichi; Sato, Seiji

    2016-01-01

    Abstract. Pseudohypoaldosteronism type II (PHA II) is a renal tubular disease that causes hyperkalemia, hypertension, and metabolic acidosis. Mutations in four genes (WNK4, WNK1, KLHL3, and CUL3) are known to cause PHA II. We report a patient with PHA II carrying a KLHL3 mutation, who also had congenital hypopituitarism. The patient, a 3-yr-old boy, experienced loss of consciousness at age 10 mo. He exhibited growth failure, hypertension, hyperkalemia, and metabolic acidosis. We diagnosed him as having PHA II because he had low plasma renin activity with normal plasma aldosterone level and a low transtubular potassium gradient. Further investigations revealed defective secretion of GH and gonadotropins and anterior pituitary gland hypoplasia. Genetic analyses revealed a previously known heterozygous KLHL3 mutation (p.Leu387Pro), but no mutation was detected in 27 genes associated with congenital hypopituitarism. He was treated with sodium restriction and recombinant human GH, which normalized growth velocity. This is the first report of a molecularly confirmed patient with PHA II complicated by congenital hypopituitarism. We speculate that both GH deficiency and metabolic acidosis contributed to growth failure. Endocrinological investigations will help to individualize the treatment of patients with PHA II presenting with growth failure. PMID:27780982

  15. A-current and type I/type II transition determine collective spiking from common input.

    PubMed

    Barreiro, Andrea K; Thilo, Evan L; Shea-Brown, Eric

    2012-09-01

    The mechanisms and impact of correlated, or synchronous, firing among pairs and groups of neurons are under intense investigation throughout the nervous system. A ubiquitous circuit feature that can give rise to such correlations consists of overlapping, or common, inputs to pairs and populations of cells, leading to common spike train responses. Here, we use computational tools to study how the transfer of common input currents into common spike outputs is modulated by the physiology of the recipient cells. We focus on a key conductance, g(A), for the A-type potassium current, which drives neurons between "type II" excitability (low g(A)), and "type I" excitability (high g(A)). Regardless of g(A), cells transform common input fluctuations into a tendency to spike nearly simultaneously. However, this process is more pronounced at low g(A) values. Thus, for a given level of common input, type II neurons produce spikes that are relatively more correlated over short time scales. Over long time scales, the trend reverses, with type II neurons producing relatively less correlated spike trains. This is because these cells' increased tendency for simultaneous spiking is balanced by an anticorrelation of spikes at larger time lags. These findings extend and interpret prior findings for phase oscillators to conductance-based neuron models that cover both oscillatory (superthreshold) and subthreshold firing regimes. We demonstrate a novel implication for neural signal processing: downstream cells with long time constants are selectively driven by type I cell populations upstream and those with short time constants by type II cell populations. Our results are established via high-throughput numerical simulations and explained via the cells' filtering properties and nonlinear dynamics.

  16. Type-II Weyl cone transitions in driven semimetals

    NASA Astrophysics Data System (ADS)

    Chan, Ching-Kit; Oh, Yun-Tak; Han, Jung Hoon; Lee, Patrick A.

    2016-09-01

    Periodically driven systems provide tunable platforms to realize interesting Floquet topological phases and phase transitions. In electronic systems with Weyl dispersions, the band crossings are topologically protected even in the presence of time-periodic perturbations. This robustness permits various routes to shift and tilt the Weyl spectra in the momentum and energy space using circularly polarized light of sufficient intensity. We show that type-II Weyl fermions, in which the Weyl dispersions are tilted with the appearance of pocketlike Fermi surfaces, can be induced in driven Dirac semimetals and line node semimetals. Under a circularly polarized drive, both semimetal systems immediately generate Weyl node pairs whose types can be further controlled by the driving amplitude and direction. The resultant phase diagrams demonstrate experimental feasibilities.

  17. Exotic dual of type II double field theory

    NASA Astrophysics Data System (ADS)

    Bergshoeff, Eric A.; Hohm, Olaf; Riccioni, Fabio

    2017-04-01

    We perform an exotic dualization of the Ramond-Ramond fields in type II double field theory, in which they are encoded in a Majorana-Weyl spinor of O (D , D). Starting from a first-order master action, the dual theory in terms of a tensor-spinor of O (D , D) is determined. This tensor-spinor is subject to an exotic version of the (self-)duality constraint needed for a democratic formulation. We show that in components, reducing O (D , D) to GL (D), one obtains the expected exotically dual theory in terms of mixed Young tableaux fields. To this end, we generalize exotic dualizations to self-dual fields, such as the 4-form in type IIB string theory.

  18. Adenosine-A1 receptor agonist induced hyperalgesic priming type II.

    PubMed

    Araldi, Dioneia; Ferrari, Luiz F; Levine, Jon D

    2016-03-01

    We have recently shown that repeated exposure of the peripheral terminal of the primary afferent nociceptor to the mu-opioid receptor (MOR) agonist DAMGO ([D-Ala, N-Me-Phe, Gly-ol]-enkephalin acetate salt) induces a model of transition to chronic pain that we have termed type II hyperalgesic priming. Similar to type I hyperalgesic priming, there is a markedly prolonged response to subsequent administration of proalgesic cytokines, prototypically prostaglandin E2 (PGE2). However, type II hyperalgesic priming differs from type I in being rapidly induced, protein kinase A (PKA), rather than PKCε dependent, not reversed by a protein translation inhibitor, occurring in female as well as in male rats, and isolectin B4-negative neuron dependent. We report that, as with the repeated injection of a MOR agonist, the repeated administration of an agonist at the A1-adenosine receptor, also a Gi-protein coupled receptor, N-cyclopentyladenosine (CPA), also produces priming similar to DAMGO-induced type II hyperalgesic priming. In this study, we demonstrate that priming induced by repeated exposure to this A1-adenosine receptor agonist shares the same mechanisms, as MOR-agonist induced priming. However, the prolongation of PGE2 hyperalgesia induced by repeated administration of CPA depends on G-protein αi subunit activation, differently from DAMGO-induced type II priming, in which it depends on the β/γ subunit. These data implicate a novel form of Gi-protein signaling pathway in the type II hyperalgesic priming induced by repeated administration of an agonist at A1-adenosine receptor to the peripheral terminal of the nociceptor.

  19. Adenosine-A1 Receptor Agonist Induced Hyperalgesic Priming Type II

    PubMed Central

    Araldi, Dioneia; Ferrari, Luiz F.; Levine, Jon D.

    2016-01-01

    We have recently shown that repeated exposure of the peripheral terminal of the primary afferent nociceptor to the mu-opioid receptor (MOR) agonist DAMGO ([D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin acetate salt) induces a model of the transition to chronic pain that we have termed Type II hyperalgesic priming. Similar to Type I hyperalgesic priming, there is a markedly prolonged response to subsequent administration of proalgesic cytokines, prototypically prostaglandin E2 (PGE2). However, Type II hyperalgesic priming differs from Type I in being rapidly induced, protein kinase A (PKA), rather than PKCε dependent, not reversed by a protein translation inhibitor, occurring in female as well as in male rats, and isolectin B4-negative neuron dependent. We report that as with the repeated injection of a MOR agonist, the repeated administration of an agonist at the A1-adenosine receptor, also a Gi-protein coupled receptor, N6-Cyclopentyladenosine (CPA), also produces priming similar to DAMGO-induced Type II hyperalgesic priming. In this study we demonstrate that priming induced by repeated exposure to this A1-adenosine receptor agonist shares the same mechanisms as MOR-agonist induced priming. However, the prolongation of PGE2 hyperalgesia induced by repeated administration of CPA depends on G-protein αi subunit activation, differently from DAMGO-induced Type II priming, in which it depends on the β/γ subunit. These data implicate a novel form of Gi-protein signaling pathway in the Type II hyperalgesic priming induced by repeated administration of an agonist at A1-adenosine receptor to the peripheral terminal of the nociceptor. PMID:26588695

  20. Feeding problems and malnutrition in spinal muscular atrophy type II.

    PubMed

    Messina, Sonia; Pane, Marika; De Rose, Paola; Vasta, Isabella; Sorleti, Domenica; Aloysius, Annie; Sciarra, Federico; Mangiola, Fortunato; Kinali, Maria; Bertini, Enrico; Mercuri, Eugenio

    2008-05-01

    The aim of the study was to conduct a survey using a dedicated questionnaire to assess feeding difficulties and weight gain in a population of 122 Spinal Muscular Atrophy (SMA) type II patients, aged between 1 and 47 years. All the answers were entered in a database and were analysed subdividing the cohort into age groups (1-5, 6-10, 11-14, 15-19, 20-29, and 30-50 years). Six out of our 122 patients (5%), all younger than 11 years, had weights more than 2SD above the median for age matched controls, whilst 45 (37%) had weights less than 2SD below the median. Chewing difficulties were reported in 34 of the 122 patients (28%) and limitation in the ability to open the mouth in 36 (30%) and both were increasingly more frequent with age. Swallowing difficulties were reported in 30 patients (25%). The results of our survey suggest that a number of patients with SMA type II have limited jaw opening, and chewing and swallowing difficulties. Our findings raise a few issues concerning standards of care that should be implemented in the monitoring and management of feeding difficulties and weight gain.

  1. Model light curves of linear Type II supernovae

    SciTech Connect

    Swartz, D.A.; Wheeler, J.C.; Harkness, R.P. )

    1991-06-01

    Light curves computed from hydrodynamic models of supernova are compared graphically with the average observed B and V-band light curves of linear Type II supernovae. Models are based on the following explosion scenarios: carbon deflagration within a C + O core near the Chandrasekhar mass, electron-capture-induced core collapse of an O-Ne-Mg core of the Chandrasekhar mass, and collapse of an Fe core in a massive star. A range of envelope mass, initial radius, and composition is investigated. Only a narrow range of values of these parameters are consistent with observations. Within this narrow range, most of the observed light curve properties can be obtained in part, but none of the models can reproduce the entire light curve shape and absolute magnitude over the full 200 day comparison period. The observed lack of a plateau phase is explained in terms of a combination of small envelope mass and envelope helium enhancement. The final cobalt tail phase of the light curve can be reproduced only if the mass of explosively synthesized radioactive Ni-56 is small. The results presented here, in conjunction with the observed homogeneity among individual members of the supernova subclass, argue favorably for the O-Ne-Mg core collapse mechanism as an explanation for linear Type II supernovae. The Crab Nebula may arisen from such an explosion. Carbon deflagrations may lead to brighter events like SN 1979C. 62 refs.

  2. Isolation and molecular characterization of type I and type II feline coronavirus in Malaysia

    PubMed Central

    2012-01-01

    Background Feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV) are two important coronaviruses of domestic cat worldwide. Although FCoV is prevalent among cats; the fastidious nature of type I FCoV to grow on cell culture has limited further studies on tissue tropism and pathogenesis of FCoV. While several studies reported serological evidence for FCoV in Malaysia, neither the circulating FCoV isolated nor its biotypes determined. This study for the first time, describes the isolation and biotypes determination of type I and type II FCoV from naturally infected cats in Malaysia. Findings Of the total number of cats sampled, 95% (40/42) were RT-PCR positive for FCoV. Inoculation of clinical samples into Crandell feline kidney cells (CrFK), and Feline catus whole fetus-4 cells (Fcwf-4), show cytopathic effect (CPE) characterized by syncytial cells formation and later cell detachment. Differentiation of FCoV biotypes using RT-PCR assay revealed that, 97.5% and 2.5% of local isolates were type I and type II FCoV, respectively. These isolates had high sequence homology and phylogenetic similarity with several FCoV isolates from Europe, South East Asia and USA. Conclusions This study reported the successful isolation of local type I and type II FCoV evident with formation of cytopathic effects in two types of cell cultures namely the CrFK and Fcwf-4 , where the later cells being more permissive. However, the RT-PCR assay is more sensitive in detecting the antigen in suspected samples as compared to virus isolation in cell culture. The present study indicated that type I FCoV is more prevalent among cats in Malaysia. PMID:23171743

  3. Supernova 1993J as a spectroscopic link between type II and type Ib supernovae

    NASA Technical Reports Server (NTRS)

    Swartz, D. A.; Clocchiatti, A.; Benjamin, R.; Lester, D. F.; Wheeler, J. C.

    1993-01-01

    Supernova 1993J in the nearby galaxy M81 is one of the closest - and hence brightest - supernovae to be witnessed this century. The early spectrum of SN1993J showed the characteristic hydrogen signature of type II supernovae, but its subsequent evolution is atypical for this class of supernova. Here we present optical and infrared spectra of SN1993J up to 43 days after outburst, which reveal the onset of the helium absorption and emission features more commonly associated with hydrogen-free type Ib supernovae. Corresponding model spectra show that the progenitor star must have possessed an unusually thin (for type II supernovae) hydrogen-rich envelope overlying a helium-rich mantle. Moreover, the supernova ejecta must have remained compositionally stratified, with little transport of the hydrogen-rich material down into the underlying helium layer or mixing of heavier elements outwards. SN1993J therefore represents a transition object between hydrogen-dominated type II supernovae, and hydrogen-free, helium-dominated type Ib supernovae.

  4. Magnetic description of the Fermi arc in type-I and type-II Weyl semimetals

    NASA Astrophysics Data System (ADS)

    Tchoumakov, Serguei; Civelli, Marcello; Goerbig, Mark O.

    2017-03-01

    We consider finite-sized interfaces of a Weyl semimetal and show that the corresponding confinement potential is similar to the application of a magnetic field. Among the numerous states, which can be labeled by indices n like in Landau levels, the n =0 surface state describes the Weyl semimetal Fermi arc at a given chemical potential. Moreover, the analogy with a magnetic field shows that an external in-plane magnetic field can be used to distort the Fermi arc and would explain some features of magnetotransport in Weyl semimetals. We derive the Fermi arc for type-I and type-II Weyl semimetals where we deal with the tilt anisotropy by the use of Lorentz boosts. In the case of type-II Weyl semimetals, this leads to many additional topologically trivial surface states at low energy. Finally, we extend the Aharonov-Casher argument and demonstrate the stability of the Fermi arc over fluctuations of the surface potential.

  5. The adaptor protein SAP regulates type II NKT-cell development, cytokine production, and cytotoxicity against lymphoma.

    PubMed

    Weng, Xiufang; Liao, Chia-Min; Bagchi, Sreya; Cardell, Susanna L; Stein, Paul L; Wang, Chyung-Ru

    2014-12-01

    CD1d-restricted NKT cells represent a unique lineage of immunoregulatory T cells that are divided into two groups, type I and type II, based on their TCR usage. Because there are no specific tools to identify type II NKT cells, little is known about their developmental requirements and functional regulation. In our previous study, we showed that signaling lymphocytic activation molecule associated protein (SAP) is essential for the development of type II NKT cells. Here, using a type II NKT-cell TCR transgenic mouse model, we demonstrated that CD1d-expressing hematopoietic cells, but not thymic epithelial cells, meditate efficient selection of type II NKT cells. Furthermore, we showed that SAP regulates type II NKT-cell development by controlling early growth response 2 protein and promyelocytic leukemia zinc finger expression. SAP-deficient 24αβ transgenic T cells (24αβ T cells) exhibited an immature phenotype with reduced Th2 cytokine-producing capacity and diminished cytotoxicity to CD1d-expressing lymphoma cells. The impaired IL-4 production by SAP-deficient 24αβ T cells was associated with reduced IFN regulatory factor 4 and GATA-3 induction following TCR stimulation. Collectively, these data suggest that SAP is critical for regulating type II NKT cell responses. Aberrant responses of these T cells may contribute to the immune dysregulation observed in X-linked lymphoproliferative disease caused by mutations in SAP.

  6. Piezoelectricity in collagen type II fibrils measured by scanning probe microscopy

    NASA Astrophysics Data System (ADS)

    Denning, D.; Kilpatrick, J. I.; Hsu, T.; Habelitz, S.; Fertala, A.; Rodriguez, B. J.

    2014-08-01

    The converse piezoelectric effect in collagen type II fibrils, the main collagen constituent in cartilage, was investigated using piezoresponse force microscopy. The fibrils exhibited shear piezoelectric behavior similar to that previously reported in collagen type I fibrils and followed the same cantilever-fibril angle dependence present for type I. A uniform polarization directed from the amine to carboxyl termini, as seen for collagen type I, was observed in all type II fibrils studied. The shear piezoelectric coefficient, d15, however, for type II was roughly 28-32% of the value measured for type I fibrils. Possible explanations for the reduced piezoelectric coefficient of type II collagen are provided.

  7. Neutrinos from type II supernovae - The first 100 milliseconds

    NASA Technical Reports Server (NTRS)

    Myra, Eric S.; Burrows, Adam

    1990-01-01

    The collapse of a 1.17 solar mass iron core is numerically followed through infall to 100 ms past core bounce, and the emergent neutrino spectra during each phase are highlighted. It is found that, even with fairly optimistic conditions for producing a strong, sustained core-bounce shock wave, the prompt shock stalls within 9 ms of core bounce at a radius of less than 250 km. It appears that a radical change in the character of the progenitor core or in our understanding of the relevant physics of stellar collapse is needed before the direct mechanism for type II supernovae can become viable. Expanding the number of neutrino types from one to six magnifies the debilitating effect of neutrino loss on shock propagation. At shock breakout, prompt bursts of all neutrino types are observed. The luminosities of the nonelectron types show a sudden turn-on in luminosity while that of the electron neutrinos steadily increases throughout infall as a result of accelerating electron capture.

  8. In resting COS1 cells a dominant negative approach shows that specific, anchored PDE4 cAMP phosphodiesterase isoforms gate the activation, by basal cyclic AMP production, of AKAP-tethered protein kinase A type II located in the centrosomal region.

    PubMed

    McCahill, Angela; McSorley, Theresa; Huston, Elaine; Hill, Elaine V; Lynch, Martin J; Gall, Irene; Keryer, Guy; Lygren, Birgitte; Tasken, Kjetil; van Heeke, Gino; Houslay, Miles D

    2005-09-01

    We employ a novel, dominant negative approach to identify a key role for certain tethered cyclic AMP specific phosphodiesterase-4 (PDE4) isoforms in regulating cyclic AMP dependent protein kinase A (PKA) sub-populations in resting COS1 cells. A fraction of PKA is clearly active in resting COS1 cells and this activity increases when cells are treated with the selective PDE4 inhibitor, rolipram. Point mutation of a critical, conserved aspartate residue in the catalytic site of long PDE4A4, PDE4B1, PDE4C2 and PDE4D3 isoforms renders them catalytically inactive. Overexpressed in resting COS1 cells, catalytically inactive forms of PDE4C2 and PDE4D3, but not PDE4A4 and PDE4B1, are constitutively PKA phosphorylated while overexpressed active versions of all these isoforms are not. Inactive and active versions of all these isoforms are PKA phosphorylated in cells where protein kinase A is maximally activated with forskolin and IBMX. By contrast, rolipram challenge of COS1 cells selectively triggers the PKA phosphorylation of recombinant, active PDE4D3 and PDE4C2 but not recombinant, active PDE4A4 and PDE4B1. Purified, recombinant PDE4D3 and PDE4A4 show a similar dose-dependency for in vitro phosphorylation by PKA. Disruption of the tethering of PKA type-II to PKA anchor proteins (AKAPs), achieved using the peptide Ht31, prevents inactive forms of PDE4C2 and PDE4D3 being constitutively PKA phosphorylated in resting cells as does siRNA-mediated knockdown of PKA-RII, but not PKA-RI. PDE4C2 and PDE4D3 co-immunoprecipitate from COS1 cell lysates with 250 kDa and 450 kDa AKAPs that tether PKA type-II and not PKA type-I. PKA type-II co-localises with AKAP450 in the centrosomal region of COS1 cells. The perinuclear distribution of recombinant, inactive PDE4D3, but not inactive PDE4A4, overlaps with AKAP450 and PKA type-II. The distribution of PKA phosphorylated inactive PDE4D3 also overlaps with that of AKAP450 in the centrosomal region of COS1 cells. We propose that a novel role

  9. Characterization of Collagen Type I and II Blended Hydrogels for Articular Cartilage Tissue Engineering.

    PubMed

    Vázquez-Portalatı N, Nelda; Kilmer, Claire E; Panitch, Alyssa; Liu, Julie C

    2016-10-10

    Biomaterials that provide signals present in the native extracellular matrix have been proposed as scaffolds to support improved cartilage regeneration. This study harnesses the biological activity of collagen type II and the superior mechanical properties of collagen type I by characterizing gels made of collagen type I and II blends. The collagen blend hydrogels were able to incorporate both types of collagen and retained chondroitin sulfate and hyaluronic acid. Cryo-scanning electron microscopy images showed that the 3:1 ratio of collagen type I to type II gels had a lower void space percentage (36.4%) than the 1:1 gels (46.5%). The complex modulus was larger for the 3:1 gels (G* = 5.0 Pa) compared to the 1:1 gels (G* = 1.2 Pa). The 3:1 blend consistently formed gels with superior mechanical properties compared to the other blends and has the potential to be implemented as a scaffold for articular cartilage engineering.

  10. An unobscured type II quasar candidate: SDSS J012032.19-005501.9

    SciTech Connect

    Li, Y.; Yuan, W.; Komossa, S.; Zhou, H. Y.; Liu, W. J.; Ai, Y. L.; Boisvert, J. H.

    2015-02-01

    We report the finding of an unobscured type II active galactic nucleus (AGN) candidate, SDSS J012032.19-005501.9, at a relatively high redshift of 0.601, which shows a number of unusual properties. It varies significantly on timescales of years, typical of type I AGNs, and marginally on timescales of weeks. The color–magnitude relation and the structure function are also consistent with that of type I AGNs, which implies that its variability likely originates from the black hole accretion system. However, no broad emission line (BEL) is detected in the Sloan Digital Sky Survey spectrum, and the upper limit of the equivalent width of the Hβ BEL is much less than that of type I AGNs. These properties suggest that SDSS J012032.19-005501.9 may be an unobscured quasar without intrinsically broad emission lines, namely, an unobscured type II AGN or “true” type II AGN. Furthermore, its continuum luminosity is at least one order of magnitude fainter than the average value over the past century from the [O iii] emission line. This indicates that SDSS J012032.19-005501.9 may be switching off. Additional possible scenarios to explain this intriguing source are also discussed. Future deep observations at multiwavelengths are needed to reveal the nature of this peculiar and intriguing AGN.

  11. Phosphorylation of DNA topoisomerase II by casein kinase II: modulation of eukaryotic topoisomerase II activity in vitro.

    PubMed Central

    Ackerman, P; Glover, C V; Osheroff, N

    1985-01-01

    The phosphorylation of Drosophila melanogaster DNA topoisomerase II by purified casein kinase II was characterized in vitro. Under the conditions used, the kinase incorporated a maximum of 2-3 molecules of phosphate per homodimer of topoisomerase II. No autophosphorylation of the topoisomerase was observed. The only amino acid residue modified by casein kinase II was serine. Apparent Km and Vmax values for the phosphorylation reaction were 0.4 microM topoisomerase II and 3.3 mumol of phosphate incorporated per min per mg of kinase, respectively. Phosphorylation stimulated the DNA relaxation activity of topoisomerase II by 3-fold over that of the dephosphorylated enzyme, and the effects of modification could be reversed by treatment with alkaline phosphatase. Therefore, this study demonstrates that post-translational enzymatic modifications can be used to modulate the interaction between topoisomerase II and DNA. Images PMID:2987912

  12. Adsorption of Cd(II) and Pb(II) from aqueous solutions on activated alumina.

    PubMed

    Naiya, Tarun Kumar; Bhattacharya, Ashim Kumar; Das, Sudip Kumar

    2009-05-01

    The ability of activated alumina as synthetic adsorbent was investigated for adsorptive removal of Cd(II) and Pb(II) ions from aqueous solutions. Various physico-chemical parameters such as pH, initial metal ion concentration, and adsorbent dosage level and equilibrium contact time were studied. The optimum solution pH for adsorption of Cd(II) and Pb(II) from aqueous solutions was found to be 5. Kinetics data were best described by pseudo-second order model. The effective particle diffusion coefficient of Cd(II) and Pb(II) are of the order of 10(-10) m(2)/s. Values of mass transfer coefficient were estimated as 4.868x10(-6) cm/s and 6.85x10(-6) cm/s for Cd(II) and Pb(II) adsorption respectively. The equilibrium adsorption data for Cd(II) and Pb(II) were better fitted to Langmuir adsorption isotherm model. The thermodynamic studies indicated that the adsorption was spontaneous and exothermic for Cd(II) adsorption and endothermic for Pb(II). The sorption energy calculated from Dubinin-Radushkevich isotherm were 11.85 kJ/mol and 11.8 kJ/mol for the adsorption of Cd(II) and Pb(II) respectively which indicated that both the adsorption processes were chemical in nature. Desorption studies were carried out using dilute mineral acids. Application studies carried out using industrial waste water samples containing Cd(II) and Pb(II) showed the suitability of activated alumina in waste water treatment plant operation.

  13. Synthesis, antimicrobial activity, structural and spectral characterization and DFT calculations of Co(II), Ni(II), Cu(II) and Pd(II) complexes of 4-amino-5-pyrimidinecarbonitrile.

    PubMed

    Mohamed, Tarek A; Shaaban, Ibrahim A; Farag, Rabei S; Zoghaib, Wajdi M; Afifi, Mahmoud S

    2015-01-25

    Co(II), Ni(II), Cu(II) and Pd(II) complexes of 4-amino-5-pyrimidinecarbonitrile (APC) have been synthesized and characterized using elemental analysis, magnetic susceptibility, mass spectrometry, infrared (4000-200 cm(-1)), UV-Visible (200-1100 nm), (1)H NMR and ESR spectroscopy as well as TGA analysis. The molar conductance measurements in DMSO imply non-electrolytic complexes, formulated as [M(APC)2Cl2] where M=Co(II), Ni(II), Cu(II) and Pd(II). The infrared spectra of Co(II), Ni(II) and Cu(II) complexes indicate a bidentate type of bonding for APC through the exocyclic amino and adjacent pyrimidine nitrogen as donors whereas APC coordinated to Pd(II) ion as a monodentated ligand via a pyrimidine nitrogen donor. The magnetic measurements and the electronic absorption spectra support distorted octahedral geometries for Co(II), Ni(II) and Cu(II) complexes however a square planar complex was favored for the Pd(II) complex (C2h skeleton symmetry). In addition, we carried out B3LYP and ω-B97XD geometry optimization at 6-31G(d) basis set except for Pd(II) where we implemented LanL2DZ/6-31G(d) combined basis set. The computational results favor all trans geometrical isomers where amino N, pyrimidine N and Cl are trans to each other (structure 1). Finally, APC and its divalent metal ion complexes were screened for their antibacterial activity, and the synthesized complexes were found to be more potent antimicrobial agents than APC against one or more microbial species.

  14. Synthesis, antimicrobial activity, structural and spectral characterization and DFT calculations of Co(II), Ni(II), Cu(II) and Pd(II) complexes of 4-amino-5-pyrimidinecarbonitrile

    NASA Astrophysics Data System (ADS)

    Mohamed, Tarek A.; Shaaban, Ibrahim A.; Farag, Rabei S.; Zoghaib, Wajdi M.; Afifi, Mahmoud S.

    2015-01-01

    Co(II), Ni(II), Cu(II) and Pd(II) complexes of 4-amino-5-pyrimidinecarbonitrile (APC) have been synthesized and characterized using elemental analysis, magnetic susceptibility, mass spectrometry, infrared (4000-200 cm-1), UV-Visible (200-1100 nm), 1H NMR and ESR spectroscopy as well as TGA analysis. The molar conductance measurements in DMSO imply non-electrolytic complexes, formulated as [M(APC)2Cl2] where M = Co(II), Ni(II), Cu(II) and Pd(II). The infrared spectra of Co(II), Ni(II) and Cu(II) complexes indicate a bidentate type of bonding for APC through the exocyclic amino and adjacent pyrimidine nitrogen as donors whereas APC coordinated to Pd(II) ion as a monodentated ligand via a pyrimidine nitrogen donor. The magnetic measurements and the electronic absorption spectra support distorted octahedral geometries for Co(II), Ni(II) and Cu(II) complexes however a square planar complex was favored for the Pd(II) complex (C2h skeleton symmetry). In addition, we carried out B3LYP and ω-B97XD geometry optimization at 6-31G(d) basis set except for Pd(II) where we implemented LanL2DZ/6-31G(d) combined basis set. The computational results favor all trans geometrical isomers where amino N, pyrimidine N and Cl are trans to each other (structure 1). Finally, APC and its divalent metal ion complexes were screened for their antibacterial activity, and the synthesized complexes were found to be more potent antimicrobial agents than APC against one or more microbial species.

  15. Type-II nanorod heterostructure formation through one-step cation exchange.

    PubMed

    Chen, Meng-Yu; Hsu, Yung-Jung

    2013-01-07

    A novel one-step cation exchange approach has been developed to prepare ZnO-decorated ZnSe nanorods (ZnSe-ZnO NRs), a prototype type-II semiconductor nanoheterostructure. Because of the staggered band offset which promoted effective charge separation, the as-synthesized ZnSe-ZnO NRs exhibited remarkable photocatalytic activities under visible light illumination, demonstrating their promising potentials in relevant photoconversion applications.

  16. Rational drug design and synthesis of molecules targeting the angiotensin II type 1 and type 2 receptors.

    PubMed

    Kellici, Tahsin F; Tzakos, Andreas G; Mavromoustakos, Thomas

    2015-03-02

    The angiotensin II (Ang II) type 1 and type 2 receptors (AT1R and AT2R) orchestrate an array of biological processes that regulate human health. Aberrant function of these receptors triggers pathophysiological responses that can ultimately lead to death. Therefore, it is important to design and synthesize compounds that affect beneficially these two receptors. Cardiovascular disease, which is attributed to the overactivation of the vasoactive peptide hormone Αng II, can now be treated with commercial AT1R antagonists. Herein, recent achievements in rational drug design and synthesis of molecules acting on the two AT receptors are reviewed. Quantitative structure activity relationships (QSAR) and molecular modeling on the two receptors aim to assist the search for new active compounds. As AT1R and AT2R are GPCRs and drug action is localized in the transmembrane region the role of membrane bilayers is exploited. The future perspectives in this field are outlined. Tremendous progress in the field is expected if the two receptors are crystallized, as this will assist the structure based screening of the chemical space and lead to new potent therapeutic agents in cardiovascular and other diseases.

  17. HTLV type I and HTLV type II infection among Indians and natives from Argentina.

    PubMed

    Bouzas, M B; Zapiola, I; Quiruelas, S; Gorvein, D; Panzita, A; Rey, J; Carnese, F P; Corral, R; Perez, C; Zala, C

    1994-11-01

    Endemic foci for HTLV-II infection have been identified in several Amerindian populations. To determine HTLV-I and/or HTLV-II infection among Amerindians living in Argentina we studied 454 sera or plasmas from Indians and natives from different areas of our country. All samples were tested by the particle agglutination technique, and positive reactions were confirmed by the immunofluorescence assay (IFA). IFA titration was used to differentiate HTLV-I and HTLV-II antibodies. Twenty-three of 222 samples (10.4%) were found positive among the Tobas Indians; 22 samples were typed as HTLV-II and 1 as HTLV-I. Antibodies for HTLV-I were found in the serum and CSF of three natives from Salta with a TSP diagnosis. No positive samples were found among 96 Mapuche Indians and 133 natives from San Luis. Our results indicate that HTLV-II is endemic among the Tobas Indians. In this study, infection by these retroviruses in Argentinian Amerindians seems to have a marked geographic distribution.

  18. Inhibition Kinetics And Emodin Cocrystal Structure of a Type II Polyketide Ketoreductase

    SciTech Connect

    Korman, T.P.; Tan, Y.-H.; Wong, J.; Luo, R.; Tsai, S.-C.

    2009-05-20

    Type II polyketides are a class of natural products that include pharmaceutically important aromatic compounds such as the antibiotic tetracycline and antitumor compound doxorubicin. The type II polyketide synthase (PKS) is a complex consisting of 5-10 standalone domains homologous to fatty acid synthase (FAS). Polyketide ketoreductase (KR) provides regio- and stereochemical diversity during the reduction. How the type II polyketide KR specifically reduces only the C9 carbonyl group is not well understood. The cocrystal structures of actinorhodin polyketide ketoreductase (actKR) bound with NADPH or NADP{sup +} and the inhibitor emodin were solved with the wild type and P94L mutant of actKR, revealing the first observation of a bent p-quinone in an enzyme active site. Molecular dynamics simulation help explain the origin of the bent geometry. Extensive screening for in vitro substrates shows that unlike FAS KR, the actKR prefers bicyclic substrates. Inhibition kinetics indicate that actKR follows an ordered Bi Bi mechanism. Together with docking simulations that identified a potential phosphopantetheine binding groove, the structural and functional studies reveal that the C9 specificity is a result of active site geometry and substrate ring constraints. The results lay the foundation for the design of novel aromatic polyketide natural products with different reduction patterns.

  19. The importance of type II error and falsifiability.

    PubMed

    Matsuda, Hiroyuki

    2004-01-01

    Before intergovernmental consensus under the Rio Declaration in 1992, ignorance of type I errors had been disfavored in science. However, the Precautionary Principle (PP) counsels the avoidance of type II errors, rather than of type I errors. We need a new academic code for the PP. The risk of extinction has usually been evaluated based on conservative estimates of the present population size. I define the weight of evidence as the extinction risk of Japanese vascular plants based on unbiased estimates. Catch quotas in the fisheries are usually decided by precautionary approach. I calculate the long-term yield and risk of stock collapse under a simple stock dynamics model. The weight of evidence depends on the frequency of grids with size unknown. In a few plant species, rankings based on conservative estimates have differed from rankings based on unbiased estimates. In fishery management, a catch quota based on a precautionary approach proved neither sufficient nor necessary to avoid stock collapse. The precautionary approach is one of the reasons that prevent us from maximizing a sustainable yield. We need to clarify the end-point of risks, and check whether it is necessary to adopt a PP. We can obtain the weight of evidence that is measured under unbiased estimates, while the risk based on a PP is measured under conservative estimates.

  20. Proposal for strained type II superlattice infrared detectors

    NASA Astrophysics Data System (ADS)

    Smith, D. L.; Mailhiot, C.

    1987-09-01

    It is shown that strained type II superlattices made of InAs-Ga(1-x)In(x)Sb(x) about 0.4 have favorable optical properties for infrared detection. By adjusting the layer thicknesses and the alloy composition, a wide range of wavelengths can be reached. Optical absorption calculations for a case where the cutoff wavelength is about 10 microns show that, near threshold, the absorption is as good as for the HgCdTe alloy with the same band gap. The electron effective mass is nearly isotropic and equal to 0.04 m. This effective mass should give favorable electrical properties, such as small diode tunneling currents and good mobilities, and diffusion lengths.

  1. Type II seesaw model and multilepton signatures at hadron colliders

    NASA Astrophysics Data System (ADS)

    Mitra, Manimala; Niyogi, Saurabh; Spannowsky, Michael

    2017-02-01

    We investigate multilepton signatures, arising from the decays of doubly charged and singly charged Higgs bosons in the Type II seesaw model. Depending on the vacuum expectation value of the triplet vΔ , the doubly and singly charged Higgs bosons can decay into a large variety of multilepton final states. We explore all possible decay modes corresponding to different regimes of vΔ that generate distinguishing four and five leptonic signatures. We focus on the 13 TeV Large Hadron Collider (LHC) and further extend the study to a very high energy proton-proton collider (VLHC) with a center-of-mass energy of 100 TeV. We find that a doubly charged Higgs boson of masses around 375 GeV can be discovered at immediate LHC runs. A heavier mass of 630 GeV can instead be discovered at the high-luminosity run of the LHC or at the VLHC with 30 fb-1 .

  2. Sweet taste and diet in type II diabetes.

    PubMed

    Tepper, B J; Hartfiel, L M; Schneider, S H

    1996-07-01

    The relationship between sweet taste function and dietary intake was studied in 21 patients with type II diabetes mellitus and 16 age-, weight-, and sex-matched controls. Subjects rated the sweetness intensity and pleasantness of a series of beverage samples sweetened with sucrose: 1.5-24%, fructose: 1-18%, or aspartame: 0.25-4%. They also kept 7-day food records. No group differences were found in sweet taste perception, pleasantness ratings, daily energy intakes, or macronutrient composition of the diets. However, subjects with diabetes consumed less sucrose but 3.5 times more alternative sweeteners than did controls. Peak pleasantness ratings for the beverage samples were positively correlated with dietary sweetness content in the subjects with diabetes but not the controls. These findings suggest that in diabetes, hedonic ratings for a sweetened beverage were related to dietary sweetness intake rather than changes in sweet taste perception.

  3. Type II congenital pulmonary airway malformation in an esophageal lung

    PubMed Central

    Martínez-Martínez, Blanca Estela; Furuya, María Elena Yuriko; Martínez-Muñiz, Irma; Vargas, Mario H; Flores-Salgado, Rosalinda

    2013-01-01

    A seven-month-old girl, born prematurely (birth weight 1000 g) from a twin pregnancy, was admitted to hospital due to recurrent pneumonia and atelectasis. She experienced cough and respiratory distress during feeding. The right hemithorax was smaller than the left, with diminished breath sounds and dullness. Chest x-rays revealed decreased lung volume and multiple radiolucent images in the right lung, as well as overdistention of the left lung. An esophagogram revealed three bronchial branches arising from the lower one-third of the esophagus, corresponding to the right lung and ending in a cul-de-sac. A diagnosis of esophageal lung was established. On bronchography, the right lung was absent and the trachea only continued into the left main bronchus. Echocardiography and angiotomography revealed agenesis of the pulmonary artery right branch. The surgical finding was an esophageal right lung, which was removed; the histopathological diagnosis was type II congenital pulmonary airway malformation in an esophageal lung. PMID:23762890

  4. Vorticity and magnetic shielding in a type-II superconductor.

    PubMed

    Cardoso, Marco; Bicudo, Pedro; Sacramento, Pedro D

    2006-09-20

    We study in detail, solving the Bogoliubov-de Gennes equations, the magnetic field, supercurrent and order parameter profiles originated by a solenoid or magnetic whisker inserted in a type-II superconductor. We consider solutions of different vorticities, n, in the various cases. The results confirm the connection between the vorticity, the internal currents and the boundstates in a self-consistent way. The number of boundstates is given by the vorticity of the phase of the gap function as in the case with no external solenoid. In the limiting case of an infinitely thin solenoid, like a Dirac string, the solution is qualitatively different. The quasiparticle spectrum and wavefunctions are a function of n-n(ext), where n(ext) is the vorticity of the solenoid. The flux is in all cases determined by the vorticity of the gap function.

  5. Unusual approach for the treatment of a type II endoleak.

    PubMed

    Ciampi Dopazo, J J; Gastaldo, F; Lanciego Pérez, C

    2016-01-01

    This case presentation is about an 88 years-old male patient with previous endovascular aortic aneurysm repairment history and aortic endoleak type II (EL2). The direct lumbar artery catheterization was considered an alternative to solve EL2, associated with aortic endovascular prosthesis and due to an incomplete sealing or exclusion of the aneurysmal sac or a vascular segment demonstrated by imaging studies, when other treatment alternative failed (transarterial embolization) to control the aneurysm growing. Performing translumbar approach was decided by puncturing the artery lumbar (L4) left, previously the lumbar arteries (L4) were evaluated in the abdominal CT arterial phase to guide a puncture/access under flouroscopy control. Diagnostic angiogram clearly demonstrated the median sacral and right lumbar arteries inflow into the aneurysm sac. Transcatheter embolization with fibered platinum microcoils was performed of the median sacral artery and lumbar left and right arteries (L4), showing satisfactory endoleak devascularization.

  6. Type II Diabetes Mellitus in Arabic-Speaking Countries

    PubMed Central

    Badran, Mohammad; Laher, Ismail

    2012-01-01

    The global epidemic of diabetes has not spared the Arabic-speaking countries, which have some of the highest prevalence of type II diabetes. This is particularly true of the Arab Gulf, a conglomerate of high income, oil-producing countries where prevalence rates are the highest. The prevalence rates among adults of the Arabic speaking countries as a whole range between 4%–21%, with the lowest being in Somalia and the highest in Kuwait. As economic growth has accelerated, so has the movement of the populations to urban centers where people are more likely to adopt lifestyles that embrace increased high-calorie food consumption and sedentary lifestyles. These factors likely contribute to the increased prevalence of obesity and diabetes in the Arabic speaking countries. PMID:22851968

  7. Type II congenital cystic pulmonary malformation in an esophageal lung.

    PubMed

    Martínez-Martínez, Blanca E; Furuya, María Elena Yuriko; Martínez-Muñiz, Irma; Vargas, Mario H; Flores-Salgado, Rosalinda

    2013-01-01

    A seven-month-old girl, born prematurely (birth weight 1000 g) from a twin pregnancy, was admitted to hospital due to recurrent pneumonia and atelectasis. She experienced cough and respiratory distress during feeding. The right hemithorax was smaller than the left, with diminished breath sounds and dullness. Chest x-rays revealed decreased lung volume and multiple radiolucent images in the right lung, as well as overdistention of the left lung. An esophagogram revealed three bronchial branches arising from the lower one-third of the esophagus, corresponding to the right lung and ending in a cul-de-sac. A diagnosis of esophageal lung was established. On bronchography, the right lung was absent and the trachea only continued into the left main bronchus. Echocardiography and angiotomography revealed agenesis of the pulmonary artery right branch. The surgical finding was an esophageal right lung, which was removed; the histopathological diagnosis was type II congenital pulmonary airway malformation in an esophageal lung.

  8. Majewski osteodysplastic primordial dwarfism type II (MOPD II): expanding the vascular phenotype.

    PubMed

    Bober, Michael B; Khan, Nadia; Kaplan, Jennifer; Lewis, Kristi; Feinstein, Jeffrey A; Scott, Charles I; Steinberg, Gary K

    2010-04-01

    Majewski Osteodysplastic Primordial Dwarfism, Type II (MOPD II) is a rare, autosomal recessive disorder. Features include severe intrauterine growth retardation (IUGR), poor postnatal growth (adult stature approximately 100 cm), severe microcephaly, skeletal dysplasia, characteristic facial features, and normal or near normal intelligence. An Institutional Review Board (IRB) approved registry was created and currently follows 25 patients with a diagnosis of MOPD II. Based on previous studies, a neurovascular screening program was implemented and 13 (52%) of these patients have been found to have cerebral neurovascular abnormalities including moyamoya angiopathy and/or intracranial aneurysms. The typical moyamoya pathogenesis begins with vessel narrowing in the supraclinoid internal carotid artery, anterior cerebral (A1) or middle cerebral (M1) artery segments. The narrowing may predominate initially on one side, progresses to bilateral stenosis, with subsequent occlusion of the vessels and collateral formation. We present four patients who, on neurovascular screening, were found to have cerebrovascular changes. Two were asymptomatic, one presented with a severe headache and projectile vomiting related to a ruptured aneurysm, and one presented after an apparent decline in cognitive functioning. Analysis of the registry suggests screening for moyamoya disease be performed at the time of MOPD II diagnosis and at least every 12-18 months using MRA or computerized tomographic angiography (CTA). We believe this is imperative. If diagnosed early enough, re-vascularization and aneurysm treatment in skilled hands can be performed safely and prevent or minimize long-term sequelae in this population. Emergent evaluation is also needed when other neurologic or cardiac symptoms are present.

  9. The MicroRNA 29 Family Promotes Type II Cell Differentiation in Developing Lung.

    PubMed

    Guo, Wei; Benlhabib, Houda; Mendelson, Carole R

    2016-08-15

    Lung alveolar type II cells uniquely synthesize surfactant, a developmentally regulated lipoprotein that is essential for breathing. Expression of the gene (SFTPA) encoding the major surfactant protein, SP-A, in midgestation human fetal lung (HFL) is dramatically induced by cyclic AMP (cAMP). cAMP induction of SP-A expression is repressed by transforming growth factor β (TGF-β) and by hypoxia. In this study, we found that expression of the microRNA 29 (miR-29) family was significantly upregulated in epithelial cells isolated from mouse fetal lung during late gestation and in epithelial cells isolated from HFL explants during type II cell differentiation in culture. miR-29 expression in cultured HFL epithelial cells was increased by cAMP and inhibited by hypoxia, whereas the miR-29 target, TGF-β2, was coordinately decreased. Knockdown of the miR-29 family in cultured HFL type II cells blocked cAMP-induced SP-A expression and accumulation of surfactant-containing lamellar bodies, suggesting their physiological relevance. This occurred through derepression of TGF-β signaling. Notably, cAMP increased binding of endogenous thyroid transcription factor 1 (TTF-1/Nkx2.1) to the miR-29ab1 promoter in HFL type II cells, and TTF-1 increased miR-29ab1 promoter-driven luciferase activity in cotransfection assays. Together, these findings identify miR-29 family members as TTF-1-driven mediators of SP-A expression and type II cell differentiation through repression of TGF-β signaling.

  10. The MicroRNA 29 Family Promotes Type II Cell Differentiation in Developing Lung

    PubMed Central

    Guo, Wei; Benlhabib, Houda

    2016-01-01

    Lung alveolar type II cells uniquely synthesize surfactant, a developmentally regulated lipoprotein that is essential for breathing. Expression of the gene (SFTPA) encoding the major surfactant protein, SP-A, in midgestation human fetal lung (HFL) is dramatically induced by cyclic AMP (cAMP). cAMP induction of SP-A expression is repressed by transforming growth factor β (TGF-β) and by hypoxia. In this study, we found that expression of the microRNA 29 (miR-29) family was significantly upregulated in epithelial cells isolated from mouse fetal lung during late gestation and in epithelial cells isolated from HFL explants during type II cell differentiation in culture. miR-29 expression in cultured HFL epithelial cells was increased by cAMP and inhibited by hypoxia, whereas the miR-29 target, TGF-β2, was coordinately decreased. Knockdown of the miR-29 family in cultured HFL type II cells blocked cAMP-induced SP-A expression and accumulation of surfactant-containing lamellar bodies, suggesting their physiological relevance. This occurred through derepression of TGF-β signaling. Notably, cAMP increased binding of endogenous thyroid transcription factor 1 (TTF-1/Nkx2.1) to the miR-29ab1 promoter in HFL type II cells, and TTF-1 increased miR-29ab1 promoter-driven luciferase activity in cotransfection assays. Together, these findings identify miR-29 family members as TTF-1-driven mediators of SP-A expression and type II cell differentiation through repression of TGF-β signaling. PMID:27215389

  11. Type-II superlattice materials for mid-infrared detection

    NASA Astrophysics Data System (ADS)

    Brown, Gail J.; Haugan, Heather; Szmulowicz, Frank; Mahalingam, Krishnamur; Grazulis, L.; Houston, Shanee

    2005-03-01

    Type-II superlattices composed of alternating thin layers of InAs and GaSb, have been shown to be a highly flexible infrared materials system in which the energy band gap can be adjusted anywhere between 360 meV and 40 meV. These superlattices (SLs) are the III-V equivalent to the well established HgxCd1-xTe alloys used for infrared detection in the short, mid and long wavelength bands of the infrared spectrum. There are many possible designs for these superlattices that will produce the same narrow band gap by adjusting individual layer thicknesses and interface composition. Systematic growth and characterization studies were performed to determine optimum superlattice designs suitable for infrared detection in the 3 to 5 μm wavelength band. For these studies the individual layer thicknesses were less than 35Å. The effects of adding different thickness InSb-like interfaces were also studied. Through precision molecular beam epitaxy, design changes as small as 3Å to the SL layers could be studied. Significant changes were observed in the infrared photoresponse spectra of the various SL samples. The infrared properties of the various designs of these type-II superlattices were modeled using an 8-band Envelope Function Approximation. The infrared photoresponse spectra, combined with quantum mechanical modeling of predicted absorption spectra, were a key factor in the design optimization of the InAs/GaSb superlattices with band gaps in the range of 200 to 360 meV.

  12. Bilateral internal auditory canal gangliogliomas mimicking neurofibromatosis Type II

    PubMed Central

    Hooten, Kristopher G.; Oliveria, Seth F.; Sadrameli, Saeed S.; Gandhi, Shashank; Yachnis, Anthony T.; Lewis, Stephen B.

    2016-01-01

    Background: Gangliogliomas are rare low grade, typically well-differentiated, tumors that are composed of mature ganglion cells and neoplastic glial cells. These tumors can appear at virtually any location along the neuroaxis but classically occur in the temporal lobe of young patients. In a small number of cases, gangliogliomas have presented as masses in the brainstem or involving cranial nerves. With the exception of vestibular schwannomas, bilateral tumors in the region of the internal auditory canal (IAC) or cerebellopontine angle (CPA) are exceedingly rare. Case Description: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma. Description: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma. Conclusion: This is the first reported case of bilateral IAC/CPA gangliogliomas. When evaluating bilateral IAC/CPA lesions with unusual imaging characteristics, ganglioglioma should be included in the differential diagnosis. PMID:27127704

  13. Type II collagen defects in the chondrodysplasias. I. Spondyloepiphyseal dysplasias.

    PubMed Central

    Murray, L W; Bautista, J; James, P L; Rimoin, D L

    1989-01-01

    The spondyloepiphyseal dysplasias (SEDs) and spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of skeletal dysplasias (dwarfing disorders) characterized by abnormal epiphyses, with and without varying degrees of metaphyseal irregularities, flattened vertebral bodies, and myopia. To better define the underlying cause of these disorders, we have analyzed the collagens from costal cartilage from several of these patients, using SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and high-performance liquid chromatography (HPLC) of intact chains and cyanogen bromide (CNBr) peptides and amino acid analysis. In almost all of the patients in this study group, the type II collagen exhibited a slower electrophoretic mobility when compared with that in normal controls. The mobility of many, but not all, of the CNBr peptides was also retarded. Peptides near the amino terminus were almost always altered, while the mobility of peptides close to the carboxyl terminus were normal in all but the severely affected cases. Analysis of the CNBr peptides on an HPLC sieving column confirmed that the electrophoretically abnormal peptides were of a higher molecular weight than were control peptides. Amino acid analysis indicated that the abnormal collagens have a higher ratio of hydroxylysine to lysine than does control collagen, suggesting that overmodification may be involved in the altered mobility. Our results are consistent with a defect in the collagen helix that results in overmodification of the molecule from that point toward the amino terminus. We propose that some forms of SED and SEMD are associated with abnormalities in type II collagen that results in delayed helix formation and consequent overmodification of the collagen. Cases of SED fit onto a continuous spectrum of clinical severity that correlates positively with both the extent of alteration and the proximity of the defect to the carboxyl terminus. Images Figure 1 Figure 2 PMID:2741952

  14. Localization of pro-collagen type II mRNA and collagen type II in the healing tooth socket of the rat.

    PubMed

    Devlin, H; Hoyland, J; Freemont, A J; Sloan, P

    1995-03-01

    Sprague-Dawley rats (50 days old) were anaesthetized and the maxillary right molars extracted. The rats were killed at 2, 3, 6, 8 and 10 days after extraction. The maxillae were dissected and prepared for either routine histology, in situ hybridization for pro-collagen type II mRNA, or immunohistochemical detection of collagen type II. Pro-collagen type II mRNA was expressed maximally in the healing tooth socket at 8 days after the extractions, but the protein was not expressed at any time. This suggests that the translation of pro-collagen type II mRNA does not occur in osteoblasts following tooth extraction. Ossification was present in the socket at 6 days after the extractions, which is consistent with the suggestion that an early feature of osteoblastic differentiation may be the expression of type II pro-collagen mRNA.

  15. An immunohistochemical study on the localization of type II collagen in the developing mouse mandibular condyle.

    PubMed

    Kenzaki, Keiichi; Tsuchikawa, Kohzo; Kuwahara, Toru

    2011-08-01

    The present chronological investigation assessed the distribution of type II collagen expression in the developing mouse mandibular condyle using immunohistochemical staining with respect to the anatomy of the anlage of the mandibular condyle, the histological characteristics of which were disclosed in our previous investigation. We analyzed fetuses, obtained by cross breeding of ICR strain mice, between 14.0 and 19.0 days post-conception (dpc) and pups on 1, 3, and 5 days post-natal (dpn) using immunohistochemical staining with 2 anti-type II collagen antibodies. The expression of type II collagen was first detected at 15.0 dpc in the lower part of the hypertrophic chondrocyte zone; thereafter, this type II collagen-positive layer was expanded and intensified (P1 layer). At 17.0 dpc, we identified a type II collagen-negative layer (N layer) around the P1 layer and we also identified another newly formed type II collagen-positive layer (P, layer) on the outer surface of the N layer. The most typical and conspicuous 3-layered distribution was observed at 1 dpn; thereafter, there was a reduction in the intensity of expression, and with it, the demarcation between the layers was weakened by 5 dpn. The P1 layer was derived from the central region of the core cell aggregate of the anlage of the mandibular condyle and participated in endochondral bone formation. The N layer was derived from the fringe of the core cell aggregate of the anlage, formed the bone collar at the side of the condyle by intramembranous bone formation, and showed a high level of proliferative activity at the vault. The P2 layer was formed from the outgrowth of the N layer, and could be considered as the secondary cartilage. The intensive expression of type II collagen from 17.0 dpc to 3 dpn was detected in the fibrous sheath covering the condylar head, which is derived from the peripheral cell aggregate of the anlage. Since its expression in the fibrous sheath was not detected in the neighboring

  16. Rescue of Isolated GH Deficiency Type II (IGHD II) via Pharmacologic Modulation of GH-1 Splicing.

    PubMed

    Miletta, Maria Consolata; Petkovic, Vibor; Eblé, Andrée; Flück, Christa E; Mullis, Primus-E

    2016-10-01

    Isolated GH deficiency (IGHD) type II, the autosomal dominant form of GHD, is mainly caused by mutations that affect splicing of GH-1. When misspliced RNA is translated, it produces a toxic 17.5-kDa GH isoform that reduces the accumulation and secretion of wild-type-human GH (wt-hGH). Usually, isolated GHD type II patients are treated with daily injections of recombinant human GH in order to maintain normal growth. However, this type of replacement therapy does not prevent toxic effects of the 17.5-kDa GH isoform on the pituitary gland, which can eventually lead to other hormonal deficiencies. Here, we tested the possibility to restore the constitutive splicing pattern of GH-1 by using butyrate, a drug that mainly acts as histone deacetylase inhibitor. To this aim, wt-hGH and/or different hGH-splice site mutants (GH-IVS3+2, GH-IVS3+6, and GH-ISE+28) were transfected in rat pituitary cells expressing human GHRH receptor (GHRHR) (GC-GHRHR). Upon butyrate treatment, GC-GHRHR cells coexpressing wt-hGH and each of the mutants displayed increased GH transcript level, intracellular GH content, and GH secretion when compared with the corresponding untreated condition. The effect of butyrate was most likely mediated by the alternative splicing factor/splicing factor 2. Overexpression of alternative ASF/SF2 in the same experimental setting, indeed, promoted the amount of full-length transcripts thus increasing synthesis and secretion of the 22-kDa GH isoform. In conclusion, our results support the hypothesis that modulation of GH-1 splicing pattern to increase the 22-kDa GH isoform levels can be clinically beneficial and hence a crucial challenge in GHD research.

  17. Preserving the longevity of long-lived type II collagen and its implication for cartilage therapeutics.

    PubMed

    Tiku, Moti L; Madhan, Balaraman

    2016-07-01

    Human life expectancy has been steadily increasing at a rapid rate, but this increasing life span also brings about increases in diseases, dementia, and disability. A global burden of disease 2010 study revealed that hip and knee osteoarthritis ranked the 11th highest in terms of years lived with disability. Wear and tear can greatly influence the quality of life during ageing. In particular, wear and tear of the articular cartilage have adverse effects on joints and result in osteoarthritis. The articular cartilage uses longevity of type II collagen as the foundation around which turnover of proteoglycans and the homeostatic activity of chondrocytes play central roles thereby maintaining the function of articular cartilage in the ageing. The longevity of type II collagen involves a complex interaction of the scaffolding needs of the cartilage and its biochemical, structural and mechanical characteristics. The covalent cross-linking of heterotypic polymers of collagens type II, type IX and type XI hold together cartilage, allowing it to withstand ageing stresses. Discerning the biological clues in the armamentarium for preserving cartilage appears to be collagen cross-linking. Therapeutic methods to crosslink in in-vivo are non-existent. However intra-articular injections of polyphenols in vivo stabilize the cartilage and make it resistant to degradation, opening a new therapeutic possibility for prevention and intervention of cartilage degradation in osteoarthritis of aging.

  18. Magnetization studies of II-VI semiconductor columnar quantum dots with type-II band alignment

    NASA Astrophysics Data System (ADS)

    Eginligil, M.; Sellers, I. R.; McCombe, B. D.; Chou, W.-C.; Kuskovsky, I. L.

    2009-03-01

    We report SQUID magnetization measurements of MBE-grown type-II, II-VI semiconductor quantum dot (QD) samples, with and without Mn incorporation. In all samples, the easy axis is out-of-plane, possibly due to columnar QD formation that arises from strain interaction between adjacent thin dot-containing layers. In addition, both types of QDs display a non-zero spontaneous magnetic ordering at 300 K. One set of samples consists of five-layers of (Zn,Mn)Te/ZnSe with a nominal (Zn,Mn)Te thickness of 3 nm, and ZnSe spacer thickness of 5 nm and 20 nm. These magnetic QD samples show magnetization vs. temperature behavior that can be interpreted in terms of two independent FM phases characterized by transition temperatures TC1 < TC2. A sample containing no Mn consists of 130 ZnTe/ZnSe layers, which forms Zn(Se,Te) QD layers separated by ZnSe spacers. Evidence of ferromagnetism is also seen in this structure, but the spontaneous magnetization is much weaker. For this sample only one phase is seen with TC above 300 K. Results will be discussed in terms of magneto-polaronic effects and defect-level induced ferromagnetism.

  19. Oxidative stress in patients with mucopolysaccharidosis type II before and during enzyme replacement therapy.

    PubMed

    Filippon, Letícia; Vanzin, Camila S; Biancini, Giovana B; Pereira, Izabela N; Manfredini, Vanusa; Sitta, Angela; Peralba, Maria do Carmo R; Schwartz, Ida V D; Giugliani, Roberto; Vargas, Carmen R

    2011-06-01

    Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulfatase, responsible for the degradation of glycosaminoglycans dermatan and heparan sulfate. Once the generation of free radicals is involved in the pathogenesis of many diseases, including some inborn errors of metabolism, the aim of this study was to evaluate blood oxidative stress parameters in MPS II patients, before and during 6 months of enzyme replacement therapy. We found significantly increased levels of malondialdehyde and carbonyl groups in plasma as well as erythrocyte catalase activity in patients before treatment compared to the control group. Plasma sulfhydryl group content and total antioxidant status were significantly reduced before treatment, while superoxide dismutase enzyme was not altered at this time when compared to controls. During enzyme replacement therapy, there was a significant reduction in levels of malondialdehyde when compared to pretreatment. Sulfhydryl groups were significantly increased until three months of treatment in MPS II patients in comparison to pretreatment. There were no significant alterations in plasma total antioxidant status and carbonyl groups as well as in catalase and superoxide dismutase activities during treatment in relation to pretreatment. The results indicate that MPS II patients are subject to lipid and protein oxidative damage and present reduction in non-enzymatic antioxidants, suggesting a possible involvement of free radicals in the pathophysiology of this disease. Also, the results may suggest that enzyme replacement therapy seems to protect against lipid peroxidation and protein damage in these patients.

  20. Glutathione reductase targeted to type II cells does not protect mice from hyperoxic lung injury.

    PubMed

    Heyob, Kathryn M; Rogers, Lynette K; Welty, Stephen E

    2008-12-01

    Exposure of the lung epithelium to reactive oxygen species without adequate antioxidant defenses leads to airway inflammation, and may contribute to lung injury. Glutathione peroxidase catalyzes the reduction of peroxides by oxidation of glutathione (GSH) to glutathione disulfide (GSSG), which can in turn be reduced by glutathione reductase (GR). Increased levels of GSSG have been shown to correlate negatively with outcome after oxidant exposure, and increased GR activity has been protective against hyperoxia in lung epithelial cells in vitro. We tested the hypothesis that increased GR expression targeted to type II alveolar epithelial cells would improve outcome in hyperoxia-induced lung injury. Human GR with a mitochondrial targeting sequence was targeted to mouse type II cells using the SPC promoter. Two transgenic lines were identified, with Line 2 having higher lung GR activities than Line 1. Both transgenic lines had lower lung GSSG levels and higher GSH/GSSG ratios than wild-type. Six-week-old wild-type and transgenic mice were exposed to greater than 95% O2 or room air (RA) for 84 hours. After exposure, Line 2 mice had higher right lung/body weight ratios and lavage protein concentrations than wild-type mice, and both lines 1 and 2 had lower GSSG levels than wild-type mice. These findings suggest that GSSG accumulation in the lung may not play a significant role in the development of hyperoxic lung injury, or that compensatory responses to unregulated GR expression render animals more susceptible to hyperoxic lung injury.

  1. Magnetic-Field-Induced Relativistic Properties in Type-I and Type-II Weyl Semimetals

    NASA Astrophysics Data System (ADS)

    Tchoumakov, Serguei; Civelli, Marcello; Goerbig, Mark O.

    2016-08-01

    We investigate Weyl semimetals with tilted conical bands in a magnetic field. Even when the cones are overtilted (type-II Weyl semimetal), Landau-level quantization can be possible as long as the magnetic field is oriented close to the tilt direction. Most saliently, the tilt can be described within the relativistic framework of Lorentz transformations that give rise to a rich spectrum, displaying new transitions beyond the usual dipolar ones in the optical conductivity. We identify particular features in the latter that allow one to distinguish between semimetals of different types.

  2. MT1-MMP and Type II Collagen Specify Skeletal Stem Cells and Their Bone and Cartilage Progeny

    PubMed Central

    Szabova, Ludmila; Yamada, Susan S.; Wimer, Helen; Chrysovergis, Kaliopi; Ingvarsen, Signe; Behrendt, Niels; Engelholm, Lars H.

    2009-01-01

    Skeletal formation is dependent on timely recruitment of skeletal stem cells and their ensuing synthesis and remodeling of the major fibrillar collagens, type I collagen and type II collagen, in bone and cartilage tissues during development and postnatal growth. Loss of the major collagenolytic activity associated with the membrane-type 1 matrix metalloproteinase (MT1-MMP) results in disrupted skeletal development and growth in both cartilage and bone, where MT1-MMP is required for pericellular collagen dissolution. We show here that reconstitution of MT1-MMP activity in the type II collagen–expressing cells of the skeleton rescues not only diminished chondrocyte proliferation, but surprisingly, also results in amelioration of the severe skeletal dysplasia associated with MT1-MMP deficiency through enhanced bone formation. Consistent with this increased bone formation, type II collagen was identified in bone cells and skeletal stem/progenitor cells of wildtype mice. Moreover, bone marrow stromal cells isolated from mice expressing MT1-MMP under the control of the type II collagen promoter in an MT1-MMP–deficient background showed enhanced bone formation in vitro and in vivo compared with cells derived from nontransgenic MT1-MMP–deficient littermates. These observations show that type II collagen is not stringently confined to the chondrocyte but is expressed in skeletal stem/progenitor cells (able to regenerate bone, cartilage, myelosupportive stroma, marrow adipocytes) and in the chondrogenic and osteogenic lineage progeny where collagenolytic activity is a requisite for proper cell and tissue function. PMID:19419317

  3. Molecular determinants on the insect sodium channel for the specific action of type II pyrethroid insecticides

    SciTech Connect

    Du Yuzhe; Nomura, Yoshiko; Luo Ningguang; Liu Zhiqi; Lee, Jung-Eun; Khambay, Bhupinder; Dong Ke

    2009-01-15

    Pyrethroid insecticides are classified as type I or type II based on their distinct symptomology and effects on sodium channel gating. Structurally, type II pyrethroids possess an {alpha}-cyano group at the phenylbenzyl alcohol position, which is lacking in type I pyrethroids. Both type I and type II pyrethroids inhibit deactivation consequently prolonging the opening of sodium channels. However, type II pyrethroids inhibit the deactivation of sodium channels to a greater extent than type I pyrethroids inducing much slower decaying of tail currents upon repolarization. The molecular basis of a type II-specific action, however, is not known. Here we report the identification of a residue G{sup 1111} and two positively charged lysines immediately downstream of G{sup 1111} in the intracellular linker connecting domains II and III of the cockroach sodium channel that are specifically involved in the action of type II pyrethroids, but not in the action of type I pyrethroids. Deletion of G{sup 1111}, a consequence of alternative splicing, reduced the sodium channel sensitivity to type II pyrethroids, but had no effect on channel sensitivity to type I pyrethroids. Interestingly, charge neutralization or charge reversal of two positively charged lysines (Ks) downstream of G{sup 1111} had a similar effect. These results provide the molecular insight into the type II-specific interaction of pyrethroids with the sodium channel at the molecular level.

  4. Preparation, characterization and biological activity of Fe(III), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and UO 2(II) complexes of new cyclodiphosph(V)azane of sulfaguanidine

    NASA Astrophysics Data System (ADS)

    Sharaby, Carmen M.

    2005-11-01

    Novel hexachlorocyclodiphosph(V)azane of sulfaguanidine, H 4L, l,3-[ N'-amidino-sulfanilamide]-2,2,2,4,4,4-hexachlorocyclodiphosph(V)azane was prepared and its coordination behaviour towards the transition metal ions Fe(III), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and UO 2(II) was studied. The structures of the isolated products are proposed based on elemental analyses, IR, UV-vis, 1H NMR, mass spectra, reflectance, magnetic susceptibility measurements and thermogravimetric analysis (TGA). The hyperfine interactions in the isolated complex compounds were studied using 14.4 keV γ-ray from radioactive 57Co (Mössbauer spectroscopy). The data show that the ligand are coordinated to the metal ions via the sulfonamide O and deprotonated NH atoms in an octahedral manner. The H 4L ligand forms complexes of the general formulae [(MX z) 2(H 2L)H 2O) n] and [(FeSO 4) 2 (H 4L) (H 2O) 4], where X = NO 3 in case of UO 2(II) and Cl in case of Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II). The molar conductance data show that the complexes are non-electrolytes. The thermal behaviour of the complexes was studied and different thermodynamic parameters were calculated using Coats-Redfern method. Most of the prepared complexes showed high bactericidal activity and some of the complexes show more activity compared with the ligand and standards.

  5. Therapeutic efficacy of undenatured type-II collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horses.

    PubMed

    Gupta, R C; Canerdy, T D; Skaggs, P; Stocker, A; Zyrkowski, G; Burke, R; Wegford, K; Goad, J T; Rohde, K; Barnett, D; DeWees, W; Bagchi, M; Bagchi, D

    2009-12-01

    The present investigation evaluated arthritic pain in horses receiving daily placebo, undenatured type II collagen (UC-II) at 320, 480, or 640 mg (providing 80, 120, and 160 mg active UC-II, respectively), and glucosamine and chondroitin (5.4 and 1.8 g, respectively, bid for the first month, and thereafter once daily) for 150 days. Horses were evaluated for overall pain, pain upon limb manipulation, physical examination, and liver and kidney functions. Evaluation of overall pain was based upon a consistent observation of all subjects during a walk and a trot in the same pattern on the same surface. Pain upon limb manipulation was conducted after the walk and trot. It consisted of placing the affected joint in severe flexion for a period of 60 sec. The limb was then placed to the ground and the animal trotted off. The response to the flexion test was then noted with the first couple of strides the animal took. Flexion test was consistent with determining clinically the degree of osteoarthritis in a joint. Horses receiving placebo showed no change in arthritic condition, while those receiving 320 or 480 or 640 mg UC-II exhibited significant reduction in arthritic pain (P < 0.05). UC-II at 480 or 640 mg dose provided equal effects, and therefore, 480 mg dose was considered optimal. With this dose, reduction in overall pain was from 5.7 +/- 0.42 (100%) to 0.7 +/- 0.42 (12%); and in pain upon limb manipulation from 2.35 +/- 0.37 (100%) to 0.52 +/- 0.18 (22%). Although glucosamine and chondroitin treated group showed significant (P < 0.05) reduction in pain compared with pretreated values, the efficacy was less compared with that observed with UC-II. In fact, UC-II at 480 or 640 mg dose was found to be more effective than glucosamine and chondroitin in arthritic horses. Clinical condition (body weight, body temperature, respiration rate, and pulse rate), and liver (bilirubin, GGT, and ALP) and kidney (BUN and creatinine) functions remained unchanged, suggesting that

  6. Induction of tolerance against the arthritogenic antigen with type-II collagen peptide-linked soluble MHC class II molecules.

    PubMed

    Park, Yoon-Kyung; Jung, Sundo; Park, Se-Ho

    2016-06-01

    In murine collagen-induced arthritis (CIA), self-reactive T cells can recognize peptide antigens derived from type-II collagen (CII). Activation of T cells is an important mediator of autoimmune diseases. Thus, T cells have become a focal point of study to treat autoimmune diseases. In this study, we evaluated the efficacy of recombinant MHC class II molecules in the regulation of antigen-specific T cells by using a self peptide derived from CII (CII260-274; IAGFKGEQGPKGEPG) linked to mouse I-A(q) in a murine CIA model. We found that recombinant I-A(q)/CII260-274 molecules could be recognized by CII-specific T cells and inhibit the same T cells in vitro. Furthermore, the development of CIA in mice was successfully prevented by in vivo injection of recombinant I-A(q)/CII260-274 molecules. Thus, treatment with recombinant soluble MHC class II molecules in complex with an immunodominant self-peptide might offer a potential therapeutic for chronic inflammation in autoimmune disease such as rheumatoid arthritis. [BMB Reports 2016; 49(6): 331-336].

  7. The vertebrate alcohol dehydrogenase system: variable class II type form elucidates separate stages of enzymogenesis.

    PubMed Central

    Hjelmqvist, L; Estonius, M; Jörnvall, H

    1995-01-01

    A mixed-class alcohol dehydrogenase has been characterized from avian liver. Its functional properties resemble the classical class I type enzyme in livers of humans and animals by exhibiting low Km and kcat values with alcohols (Km = 0.7 mM with ethanol) and low Ki values with 4-methylpyrazole (4 microM). These values are markedly different from corresponding parameters of class II and III enzymes. In contrast, the primary structure of this avian liver alcohol dehydrogenase reveals an overall relationship closer to class II and to some extent class III (69 and 65% residue identities, respectively) than to class I or the other classes of the human alcohol dehydrogenases (52-61%), the presence of an insertion (four positions in a segment close to position 120) as in class II but in no other class of the human enzymes, and the presence of several active site residues considered typical of the class II enzyme. Hence, the avian enzyme has mixed-class properties, being functionally similar to class I, yet structurally similar to class II, with which it also clusters in phylogenetic trees of characterized vertebrate alcohol dehydrogenases. Comparisons reveal that the class II enzyme is approximately 25% more variable than the "variable" class I enzyme, which itself is more variable than the "constant" class III enzyme. The overall extreme, and the unusual chromatographic behavior may explain why the class II enzyme has previously not been found outside mammals. The properties define a consistent pattern with apparently repeated generation of novel enzyme activities after separate gene duplications. Images Fig. 3 PMID:7479907

  8. Adjuvant arthritis pretreatment with type II collagen and Mycobacterium butyricum.

    PubMed

    Franch, A; Cassany, S; Castellote, C; Castell, M

    1992-11-01

    A treatment previous to adjuvant arthritis induction has been performed with type II collagen (CII) or Mycobacterium butyricum (Mb), which is the inducer of the pathology. Pretreatment was administered in two different ways: a) subcutaneously or intradermally 14 days before arthritis induction, and b) intravenously 3 days before induction. In order to relate the change in inflammation to the corresponding antigen immune response, serum antibodies and delayed type hypersensitivity (DTH) against CII or Mb were studied. Pretreatment with s.c. CII 14 days before induction produced slight protection against arthritis and significantly delayed its onset; systemic inflammation showed good positive correlation with anti-CII antibodies. The CII administered i.v. 3 days before arthritic challenge did not significantly modify the inflammatory process. The use of i.d. subarthritogenic doses of Mb 14 days before induction protected a high percentage of the animals from the posterior arthritic challenge; this protection was accompanied by high anti-Mb antibody titers and DTH reaction. When Mb was given i.v. 3 days before induction, a partial protection of inflammation was observed; arthritis was milder and its onset was delayed. These changes were accompanied by reduced humoral and cellular response to Mb.

  9. Localization of types I, II, and III collagen mRNAs in developing human skeletal tissues by in situ hybridization

    PubMed Central

    1987-01-01

    Paraffin sections of human skeletal tissues were studied in order to identify cells responsible for production of types I, II, and III collagens by in situ hybridization. Northern hybridization and sequence information were used to select restriction fragments of cDNA clones for the corresponding mRNAs to obtain probes with a minimum of cross- hybridization. The specificity of the probes was proven in hybridizations to sections of developing fingers: osteoblasts and chondrocytes, known to produce only one type of fibrillar collagen each (I and II, respectively) were only recognized by the corresponding cDNA probes. Smooth connective tissues exhibited variable hybridization intensities with types I and III collagen cDNA probes. The technique was used to localize the activity of type II collagen production in the different zones of cartilage during the growth of long bones. Visual inspection and grain counting revealed the highest levels of pro alpha 1(II) collagen mRNAs in chondrocytes of the lower proliferative and upper hypertrophic zones of the growth plate cartilage. This finding was confirmed by Northern blotting of RNAs isolated from epiphyseal (resting) cartilage and from growth zone cartilage. Analysis of the osseochondral junction revealed virtually no overlap between hybridization patterns obtained with probes specific for type I and type II collagen mRNAs. Only a fraction of the chondrocytes in the degenerative zone were recognized by the pro alpha 1(II) collagen cDNA probe, and none by the type I collagen cDNA probe. In the mineralizing zone virtually all cells were recognized by the type I collagen cDNA probe, but only very few scattered cells appeared to contain type II collagen mRNA. These data indicate that in situ hybridization is a valuable tool for identification of connective tissue cells which are actively producing different types of collagens at the various stages of development, differentiation, and growth. PMID:3558480

  10. Anti-type II collagen antibodies detection and avidity in patients with oligoarticular and polyarticular forms of juvenile idiopathic arthritis.

    PubMed

    Araujo, Galber R; Fonseca, João E; Fujimura, Patricia T; Cunha-Junior, Jair P; Silva, Carlos H M; Mourão, Ana F; Canhão, Helena; Goulart, Luiz R; Gonçalves, João; Ueira-Vieira, Carlos

    2015-05-01

    Juvenile idiopathic arthritis (JIA) refers to a heterogeneous group of illnesses that have in common the occurrence of chronic joint inflammation in children younger than 16 years of age. The diagnosis is made only on clinical assessment. The identification of antibody markers could improve the early diagnosis, optimizing the clinical management of patients. Type II collagen is one potential autoantigen that has been implicated in the process of arthritis development. The aims of our study were to investigate the occurrence of anti-type II collagen antibodies and also to determine the avidity of the antibody-antigen binding. Ninety-six patients with oligoarticular or polyarticular JIA, 13 patients with ankylosing spondylitis (AS) and 61 healthy controls (HC) were tested for anti-type II collagen antibodies by ELISA and avidity ELISA. Sensitivity and specificity were determined by the receiver operating characteristic (ROC) curve analysis. Forty-two JIA patients (44%) were positive for antibodies against type II collagen. Its detection was significantly higher in JIA patients than in AS patients (p=0.006) and HCs (p<0.0001). Furthermore, anti-type II collagen antibody detection was significantly more frequent in patients with JIA of ≤6 months duration (p=0.0007). Antibodies displaying high avidity to type II collagen were associated with disease activity (p=0.004). This study demonstrates that antibodies against type II collagen are present in the serum of patients with oligoarticular and polyarticular JIA, being its presence more prevalent in patients with early disease. It also demonstrates that JIA patients with active disease present antibodies with high avidity against type II collagen.

  11. Relative potencies of Type I and Type II pyrethroids for inhibition of spontaneous firing in neuronal networks.

    EPA Science Inventory

    Pyrethroids insecticides commonly used in pest control disrupt the normal function of voltage-sensitive sodium channels. We have previously demonstrated that permethrin (a Type I pyrethroid) and deltamethrin (a Type II pyrethroid) inhibit sodium channel-dependent spontaneous netw...

  12. Gallium nitrate ameliorates type II collagen-induced arthritis in mice.

    PubMed

    Choi, Jae-Hyeog; Lee, Jong-Hwan; Roh, Kug-Hwan; Seo, Su-Kil; Choi, Il-Whan; Park, Sae-Gwang; Lim, Jun-Goo; Lee, Won-Jin; Kim, Myoung-Hun; Cho, Kwang-rae; Kim, Young-Jae

    2014-05-01

    Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Gallium nitrate has been reported to reserve immunosuppressive activities. Therefore, we assessed the therapeutic effects of gallium nitrate in the mouse model of developed type II collagen-induced arthritis (CIA). CIA was induced by bovine type II collagen with Complete Freund's adjuvant. CIA mice were intraperitoneally treated from day 36 to day 49 after immunization with 3.5mg/kg/day, 7mg/kg/day gallium nitrate or vehicle. Gallium nitrate ameliorated the progression of mice with CIA. The clinical symptoms of collagen-induced arthritis did not progress after treatment with gallium nitrate. Gallium nitrate inhibited the increase of CD4(+) T cell populations (p<0.05) and also inhibited the type II collagen-specific IgG2a-isotype autoantibodies (p<0.05). Gallium nitrate reduced the serum levels of TNF-α, IL-6 and IFN-γ (p<0.05) and the mRNA expression levels of these cytokine and MMPs (MMP2 and MMP9) in joint tissues. Western blotting of members of the NF-κB signaling pathway revealed that gallium nitrate inhibits the activation of NF-κB by blocking IκB degradation. These data suggest that gallium nitrate is a potential therapeutic agent for autoimmune inflammatory arthritis through its inhibition of the NF-κB pathway, and these results may help to elucidate gallium nitrate-mediated mechanisms of immunosuppression in patients with RA.

  13. Evaluation of mono or mixed cultures of lactic acid bacteria in type II sourdough system.

    PubMed

    Ekinci, Raci; Şimşek, Ömer; Küçükçuban, Ayca; Nas, Sebahattin

    2016-01-01

    The aim of this study was to evaluate the use of mono and mixed lactic acid bacteria (LAB) cultures to determine suitable LAB combinations for a type II sourdough system. In this context, previously isolated sourdough LAB strains with antimicrobial activity, which included Lactobacillus plantarum PFC22, Lactobacillus brevis PFC31, Pediococcus acidilactici PFC38, and Lactobacillus sanfranciscensis PFC80, were used as mono or mixed culture combinations in a fermentation system to produce type II sourdough, and subsequently in bread dough production. Compared to the monoculture fermentation of dough, the use of mixed cultures shortened the adaptation period by half. In addition, the use of mixed cultures ensured higher microbial viability, and enhanced the fruity flavor during bread dough production. It was determined that the combination of L. plantarum PFC22 + P. acidilactici PFC38 + L. sanfranciscensis PFC80 is a promising culture mixture that can be used in the production of type II sourdough systems, and that may also contribute to an increase in metabolic activity during bread production process.

  14. The glucocorticoid receptor type II complex is a target of the HIV-1 vpr gene product.

    PubMed Central

    Refaeli, Y; Levy, D N; Weiner, D B

    1995-01-01

    The vpr gene of human immunodeficiency virus type 1 (HIV-1) encodes a 15-kDa virion-associated protein that functions as a regulator of cellular processes linked to the HIV life cycle. We report the interaction of a 41-kDa cytosolic viral protein R interacting protein 1 (Rip-1) with Vpr in vitro. Rip-1 displays a wide tissue distribution, including relevant targets of HIV infection. Vpr protein induced nuclear translocation of Rip-1, as did glucocorticoid receptor (GR)-II-stimulating steroids. Importantly, Vpr and Rip-1 coimmunoprecipitated with the human GR as part of an activated receptor complex. Vpr complementation of a vpr mutant virus was also mimicked by GR-II-stimulating steroids. Vpr and GR-II actions were inhibited by mifepristone, a GR-II pathway inhibitor. Together these data directly link the activity of the vpr gene product to the glucocorticoid steroid pathway and provide a biochemical mechanism for the cellular and viral activity of Vpr, as well as suggest that a unique class of antivirals, which includes mifepristone (RU486), may influence HIV-1 replication. Images Fig. 1 Fig. 2 Fig. 3 Fig. 5 PMID:7724608

  15. Evaporation and recondensation of sodium in Semarkona Type II chondrules

    NASA Astrophysics Data System (ADS)

    Hewins, Roger H.; Zanda, Brigitte; Bendersky, Claire

    2012-02-01

    We have investigated the Na distributions in Semarkona Type II chondrules by electron microprobe, analyzing olivine and melt inclusions in it, mesostasis and bulk chondrule, to see whether they indicate interactions with an ambient gas during chondrule formation. Sodium concentrations of bulk chondrule liquids, melt inclusions and mesostases can be explained to a first approximation by fractional crystallization of olivine ± pyroxene. The most primitive olivine cores in each chondrule are mostly between Fa 8 and Fa 13, with 0.0022-0.0069 ± 0.0013 wt.% Na 2O. Type IIA chondrule olivines have consistently higher Na contents than olivines in Type IIAB chondrules. We used the dependence of olivine-liquid Na partitioning on FeO in olivine as a measure of equilibration. Extreme olivine rim compositions are ˜Fa 35 and 0.03 wt.% Na 2O and are close to being in equilibrium with the mesostasis glass. Olivine cores compared with the bulk chondrule compositions, particularly in IIA chondrules, show very high apparent D Na, indicating disequilibrium and suggesting that chondrule initial melts were more Na-rich than present chondrule bulk compositions. The apparent D Na values correlate with the Na concentrations of the olivine, but not with concentrations in the bulk melt. We use equilibrium D Na to find the Na content of the true parent liquid and estimate that Type IIA chondrules lost more than half their Na and recondensation was incomplete, whereas Type IIAB chondrules recovered most of theirs in their mesostases . Glass inclusions in olivine have lower Na than expected from fractionation of bulk composition liquids, and mesostases have higher Na than expected in calculated daughter liquids formed by fractional crystallization alone. These observations also require open system behavior of chondrules, specifically evaporation of Na before formation of melt inclusions followed by recondensation of Na in mesostases. Within this record of evaporation followed by

  16. Collagen type II, alpha 1 protein: a bioactive component of shark cartilage.

    PubMed

    Merly, Liza; Smith, Sylvia L

    2013-02-01

    Previous studies have shown that extracts of shark cartilage induce a cytokine response in human leukocytes, but the nature of the bioactive component(s) is unknown. Extracts treated with proteases lost 80% of their cytokine-inducing property, suggesting that the active component(s) was likely a complex protein. The aim of the present study was to determine the nature of the bioactive molecule(s). Solid phase extraction followed by ion exchange chromatography and electrophoretic separation were used to partially purify a bioactive preparation from commercial shark cartilage that has been identified as a small glycoprotein. LC-MS analysis yielded peptides with 100% molecular identity with collagen type II, alpha I protein from the lesser spotted catshark, Scyliorhinus canicula. The implications for the consumption of shark cartilage as a dietary supplement are discussed given the presence of collagen type II, alpha 1 protein in extracts.

  17. Glutaric aciduria type II presenting as myopathy and rhabdomyolysis in a teenager.

    PubMed

    Prasad, Manish; Hussain, Shanawaz

    2015-01-01

    Late-onset glutaric aciduria type II has been described recently as a rare but treatable cause of proximal myopathy in teenagers and adults. It is an autosomal recessive disease affecting fatty acid, amino acid, and choline metabolism. This is usually a result of 2 defective flavoproteins: either electron transfer flavoprotein (ETF) or electron transfer flavoprotein-ubiquinone oxidoreductase (ETF:QO). We present a 14-year-old boy with a background of autistic spectrum disorder who presented with severe muscle weakness and significant rhabdomyolysis. Before the onset of muscle weakness, he was very active but was completely bedridden at presentation. Diagnosis was established quickly by urine organic acid and plasma acylcarnitine analysis. He has shown significant improvement after starting oral riboflavin supplementation and is now fully mobile. This case highlights that late-onset glutaric aciduria type II is an important differential diagnosis to consider in teenagers presenting with proximal myopathy and rhabdomyolysis and it may not be associated with hypoglycemia.

  18. Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis

    NASA Astrophysics Data System (ADS)

    Trentham, David E.; Dynesius-Trentham, Roselynn A.; Orav, E. John; Combitchi, Daniel; Lorenzo, Carlos; Sewell, Kathryn Lea; Hafler, David A.; Weiner, Howard L.

    1993-09-01

    Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.

  19. Angiotensin II Contributes to Renal Fibrosis Independently of Notch Pathway Activation

    PubMed Central

    Lavoz, Carolina; Rodrigues-Diez, Raquel; Benito-Martin, Alberto; Rayego-Mateos, Sandra; Rodrigues-Diez, Raúl R.; Alique, Matilde; Ortiz, Alberto; Mezzano, Sergio; Egido, Jesús; Ruiz-Ortega, Marta

    2012-01-01

    Recent studies have described that the Notch signaling pathway is activated in a wide range of renal diseases. Angiotensin II (AngII) plays a key role in the progression of kidney diseases. AngII contributes to renal fibrosis by upregulation of profibrotic factors, induction of epithelial mesenchymal transition and accumulation of extracellular matrix proteins. In cultured human tubular epithelial cells the Notch activation by transforming growth factor-β1 (TGF-β1) has been involved in epithelial mesenchymal transition. AngII mimics many profibrotic actions of TGF-β1. For these reasons, our aim was to investigate whether AngII could regulate the Notch/Jagged system in the kidney, and its potential role in AngII-induced responses. In cultured human tubular epithelial cells, TGF-β1, but not AngII, increased the Notch pathway-related gene expression, Jagged-1 synthesis, and caused nuclear translocation of the activated Notch. In podocytes and renal fibroblasts, AngII did not modulate the Notch pathway. In tubular epithelial cells, pharmacological Notch inhibition did not modify AngII-induced changes in epithelial mesenchymal markers, profibrotic factors and extracellular matrix proteins. Systemic infusion of AngII into rats for 2 weeks caused tubulointerstitial fibrosis, but did not upregulate renal expression of activated Notch-1 or Jagged-1, as observed in spontaneously hypertensive rats. Moreover, the Notch/Jagged system was not modulated by AngII type I receptor blockade in the model of unilateral ureteral obstruction in mice. These data clearly indicate that AngII does not regulate the Notch/Jagged signaling system in the kidney, in vivo and in vitro. Our findings showing that the Notch pathway is not involved in AngII-induced fibrosis could provide important information to understand the complex role of Notch system in the regulation of renal regeneration vs damage progression. PMID:22792351

  20. Solar flares associated coronal mass ejections in case of type II radio bursts

    NASA Astrophysics Data System (ADS)

    Bhatt, Beena; Prasad, Lalan; Chandra, Harish; Garia, Suman

    2016-08-01

    We have statistically studied 220 events from 1996 to 2008 (i.e. solar cycle 23). Two set of flare-CME is examined one with Deca-hectometric (DH) type II and other without DH type II radio burst. Out of 220 events 135 (flare-halo CME) are accompanied with DH type II radio burst and 85 are without DH type II radio burst. Statistical analysis is performed to examine the distribution of solar flare-halo CME around the solar disk and to investigate the relationship between solar flare and halo CME parameters in case of with and without DH type II radio burst. In our analysis we have observed that: (i) 10-20° latitudinal belt is more effective than the other belts for DH type II and without DH type II radio burst. In this belt, the southern region is more effective in case of DH type II radio burst, whereas in case of without DH type II radio burst dominance exits in the northern region. (ii) 0-10° longitudinal belt is more effective than the other belts for DH type II radio burst and without DH type II radio burst. In this belt, the western region is more effective in case of DH type II radio burst, while in case of without DH type II radio burst dominance exits in the eastern region. (iii) Mean speed of halo CMEs (1382 km/s) with DH type II radio burst is more than the mean speed of halo CMEs (775 km/s) without DH type II radio burst. (iv) Maximum number of M-class flares is found in both the cases. (v) Average speed of halo CMEs in each class accompanied with DH type II radio burst is higher than the average speed of halo CMEs in each class without DH type II radio burst. (vi) Average speed of halo CMEs, associated with X-class flares, is greater than the other class of solar flares in both the cases.

  1. Altered lipid synthesis in type II pneumonocytes exposed to lung surfactant.

    PubMed Central

    Thakur, N R; Tesan, M; Tyler, N E; Bleasdale, J E

    1986-01-01

    When type II pneumonocytes were exposed to purified lung surfactant that contained 1-palmitoyl-2-[3H]palmitoyl-glycero-3-phosphocholine, radiolabelled surfactant was apparently taken up by the cells since it could not be removed by either repeated washing or exchange with non-radiolabelled surfactant, but was released when the cells were lysed. After 4 h of exposure to [3H]surfactant, more than half of the 3H within cells remained in disaturated phosphatidylcholine. Incorporation of [3H]choline, [14C]palmitate and [14C]acetate into glycerophospholipids was decreased in type II cells exposed to surfactant and this inhibition, like surfactant uptake, was half-maximal when the extracellular concentration of surfactant was approx. 0.1 mumol of lipid P/ml. Inhibition of incorporation of radiolabelled precursors by surfactant occurred rapidly and reversibly and was not due solely to dilution of the specific radioactivity of intracellular precursors. Activity of dihydroxyacetone-phosphate acyltransferase, but not glycerol-3-phosphate acyltransferase, was decreased in type II cells exposed to surfactant and this was reflected by a decrease in the 14C/3H ratio of total lipids synthesized when cells incubated with [U-14C]glycerol and [2-3H]glycerol were exposed to surfactant. Phosphatidylcholine, phosphatidylglycerol and cholesterol, either individually or mixed in the molar ratio found in surfactant, did not mimic purified surfactant in the inhibition of glycerophospholipid synthesis. In contrast, an apoprotein fraction isolated from surfactant inhibited greatly the incorporation of [3H]choline into lipids and this inhibitory activity was labile to heat and to trypsin. It is concluded that the apparent uptake of surfactant by type II cells in vitro is accompanied by an inhibition of glycerophospholipid synthesis via a mechanism that involves a surfactant apoprotein. Images Fig. 4. PMID:3827860

  2. Automatic Keypress Activation in Skilled Typing

    ERIC Educational Resources Information Center

    Rieger, Martina

    2004-01-01

    The assumption that letters automatically activate corresponding keypresses in skilled typing was investigated. Participants responded to the color of letters (congruent condition: responding finger was the one usually used to type the letter). Participants skilled in typing showed a congruency effect: unskilled participants did not (Experiment…

  3. Characteristics of DH type II bursts, CMEs and flares with respect to the acceleration of CMEs

    NASA Astrophysics Data System (ADS)

    Prakash, O.; Umapathy, S.; Shanmugaraju, A.; Pappa Kalaivani, P.; Vršnak, Bojan

    2012-01-01

    A detailed investigation on DH-type-II radio bursts recorded in Deca-Hectometer (hereinafter DH-type-II) wavelength range and their associated CMEs observed during the year 1997-2008 is presented. The sample of 212 DH-type-II associated with CMEs are classified into three populations: (i) Group I (43 events): DH-type-II associated CMEs are accelerating in the LASCO field view ( a>15 m s-2); (ii) Group II (99 events): approximately constant velocity CMEs (-15< a<15 m s-2) and (iii) Group III (70 events): represents decelerating CMEs ( a<-15 m s-2). Our study consists of three steps: (i) statistical properties of DH-type-II bursts of Group I, II and III events; (ii) analysis of time lags between onsets of flares and CMEs associated with DH-type-II bursts and (iii) statistical properties of flares and CMEs of Group I, II and III events. We found statistically significant differences between the properties of DH-type-II bursts of Group I, II and III events. The significance ( P a ) is found using the one-way ANOVA-test to examine the differences between means of groups. For example, there is significant difference in the duration ( P a =5%), ending frequency ( P a =4%) and bandwidth ( P a =4%). The accelerating and decelerating CMEs have more kinetic energy than the constant speed CMEs. There is a significant difference between the nose height of CMEs at the end time of DH-type-IIs ( P a ≪1%). From the time delay analysis, we found: (i) there is no significant difference in the delay (flare start—DH-type-II start and flare peak—DH-type-II start); (ii) small differences in the time delay between the CME onset and DH-type-II start, delay between the flare start and CME onset times. However, there are high significant differences in: flare duration ( P a =1%), flare rise time ( P a =0.5%), flare decay time ( P a =5%) and CMEs speed ( P a ≪1%) of Group I, II and III events. The general LASCO CMEs have lower width and speeds when compared to the DH CMEs. It seems

  4. Active site-specific reconstituted copper(II) horse liver alcohol dehydrogenase: a biological model for type 1 Cu2+ and its changes upon ligand binding and conformational transitions.

    PubMed

    Maret, W; Dietrich, H; Ruf, H H; Zeppezauer, M

    1980-06-01

    Insertion of Cu2+ ions into horse liver alcohol dehydrogenase depleted of its catalytic Zn2+ ions creates an artificial blue copper center similar to that of plastocyanin and similar copper proteins. The esr spectrum of a frozen solution and the optical spectra at 296 and 77 K are reported, together with the corresponding data for binary and ternary complexes with NAD+ and pyrazole. The binary complex of the cupric enzyme with pyrazole establishes a novel type of copper proteins having the optical characteristics of Type 1 and the esr parameters of Type 2 Cu2+. Ternary complex formation with NAD+ converts the Cu2+ ion to a Type 1 center. By an intramolecular redox reaction the cuprous enzyme is formed from the cupric enzyme. Whereas the activity of the cupric alcohol dehydrogenase is difficult to assess (0.5%-1% that of the native enzyme), the cuprous enzyme is distinctly active (8% of the native enzyme). The implications of these findings are discussed in view of the coordination of the metal in native copper proteins.

  5. Type II topoisomerases--inhibitors, repair mechanisms and mutations.

    PubMed

    Heisig, Peter

    2009-11-01

    Type II topoisomerases are ubiquitous enzymes that play an essential role in the control of replicative DNA synthesis and share structural and functional homology among different prokaryotic and eukaryotic organisms. Antibacterial fluoroquinolones target prokaryotic topoisomerases at concentrations 100- to 1000-fold lower than mammalian enzymes, the preferred targets of anticancer drugs such as etoposide. The mechanisms of action of both of these types of inhibitors involve the fixation of an intermediate reaction step, where the enzyme is covalently bound to an enzyme-mediated DNA double-strand break (DSB). The resulting ternary drug-enzyme-DNA complexes can then be converted to cleavage complexes that block further movement of the DNA replication fork, subsequently inducing stress responses. In haploid prokaryotic cells, stress responses include error-free and error-prone DNA damage repair pathways, such as homologous recombination and translesion synthesis, respectively. The latter can result in the acquisition of point mutations. Diploid mammalian cells are assumed to preferentially use recombination mechanisms for the repair of DSBs, an example of which, non-homologous end joining, is a major error-prone repair mechanism associated with an increased frequency of detectable small deletions, insertions and translocations. However, results obtained from safety testing of novel fluoroquinolones at high concentrations indicate that point mutations may also occur in mammalian cells. Recent data provide evidence for translesion synthesis catalysed by error-prone repair polymerases as a damage-tolerance repair mechanism of DSBs in eukaryotic cells. This paper discusses possible roles of different mechanisms for the repair of DSBs operating in both eukaryotic and prokaryotic cells that result in recombinational rearrangements, deletions/insertions as well as point mutations.

  6. Bolometric Lightcurves of Peculiar Type II-P Supernovae

    NASA Astrophysics Data System (ADS)

    Lusk, Jeremy A.; Baron, Edward A.

    2017-01-01

    We examine the bolometric lightcurves of five Type II-P supernovae (SNe 1998A, 2000cb, 2006V, 2006au and 2009E) which are thought to originate from blue supergiant progenitors using a new python package named SuperBoL. With this code, we calculate SNe lightcurves using three different techniques common in the literature: the quasi-bolometric method, which integrates the observed photometry, the direct integration method, which additionally corrects for unobserved flux in the UV and IR, and the bolometric correction method, which uses correlations between observed colors and V-band bolometric corrections. We present here the lightcurves calculated by SuperBoL along with previously published lightcurves, as well as peak luminosities and 56Ni yields. We find that the direct integration and bolometric correction lightcurves largely agree with previously published lightcurves, but with what we believe to be more robust error calculations, with 0.2 ≤ δL/L ≤ 0.5. Peak luminosities and 56Ni masses are similarly comparable to previous work. SN 2000cb remains an unusual member of this sub-group, owing to the faster rise and flatter plateau than the other supernovae in the sample. Initial comparisons with the NLTE atmosphere code PHOENIX show that the direct integration technique reproduces the luminosity of a model supernova spectrum to ˜5% when given synthetic photometry of the spectrum as input. Our code is publicly available. The ability to produce bolometric lightcurves from observed sets of broad-band light curves should be helpful in the interpretation of other types of supernovae, particularly those that are not well characterized, such as extremely luminous supernovae and faint fast objects.

  7. Bolometric Light Curves of Peculiar Type II-P Supernovae

    NASA Astrophysics Data System (ADS)

    Lusk, Jeremy A.; Baron, E.

    2017-04-01

    We examine the bolometric light curves of five Type II-P supernovae (SNe 1998A, 2000cb, 2006V, 2006au, and 2009E), which are thought to originate from blue supergiant progenitors like that of SN 1987A, using a new python package named SuperBoL. With this code, we calculate SNe light curves using three different common techniques common from the literature: the quasi-bolometric method, which integrates the observed photometry, the direct integration method, which additionally corrects for unobserved flux in the UV and IR, and the bolometric correction method, which uses correlations between observed colors and V-band bolometric corrections. We present here the light curves calculated by SuperBoL, along with previously published light curves, as well as peak luminosities and 56Ni yields. We find that the direct integration and bolometric correction light curves largely agree with previously published light curves, but with what we believe to be more robust error calculations, with 0.2≲ δ {L}{bol}/{L}{bol}≲ 0.5. Peak luminosities and 56Ni masses are similarly comparable to previous work. SN 2000cb remains an unusual member of this sub-group, owing to the faster rise and flatter plateau than the other supernovae in the sample. Initial comparisons with the NLTE atmosphere code PHOENIX show that the direct integration technique reproduces the luminosity of a model supernova spectrum to ∼5% when given synthetic photometry of the spectrum as input. Our code is publicly available. The ability to produce bolometric light curves from observed sets of broadband light curves should be helpful in the interpretation of other types of supernovae, particularly those that are not well characterized, such as extremely luminous supernovae and faint fast objects.

  8. Isolation of cDNA and genomic DNA clones encoding type II collagen.

    PubMed Central

    Young, M F; Vogeli, G; Nunez, A M; Fernandez, M P; Sullivan, M; Sobel, M E

    1984-01-01

    A cDNA library constructed from total chick embryo RNA was screened with an enriched fraction of type II collagen mRNA. Two overlapping cDNA clones were characterized and shown to encode the COOH propeptide of type II collagen. In addition, a type II collagen clone was isolated from a Charon 4A library of chick genomic fragments. Definitive identification of the clones was based on DNA sequence analysis. The 3' end of the type II collagen gene appears to be similar to that of other interstitial collagen genes. Northern hybridization data indicates that there is a marked decrease in type II collagen mRNA levels in chondrocytes treated with the dedifferentiating agent 5-bromodeoxyuridine. The major type II collagen mRNA species is 5300 bases long, similar to that of other interstitial collagen RNAs. Images PMID:6203098

  9. Sulforaphane Prevents Angiotensin II-Induced Testicular Cell Death via Activation of NRF2

    PubMed Central

    Wang, Yonggang; Xin, Ying; Tan, Yi

    2017-01-01

    Although angiotensin II (Ang II) was reported to facilitate sperm motility and intratesticular sperm transport, recent findings shed light on the efficacy of Ang II in stimulating inflammatory events in testicular peritubular cells, effect of which may play a role in male infertility. It is still unknown whether Ang II can induce testicular apoptotic cell death, which may be a more direct action of Ang II in male infertility. Therefore, the present study aims to determine whether Ang II can induce testicular apoptotic cell death and whether this action can be prevented by sulforaphane (SFN) via activating nuclear factor (erythroid-derived 2)-like 2 (NRF2), the governor of antioxidant-redox signalling. Eight-week-old male C57BL/6J wild type (WT) and Nrf2 gene knockout mice were treated with Ang II, in the presence or absence of SFN. In WT mice, SFN activated testicular NRF2 expression and function, along with a marked attenuation in Ang II-induced testicular oxidative stress, inflammation, endoplasmic reticulum stress, and apoptotic cell death. Deletion of the Nrf2 gene led to a complete abolishment of these efficacies of SFN. The present study indicated that Ang II may result in testicular apoptotic cell death, which can be prevented by SFN via the activation of NRF2. PMID:28191275

  10. Alternative Splicing of Type II Procollagen: IIB or not IIB?

    PubMed Central

    McAlinden, Audrey

    2015-01-01

    Over two decades ago, two isoforms of the type II procollagen gene (COL2A1) were discovered. These isoforms, named IIA and IIB, are generated in a developmentally-regulated manner by alternative splicing of exon 2. Chondroprogenitor cells synthesize predominantly IIA isoforms (containing exon 2) while differentiated chondrocytes produce mainly IIB transcripts (devoid of exon 2). Importantly, this IIA-to-IIB alternative splicing switch occurs only during chondrogenesis. More recently, two other isoforms have been reported (IIC and IID) that also involve splicing of exon 2; these findings highlight the complexities involving regulation of COL2A1 expression. The biological significance of why different isoforms of COL2A1 exist within the context of skeletal development and maintenance is still not completely understood. This review will provide current knowledge on COL2A1 isoform expression during chondrocyte differentiation and what is known about some of the mechanisms that control exon 2 alternative splicing. Utilization of mouse models to address the biological significance of Col2a1 alternative splicing in vivo will also be discussed. From the knowledge acquired to date, some new questions and concepts are now being proposed on the importance of Col2a1 alternative splicing in regulating extracellular matrix assembly and how this may subsequently affect cartilage and endochondral bone quality and function. PMID:24669942

  11. Type II supernovae as a significant source of interstellar dust.

    PubMed

    Dunne, Loretta; Eales, Stephen; Ivison, Rob; Morgan, Haley; Edmunds, Mike

    2003-07-17

    Large amounts of dust (>10(8)M(o)) have recently been discovered in high-redshift quasars and galaxies corresponding to a time when the Universe was less than one-tenth of its present age. The stellar winds produced by stars in the late stages of their evolution (on the asymptotic giant branch of the Hertzsprung-Russell diagram) are thought to be the main source of dust in galaxies, but they cannot produce that dust on a short enough timescale (&<1 Gyr) to explain the results in the high-redshift galaxies. Supernova explosions of massive stars (type II) are also a potential source, with models predicting 0.2-4M(o) of dust. As massive stars evolve rapidly, on timescales of a few Myr, these supernovae could be responsible for the high-redshift dust. Observations of supernova remnants in the Milky Way, however, have hitherto revealed only 10(-7)-10(-3)M(o) each, which is insufficient to explain the high-redshift data. Here we report the detection of approximately 2-4M(o) of cold dust in the youngest known Galactic supernova remnant, Cassiopeia A. This observation implies that supernovae are at least as important as stellar winds in producing dust in our Galaxy and would have been the dominant source of dust at high redshifts.

  12. Inert dark matter in type-II seesaw

    NASA Astrophysics Data System (ADS)

    Chen, Chuan-Hung; Nomura, Takaaki

    2014-09-01

    Weakly interacting massive particle (WIMP) as a dark matter (DM) candidate is further inspired by recent AMS-02 data, which confirm the excess of positron fraction observed earlier by PAMELA and Fermi-LAT experiments. Additionally, the excess of positron+electron flux is still significant in the measurement of Fermi-LAT. For solving the problems of massive neutrinos and observed excess of cosmic-ray, we study the model with an inert Higgs doublet (IHD) in the framework of type-II seesaw model by imposing a Z 2 symmetry on the IHD, where the lightest particle of IHD is the DM candidate and the neutrino masses originate from the Yukawa couplings of Higgs triplet and leptons. We calculate the cosmic-ray production in our model by using three kinds of neutrino mass spectra, which are classified by normal ordering, inverted ordering and quasi-degeneracy. We find that when the constraints of DM relic density and comic-ray antiproton spectrum are taken into account, the observed excess of positron/electron flux could be explained well in normal ordered neutrino mass spectrum. Moreover, excess of comic-ray neutrinos is implied in our model. We find that our results on < σv> are satisfied with and close to the upper limit of IceCube analysis. More data from comic-ray neutrinos could test our model.

  13. Type II dehydroquinase: molecular replacement with many copies

    PubMed Central

    Stewart, Kirsty Anne; Robinson, David Alexander; Lapthorn, Adrian Jonathan

    2008-01-01

    Type II dehydroquinase is a small (150-amino-acid) protein which in solution packs together to form a dodecamer with 23 cubic symmetry. In crystals of this protein the symmetry of the biological unit can be coincident with the crystallographic symmetry, giving rise to cubic crystal forms with a single monomer in the asymmetric unit. In crystals where this is not the case, multiple copies of the monomer are present, giving rise to significant and often confusing noncrystallographic symmetry in low-symmetry crystal systems. These different crystal forms pose a variety of challenges for solution by molecular replacement. Three examples of structure solutions, including a highly unusual triclinic crystal form with 16 dodecamers (192 monomers) in the unit cell, are described. Four commonly used molecular-replacement packages are assessed against two of these examples, one of high symmetry and the other of low symmetry; this study highlights how program performance can vary significantly depending on the given problem. In addition, the final refined structure of the 16-dodecamer triclinic crystal form is analysed and shown not to be a superlattice structure, but rather an F-centred cubic crystal with frustrated crystallographic symmetry. PMID:18094474

  14. Health perceptions among urban American Indians with type II diabetes.

    PubMed

    Patel, Sachin; Davila, Javier; Patel, Sonam; Norman, Dennis

    2014-01-01

    Since the 1940s, American Indians (AIs) have increasingly urbanized, moving off of reservations in large part due to federal policies of tribal termination and relocation. Though previous AI research has largely focused on reservation-associated challenges, many of these same challenges persist among urban AI populations. One mutual concern is the growing prevalence and incidence of type II diabetes mellitus (T2DM). While behavioral, genetic, and socioeconomic determinants of T2DM have been explored, much less is known about the influence of cultural and psychosocial factors. Recent studies suggest that the way AIs perceive diabetes may affect their health trajectory and explain their poor prognosis. Through the use of the Illness Perception Questionnaire, we explored this hypothesis in a pilot study of urban AI with T2DM living in Los Angeles County. We found that the majority of participants have a neutral perception about their diabetes: They view their condition to be long lasting yet treatable and indicate reasonable understanding of its symptoms and progression. We also identified "personal control," the level of perceived control one has over his or her disease, as a strong correlate of overall illness perception and, thus, a potentially useful psychological metric.

  15. ``N'' structure for type-II superlattice photodetectors

    NASA Astrophysics Data System (ADS)

    Salihoglu, Omer; Muti, Abdullah; Kutluer, Kutlu; Tansel, Tunay; Turan, Rasit; Ergun, Yuksel; Aydinli, Atilla

    2012-08-01

    In the quest to raise the operating temperature and improve the detectivity of type II superlattice (T2SL) photodetectors, we introduce a design approach that we call the "N structure." N structure aims to improve absorption by manipulating electron and hole wavefunctions that are spatially separated in T2SLs, increasing the absorption while decreasing the dark current. In order to engineer the wavefunctions, we introduce a thin AlSb layer between InAs and GaSb layers in the growth direction which also acts as a unipolar electron barrier. Unlike the symmetrical insertion of AlSb into GaSb layers, N design aims to exploit the shifting of the electron and hole wavefunctions under reverse bias. With cutoff wavelength of 4.3 μm at 77 K, temperature dependent dark current and detectivity measurements show that the dark current density is 3.6 × 10-9 A/cm2, under zero bias. Photodetector reaches background limited infrared photodetection (BLIP) condition at 125 K with the BLIP detectivity (D*BLIP) of 2.6 × 1010 Jones under 300 K background and -0.3 V bias voltage.

  16. Type II Radio Bursts as an Indicator of CME Location

    NASA Astrophysics Data System (ADS)

    Quirk, C. A.; St Cyr, O. C.; Henning, C.; Xie, H.; Gilbert, H. R.; Orlove, M.; Gopalswamy, N.; Odstrcil, D.

    2011-12-01

    We examined a subset of nine low-frequency radio events with type II radio bursts that drifted below 2 megahertz and were detected by the WAVES investigation on the WIND spacecraft. For each event, we identified the associated coronal mass ejection (CME) and derived the electron density using a model of solar wind plasma frequency (fp ≈ 9 * ne1/2, where fp is plasma frequency in kHz and ne is electron density in cm-3) . We also used the pb_inverter program in SolarSoft developed by Howard and Hayes to examine the electron density structure. Expanding on the Van De Hulst process of inverting polarized brightness measurements, the program inverts total brightness measurements from SOHO LASCO images to extract electron density information. From the electron density inferred from radio spectra, we derived the location of the CME using five standard electron density to height models (Leblanc, 1996; Saito, 1977; Bougeret, 1984; Alvarez, 1973; and Fainberg, 1971). Using images from the LASCO instrument on SOHO and the SECCHI instrument on STEREO, we extracted locations of the leading edge of the CME and compared the heights and velocities to those found using the frequency data. For the lowest frequency events, we also compared our results to the outputs of ENLIL, a time-dependent, three-dimensional, MHD model of the heliosphere hosted by the Community Coordinated Modeling Center (CCMC) at NASA Goddard Space Flight Center.

  17. Increased hepatic expression of nitric oxide synthase type II in cirrhotic rats

    PubMed Central

    Wang, Hai; Chen, Xiao-Ping; Qiu, Fa-Zu

    2004-01-01

    AIM: To determine the role and effect of nitric oxide synthase type II (NOS II) in cirrhotic rats. METHODS: Expression of NOS II mRNA was detected by real time RT-PCR. The activity of nitric oxide synthase and serum levels of NO, systemic and portal hemodynamics and degrees of cirrhosis were measured with high sensitive methods. Chinese traditional medicine tetrandrine was used to treat cirrhotic rats and to evaluate the function of NO. Double-blind method was applied during the experiment. RESULTS: The concentration of NO and the activity of NOS were increased markedly at all stages of cirrhosis, and iNOSmRNA was greatly expressed. Meanwhile the portal-venous-pressure (PVP), and portal-venous-flow (PVF) were significantly increased. NO, NOS and iNOSmRNA were positively correlated to the quantity of hepatic fibrosis. Tetrandrine significantly inhibited NO production and the expression of iNOSmRNA. CONCLUSION: Increased hepatic expression of NOS II is one of the important causes of hepatic cirrhosis and portal hypertension. PMID:15222038

  18. Redesigning the type II' β-turn in green fluorescent protein to type I': implications for folding kinetics and stability.

    PubMed

    Madan, Bharat; Sokalingam, Sriram; Raghunathan, Govindan; Lee, Sun-Gu

    2014-10-01

    Both Type I' and Type II' β-turns have the same sense of the β-turn twist that is compatible with the β-sheet twist. They occur predominantly in two residue β-hairpins, but the occurrence of Type I' β-turns is two times higher than Type II' β-turns. This suggests that Type I' β-turns may be more stable than Type II' β-turns, and Type I' β-turn sequence and structure can be more favorable for protein folding than Type II' β-turns. Here, we redesigned the native Type II' β-turn in GFP to Type I' β-turn, and investigated its effect on protein folding and stability. The Type I' β-turns were designed based on the statistical analysis of residues in natural Type I' β-turns. The substitution of the native "GD" sequence of i+1 and i+2 residues with Type I' preferred "(N/D)G" sequence motif increased the folding rate by 50% and slightly improved the thermodynamic stability. Despite the enhancement of in vitro refolding kinetics and stability of the redesigned mutants, they showed poor soluble expression level compared to wild type. To overcome this problem, i and i + 3 residues of the designed Type I' β-turn were further engineered. The mutation of Thr to Lys at i + 3 could restore the in vivo soluble expression of the Type I' mutant. This study indicates that Type II' β-turns in natural β-hairpins can be further optimized by converting the sequence to Type I'.

  19. Synthesis, characterization and in vitro anticancer activity of 18-membered octaazamacrocyclic complexes of Co(II), Ni(II), Cd(II) and Sn(II)

    NASA Astrophysics Data System (ADS)

    Kareem, Abdul; Zafar, Hina; Sherwani, Asif; Mohammad, Owais; Khan, Tahir Ali

    2014-10-01

    An effective series of 18 membered octaazamacrocyclic complexes of the type [MLX2], where X = Cl or NO3 have been synthesized by template condensation reaction of oxalyl dihydrazide with dibenzoylmethane and metal salt in 2:2:1 molar ratio. The formation of macrocyclic framework, stereochemistry and their overall geometry have been characterized by various physico-chemical studies viz., elemental analysis, electron spray ionization-mass spectrometry (ESI-MS), I.R, UV-Vis, 1H NMR, 13C NMR spectroscopy, X-ray diffraction (XRD) and TGA/DTA studies. These studies suggest formation of octahedral macrocyclic complexes of Co(II), Ni(II), Cd(II) and Sn(II). The molar conductance values suggest nonelectrolytic nature for all the complexes. Thermogravimatric analysis shows that all the complexes are stable up to 600 °C. All these complexes have been tested against different human cancer cell lines i.e. human hepatocellular carcinoma (Hep3B), human cervical carcinoma (HeLa), human breast adenocarcinoma (MCF7) and normal cells (PBMC). The newly synthesized 18-membered octaazamacrocyclic complexes during in vitro anticancer evaluation, displayed moderate to good cytotoxicity on liver (Hep3B), cervical (HeLa) and breast (MCF7) cancer cell lines, respectively. The most effective anticancer cadmium complex (C34H28N10CdO10) was found to be active with IC50 values, 2.44 ± 1.500, 3.55 ± 1.600 and 4.82 ± 1.400 in micro-molar on liver, cervical and breast cancer cell lines, respectively.

  20. Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes

    PubMed Central

    Matsumoto, Yasuhiko; Ishii, Masaki; Hayashi, Yohei; Miyazaki, Shinya; Sugita, Takuya; Sumiya, Eriko; Sekimizu, Kazuhisa

    2015-01-01

    We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1 h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18 h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes. PMID:26024298

  1. Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes.

    PubMed

    Matsumoto, Yasuhiko; Ishii, Masaki; Hayashi, Yohei; Miyazaki, Shinya; Sugita, Takuya; Sumiya, Eriko; Sekimizu, Kazuhisa

    2015-05-29

    We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1 h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18 h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes.

  2. Lamprey type II collagen and Sox9 reveal an ancient origin of the vertebrate collagenous skeleton.

    PubMed

    Zhang, Guangjun; Miyamoto, Michael M; Cohn, Martin J

    2006-02-28

    Type II collagen is the major cartilage matrix protein in the jawed vertebrate skeleton. Lampreys and hagfishes, by contrast, are thought to have noncollagenous cartilage. This difference in skeletal structure has led to the hypothesis that the vertebrate common ancestor had a noncollagenous skeleton, with type II collagen becoming the predominant cartilage matrix protein after the divergence of jawless fish from the jawed vertebrates approximately 500 million years ago. Here we report that lampreys have two type II collagen (Col2alpha1) genes that are expressed during development of the cartilaginous skeleton. We also demonstrate that the adult lamprey skeleton is rich in Col2alpha1 protein. Furthermore, we have isolated a lamprey orthologue of Sox9, a direct transcriptional regulator of Col2alpha1 in jawed vertebrates, and show that it is coexpressed with both Col2alpha1 genes during skeletal development. These results reveal that the genetic pathway for chondrogenesis in lampreys and gnathostomes is conserved through the activation of cartilage matrix molecules and suggest that a collagenous skeleton evolved surprisingly early in vertebrate evolution.

  3. Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors

    PubMed Central

    Canning, Peter; Ruan, Qui; Schwerd, Tobias; Hrdinka, Matous; Maki, Jenny L.; Saleh, Danish; Suebsuwong, Chalada; Ray, Soumya; Brennan, Paul E.; Cuny, Gregory D.; Uhlig, Holm H.; Gyrd-Hansen, Mads; Degterev, Alexei; Bullock, Alex N.

    2015-01-01

    Summary RIPK2 mediates pro-inflammatory signaling from the bacterial sensors NOD1 and NOD2, and is an emerging therapeutic target in autoimmune and inflammatory diseases. We observed that cellular RIPK2 can be potently inhibited by type II inhibitors that displace the kinase activation segment, whereas ATP-competitive type I inhibition was only poorly effective. The most potent RIPK2 inhibitors were the US Food and Drug Administration-approved drugs ponatinib and regorafenib. Their mechanism of action was independent of NOD2 interaction and involved loss of downstream kinase activation as evidenced by lack of RIPK2 autophosphorylation. Notably, these molecules also blocked RIPK2 ubiquitination and, consequently, inflammatory nuclear factor κB signaling. In monocytes, the inhibitors selectively blocked NOD-dependent tumor necrosis factor production without affecting lipopolysaccharide-dependent pathways. We also determined the first crystal structure of RIPK2 bound to ponatinib, and identified an allosteric site for inhibitor development. These results highlight the potential for type II inhibitors to treat indications of RIPK2 activation as well as inflammation-associated cancers. PMID:26320862

  4. Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors.

    PubMed

    Canning, Peter; Ruan, Qui; Schwerd, Tobias; Hrdinka, Matous; Maki, Jenny L; Saleh, Danish; Suebsuwong, Chalada; Ray, Soumya; Brennan, Paul E; Cuny, Gregory D; Uhlig, Holm H; Gyrd-Hansen, Mads; Degterev, Alexei; Bullock, Alex N

    2015-09-17

    RIPK2 mediates pro-inflammatory signaling from the bacterial sensors NOD1 and NOD2, and is an emerging therapeutic target in autoimmune and inflammatory diseases. We observed that cellular RIPK2 can be potently inhibited by type II inhibitors that displace the kinase activation segment, whereas ATP-competitive type I inhibition was only poorly effective. The most potent RIPK2 inhibitors were the US Food and Drug Administration-approved drugs ponatinib and regorafenib. Their mechanism of action was independent of NOD2 interaction and involved loss of downstream kinase activation as evidenced by lack of RIPK2 autophosphorylation. Notably, these molecules also blocked RIPK2 ubiquitination and, consequently, inflammatory nuclear factor κB signaling. In monocytes, the inhibitors selectively blocked NOD-dependent tumor necrosis factor production without affecting lipopolysaccharide-dependent pathways. We also determined the first crystal structure of RIPK2 bound to ponatinib, and identified an allosteric site for inhibitor development. These results highlight the potential for type II inhibitors to treat indications of RIPK2 activation as well as inflammation-associated cancers.

  5. Higgs potential in the type II seesaw model

    SciTech Connect

    Arhrib, A.; Benbrik, R.; Chabab, M.; Rahili, L.; Ramadan, J.; Moultaka, G.; Peyranere, M. C.

    2011-11-01

    The standard model Higgs sector, extended by one weak gauge triplet of scalar fields with a very small vacuum expectation value, is a very promising setting to account for neutrino masses through the so-called type II seesaw mechanism. In this paper we consider the general renormalizable doublet/triplet Higgs potential of this model. We perform a detailed study of its main dynamical features that depend on five dimensionless couplings and two mass parameters after spontaneous symmetry breaking, and highlight the implications for the Higgs phenomenology. In particular, we determine (i) the complete set of tree-level unitarity constraints on the couplings of the potential and (ii) the exact tree-level boundedness from below constraints on these couplings, valid for all directions. When combined, these constraints delineate precisely the theoretically allowed parameter space domain within our perturbative approximation. Among the seven physical Higgs states of this model, the mass of the lighter (heavier) CP{sub even} state h{sup 0} (H{sup 0}) will always satisfy a theoretical upper (lower) bound that is reached for a critical value {mu}{sub c} of {mu} (the mass parameter controlling triple couplings among the doublet/triplet Higgses). Saturating the unitarity bounds, we find an upper bound m{sub h}{sup 0} or approx. {mu}{sub c} and {mu} < or approx. {mu}{sub c}. In the first regime the Higgs sector is typically very heavy, and only h{sup 0} that becomes SM-like could be accessible to the LHC. In contrast, in the second regime, somewhat overlooked in the literature, most of the Higgs sector is light. In particular, the heaviest state H{sup 0} becomes SM-like, the lighter states being the CP{sub odd} Higgs, the (doubly) charged Higgses, and a decoupled h{sup 0}, possibly

  6. Angiotensin-(1–7) Suppresses Hepatocellular Carcinoma Growth and Angiogenesis via Complex Interactions of Angiotensin II Type 1 Receptor, Angiotensin II Type 2 Receptor and Mas Receptor

    PubMed Central

    Liu, Yanping; Li, Bin; Wang, Ximing; Li, Guishuang; Shang, Rui; Yang, Jianmin; Wang, Jiali; Zhang, Meng; Chen, Yuguo; Zhang, Yun; Zhang, Cheng; Hao, Panpan

    2015-01-01

    We recently confirmed that angiotensin II (Ang II) type 1 receptor (AT1R) was overexpressed in hepatocellular carcinoma tissue using a murine hepatoma model. Angiotensin(Ang)-(1–7) has been found beneficial in ameliorating lung cancer and prostate cancer. Which receptor of Ang-(1–7) is activated to mediate its effects is much speculated. This study was designed to investigate the effects of Ang-(1–7) on hepatocellular carcinoma, as well as the probable mechanisms. H22 hepatoma-bearing mice were randomly divided into five groups for treatment: mock group, low-dose Ang-(1–7), high-dose Ang-(1–7), high-dose Ang-(1–7) + A779 and high-dose Ang-(1–7) + PD123319. Ang-(1–7) treatment inhibited tumor growth time- and dose-dependently by arresting tumor proliferation and promoting tumor apoptosis as well as inhibiting tumor angiogenesis. The effects of Ang-(1–7) on tumor proliferation and apoptosis were reversed by coadministration with A779 or PD123319, whereas the effects on tumor angiogenesis were completely reversed by A779 but not by PD123319. Moreover, Ang-(1–7) downregulated AT1R mRNA, upregulated mRNA levels of Ang II type 2 receptor (AT2R) and Mas receptor (MasR) and p38-MAPK phosphorylation and suppressed H22 cell–endothelial cell communication. Thus, Ang-(1–7) administration suppresses hepatocellular carcinoma via complex interactions of AT1R, AT2R and MasR and may provide a novel and promising approach for the treatment of hepatocellular carcinoma. PMID:26225830

  7. Angiotensin-(1-7) Suppresses Hepatocellular Carcinoma Growth and Angiogenesis via Complex Interactions of Angiotensin II Type 1 Receptor, Angiotensin II Type 2 Receptor and Mas Receptor.

    PubMed

    Liu, Yanping; Li, Bin; Wang, Ximing; Li, Guishuang; Shang, Rui; Yang, Jianmin; Wang, Jiali; Zhang, Meng; Chen, Yuguo; Zhang, Yun; Zhang, Cheng; Hao, Panpan

    2015-07-27

    We recently confirmed that angiotensin II (Ang II) type 1 receptor (AT1R) was overexpressed in hepatocellular carcinoma tissue using a murine hepatoma model. Angiotensin(Ang)-(1-7) has been found beneficial in ameliorating lung cancer and prostate cancer. Which receptor of Ang-(1-7) is activated to mediate its effects is much speculated. This study was designed to investigate the effects of Ang-(1-7) on hepatocellular carcinoma, as well as the probable mechanisms. H22 hepatoma-bearing mice were randomly divided into five groups for treatment: mock group, low-dose Ang-(1-7), high-dose Ang-(1-7), high-dose Ang-(1-7) + A779 and high-dose Ang-(1-7) + PD123319. Ang-(1-7) treatment inhibited tumor growth time- and dose-dependently by arresting tumor proliferation and promoting tumor apoptosis as well as inhibiting tumor angiogenesis. The effects of Ang-(1-7) on tumor proliferation and apoptosis were reversed by coadministration with A779 or PD123319, whereas the effects on tumor angiogenesis were completely reversed by A779 but not by PD123319. Moreover, Ang-(1-7) downregulated AT1R mRNA, upregulated mRNA levels of Ang II type 2 receptor (AT2R) and Mas receptor (MasR) and p38-MAPK phosphorylation and suppressed H22 cell-endothelial cell communication. Thus, Ang-(1-7) administration suppresses hepatocellular carcinoma via complex interactions of AT1R, AT2R and MasR and may provide a novel and promising approach for the treatment of hepatocellular carcinoma.

  8. ADHERENCE AND QUALITY OF LIFE IN PATIENTS WITH TYPE II DIABETES MELLITUS IN NORTHERN GREECE

    PubMed Central

    Zioga, Efrosini; Kazakos, Kyriakos; Dimopoulos, Evagelos; Koutras, Christos; Marmara, Kalliopi; Marmara, Eleni-Efrosini; Marmaras, Athanasios; Lavdaniti, Maria

    2016-01-01

    Introduction: Adherence as a concept includes various types of health-related behavior. Better medical adherence leads to improved disease control and fewer diabetes–related complications. Quality of life and medication adherence are interrelated. Patients with diabetes who adhere to their treatment can experience an improvement in quality of life and vice versa. Aim: To assess treatment adherence in patients with type II diabetes, as well as the connection between adherence and quality of life. Methodology: A descriptive non-experimental study was conducted in a provincial hospital in Northern Greece. The sample examined was a convenience sample consisting of 108 patients with type II diabetes mellitus. They completed the “Diabetes Self-Care Activities Questionnaire” and SF-36 “Quality of Life Questionnaire”. Results: Participants demonstrated good adherence to diet and blood test / blood glucose test routines, but did not experience high levels of quality of life. The type of treatment affected the adherence to blood tests with a statistically significant difference (p=0,000). Also, marital status affected mental health with a statistically significant difference (p=0,032). The adherence sub scales are correlated with the all domains of quality of life. Conclusions: According to our findings, it is important to plan interventions to enhance adherence to other types of treatment and to help patients to further improve their quality of life. PMID:27698597

  9. Introductory Industrial Technology II. Laboratory Activities.

    ERIC Educational Resources Information Center

    Towler, Alan L.

    This guide contains 29 learning modules intended for use by technology teachers and students in grade 8. Each module includes a student laboratory activity and instructor's resource sheet. Each student activity includes the following: activity topic and overview, challenge statement, objectives, vocabulary/concepts reinforced, equipment/supplies,…

  10. 46 CFR 171.070 - Subdivision requirements--Type II.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... have a collision bulkhead. (d) Paragraph (c) of this section applies to a ferry vessel that— (1) Is 150... other main transverse watertight bulkhead; (ii) The collision bulkhead; and (iii) The aftermost point on... transverse watertight bulkhead; (ii) The collision bulkhead; and (iii) The aftermost point on the...

  11. 46 CFR 171.070 - Subdivision requirements--Type II.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... have a collision bulkhead. (d) Paragraph (c) of this section applies to a ferry vessel that— (1) Is 150... other main transverse watertight bulkhead; (ii) The collision bulkhead; and (iii) The aftermost point on... transverse watertight bulkhead; (ii) The collision bulkhead; and (iii) The aftermost point on the...

  12. Phosphatidylinositol 3-kinase, MEK-1 and p38 mediate leptin/interferon-gamma synergistic NOS type II induction in chondrocytes.

    PubMed

    Otero, Miguel; Lago, Rocío; Gómez, Rodolfo; Lago, Francisca; Gomez-Reino, Juan Jesús; Gualillo, Oreste

    2007-10-27

    In a previous study, we established that leptin acts synergistically with interferon-gamma in inducing nitric oxide synthase type II in cultured chondrocytes via Janus kinase-2 activation. However, the exact molecular mechanism that accounts for this synergism is not completely understood. The aim of the present study was to further delineate the signalling pathway used by leptin/interferon-gamma in the nitric oxide synthase type II induction in chondrocytes. Consequently, the roles of PI-3 kinase, MEK1 and p38 kinase were investigated using specific pharmacological inhibitors (Wortmannin, LY 294002, PD 098,059 and SB 203580). For this purpose, the amount of stable nitrite, the end product of NO generation by activated chondrocytes, has been evaluated by Griess colorimetric reaction in culture medium of human primary chondrocytes and in the murine ATDC5 cell line stimulated with leptin (400 nM) and interferon-gamma (1 ng/ml), alone or in combination. Specific inhibitors for PI-3K, MEK1 and p38 were added 1 h before stimulation. Nitric oxide synthase type II mRNA was investigated by real-time RT-PCR and NOS type II protein expression has been evaluated by western blot analysis. Our results showed that, as expected, leptin synergizes with IFN-gamma in inducing NO accumulation in the supernatant of co-stimulated cells. Pre-treatment with Wortmannin, LY 294002, PD 098,059 and SB 203580 caused a significant decrease in nitrite production, NOS type II protein expression and NOS type II mRNA expression induced by leptin and interferon-gamma co-stimulation. These findings were confirmed in 15 and 21-day differentiated ATDC5 cells, and in normal human primary chondrocytes. This is the first report showing that NOS type II induction triggered by co-stimulation with leptin and interferon-gamma is mediated by a signaling pathway involving PI-3K, MEK1 and p38.

  13. Limiting angiotensin II signaling with a cell penetrating peptide mimicking the second intracellular loop of the angiotensin II type I receptor

    PubMed Central

    Yu, Jun; Taylor, Linda; Mierke, Dale; Berg, Eric; Shia, Michael; Fishman, Jordan; Sallum, Christine; Polgar, Peter

    2010-01-01

    A cell-penetrating peptide consisting of the second intracellular loop (IC2) of the Angiotensin II (AngII) type I receptor (AT1) linked to the HIV transactivating regulatory protein (TAT) domain was used to identify the role of this motif for intracellular signal transduction. HEK-293 cells stably transfected with AT1R cDNA and primary cultures of human pulmonary artery smooth muscle cells expressing endogenous AT1 receptor were exposed to the cell-penetrating peptide construct and the effect on angiotensin II signaling determined. The AT1 IC2 peptide effectively inhibited AngII stimulated phosphatidylinositol turnover and calcium influx. It also limited the activation of Akt/PKB as determined by an inhibition of phosphorylation of Akt at Ser473 and completely abolished the AngII dependent activation of the transcriptional factor NFκB. In contrast, the AT1 IC2 peptide had no effect on AngII/AT1 receptor activation of ERK. These results illustrate the potential of using cell penetrating peptides to both delineate receptor-mediated signal transduction as well as to selectively regulate G protein coupled receptor signaling. PMID:20492449

  14. Matrix composition of cartilaginous anlagen in achondrogenesis type II (Langer-Saldino).

    PubMed

    Dertinger, Susanne; Söeder, Stephan; Bösch, Hubert; Aigner, Thomas

    2005-01-01

    Skeletal dysplasias represent in vivo models of genetic defects. Achondrogenesis type II (Langer-Saldino), caused by a genetic defect in the major cartilage matrix protein, collagen type II, is a rare and severe skeletal dysplasia. It comprises a severe derangement of the fetal growth plate cartilage with subsequent ossification defects. In this study, we analyzed the matrix composition and cell differentiation pattern in 3 relatives with achondrogenesis type II. Most strikingly we found a strongly reduced collagen type II and moderately reduced aggrecan proteoglycan content in the dysplastic cartilage matrix. Type II collagen is, at least to some extent, replaced by collagens type I III, and VI. Ultrastructural analysis of the dysplastic cartilage matrix demonstrated a distended rER (rough endoplasmic reticulum), which is typical for this condition and most likely related to improper processing and retention of genetically altered type II collagen. Immunostaining for type IIA and X collagens suggest a severe delay in chondrocyte maturation. Thus, the genetic defect in the present cases leads most likely to a severe retention of collagen type II in the rER and, therefore, a strongly reduced collagen deposition and replacement by other interstitial collagens. However, the latter are less efficient in binding aggrecan proteoglycans in the dysplastic cartilage matrix. Additionally, a delay in chondrocyte maturation appears to be important in achondrogenesis type II.

  15. Investigation of resistive losses in type II superconductors

    NASA Astrophysics Data System (ADS)

    Benapfl, Brendan W.

    For low-TC materials, the superconducting transition temperature (TC) is depressed by the application of a magnetic field. In contrast, one of the remarkable features of cuprate high-TC materials is that the superconducting transition is broadened by the application of a magnetic field. Tinkham presented a model for the field-dependent resistive transition of high-T C materials, arising from "phase slippage at a complicated network of channels." Coffey & Clem did not include this field-broadening effect in their sophisticated model for the field and temperature dependence of the surface resistance in type-II superconductors. From the model by Lee & Stroud, treating Josephson Junction-coupled superconducting segments, it is concluded that doped, layered superconductors are certain to have a field-broadened superconducting transition. This effect can be identified by measurements of the resistivity as a function of temperature, magnetic field strength, angle of field with respect to the crystal axis as well as with respect to an induced current density. The iron pnictide materials such as Ba0.6K0.4Fe2As2 (BaK122) have chemical layers with different compositions, differentiating them from elemental type-II superconductors such as niobium, and also from cuprates, by the absence of copper. Experimental data on BaK122 indicate a field-broadened transition in conjunction with a field-depressed superconducting transition temperature. In this work, techniques associated with Electron Spin Resonance (ESR) spectroscopy were used to measure the temperature and field-induced changes in the surface resistance of single-crystal BaK122 samples. In addition, polycrystalline foils of niobium and a NbTi (70/30) alloy were measured using the same techniques to provide comparison. Measurements were taken as a function of applied magnetic field, temperature, rf field intensity, and angle of the applied field with respect to the rf-induced current. BaK122 sample field-dependent surface

  16. Unusual compactness of a polyproline type II structure

    PubMed Central

    Zagrovic, Bojan; Lipfert, Jan; Sorin, Eric J.; Millett, Ian S.; van Gunsteren, Wilfred F.; Doniach, Sebastian; Pande, Vijay S.

    2005-01-01

    Polyproline type II (PPII) helix has emerged recently as the dominant paradigm for describing the conformation of unfolded polypeptides. However, most experimental observables used to characterize unfolded proteins typically provide only short-range, sequence-local structural information that is both time- and ensemble-averaged, giving limited detail about the long-range structure of the chain. Here, we report a study of a long-range property: the radius of gyration of an alanine-based peptide, Ace-(diaminobutyric acid)2-(Ala)7-(ornithine)2-NH2. This molecule has previously been studied as a model for the unfolded state of proteins under folding conditions and is believed to adopt a PPII fold based on short-range techniques such as NMR and CD. By using synchrotron radiation and small-angle x-ray scattering, we have determined the radius of gyration of this peptide to be 7.4 ± 0.5 Å, which is significantly less than the value expected from an ideal PPII helix in solution (13.1 Å). To further study this contradiction, we have used molecular dynamics simulations using six variants of the AMBER force field and the GROMOS 53A6 force field. However, in all cases, the simulated ensembles underestimate the PPII content while overestimating the experimental radius of gyration. The conformational model that we propose, based on our small angle x-ray scattering results and what is known about this molecule from before, is that of a very flexible, fluctuating structure that on the level of individual residues explores a wide basin around the ideal PPII geometry but is never, or only rarely, in the ideal extended PPII helical conformation. PMID:16085707

  17. Screening of three Usher syndrome type II candidate genes

    SciTech Connect

    Bloemker, B.K.; Swaroop, A.; Kimberling, W.J.

    1994-09-01

    Usher syndrome type II (US2) is an autosomal recessive disorder that results in blindness due to retinitis pigmentosa and congenital hearing loss. The disease affects approximately 1 in 20,000 individuals in the general population and is responsible for over 50% of all cases of deafness with blindness. The underlying US2 defect is unknown. The US2 gene has been localized to the 1q41 region of chromosome 1 by linkage studies. Three genes previously localized to 1q were analyzed to assess their candidacy as the US2 gene. These were evaluated by PCR assays using DNA from a YAC contig spanning the US2 region on chromosome 1. The first gene evaluated was the human choroideremia-like gene (hCHML), which had been mapped to chromosome 1q. The sequence on 1q is a homologue of the human choroideremia gene on chromosome X. Choroideremia is a degenerative disorder causing ocular pathology similar to that observed in US2 patients. Therefore, hCHML is a candidate for the US2 gene. Two cDNAs (A and B) from an enriched human retinal pigment epithelium library have been mapped to 1q41 by in situ hybridization. Both cDNAs are considered good candidates. The hCHML and cDNA A were ruled out as candidates for the US2 gene based on negative results from PCR assays performed on YACs spanning the US2 region. cDNA B could not be ruled out as a candidate for the US2 gene by these assays. Answers to many clinical questions regarding US2 will only be resolved after the gene is identified and characterized. Eventually, understanding the function and expression of the US2 gene will provide a basis for the development of therapy.

  18. Radiation-hydrodynamical modelling of underluminous Type II plateau supernovae

    NASA Astrophysics Data System (ADS)

    Pumo, M. L.; Zampieri, L.; Spiro, S.; Pastorello, A.; Benetti, S.; Cappellaro, E.; Manicò, G.; Turatto, M.

    2017-01-01

    With the aim of improving our knowledge about the nature of the progenitors of low-luminosity Type II plateau supernovae (LL SNe IIP), we made radiation-hydrodynamical models of the well-sampled LL SNe IIP 2003Z, 2008bk and 2009md. For these three SNe, we infer explosion energies of 0.16-0.18 foe, radii at explosion of 1.8-3.5 × 1013 cm and ejected masses of 10-11.3 M⊙. The estimated progenitor mass on the main sequence is in the range ˜13.2-15.1 M⊙ for SN 2003Z and ˜11.4-12.9 M⊙ for SNe 2008bk and 2009md, in agreement with estimates from observations of the progenitors. These results together with those for other LL SNe IIP modelled in the same way enable us also to conduct a comparative study on this SN sub-group. The results suggest that (a) the progenitors of faint SNe IIP are slightly less massive and have less energetic explosions than those of intermediate-luminosity SNe IIP; (b) both faint and intermediate-luminosity SNe IIP originate from low-energy explosions of red (or yellow) supergiant stars of low to intermediate mass; (c) some faint objects may also be explained as electron-capture SNe from massive super-asymptotic giant branch stars; and (d) LL SNe IIP form the underluminous tail of the SNe IIP family, where the main parameter `guiding' the distribution seems to be the ratio of the total explosion energy to the ejected mass. Further hydrodynamical studies should be performed and compared to a more extended sample of LL SNe IIP before drawing any conclusion on the relevance of fall-back to this class of events.

  19. Macrovascular complications in Mexican Americans with type II diabetes.

    PubMed

    Haffner, S M; Mitchell, B D; Stern, M P; Hazuda, H P

    1991-07-01

    Mexican Americans have a threefold greater prevalence of non-insulin-dependent (type II) diabetes mellitus than non-Hispanic whites in the San Antonio Heart Study, a population-based study of diabetes. In addition, Mexican-American diabetic subjects (n = 365) have greater fasting glycemia than non-Hispanic white diabetic subjects (P less than 0.001). Despite these findings, and despite a higher prevalence of microvascular complications among Mexican Americans, there does not appear to be a marked difference in prevalence of macrovascular complications between Mexican-American and non-Hispanic white diabetic subjects. Mexican-American diabetic subjects have only a moderate excess of peripheral vascular disease (as judged by ankle-arm blood pressure ratios) relative to non-Hispanic white diabetic subjects (sex-adjusted Mantel-Haenszel odds ratio 1.84, 95% confidence interval 0.75-4.49). Mexican-American diabetic subjects actually reported fewer myocardial infarctions than non-Hispanic white diabetic subjects (sex-adjusted Mantel-Haenszel odds ratio 0.73, 95% confidence interval 0.31-1.71). Duration was not associated with either peripheral vascular disease or myocardial infarction. Severity of glycemia was only mildly associated with presence of peripheral vascular disease and negatively associated with self-reported myocardial infarction. This latter finding may represent a survival bias in that more severe diabetic subjects have already died and are not ascertained in a prevalence study. The absence of an ethnic difference in the prevalence of macrovascular disease contrasts with our previous reports from the San Antonio Heart Study, in which the prevalence of both retinopathy and proteinuria was observed to be higher in Mexican-American diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Analytic Approximation of Carbon Condensation Issues in Type ii Supernovae

    NASA Astrophysics Data System (ADS)

    Clayton, Donald D.

    2013-01-01

    I present analytic approximations for some issues related to condensation of graphite, TiC, and silicon carbide in oxygen-rich cores of supernovae of Type II. Increased understanding, which mathematical analysis can support, renders researchers more receptive to condensation in O-rich supernova gases. Taking SN 1987A as typical, my first analysis shows why the abundance of CO molecules reaches an early maximum in which free carbon remains more abundant than CO. This analysis clarifies why O-rich gas cannot oxidize C if 56Co radioactivity is as strong as in SN 1987A. My next analysis shows that the CO abundance could be regarded as being in chemical equilibrium if the CO molecule is given an effective binding energy rather than its laboratory dissociation energy. The effective binding energy makes the thermal dissociation rate of CO equal to its radioactive dissociation rate. This preserves possible relevance for the concept of chemical equilibrium. My next analysis shows that the observed abundances of CO and SiO molecules in SN 1987A rule out frequent suggestions that equilibrium condensation of SUNOCONs has occurred following atomic mixing of the He-burning shell with more central zones in such a way as to reproduce roughly the observed spectrum of isotopes in SUNOCONs while preserving C/O > 1. He atoms admixed along with the excess carbon would destroy CO and SiO molecules, leaving their observed abundances unexplained. The final analysis argues that a chemical quasiequilibrium among grains (but not gas) may exist approximately during condensation, so that its computational use is partially justified as a guide to which mineral phases would be stable against reactions with gas. I illustrate this point with quasiequilibrium calculations by Ebel & Grossman that have shown that graphite is stable even when O/C >1 if prominent molecules are justifiably excluded from the calculation of chemical equilibrium.

  1. Identification of Unique Type II Polyketide Synthase Genes in Soil

    PubMed Central

    Wawrik, Boris; Kerkhof, Lee; Zylstra, Gerben J.; Kukor, Jerome J.

    2005-01-01

    Many bacteria, particularly actinomycetes, are known to produce secondary metabolites synthesized by polyketide synthases (PKS). Bacterial polyketides are a particularly rich source of bioactive molecules, many of which are of potential pharmaceutical relevance. To directly access PKS gene diversity from soil, we developed degenerate PCR primers for actinomycete type II KSα (ketosynthase) genes. Twenty-one soil samples were collected from diverse sources in New Jersey, and their bacterial communities were compared by terminal restriction fragment length polymorphism (TRFLP) analysis of PCR products generated using bacterial 16S rRNA gene primers (27F and 1525R) as well as an actinomycete-specific forward primer. The distribution of actinomycetes was highly variable but correlated with the overall bacterial species composition as determined by TRFLP. Two samples were identified to contain a particularly rich and unique actinomycete community based on their TRFLP patterns. The same samples also contained the greatest diversity of KSα genes as determined by TRFLP analysis of KSα PCR products. KSα PCR products from these and three additional samples with interesting TRFLP pattern were cloned, and seven novel clades of KSα genes were identified. Greatest sequence diversity was observed in a sample containing a moderate number of peaks in its KSα TRFLP. The nucleotide sequences were between 74 and 81% identical to known sequences in GenBank. One cluster of sequences was most similar to the KSα involved in ardacin (glycopeptide antibiotic) production by Kibdelosporangium aridum. The remaining sequences showed greatest similarity to the KSα genes in pathways producing the angucycline-derived antibiotics simocyclinone, pradimicin, and jasomycin. PMID:15870305

  2. Targeting GH-1 splicing as a novel pharmacological strategy for growth hormone deficiency type II.

    PubMed

    Miletta, Maria Consolata; Flück, Christa E; Mullis, Primus-E

    2017-01-15

    Isolated growth hormone deficiency type II (IGHD II) is a rare genetic splicing disorder characterized by reduced growth hormone (GH) secretion and short stature. It is mainly caused by autosomal dominant-negative mutations within the growth hormone gene (GH-1) which results in missplicing at the mRNA level and the subsequent loss of exon 3, producing the 17.5-kDa GH isoform: a mutant and inactive GH protein that reduces the stability and the secretion of the 22-kDa GH isoform, the main biologically active GH form. At present, patients suffering from IGHD II are treated with daily injections of recombinant human GH (rhGH) in order to reach normal height. However, this type of replacement therapy, although effective in terms of growth, does not prevent the toxic effects of the 17.5-kDa mutant on the pituitary gland, which may eventually lead to other hormonal deficiencies. As the severity of the disease inversely correlates with the 17.5-kDa/22-kDa ratio, increasing the inclusion of exon 3 is expected to ameliorate disease symptoms. This review focuses on the recent advances in experimental and therapeutic strategies applicable to treat IGHD II in clinical and preclinical contexts. Several avenues for alternative IGHD II therapy will be discussed including the use of small interfering RNA (siRNA) and short hairpin RNA (shRNA) constructs that specifically target the exon 3-deleted transcripts as well as the application of histone deacetylase inhibitors (HDACi) and antisense oligonucleotides (AONs) to enhance full-length GH-1 transcription, correct GH-1 exon 3 splicing and manipulate GH pathway.

  3. Science Activities in Energy: Solar Energy II.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Included in this science activities energy package are 14 activities related to solar energy for secondary students. Each activity is outlined on a single card and is introduced by a question such as: (1) how much solar heat comes from the sun? or (2) how many times do you have to run water through a flat-plate collector to get a 10 degree rise in…

  4. Glutamate-dependent ectodomain shedding of neuregulin-1 type II precursors in rat forebrain neurons

    PubMed Central

    Iwakura, Yuriko; Wang, Ran; Inamura, Naoko; Araki, Kazuaki; Higashiyama, Shigeki; Takei, Nobuyuki; Nawa, Hiroyuki

    2017-01-01

    The neurotrophic factor neuregulin 1 (NRG1) regulates neuronal development, glial differentiation, and excitatory synapse maturation. NRG1 is synthesized as a membrane-anchored precursor and is then liberated by proteolytic processing or exocytosis. Mature NRG1 then binds to its receptors expressed by neighboring neurons or glial cells. However, the molecular mechanisms that govern this process in the nervous system are not defined in detail. Here we prepared neuron-enriched and glia-enriched cultures from embryonic rat neocortex to investigate the role of neurotransmitters that regulate the liberation/release of NRG1 from the membrane of neurons or glial cells. Using a two-site enzyme immunoassay to detect soluble NRG1, we show that, of various neurotransmitters, glutamate was the most potent inducer of NRG1 release in neuron-enriched cultures. NRG1 release in glia-enriched cultures was relatively limited. Furthermore, among glutamate receptor agonists, N-Methyl-D-Aspartate (NMDA) and kainate (KA), but not AMPA or tACPD, mimicked the effects of glutamate. Similar findings were acquired from analysis of the hippocampus of rats with KA-induced seizures. To evaluate the contribution of members of a disintegrin and metalloproteinase (ADAM) families to NRG1 release, we transfected primary cultures of neurons with cDNA vectors encoding NRG1 types I, II, or III precursors, each tagged with the alkaline phosphatase reporter. Analysis of alkaline phosphatase activity revealed that the NRG1 type II precursor was subjected to tumor necrosis factor-α-converting enzyme (TACE) / a Disintegrin And Metalloproteinase 17 (ADAM17) -dependent ectodomain shedding in a protein kinase C-dependent manner. These results suggest that glutamatergic neurotransmission positively regulates the ectodomain shedding of NRG1 type II precursors and liberates the active NRG1 domain in an activity-dependent manner. PMID:28350885

  5. Biophysical Insights into How Spike Threshold Depends on the Rate of Membrane Potential Depolarization in Type I and Type II Neurons

    PubMed Central

    Yi, Guo-Sheng; Wang, Jiang; Tsang, Kai-Ming; Wei, Xi-Le; Deng, Bin

    2015-01-01

    Dynamic spike threshold plays a critical role in neuronal input-output relations. In many neurons, the threshold potential depends on the rate of membrane potential depolarization (dV/dt) preceding a spike. There are two basic classes of neural excitability, i.e., Type I and Type II, according to input-output properties. Although the dynamical and biophysical basis of their spike initiation has been established, the spike threshold dynamic for each cell type has not been well described. Here, we use a biophysical model to investigate how spike threshold depends on dV/dt in two types of neuron. It is observed that Type II spike threshold is more depolarized and more sensitive to dV/dt than Type I. With phase plane analysis, we show that each threshold dynamic arises from the different separatrix and K+ current kinetics. By analyzing subthreshold properties of membrane currents, we find the activation of hyperpolarizing current prior to spike initiation is a major factor that regulates the threshold dynamics. The outward K+ current in Type I neuron does not activate at the perithresholds, which makes its spike threshold insensitive to dV/dt. The Type II K+ current activates prior to spike initiation and there is a large net hyperpolarizing current at the perithresholds, which results in a depolarized threshold as well as a pronounced threshold dynamic. These predictions are further attested in several other functionally equivalent cases of neural excitability. Our study provides a fundamental description about how intrinsic biophysical properties contribute to the threshold dynamics in Type I and Type II neurons, which could decipher their significant functions in neural coding. PMID:26083350

  6. [Extraction, purification and identification of type II collagen from Agkistrodon acutus].

    PubMed

    Gu, Heng-Cun; Hu, Jin-Bo; Ding, Zhi-Shan; Fan, Yong-Sheng; Ding, Xing-Hong

    2013-11-01

    The object of the research was to extract, purify and identify the type II collagen of Agkistrodon acutus. Type II collagen of A. acutus was extracted by enzyme decomposition method, and purified by ion exchange column chromatography. It was characterized by SDS-PAGE gel electrophoresis, ultraviolet spectrophotometry, infrared absorption spectroscopy and mass spectroscopy. The results showed that the size of C II was about 130 kDa. It absorbed at 223 nm. IR spectrum obtained showed that the triple helical domains of amino-acid sequences were characterized by the repetition of triplets Gly-X-Y. The MS spectrum graphically stated that C II extracted from cow and A. acutus have the similar peptides. The C II of A. acutus was obtained by extraction and purification. Appraisal analysis by SDS-PAGE, UV, IR and MS, C II of A. acutus was consistent with the standard C II of cow. It was proved that the extracted protein was C II.

  7. Lipid II-based antimicrobial activity of the lantibiotic plantaricin C.

    PubMed

    Wiedemann, Imke; Böttiger, Tim; Bonelli, Raquel Regina; Schneider, Tanja; Sahl, Hans-Georg; Martínez, Beatriz

    2006-04-01

    We analyzed the mode of action of the lantibiotic plantaricin C (PlnC), produced by Lactobacillus plantarum LL441. Compared to the well-characterized type A lantibiotic nisin and type B lantibiotic mersacidin, which are both able to interact with the cell wall precursor lipid II, PlnC displays structural features of both prototypes. In this regard, we found that lipid II plays a key role in the antimicrobial activity of PlnC besides that of pore formation. The pore forming activity of PlnC in whole cells was prevented by shielding lipid II on the cell surface. However, in contrast to nisin, PlnC was not able to permeabilize Lactococcus lactis cells or to form pores in 1,2-dioleoyl-sn-glycero-3-phosphocholine liposomes supplemented with 0.1 mol% purified lipid II. This emphasized the different requirements of these lantibiotics for pore formation. Using cell wall synthesis assays, we identified PlnC as a potent inhibitor of (i) lipid II synthesis and (ii) the FemX reaction, i.e., the addition of the first Gly to the pentapeptide side chain of lipid II. As revealed by thin-layer chromatography, both reactions were clearly blocked by the formation of a PlnC-lipid I and/or PlnC-lipid II complex. On the basis of the in vivo and in vitro activities of PlnC shown in this study and the structural lipid II binding motifs described for other lantibiotics, the specific interaction of PlnC with lipid II is discussed.

  8. Cervical cancer: is herpes simplex virus type II a cofactor?

    PubMed Central

    Jones, C

    1995-01-01

    In many ways, cervical cancer behaves as a sexually transmitted disease. The major risk factors are multiple sexual partners and early onset of sexual activity. Although high-risk types of human papillomaviruses (HPV) play an important role in the development of nearly all cases of cervical cancer, other sexually transmitted infectious agents may be cofactors. Herpes simplex virus type 2 (HSV-2) is transmitted primarily by sexual contact and therefore has been implicated as a risk factor. Several independent studies suggest that HSV-2 infections correlate with a higher than normal incidence of cervical cancer. In contrast, other epidemiological studies have concluded that infection with HSV-2 is not a major risk factor. Two separate transforming domains have been identified within the HSV-2 genome, but continued viral gene expression apparently is not necessary for neoplastic transformation. HSV infections lead to unscheduled cellular DNA synthesis, chromosomal amplifications, and mutations. These observations suggest that HSV-2 is not a typical DNA tumor virus. It is hypothesized that persistent or abortive infections induce permanent genetic alterations that interfere with differentiation of cervical epithelium and subsequently induce abnormal proliferation. Thus, HSV-2 may be a cofactor in some but not all cases of cervical cancer. PMID:8665469

  9. Unifying Type II Supernova Light Curves with Dense Circumstellar Material

    NASA Astrophysics Data System (ADS)

    Morozova, Viktoriya; Piro, Anthony L.; Valenti, Stefano

    2017-03-01

    A longstanding problem in the study of supernovae (SNe) has been the relationship between the Type IIP and Type IIL subclasses. Whether they come from distinct progenitors or they are from similar stars with some property that smoothly transitions from one class to another has been the subject of much debate. Here, using one-dimensional radiation-hydrodynamic SN models, we show that the multi-band light curves of SNe IIL are well fit by ordinary red supergiants surrounded by dense circumstellar material (CSM). The inferred extent of this material, coupled with a typical wind velocity of ∼ 10{--}100 {km} {{{s}}}-1, suggests enhanced activity by these stars during the last ~months to ∼years of their lives, which may be connected with advanced stages of nuclear burning. Furthermore, we find that, even for more plateau-like SNe, dense CSM provides a better fit to the first ∼ 20 days of their light curves, indicating that the presence of such material may be more widespread than previously appreciated. Here we choose to model the CSM with a wind-like density profile, but it is unclear whether this just generally represents some other mass distribution, such as a recent mass ejection, thick disk, or even inflated envelope material. Better understanding the exact geometry and density distribution of this material will be an important question for future studies.

  10. The Angiotensin II Type 2 Receptor in Brain Functions: An Update

    PubMed Central

    Guimond, Marie-Odile; Gallo-Payet, Nicole

    2012-01-01

    Angiotensin II (Ang II) is the main active product of the renin-angiotensin system (RAS), mediating its action via two major receptors, namely, the Ang II type 1 (AT1) receptor and the type 2 (AT2) receptor. Recent results also implicate several other members of the renin-angiotensin system in various aspects of brain functions. The first aim of this paper is to summarize the current state of knowledge regarding the properties and signaling of the AT2 receptor, its expression in the brain, and its well-established effects. Secondly, we will highlight the potential role of the AT2 receptor in cognitive function, neurological disorders and in the regulation of appetite and the possible link with development of metabolic disorders. The potential utility of novel nonpeptide selective AT2 receptor ligands in clarifying potential roles of this receptor in physiology will also be discussed. If confirmed, these new pharmacological tools should help to improve impaired cognitive performance, not only through its action on brain microcirculation and inflammation, but also through more specific effects on neurons. However, the overall physiological relevance of the AT2 receptor in the brain must also consider the Ang IV/AT4 receptor. PMID:23320146

  11. Bacopa monniera (L.) wettst inhibits type II collagen-induced arthritis in rats.

    PubMed

    Viji, V; Kavitha, S K; Helen, A

    2010-09-01

    Bacopa monniera (L.) Wettst is an Ayurvedic herb with antirheumatic potential. This study investigated the therapeutic efficacy of Bacopa monniera in treating rheumatoid arthritis using a type II collagen-induced arthritis rat model. Arthritis was induced in male Wistar rats by immunization with bovine type II collagen in complete Freund's adjuvant. Bacopa monniera extract (BME) was administered after the development of arthritis from day 14 onwards. The total duration of experiment was 60 days. Paw swelling, arthritic index, inflammatory mediators such as cyclooxygenase, lipoxygenase, myeloperoxidase and serum anti-collagen IgG and IgM levels were analysed in control and experimental rats. Arthritic induction significantly increased paw edema and other classical signs of arthritis coupled to upregulation of inflammatory mediators such as cyclooxygenase, lipoxygenase, neutrophil infiltration and increased anti-collagen IgM and IgG levels in serum. BME significantly inhibited the footpad swelling and arthritic symptoms. BME was effective in inhibiting cyclooxygenase and lipoxygenase activities in arthritic rats. Decreased neutrophil infiltration was evident from decreased myeloperoxidase activity and histopathological data where an improvement in joint architecture was also observed. Serum anti-collagen IgM and IgG levels were consistently decreased. Thus the study demonstrates the potential antiarthritic effect of Bacopa monniera for treating arthritis which might confer its antirheumatic activity.

  12. Cilostazol prevents the degradation of collagen type II in human chondrocytes.

    PubMed

    Wang, Weidong; Kang, Weibiao; Tang, Qiang; Yao, Guanfeng; Chen, Yuchun; Cheng, Bizhen; Kong, Kangmei

    2014-08-29

    The alteration of extracellular matrix (ECM) in cartilage during the pathological development of Osteoarthritis (OA) changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. Healthy cartilage matrix mainly contains collagen type II, which is degraded by matrix metalloproteinase13 (MMP13), an important molecules responsible for joint damage in OA. Cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2-(1H)-quinolinone) is a medication approved by the US Food and Drug Administration and used in the alleviation of the symptom of intermittent claudication in individuals with peripheral vascular disease. In this study, we reported that cilostazol is able to suppress the degradation of type II collagen in human chondrocytes induced by IL-1β. Mechanistically, cilostazol treatment leads to inhibiting the expression of IRF-1, thereby prevents the induction of MMP-13. Signal transducers and activator of transcription 1 (STAT1) has been reported to play an essential role in regulating the activation of IRF-1. Our results indicated that cilostazol suppresses the activation of STAT1 by mitigating the phosphorylation of STAT1 at Ser727 and tyrosine phosphorylation of STAT1 at position 701 (Tyr701).

  13. Comparative therapeutic efficacy and safety of type-II collagen (UC-II), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate.

    PubMed

    Gupta, R C; Canerdy, T D; Lindley, J; Konemann, M; Minniear, J; Carroll, B A; Hendrick, C; Goad, J T; Rohde, K; Doss, R; Bagchi, M; Bagchi, D

    2012-10-01

    The investigation was conducted on client-owned moderately arthritic dogs with two objectives: (i) to evaluate therapeutic efficacy of type-II collagen (UC-II) alone or in combination with glucosamine hydrochloride (GLU) and chondroitin sulphate (CHO), and (ii) to determine their tolerability and safety. Dogs in four groups (n = 7-10), were treated daily for a period of 150 days with placebo (Group-I), 10 mg active UC-II (Group-II), 2000 mg GLU + 1600 mg CHO (Group-III), and UC-II + GLU + CHO (Group-IV). On a monthly basis, dogs were evaluated for observational pain (overall pain, pain upon limb manipulation, and pain after physical exertion) using different numeric scales. Pain level was also measured objectively using piezoelectric sensor-based GFP for peak vertical force and impulse area. Dogs were also examined every month for physical, hepatic (ALP, ALT and bilirubin) and renal (BUN and creatinine) functions. Based on observations, significant (p < 0.05) reduction in pain was noted in Group-II, III, and IV dogs. Using GFP, significant increases in peak vertical force (N/kg body wt) and impulse area (N s/kg body wt), indicative of a decrease in arthritis associated pain, were observed in Group-II dogs only. None of the dogs in any group showed changes in physical, hepatic or renal functions. In conclusion, based on GFP data, moderately arthritic dogs treated with UC-II (10 mg) showed a marked reduction in arthritic pain with maximum improvement by day 150. UC-II, GLU and CHO operate through different mechanisms of action, and were well tolerated over a period of 150 days.

  14. 33 CFR 159.126a - Suspended solids test: Type II devices.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Suspended solids test: Type II... Suspended solids test: Type II devices. During the sewage processing test (§ 159.121) 40 effluent samples... suspended solids in accordance with 40 CFR Part 136. The arithmetic mean of the total suspended solids in...

  15. 33 CFR 159.126a - Suspended solids test: Type II devices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Suspended solids test: Type II... Suspended solids test: Type II devices. During the sewage processing test (§ 159.121) 40 effluent samples... suspended solids in accordance with 40 CFR part 136. The arithmetic mean of the total suspended solids in...

  16. Interband cascade light emitting devices based on type-II quantum wells

    SciTech Connect

    Yang, Rui Q.; Lin, C.H.; Murry, S.J.

    1997-06-01

    The authors discuss physical processes in the newly developed type-II interband cascade light emitting devices, and review their recent progress in the demonstration of the first type-II interband cascade lasers and the observation of interband cascade electroluminescence up to room temperature in a broad mid-infrared wavelength region (extended to 9 {mu}m).

  17. Characteristics of coronal mass ejections associated with solar frontside and backside metric Type II bursts

    NASA Technical Reports Server (NTRS)

    Kahler, S. W.; Cliver, E. W.; Sheeley, N. R.; Howard, R. A.; Michels, D. J.; Koomen, M. J.

    1985-01-01

    Fast velocities of 500 km/s or greater coronal mass ejections (CME's) are compared with reported metric type II bursts to study the properties of CME's associated with coronal shocks. An earlier report of fast frontside CME's with no associated metric type II bursts is confirmed, and it is calculated that 33 + or - 15 percent of all fast frontside CME's are not associated with such bursts. Faster CME's are more likely to be associated with type II bursts, as expected from the hypothesis of piston-driven shocks. However, CME brightness and associated peak 3-cm burst intensity are also important factors, as might be inferred from the Wagner and MacQueen (1983) view of type II shocks decoupled from associated CME's. The equal visibility of solar frontside and backside CME's is used to deduce the observability of backside type II bursts. It is calculated that 23 + or - 7 percent of all backside type II bursts associated with fast CME's can be observed at the earth and that 13 + or - 4 percent of all type II bursts originate in backside flares. CME speed again is the most important factor in the obervability of backside type II bursts.

  18. 46 CFR 171.072 - Calculation of permeability for Type II subdivision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Calculation of permeability for Type II subdivision. 171... permeability for Type II subdivision. When doing calcualtions to show compliance with § 171.070, the following uniform average permeabilities must be assumed: (a) 85 percent in the machinery space. (b) 60 percent...

  19. 46 CFR 171.072 - Calculation of permeability for Type II subdivision.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Calculation of permeability for Type II subdivision. 171... Calculation of permeability for Type II subdivision. When doing calcualtions to show compliance with § 171.070, the following uniform average permeabilities must be assumed: (a) 85 percent in the machinery...

  20. Stimulation of DNA synthesis in cultured rat alveolar type II cells

    SciTech Connect

    Leslie, C.C.; McCormick-Shannon, K.; Robinson, P.C.; Mason, R.J.

    1985-01-01

    Restoration of the alveolar epithelium after injury is thought to be dependent on the proliferation of alveolar type II cells. To understand the factors that may be involved in promoting type II cell proliferation in vivo, we determined the effect of potential mitogens and culture substrata on DNA synthesis in rat alveolar type II cells in primary culture. Type II cells cultured in basal medium containing 10% fetal bovine serum (FBS) exhibited essentially no DNA synthesis. Factors that stimulated /sup 3/H-thymidine incorporation included cholera toxin, epidermal growth factor, and rat serum. The greatest degree of stimulation was achieved by plating type II cells on an extracellular matrix prepared from bovine corneal endothelial cells and then by culturing the pneumocytes in medium containing rat serum, cholera toxin, insulin, and epidermal growth factor. Under conditions of stimulation of /sup 3/H-thymidine incorporation there was an increased DNA content per culture dish but no increase in cell number. The ability of various culture conditions to promote DNA synthesis in type II cells was verified by autoradiography. Type II cells were identified by the presence of cytoplasmic inclusions, which were visualized by tannic acid staining before autoradiography. These results demonstrate the importance of soluble factors and culture substratum in stimulating DNA synthesis in rat alveolar type II cells in primary culture.

  1. The mitochondrial type II peroxiredoxin F is essential for redox homeostasis and root growth of Arabidopsis thaliana under stress.

    PubMed

    Finkemeier, Iris; Goodman, Megan; Lamkemeyer, Petra; Kandlbinder, Andrea; Sweetlove, Lee J; Dietz, Karl-Josef

    2005-04-01

    Peroxiredoxins (Prx) have recently moved into the focus of plant and animal research in the context of development, adaptation, and disease, as they function both in antioxidant defense by reducing a broad range of toxic peroxides and in redox signaling relating to the adjustment of cell redox and antioxidant metabolism. At-PrxII F is one of six type II Prx identified in the genome of Arabidopsis thaliana and the only Prx that is targeted to the plant mitochondrion. Therefore, it might be assumed to have functions similar to the human 2-Cys Prx (PRDX3) and type II Prx (PRDX5) and yeast 1-Cys Prx that likewise have mitochondrial localizations. This paper presents a characterization of PrxII F at the level of subcellular distribution, activity, and reductive regeneration by mitochondrial thioredoxin and glutaredoxin. By employing tDNA insertion mutants of A. thaliana lacking expression of AtprxII F (KO-AtPrxII F), it is shown that under optimal environmental conditions the absence of PrxII F is almost fully compensated for, possibly by increases in activity of mitochondrial ascorbate peroxidase and glutathione-dependent peroxidase. However, a stronger inhibition of root growth in KO-AtPrxII F seedlings as compared with wild type is observed under stress conditions induced by CdCl2 as well as after administration of salicylhydroxamic acid, an inhibitor of cyanide-insensitive respiration. Simultaneously, major changes in the abundance of both nuclear and mitochondria-encoded transcripts were observed. These results assign a principal role to PrxII F in antioxidant defense and possibly redox signaling in plants cells.

  2. Nucleosynthesis in the accretion disks of Type II collapsars

    NASA Astrophysics Data System (ADS)

    Banerjee, Indrani; Mukhopadhyay, Banibrata

    2013-09-01

    We investigate nucleosynthesis inside the gamma-ray burst (GRB) accretion disks formed by the Type II collapsars. In these collapsars, the core collapse of massive stars first leads to the formation of a proto-neutron star. After that, an outward moving shock triggers a successful supernova. However, the supernova ejecta lacks momentum and within a few seconds the newly formed neutron star gets transformed to a stellar mass black hole via massive fallback. The hydrodynamics of such an accretion disk formed from the fallback material of the supernova ejecta has been studied extensively in the past. We use these well-established hydrodynamic models for our accretion disk in order to understand nucleosynthesis, which is mainly advection dominated in the outer regions. Neutrino cooling becomes important in the inner disk where the temperature and density are higher. The higher the accretion rate (dot M) is, the higher the density and temperature are in the disks. We deal with accretion disks with relatively low accretion rates: 0.001 Msolar s-1 ≲ dot M ≲ 0.01 Msolar s-1 and hence these disks are predominantly advection dominated. We use He-rich and Sirich abundances as the initial condition of nucleosynthesis at the outer disk, and being equipped with the disk hydrodynamics and the nuclear network code, we study the abundance evolution as matter inflows and falls into the central object. We investigate the variation in the nucleosynthesis products in the disk with the change in the initial abundance at the outer disk and also with the change in the mass accretion rate. We report the synthesis of several unusual nuclei like 31P, 39K, 43Sc, 35Cl and various isotopes of titanium, vanadium, chromium, manganese and copper. We also confirm that isotopes of iron, cobalt, nickel, argon, calcium, sulphur and silicon get synthesized in the disk, as shown by previous authors. Much of these heavy elements thus synthesized are ejected from the disk via outflows and hence they

  3. Type II SOCS as a feedback repressor for GH-induced Igf1 expression in carp hepatocytes.

    PubMed

    Jiang, Xue; Xiao, Jia; He, Mulan; Ma, Ani; Wong, Anderson O L

    2016-05-01

    Type II suppressor of cytokine signaling (SOCS) serve as feedback repressors for cytokines and are known to inhibit growth hormone (GH) actions. However, direct evidence for SOCS modulation of GH-induced insulin-like growth factor 1 (Igf1) expression is lacking, and the post-receptor signaling for SOCS expression at the hepatic level is still unclear. To shed light on the comparative aspects of SOCS in GH functions, grass carp was used as a model to study the role of type II SOCS in GH-induced Igf1 expression. Structural identity of type II SOCS, Socs1-3 and cytokine-inducible SH2-containing protein (Cish), was established in grass carp by 5'/3'-RACE, and their expression at both transcript and protein levels were confirmed in the liver by RT-PCR and LC/MS/MS respectively. In carp hepatocytes, GH treatment induced rapid phosphorylation of JAK2, STATs, MAPK, PI3K, and protein kinase B (Akt) with parallel rises in socs1-3 and cish mRNA levels, and these stimulatory effects on type II SOCS were shown to occur before the gradual loss of igf1 gene expression caused by prolonged exposure of GH. Furthermore, GH-induced type II SOCS gene expression could be negated by inhibiting JAK2, STATs, MEK1/2, P38 (MAPK), PI3K, and/or Akt respectively. In CHO cells transfected with carp GH receptor, over-expression of these newly cloned type II SOCS not only suppressed JAK2/STAT5 signaling with GH treatment but also inhibited GH-induced grass carp Igf1 promoter activity. These results, taken together, suggest that type II SOCS could be induced by GH in the carp liver via JAK2/STATs, MAPK, and PI3K/Akt cascades and serve as feedback repressors for GH signaling and induction of igf1 gene expression.

  4. Investigation of the Geoeffectiveness of CMEs Associated with IP Type II Radio Bursts

    NASA Astrophysics Data System (ADS)

    Vasanth, V.; Chen, Y.; Kong, X. L.; Wang, B.

    2015-06-01

    We perform a statistical analysis of the geoeffectiveness of coronal mass ejections (CMEs) that are associated with interplanetary (IP) type II bursts in Solar Cycle 23 during the period 1997 - 2008. About 47 % (109 out of 232) of IP type II bursts are found to be associated with geomagnetic storms. Of these 47 %, 27 % are associated with moderate, 14 % with intense, and 6 % with severe geomagnetic storms. We find that the IP type II bursts and their corresponding end frequencies can be used as indicators of CME geoeffectiveness: the lower the type II burst end frequency, the higher the possibility of having a stronger storm. In addition, we show that various combinations of CME remote-sensing and IP type II parameters can be used to improve geomagnetic storm forecasting.

  5. Organotypic culture of fetal lung type II alveolar epithelial cells: applications to pulmonary toxicology.

    PubMed Central

    Shami, S G; Aghajanian, J D; Sanders, R L

    1984-01-01

    Techniques for isolation and culture of fetal Type II alveolar epithelial cells, as well as the morphologic and biochemical characteristics of these histotypic cultures, are described. Type II alveolar epithelial cells can be isolated from fetal rat lungs and grown in an organotypic culture system as described in this review. The fetal Type II cells resemble differentiated rat Type II cells in morphology, biochemistry, and karyotype as they grow in culture for up to 5 weeks. The cells of the mature organotypic cultures form alveolarlike structures while growing on a gelatin sponge matrix. The Type II cells also synthesize and secrete pulmonary surfactant similar in biochemical composition to that produced in vivo. This system has been used to study the effects of hormones on surfactant production and composition. The organotypic model has many potential applications to the study of pulmonary toxicology. Images FIGURE 1. FIGURE 2. PMID:6548184

  6. Treatment of Type II Endoleaks After Endovascular Repair of Abdominal Aortic Aneurysms: Transcaval Approach

    SciTech Connect

    Mansueto, Giancarlo Cenzi, Daniela; D'Onofrio, Mirko; Petrella, Enrico; Gumbs, Andrew A.; Mucelli, Roberto Pozzi

    2005-06-15

    The purpose of the note is to describe a new technique for type II endoleak treatment, using an alternative approach through femoral venous access. Three patients who developed type II endoleak after endovascular repair of abdominal aortic aneurysm were treated with direct transcaval puncture and embolization inside the aneurysm sac. The detailed technique is described. All patients were treated without any complications and discharged 48 hours after the treatment. At 1 month follow-up the computed tomograph scan did not show a recurrence of a type II endoleak. The management of patients with type II endoleak is a controversial issue and different techniques have been proposed. We suggest an alternative technique for type II endoleak treatment. The feasibility and the advantages of this approach can offer new possibilities for the diagnosis as well as for the treatment of this complication.

  7. Aldosterone-induced brain MAPK signaling and sympathetic excitation are angiotensin II type-1 receptor dependent.

    PubMed

    Zhang, Zhi-Hua; Yu, Yang; Wei, Shun-Guang; Felder, Robert B

    2012-02-01

    Angiotensin II (ANG II)-induced mitogen-activated protein kinase (MAPK) signaling upregulates angiotensin II type-1 receptors (AT(1)R) in hypothalamic paraventricular nucleus (PVN) and contributes to AT(1)R-mediated sympathetic excitation in heart failure. Aldosterone has similar effects to increase AT(1)R expression in the PVN and sympathetic drive. The present study was undertaken to determine whether aldosterone also activates the sympathetic nervous system via MAPK signaling and, if so, whether its effect is independent of ANG II and AT(1)R. In anesthetized rats, a 4-h intravenous infusion of aldosterone induced increases (P < 0.05) in phosphorylated (p-) p44/42 MAPK in PVN, PVN neuronal excitation, renal sympathetic nerve activity (RSNA), mean blood pressure (MBP), and heart rate (HR). Intracerebroventricular or bilateral PVN microinjection of the p44/42 MAPK inhibitor PD-98059 reduced the aldosterone-induced RSNA, HR, and MBP responses. Intracerebroventricular pretreatment (5 days earlier) with pooled small interfering RNAs targeting p44/42 MAPK reduced total and p-p44/42 MAPK, aldosterone-induced c-Fos expression in the PVN, and the aldosterone-induced increases in RSNA, HR, and MBP. Intracerebroventricular infusion of either the mineralocorticoid receptor antagonist RU-28318 or the AT(1)R antagonist losartan blocked aldosterone-induced phosphorylation of p44/42 MAPK and prevented the increases in RSNA, HR, and MBP. These data suggest that aldosterone-induced sympathetic excitation depends upon that AT(1)R-induced MAPK signaling in the brain. The short time course of this interaction suggests a nongenomic mechanism, perhaps via an aldosterone-induced transactivation of the AT(1)R as described in peripheral tissues.

  8. Mg II Spectral Atlas and Flux Catalog for Late-Type Stars in the Hyades Cluster

    NASA Technical Reports Server (NTRS)

    Simon, Theodore

    2001-01-01

    In the course of a long-running IUE Guest Observer program, UV spectral images were obtained for more than 60 late-type members of the Hyades Cluster in order to investigate their chromospheric emissions. The emission line fluxes extracted from those observations were used to study the dependence of stellar dynamo activity upon age and rotation (IUE Observations of Rapidly Rotating Low-Mass Stars in Young Clusters: The Relation between Chromospheric Activity and Rotation). However, the details of those measurements, including a tabulation of the line fluxes, were never published. The purpose of the investigation summarized here was to extract all of the existing Hyades long-wavelength Mg II spectra in the IUE public archives in order to survey UV chromospheric emission in the cluster, thereby providing a consistent dataset for statistical and correlative studies of the relationship between stellar dynamo activity, rotation, and age over a broad range in mass.

  9. Pressor responsiveness to angiotensin II in female mice is enhanced with age: role of the angiotensin type 2 receptor

    PubMed Central

    2014-01-01

    Background The pressor response to angiotensin II (AngII) is attenuated in adult females as compared to males via an angiotensin type 2 receptor (AT2R)-dependent pathway. We hypothesized that adult female mice are protected against AngII-induced hypertension via an enhanced AT2R-mediated pathway and that in reproductively senescent females this pathway is no longer operative. Methods Mean arterial pressure was measured via telemetry in 4-month-old (adult) and 16-month-old (aged) and aged ovariectomized (aged-OVX) wild-type and AT2R knockout (AT2R-KO) female mice during baseline and 14-day infusion of vehicle (saline) or AngII (600 ng/kg/min s.c.). Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to determine renal gene expression of angiotensin receptors and angiotensin-converting enzyme 2 in response to 14-day treatment with vehicle or AngII. Results Basal mean arterial pressure was similar between the groups. The pressor response to AngII was augmented in adult AT2R-KO compared to adult wild-type mice (29 ± 3 mmHg versus 10 ± 4 mmHg, respectively, on day 14 as compared to basal mean arterial pressure, P = 0.002). In wild-type mice, pressor responsiveness to AngII was augmented with age, such that the pressor response to AngII was similar between aged AT2R-KO and wild-type female mice (31 ± 4 mmHg versus 34 ± 3 mmHg, respectively, on day 14, P = 0.9). There were no significant differences in pressor responsiveness to AngII between aged and aged-OVX mice. Vehicle-treated aged wild-type mice had a lower renal AT2R/AT1R balance as compared to adult counterparts. In response to AngII, the renal AT2R/AT1R balance in aged wild-type females was greater than that observed in vehicle-treated aged wild-type females and adult wild-type females, yet the protective effects of AT2R activation were not restored. Conclusions The protective role of the AT2R depressor pathway is lost with age in female mice. Therefore

  10. The optical flares of active star II Pegasi in 2005

    NASA Astrophysics Data System (ADS)

    Gu, Shenghong; Kim, Kang Min; Lee, Byeong-Cheol

    2015-08-01

    We observed the active star II Peg using high-resolution spectrographs of 2.16m telescope at Xinglong station of NAOC and 1.8m telescope at BOAO of KASI from November to December, 2005. By means of spectral subtraction technique, the chromospheric activities of II Peg are analyzed at several activity indicators, including CaII IRT, Hα, NaI D1D2 and HeI D3 lines. The results demonstrate that the magnetic activity of II Peg is very strong, and its chromospheric activities show rotational modulations which imply there are active regions in its chromosphere. Two flare events were hunted during the observations, which were identified by HeI D3 line emission above the continuum. The first flare was happened in November 2005, the second one in December 2005, and they were located in different hemisphere of the star. This may indicate the evolution of active regions. Considering the photospheric spot activities, the possible origin of the detected flares is discussed.

  11. Workjobs II: Number Activities for Early Childhood.

    ERIC Educational Resources Information Center

    Baratta-Lorton, Mary

    This curriculum guide presents a program of 20 open-ended math activities to be used to supplement the math programs in kindergarten, first, or second grade classrooms. The program consists of child-oriented counters and gameboards used to explore the concept of number from counting to making up and solving addition and subtraction equations. Each…

  12. Diverse effects of type II collagen on osteogenic and adipogenic differentiation of mesenchymal stem cells.

    PubMed

    Chiu, Li-Hsuan; Yeh, Tien-Shun; Huang, Huei-Mei; Leu, Sy-Jye; Yang, Charng-Bin; Tsai, Yu-Hui

    2012-06-01

    Type II collagen is known to modulate chondrogenesis of mesenchymal stem cells (MSCs). In this study, MSCs from human bone marrow aspirates were used to study the modulating effects of type II collagen on MSC differentiation during the early stages of osteogenesis and adipogenesis. With osteogenic induction, MSCs cultured on the type II collagen-coated surface showed an enhanced calcium deposition level with increasing mRNA expressions of RUNX2, osteocalcin, and alkaline phosphatase. A synthetic integrin binding peptide, which specifically interacts with the I-domain of α(1)β(1)/α(2)β(1) integrins significantly blocks the mineralization-enhancing effect of type II collagen. MSCs attached on the type II collagen-coated plates exhibited expanded cell morphology with increasing spreading area, and the pretreatment of cells with integrin α(1)β(1) or α(2)β(1)-blocking antibody reduced the effect. The phosphorylation levels of FAK, ERK, and JNK significantly increased in the MSCs that attached on the type II collagen-coated plates. On the contrary, the mineralization-enhancing effect of type II collagen was diminished by JNK and MEK inhibitors. Furthermore, type II collagen blocked the adipogenic differentiation of MSCs, and this effect is rescued by JNK and MEK inhibitors. In conclusion, type II collagen facilitates osteogenesis and suppresses adipogenesis during early stage MSC differentiation. Such effects are integrin binding-mediated and conducted through FAK-JNK and/or FAK-ERK signaling cascades. These results inspire a novel strategy encompassing type II collagen in bone tissue engineering.

  13. Psychosocial stress inhibits amplitude of gonadotropin-releasing hormone pulses independent of cortisol action on the type II glucocorticoid receptor.

    PubMed

    Wagenmaker, Elizabeth R; Breen, Kellie M; Oakley, Amy E; Tilbrook, Alan J; Karsch, Fred J

    2009-02-01

    Our laboratory has developed a paradigm of psychosocial stress (sequential layering of isolation, blindfold, and predator cues) that robustly elevates cortisol secretion and decreases LH pulse amplitude in ovariectomized ewes. This decrease in LH pulse amplitude is due, at least in part, to a reduction in pituitary responsiveness to GnRH, caused by cortisol acting via the type II glucocorticoid receptor (GR). The first experiment of the current study aimed to determine whether this layered psychosocial stress also inhibits pulsatile GnRH release into pituitary portal blood. The stress paradigm significantly reduced GnRH pulse amplitude compared with nonstressed ovariectomized ewes. The second experiment tested if this stress-induced decrease in GnRH pulse amplitude is mediated by cortisol action on the type II GR. Ovariectomized ewes were allocated to three groups: nonstress control, stress, and stress plus the type II GR antagonist RU486. The layered psychosocial stress paradigm decreased GnRH and LH pulse amplitude compared with nonstress controls. Importantly, the stress also lowered GnRH pulse amplitude to a comparable extent in ewes in which cortisol action via the type II GR was antagonized. Therefore, we conclude that psychosocial stress reduces the amplitude of GnRH pulses independent of cortisol action on the type II GR. The present findings, combined with our recent observations, suggest that the mechanisms by which psychosocial stress inhibits reproductive neuroendocrine activity at the hypothalamic and pituitary levels are fundamentally different.

  14. The effect of vascular endothelial growth factor on aggrecan and type II collagen expression in rat articular chondrocytes.

    PubMed

    Chen, Xuan-Yin; Hao, Ya-Rong; Wang, Zhe; Zhou, Jian-Lin; Jia, Qi-Xue; Qiu, Bo

    2012-11-01

    The expression of vascular endothelial growth factor (VEGF) directly correlates with the Mankin score and the degree of cartilage destruction. The biological activity of VEGF on articular cartilage remains unknown, so this study was performed to investigate the effect of VEGF on aggrecan and type II collagen expression in vitro. We carried out this study at the Center Laboratory of Renmin Hospital at Wuhan University. Rat articular chondrocytes were cultured in a monolayer. Then, the experiment was divided into 4 groups: group A (control group), without any disposal; group B, treated with 10 ng/ml VEGF; group C, treated with 10 ng/ml IL-1β; and group D, treated with 10 ng/ml VEGF + 10 ng/ml IL-1β. After 48 h, messenger RNA (mRNA) expression of aggrecan and type II collagen was evaluated by real-time polymerase chain reaction (real-Time PCR), and protein expression of aggrecan and type II collagen was detected by Western blotting. VEGF was found to significantly inhibit the expression of aggrecan and type II collagen at the gene and protein levels. These findings suggest that VEGF may result in degeneration of articular cartilage by inhibiting the synthesis and expression of aggrecan and type II collagen.

  15. Regional differences of type II collagen synthesis in the human temporomandibular joint disc: immunolocalization study of carboxy-terminal type II procollagen peptide (chondrocalcin).

    PubMed

    Kondoh, Toshirou; Hamada, Yoshiki; Iino, Mitsuyoshi; Takahashi, Tetsu; Kikuchi, Toshiyuki; Fujikawa, Kyousuke; Seto, Kannichi

    2003-09-01

    The purpose of this study was to determine the regional differences of distribution of the carboxy-terminal type II procollagen peptide (pCOL-II-C; chondrocalcin) as markers of cartilaginous expression in the human temporomandibular joint (TMJ) disc. Twelve human TMJ discs without morphologic abnormalities were obtained from 12 fresh cadavers. All specimens were analysed for pCOL-II-C expression using polyclonal rabbit anti-human pCOL-II-C antibody in avidin-biotin-peroxidase complex staining. The results were demonstrated that the percentage of pCOL-II-C immunoreactive disc cells was significantly higher in the outer part (the articular surfaces) than in the inner part (the deep central areas) of the disc. These findings suggest that the tissue heterogeneity of cartilaginous expression reflects the functional demands of the remodelling process in the human TMJ disc.

  16. PREDICTION OF TYPE II SOLAR RADIO BURSTS BY THREE-DIMENSIONAL MHD CORONAL MASS EJECTION AND KINETIC RADIO EMISSION SIMULATIONS

    SciTech Connect

    Schmidt, J. M.; Cairns, Iver H.; Hillan, D. S.

    2013-08-20

    Type II solar radio bursts are the primary radio emissions generated by shocks and they are linked with impending space weather events at Earth. We simulate type II bursts by combining elaborate three-dimensional MHD simulations of realistic coronal mass ejections (CMEs) at the Sun with an analytic kinetic radiation theory developed recently. The modeling includes initialization with solar magnetic and active region fields reconstructed from magnetograms of the Sun, a flux rope of the initial CME dimensioned with STEREO spacecraft observations, and a solar wind driven with averaged empirical data. We demonstrate impressive accuracy in time, frequency, and intensity for the CME and type II burst observed on 2011 February 15. This implies real understanding of the physical processes involved regarding the radio emission excitation by shocks and supports the near-term development of a capability to predict and track these events for space weather prediction.

  17. p120-Catenin Expressed in Alveolar Type II Cells Is Essential for the Regulation of Lung Innate Immune Response

    PubMed Central

    Chignalia, Andreia Z.; Vogel, Stephen M.; Reynolds, Albert B.; Mehta, Dolly; Dull, Randal O.; Minshall, Richard D.; Malik, Asrar B.; Liu, Yuru

    2016-01-01

    The integrity of the lung alveolar epithelial barrier is required for the gas exchange and is important for immune regulation. Alveolar epithelial barrier is composed of flat type I cells, which make up approximately 95% of the gas-exchange surface, and cuboidal type II cells, which secrete surfactants and modulate lung immunity. p120-catenin (p120; gene symbol CTNND1) is an important component of adherens junctions of epithelial cells; however, its function in lung alveolar epithelial barrier has not been addressed in genetic models. Here, we created an inducible type II cell–specific p120-knockout mouse (p120EKO). The mutant lungs showed chronic inflammation, and the alveolar epithelial barrier was leaky to 125I-albumin tracer compared to wild type. The mutant lungs also demonstrated marked infiltration of inflammatory cells and activation of NF-κB. Intracellular adhesion molecule 1, Toll-like receptor 4, and macrophage inflammatory protein 2 were all up-regulated. p120EKO lungs showed increased expression of the surfactant proteins Sp-B, Sp-C, and Sp-D, and displayed severe inflammation after pneumonia caused by Pseudomonas aeruginosa compared with wild type. In p120-deficient type II cell monolayers, we observed reduced transepithelial resistance compared to control, consistent with formation of defective adherens junctions. Thus, although type II cells constitute only 5% of the alveolar surface area, p120 expressed in these cells plays a critical role in regulating the innate immunity of the entire lung. PMID:25773174

  18. A kinetic model for type I and II IP3R accounting for mode changes.

    PubMed

    Siekmann, Ivo; Wagner, Larry E; Yule, David; Crampin, Edmund J; Sneyd, James

    2012-08-22

    Based upon an extensive single-channel data set, a Markov model for types I and II inositol trisphosphate receptors (IP(3)R) is developed. The model aims to represent accurately the kinetics of both receptor types of IP(3)R depending on the concentrations of inositol trisphosphate (IP(3)), adenosine trisphosphate (ATP), and intracellular calcium (Ca(2+)). In particular, the model takes into account that for some combinations of ligands the IP(3)R switches between extended pe