Angiotensin II induces tumor necrosis factor biosynthesis in the adult mammalian heart through a protein kinase C-dependent pathway.

PubMed

Kalra, Dinesh; Sivasubramanian, Natarajan; Mann, Douglas L

2002-05-07

Previous studies suggest that angiotensin II (Ang II) upregulates the expression of tumor necrosis factor (TNF) in nonmyocyte cell types; however, the effect of Ang II on TNF expression in the adult mammalian heart is not known. To determine whether Ang II was sufficient to provoke TNF biosynthesis in the adult heart, we examined the effects of Ang II in isolated buffer-perfused Langendorff feline hearts. Ang II (10(-7) mol/L) treatment resulted in a time- and dose-dependent increase in myocardial TNF mRNA and protein biosynthesis in the heart as well as in cultured adult cardiac myocytes. The effects of Ang II on myocardial TNF mRNA and protein synthesis were mediated through the angiotensin type 1 receptor (AT1R), insofar as an AT1R antagonist (AT1a) blocked the effects of Ang II, whereas an angiotensin type 2 receptor (AT2R) antagonist (AT2a) had no effect. Stimulation with Ang II led to the activation of nuclear factor-kappaB and activator protein-1 (AP-1), two transcription factors that are important for TNF gene expression. Nuclear factor-kappaB activation was accompanied by phosphorylation of IkappaBalpha on serine 32 as well as degradation of IkappaBalpha, suggesting that the effects of Ang II were mediated through an IkappaBalpha-dependent pathway. The important role of protein kinase C (PKC) was suggested by studies in which a phorbol ester triggered TNF biosynthesis, and a PKC inhibitor abrogated Ang II-induced TNF biosynthesis. These studies suggest that Ang II provokes TNF biosynthesis in the adult mammalian heart through a PKC-dependent pathway.

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

EFFECT OF GROWTH FACTOR-FIBRONECTIN MATRIX INTERACTION ON RAT TYPE II CELL ADHESION AND DNA SYTHESIS

EPA Science Inventory

ABSTRACT

Type II cells attach, migrate and proliferate on a provisional fibronectin-rich matrix during alveolar wall repair after lung injury. The combination of cell-substratum interactions via integrin receptors and exposure to local growth factors are likely to initiat...

Identification of type II and type III pyoverdine receptors from Pseudomonas aeruginosa.

PubMed

de Chial, Magaly; Ghysels, Bart; Beatson, Scott A; Geoffroy, Valérie; Meyer, Jean Marie; Pattery, Theresa; Baysse, Christine; Chablain, Patrice; Parsons, Yasmin N; Winstanley, Craig; Cordwell, Stuart J; Cornelis, Pierre

2003-04-01

Pseudomonas aeruginosa produces, under conditions of iron limitation, a high-affinity siderophore, pyoverdine (PVD), which is recognized at the level of the outer membrane by a specific TonB-dependent receptor, FpvA. So far, for P. aeruginosa, three different PVDs, differing in their peptide chain, have been described (types I-III), but only the FpvA receptor for type I is known. Two PVD-producing P. aeruginosa strains, one type II and one type III, were mutagenized by a mini-TnphoA3 transposon. In each case, one mutant unable to grow in the presence of the strong iron chelator ethylenediaminedihydroxyphenylacetic acid (EDDHA) and the cognate PVD was selected. The first mutant, which had an insertion in the pvdE gene, upstream of fpvA, was unable to take up type II PVD and showed resistance to pyocin S3, which is known to use type II FpvA as receptor. The second mutant was unable to take up type III PVD and had the transposon insertion in fpvA. Cosmid libraries of the respective type II and type III PVD wild-type strains were constructed and screened for clones restoring the capacity to grow in the presence of PVD. From the respective complementing genomic fragments, type II and type III fpvA sequences were determined. When in trans, type II and type III fpvA restored PVD production, uptake, growth in the presence of EDDHA and, in the case of type II fpvA, pyocin S3 sensitivity. Complementation of fpvA mutants obtained by allelic exchange was achieved by the presence of cognate fpvA in trans. All three receptors posses an N-terminal extension of about 70 amino acids, similar to FecA of Escherichia coli, but only FpvAI has a TAT export sequence at its N-terminal end.

The growth hormone-insulin-like growth factor axis in glycogen storage disease type 1: evidence of different growth patterns and insulin-like growth factor levels in patients with glycogen storage disease type 1a and 1b.

PubMed

Melis, Daniela; Pivonello, Rosario; Parenti, Giancarlo; Della Casa, Roberto; Salerno, Mariacarolina; Balivo, Francesca; Piccolo, Pasquale; Di Somma, Carolina; Colao, Annamaria; Andria, Generoso

2010-04-01

To investigate the growth hormone (GH)-insulin-like growth factor (IGF) system in patients with glycogen storage disease type 1 (GSD1). This was a prospective, case-control study. Ten patients with GSD1a and 7 patients with GSD1b who were given dietary treatment and 34 sex-, age-, body mass index-, and pubertal stage-matched control subjects entered the study. Auxological parameters were correlated with circulating GH, either at basal or after growth hormone releasing hormone plus arginine test, insulin-like growth factors (IGF-I and IGF-II), and anti-pituitary antibodies (APA). Short stature was detected in 10.0% of patients with GSD1a, 42.9% of patients with GSD1b (P = .02), and none of the control subjects. Serum IGF-I levels were lower in patients with GSD1b (P = .0001). An impaired GH secretion was found in 40% of patients with GSD1a (P = .008), 57.1% of patients with GSD1b (P = .006), and none of the control subjects. Short stature was demonstrated in 3 of 4 patients with GSD1b and GH deficiency. The prevalence of APA was significantly higher in patients with GSD1b than in patients with GSD1a (P = .02) and control subjects (P = .03). The GH response to the provocative test inversely correlated with the presence of APA (P = .003). Compared with levels in control subjects, serum IGF-II and insulin levels were higher in both groups of patients, in whom IGF-II levels directly correlated with height SD scores (P = .003). Patients with GSD1a have an impaired GH secretion associated with reference range serum IGF-I levels and normal stature, whereas in patients with GSD1b, the impaired GH secretion, probably because of the presence of APA, was associated with reduced IGF-I levels and increased prevalence of short stature. The increased IGF-II levels, probably caused by increased insulin levels, in patients with GSD1 are presumably responsible for the improved growth pattern observed in patients receiving strict dietary treatment. Copyright 2010 Mosby, Inc. All

Demonstration of a viable quantitative theory for interplanetary type II radio bursts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidt, J. M., E-mail: jschmidt@physics.usyd.edu.au; Cairns, Iver H.

Between 29 November and 1 December 2013 the two widely separated spacecraft STEREO A and B observed a long lasting, intermittent, type II radio burst for the extended frequency range ≈ 4 MHz to 30 kHz, including an intensification when the shock wave of the associated coronal mass ejection (CME) reached STEREO A. We demonstrate for the first time our ability to quantitatively and accurately simulate the fundamental (F) and harmonic (H) emission of type II bursts from the higher corona (near 11 solar radii) to 1 AU. Our modeling requires the combination of data-driven three-dimensional magnetohydrodynamic simulations for the CME andmore » plasma background, carried out with the BATS-R-US code, with an analytic quantitative kinetic model for both F and H radio emission, including the electron reflection at the shock, growth of Langmuir waves and radio waves, and the radiations propagation to an arbitrary observer. The intensities and frequencies of the observed radio emissions vary hugely by factors ≈ 10{sup 6} and ≈ 10{sup 3}, respectively; the theoretical predictions are impressively accurate, being typically in error by less than a factor of 10 and 20 %, for both STEREO A and B. We also obtain accurate predictions for the timing and characteristics of the shock and local radio onsets at STEREO A, the lack of such onsets at STEREO B, and the z-component of the magnetic field at STEREO A ahead of the shock, and in the sheath. Very strong support is provided by these multiple agreements for the theory, the efficacy of the BATS-R-US code, and the vision of using type IIs and associated data-theory iterations to predict whether a CME will impact Earth’s magnetosphere and drive space weather events.« less

Demonstration of a viable quantitative theory for interplanetary type II radio bursts

NASA Astrophysics Data System (ADS)

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

2016-03-01

Between 29 November and 1 December 2013 the two widely separated spacecraft STEREO A and B observed a long lasting, intermittent, type II radio burst for the extended frequency range ≈ 4 MHz to 30 kHz, including an intensification when the shock wave of the associated coronal mass ejection (CME) reached STEREO A. We demonstrate for the first time our ability to quantitatively and accurately simulate the fundamental (F) and harmonic (H) emission of type II bursts from the higher corona (near 11 solar radii) to 1 AU. Our modeling requires the combination of data-driven three-dimensional magnetohydrodynamic simulations for the CME and plasma background, carried out with the BATS-R-US code, with an analytic quantitative kinetic model for both F and H radio emission, including the electron reflection at the shock, growth of Langmuir waves and radio waves, and the radiations propagation to an arbitrary observer. The intensities and frequencies of the observed radio emissions vary hugely by factors ≈ 106 and ≈ 103, respectively; the theoretical predictions are impressively accurate, being typically in error by less than a factor of 10 and 20 %, for both STEREO A and B. We also obtain accurate predictions for the timing and characteristics of the shock and local radio onsets at STEREO A, the lack of such onsets at STEREO B, and the z-component of the magnetic field at STEREO A ahead of the shock, and in the sheath. Very strong support is provided by these multiple agreements for the theory, the efficacy of the BATS-R-US code, and the vision of using type IIs and associated data-theory iterations to predict whether a CME will impact Earth's magnetosphere and drive space weather events.

Inhibition of toxigenesis of group II (nonproteolytic) Clostridium botulinum type B in meat products by using a reduced level of nitrite.

PubMed

Keto-Timonen, Riikka; Lindström, Miia; Puolanne, Eero; Niemistö, Markku; Korkeala, Hannu

2012-07-01

The effect of three different concentrations of sodium nitrite (0, 75, and 120 mg/kg) on growth and toxigenesis of group II (nonproteolytic) Clostridium botulinum type B was studied in Finnish wiener-type sausage, bologna-type sausage, and cooked ham. A low level of inoculum (2.0 log CFU/g) was used for wiener-type sausage and bologna-type sausage, and both low (2.0 log CFU/g) and high (4.0 log CFU/g) levels were used for cooked ham. The products were formulated and processed under simulated commercial conditions and stored at 8°C for 5 weeks. C. botulinum counts were determined in five replicate samples of each nitrite concentration at 1, 3, and 5 weeks after thermal processing. All samples were positive for C. botulinum type B. The highest C. botulinum counts were detected in nitrite-free products. Toxigenesis was observed in nitrite-free products during storage, but products containing either 75 or 120 mg/kg nitrite remained nontoxic during the 5-week study period, suggesting that spores surviving the heat treatment were unable to germinate and develop into a toxic culture in the presence of nitrite. The results suggest that the safety of processed meat products with respect to group II C. botulinum type B can be maintained even with a reduced concentration (75 mg/kg) of sodium nitrite.

Effects of selective type I and II adrenal steroid agonists on immune cell distribution.

PubMed

Miller, A H; Spencer, R L; hassett, J; Kim, C; Rhee, R; Ciurea, D; Dhabhar, F; McEwen, B; Stein, M

1994-11-01

Adrenal steroids exert their effects through two distinct adrenal steroid receptor subtypes; the high affinity type I, or mineralocorticoid, receptor and the lower affinity type II, or glucocorticoid, receptor. Adrenal steroids have well known effects on immune cell distribution, and although both type I and II receptors are expressed in immune cells and tissues, few data exist on the relative effects mediated through these two receptor subtypes. Accordingly, we administered selective type I and II adrenal steroid receptor agonists to young adult male Sprague-Dawley rats for 7 days and then measured immune cell distribution in the peripheral blood and spleen. Results were compared with those of similar studies using the naturally occurring glucocorticoid of the rat, corticosterone, which binds both type I and II receptors. The majority of the well characterized effects of adrenal steroids on peripheral blood immune cells (increased neutrophils and decreased lymphocytes and monocytes) were reproduced by the type II receptor agonist, RU28362. RU28362 decreased the numbers of all lymphocyte subsets [T-cells, B-cells, and natural killer (NK) cells] to very low absolute levels. The largest relative decrease (i.e. in percentage) was seen in B-cells, whereas NK cells exhibited the least relative decrease and actually showed a 2-fold increase in relative percentage during RU28362 treatment. Similar to RU28362, the type I receptor agonist, aldosterone, significantly reduced the number of lymphocytes and monocytes. In contrast to RU28362, however, aldosterone significantly decreased the number of neutrophils. Moreover, aldosterone decreased the number of T-helper cells and NK cells, while having no effect on the number of B-cells or T-suppressor/cytotoxic cells. Corticosterone at physiologically relevant concentrations had potent effects on immune cell distribution, which were indistinguishable from those of the type II receptor agonist, RU28362. Taken together, these

Transgenic mice overexpressing insulin-like growth factor-II in β cells develop type 2 diabetes

PubMed Central

Devedjian, Jean-Christophe; George, Monica; Casellas, Alba; Pujol, Anna; Visa, Joana; Pelegrín, Mireia; Gros, Laurent; Bosch, Fatima

2000-01-01

During embryonic development, insulin-like growth factor-II (IGF-II) participates in the regulation of islet growth and differentiation. We generated transgenic mice (C57BL6/SJL) expressing IGF-II in β cells under control of the rat Insulin I promoter in order to study the role of islet hyperplasia and hyperinsulinemia in the development of type 2 diabetes. In contrast to islets from control mice, islets from transgenic mice displayed high levels of IGF-II mRNA and protein. Pancreases from transgenic mice showed an increase in β-cell mass (about 3-fold) and in insulin mRNA levels. However, the organization of cells within transgenic islets was disrupted, with glucagon-producing cells randomly distributed throughout the core. We also observed enhanced glucose-stimulated insulin secretion and glucose utilization in islets from transgenic mice. These mice displayed hyperinsulinemia, mild hyperglycemia, and altered glucose and insulin tolerance tests, and about 30% of these animals developed overt diabetes when fed a high-fat diet. Furthermore, transgenic mice obtained from the N1 backcross to C57KsJ mice showed high islet hyperplasia and insulin resistance, but they also developed fatty liver and obesity. These results indicate that local overexpression of IGF-II in islets might lead to type 2 diabetes and that islet hyperplasia and hypersecretion of insulin might occur early in the pathogenesis of this disease. PMID:10727441

Neuregulin 1 Type II-ErbB Signaling Promotes Cell Divisions Generating Neurons from Neural Progenitor Cells in the Developing Zebrafish Brain.

PubMed

Sato, Tomomi; Sato, Fuminori; Kamezaki, Aosa; Sakaguchi, Kazuya; Tanigome, Ryoma; Kawakami, Koichi; Sehara-Fujisawa, Atsuko

2015-01-01

Post-mitotic neurons are generated from neural progenitor cells (NPCs) at the expense of their proliferation. Molecular and cellular mechanisms that regulate neuron production temporally and spatially should impact on the size and shape of the brain. While transcription factors such as neurogenin1 (neurog1) and neurod govern progression of neurogenesis as cell-intrinsic mechanisms, recent studies show regulatory roles of several cell-extrinsic or intercellular signaling molecules including Notch, FGF and Wnt in production of neurons/neural progenitor cells from neural stem cells/radial glial cells (NSCs/RGCs) in the ventricular zone (VZ). However, it remains elusive how production of post-mitotic neurons from neural progenitor cells is regulated in the sub-ventricular zone (SVZ). Here we show that newborn neurons accumulate in the basal-to-apical direction in the optic tectum (OT) of zebrafish embryos. While neural progenitor cells are amplified by mitoses in the apical ventricular zone, neurons are exclusively produced through mitoses of neural progenitor cells in the sub-basal zone, later in the sub-ventricular zone, and accumulate apically onto older neurons. This neurogenesis depends on Neuregulin 1 type II (NRG1-II)-ErbB signaling. Treatment with an ErbB inhibitor, AG1478 impairs mitoses in the sub-ventricular zone of the optic tectum. Removal of AG1478 resumes sub-ventricular mitoses without precedent mitoses in the apical ventricular zone prior to basal-to-apical accumulation of neurons, suggesting critical roles of ErbB signaling in mitoses for post-mitotic neuron production. Knockdown of NRG1-II impairs both mitoses in the sub-basal/sub-ventricular zone and the ventricular zone. Injection of soluble human NRG1 into the developing brain ameliorates neurogenesis of NRG1-II-knockdown embryos, suggesting a conserved role of NRG1 as a cell-extrinsic signal. From these results, we propose that NRG1-ErbB signaling stimulates cell divisions generating neurons from

Using Factor Mixture Models to Evaluate the Type A/B Classification of Alcohol Use Disorders in a Heterogeneous Treatment Sample

PubMed Central

Hildebrandt, Tom; Epstein, Elizabeth E.; Sysko, Robyn; Bux, Donald A.

2017-01-01

Background The type A/B classification model for alcohol use disorders (AUDs) has received considerable empirical support. However, few studies examine the underlying latent structure of this subtyping model, which has been challenged as a dichotomization of a single drinking severity dimension. Type B, relative to type A, alcoholics represent those with early age of onset, greater familial risk, and worse outcomes from alcohol use. Method We examined the latent structure of the type A/B model using categorical, dimensional, and factor mixture models in a mixed gender community treatment-seeking sample of adults with an AUD. Results Factor analytic models identified 2-factors (drinking severity/externalizing psychopathology and internalizing psychopathology) underlying the type A/B indicators. A factor mixture model with 2-dimensions and 3-classes emerged as the best overall fitting model. The classes reflected a type A class and two type B classes (B1 and B2) that differed on the respective level of drinking severity/externalizing pathology and internalizing pathology. Type B1 had a greater prevalence of women and more internalizing pathology and B2 had a greater prevalence of men and more drinking severity/externalizing pathology. The 2-factor, 3-class model also exhibited predictive validity by explaining significant variance in 12-month drinking and drug use outcomes. Conclusions The model identified in the current study may provide a basis for examining different sources of heterogeneity in the course and outcome of AUDs. PMID:28247423

Estrogen Modulation of MgATPase Activity of Nonmuscle Myosin-II-B Filaments

PubMed Central

Gorodeski, George I.

2008-01-01

The study tested the hypothesis that estrogen controls epithelial paracellular resistance through modulation of myosin. The objective was to understand how estrogen modulates non-muscle myosin-II-B (NMM-II-B), the main component of the cortical actomyosin in human epithelial cervical cells. Experiments used human cervical epithelial cells CaSki as a model, and end points were NMM-II-B phosphorylation, filamentation, and MgATPase activity. The results were as follows: 1) treatment with estrogen increased phosphorylation and MgATPase activity and decreased NMM-II-B filamentation; 2) estrogen effects could be blocked by antisense nucleotides for the estrogen receptor-α and by ICI-182,780, tamoxifen, and the casein kinase-II (CK2) inhibitor, 5,6-dichloro-1-β-(D)-ribofuranosylbenzimidazole and attenuated by AG1478 and PD98059 (inhibitors of epithelial growth factor receptor and ERK/MAPK) but not staurosporine [blocker of protein kinase C (PKC)]; 3) treatments with the PKC activator sn-1,2-di-octanoyl diglyceride induced biphasic effect on NMM-II-B MgATPase activity: an increase at 1 nM to 1 μM and a decrease in activity at more than 1 μM; 4) sn-1,2-dioctanoyl diglyceride also decreased NMM-II-B filamentation in a monophasic and saturable dose dependence (EC50 1–10 μM); 5) when coincubated directly with purified NMM-II-B filaments, both CK2 and PKC decreased filamentation and increased MgATPase activity; 6) assays done on disassembled NMM-II-B filaments showed MgATPase activity in filaments obtained from estrogen-treated cells but not estrogen-depleted cells; and 7) incubations in vitro with CK2, but not PKC, facilitated MgATPase activity, even in disassembled NMM-II-B filaments. The results suggest that estrogen, in an effect mediated by estrogen receptor-α and CK2 and involving the epithelial growth factor receptor and ERK/MAPK cascades, increases NMM-II-B MgATPase activity independent of NMM-II-B filamentation status. PMID:17023528

Evaluation of Type II Fast Packs for Electrostatic Discharge Properties.

DTIC Science & Technology

1983-08-01

34 x 8" x 1 3/4") consisting of a reclosable cushioned carrier which mates into an outer fiberboard sleeve. A cushioning insert is used consisting of a... RECLOSABLE CUSHIONED CARRIER TEST LOAD FIGURE 1: Cancel Caddy Pack * CONVOLUTED 4* CUSHIONED I FIGURE 2: Type II Fast Pack (PPP-B-1672) TYPE II FAST PACK

[The results of combined ozone therapy using in complex treatment of soft tissues infections in patients with diabetes mellitus type II].

PubMed

Vinnik, Iu S; Salmina, A B; Tepliakova, O V; Drobushevskaia, A I; Pozhilenkova, E A; Morgun, A V; Shapran, M V; Kovalenko, A O

2015-01-01

Levels of interleukins-6, 8, 10, TNF-alpha and basic fibroblast growth factor (bFGF) were examined in peripheral blood of 60 patients with diabetes mellitus type II and soft tissues infections. It was revealed the elevated levels of proinflammatory (IL-6, 8), anti-inflammatory (IL-10) cytokines and basic fibroblast growth factor at the time of admission. Application of combined ozone therapy including ozonated autohemotherapy and superficial management of wounds with ozone-oxygen mixture resulted in significant decrease of IL-6, 8, 10 production and high level of bFGF on blood serum. Thus effective local bactericidal impact of ozone in combination with normalization of proinflammatory cytokines levels and preserved high level of bFGF in peripheral blood provide better results of wound healing process in patients with diabetes mellitus type II.

30 CFR 57.22232 - Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). 57.22232 Section 57.22232 Mineral Resources MINE SAFETY AND HEALTH....22232 Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). If methane reaches 0.5...

30 CFR 57.22232 - Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 0.5 percent methane (I-B, II-A, II-B...-UNDERGROUND METAL AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22232 Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). If methane reaches 0.5...

Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs.

PubMed

Murakami, S; Takayama, S; Kitamura, M; Shimabukuro, Y; Yanagi, K; Ikezawa, K; Saho, T; Nozaki, T; Okada, H

2003-02-01

Several growth factors (or cytokines) have been recently investigated for their use as potential therapeutics for periodontal tissue regeneration. The objective of this study was to evaluate periodontal tissue regeneration, including new bone and cementum formation, following topical application of recombinant basic fibroblast growth factor (bFGF, FGF-2) to furcation class II defects. Twelve furcation class II bone defects were surgically created in six beagle dogs, then recombinant bFGF (30 micro g/site) + gelatinous carrier was topically applied to the bony defects. Six weeks after application, periodontal regeneration was analyzed. In all sites where bFGF was applied, periodontal ligament formation with new cementum deposits and new bone formation was observed histomorphometrically, in amounts greater than in the control sites. Basic FGF-applied sites exhibited significant regeneration as represented by the new bone formation rate (NBR) (83.6 +/- 14.3%), new trabecular bone formation rate (NTBR) (44.1 +/- 9.5%), and new cementum formation rate (NCR) (97.0 +/- 7.5%). In contrast, in the carrier-only sites, the NBR, NTBR, and NCR were 35.4 +/- 8.9%, 16.6 +/- 6.2%, and 37.2 +/- 15.1%, respectively. Moreover, no instances of epithelial down growth, ankylosis, or root resorption were observed in the bFGF-applied sites examined. The present results indicate that topical application of bFGF can enhance considerable periodontal regeneration in artificially created furcation class II bone defects of beagle dogs.

Risk factors and rate of progression for zone I versus zone II type 1 retinopathy of prematurity.

PubMed

Shin, Dong Hoon; Kong, Mingui; Kim, Sang Jin; Ham, Don Il; Kang, Se Woong; Chang, Yun Sil; Park, Won Soon

2014-04-01

To compare the risk factors and rate of progression of zone I versus zone II type 1 retinopathy of prematurity (ROP). The medical records of consecutive preterm infants with bilateral type 1 ROP in zone I and age-matched control infants with type 1 ROP in zone II were retrospectively analyzed. Fundus findings at each screening examination and systemic parameters were compared between groups. Univariate and conditional multivariate regression analyses were employed to identify variables significantly associated with zone I ROP. A total of 30 cases and 30 controls were included. The mean gestational age of included infants was 24.6 weeks in both groups, and the mean birth weights were 685 g in the zone I group and 667 g in the zone II group. The postmenstrual age (PMA) at the time of initial ROP detection did not differ between groups, but the PMA at the time of type 1 ROP detection was significantly earlier in the zone I group (mean, 34.9 vs 37.6 weeks). Conditional multiple logistic regression revealed that mechanical ventilation for 30 days or more was significantly associated with the type 1 ROP in zone I compared with zone II (OR, 3.5; 95% CI, 1.2-10.0). Zone I ROP exhibited rapid progression, necessitating close monitoring and prompt treatment. Compromised pulmonary function with associated mechanical ventilation in early life may restrict retinal vascular growth and increase the likelihood of zone I type 1 ROP. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

The angiotensin II receptor type 1b is the primary sensor of intraluminal pressure in cerebral artery smooth muscle cells.

PubMed

Pires, Paulo W; Ko, Eun-A; Pritchard, Harry A T; Rudokas, Michael; Yamasaki, Evan; Earley, Scott

2017-07-15

The angiotensin II receptor type 1b (AT 1 R b ) is the primary sensor of intraluminal pressure in cerebral arteries. Pressure or membrane-stretch induced stimulation of AT 1 R b activates the TRPM4 channel and results in inward transient cation currents that depolarize smooth muscle cells, leading to vasoconstriction. Activation of either AT 1 R a or AT 1 R b with angiotensin II stimulates TRPM4 currents in cerebral artery myocytes and vasoconstriction of cerebral arteries. The expression of AT 1 R b mRNA is ∼30-fold higher than AT 1 R a in whole cerebral arteries and ∼45-fold higher in isolated cerebral artery smooth muscle cells. Higher levels of expression are likely to account for the obligatory role of AT 1 R b for pressure-induced vasoconstriction . ABSTRACT: Myogenic vasoconstriction, which reflects the intrinsic ability of smooth muscle cells to contract in response to increases in intraluminal pressure, is critically important for the autoregulation of blood flow. In smooth muscle cells from cerebral arteries, increasing intraluminal pressure engages a signalling cascade that stimulates cation influx through transient receptor potential (TRP) melastatin 4 (TRPM4) channels to cause membrane depolarization and vasoconstriction. Substantial evidence indicates that the angiotensin II receptor type 1 (AT 1 R) is inherently mechanosensitive and initiates this signalling pathway. Rodents express two types of AT 1 R - AT 1 R a and AT 1 R b - and conflicting studies provide support for either isoform as the primary sensor of intraluminal pressure in peripheral arteries. We hypothesized that mechanical activation of AT 1 R a increases TRPM4 currents to induce myogenic constriction of cerebral arteries. However, we found that development of myogenic tone was greater in arteries from AT 1 R a knockout animals compared with controls. In patch-clamp experiments using native cerebral arterial myocytes, membrane stretch-induced cation currents were blocked by the TRPM

Type II universal spacetimes

NASA Astrophysics Data System (ADS)

Hervik, S.; Málek, T.; Pravda, V.; Pravdová, A.

2015-12-01

We study type II universal metrics of the Lorentzian signature. These metrics simultaneously solve vacuum field equations of all theories of gravitation with the Lagrangian being a polynomial curvature invariant constructed from the metric, the Riemann tensor and its covariant derivatives of an arbitrary order. We provide examples of type II universal metrics for all composite number dimensions. On the other hand, we have no examples for prime number dimensions and we prove the non-existence of type II universal spacetimes in five dimensions. We also present type II vacuum solutions of selected classes of gravitational theories, such as Lovelock, quadratic and L({{Riemann}}) gravities.

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family.

PubMed

Antonets, Denis V; Nepomnyashchikh, Tatyana S; Shchelkunov, Sergei N

2010-10-27

Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.

Boron Abundances in A and B-type Stars

NASA Technical Reports Server (NTRS)

Lambert, David L.

1997-01-01

Boron abundances in A- and B-type stars may be a successful way to track evolutionary effects in these hot stars. The light elements - Li, Be, and B - are tracers of exposure to temperatures more moderate than those in which the H-burning CN-cycle operates. Thus, any exposure of surface stellar layers to deeper layers will affect these light element abundances. Li and Be are used in this role in investigations of evolutionary processes in cool stars, but are not observable in hotter stars. An investigation of boron, however, is possible through the B II 1362 A resonance line. We have gathered high resolution spectra from the IUE database of A- and B-type stars near 10 solar mass for which nitrogen abundances have been determined. The B II 1362 A line is blended throughout; the temperature range of this program, requiring spectrum syntheses to recover the boron abundances. For no star could we synthesize the 1362 A region using the meteoritic/solar boron abundance of log e (B) = 2.88; a lower boron abundance was necessary which may reflect evolutionary effects (e.g., mass loss or mixing near the main-sequence), the natal composition of the star forming regions, or a systematic error in the analyses (e.g., non-LTE effects). Regardless of the initial boron abundance, and despite the possibility of non-LTE effects, it seems clear that boron is severely depleted in some stars. It may be that the nitrogen and boron abundances are anticorrelated, as would be expected from mixing between the H-burning and outer stellar layers. If, as we suspect, a residue of boron is present in the A-type supergiants, we may exclude a scenario in which mixing occurs continuously between the surface and the deep layers operating the CN-cycle. Further exploitation of the B II 1362 A line as an indicator of the evolutionary status of A- and B-type stars will require a larger stellar sample to be observed with higher signal-to-noise as attainable with the Hubble Space Telescope.

30 CFR 57.22201 - Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22201 Section 57.22201 Mineral Resources MINE SAFETY AND HEALTH....22201 Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). All mines shall...

30 CFR 57.22201 - Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22201 Section 57.22201 Mineral Resources MINE SAFETY AND HEALTH....22201 Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). All mines shall...

The risk for type B aortic dissection in Marfan syndrome.

PubMed

den Hartog, Alexander W; Franken, Romy; Zwinderman, Aeilko H; Timmermans, Janneke; Scholte, Arthur J; van den Berg, Maarten P; de Waard, Vivian; Pals, Gerard; Mulder, Barbara J M; Groenink, Maarten

2015-01-27

Aortic dissections involving the descending aorta are a major clinical problem in patients with Marfan syndrome. The purpose of this study was to identify clinical parameters associated with type B aortic dissection and to develop a risk model to predict type B aortic dissection in patients with Marfan syndrome. Patients with the diagnosis of Marfan syndrome and magnetic resonance imaging or computed tomographic imaging of the aorta were followed for a median of 6 years for the occurrence of type B dissection or the combined end point of type B aortic dissection, distal aortic surgery, and death. A model using various clinical parameters as well as genotyping was developed to predict the risk for type B dissection in patients with Marfan syndrome. Between 1998 and 2013, 54 type B aortic dissections occurred in 600 patients with Marfan syndrome (mean age 36 ± 14 years, 52% male). Independent variables associated with type B aortic dissection were prior prophylactic aortic surgery (hazard ratio: 2.1; 95% confidence interval: 1.2 to 3.8; p = 0.010) and a proximal descending aorta diameter ≥27 mm (hazard ratio: 2.2; 95% confidence interval: 1.1 to 4.3; p = 0.020). In the risk model, the 10-year occurrence of type B aortic dissection in low-, moderate-, and high-risk patients was 6%, 19%, and 34%, respectively. Angiotensin II receptor blocker therapy was associated with fewer type B aortic dissections (hazard ratio: 0.3; 95% confidence interval: 0.1 to 0.9; p = 0.030). Patients with Marfan syndrome with prior prophylactic aortic surgery are at substantial risk for type B aortic dissection, even when the descending aorta is only slightly dilated. Angiotensin II receptor blocker therapy may be protective in the prevention of type B aortic dissections. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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. Copyright © 2014 Elsevier B.V. All rights reserved.

Observational calibration of the projection factor of Cepheids. I. The type II Cepheid κ Pavonis

NASA Astrophysics Data System (ADS)

Breitfelder, J.; Kervella, P.; Mérand, A.; Gallenne, A.; Szabados, L.; Anderson, R. I.; Willson, M.; Le Bouquin, J.-B.

2015-04-01

Context. The distance of pulsating stars, in particular Cepheids, are commonly measured using the parallax of pulsation technique. The different versions of this technique combine measurements of the linear diameter variation (from spectroscopy) and the angular diameter variation (from photometry or interferometry) amplitudes, to retrieve the distance in a quasi-geometrical way. However, the linear diameter amplitude is directly proportional to the projection factor (hereafter p-factor), which is used to convert spectroscopic radial velocities (i.e., disk integrated) into pulsating (i.e., photospheric) velocities. The value of the p-factor and its possible dependence on the pulsation period are still widely debated. Aims: Our goal is to measure an observational value of the p-factor of the type-II Cepheid κ Pavonis. Methods: The parallax of the type-II Cepheid κ Pav was measured with an accuracy of 5% using HST/FGS. We used this parallax as a starting point to derive the p-factor of κ Pav, using the SPIPS technique (Spectro-Photo-Interferometry of Pulsating Stars), which is a robust version of the parallax-of-pulsation method that employs radial velocity, interferometric and photometric data. We applied this technique to a combination of new VLTI/PIONIER optical interferometric angular diameters, new CORALIE and HARPS radial velocities, as well as multi-colour photometry and radial velocities from the literature. Results: We obtain a value of p = 1.26 ± 0.07 for the p-factor of κ Pav. This result agrees with several of the recently derived Period-p-factor relationships from the literature, as well as previous observational determinations for Cepheids. Conclusions: Individual estimates of the p-factor are fundamental to calibrating the parallax of pulsation distances of Cepheids. Together with previous observational estimates, the projection factor we obtain points to a weak dependence of the p-factor on period. Based on observations realized with ESO

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22501 Section 57.22501 Mineral Resources MINE SAFETY AND... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22501 Section 57.22501 Mineral Resources MINE SAFETY AND... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines...

Sugar-sweetened beverage intake and the risk of type I and type II endometrial cancer among postmenopausal women.

PubMed

Inoue-Choi, Maki; Robien, Kim; Mariani, Andrea; Cerhan, James R; Anderson, Kristin E

2013-12-01

Sugar-sweetened beverage (SSB) intake has been associated with an increased risk of obesity and type II diabetes. However, its association with endometrial cancer is unclear. We evaluated dietary intake of SSB, fruit juice, sugar-free beverages, sweets/baked goods, starch, and sugars among 23,039 postmenopausal women in the Iowa Women's Health Study. Incident estrogen-dependent type I and estrogen-independent type II endometrial cancers were identified via linkage with the Surveillance Epidemiology and End Results Registry. Risks of type I and type II endometrial cancers were separately compared by energy-adjusted dietary intake in Cox proportional hazards regression models. From 1986 to 2010, 506 type I and 89 type II incident endometrial cancers were identified. An increased risk of type I endometrial cancer was observed with increasing SSB intake after adjustment for body mass index (BMI) and other cofounders (Ptrend = 0.0005). Compared with nondrinkers of SSB, the risk was 78% higher [95% confidence intervals (CI), 1.32-2.40] among women in the highest quintile of SSB intake. The observed association was not modified by BMI, physical activity, history of diabetes, or cigarette smoking. Higher risk of type I endometrial cancer was also observed with higher intake of sugars. None of the dietary items included in the analysis was associated with type II endometrial cancer risk. Higher intake of SSB and sugars was associated with an increased risk of type I, but not type II, endometrial cancer. SSB intake may be a risk factor for type I endometrial cancer regardless of other lifestyle factors. ©2013 AACR.

Preclinical Validation of Anti-Nuclear Factor Kappa B Therapy Against Vestibular Schwannoma and Neurofibromatosis Type II

DTIC Science & Technology

2016-06-01

therapies that simply reduce tumor volume and retard growth can be life- saving. The most successful drug used today to treat NF2, bevacizumab, works...in only about 50% of patients in halting tumor growth or causing tumor shrinkage. Bevacizumab is known to inhibit vascular endothelial growth factor...of TNF (and hence of NFkB) may prevent both VS growth and the associated hearing loss. Using human volumetric VS measurements in a retrospective

30 CFR 57.22227 - Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22227 Section 57.22227 Mineral Resources MINE SAFETY AND... Ventilation § 57.22227 Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). (a...

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family

PubMed Central

2010-01-01

Background Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. Findings De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Conclusions Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein. PMID:20979600

Transcription factor Etv5 is essential for the maintenance of alveolar type II cells.

PubMed

Zhang, Zhen; Newton, Kim; Kummerfeld, Sarah K; Webster, Joshua; Kirkpatrick, Donald S; Phu, Lilian; Eastham-Anderson, Jeffrey; Liu, Jinfeng; Lee, Wyne P; Wu, Jiansheng; Li, Hong; Junttila, Melissa R; Dixit, Vishva M

2017-04-11

Alveolar type II (AT2) cell dysfunction contributes to a number of significant human pathologies including respiratory distress syndrome, lung adenocarcinoma, and debilitating fibrotic diseases, but the critical transcription factors that maintain AT2 cell identity are unknown. Here we show that the E26 transformation-specific (ETS) family transcription factor Etv5 is essential to maintain AT2 cell identity. Deletion of Etv5 from AT2 cells produced gene and protein signatures characteristic of differentiated alveolar type I (AT1) cells. Consistent with a defect in the AT2 stem cell population, Etv5 deficiency markedly reduced recovery following bleomycin-induced lung injury. Lung tumorigenesis driven by mutant KrasG12D was also compromised by Etv5 deficiency. ERK activation downstream of Ras was found to stabilize Etv5 through inactivation of the cullin-RING ubiquitin ligase CRL4 COP1/DET1 that targets Etv5 for proteasomal degradation. These findings identify Etv5 as a critical output of Ras signaling in AT2 cells, contributing to both lung homeostasis and tumor initiation.

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

Angiotensin II type 1 receptor blockers prevent tumor necrosis factor-alpha-mediated endothelial nitric oxide synthase reduction and superoxide production in human umbilical vein endothelial cells.

PubMed

Kataoka, Hiroki; Murakami, Ryuichiro; Numaguchi, Yasushi; Okumura, Kenji; Murohara, Toyoaki

2010-06-25

Decrease in endothelial nitric oxide synthase (eNOS) expression is one of the adverse outcomes of endothelial dysfunction. Tumor necrosis factor-alpha (TNF-alpha) is known to decrease eNOS expression and is an important mediator of endothelial dysfunction. We hypothesized that an angiotensin II type 1 (AT1) receptor blocker would improve endothelial function via not only inhibition of the angiotensin II signaling but also inhibition of the TNF-alpha-mediated signaling. Therefore we investigated whether an AT1 receptor blocker would restore the TNF-alpha-induced decrease in eNOS expression in cultured human umbilical vein endothelial cells (HUVEC). Pretreatment of HUVEC with an antioxidant (superoxide dismutase, alpha-tocopherol) or AT1 receptor blockers (olmesartan or candesartan) restored the TNF-alpha-dependent reduction of eNOS. The AT1 receptor blocker decreased the TNF-alpha-dependent increase of 8-isoprostane. The superoxide dismutase activities in HUVEC were stable during AT1 receptor blocker treatment, and the AT1 receptor blocker did not scavenge superoxide directly. The AT1 receptor blocker also decreased TNF-alpha-induced phosphorylation of I kappaB alpha and cell death. These results suggest that AT1 receptor blockers are able to ameliorate TNF-alpha-dependent eNOS reduction or cell injury by inhibiting superoxide production or nuclear factor-kappaB activation. (c) 2010 Elsevier B.V. All rights reserved.

Factors Associated with Participation in Pulmonary Tuberculosis Screening Using Chest X-Ray among Diabetes Mellitus Type II Patients in Denpasar, Bali, Indonesia.

PubMed

Putra, I Gusti Ngurah Edi; Astuti, Putu Ayu Swandewi; Suarjana, I Ketut; Mulyawan, Ketut Hari; Duana, I Made Kerta; Kurniasari, Ni Made Dian; Putra, I Wayan Gede Artawan Eka

2018-01-01

Diabetes mellitus (DM) increases the risk of developing pulmonary tuberculosis (TB) disease. Therefore, pulmonary TB screening among DM patients is essential. This study aimed to identify factors associated with participation of DM type II patients in pulmonary TB screening using chest X-ray. This was a cross-sectional analytic study and was part of TB-DM screening study in Denpasar, Bali, Indonesia. The sample consisted of 365 DM type II patients selected by quota sampling among DM type II patients joining the screening program from January until March 2016 in 11 public health centres in Denpasar. Data were collected via structured interviews. The contributing factors were determined by modified Poisson regression test for cross-sectional data. From the findings, less than half (45.48%) of DM type II patients participated in chest X-ray examination for TB. Factors associated with participation in pulmonary TB screening were having a higher educational level [APR = 1.34, 95% CI (1.07-1.67)], having family member who developed pulmonary TB disease [APR = 1.47, 95% CI (1.12-1.93)], the travel time to referral hospital for screening being ≤ 15 minutes [APR = 1.6, 95% CI (1.26-2.03)], having health insurance [APR = 2.69, 95% CI (1.10-6.56)], and receiving good support from health provider [APR = 1.35, 95% CI (1.06-1.70)]. Therefore, training for health provider on providing counselling, involvement of family members in screening process, and improving the health insurance coverage and referral system are worth considering.

Porcine circovirus type 2 induces the activation of nuclear factor kappa B by I{kappa}B{alpha} degradation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei Li; Kwang, Jimmy; Wang Jin

The transcription factor NF-{kappa}B is commonly activated upon virus infection and a key player in the induction and regulation of the host immune response. The present study demonstrated for the first time that porcine circovirus type 2 (PCV2), which is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome, can activate NF-{kappa}B in PCV2-infected PK15 cells. In PCV2-infected cells, NF-{kappa}B was activated concomitantly with viral replication, which was characterized by increased DNA binding activity, translocation of NF-{kappa}B p65 from the cytoplasm to the nucleus, as well as degradation and phosphorylation of I{kappa}B{alpha} protein. We further demonstratedmore » PCV2-induced activation of NF-{kappa}B and colocalization of p65 nuclear translocation with virus replication in cultured cells. Treatment of cells with CAPE, a selective inhibitor of NF-{kappa}B activation, reduced virus protein expression and progeny production followed by decreasing PCV2-induced apoptotic caspase activity, indicating the involvement of this transcription factor in induction of cell death. Taken together, these data suggest that NF-{kappa}B activation is important for PCV2 replication and contributes to virus-mediated changes in host cells. The results presented here provide a basis for understanding molecular mechanism of PCV2 infection.« less

Type-II Weyl semimetals.

PubMed

Soluyanov, Alexey A; Gresch, Dominik; Wang, Zhijun; Wu, QuanSheng; Troyer, Matthias; Dai, Xi; Bernevig, B Andrei

2015-11-26

Fermions--elementary particles such as electrons--are classified as Dirac, Majorana or Weyl. Majorana and Weyl fermions had not been observed experimentally until the recent discovery of condensed matter systems such as topological superconductors and semimetals, in which they arise as low-energy excitations. Here we propose the existence of a previously overlooked type of Weyl fermion that emerges at the boundary between electron and hole pockets in a new phase of matter. This particle was missed by Weyl because it breaks the stringent Lorentz symmetry in high-energy physics. Lorentz invariance, however, is not present in condensed matter physics, and by generalizing the Dirac equation, we find the new type of Weyl fermion. In particular, whereas Weyl semimetals--materials hosting Weyl fermions--were previously thought to have standard Weyl points with a point-like Fermi surface (which we refer to as type-I), we discover a type-II Weyl point, which is still a protected crossing, but appears at the contact of electron and hole pockets in type-II Weyl semimetals. We predict that WTe2 is an example of a topological semimetal hosting the new particle as a low-energy excitation around such a type-II Weyl point. The existence of type-II Weyl points in WTe2 means that many of its physical properties are very different to those of standard Weyl semimetals with point-like Fermi surfaces.

Factors affecting primary patency of stenting for TransAtlantic Inter-Society (TASC II) type B, C, and D iliac occlusive disease.

PubMed

Kavaliauskienė, Zana; Benetis, Rimantas; Inčiūra, Donatas; Aleksynas, Nerijus; Kaupas, Rytis Stasys; Antuševas, Aleksandras

2014-01-01

The purpose of our study was to evaluate 1- and 2-year results and the influence of risk factors on the outcome in the patients undergoing iliac artery stenting for TASC II type B, C, and D iliac lesions. In this prospective nonrandomized study conducted between April 15, 2011, and April 15, 2013, 316 patients underwent angiography with a diagnosis of aortoiliac atherosclerotic disease. Of these, 62 iliac endovascular procedures (87 stents) were performed in 54 patients. The indications for revascularization were disabling claudication (Rutherford 2, 5.9%; Rutherford 3, 35.2%), rest pain (Rutherford 4, 22.2%), and gangrene (Rutherford 5, 16.7%). The overall complication rate was 9.2%. The cumulative primary stent patency at 1 and 2 years was 83.0%±5.2% and 79.9%±5.8%, respectively. Early stent thrombosis in ≤30 days was detected in two patients (3.7%). The primary patency rates for the stents ≤61mm at 12 and 24 months were 90.6%±4.5% and 86.6%±5.8%, respectively; those for the stents >61mm were 67.7%±10.9% and 60.2%±12.0%, respectively (P=0.016). The multivariate Cox regression analysis enabled the localization of a stent in both the CIA and the EIA (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.1-9.5; P=0.021) and poor runoff (HR, 3.2; 95%, CI 1.0-10.0; P=0.047) as independent predictors of decreased stent primary patency. The localization of a stent in both iliac (CIA and EIA) arteries and poor runoff significantly reduce the primary stent patency. Patients with stents >61mm have a higher risk of stent thrombosis or in-stent restenosis development. Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Type-II Dirac photons

NASA Astrophysics Data System (ADS)

Wang, Hai-Xiao; Chen, Yige; Hang, Zhi Hong; Kee, Hae-Young; Jiang, Jian-Hua

2017-09-01

The Dirac equation for relativistic electron waves is the parent model for Weyl and Majorana fermions as well as topological insulators. Simulation of Dirac physics in three-dimensional photonic crystals, though fundamentally important for topological phenomena at optical frequencies, encounters the challenge of synthesis of both Kramers double degeneracy and parity inversion. Here we show how type-II Dirac points—exotic Dirac relativistic waves yet to be discovered—are robustly realized through the nonsymmorphic screw symmetry. The emergent type-II Dirac points carry nontrivial topology and are the mother states of type-II Weyl points. The proposed all-dielectric architecture enables robust cavity states at photonic-crystal—air interfaces and anomalous refraction, with very low energy dissipation.

Niacin supplementation induces type II to type I muscle fiber transition in skeletal muscle of sheep.

PubMed

Khan, Muckta; Couturier, Aline; Kubens, Johanna F; Most, Erika; Mooren, Frank-Christoph; Krüger, Karsten; Ringseis, Robert; Eder, Klaus

2013-11-22

It was recently shown that niacin supplementation counteracts the obesity-induced muscle fiber transition from oxidative type I to glycolytic type II and increases the number of type I fibers in skeletal muscle of obese Zucker rats. These effects were likely mediated by the induction of key regulators of fiber transition, PPARδ (encoded by PPARD), PGC-1α (encoded by PPARGC1A) and PGC-1β (encoded by PPARGC1B), leading to type II to type I fiber transition and upregulation of genes involved in oxidative metabolism. The aim of the present study was to investigate whether niacin administration also influences fiber distribution and the metabolic phenotype of different muscles [M. longissimus dorsi (LD), M. semimembranosus (SM), M. semitendinosus (ST)] in sheep as a model for ruminants. For this purpose, 16 male, 11 wk old Rhoen sheep were randomly allocated to two groups of 8 sheep each administered either no (control group) or 1 g niacin per day (niacin group) for 4 wk. After 4 wk, the percentage number of type I fibers in LD, SM and ST muscles was greater in the niacin group, whereas the percentage number of type II fibers was less in niacin group than in the control group (P < 0.05). The mRNA levels of PPARGC1A, PPARGC1B, and PPARD and the relative mRNA levels of genes involved in mitochondrial fatty acid uptake (CPT1B, SLC25A20), tricarboxylic acid cycle (SDHA), mitochondrial respiratory chain (COX5A, COX6A1), and angiogenesis (VEGFA) in LD, SM and ST muscles were greater (P < 0.05) or tended to be greater (P < 0.15) in the niacin group than in the control group. The study shows that niacin supplementation induces muscle fiber transition from type II to type I, and thereby an oxidative metabolic phenotype of skeletal muscle in sheep as a model for ruminants. The enhanced capacity of skeletal muscle to utilize fatty acids in ruminants might be particularly useful during metabolic states in which fatty acids are excessively mobilized from adipose

Major contribution of the type II beta carbonic anhydrase CanB (Cj0237) to the capnophilic growth phenotype of Campylobacter jejuni.

PubMed

Al-Haideri, Halah; White, Michael A; Kelly, David J

2016-02-01

Campylobacter jejuni, the leading cause of human bacterial gastroenteritis, requires low environmental oxygen and high carbon dioxide for optimum growth, but the molecular basis for the carbon dioxide requirement is unclear. One factor may be inefficient conversion of gaseous CO2 to bicarbonate, the required substrate of various carboxylases. Two putative carbonic anhydrases (CAs) are encoded in the genome of C. jejuni strain NCTC 11168 (Cj0229 and Cj0237). Here, we show that the deletion of the cj0237 (canB) gene alone prevents growth in complex media at low (1% v/v) CO2 and significantly reduces the growth rate at high (5% v/v) CO2. In minimal media incubated under high CO2, the canB mutant grew on L-aspartate but not on the key C3 compounds L-serine, pyruvate and L-lactate, showing that CanB is crucial in bicarbonate provision for pyruvate carboxylase-mediated oxaloacetate synthesis. Nevertheless, purified CanB (a dimeric, anion and acetazolamide sensitive, zinc-containing type II beta-class enzyme) hydrates CO2 actively only above pH 8 and with a high Km (∼ 34 mM). At typical cytoplasmic pH values and low CO2, these kinetic properties might limit intracellular bicarbonate availability. Taken together, our data suggest CanB is a major contributor to the capnophilic growth phenotype of C. jejuni. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

CDF-II and B physics

NASA Astrophysics Data System (ADS)

Lockyer, Nigel S.

1998-02-01

This paper reports on the CDF-II B physics goals and new detector systems presently being built for Run-II of the Tevatron collider in the year 2000. The B physics goals are focused towards observing and studying CP violation and B s flavor oscillations. Estimates of expected performance are reported. The new detector systems described are: the 5-layer 3-D silicon vertex detector, the intermedia silicon tracking layers, the central tracking drift chamber, muon system upgrades, and a proposed time-of-flight system.

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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Bianchi Type-II String Cosmological Model with Magnetic Field in f ( R, T) Gravity

NASA Astrophysics Data System (ADS)

Sharma, N. K.; Singh, J. K.

2014-09-01

The spatially homogeneous and totally anisotropic Bianchi type-II cosmological solutions of massive strings have been investigated in the presence of the magnetic field in the framework of f( R, T) gravity proposed by Harko et al. (Phys Rev D 84:024020, 2011). With the help of special law of variation for Hubble's parameter proposed by Berman (Nuovo Cimento B 74:182, 1983) cosmological model is obtained in this theory. We consider f( R, T) model and investigate the modification R+ f( T) in Bianchi type-II cosmology with an appropriate choice of a function f( T)= μ T. We use the power law relation between average Hubble parameter H and average scale factor R to find the solution. The assumption of constant deceleration parameter leads to two models of universe, i.e. power law model and exponential model. Some physical and kinematical properties of the model are also discussed.

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

Relationship between Ni(II) and Zn(II) Coordination and Nucleotide Binding by the Helicobacter pylori [NiFe]-Hydrogenase and Urease Maturation Factor HypB*

PubMed Central

Sydor, Andrew M.; Lebrette, Hugo; Ariyakumaran, Rishikesh; Cavazza, Christine; Zamble, Deborah B.

2014-01-01

The pathogen Helicobacter pylori requires two nickel-containing enzymes, urease and [NiFe]-hydrogenase, for efficient colonization of the human gastric mucosa. These enzymes possess complex metallocenters that are assembled by teams of proteins in multistep pathways. One essential accessory protein is the GTPase HypB, which is required for Ni(II) delivery to [NiFe]-hydrogenase and participates in urease maturation. Ni(II) or Zn(II) binding to a site embedded in the GTPase domain of HypB modulates the enzymatic activity, suggesting a mechanism of regulation. In this study, biochemical and structural analyses of H. pylori HypB (HpHypB) revealed an intricate link between nucleotide and metal binding. HpHypB nickel coordination, stoichiometry, and affinity were modulated by GTP and GDP, an effect not observed for zinc, and biochemical evidence suggests that His-107 coordination to nickel toggles on and off in a nucleotide-dependent manner. These results are consistent with the crystal structure of HpHypB loaded with Ni(II), GDP, and Pi, which reveals a nickel site distinct from that of zinc-loaded Methanocaldococcus jannaschii HypB as well as subtle changes to the protein structure. Furthermore, Cys-142, a metal ligand from the Switch II GTPase motif, was identified as a key component of the signal transduction between metal binding and the enzymatic activity. Finally, potassium accelerated the enzymatic activity of HpHypB but had no effect on the other biochemical properties of the protein. Altogether, this molecular level information about HpHypB provides insight into its cellular function and illuminates a possible mechanism of metal ion discrimination. PMID:24338018

Relationship between Ni(II) and Zn(II) coordination and nucleotide binding by the Helicobacter pylori [NiFe]-hydrogenase and urease maturation factor HypB.

PubMed

Sydor, Andrew M; Lebrette, Hugo; Ariyakumaran, Rishikesh; Cavazza, Christine; Zamble, Deborah B

2014-02-14

The pathogen Helicobacter pylori requires two nickel-containing enzymes, urease and [NiFe]-hydrogenase, for efficient colonization of the human gastric mucosa. These enzymes possess complex metallocenters that are assembled by teams of proteins in multistep pathways. One essential accessory protein is the GTPase HypB, which is required for Ni(II) delivery to [NiFe]-hydrogenase and participates in urease maturation. Ni(II) or Zn(II) binding to a site embedded in the GTPase domain of HypB modulates the enzymatic activity, suggesting a mechanism of regulation. In this study, biochemical and structural analyses of H. pylori HypB (HpHypB) revealed an intricate link between nucleotide and metal binding. HpHypB nickel coordination, stoichiometry, and affinity were modulated by GTP and GDP, an effect not observed for zinc, and biochemical evidence suggests that His-107 coordination to nickel toggles on and off in a nucleotide-dependent manner. These results are consistent with the crystal structure of HpHypB loaded with Ni(II), GDP, and Pi, which reveals a nickel site distinct from that of zinc-loaded Methanocaldococcus jannaschii HypB as well as subtle changes to the protein structure. Furthermore, Cys-142, a metal ligand from the Switch II GTPase motif, was identified as a key component of the signal transduction between metal binding and the enzymatic activity. Finally, potassium accelerated the enzymatic activity of HpHypB but had no effect on the other biochemical properties of the protein. Altogether, this molecular level information about HpHypB provides insight into its cellular function and illuminates a possible mechanism of metal ion discrimination.

The Transcription Factor Rbf1 Is the Master Regulator for b-Mating Type Controlled Pathogenic Development in Ustilago maydis

PubMed Central

Vranes, Miroslav; Wahl, Ramon; Pothiratana, Chetsada; Schuler, David; Vincon, Volker; Finkernagel, Florian; Flor-Parra, Ignacio; Kämper, Jörg

2010-01-01

In the phytopathogenic basidiomycete Ustilago maydis, sexual and pathogenic development are tightly connected and controlled by the heterodimeric bE/bW transcription factor complex encoded by the b-mating type locus. The formation of the active bE/bW heterodimer leads to the formation of filaments, induces a G2 cell cycle arrest, and triggers pathogenicity. Here, we identify a set of 345 bE/bW responsive genes which show altered expression during these developmental changes; several of these genes are associated with cell cycle coordination, morphogenesis and pathogenicity. 90% of the genes that show altered expression upon bE/bW-activation require the zinc finger transcription factor Rbf1, one of the few factors directly regulated by the bE/bW heterodimer. Rbf1 is a novel master regulator in a multilayered network of transcription factors that facilitates the complex regulatory traits of sexual and pathogenic development. PMID:20700446

An investigation into the effect of type I and type II diabetes duration on employment and wages.

PubMed

Minor, Travis

2013-12-01

Using data from the National Longitudinal Survey of Youth 1979, the current study examines the effect of type I and type II diabetes on employment status and wages. The results suggest that both the probability of employment and wages are negatively related to the number of years since the initial diagnosis of diabetes. Moreover, the effect of diabetes duration on the probability of employment appears to be nonlinear, peaking around 16 years for females and 10 years for males. A similar negative effect on wages is found only in male diabetics. Finally, the results suggest that failure to distinguish between type I and type II diabetics may lead to some counterintuitive results. Published by Elsevier B.V.

Moving beyond Type I and Type II neuron types.

PubMed

Skinner, Frances K

2013-01-01

In 1948, Hodgkin delineated different classes of axonal firing.  This has been mathematically translated allowing insight and understanding to emerge.  As such, the terminology of 'Type I' and 'Type II' neurons is commonplace in the Neuroscience literature today.  Theoretical insights have helped us realize that, for example, network synchronization depends on whether neurons are Type I or Type II.  Mathematical models are precise with analyses (considering Type I/II aspects), but experimentally, the distinction can be less clear.  On the other hand, experiments are becoming more sophisticated in terms of distinguishing and manipulating particular cell types but are limited in terms of being able to consider network aspects simultaneously.   Although there is much work going on mathematically and experimentally, in my opinion it is becoming common that models are either superficially linked with experiment or not described in enough detail to appreciate the biological context.  Overall, we all suffer in terms of impeding our understanding of brain networks and applying our understanding to neurological disease.  I suggest that more modelers become familiar with experimental details and that more experimentalists appreciate modeling assumptions. In other words, we need to move beyond our comfort zones.

Autosomal Dominant Growth Hormone Deficiency (Type II).

PubMed

Alatzoglou, Kyriaki S; Kular, Dalvir; Dattani, Mehul T

2015-06-01

Isolated growth hormone deficiency (IGHD) is the commonest pituitary hormone deficiency resulting from congenital or acquired causes, although for most patients its etiology remains unknown. Among the known factors, heterozygous mutations in the growth hormone gene (GH1) lead to the autosomal dominant form of GHD, also known as type II GHD. In many cohorts this is the commonest form of congenital isolated GHD and is mainly caused by mutations that affect the correct splicing of GH-1. These mutations cause skipping of the third exon and lead to the production of a 17.5-kDa GH isoform that exerts a dominant negative effect on the secretion of the wild type GH. The identification of these mutations has clinical implications for the management of patients, as there is a well-documented correlation between the severity of the phenotype and the increased expression of the 17.5-kDa isoform. Patients with type II GHD have a variable height deficit and severity of GHD and may develop additional pituitary hormone defiencies over time, including ACTH, TSH and gonadotropin deficiencies. Therefore, their lifelong follow-up is recommended. Detailed studies on the effect of heterozygous GH1 mutations on the trafficking, secretion and action of growth hormone can elucidate their mechanism on a cellular level and may influence future treatment options for GHD type II.

[Management and outcome of type II fractures of the odontoid process].

PubMed

Meyer, Carolin; Oppermann, Johannes; Meermeyer, Ingo; Eysel, Peer; Müller, Lars Peter; Stein, Gregor

2018-05-01

The most effective treatment of type II dens fractures according to Anderson and D'Alonzo remains controversial as there is no guidance on the choice of conservative or surgical therapy and if the anterior or the posterior approach is more advantageous. In 1993 Eysel and Roosen showed that the consolidation rate of type II odontoid fractures mostly depends on the morphology of the fracture and established a classification with corresponding treatment recommendations. The investigation aimed at clarifying the outcome of type II dens fractures treated according to the recommendations of Eysel and Roosen. Data of dens fractures from 72 patients were analyzed and categorized according to the Eysel and Roosen classification. Furthermore, the treatment was analyzed and the outcome was evaluated retrospectively using radiographs acquired during follow-up. The mean age of the 72 patients was 70.7 years. Of the patients 19.4% suffered from type A, 75% from type B and 5.6% from type C fractures according to Eysel and Roosen. Out of the 72 patients 45 were assessed by computed tomography (CT) scan during follow-up. According to the recommendations of the authors 34 of the 41 patients with type A or type B fractures underwent anterior screw fixation of the dens and 3 out of the 4 patients with a type C fracture underwent a dorsal C1 and C2 fusion. After a mean follow-up of 7 months non-union was observed in 15.6% of the patients whereby 6 of the these patients were treated by surgery and 1 patient was managed conservatively. All of the patients who developed a non-union had a type B fracture. The simple clinical applicability together with the low rate of non-union development shows that the Eysel and Roosen classification appears to be a suitable guide for clinical use when deciding on the appropriate treatment regimen.

Analysis of tumor necrosis factor-alpha promoter polymorphism in type 1 diabetes: HLA-B and -DRB1 alleles are primarily associated with the disease in Japanese.

PubMed

Hamaguchi, K; Kimura, A; Seki, N; Higuchi, T; Yasunaga, S; Takahashi, M; Sasazuki, T; Kusuda, Y; Okeda, T; Itoh, K; Sakata, T

2000-01-01

Polymorphisms in the 5'-flanking region of the tumor necrosis factor (TNF)-alpha gene were examined to study the genetic background of type 1 diabetes in Japanese. Five different biallelic polymorphisms were examined in 136 type 1 diabetic patients and 300 control subjects. The frequencies of individuals carrying TNF-alpha-857T allele (designated as TNFP-D allele) or -863A/-1,031C allele (designated as TNFP-B allele) were significantly increased in the patients as compared with the controls. Since these TNF-alpha alleles are in linkage disequilibria with certain DRB1 and HLA-B alleles, two-locus analyses were carried out. The TNFP-D allele did not increase the risk in either the presence or absence of the DRB1*0405 or HLA-B54 allele, while the DRB1*0405 and HLA-B54 alleles per se could confer susceptibility in both the TNFP-D allele-positive and -negative populations. Moreover, an odds ratio was remarkably elevated in the population carrying both DRB1*0405 and HLA-B54. Similarly, the TNFP-B allele did not show significant association with the disease in either the HLA-B61-positive or -negative population, while the HLA-B61 allele could significantly increase the risk in the TNFP-B allele-positive population. These data suggest that the associations of TNFP-D and -B alleles may be secondary to their linkage disequilibria with the susceptible HLA class I and class II alleles. Because HLA-B and DRB1 genes were independently associated, both of these genes may be contributed primarily to the pathogenesis of type 1 diabetes in Japanese.

The Type Ia supernova 1989B in NGC 3627 (M66)

NASA Technical Reports Server (NTRS)

Wells, Lisa A.; Phillips, M. M.; Suntzeff, Nicholas B.; Heathcote, S. R.; Hamuy, Mario; Navarrete, M.; Fernandez, M.; Weller, W. G.; Schommer, R. A.; Kirshner, Robert P.

1994-01-01

We report extensive optical photometry and spectroscopy of the Type Ia supernova 1989B. Maximum light in B occurred approximately seven days after discovery on JD 2447565.3 +/- 1.0 (1989 February 7.8 +/- 1.0) at a magnitude of 12.34 +/- 0.05. The UBV light curves of this supernova were very similar to those of other well observed Type Ia events such as SN 1981B and SN 1980N. From a comparison of the UBVRIJHK photometry, we derive an extinction for SN 1989B of E(B-V) = 0.37 +/- 0.03 mags relative to the unobscured Type Ia SN 1980N. The properties of the dust responsible for the reddening of SN 1989B appear to have been similar to those of normal dust in the Milky Way. In particular, we find no evidence for an unusually low value of the ratio of the total to selective absorption. We derive a distance modulus of delta mu(sub 0) = -1.62 +/- 0.03 mag relative to the Type Ia SN 1980N. We present optical spectra which provide essentially continuous coverage of the spectral evolution of SN 1989B over the first month following B maximum. These data show the transition from the maximum-light spectrum, in which lines of elements such as Ca, Si, S, Mg, and O are most prominent, to the Fe-dominated spectrum observed a few weeks after maximum. This transition occurred quite smoothly over a two-week period following B maximum. Comparison of the spectra of SN 1989B with data for two other well observed Type Ia supernovae -- 1981B and 1986G -- reveals subtle differences in the relative strengths of the S II and Si II absorption lines at maximum light. However, these differences disappeared within a week or so after maximum with the onset of the Fe-dominated phase.

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

The potential mechanism of Bursal-derived BPP-II on the antibody production and avian pre-B cell.

PubMed

Feng, Xiuli; Cao, Ruibing; Zhou, Bin; Liu, Qingtao; Liu, Ke; Liu, Xiaodong; Zhang, Yuanpeng; Gu, Jinyan; Miao, Denian; Chen, Puyan

2013-03-01

The bursa of Fabricius is critical for the normal development of the B lymphocytes responsible for antibody production. However, the mechanism of the bursal-derived bioactive factor on B cell development is little reported. In this paper, chicks were immunized with BPP-II and AIV vaccine or AIV antigen, and antibody and IL-4 production were detected. The results showed that BPP-II played strongly inducing roles on the humoral immune responses. To investigate the gene expression at transcriptional level, avian pre-B lymphocyte DT40 cells were treated with BPP-II, and were analyzed with the gene microarray. The results proved that BPP-II treatment regulated 11 pathways, in which homologous recombination is a vital mechanism which is involved in antibody Ig gene conversion and diversification during B cell development. These results suggested Bursal-derived biological active factor BPP-II might be involved in the antibody production processes and B cell development, which is vital to the humoral central immune organ, the bursa of Fabricius. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy.

PubMed

Stagg, John; Loi, Sherene; Divisekera, Upulie; Ngiow, Shin Foong; Duret, Helene; Yagita, Hideo; Teng, Michele W; Smyth, Mark J

2011-04-26

Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor-2 (HER2/ErbB-2), has become the mainstay of treatment for HER2-positive breast cancer. Nevertheless, its exact mechanism of action has not been fully elucidated. Although several studies suggest that Fc receptor-expressing immune cells are involved in trastuzumab therapy, the relative contribution of lymphocyte-mediated cellular cytotoxicity and antitumor cytokines remains unknown. We report here that anti-ErbB-2 mAb therapy is dependent on the release of type I and type II IFNs but is independent of perforin or FasL. Our study thus challenges the notion that classical antibody-dependent, lymphocyte-mediated cellular cytotoxicity is important for trastuzumab. We demonstrate that anti-ErbB-2 mAb therapy of experimental tumors derived from MMTV-ErbB-2 transgenic mice triggers MyD88-dependent signaling and primes IFN-γ-producing CD8+ T cells. Adoptive cell transfer of purified T cell subsets confirmed the essential role of IFN-γ-producing CD8+ T cells. Notably, anti-ErbB-2 mAb therapy was independent of IL-1R or IL-17Ra signaling. Finally, we investigated whether immunostimulatory approaches with antibodies against programmed death-1 (PD-1) or 41BB (CD137) could be used to capitalize on the immune-mediated effects of trastuzumab. We demonstrate that anti-PD-1 or anti-CD137 mAb can significantly improve the therapeutic activity of anti-ErbB-2 mAb in immunocompetent mice.

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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y.

PubMed

Tosi, Giovanna; Pilotti, Elisabetta; Mortara, Lorenzo; De Lerma Barbaro, Andrea; Casoli, Claudio; Accolla, Roberto S

2006-08-22

The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from positions 64-144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300/CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells.

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.

Nonmuscle Myosin II Is Required for Internalization of the Epidermal Growth Factor Receptor and Modulation of Downstream Signaling*

PubMed Central

Kim, Jong Hyun; Wang, Aibing; Conti, Mary Anne; Adelstein, Robert S.

2012-01-01

Ligand-induced internalization of the epidermal growth factor receptor (EGFR) is an important process for regulating signal transduction, cellular dynamics, and cell-cell communication. Here, we demonstrate that nonmuscle myosin II (NM II) is required for the internalization of the EGFR and to trigger the EGFR-dependent activation of ERK and AKT. The EGFR was identified as a protein that interacts with NM II by co-immunoprecipitation and mass spectrometry analysis. This interaction requires both the regulatory light chain 20 (RLC20) of NM II and the kinase domain of the EGFR. Two paralogs of NM II, NM II-A, and NM II-B can act to internalize the EGFR, depending on the cell type and paralog content of the cell line. Loss (siRNA) or inhibition (25 μm blebbistatin) of NM II attenuates the internalization of the EGFR and impairs EGFR-dependent activation of ERK and AKT. Both internalization of the EGFR and downstream signaling to ERK and AKT can be partially restored in siRNA-treated cells by introduction of wild type (WT) GFP-NM II, but cannot be restored by motor mutant NM II. Taken together, these results suggest that NM II plays a role in the internalization of the EGFR and EGFR-mediated signaling pathways. PMID:22718763

Subneurotoxic copper(II)-induced NF-κB-dependent microglial activation is associated with mitochondrial ROS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Zhuqin; Yu, Fengxiang; Gong, Ping

2014-04-15

Microglia-mediated neuroinflammation and the associated neuronal damage play critical roles in the pathogenesis of neurodegenerative disorders. Evidence shows an elevated concentration of extracellular copper(II) in the brains of these disorders, which may contribute to neuronal death through direct neurotoxicity. Here we explored whether extracellular copper(II) triggers microglial activation. Primary rat microglia and murine microglial cell line BV-2 cells were cultured and treated with copper(II). The content of tumor necrosis factor-α (TNF-α) and nitric oxide in the medium was determined. Extracellular hydrogen peroxide was quantified by a fluorometric assay with Amplex Red. Mitochondrial superoxide was measured by MitoSOX oxidation. At subneurotoxicmore » concentrations, copper(II) treatment induced a dose- and time-dependent release of TNF-α and nitric oxide from microglial cells, and caused an indirect, microglia-mediated neurotoxicity that was blocked by inhibition of TNF-α and nitric oxide production. Copper(II)-initiated microglial activation was accompanied with reduced IkB-α expression as well as phosphorylation and translocation of nuclear factor-κB (NF-κB) p65 and was blocked by NF-κB inhibitors (BAY11-7082 and SC-514). Moreover, copper(II) treatment evoked a rapid release of hydrogen peroxide from microglial cells, an effect that was not affected by NADPH oxidase inhibitors. N-acetyl-cysteine, a scavenger of reactive oxygen species (ROS), abrogated copper(II)-elicited microglial release of TNF-α and nitric oxide and subsequent neurotoxicity. Importantly, mitochondrial production of superoxide, paralleled to extracellular release of hydrogen peroxide, was induced after copper(II) stimulation. Our findings suggest that extracellular copper(II) at subneurotoxic concentrations could trigger NF-κB-dependent microglial activation and subsequent neurotoxicity. NADPH oxidase-independent, mitochondria-derived ROS may be involved in this activation

Induction of Epstein-Barr Virus Oncoprotein LMP1 by Transcription Factors AP-2 and Early B Cell Factor

PubMed Central

Noda, Chieko; Narita, Yohei; Watanabe, Takahiro; Yoshida, Masahiro; Ashio, Keiji; Sato, Yoshitaka; Goshima, Fumi; Kanda, Teru; Yoshiyama, Hironori; Tsurumi, Tatsuya; Kimura, Hiroshi

2016-01-01

ABSTRACT Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter. IMPORTANCE Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is crucial for B cell transformation and oncogenesis of other EBV-related malignancies, such as nasopharyngeal carcinoma and T/NK lymphoma. Its expression is largely dependent on the cell type or condition, and some transcription factors have been implicated in its regulation. However, these previous reports evaluated the significance of specific factors mostly by reporter assay. In this study, we prepared point-mutated EBV at the binding sites of such transcription factors and confirmed the importance of AP-2, EBF, PU.1, and POU domain factors. Our results will provide insight into the transcriptional regulation of the major oncogene LMP1. PMID:26819314

Effect of cholesterol depletion on exocytosis of alveolar type II cells.

PubMed

Chintagari, Narendranath Reddy; Jin, Nili; Wang, Pengcheng; Narasaraju, Telugu Akula; Chen, Jiwang; Liu, Lin

2006-06-01

Alveolar epithelial type II cells secrete lung surfactant via exocytosis. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) are implicated in this process. Lipid rafts, the cholesterol- and sphingolipid-rich microdomains, may offer a platform for protein organization on the cell membrane. We tested the hypothesis that lipid rafts organize exocytotic proteins in type II cells and are essential for the fusion of lamellar bodies, the secretory granules of type II cells, with the plasma membrane. The lipid rafts, isolated from type II cells using 1% Triton X-100 and a sucrose gradient centrifugation, contained the lipid raft markers, flotillin-1 and -2, whereas they excluded the nonraft marker, Na+-K+ ATPase. SNAP-23, syntaxin 2, and VAMP-2 were enriched in lipid rafts. When type II cells were depleted of cholesterol, the association of SNAREs with the lipid rafts was disrupted and the formation of fusion pore was inhibited. Furthermore, the cholesterol-depleted plasma membrane had less ability to fuse with lamellar bodies, a process mediated by annexin A2. The secretagogue-stimulated secretion of lung surfactant from type II cells was also reduced by methyl-beta-cyclodextrin. When the raft-associated cell surface protein, CD44, was cross-linked using anti-CD44 antibodies, the CD44 clusters were observed. Syntaxin 2, SNAP-23, and annexin A2 co-localized with the CD44 clusters, which were cholesterol dependent. Our results suggested that lipid rafts may form a functional platform for surfactant secretion in alveolar type II cells, and raft integrity was essential for the fusion between lamellar bodies with the plasma membrane.

Angiotensin II modulates interleukin-1{beta}-induced inflammatory gene expression in vascular smooth muscle cells via interfering with ERK-NF-{kappa}B crosstalk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Shanqin; Zhi, Hui; Hou, Xiuyun

2011-07-08

Highlights: {yields} We examine how angiotensin II modulates ERK-NF-{kappa}B crosstalk and gene expression. {yields} Angiotensin II suppresses IL-1{beta}-induced prolonged ERK and NF-{kappa}B activation. {yields} ERK-RSK1 signaling is required for IL-1{beta}-induced prolonged NF-{kappa}B activation. {yields} Angiotensin II modulates NF-{kappa}B responsive genes via regulating ERK-NF-{kappa}B crosstalk. {yields} ERK-NF-{kappa}B crosstalk is a novel mechanism regulating inflammatory gene expression. -- Abstract: Angiotensin II is implicated in cardiovascular diseases, which is associated with a role in increasing vascular inflammation. The present study investigated how angiotensin II modulates vascular inflammatory signaling and expression of inducible nitric oxide synthase (iNOS) and vascular cell adhesion molecule (VCAM)-1. Inmore » cultured rat aortic vascular smooth muscle cells (VSMCs), angiotensin II suppressed interleukin-1{beta}-induced prolonged phosphorylation of extracellular signal-regulated kinase (ERK) and ribosomal S6 kinase (RSK)-1, and nuclear translocation of nuclear factor (NF)-{kappa}B, leading to decreased iNOS but enhanced VCAM-1 expression, associated with an up-regulation of mitogen-activated protein kinase phosphatase-1 expression. Knock-down of RSK1 selectively down regulated interleukin-1{beta}-induced iNOS expression without influencing VCAM-1 expression. In vivo experiments showed that interleukin-1{beta}, iNOS, and VCAM-1 expression were detectable in the aortic arches of both wild-type and apolipoprotein E-deficient (ApoE{sup -/-}) mice. VCAM-1 and iNOS expression were higher in ApoE{sup -/-} than in wild type mouse aortic arches. Angiotensin II infusion (3.2 mg/kg/day, for 6 days, via subcutaneous osmotic pump) in ApoE{sup -/-} mice enhanced endothelial and adventitial VCAM-1 and iNOS expression, but reduced medial smooth muscle iNOS expression associated with reduced phosphorylation of ERK and RSK-1. These results indicate that

UBVRIz LIGHT CURVES OF 51 TYPE II SUPERNOVAE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galbany, Lluis; Hamuy, Mario; Jaeger, Thomas de

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) frommore » 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.« less

The nature of the late B-type stars HD 67044 and HD 42035

NASA Astrophysics Data System (ADS)

Monier, R.; Gebran, M.; Royer, F.

2016-04-01

While monitoring a sample of apparently slowly rotating superficially normal bright late B and early A stars in the northern hemisphere, we have discovered that HD 67044 and HD 42035, hitherto classified as normal late B-type stars, are actually respectively a new chemically peculiar star and a new spectroscopic binary containing a very slow rotator HD 42035 S with ultra-sharp lines (v_{{e}}sin i= 3.7 km s^{-1}) and a fast rotator HD 42035 B with broad lines. The lines of Ti ii, Cr ii, Mn ii, Sr ii, Y ii, Zr ii and Ba ii are conspicuous features in the high resolution SOPHIE spectrum (R=75000) of HD 67044. The Hg ii line at 3983.93 Å is also present as a weak feature. The composite spectrum of HD 42035 is characterised by very sharp lines formed in HD 42035 S superimposed onto the shallow and broad lines of HD 42035 B. These very sharp lines are mostly due to light elements from C to Ni, the only heavy species definitely present are strontium and barium. Selected lines of 21 chemical elements from He up to Hg have been synthesized using model atmospheres computed with ATLAS9 and the spectrum synthesis code SYNSPEC48 including hyperfine structure of various isotopes when relevant. These synthetic spectra have been adjusted to high resolution high signal-to-noise spectra of HD 67044 and HD 42035 S in order to derive abundances of these key elements. HD 67044 is found to have distinct enhancements of Ti, Cr, Mn, Sr, Y, Zr, Ba and Hg and underabundances in He, C, O, Ca and Sc which shows that this star is not a superficially normal late B-type star, but actually is a new CP star most likely of the HgMn type. HD 42035 S has provisional underabundances of the light elements from C to Ti and overabundances of heavier elements (except for Fe and Sr which are also underabundant) up to barium. These values are lower limits to the actual abundances as we cannot currently place properly the continuum of HD 42035 S. More accurate fundamental parameters and abundances for HD

Human Rehabilitation Techniques. Disability Analyses: Behavioral Disabilities. Volume II, Part B.

ERIC Educational Resources Information Center

Sigelman, C.; And Others

Volume II, Section B of a six-volume final report (which covers the findings of a research project on policy and technology related to rehabilitation of disabled individuals) presents a review of literature on three types of behavior disabilities--epilepsy, mental retardation, and schizophrenia. Individual chapters on each disability cover the…

Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.

PubMed

Ji, Rong; Lee, Clement M; Gonzales, Linda W; Yang, Yi; Aksoy, Mark O; Wang, Ping; Brailoiu, Eugen; Dun, Nae; Hurford, Matthew T; Kelsen, Steven G

2008-06-01

Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca(2+) activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.

Relation Between Type II Bursts and CMEs Inferred from STEREO Observations

NASA Technical Reports Server (NTRS)

Gopalswamy, N.; Thompson, W.; Davila, J.; Kaiser, M. L.; Yashiro, S.; Maekelae, P.; Michalek, G.; Bougeret, J.-L.; Hoawrd, R. A.

2010-01-01

The inner coronagraph (COR1) of the Solar Terrestrial Relations Observatory (STEREO) mission has made it possible to observe coronal mass ejections (CMEs) a in the spatial domain overlapping with that of the metric type II radio bursts. The type II bursts were associated with generally weak flares (mostly B and C class soft X-ray flares), but the CMEs were quite energetic. Using CME data for a set of type II bursts during the declining phase of solar cycle 23, we determine the CME height when the type II bursts start, thus giving an estimate of the heliocentric distance at which CME-driven shocks form. This distance has been determined to be approximately 1.5Rs (solar radii), which coincides with the distance at which the Alfv?n speed profile has a minimum value. We also use type II radio observations from STEREO/WAVES and Wind/WAVES observations to show that CMEs with moderate speed drive either weak shocks or no shock at all when they attain a height where the Alfv?n speed peaks (?3Rs ? 4Rs). Thus the shocks seem to be most efficient in accelerating electrons in the heliocentric distance range of 1.5Rs to 4Rs. By combining the radial variation of the CME speed in the inner corona (CME speed increase) and interplanetary medium (speed decrease) we were able to correctly account for the deviations from the universal drift-rate spectrum of type II bursts, thus confirming the close physical connection between type II bursts and CMEs. The average height (approximately 1.5 Rs) of STEREO CMEs at the time of type II bursts is smaller than that (2.2 Rs) obtained for SOHO (Solar and Heliospheric Observatory) CMEs. We suggest that this may indicate, at least partly, the density reduction in the corona between the maximum and declining phases, so a given plasma level occurs closer to the Sun in the latter phase. In two cases, there was a diffuse shock-like feature ahead of the main body of the CME, indicating a standoff distance of 1Rs - 2Rs by the time the CME left the LASCO

Relation Between Type II Bursts and CMEs Inferred from STEREO Observations

NASA Technical Reports Server (NTRS)

Gopalswamy, N.; Thompson, W.; Davila, J.; Kaiser, M.; Yashiro, S.; Maelekae, P.; Michalek, G.; Bougret, J.-L.; Howard, R. A.

2009-01-01

The inner coronagraph (COR1) of the Solar Terrestrial Relations Observatory (STEREO) mission has made it possible to observe CMEs in the spatial domain overlapping with that of the metric type II radio bursts. The type II bursts were associated with generally weak flares (mostly B and C class soft X-ray flares), but the CMEs were quite energetic. Using CME data for a set of type II bursts during the declining phase of solar cycle 23, we determine the CME height when the type II bursts start, thus giving an estimate of the heliocentric distance at which CME-driven shocks form. This distance has been determined to be approx. 1.5Rs (solar radii), which coincides with the distance at which the Alfven speed profile has a minimum value.We also use type II radio observations from STEREO/WAVES and Wind/WAVES observations to show that CMEs with moderate speed drive either weak shocks or no shock at all when they attain a height where the Alfven speed peaks (approx. 3Rs - 4Rs). Thus the shocks seem to be most efficient in accelerating electrons in the heliocentric distance range of 1.5Rs to 4Rs. By combining the radial variation of the CME speed in the inner corona (CME speed increase) and interplanetary medium (speed decrease) we were able to correctly account for the deviations from the universal drift-rate spectrum of type II bursts, thus confirming the close physical connection between type II bursts and CMEs. The average height (approx 1.5Rs) of STEREO CMEs at the time of type II bursts is smaller than that (2.2Rs) obtained for SOHO (Solar and Heliospheric Observatory) CMEs. We suggest that this may indicate, at least partly, the density reduction in the corona between the maximum and declining phases, so a given plasma level occurs closer to the Sun in the latter phase. In two cases, there was a diffuse shock-like feature ahead of the main body of the CME, indicating a standoff distance of 1Rs - 2Rs by the time the CME left the LASCO field of view.

Prediction of CMEs and Type II Bursts from Sun to Earth

NASA Astrophysics Data System (ADS)

Cairns, I. H.; Schmidt, J. M.; Gopalswamy, N.; van der Holst, B.

2017-12-01

Most major space weather events are due to fast CMEs and their shocks interacting with Earth's magnetosphere. SImilarly, type II solar radio bursts are well-known signatures of CMEs and their shocks moving through the corona and solar wind. The properties of the space weather events and the type II radio bursts depend sensitively on the CME velocity, shape, and evolution as functions of position and time, as well as on the magnetic field vector in the coronal and solar wind plasma, downstream of the CME shock, and inside the CME. We report simulations of CMEs and type II bursts from the Sun to Earth with the Space Weather Modelling Framework (2015 and 2016 versions), set up carefully using relevant data, and a kinetic radio emission theory. Excellent agreement between observations, simulations, and theory are found for the coronal (metric) type II burst of 7 September 2014 and associated CME, including the lack of radio emission in the solar wind beyond about 10 solar radii. Similarly, simulation of a CME and type II burst from the Sun to 1 AU over the period 29 November - 1 December 2013 yield excellent agreement for the radio burst from 10 MHz to 30 kHz for STEREO A and B and Wind, arrival of the CME at STEREO A within 1 hour reported time, deceleration of the CME in agreement with the Gopalswamy et al. [2011] observational analyses, and Bz rotations at STEREO A from upstream of the CME shock to within the CME. These results provide strong support for the type II theory and also that the Space WeatherModeling Framework can accurately predict the properties and evolution of CMEs and the interplanetary magnetic field and plasma from the Sun to 1 AU when sufficiently carefully initialized.

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

Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency

PubMed Central

Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

2017-01-01

Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels. PMID:28095507

Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency.

PubMed

Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

2017-01-01

Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels.

Dynamic expression of transcription factor Brn3b during mouse cranial nerve development

PubMed Central

Sajgo, Szilard; Ali, Seid; Popescu, Octavian; Badea, Tudor Constantin

2015-01-01

During development transcription factor combinatorial codes define a large variety of morphologically and physiologically distinct neurons. Such a combinatorial code has been proposed for the differentiation of projection neurons of the somatic and visceral components of cranial nerves. It is possible that individual neuronal cell types are not specified by unique transcription factors, but rather emerge through the intersection of their expression domains. Brn3a, Brn3b and Brn3c, in combination with each other and/or transcription factors of other families, can define subgroups of Retinal Ganglion Cells (RGC), Spiral and Vestibular Ganglia, inner ear and vestibular hair cell neurons in the vestibuloacoustic system, and groups of somatosensory neurons in the Dorsal Root Ganglia (DRG). In the present study we investigated the expression and potential role of the Brn3b transcription factor in cranial nerves and associated nuclei of the brainstem. We report the dynamic expression of Brn3b in the somatosensory component of cranial nerves II, V, VII and VIII and visceromotor nuclei of nerves VII, IX, X, as well as other brainstem nuclei during different stages of development into adult stage. We find that genetically identified Brn3bKO RGC axons show correct but delayed pathfinding during the early stages of embryonic development. However loss of Brn3b does not affect the anatomy of the other cranial nerves normally expressing this transcription factor. PMID:26356988

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.

Maternal insulin-like growth factor-II promotes placental functional development via the type 2 IGF receptor in the guinea pig.

PubMed

Sferruzzi-Perri, A N; Owens, J A; Standen, P; Roberts, C T

2008-04-01

In guinea pigs, maternal insulin-like growth factor (IGF) infusion in early-pregnancy enhances placental transport near-term, increasing fetal growth and survival. The effects of IGF-II, but not IGF-I, appear due to enhanced placental labyrinthine (exchange) development. To determine if the type-2 IGF receptor (IGF2R) mediates these distinct actions of exogenous IGF-II in the mother, we compared the impact of IGF-II with an IGF-II analogue, Leu(27)-IGF-II, which only binds the IGF2R. IGF-II, Leu(27)-IGF-II (1mg/kg per day.sc) or vehicle were infused from days 20-38 of pregnancy (term = 67 days) and placental structure and uptake and transfer of [(3)H]-methyl-D-glucose (MG) and [(14)C]-amino-isobutyric acid (AIB) and fetal growth and plasma metabolites, were measured on day 62. Both IGF-II and Leu(27)-IGF-II increased the volume of placental labyrinth, trophoblast and maternal blood space within the labyrinth and total surface area of trophoblast for exchange, compared to vehicle. Leu(27)-IGF-II also reduced the barrier to diffusion (trophoblast thickness) compared to vehicle and IGF-II. Both IGF-II and Leu(27)-IGF-II increased fetal plasma amino acid concentrations and placental transfer of MG to the fetus compared to vehicle, with Leu(27)-IGF-II also increasing AIB transport compared with vehicle and IGF-II. In addition, Leu(27)-IGF-II increased fetal weight compared to vehicle. In conclusion, maternal treatment with IGF-II or Leu(27)-IGF-II in early gestation, induce similar placental and fetal outcomes near term. This suggests that maternal IGF-II in early gestation acts in part via the IGF2R to persistently enhance placental functional development and nutrient delivery and promote fetal growth.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cody, Vivian, E-mail: cody@hwi.buffalo.edu; University at Buffalo, 700 Ellicott Street, Buffalo, NY 14203; Pace, Jim

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}, butmore » 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

A Type II Supernova Hubble Diagram from the CSP-I, SDSS-II, and SNLS Surveys

NASA Astrophysics Data System (ADS)

de Jaeger, T.; González-Gaitán, S.; Hamuy, M.; Galbany, L.; Anderson, J. P.; Phillips, M. M.; Stritzinger, M. D.; Carlberg, R. G.; Sullivan, M.; Gutiérrez, C. P.; Hook, I. M.; Howell, D. Andrew; Hsiao, E. Y.; Kuncarayakti, H.; Ruhlmann-Kleider, V.; Folatelli, G.; Pritchet, C.; Basa, S.

2017-02-01

The coming era of large photometric wide-field surveys will increase the detection rate of supernovae by orders of magnitude. Such numbers will restrict spectroscopic follow-up in the vast majority of cases, and hence new methods based solely on photometric data must be developed. Here, we construct a complete Hubble diagram of Type II supernovae (SNe II) combining data from three different samples: the Carnegie Supernova Project-I, the Sloan Digital Sky Survey II SN, and the Supernova Legacy Survey. Applying the Photometric Color Method (PCM) to 73 SNe II with a redshift range of 0.01-0.5 and with no spectral information, we derive an intrinsic dispersion of 0.35 mag. A comparison with the Standard Candle Method (SCM) using 61 SNe II is also performed and an intrinsic dispersion in the Hubble diagram of 0.27 mag, I.e., 13% in distance uncertainties, is derived. Due to the lack of good statistics at higher redshifts for both methods, only weak constraints on the cosmological parameters are obtained. However, assuming a flat universe and using the PCM, we derive the universe’s matter density: {{{Ω }}}m={0.32}-0.21+0.30 providing a new independent evidence for dark energy at the level of two sigma. This paper includes data gathered with the 6.5 m Magellan Telescopes, with the du Pont and Swope telescopes located at Las Campanas Observatory, Chile; and the Gemini Observatory, Cerro Pachon, Chile (Gemini Program N-2005A-Q-11, GN-2005B-Q-7, GN-2006A-Q-7, GS-2005A-Q-11, GS-2005B-Q-6, and GS-2008B-Q-56). Based on observations collected at the European Organization for Astronomical Research in the Southern Hemisphere, Chile (ESO Programmes 076.A-0156,078.D-0048, 080.A-0516, and 082.A-0526).

Central sympathoexcitatory actions of angiotensin II: role of type 1 angiotensin II receptors.

PubMed

DiBona, G F

1999-01-01

The role of the renin-angiotensin system in the control of sympathetic nerve activity is reviewed. Two general mechanisms are considered, one that involves the effects of circulating angiotensin II (AngII) on the central nervous system and a second that involves the central nervous system effects of AngII that originates within the central nervous system. The role of type 1 AngII receptors in discrete brain sites that mediate the sympathoexcitatory actions of AngII of either circulating or central nervous system origin is examined. AngII of circulating origin has ready access to the subfornical organ and area postrema, where it can bind to type 1 AngII receptors on neurons whose connections to the nucleus tractus solitarius and rostral ventrolateral medulla result in sympathoexcitation. In the rostral ventrolateral medulla, angiotensin peptides of central nervous system origin, likely involving angiotensin species in addition to AngII and binding to receptors other than type 1 or 2 AngII receptors, tonically support sympathetic nerve activity.

6β-HYDROXYTESTOSTERONE, A CYTOCHROME P450 1B1-TESTOSTERONE-METABOLITE, MEDIATES ANGIOTENSIN II-INDUCED RENAL DYSFUNCTION IN MALE MICE

PubMed Central

Pingili, Ajeeth K.; Thirunavukkarasu, Shyamala; Kara, Mehmet; Brand, David; Katsurada, Akemi; Majid, Dewan S. A.; Navar, L. Gabriel; Gonzalez, Frank J.; Malik, Kafait U.

2016-01-01

6β-hydroxytestosterone, a cytochrome P450 1B1-derived metabolite of testosterone, contributes to the development of angiotensin II-induced hypertension and associated cardiovascular pathophysiology. In view of the critical role of angiotensin II in the maintenance of renal homeostasis, development of hypertension and end organ damage, this study was conducted to determine the contribution of 6β-hydroxytestosterone to angiotensin II actions on water consumption and renal function in male Cyp1b1+/+ and Cyp1b1−/− mice. Castration of Cyp1b1+/+ mice or Cyp1b1−/− gene disruption minimized the angiotensin II-induced increase in water consumption, urine output, proteinuria, and sodium excretion and decreases in urine osmolality. 6β-hydroxytestosterone did not alter angiotensin II-induced increases in water intake, urine output, proteinuria, and sodium excretion or decreases in osmolality in Cyp1b1+/+ mice, but restored these effects of angiotensin II in Cyp1b1−/− or castrated mice Cyp1b1+/+ mice. Cyp1b1 gene disruption or castration prevented angiotensin II-induced renal fibrosis, oxidative stress, inflammation, urinary excretion of angiotensinogen, expression of angiotensin II type 1 receptor, and angiotensin converting enzyme. 6β-hydroxytestosterone did not alter angiotensin II-induced renal fibrosis, inflammation, oxidative stress, urinary excretion angiotensinogen, expression of angiotensin II type 1 receptor, or angiotensin converting enzyme in Cyp1b1+/+ mice; however, in Cyp1b1−/− or castrated mice Cyp1b1+/+ mice, it restored these effects of angiotensin II. These data indicate that 6β-hydroxytestosterone contributes to increased thirst, impairment of renal function, and end organ injury associated with angiotensin II-induced hypertension in male mice and that cytochrome P450 1B1 could serve as a novel target for treating renal disease and hypertension in males. PMID:26928804

Preliminary crystallographic analysis of mouse Elf3 C-terminal DNA-binding domain in complex with type II TGF-[beta] receptor promoter DNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarkar, Vinod B.; Babayeva, Nigar D.; Rizzino, Angie

2010-10-08

Ets proteins are transcription factors that activate or repress the expression of genes that are involved in various biological processes, including cellular proliferation, differentiation, development, transformation and apoptosis. Like other Ets-family members, Elf3 functions as a sequence-specific DNA-binding transcriptional factor. A mouse Elf3 C-terminal fragment (amino-acid residues 269-371) containing the DNA-binding domain has been crystallized in complex with mouse type II TGF-{beta} receptor promoter (TR-II) DNA. The crystals belonged to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 42.66, b = 52, c = 99.78 {angstrom}, and diffracted to a resolution of 2.2 {angstrom}.

Development of type-I/type-II hybrid dye sensitizer with both pyridyl group and catechol unit as anchoring group for type-I/type-II dye-sensitized solar cell.

PubMed

Ooyama, Yousuke; Furue, Kensuke; Enoki, Toshiaki; Kanda, Masahiro; Adachi, Yohei; Ohshita, Joji

2016-11-09

A type-I/type-II hybrid dye sensitizer with a pyridyl group and a catechol unit as the anchoring group has been developed and its photovoltaic performance in dye-sensitized solar cells (DSSCs) is investigated. The sensitizer has the ability to adsorb on a TiO 2 electrode through both the coordination bond at Lewis acid sites and the bidentate binuclear bridging linkage at Brønsted acid sites on the TiO 2 surface, which makes it possible to inject an electron into the conduction band of the TiO 2 electrode by the intramolecular charge-transfer (ICT) excitation (type-I pathway) and by the photoexcitation of the dye-to-TiO 2 charge transfer (DTCT) band (type-II pathway). It was found that the type-I/type-II hybrid dye sensitizer adsorbed on TiO 2 film exhibits a broad photoabsorption band originating from ICT and DTCT characteristics. Here we reveal the photophysical and electrochemical properties of the type-I/type-II hybrid dye sensitizer bearing a pyridyl group and a catechol unit, along with its adsorption modes onto TiO 2 film, and its photovoltaic performance in type-I/type-II DSSC, based on optical (photoabsorption and fluorescence spectroscopy) and electrochemical measurements (cyclic voltammetry), density functional theory (DFT) calculation, FT-IR spectroscopy of the dyes adsorbed on TiO 2 film, photocurrent-voltage (I-V) curves, incident photon-to-current conversion efficiency (IPCE) spectra, and electrochemical impedance spectroscopy (EIS) for DSSC.

Mg II Spectra of Late Type Stars Used to Probe the LISM

NASA Technical Reports Server (NTRS)

Beckman, J. E.; Crivellari, L.; Franco, M.; Molaro, P.; Vladilo, G.

1984-01-01

IUE spectra of Mg II h and k in late type dwarfs and giants were used to detect and measure absorption components due to the LISM. This technique gives a method of probing the awkward range from d = 3 pc to d = 80 pc from the Sun. In spite of interpretational uncertainties the HI component of the LISM can be plotted well enough to confirm it as a cloud some 20 to 30 pc in extent, peaking sharply in density towards l(II)-25 deg., moving towards the Sun from l(II)-25 deg, b(II) = + 10 deg., at 28 Km/sec. The hole towards l(II) = 150 deg is confirmed, suggesting a solar position close to the cloud's edge in this direction.

Case 22:Type II diabetes

USDA-ARS?s Scientific Manuscript database

Diabetes mellitus is characterized by elevated blood glucose levels. It is composed of two types depending on the pathogenesis. Type I diabetes is characterized by insulin deficiency and usually has its onset during childhood or teenage years. This is also called ketosis-prone diabetes. Type II diab...

sRAGE attenuates angiotensin II-induced cardiomyocyte hypertrophy by inhibiting RAGE-NFκB-NLRP3 activation.

PubMed

Lim, Soyeon; Lee, Myung Eun; Jeong, Jisu; Lee, Jiye; Cho, Soyoung; Seo, Miran; Park, Sungha

2018-05-23

The receptor for advanced glycation endproducts (RAGE) is an innate immunity receptor that has been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, the possibility that RAGE-mediated signaling is involved in angiotensin II (Ang II)-induced cardiac left ventricular hypertrophy has yet to be investigated. We therefore determined whether RAGE has a role in regulating pathological cardiac hypertrophy. Protein abundance was estimated using Western blotting and intracellular ROS level and phospho-p65 were detected using fluorescence microscopy. Enzyme-linked immunosorbent assay was used to detect HMGB1 and IL-1β. All in vitro experiments were performed using H9C2 cells. To induce cardiomyocyte hypertrophy, 300 nM Ang II was treated for 48 h and 2 µg/ml sRAGE was treated 1 h prior to addition of Ang II. sRAGE attenuated Ang II-induced cardiomyocyte hypertrophy by downregulating RAGE and angiotensin II type 1 receptor expression. Secretion levels of high motility group box 1 and interleukin-1β, estimated from a cell culture medium, were significantly reduced by sRAGE. Activated PKCs and ERK1/2, important signals in left ventricular hypertrophy (LVH) development, were downregulated by sRAGE treatment. Furthermore, we found that nuclear factor-κB and NOD-like receptor protein 3 (NLRP3) were associated with RAGE-mediated cardiomyocyte hypertrophy. In the context of these results, we conclude that RAGE induces cardiac hypertrophy through the activation of the PKCs-ERK1/2 and NF-κB-NLRP3-IL1β signaling pathway, and suggest that RAGE-NLRP3 may be an important mediator of Ang II-induced cardiomyocyte hypertrophy. In addition, we determined that inhibition of RAGE activation with soluble RAGE (sRAGE) has a protective effect on Ang II-induced cardiomyocyte hypertrophy.

Hypoxia-inducible factor-1α in vascular smooth muscle regulates blood pressure homeostasis through a peroxisome proliferator-activated receptor-γ-angiotensin II receptor type 1 axis.

PubMed

Huang, Yan; Di Lorenzo, Annarita; Jiang, Weidong; Cantalupo, Anna; Sessa, William C; Giordano, Frank J

2013-09-01

Hypertension is a major worldwide health issue for which only a small proportion of cases have a known mechanistic pathogenesis. Of the defined causes, none have been directly linked to heightened vasoconstrictor responsiveness, despite the fact that vasomotor tone in resistance vessels is a fundamental determinant of blood pressure. Here, we reported a previously undescribed role for smooth muscle hypoxia-inducible factor-1α (HIF-1α) in controlling blood pressure homeostasis. The lack of HIF-1α in smooth muscle caused hypertension in vivo and hyperresponsiveness of resistance vessels to angiotensin II stimulation ex vivo. These data correlated with an increased expression of angiotensin II receptor type I in the vasculature. Specifically, we show that HIF-1α, through peroxisome proliferator-activated receptor-γ, reciprocally defined angiotensin II receptor type I levels in the vessel wall. Indeed, pharmacological blockade of angiotensin II receptor type I by telmisartan abolished the hypertensive phenotype in smooth muscle cell-HIF-1α-KO mice. These data revealed a determinant role of a smooth muscle HIF-1α/peroxisome proliferator-activated receptor-γ/angiotensin II receptor type I axis in controlling vasomotor responsiveness and highlighted an important pathway, the alterations of which may be critical in a variety of hypertensive-based clinical settings.

Genetics Home Reference: distal hereditary motor neuropathy, type II

MedlinePlus

... hereditary motor neuropathy, type II Distal hereditary motor neuropathy, type II Printable PDF Open All Close All ... the expand/collapse boxes. Description Distal hereditary motor neuropathy, type II is a progressive disorder that affects ...

30 CFR 57.22238 - Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). 57.22238 Section 57.22238 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 2.0 percent in the mine...

30 CFR 57.22231 - Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines). 57.22231 Section 57.22231 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 0.25 percent in the...

30 CFR 57.22238 - Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 2.0 percent methane (I-B, II-B, V-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22238 Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 2.0 percent in the mine...

30 CFR 57.22231 - Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 0.25 percent methane (I-B, II-B, V-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22231 Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 0.25 percent in the...

Dynamic adsorption of mixtures of Rhodamine B, Pb (II), Cu (II) and Zn(II) ions on composites chitosan-silica-polyethylene glycol membrane

NASA Astrophysics Data System (ADS)

Mahatmanti, F. W.; Rengga, W. D. P.; Kusumastuti, E.; Nuryono

2018-04-01

The adsorption of a solution mixture of Rhodamine B, Pb (II), Cu (II) and Zn(II) was studied using dynamic methods employing chitosan-silica-polyethylene glycol (Ch/Si/P) composite membrane as an adsorptive membrane. The composite Ch/Si/P membrane was prepared by mixing a chitosan-based membrane with silica isolated from rice husk ash (ASP) and polyethylene glycol (PEG) as a plasticizer. The resultant composite membrane was a stronger and more flexible membrane than the original chitosan-based membrane as indicated by the maximum percentage of elongation (20.5 %) and minimum Young’s Modulus (80.5 MPa). The composite membrane also showed increased mechanical and hydrophilic properties compared to the chitosan membranes. The membrane was used as adsorption membrane for Pb (II), Cu (II), Cd (II) ions and Rhodamine B dyes in a dynamic system where the permeation and selectivity were determined. The permeation of the components was observed to be in the following order: Rhodamine B > Cd (II) > Pb (II) > Cu (II) whereas the selectivity was shown to decrease the order of Cu (II) > Pb (II) > Cd (II) > Rhodamine B.

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

High cell surface death receptor expression determines type I versus type II signaling.

PubMed

Meng, Xue Wei; Peterson, Kevin L; Dai, Haiming; Schneider, Paula; Lee, Sun-Hee; Zhang, Jin-San; Koenig, Alexander; Bronk, Steve; Billadeau, Daniel D; Gores, Gregory J; Kaufmann, Scott H

2011-10-14

Previous studies have suggested that there are two signaling pathways leading from ligation of the Fas receptor to induction of apoptosis. Type I signaling involves Fas ligand-induced recruitment of large amounts of FADD (FAS-associated death domain protein) and procaspase 8, leading to direct activation of caspase 3, whereas type II signaling involves Bid-mediated mitochondrial perturbation to amplify a more modest death receptor-initiated signal. The biochemical basis for this dichotomy has previously been unclear. Here we show that type I cells have a longer half-life for Fas message and express higher amounts of cell surface Fas, explaining the increased recruitment of FADD and subsequent signaling. Moreover, we demonstrate that cells with type II Fas signaling (Jurkat or HCT-15) can signal through a type I pathway upon forced receptor overexpression and that shRNA-mediated Fas down-regulation converts cells with type I signaling (A498) to type II signaling. Importantly, the same cells can exhibit type I signaling for Fas and type II signaling for TRAIL (TNF-α-related apoptosis-inducing ligand), indicating that the choice of signaling pathway is related to the specific receptor, not some other cellular feature. Additional experiments revealed that up-regulation of cell surface death receptor 5 levels by treatment with 7-ethyl-10-hydroxy-camptothecin converted TRAIL signaling in HCT116 cells from type II to type I. Collectively, these results suggest that the type I/type II dichotomy reflects differences in cell surface death receptor expression.

Variation of the ground spin state in homo- and hetero-octanuclear copper(II) and nickel(II) double-star complexes with a meso-helicate-type metallacryptand core.

PubMed

Pardo, Emilio; Dul, Marie-Claire; Lescouëzec, Rodrigue; Chamoreau, Lise-Marie; Journaux, Yves; Pasán, Jorge; Ruiz-Pérez, Catalina; Julve, Miguel; Lloret, Francesc; Ruiz-García, Rafael; Cano, Joan

2010-05-28

Homo- and heterometallic octanuclear complexes of formula Na₂{[Cu₂(mpba)₃][Cu(Me₅dien)]₆}-(ClO₄)₆·12H₂O (1), Na₂{[Cu₂(Mempba)₃][Cu(Me₅dien)]₆}(ClO₄)₆·12H₂O (2), Na₂{[Ni₂(mpba)₃]-[Cu(Me₅dien)]₆}(ClO₄)₆·12H₂O (3), Na₂{[Ni₂(Mempba)₃][Cu(Me₅dien)]₆}(ClO₄)₆·9H₂O (4), {[Ni₂(mpba)₃][Ni(dipn)(H₂O)]₆}(ClO₄)₄·12.5H₂O (5), and {[Ni₂(Mempba)₃][Ni(dipn)-(H₂O)]₆}(ClO₄)₄·12H₂O (6) [mpba = 1,3-phenylenebis(oxamate), Mempba = 4-methyl-1,3-phenylenebis(oxamate), Me₅dien = N,N,N',N'',N''-pentamethyldiethylenetriamine, and dipn = dipropylenetriamine] have been synthesized through the "complex-as-ligand/complex-as-metal" strategy. Single-crystal X-ray diffraction analyses of 1, 3, and 5 show cationic M(II)₂M'(II)₆ entities (M, M' = Cu and Ni) with an overall double-star architecture, which is made up of two oxamato-bridged M(II)M'(II)₃ star units connected through three meta-phenylenediamidate bridges between the two central metal atoms leading to a binuclear metallacryptand core of the meso-helicate-type. Dc magnetic susceptibility data for 1-6 in the temperature range 2-300 K have been analyzed through a "dimer-of-tetramers" model [H = - J(S(1A)·S(3A) + S(1A)·S(4A) + S(1A)·S(5A) + S(2B)·S(6B) + S(2B)·S(7B) + S(2B)·S(8B)) - J'S(1A)·S(2B), with S(1A) = S(2B) = S(M) and S(3A) = S(4A) = S(5A) = S(6B) = S(7B) = S(8B) = S(M')]. The moderate to strong antiferromagnetic coupling between the M(II) and M'(II) ions through the oxamate bridge in 1-6 (-J(Cu-Cu) = 52.0-57.0 cm⁻¹, -J(Ni-Cu) = 39.1-44.7 cm⁻¹, and -J(Ni-Ni) = 26.3-26.6 cm⁻¹) leads to a non-compensation of the ground spin state for the tetranuclear M(II)M'(II)₃ star units [S(A) = S(B) = 3S(M') - S(M) = 1 (1 and 2), 1/2 (3 and 4), and 2 (5 and 6)]. Within the binuclear M(II)₂ meso-helicate cores of 1-4, a moderate to weak antiferromagnetic coupling between the M(II) ions (-J'(Cu-Cu) = 28.0-48.0 cm⁻¹ and -J

MHC class II molecules control murine B cell responsiveness to lipopolysaccharide stimulation.

PubMed

Rodo, Joana; Gonçalves, Lígia A; Demengeot, Jocelyne; Coutinho, António; Penha-Gonçalves, Carlos

2006-10-01

LPS is a strong stimulator of the innate immune system and inducer of B lymphocyte activation. Two TLRs, TLR4 and RP105 (CD180), have been identified as mediators of LPS signaling in murine B cells, but little is known about genetic factors that are able to control LPS-induced cell activation. We performed a mouse genome-wide screen that aside from identifying a controlling locus mapping in the TLR4 region (logarithm of odds score, 2.77), also revealed that a locus closely linked to the MHC region (logarithm of odds score, 3.4) governed B cell responsiveness to LPS stimulation. Using purified B cells obtained from MHC congenic strains, we demonstrated that the MHC(b) haplotype is accountable for higher cell activation, cell proliferation, and IgM secretion, after LPS stimulation, when compared with the MHC(d) haplotype. Furthermore, B cells from MHC class II(-/-) mice displayed enhanced activation and proliferation in response to LPS. In addition, we showed that the MHC haplotype partially controls expression of RP105 (a LPS receptor molecule), following a pattern that resembles the LPS responsiveness phenotype. Together, our results strongly suggest that murine MHC class II molecules play a role in constraining the B cell response to LPS and that genetic variation at the MHC locus is an important component in controlling B cell responsiveness to LPS stimulation. This work raises the possibility that constraining of B cell responsiveness by MHC class II molecules may represent a functional interaction between adaptive and innate immune systems.

Effects of type I/type II interferons and transforming growth factor-beta on B-cell differentiation and proliferation. Definition of costimulation and cytokine requirements for immunoglobulin synthesis and expression.

PubMed

Estes, D M; Tuo, W; Brown, W C; Goin, J

1998-12-01

In this report, we sought to determine the role of selected type I interferons [interferon-alpha (IFN-alpha) and interferon-tau (IFN-tau)], IFN-gamma and transforming growth factor-beta (TGF-beta) in the regulation of bovine antibody responses. B cells were stimulated via CD40 in the presence or absence of B-cell receptor (BCR) cross-linking. IFN-alpha enhanced IgM, IgG2 and IgA responses but did not enhance IgG1 responses. BCR signalling alone was more effective at inducing IgG2 responses with IFN-alpha than dual cross-linking with CD40. Recombinant ovine IFN-tau was less effective at inducing IgG2 responses when compared with IFN-alpha, though IgA responses were similar in magnitude following BCR cross-linking. At higher concentrations, IFN-tau enhanced IgA responses greater than twofold over the levels observed with IFN-alpha. Previous studies have shown that addition of IFN-gamma to BCR or pokeweed mitogen-activated bovine B cells stimulates IgG2 production. However, following CD40 stimulation alone, IFN-gamma was relatively ineffective at stimulating high-rate synthesis of any non-IgM isotype. Dual cross-linking via CD40 and the BCR resulted in decreased synthesis of IgM with a concomitant increase in IgA and similar levels of IgG2 production to those obtained via the BCR alone. We also assessed the effects of endogenous and exogenous TGF-beta on immunoglobulin synthesis by bovine B cells. Exogenous TGF-beta stimulates both IgG2 and IgA production following CD40 and BCR cross-linking in the presence of IL-2. Blocking endogenous TGF-beta did not inhibit the up-regulation of IgG2 or IgA by interferons.

An updated Type II supernova Hubble diagram

NASA Astrophysics Data System (ADS)

Gall, E. E. E.; Kotak, R.; Leibundgut, B.; Taubenberger, S.; Hillebrandt, W.; Kromer, M.; Burgett, W. S.; Chambers, K.; Flewelling, H.; Huber, M. E.; Kaiser, N.; Kudritzki, R. P.; Magnier, E. A.; Metcalfe, N.; Smith, K.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.

2018-03-01

We present photometry and spectroscopy of nine Type II-P/L supernovae (SNe) with redshifts in the 0.045 ≲ z ≲ 0.335 range, with a view to re-examining their utility as distance indicators. Specifically, we apply the expanding photosphere method (EPM) and the standardized candle method (SCM) to each target, and find that both methods yield distances that are in reasonable agreement with each other. The current record-holder for the highest-redshift spectroscopically confirmed supernova (SN) II-P is PS1-13bni (z = 0.335-0.012+0.009), and illustrates the promise of Type II SNe as cosmological tools. We updated existing EPM and SCM Hubble diagrams by adding our sample to those previously published. Within the context of Type II SN distance measuring techniques, we investigated two related questions. First, we explored the possibility of utilising spectral lines other than the traditionally used Fe IIλ5169 to infer the photospheric velocity of SN ejecta. Using local well-observed objects, we derive an epoch-dependent relation between the strong Balmer line and Fe IIλ5169 velocities that is applicable 30 to 40 days post-explosion. Motivated in part by the continuum of key observables such as rise time and decline rates exhibited from II-P to II-L SNe, we assessed the possibility of using Hubble-flow Type II-L SNe as distance indicators. These yield similar distances as the Type II-P SNe. Although these initial results are encouraging, a significantly larger sample of SNe II-L would be required to draw definitive conclusions. Tables A.1, A.3, A.5, A.7, A.9, A.11, A.13, A.15 and A.17 are also available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/611/A25

Epidermal growth factor increases cortisol production and type II 3 beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase expression in human adrenocortical carcinoma cells: evidence for a Stat5-dependent mechanism.

PubMed

Feltus, F Alex; Kovacs, William J; Nicholson, Wendell; Silva, Corrine M; Nagdas, Subir K; Ducharme, Nicole A; Melner, Michael H

2003-05-01

We tested the ability of epidermal growth factor (EGF) to regulate a key enzyme in the adrenal synthesis of glucocorticoids: human type II 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3 beta HSD). EGF treatment (25 ng/ml) of human adrenocortical carcinoma cells (H295R) resulted in a 5-fold increase in cortisol production and a corresponding 2-fold increase in 3 beta HSD mRNA. Experiments were performed to determine whether EGF is acting through a previously identified signal transducer and activator of transcription 5 (Stat5)-responsive element located from -110 to -118 in the human type II 3 beta HSD promoter. A Stat5 expression construct was cotransfected with a 3 beta HSD-chloramphenol acetyltransferase (CAT) reporter construct comprised of nucleotides -301-->+45 of the human type II 3 beta HSD promoter linked to the CAT reporter gene sequence. The addition of EGF at doses as low as 10 ng/ml resulted in an 11- to 15-fold increase in CAT activity. The introduction of 3-bp point mutations into critical nucleotides in the Stat5 response element obviated the EGF response. Either Stat5a or Stat5b isoforms induced CAT reporter expression upon treatment with EGF. These results demonstrate the ability of EGF to regulate the expression of a critical enzyme (3 beta HSD) in the production of cortisol and suggest a molecular mechanism by which this regulation occurs.

Non alcoholic fatty liver disease in a Nigerian population with type II diabetes mellitus.

PubMed

Olusanya, Titilola Osawaye; Lesi, Olufunmilayo Adenike; Adeyomoye, Adekunle Ayokunle; Fasanmade, Olufemi Adetola

2016-01-01

Worldwide, Non-alcoholic fatty liver disease (NAFLD) has become an important cause of chronic liver disease and cardiovascular morbidity, even more so in subjects with Type II Diabetes Mellitus (T2DM). The aim of this study was to determine the prevalence and risk factors of NAFLD in an African population with Type II Diabetes Mellitus. We performed a case control study and evaluated anthropometric and biochemical risk factors for NAFLD in 336 subjects (T2DM and non-diabetic controls). Parameters assessed included estimation of BMI (Body Mass Index), measurement of waist circumference (WC), serum cholesterol including HDL-C, LDL-C and triglyceride and serum transaminases (ALT and AST). Hepatitis B and C viral antibody screening was also performed. The diagnosis of NAFLD was confirmed by identification of hepatic steatosis on abdominal ultrasound scan evaluation and exclusion of significant alcohol consumption. NAFLD was identified in 16.7% (28 of 168) patients with T2DM compared with 1.2% (2 of 168) non-diabetic controls (Odds Ratio 16.6; p < 0.001). Central obesity (WC > 102cm) and dyslipidaemia (HDL-c < 40mg/dl) were independently associated with NAFLD in male subjects with T2DM (p = 0.03 and p = 0.04 respectively). NAFLD occurred more frequently in patients with T2DM than controls and was associated with central obesity and dyslipidaemia. The diabetic subjects with NAFLD will require more intensive therapy to decrease the risk of hepatic, cardiovascular and other adverse events.

Electronic transition moment for the B(2)II-X(2)II system of NO

NASA Technical Reports Server (NTRS)

Luque, Jorge; Crosley, David R.

1995-01-01

The upsilon' = 0-3 and 7 vibrational levels of the NO B(2)II state have been selectively excited by laser radiation. The fluorescence spectra together with calculated Franck-Condon factors and r-centroids have been used to evaluate the electronic transition moment. The results for upsilon' = 0-3 are in very good agreement with recent chemiluminescence measurements and ab initio calculations. Furthermore, the data from upsilon' = 7 have been used to extend the empirically determined moment to limits 1.23 and 1.78 A, improving agreement with experimentally determined lifetimes.

Angiotensin II type 1 and type 2 receptor-induced cell signaling.

PubMed

Akazawa, Hiroshi; Yano, Masamichi; Yabumoto, Chizuru; Kudo-Sakamoto, Yoko; Komuro, Issei

2013-01-01

The octapeptide angiotensin II (Ang II) plays a homeostatic role in the regulation of blood pressure and water and electrolyte balance, and also contributes to the progression of cardiovascular remodeling. Ang II activates Ang II type 1 (AT1) receptor and type 2 (AT2) receptor, both of which belong to the seven-transmembrane, G protein-coupled receptor family. Most of the actions of Ang II such as promotion of cellular prolifaration, hypertrophy, and fibrosis are mediated by AT1 receptor. However, in some pathological situations, AT2 receptor shows an increase in tissue expression and functions to antagonize the actions induced by AT1 receptor. Recent studies have advanced our understanding of the molecular mechanisms underlying receptor activation and signal transduction of AT1 and AT2 receptor in the cardiovascular system.

Factor II assay

MedlinePlus

... this page: //medlineplus.gov/ency/article/003674.htm Factor II assay To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

Emergent properties resulting from type-II band alignment in semiconductor nanoheterostructures.

PubMed

Lo, Shun S; Mirkovic, Tihana; Chuang, Chi-Hung; Burda, Clemens; Scholes, Gregory D

2011-01-11

The development of elegant synthetic methodologies for the preparation of monocomponent nanocrystalline particles has opened many possibilities for the preparation of heterostructured semiconductor nanostructures. Each of the integrated nanodomains is characterized by its individual physical properties, surface chemistry, and morphology, yet, these multicomponent hybrid particles present ideal systems for the investigation of the synergetic properties that arise from the material combination in a non-additive fashion. Of particular interest are type-II heterostructures, where the relative band alignment of their constituent semiconductor materials promotes a spatial separation of the electron and hole following photoexcitation, a highly desirable property for photovoltaic applications. This article highlights recent progress in both synthetic strategies, which allow for material and architectural modulation of novel nanoheterostructures, as well as the experimental work that provides insight into the photophysical properties of type-II heterostructures. The effects of external factors, such as electric fields, temperature, and solvent are explored in conjunction with exciton and multiexciton dynamics and charge transfer processes typical for type-II semiconductor heterostructures.

40 CFR Table II-1 to Subpart II of... - Emission Factors

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Emission Factors II Table II-1 to Subpart II of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Industrial Wastewater Treatment Pt. 98, Subpt. II, Table II-1...

40 CFR Table II-1 to Subpart II of... - Emission Factors

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Emission Factors II Table II-1 to Subpart II of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Industrial Wastewater Treatment Pt. 98, Subpt. II, Table II-1...

Transcriptional up-regulation of nitric oxide synthase II by nuclear factor-kappaB at rostral ventrolateral medulla in a rat mevinphos intoxication model of brain stem death.

PubMed

Chan, Julie Y H; Wu, Carol H Y; Tsai, Ching-Yi; Cheng, Hsiao-Lei; Dai, Kuang-Yu; Chan, Samuel H H; Chang, Alice Y W

2007-06-15

As the origin of a 'life-and-death' signal that reflects central cardiovascular regulatory failure during brain stem death, the rostral ventrolateral medulla (RVLM) is a suitable neural substrate for mechanistic delineation of this vital phenomenon. Using a clinically relevant animal model that employed the organophosphate pesticide mevinphos (Mev) as the experimental insult, we evaluated the hypothesis that transcriptional up-regulation of nitric oxide synthase I or II (NOS I or II) gene expression by nuclear factor-kappaB (NF-kappaB) on activation of muscarinic receptors in the RVLM underlies brain stem death. In Sprague-Dawley rats maintained under propofol anaesthesia, co-microinjection of muscarinic M2R (methoctramine) or M4R (tropicamide), but not M1R (pirenzepine) or M3R (4-diphenylacetoxy-N-dimethylpiperidinium) antagonist significantly reduced the enhanced NOS I-protein kinase G signalling ('pro-life' phase) or augmented NOS II-peroxynitrite cascade ('pro-death' phase) in ventrolateral medulla, blunted the biphasic increase and decrease in baroreceptor reflex-mediated sympathetic vasomotor tone that reflect the transition from life to death, and diminished the elevated DNA binding activity or nucleus-bound translocation of NF-kappaB in RVLM neurons induced by microinjection of Mev into the bilateral RVLM. However, NF-kappaB inhibitors (diethyldithiocarbamate or pyrrolidine dithiocarbamate) or double-stranded kappaB decoy DNA preferentially antagonized the augmented NOS II-peroxynitrite cascade and the associated cardiovascular depression exhibited during the 'pro-death' phase. We conclude that transcriptional up-regulation of NOS II gene expression by activation of NF-kappaB on selective stimulation of muscarinic M2 or M4 subtype receptors in the RVLM underlies the elicited cardiovascular depression during the 'pro-death' phase in our Mev intoxication model of brain stem death.

Seasonal plasticity of auditory saccular sensitivity in "sneaker" type II male plainfin midshipman fish, Porichthys notatus.

PubMed

Bhandiwad, Ashwin A; Whitchurch, Elizabeth A; Colleye, Orphal; Zeddies, David G; Sisneros, Joseph A

2017-03-01

Adult female and nesting (type I) male midshipman fish (Porichthys notatus) exhibit an adaptive form of auditory plasticity for the enhanced detection of social acoustic signals. Whether this adaptive plasticity also occurs in "sneaker" type II males is unknown. Here, we characterize auditory-evoked potentials recorded from hair cells in the saccule of reproductive and non-reproductive "sneaker" type II male midshipman to determine whether this sexual phenotype exhibits seasonal, reproductive state-dependent changes in auditory sensitivity and frequency response to behaviorally relevant auditory stimuli. Saccular potentials were recorded from the middle and caudal region of the saccule while sound was presented via an underwater speaker. Our results indicate saccular hair cells from reproductive type II males had thresholds based on measures of sound pressure and acceleration (re. 1 µPa and 1 ms -2 , respectively) that were ~8-21 dB lower than non-reproductive type II males across a broad range of frequencies, which include the dominant higher frequencies in type I male vocalizations. This increase in type II auditory sensitivity may potentially facilitate eavesdropping by sneaker males and their assessment of vocal type I males for the selection of cuckoldry sites during the breeding season.

PfeT, a P1B4 -type ATPase, effluxes ferrous iron and protects Bacillus subtilis against iron intoxication.

PubMed

Guan, Guohua; Pinochet-Barros, Azul; Gaballa, Ahmed; Patel, Sarju J; Argüello, José M; Helmann, John D

2015-11-01

Iron is an essential element for nearly all cells and limited iron availability often restricts growth. However, excess iron can also be deleterious, particularly when cells expressing high affinity iron uptake systems transition to iron rich environments. Bacillus subtilis expresses numerous iron importers, but iron efflux has not been reported. Here, we describe the B. subtilis PfeT protein (formerly YkvW/ZosA) as a P1B4 -type ATPase in the PerR regulon that serves as an Fe(II) efflux pump and protects cells against iron intoxication. Iron and manganese homeostasis in B. subtilis are closely intertwined: a pfeT mutant is iron sensitive, and this sensitivity can be suppressed by low levels of Mn(II). Conversely, a pfeT mutant is more resistant to Mn(II) overload. In vitro, the PfeT ATPase is activated by both Fe(II) and Co(II), although only Fe(II) efflux is physiologically relevant in wild-type cells, and null mutants accumulate elevated levels of intracellular iron. Genetic studies indicate that PfeT together with the ferric uptake repressor (Fur) cooperate to prevent iron intoxication, with iron sequestration by the MrgA mini-ferritin playing a secondary role. Protection against iron toxicity may also be a key role for related P1B4 -type ATPases previously implicated in bacterial pathogenesis. © 2015 John Wiley & Sons Ltd.

Super-luminous Type II supernovae powered by magnetars

NASA Astrophysics Data System (ADS)

Dessart, Luc; Audit, Edouard

2018-05-01

Magnetar power is believed to be at the origin of numerous super-luminous supernovae (SNe) of Type Ic, arising from compact, hydrogen-deficient, Wolf-Rayet type stars. Here, we investigate the properties that magnetar power would have on standard-energy SNe associated with 15-20 M⊙ supergiant stars, either red (RSG; extended) or blue (BSG; more compact). We have used a combination of Eulerian gray radiation-hydrodynamics and non-LTE steady-state radiative transfer to study their dynamical, photometric, and spectroscopic properties. Adopting magnetar fields of 1, 3.5, 7 × 1014 G and rotational energies of 0.4, 1, and 3 × 1051 erg, we produce bolometric light curves with a broad maximum covering 50-150 d and a magnitude of 1043-1044 erg s-1. The spectra at maximum light are analogous to those of standard SNe II-P but bluer. Although the magnetar energy is channelled in equal proportion between SN kinetic energy and SN luminosity, the latter may be boosted by a factor of 10-100 compared to a standard SN II. This influence breaks the observed relation between brightness and ejecta expansion rate of standard Type II SNe. Magnetar energy injection also delays recombination and may even cause re-ionization, with a reversal in photospheric temperature and velocity. Depositing the magnetar energy in a narrow mass shell at the ejecta base leads to the formation of a dense shell at a few 1000 km s-1, which causes a light-curve bump at the end of the photospheric phase. Depositing this energy over a broad range of mass in the inner ejecta, to mimic the effect of multi-dimensional fluid instabilities, prevents the formation of a dense shell and produces an earlier-rising and smoother light curve. The magnetar influence on the SN radiation is generally not visible prior to 20-30 d, during which one may discern a BSG from a RSG progenitor. We propose a magnetar model for the super-luminous Type II SN OGLE-SN14-073.

Analysis of type II and type III solar radio bursts

NASA Astrophysics Data System (ADS)

Wijesekera, J. V.; Jayaratne, K. P. S. C.; Adassuriya, J.

2018-04-01

Solar radio burst is an arrangement of a frequency space that variation with time. Most of radio burst can be identified in low frequency range such as below 200 MHz and depending on frequencies. Solar radio bursts were the first phenomenon identified in the field of radio astronomy field. Solar radio frequency range is from 70 MHz to 2.2 GHz. Most of the radio burst can be identified in a low frequency range such as below 200 MHz. Properties of low-frequency radio were analyzed this research. There are two types of solar radio bursts were analyzed, named as type II and type III radio bursts. Exponential decay type could be seen in type II, and a linear could be indicated in type III solar radio bursts. The results of the drift rate graphs show the values of each chosen solar radio burst. High drift rate values can be seen in type III solar flares whereas low to medium drift rate values can be seen in type II solar flares. In the second part of the research the Newkirk model electron density model was used to estimate the drift velocities of the solar radio bursts. Although the special origin of the solar radio burst is not known clearly we assumed. The chosen solar radio bursts were originated within the solar radius of 0.9 - 1.3 range from the photosphere. We used power low in the form of (x) = A × 10‑bx were that the electron density related to the height of the solar atmosphere. The calculation of the plasma velocity of each solar radio burst was done using the electron density model and drift rates. Therefore velocity of chosen type II solar radio bursts indicates low velocities. The values are 233.2499 Km s‑1, 815.9522 Km s‑1 and 369.5425 Km s‑1. Velocity of chosen type III solar radio bursts were 1443.058 Km s‑1and 1205.05Km s ‑1.

Type II Cepheids and Related Variables

NASA Astrophysics Data System (ADS)

Schmidt, Edward G.

2008-08-01

While type II Cepheids have considerable potential to contribute to our knowledge of a number of areas of astrophysics, their usefulness is compromised by the relatively small number of such stars known. I have undertaken a project to identify more of them in two large area sky surveys, and to determine some of the basic properties of the stars which are confirmed as type II Cepheids. In the course of this project a significant number of small amplitude stars which appear to be closely related to the type II Cepheids have been identified. The nature of these objects is also being investigated. The photometry portion of the project is complete and spectra were obtained for about half of the stars with the GCAM spectrograph on the 2.1-m telescope. This proposal requests time to obtain spectra for about 2/3 of the remaining stars.

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.

Type II diabetes mellitus and menopause: a multinational study.

PubMed

Monterrosa-Castro, A; Blümel, J E; Portela-Buelvas, K; Mezones-Holguín, E; Barón, G; Bencosme, A; Benítez, Z; Bravo, L M; Calle, A; Chedraui, P; Flores, D; Espinoza, M T; Gómez, G; Hernández-Bueno, J A; Laribezcoa, F; Lima, S; Martino, M; Mostajo, D; Ojeda, E; Onatra, W; Sánchez, H; Navarro, D; Tserotas, K; Vallejo, M S; Witis, S; Zuñiga, M C

2013-12-01

Type II diabetes mellitus causes metabolic changes that may lead to early menopause and worsen climacteric symptoms. To determine the risk factors for type II diabetes mellitus and assess the impact of this disease on the age of menopause and on climacteric symptoms. A total of 6079 women aged between 40 and 59 years from 11 Latin American countries were requested to answer the Menopause Rating Scale and Goldberg Anxiety-Depression Scale. The prevalence of diabetes was 6.7%. Diabetes mellitus was associated with arterial hypertension (odds ratio (OR) 4.49; 95% confidence interval (CI) 3.47-5.31), the use of psychotropic drugs (OR 1.54; 95% CI 1.22-1.94), hormonal therapy (OR 1.46; 95% CI 1.11-1.92), ≥ 50 years of age (OR 1.48; 95% CI 1.17-1.86), overweight or obese (OR 1.47; 95% CI 1.15-1.89), and waist circumference ≥ 88 cm (OR 1.32; 95% CI 1.06-1.65). Factors associated with lower risk of diabetes were the use of hormonal contraceptives (OR 0.55; 95% CI 0.35-0.87), alcohol (OR 0.73; 95% CI 0.54-0.98) and living in cities > 2500 meters above sea level (OR 0.70; 95% CI 0.53-0.91) or with high temperatures (OR 0.67; 95% CI 0.51-0.88). In turn, diabetes tripled the risk of menopause in women under 45 years of age. Diabetes did not increase the risk of deterioration of quality of life due to climacteric symptoms. Menopause does not increase the risk of type II diabetes mellitus. Diabetes is associated with early menopause in women under 45 years of age.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casimiro-Garcia, Agustin; Filzen, Gary F.; Flynn, Declan

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 partialmore » 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.« less

The rise-time of Type II supernovae

NASA Astrophysics Data System (ADS)

González-Gaitán, S.; Tominaga, N.; Molina, J.; Galbany, L.; Bufano, F.; Anderson, J. P.; Gutierrez, C.; Förster, F.; Pignata, G.; Bersten, M.; Howell, D. A.; Sullivan, M.; Carlberg, R.; de Jaeger, T.; Hamuy, M.; Baklanov, P. V.; Blinnikov, S. I.

2015-08-01

We investigate the early-time light curves of a large sample of 223 Type II supernovae (SNe II) from the Sloan Digital Sky Survey and the Supernova Legacy Survey. Having a cadence of a few days and sufficient non-detections prior to explosion, we constrain rise-times, i.e. the durations from estimated first to maximum light, as a function of effective wavelength. At rest-frame g' band (λeff = 4722 Å), we find a distribution of fast rise-times with median of (7.5 ± 0.3) d. Comparing these durations with analytical shock models of Rabinak & Waxman and Nakar & Sari, and hydrodynamical models of Tominaga et al., which are mostly sensitive to progenitor radius at these epochs, we find a median characteristic radius of less than 400 solar radii. The inferred radii are on average much smaller than the radii obtained for observed red supergiants (RSG). Investigating the post-maximum slopes as a function of effective wavelength in the light of theoretical models, we find that massive hydrogen envelopes are still needed to explain the plateaus of SNe II. We therefore argue that the SN II rise-times we observe are either (a) the shock cooling resulting from the core collapse of RSG with small and dense envelopes, or (b) the delayed and prolonged shock breakout of the collapse of an RSG with an extended atmosphere or embedded within pre-SN circumstellar material.

Enhanced Materials Based on Submonolayer Type-II Quantum Dots

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamargo, Maria C; Kuskovsky, Igor L.; Meriles, Carlos

2017-04-15

We have investigated a nanostructured material known as sub-monolayer type-II QDs, made from wide bandgap II-VI semiconductors. Our goal is to understand and exploit their tunable optical and electrical properties by taking advantage of the type-II band alignment and quantum confinement effects. Type-II ZnTe quantum dots (QDs) in a ZnSe host are particularly interesting because of their relatively large valence band and conduction band offsets. In the current award we have developed new materials based on sub-monolayer type-II QDs that may be advantageous for photovoltaic and spintronics applications. We have also expanded the structural characterization of these materials by refiningmore » the X-ray diffraction methodologies needed to investigate them. In particular, we have 1) demonstrated ZnCdTe/ZnCdSe type-II QDs materials that have ideal properties for the development of novel high efficiency “intermediate band solar cells”, 2) we developed a comprehensive approach to describe and model the growth of these ultra-small type-II QDs, 3) analysis of the evolution of the photoluminescence (PL) emission, combined with other characterization probes allowed us to predict the size and density of the QDs as a function of the growth conditions, 4) we developed and implemented novel sophisticated X-ray diffraction techniques from which accurate size and shape of the buried type-II QDs could be extracted, 5) a correlation of the shape anisotropy with polarization dependent PL was observed, confirming the QDs detailed shape and providing insight about the effects of this shape anisotropy on the physical properties of the type-II QD systems, and 6) a detailed “time-resolved Kerr rotation” investigation has led to the demonstration of enhanced electron spin lifetimes for the samples with large densities of type-II QDs and an understanding of the interplay between the QDs and Te-isoelectroic centers, a defect that forms in the spacer layers that separate the QDs.« less

The B2 Alternatively Spliced Isoform of Nonmuscle Myosin II-B Lacks Actin-activated MgATPase Activity and In Vitro Motility

PubMed Central

Kim, Kye-Young; Kawamoto, Sachiyo; Bao, Jianjun; Sellers, James R.; Adelstein, Robert S.

2008-01-01

We report the initial biochemical characterization of an alternatively spliced isoform of nonmuscle heavy meromyosin (HMM) II-B2 and compare it with HMM II-B0, the non-spliced isoform. HMM II-B2 is the HMM derivative of an alternatively spliced isoform of endogenous nonmuscle myosin (NM) II-B, which has 21-amino acids inserted into loop 2, near the actin-binding region. NM II-B2 is expressed in the Purkinje cells of the cerebellum as well as in other neuronal cells (Ma et al., Mol. Biol. Cell 15 (2006) 2138-2149). In contrast to any of the previously described isoforms of NM II (II-A, II-B0, II-B1, II-C0 and II-C1) or to smooth muscle myosin, the actin-activated MgATPase activity of HMM II-B2 is not significantly increased from a low, basal level by phosphorylation of the 20 kDa myosin light chain (MLC-20). Moreover, although HMM II-B2 can bind to actin in the absence of ATP and is released in its presence, it cannot propel actin in the sliding actin filament assay following MLC-20 phosphorylation. Unlike HMM II-B2, the actin-activated MgATPase activity of a chimeric HMM with the 21-amino acids II-B2 sequence inserted into the homologous location in the heavy chain of HMM II-C is increased following MLC-20 phosphorylation. This indicates that the effect of the II-B2 insert is myosin heavy chain specific. PMID:18060863

Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes.

PubMed

Saffert, Paul; Enenkel, Cordula; Wendler, Petra

2017-01-01

Protein complexes of the Type II AAA+ (ATPases associated with diverse cellular activities) family are typically hexamers of 80-150 kDa protomers that harbor two AAA+ ATPase domains. They form double ring assemblies flanked by associated domains, which can be N-terminal, intercalated or C-terminal to the ATPase domains. Most prominent members of this family include NSF (N-ethyl-maleimide sensitive factor), p97/VCP (valosin-containing protein), the Pex1/Pex6 complex and Hsp104 in eukaryotes and ClpB in bacteria. Tremendous efforts have been undertaken to understand the conformational dynamics of protein remodeling type II AAA+ complexes. A uniform mode of action has not been derived from these works. This review focuses on p97/VCP and the Pex1/6 complex, which both structurally remodel ubiquitinated substrate proteins. P97/VCP plays a role in many processes, including ER- associated protein degradation, and the Pex1/Pex6 complex dislocates and recycles the transport receptor Pex5 from the peroxisomal membrane during peroxisomal protein import. We give an introduction into existing knowledge about the biochemical and cellular activities of the complexes before discussing structural information. We particularly emphasize recent electron microscopy structures of the two AAA+ complexes and summarize their structural differences.

The Functions of Type I and Type II Natural Killer T (NKT) Cells in Inflammatory Bowel Diseases

PubMed Central

Liao, Chia-Min; Zimmer, Michael I.; Wang, Chyung-Ru

2013-01-01

CD1d-restricted natural killer T (NKT) cells are a distinct subset of T cells that rapidly produce an array of cytokines upon activation and play a critical role in regulating various immune responses. NKT cells are classified into two groups based on differences in T cell receptor (TCR) usage. Type I NKT cells have an invariant TCRα-chain and are readily detectable by α-galactosylceramide (α-GalCer)-loaded CD1d tetramers. Type II NKT cells have a more diverse TCR repertoire and cannot be directly identified. Both types of NKT cells as well as multiple CD1d-expressing cell types are present in the intestine and their interactions are likely to be modulated by pathogenic and commensal microbes, which in turn contribute to the intestinal immune responses in health and disease. Indeed, in several animal models of inflammatory bowel disease (IBD), Type I NKT cells have been shown to make both protective and pathogenic contributions to disease. In contrast, in human patients suffering from ulcerative colitis (UC), and a mouse model in which both CD1d expression and the frequency of Type II NKT cells are increased, Type II NKT cells appear to promote intestinal inflammation. In this review, we summarize present knowledge on the antigen recognition, activation and function of NKT cells with a particular focus on their role in IBD, and discuss factors that may influence the functional outcome of NKT cell responses in intestinal inflammation. PMID:23518808

Accentuated hyperparathyroidism in type II Bartter syndrome.

PubMed

Landau, Daniel; Gurevich, Evgenia; Sinai-Treiman, Levana; Shalev, Hannah

2016-07-01

Bartter syndrome (BS) may be associated with different degrees of hypercalciuria, but marked parathyroid hormone (PTH) abnormalities have not been described. We compared clinical and laboratory data of patients with either ROMK-deficient type II BS (n = 14) or Barttin-deficient type IV BS (n = 20). Only BS-IV patients remained mildly hypokalemic in spite of a higher need for potassium supplementation. Estimated glomerular filtration rate (eGFR) was mildly decreased in only four BS-IV patients. Average PTH values were significantly higher in BS-II (160.6 ± 85.8 vs. 92.5 ± 48 pg/ml in BS-IV, p = 0.006). In both groups, there was a positive correlation between age and log(PTH). Levels of 25(OH) vitamin D were not different. Total serum calcium was lower (within normal limits) and age-related serum phosphate (Pi)-SDS was increased in BS-II (1.19 ± 0.71 vs. 0.01 ± 1.04 in BS-IV, p < 0.001). The GFR threshold for Pi reabsorption was higher in BS-II (5.63 ± 1.25 vs. 4.36 ± 0.98, p = 0.002). Spot urine calcium/creatinine ratio and nephrocalcinosis rate (100 vs. 16 %) were higher in the BS-II group. PTH, serum Pi levels, and urinary threshold for Pi reabsorption are significantly elevated in type II vs. type IV BS, suggesting a PTH resistance state. This may be a response to more severe long-standing hypercalciuria, leading to a higher rate of nephrocalcinosis in BS-II.

A systematic review of the factors associated with interest in predictive genetic testing for obesity, type II diabetes and heart disease.

PubMed

Collins, J; Ryan, L; Truby, H

2014-10-01

In the future, it may be possible for individuals to take a genetic test to determine their genetic predisposition towards developing lifestyle-related chronic diseases. A systematic review of the literature was undertaken to identify the factors associated with an interest in having predictive genetic testing for obesity, type II diabetes and heart disease amongst unaffected adults. Ovid Medline, PsycINFO and EMBASE online databases were searched using predefined search terms. Publications meeting the inclusion criteria (English language, free-living adult population not selected as a result of their disease diagnosis, reporting interest as an outcome, not related to a single gene inherited disease) were assessed for quality and content. Narrative synthesis of the results was undertaken. From the 2329 publications retrieved, eight studies met the inclusion criteria and were included in the review. Overall, the evidence base was small but of positive quality. Interest was associated with personal attitudes towards disease risk and the provision of information about genetic testing, shaped by perceived risk of disease and expected outcomes of testing. The role of demographic factors was investigated with largely inconclusive findings. Interest in predictive genetic testing for obesity, type II diabetes or heart disease was greatest amongst those who perceived the risk of disease to be high and/or the outcomes of testing to be beneficial. © 2013 The British Dietetic Association Ltd.

Anomalous Nernst effect in type-II Weyl semimetals

NASA Astrophysics Data System (ADS)

Saha, Subhodip; Tewari, Sumanta

2018-01-01

Topological Weyl semimetals (WSM), a new state of quantum matter with gapless nodal bulk spectrum and open Fermi arc surface states, have recently sparked enormous interest in condensed matter physics. Based on the symmetry and fermiology, it has been proposed that WSMs can be broadly classified into two types, type-I and type-II Weyl semimetals. While the undoped, conventional, type-I WSMs have point like Fermi surface and vanishing density of states (DOS) at the Fermi energy, the type-II Weyl semimetals break Lorentz symmetry explicitly and have tilted conical spectra with electron and hole pockets producing finite DOS at the Fermi level. The tilted conical spectrum and finite DOS at Fermi level in type-II WSMs have recently been shown to produce interesting effects such as a chiral anomaly induced longitudinal magnetoresistance that is strongly anisotropic in direction and a novel anomalous Hall effect. In this work, we consider the anomalous Nernst effect in type-II WSMs in the absence of an external magnetic field using the framework of semi-classical Boltzmann theory. Based on both a linearized model of time-reversal breaking WSM with a higher energy cut-off and a more realistic lattice model, we show that the anomalous Nernst response in these systems is strongly anisotropic in space, and can serve as a reliable signature of type-II Weyl semimetals in a host of magnetic systems with spontaneously broken time reversal symmetry.

A theoretical case study of type I and type II beta-turns.

PubMed

Czinki, Eszter; Császár, Attila G; Perczel, András

2003-03-03

NMR chemical shielding anisotropy tensors have been computed by employing a medium size basis set and the GIAO-DFT(B3LYP) formalism of electronic structure theory for all of the atoms of type I and type II beta-turn models. The models contain all possible combinations of the amino acid residues Gly, Ala, Val, and Ser, with all possible side-chain orientations where applicable in a dipeptide. The several hundred structures investigated contain either constrained or optimized phi, psi, and chi dihedral angles. A statistical analysis of the resulting large database was performed and multidimensional (2D and 3D) chemical-shift/chemical-shift plots were generated. The (1)H(alpha-13)C(alpha), (13)C(alpha-1)H(alpha-13)C(beta), and (13)C(alpha-1)H(alpha-13)C' 2D and 3D plots have the notable feature that the conformers clearly cluster in distinct regions. This allows straightforward identification of the backbone and side-chain conformations of the residues forming beta-turns. Chemical shift calculations on larger For-(L-Ala)(n)-NH(2) (n=4, 6, 8) models, containing a single type I or type II beta-turn, prove that the simple models employed are adequate. A limited number of chemical shift calculations performed at the highly correlated CCSD(T) level prove the adequacy of the computational method chosen. For all nuclei, statistically averaged theoretical and experimental shifts taken from the BioMagnetic Resonance Bank (BMRB) exhibit good correlation. These results confirm and extend our previous findings that chemical shift information from selected multiple-pulse NMR experiments could be employed directly to extract folding information for polypeptides and proteins.

Differential phosphorylations of Spi-B and Spi-1 transcription factors.

PubMed

Mao, C; Ray-Gallet, D; Tavitian, A; Moreau-Gachelin, F

1996-02-15

Spi-1/PU-1 and Spi-B are hematopoietic transcription factors, which, in vitro, display similar affinities for DNA target sequences containing the consensus binding site 5'-GGAA-3'. While the role of Spi-1 in the transcriptional regulation of B cell and myeloid specific genes has been largely demonstrated, the biological function of Spi-B still remains to be elucidated. Since Spi-B and Spi-1 are very divergent in their transactivator domain, these domains might acquire functional specificity in vivo by interacting with different co-factors and/or by undergoing different phosphorylations. First, we observed that casein kinase II phosphorylates Spi-B as well as Spi-1, in vitro. Then, by affinity chromatographies and in vitro kinase assays with fusion proteins between glutathione-S-transferase and the transactivator domain of Spi-B, two kinases were identified on their ability to interact and phosphorylate this domain; the MAP kinase ERK1 and the stress activated protein kinase JNK1. The Threonine 56 was defined as the ERK1 phosphorylation site by using phosphoamino-acid analyses and a Spi-B mutant version with the substitution T56 to A56. Strikingly, ERK1 failed to phosphorylate Spi-1, in vitro, whereas JNK1, like CK II, phosphorylated Spi-B and Spi-1. In addition, other purified Spi-B-kinase activities, unidentified as yet, display similar specificity than ERK1 for Spi-B versus Spi-1. Furthermore, the evident interaction of pRb protein with the transactivator domain of Spi-B in an unphosphorylated state disappeared when this domain was first phosphorylated in vitro either by ERK1 or by the purified Spi-B-kinase activities. Our data revealed multiple phosphorylation sites within Spi-B whose some of them appeared specific for Spi-B versus Spi-1 and which may account for differential regulation of their activities.

Biochemical Characterization of Individual Human Glycosylated pro-Insulin-like Growth Factor (IGF)-II and big-IGF-II Isoforms Associated with Cancer

PubMed Central

Greenall, Sameer A.; Bentley, John D.; Pearce, Lesley A.; Scoble, Judith A.; Sparrow, Lindsay G.; Bartone, Nicola A.; Xiao, Xiaowen; Baxter, Robert C.; Cosgrove, Leah J.; Adams, Timothy E.

2013-01-01

Insulin-like growth factor II (IGF-II) is a major embryonic growth factor belonging to the insulin-like growth factor family, which includes insulin and IGF-I. Its expression in humans is tightly controlled by maternal imprinting, a genetic restraint that is lost in many cancers, resulting in up-regulation of both mature IGF-II mRNA and protein expression. Additionally, increased expression of several longer isoforms of IGF-II, termed “pro” and “big” IGF-II, has been observed. To date, it is ambiguous as to what role these IGF-II isoforms have in initiating and sustaining tumorigenesis and whether they are bioavailable. We have expressed each individual IGF-II isoform in their proper O-glycosylated format and established that all bind to the IGF-I receptor and both insulin receptors A and B, resulting in their activation and subsequent stimulation of fibroblast proliferation. We also confirmed that all isoforms are able to be sequestered into binary complexes with several IGF-binding proteins (IGFBP-2, IGFBP-3, and IGFBP-5). In contrast to this, ternary complex formation with IGFBP-3 or IGFBP-5 and the auxillary protein, acid labile subunit, was severely diminished. Furthermore, big-IGF-II isoforms bound much more weakly to purified ectodomain of the natural IGF-II scavenging receptor, IGF-IIR. IGF-II isoforms thus possess unique biological properties that may enable them to escape normal sequestration avenues and remain bioavailable in vivo to sustain oncogenic signaling. PMID:23166326

Biochemical characterization of individual human glycosylated pro-insulin-like growth factor (IGF)-II and big-IGF-II isoforms associated with cancer.

PubMed

Greenall, Sameer A; Bentley, John D; Pearce, Lesley A; Scoble, Judith A; Sparrow, Lindsay G; Bartone, Nicola A; Xiao, Xiaowen; Baxter, Robert C; Cosgrove, Leah J; Adams, Timothy E

2013-01-04

Insulin-like growth factor II (IGF-II) is a major embryonic growth factor belonging to the insulin-like growth factor family, which includes insulin and IGF-I. Its expression in humans is tightly controlled by maternal imprinting, a genetic restraint that is lost in many cancers, resulting in up-regulation of both mature IGF-II mRNA and protein expression. Additionally, increased expression of several longer isoforms of IGF-II, termed "pro" and "big" IGF-II, has been observed. To date, it is ambiguous as to what role these IGF-II isoforms have in initiating and sustaining tumorigenesis and whether they are bioavailable. We have expressed each individual IGF-II isoform in their proper O-glycosylated format and established that all bind to the IGF-I receptor and both insulin receptors A and B, resulting in their activation and subsequent stimulation of fibroblast proliferation. We also confirmed that all isoforms are able to be sequestered into binary complexes with several IGF-binding proteins (IGFBP-2, IGFBP-3, and IGFBP-5). In contrast to this, ternary complex formation with IGFBP-3 or IGFBP-5 and the auxillary protein, acid labile subunit, was severely diminished. Furthermore, big-IGF-II isoforms bound much more weakly to purified ectodomain of the natural IGF-II scavenging receptor, IGF-IIR. IGF-II isoforms thus possess unique biological properties that may enable them to escape normal sequestration avenues and remain bioavailable in vivo to sustain oncogenic signaling.

Missing in space: an evaluation of imputation methods for missing data in spatial analysis of risk factors for type II diabetes.

PubMed

Baker, Jannah; White, Nicole; Mengersen, Kerrie

2014-11-20

Spatial analysis is increasingly important for identifying modifiable geographic risk factors for disease. However, spatial health data from surveys are often incomplete, ranging from missing data for only a few variables, to missing data for many variables. For spatial analyses of health outcomes, selection of an appropriate imputation method is critical in order to produce the most accurate inferences. We present a cross-validation approach to select between three imputation methods for health survey data with correlated lifestyle covariates, using as a case study, type II diabetes mellitus (DM II) risk across 71 Queensland Local Government Areas (LGAs). We compare the accuracy of mean imputation to imputation using multivariate normal and conditional autoregressive prior distributions. Choice of imputation method depends upon the application and is not necessarily the most complex method. Mean imputation was selected as the most accurate method in this application. Selecting an appropriate imputation method for health survey data, after accounting for spatial correlation and correlation between covariates, allows more complete analysis of geographic risk factors for disease with more confidence in the results to inform public policy decision-making.

Nonlinear convective pulsation models of type II Cepheids

NASA Astrophysics Data System (ADS)

Smolec, Radoslaw

2015-08-01

We present a grid of nonlinear convective pulsation models of type-II Cepheids: BL Her stars, W Vir stars and RV Tau stars. The models cover a wide range of masses, luminosities, effective temperatures and chemical compositions. The most interesting result is detection of deterministic chaos in the models. Different routes to chaos are detected (period doubling, intermittent route) as well as variety of phenomena intrinsic to chaotic dynamics (periodic islands within chaotic bands, crisis bifurcation, type-I and type-III intermittency). Some of the phenomena (period doubling in BL Her and in RV Tau stars, irregular pulsation of RV Tau stars) are well known in the pulsation of type-II Cepheids. Prospects of discovering the other are briefly discussed. Transition from BL Her type pulsation through W Vir type till RV Tau type is analysed. In the most luminous models a dynamical instability is detected, which indicates that pulsation driven mass loss is important process occurring in type-II Cepheids.

Bipolar II disorder as a risk factor for postpartum depression.

PubMed

Mandelli, Laura; Souery, Daniel; Bartova, Lucie; Kasper, Siegfried; Montgomery, Stuart; Zohar, Joseph; Mendlewicz, Julien; Serretti, Alessandro

2016-11-01

There is evidence for a bipolar diathesis in postpartum depression (PPD) and women presenting with a first PPD frequently receive a diagnosis of bipolar type II disorder (BD-II). However formal evidence for an association between BD-II and PPD has not yet been reported. In the present study we tested a potential association between BD-II and PPD. Parous women with a diagnosis of bipolar type I disorder (BD-I) (n=93), BD-II (n=36) or major depressive disorder (MDD) (n=444) were considered in the present study. All women were retrospectively evaluated for history of PPD (DSM-IV criteria) and other clinical and socio-demographic features. Women with a history of PDD (n=139, 24%) were younger, younger at illness onset and had more family history for BD compared to women without history of PPD (n=436, 75.9%). Half of BD-II women reported PPD (50%), compared to less than one-third of BD-I and MDD women (respectively 27.5% and 21.6%) (p=0.004). Limitations include the retrospective assessment of PPD and no available data about the timing of postpartum episodes, illness onset or psychiatric care before or after childbirth, and the number of postpartum episodes. BD-II may confer a remarkable risk for PPD, which may be even higher than that of women affected by BD-I disorder. Careful monitoring of BD-II women during the pregnancy and postpartum period, as well as assessment of bipolar features in women with a PPD without a current diagnosis of BD are recommended. Copyright © 2016 Elsevier B.V. All rights reserved.

miR-34 miRNAs Regulate Cellular Senescence in Type II Alveolar Epithelial Cells of Patients with Idiopathic Pulmonary Fibrosis

PubMed Central

Disayabutr, Supparerk; Kim, Eun Kyung; Cha, Seung-Ick; Green, Gary; Naikawadi, Ram P.; Jones, Kirk D.; Golden, Jeffrey A.; Schroeder, Aaron; Matthay, Michael A.; Kukreja, Jasleen; Erle, David J.; Collard, Harold R.; Wolters, Paul J.

2016-01-01

Pathologic features of idiopathic pulmonary fibrosis (IPF) include genetic predisposition, activation of the unfolded protein response, telomere attrition, and cellular senescence. The mechanisms leading to alveolar epithelial cell (AEC) senescence are poorly understood. MicroRNAs (miRNAs) have been reported as regulators of cellular senescence. Senescence markers including p16, p21, p53, and senescence-associated β-galactosidase (SA-βgal) activity were measured in type II AECs from IPF lungs and unused donor lungs. miRNAs were quantified in type II AECs using gene expression arrays and quantitative RT-PCR. Molecular markers of senescence (p16, p21, and p53) were elevated in IPF type II AECs. SA-βgal activity was detected in a greater percentage in type II AECs isolated from IPF patients (23.1%) compared to patients with other interstitial lung diseases (1.2%) or normal controls (0.8%). The relative levels of senescence-associated miRNAs miR-34a, miR-34b, and miR-34c, but not miR-20a, miR-29c, or miR-let-7f were significantly higher in type II AECs from IPF patients. Overexpression of miR-34a, miR-34b, or miR-34c in lung epithelial cells was associated with higher SA-βgal activity (27.8%, 35.1%, and 38.2%, respectively) relative to control treated cells (8.8%). Targets of miR-34 miRNAs, including E2F1, c-Myc, and cyclin E2, were lower in IPF type II AECs. These results show that markers of senescence are uniquely elevated in IPF type II AECs and suggest that the miR-34 family of miRNAs regulate senescence in IPF type II AECs. PMID:27362652

On High and Low Starting Frequencies of Type II Radio Bursts

NASA Astrophysics Data System (ADS)

Sharma, J.; Mittal, N.

2017-06-01

We have studied the characteristics of type II radio burst during the period May 1996 to March 2015, for the solar cycle 23 and 24, observed by WIND/WAVES radio instrument. A total of 642 events were recorded by the instrument during the study period. We have divided the events with two starting frequency range (high > 1 MHz; low ≤ 1MHz) as type II1 (i.e., 1-16 MHz) radio burst and type II2 (i.e., 20 KHz - 1020 KHz) radio burst which constitute the DH and km type II radio burst observed by WIND spacecraft, and determined their time and frequency characteristics. The mean drift rate of type II1 and type II2 radio bursts is 29.76 × 10-4 MHz/s and 0.17 × 10-4 MHz/s respectively, which shows that type II1 with high start frequency hase larger drift rate than the type II2 with low starting frequencies. We have also reported that the start frequency and the drift rate of type II1 are in good correlation, with a linear correlation coefficient of 0.58.

Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism.

PubMed

Su, W C; Kitagawa, M; Xue, N; Xie, B; Garofalo, S; Cho, J; Deng, C; Horton, W A; Fu, X Y

1997-03-20

The achondroplasia class of chondrodysplasias comprises the most common genetic forms of dwarfism in humans and includes achondroplasia, hypochondroplasia and thanatophoric dysplasia types I and II (TDI and TDII), which are caused by different mutations in a fibroblast growth-factor receptor FGFR3 (ref. 1). The molecular mechanism and the mediators of these FGFR3-related growth abnormalities are not known. Here we show that mutant TDII FGFR3 has a constitutive tyrosine kinase activity which can specifically activate the transcription factor Stat1 (for signal transducer and activator of transcription). Furthermore, expression of TDII FGFR3 induced nuclear translocation of Stat1, expression of the cell-cycle inhibitor p21(WAF1/CIP1), and growth arrest of the cell. Thus, TDII FGFR3 may use Stat1 as a mediator of growth retardation in bone development. Consistent with this, Stat1 activation and increased p21(WAF1/CIP1) expression was found in the cartilage cells from the TDII fetus, but not in those from the normal fetus. Thus, abnormal STAT activation and p21(WAF1/CIP1) expression by the TDII mutant receptor may be responsible for this FGFR3-related bone disease.

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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Induction of tumor necrosis factor alpha by the group- and type-specific polysaccharides from type III group B streptococci.

PubMed Central

Mancuso, G; Tomasello, F; von Hunolstein, C; Orefici, G; Teti, G

1994-01-01

Previous studies suggested that circulating tumor necrosis factor alpha (TNF-alpha) may have a pathophysiologic role in experimental neonatal sepsis induced by group B streptococci (GBS). This study was undertaken to investigate the ability of the type III and group-specific polysaccharides of GBS to induce TNF-alpha production and TNF-alpha-dependent lethality in neonatal rats. The cytokine was detected in plasma samples by the L929 cytotoxicity assay. Intracardiac injections of either polysaccharide induced dose-dependent, transient elevations in plasma TNF-alpha levels that returned to baseline values after 5 h. The group-specific antigen induced significantly higher mean peak TNF-alpha levels than the type III antigen (125 +/- 47 versus 44 +/- 15 U/ml with 70 mg/kg of body weight). Glycogen (70 mg/kg), used as a negative control, did not induce TNF-alpha. The lipopolysaccharide-neutralizing agent polymyxin B did not decrease TNF-alpha levels induced by either polysaccharide, ruling out contamination with endotoxin as a possible cause of TNF-alpha induction. Fifty percent lethal doses of the type III and group-specific antigens given as intracardiac injections were 105 and 16 mg/kg, respectively. Salmonella endotoxin, used as a positive control, had a 50% lethal dose of 0.1 mg/kg. The lethal activities of GBS polysaccharides, as well as endotoxin, were completely prevented by pretreatment of neonatal rats with the respective specific antibodies or anti-murine TNF-alpha serum. To assess the relative importance of the type-specific substance in TNF-alpha induction by whole bacteria, two unrelated GBS transposon mutants devoid of only the type-specific capsular polysaccharide (COH1-13 and COH31-15) were employed. Each of the heat-killed unencapsulated mutants was able to produce plasma TNF-alpha level elevations or TNF-alpha-dependent lethality but was significantly less efficient in these activities than the corresponding encapsulated wild-type strain. These data

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.

TGFbeta type II receptor signaling controls Schwann cell death and proliferation in developing nerves.

PubMed

D'Antonio, Maurizio; Droggiti, Anna; Feltri, M Laura; Roes, Jürgen; Wrabetz, Lawrence; Mirsky, Rhona; Jessen, Kristján R

2006-08-16

During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF) beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGFbeta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGFbeta signaling did not appear to affect other processes in which TGFbeta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death.

Gliomatosis cerebri type II: two case reports

PubMed Central

D’Urso, Pietro Ivo; Marsigliante, Santo; Storelli, Carlo; Distante, Alessandro; Sanguedolce, Francesca; Cimmino, Antonia; Luzi, Giuseppe; Gianfreda, Cosimo Damiano; Montinaro, Antonio; Ciappetta, Pasqualino

2009-01-01

Introduction Two types of gliomatosis cerebri exist: Type I and Type II. We report the results of a histological and genetic study of two cases of gliomatosis cerebri Type II, correlating these results with therapy and prognosis. Case presentation Two patients, a 52-year-old man (Patient 1) and a 76-year-old man (Patient 2) with gliomatosis cerebri II were admitted to our institution; they underwent surgical treatment and received radiotherapy and chemotherapy. At the 24-month follow-up, Patient 1 was still alive, while Patient 2 had died. The poor prognosis of Patient 2 was underlined by molecular analysis which showed that the angiogenesis related genes VCAM1 and VEGF were overexpressed, reflecting the high degree of neovascularization. Conclusion Genes involved in drug resistance and metallothioneins were highly expressed in Patient 2 and this, associated with unmethylated O6-methylguanine methyltransferase, can explain the lack of response to chemotherapy. PMID:19830138

Self-accommodation of B19' martensite in Ti-Ni shape memory alloys - Part II. Characteristic interface structures between habit plane variants

NASA Astrophysics Data System (ADS)

Nishida, M.; Okunishi, E.; Nishiura, T.; Kawano, H.; Inamura, T.; S., Ii; Hara, T.

2012-06-01

Four characteristic interface microstructures between habit plane variants (HPVs) in the self-accommodation morphologies of B19‧ martensite in Ti-Ni alloys have been investigated by scanning transmission electron microscopy (STEM). The straight interface of a ? B19‧ type I twin is present at interface I. The relaxation of the transformation strain at interface II is achieved by a volume reduction of the minor correspondence variants (CVs) in the relevant habit plane variants (HPVs). The relaxation of the transformation strain at interface III is mainly due to the formation of a ? B19‧ type I twin between the two major CVs. Subsequently, local strain around the tips of the minor CVs perpendicular to the interface is released by the formation of micro-twins with the ⟨011⟩B19‧ type II and/or ? B19‧ type I relation. The major and minor CVs in each HPV are alternately connected through fine variants with the ? B19‧ type I twin relation parallel to interface IV. The results are compared with macroscopic observations and the predictions of PTMC analysis.

Comparison of results of endovascular stenting and bypass grafting for TransAtlantic Inter-Society (TASC II) type B, C and D iliac occlusive disease

PubMed Central

Benetis, Rimantas; Antusevas, Aleksandras; Kaupas, Rytis Stasys; Inciura, Donatas; Kinduris, Sarunas

2016-01-01

Introduction The priority use of endovascular techniques in the management of aortoiliac occlusive disease has increased in the last decade. The aim of the present article is to report 1- and 2-year results of iliac artery stenting (IAS) and aortoiliac grafting in the management of patients with TASC II type B, C and D iliac lesions and chronic limb ischaemia. Material and methods In this prospective, non-randomised, one-centre clinical study, iliac artery stents and vascular grafts used for the treatment of patients with symptomatic lesions in the iliac artery were evaluated. This study enrolled 2 groups: 54 patients in the stent group and 47 patient in the surgery group. Results The primary patency rates at 1 and 2 years were 83% and 79.9% after IAS and 97.1% and 97.1% after surgical reconstruction, respectively (p = 0.015). The assisted primary stent patency at 1 and 2 years was 87.9% and 78.2%, respectively. The complication rate was 7.4% in the stent group and 6.3% in the surgery group. There was no perioperative mortality in either group. Conclusions Our results reveal that patients with severe aortoiliac occlusive disease (TASC II types B, C and D) can be treated with IAS or surgically with satisfactory results. Iliac artery stenting is associated with decreased primary patency compared with the surgery group. Iliac artery stenting should be considered with priority in elderly patients or in patients with severe comorbidities. PMID:27186180

Type II first branchial cleft anomaly.

PubMed

Al-Mahdi, Akmam H; Al-Khurri, Luay E; Atto, Ghada Z; Dhaher, Ameer

2013-01-01

First branchial cleft anomaly is a rare disease of the head and neck. It accounts for less than 8% of all branchial abnormalities. It is classified into type I, which is thought to arise from the duplication of the membranous external ear canal and are composed of ectoderm only, and type II that have ectoderm and mesoderm. Because of its rarity, first branchial cleft anomaly is often misdiagnosed and results in inappropriate management. A 9-year-old girl presented to us with fistula in the submandibular region and discharge in the external ear. Under general anesthesia, complete surgical excision of the fistula tract was done through step-ladder approach, and the histopathologic examination confirmed the diagnosis of type II first branchial cleft anomaly.

Impact of Modifiable Risk Factors on B-type Natriuretic Peptide and Cardiac Troponin T Concentrations

PubMed Central

Srivastava, Pratyaksh K.; Pradhan, Aruna D.; Cook, Nancy R.; Ridker, Paul M.; Everett, Brendan M.

2015-01-01

Alcohol use, physical activity, diet, and cigarette smoking are modifiable cardiovascular risk factors that have a substantial impact on the risk of myocardial infarction, stroke, and cardiovascular death. We hypothesized that these behaviors may alter concentrations of cardiac troponin, a marker of myocyte injury, and B-type natriuretic peptide, a marker of myocyte stress. Both markers have shown strong association with adverse cardiovascular outcomes. In 519 women with no evidence of cardiovascular disease, we measured circulating concentrations of cardiac troponin T, using a high-sensitivity assay (hsTnT), and the amino-terminal fragment of B-type natriuretic peptide (NT-proBNP). We used logistic regression to determine if these behaviors were associated with detectable hsTnT (>3 ng/L) or with NT-proBNP in the highest quartile (≥127.3 ng/L). The median (Q1-Q3) NT-proBNP of the cohort was 68.8 (40.3–127.3), and 30.8% (160/519) of the cohort had detectable circulating hsTnT. In adjusted models, women who drank 1–6 drinks per week had lower odds of having a detectable hsTnT (0.58, 95% CI: 0.34–0.96) and lower odds of having an elevated NT-proBNP (OR 0.55, 95% CI 0.32–0.96). We were subsequently able to validate the results for B-type natriuretic peptide in a large independent cohort. In conclusion, our results suggest that regular alcohol consumption is associated with lower concentrations of hsTnT and NT-proBNP, two cardiovascular biomarkers associated with cardiovascular risk, and raise the hypothesis that the beneficial effects of alcohol consumption may be mediated by direct effects on the myocardium. PMID:26739393

Reassessing the Role of Type II Toxin-Antitoxin Systems in Formation of Escherichia coli Type II Persister Cells.

PubMed

Goormaghtigh, Frédéric; Fraikin, Nathan; Putrinš, Marta; Hallaert, Thibaut; Hauryliuk, Vasili; Garcia-Pino, Abel; Sjödin, Andreas; Kasvandik, Sergo; Udekwu, Klas; Tenson, Tanel; Kaldalu, Niilo; Van Melderen, Laurence

2018-06-12

Persistence is a reversible and low-frequency phenomenon allowing a subpopulation of a clonal bacterial population to survive antibiotic treatments. Upon removal of the antibiotic, persister cells resume growth and give rise to viable progeny. Type II toxin-antitoxin (TA) systems were assumed to play a key role in the formation of persister cells in Escherichia coli based on the observation that successive deletions of TA systems decreased persistence frequency. In addition, the model proposed that stochastic fluctuations of (p)ppGpp levels are the basis for triggering activation of TA systems. Cells in which TA systems are activated are thought to enter a dormancy state and therefore survive the antibiotic treatment. Using independently constructed strains and newly designed fluorescent reporters, we reassessed the roles of TA modules in persistence both at the population and single-cell levels. Our data confirm that the deletion of 10 TA systems does not affect persistence to ofloxacin or ampicillin. Moreover, microfluidic experiments performed with a strain reporting the induction of the yefM-yoeB TA system allowed the observation of a small number of type II persister cells that resume growth after removal of ampicillin. However, we were unable to establish a correlation between high fluorescence and persistence, since the fluorescence of persister cells was comparable to that of the bulk of the population and none of the cells showing high fluorescence were able to resume growth upon removal of the antibiotic. Altogether, these data show that there is no direct link between induction of TA systems and persistence to antibiotics. IMPORTANCE Within a growing bacterial population, a small subpopulation of cells is able to survive antibiotic treatment by entering a transient state of dormancy referred to as persistence. Persistence is thought to be the cause of relapsing bacterial infections and is a major public health concern. Type II toxin-antitoxin systems are

Localization of Usher syndrome type II to chromosome 1q.

PubMed

Kimberling, W J; Weston, M D; Möller, C; Davenport, S L; Shugart, Y Y; Priluck, I A; Martini, A; Milani, M; Smith, R J

1990-06-01

Usher syndrome is characterized by congenital hearing loss, progressive visual impairment due to retinitis pigmentosa, and variable vestibular problems. The two subtypes of Usher syndrome, types I and II, can be distinguished by the degree of hearing loss and by the presence or absence of vestibular dysfunction. Type I is characterized by a profound hearing loss and totally absent vestibular responses, while type II has a milder hearing loss and normal vestibular function. Fifty-five members of eight type II Usher syndrome families were typed for three DNA markers in the distal region of chromosome 1q: D1S65 (pEKH7.4), REN (pHRnES1.9), and D1S81 (pTHH33). Statistically significant linkage was observed for Usher syndrome type II with a maximum multipoint lod score of 6.37 at the position of the marker THH33, thus localizing the Usher type II (USH2) gene to 1q. Nine families with type I Usher syndrome failed to show linkage to the same three markers. The statistical test for heterogeneity of linkage between Usher syndrome types I and II was highly significant, thus demonstrating that they are due to mutations at different genetic loci.

BPM Breakdown Potential in the PEP-II B-factory Storage Ring Collider

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weathersby, Stephen; Novokhatski, Alexander; /SLAC

2010-02-10

High current B-Factory BPM designs incorporate a button type electrode which introduces a small gap between the button and the beam chamber. For achievable currents and bunch lengths, simulations indicate that electric potentials can be induced in this gap which are comparable to the breakdown voltage. This study characterizes beam induced voltages in the existing PEP-II storage ring collider BPM as a function of bunch length and beam current.

Type II Supernova Spectral Diversity. II. Spectroscopic and Photometric Correlations

NASA Astrophysics Data System (ADS)

Gutiérrez, Claudia P.; Anderson, Joseph P.; Hamuy, Mario; González-Gaitan, Santiago; Galbany, Lluis; Dessart, Luc; Stritzinger, Maximilian D.; Phillips, Mark M.; Morrell, Nidia; Folatelli, Gastón

2017-11-01

We present an analysis of observed trends and correlations between a large range of spectral and photometric parameters of more than 100 type II supernovae (SNe II), during the photospheric phase. We define a common epoch for all SNe of 50 days post-explosion, where the majority of the sample is likely to be under similar physical conditions. Several correlation matrices are produced to search for interesting trends between more than 30 distinct light-curve and spectral properties that characterize the diversity of SNe II. Overall, SNe with higher expansion velocities are brighter, have more rapidly declining light curves, shorter plateau durations, and higher 56Ni masses. Using a larger sample than previous studies, we argue that “Pd”—the plateau duration from the transition of the initial to “plateau” decline rates to the end of the “plateau”—is a better indicator of the hydrogen envelope mass than the traditionally used optically thick phase duration (OPTd: explosion epoch to end of plateau). This argument is supported by the fact that Pd also correlates with s 3, the light-curve decline rate at late times: lower Pd values correlate with larger s 3 decline rates. Large s 3 decline rates are likely related to lower envelope masses, which enables gamma-ray escape. We also find a significant anticorrelation between Pd and s 2 (the plateau decline rate), confirming the long standing hypothesis that faster declining SNe II (SNe IIL) are the result of explosions with lower hydrogen envelope masses and therefore have shorter Pd values. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile; and the Gemini Observatory, Cerro Pachon, Chile (Gemini Program GS- 2008B-Q-56). Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile (ESO Programs 076.A-0156, 078.D-0048, 080.A-0516, and 082.A-0526).

Edaravone suppresses degradation of type II collagen.

PubMed

Huang, Chen; Liao, Guangjun; Han, Jian; Zhang, Guofeng; Zou, Benguo

2016-05-13

Osteoarthritis (OA) is a degenerative joint disease affecting millions of people. The degradation and loss of type II collagen induced by proinflammatory cytokines secreted by chondrocytes, such as factor-α (TNF-α) is an important pathological mechanism to the progression of OA. Edaravone is a potent free radical scavenger, which has been clinically used to treat the neuronal damage following acute ischemic stroke. However, whether Edaravone has a protective effect in articular cartilage hasn't been reported before. In this study, we investigated the chondrocyte protective effects of Edaravone on TNF-α induced degradation of type Ⅱ collagen. And our results indicated that TNF-α treatment resulted in degradation of type Ⅱ collagen, which can be ameliorated by treatment with Edaravone in a dose dependent manner. Notably, it was found that the inhibitory effects of Edaravone on TNF-α-induced reduction of type Ⅱ collagen were mediated by MMP-3 and MMP-13. Mechanistically, we found that Edaravone alleviated TNF-α induced activation of STAT1 and expression of IRF-1. These findings suggest a potential protective effect of Edaravone in OA. Copyright © 2016. Published by Elsevier Inc.

Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro

NASA Astrophysics Data System (ADS)

Tamaddon, M.; Burrows, M.; Ferreira, S. A.; Dazzi, F.; Apperley, J. F.; Bradshaw, A.; Brand, D. D.; Czernuszka, J.; Gentleman, E.

2017-03-01

Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS - which was released from scaffolds quickly - significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.

Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

PubMed Central

2012-01-01

Background Distal alveolar morphogenesis is marked by differentiation of alveolar type (AT)-II to AT-I cells that give rise to the primary site of gas exchange, the alveolar/vascular interface. Endothelial-Monocyte Activating Polypeptide (EMAP) II, an endogenous protein with anti-angiogenic properties, profoundly disrupts distal lung neovascularization and alveolar formation during lung morphogenesis, and is robustly expressed in the dysplastic alveolar regions of infants with Bronchopulmonary dysplasia. Determination as to whether EMAP II has a direct or indirect affect on ATII→ATI trans-differentiation has not been explored. Method In a controlled nonvascular environment, an in vitro model of ATII→ATI cell trans-differentiation was utilized to demonstrate the contribution that one vascular mediator has on distal epithelial cell differentiation. Results Here, we show that EMAP II significantly blocked ATII→ATI cell transdifferentiation by increasing cellular apoptosis and inhibiting expression of ATI markers. Moreover, EMAP II-treated ATII cells displayed myofibroblast characteristics, including elevated cellular proliferation, increased actin cytoskeleton stress fibers and Rho-GTPase activity, and increased nuclear:cytoplasmic volume. However, EMAP II-treated cells did not express the myofibroblast markers desmin or αSMA. Conclusion Our findings demonstrate that EMAP II interferes with ATII → ATI transdifferentiation resulting in a proliferating non-myofibroblast cell. These data identify the transdifferentiating alveolar cell as a possible target for EMAP II's induction of alveolar dysplasia. PMID:22214516

RISK FACTORS FOR HTLV-II INFECTION IN PERUVIAN MEN WHO HAVE SEX WITH MEN

PubMed Central

ZUNT, JOSEPH R.; LA ROSA, ALBERTO M.; PEINADO, JESÚS; LAMA, JAVIER R.; SUAREZ, LUIS; PUN, MONICA; CABEZAS, CESAR; SANCHEZ, JORGE

2009-01-01

Human T-cell lymphotropic virus type-II (HTLV-II) infection is endemic in indigenous groups in the Americas and injection drug users (IDUs) worldwide. In Peru, HTLV-II infection was previously identified in two indigenous Amazonians. We examined risk factors for HTLV-II infection in 2,703 Peruvian men who have sex with men (MSM): 35 (1.3%) were HTLV-II positive. HTLV-II infection was associated with syphilis, HSV-2 infection, unprotected receptive anal intercourse, and older age. This is the first report of HTLV-II in a non-indigenous non-IDU population in Peru. Additional studies are needed to determine if HTLV-II is a sexually transmitted infection in this and other sexually active populations. PMID:16687704

Excess of Aminopeptidase A in the Brain Elevates Blood Pressure via the Angiotensin II Type 1 and Bradykinin B2 Receptors without Dipsogenic Effect

PubMed Central

Ishida, Akio; Ohya, Yusuke

2017-01-01

Aminopeptidase A (APA) cleaves angiotensin (Ang) II, kallidin, and other related peptides. In the brain, it activates the renin angiotensin system and causes hypertension. Limited data are available on the dipsogenic effect of APA and pressor effect of degraded peptides of APA such as bradykinin. Wistar-Kyoto rats received intracerebroventricular (icv) APA in a conscious, unrestrained state after pretreatment with (i) vehicle, (ii) 80 μg of telmisartan, an Ang II type-1 (AT1) receptor blocker, (iii) 800 nmol of amastatin, an aminopeptidase inhibitor, and (iv) 1 nmol of HOE-140, a bradykinin B2 receptor blocker. Icv administration of 400 and 800 ng of APA increased blood pressure by 12.6 ± 3.0 and 19.0 ± 3.1 mmHg, respectively. APA did not evoke drinking behavior. Pressor response to APA was attenuated on pretreatment with telmisartan (vehicle: 22.1 ± 2.2 mmHg versus telmisartan: 10.4 ± 3.2 mmHg). Pressor response to APA was also attenuated with amastatin and HOE-140 (vehicle: 26.5 ± 1.1 mmHg, amastatin: 14.4 ± 4.2 mmHg, HOE-140: 16.4 ± 2.2 mmHg). In conclusion, APA increase in the brain evokes a pressor response via enzymatic activity without dipsogenic effect. AT1 receptors and B2 receptors in the brain may contribute to the APA-induced pressor response. PMID:28421141

Progenitors of low-luminosity Type II-Plateau supernovae

NASA Astrophysics Data System (ADS)

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

2018-01-01

The progenitors of low-luminosity Type II-Plateau supernovae (SNe II-P) are believed to be red supergiant (RSG) stars, but there is much disparity in the literature concerning their mass at core collapse and therefore on the main sequence. Here, we model the SN radiation arising from the low-energy explosion of RSG stars of 12, 25 and 27 M⊙ on the main sequence and formed through single star evolution. Despite the narrow range in ejecta kinetic energy (2.5-4.2 × 1050 erg) in our model set, the SN observables from our three models are significantly distinct, reflecting the differences in progenitor structure (e.g. surface radius, H-rich envelope mass and He-core mass). Our higher mass RSG stars give rise to Type II SNe that tend to have bluer colours at early times, a shorter photospheric phase, and a faster declining V-band light curve (LC) more typical of Type II-linear SNe, in conflict with the LC plateau observed for low-luminosity SNe II. The complete fallback of the CO core in the low-energy explosions of our high-mass RSG stars prevents the ejection of any 56Ni (nor any core O or Si), in contrast to low-luminosity SNe II-P, which eject at least 0.001 M⊙ of 56Ni. In contrast to observations, Type II SN models from higher mass RSGs tend to show an H α absorption that remains broad at late times (due to a larger velocity at the base of the H-rich envelope). In agreement with the analyses of pre-explosion photometry, we conclude that low-luminosity SNe II-P likely arise from low-mass rather than high-mass RSG stars.

Biomarkers of Type II Synthetic Pyrethroid Pesticides in Freshwater Fish

PubMed Central

2014-01-01

Type II synthetic pyrethroids contain an alpha-cyano group which renders them more neurotoxic than their noncyano type I counterparts. A wide array of biomarkers have been employed to delineate the toxic responses of freshwater fish to various type II synthetic pyrethroids. These include hematological, enzymatic, cytological, genetic, omic and other types of biomarkers. This review puts together the applications of different biomarkers in freshwater fish species in response to the toxicity of the major type II pyrethroid pesticides and assesses their present status, while speculating on the possible future directions. PMID:24868555

Biomarkers of type II synthetic pyrethroid pesticides in freshwater fish.

PubMed

Kaviraj, Anilava; Gupta, Abhik

2014-01-01

Type II synthetic pyrethroids contain an alpha-cyano group which renders them more neurotoxic than their noncyano type I counterparts. A wide array of biomarkers have been employed to delineate the toxic responses of freshwater fish to various type II synthetic pyrethroids. These include hematological, enzymatic, cytological, genetic, omic and other types of biomarkers. This review puts together the applications of different biomarkers in freshwater fish species in response to the toxicity of the major type II pyrethroid pesticides and assesses their present status, while speculating on the possible future directions.

Pioglitazone inhibits angiotensin II-induced atrial fibroblasts proliferation via NF-κB/TGF-β1/TRIF/TRAF6 pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Xiao-qing; Liu, Xu, E-mail: xkliuxu@126.com; Wang, Quan-xing, E-mail: wqxejd@126.com

2015-01-01

The exact mechanisms underlying inhibitory effects of pioglitazone (Pio) on Angiotensin II (AngII)-induced atrial fibrosis are complex and remain largely unknown. In the present study, we examined the effect of Pio on AngII-induced mice atrial fibrosis in vivo and atrial fibroblasts proliferation in vitro. In vivo study showed that AngII infusion induced atrial fibrosis and increased expressions of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) and tumor necrosis factor receptor associated factor 6 (TRAF6) in mice models. However, those effects could be attenuated by Pio (P<0.01). As for in vitro experiment, Pio suppressed AngII-induced atrial fibroblasts proliferation via nuclear factor-κB/transformingmore » growth factor-β1/TRIF/TRAF6 signaling pathway in primary cultured mice atrial fibroblasts (P<0.01). In conclusion, suppression of Pio on AngII-induced atrial fibrosis might be related to its inhibitory effects on above signaling pathway. - Highlights: • Angiotensin II increased atrial fibrosis and related gene expressions in mice. • Angiotensin II induced atrial fibroblasts proliferation by activating signaling pathway. • Pioglitazone reversed both aforementioned changes.« less

Type II flavohemoglobin of Mycobacterium smegmatis oxidizes d-lactate and mediate electron transfer.

PubMed

Thakur, Naveen; Kumar, Ashwani; Dikshit, Kanak L

2018-06-01

Two distantly related flavohemoglobins (FHbs), MsFHbI and MsFHbII, having crucial differences in their heme and reductase domains, co-exist in Mycobacterium smegmatis. Function of MsFHbI is associated with nitric-oxide detoxification but physiological relevance of MsFHbII remains unknown. This study unravels some unique spectral and functional characteristics of MsFHbII. Unlike conventional type I FHbs, MsFHbII lacks nitric-oxide dioxygenase and NADH oxidase activities but utilizes d-lactate as an electron donor to mediate electron transfer. MsFHbII carries a d-lactate dehydrogenase type FAD binding motif in its reductase domain and oxidizes d-lactate in a FAD dependent manner to reduce the heme iron, suggesting that the globin is acting as an electron acceptor. Importantly, expression of MsFHbII in Escherichia coli imparted protection under oxidative stress, suggesting its important role in stress management of its host. Since M. smegmatis lacks the gene encoding for d-lactate dehydrogenase and d-lactate is produced during aerobic metabolism and also as a by-product of lipid peroxidation, the ability of MsFHbII to metabolize d-lactate may provide it a unique ability to balance the oxidative stress generated due to accumulation of d-lactate in the cell and at the same time sequester electrons and pass it to the respiratory apparatus. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

PubMed

Agrawal, Anil Kumar; Pielka, Ewa; Lipinski, Artur; Jelen, Michal; Kielan, Wojciech; Agrawal, Siddarth

2018-01-01

Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

Neutron Scattering Studies of Vortex Matter in Type-II Superconductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xinsheng Ling

2012-02-02

The proposed program is an experimental study of the fundamental properties of Abrikosov vortex matter in type-II superconductors. Most superconducting materials used in applications such as MRI are type II and their transport properties are determined by the interplay between random pinning, interaction and thermal fluctuation effects in the vortex state. Given the technological importance of these materials, a fundamental understanding of the vortex matter is necessary. The vortex lines in type-II superconductors also form a useful model system for fundamental studies of a number of important issues in condensed matter physics, such as the presence of a symmetry-breaking phasemore » transition in the presence of random pinning. Recent advances in neutron scattering facilities such as the major upgrade of the NIST cold source and the Spallation Neutron Source are providing unprecedented opportunities in addressing some of the longstanding issues in vortex physics. The core component of the proposed program is to use small angle neutron scattering and Bitter decoration experiments to provide the most stringent test of the Bragg glass theory by measuring the structure factor in both the real and reciprocal spaces. The proposed experiments include a neutron reflectometry experiment to measure the precise Q-dependence of the structure factor of the vortex lattice in the Bragg glass state. A second set of SANS experiments will be on a shear-strained Nb single crystal for testing a recently proposed theory of the stability of Bragg glass. The objective is to artificially create a set of parallel grain boundaries into a Nb single crystal and use SANS to measure the vortex matter diffraction pattern as a function of the changing angle between the applied magnetic field to the grain boundaries. The intrinsic merits of the proposed work are a new fundamental understanding of type-II superconductors on which superconducting technology is based, and a firm understanding of

30 CFR 57.22235 - Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). 57.22235 Section 57.22235 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). (a) If methane reaches 1.0 percent in the...

30 CFR 57.22235 - Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 1.0 percent methane (I-C, II-A, II-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22235 Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). (a) If methane reaches 1.0 percent in the...

Two reaction pathways for transformation of high potential cytochrome b559 of PS II into the intermediate potential form.

PubMed

Kaminskaya, Olga; Shuvalov, Vladimir A; Renger, Gernot

2007-06-01

This study describes an analysis of different treatments that influence the relative content and the midpoint potential of HP Cyt b559 in PS II membrane fragments from higher plants. Two basically different types of irreversible modification effects are distinguished: the HP form of Cyt b559 is either predominantly affected when the heme group is oxidized ("O-type" effects) or when it is reduced ("R-type" effects). Transformation of HP Cyt b559 to lower potential redox forms (IP and LP forms) by the "O-type" mechanism is induced by high pH and detergent treatments. In this case the effects consist of a gradual decrease in the relative content of HP Cyt b559 while its midpoint potential remains unaffected. Transformation of HP Cyt b559 via an "R-type" mechanism is caused by a number of exogenous compounds denoted L: herbicides, ADRY reagents and tetraphenylboron. These compounds are postulated to bind to the PS II complex at a quinone binding site designated as Q(C) which interacts with Cyt b559 and is clearly not the Q(B) site. Binding of compounds L to the Q(C) site when HP Cyt b559 is oxidized gives rise to a gradual decrease in the E(m) of HP Cyt b559 with increasing concentration of L (up to 10 K(ox)(L) values) while the relative content of HP Cyt b559 is unaffected. Higher concentrations of compounds L required for their binding to Q(C) site when HP Cyt b559 is reduced (described by K(red)(L)) induce a conversion of HP Cyt b559 to lower potential redox forms ("R-type" transformation). Two reaction pathways for transitions of Cyt b559 between the different protein conformations that are responsible for the HP and IP/LP redox forms are proposed and new insights into the functional regulation of Cyt b559 via the Q(C) site are discussed.

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

[Vitamin B12 Deficiency in Type 2 Diabetes Mellitus].

PubMed

Tavares Bello, Carlos; Capitão, Ricardo Miguel; Sequeira Duarte, João; Azinheira, Jorge; Vasconcelos, Carlos

2017-10-31

Type 2 diabetes mellitus is a common disease, affecting up to 13.1% of the Portuguese population. In addition to the known micro and macrovascular complications, drug side effects constitute a major concern, leading to changes in the treatment guidelines, which favor safety over efficacy. Metformin is the first-line pharmacological treatment for most patients with type 2 diabetes mellitus; however, it has been associated with vitamin B12 deficiency in up to 30% of treated patients. The authors describe the prevalence of vitamin B12 deficiency in a diabetic population and explore the possible underlying factors. Retrospective, observational study. Clinical and laboratory data of type 2 diabetes mellitus patients whose vitamin B12 status was evaluated in the last decade (2005 - 2016) were analyzed. Patients with known malabsorptive syndromes or having undergone bariatric surgery were excluded from the study. Statistical analysis of the data was done and the results were considered statistically significant at p values < 0.05. The study included a total of 1007 patients (58% women) with a mean age of 66.4 ± 12.2 years and 11 ± 10.4 years of type 2 diabetes mellitus duration. These patients had a high prevalence of complications: diabetic renal disease 47.7%, neuropathy 9.2%, retinopathy 14.9%, coronary artery disease 8.4%, cerebrovascular disease 10.9%, and peripheral arterial disease 5.5%. Vitamin B12 deficiency (< 174 ng / dL) was present in 21.4% of the population and this subgroup was older (68.4 vs 65.8 years, p = 0.006), had a longer type 2 diabetes mellitus duration (13.35 vs 10.36 years; p = 0.001), higher prevalence of retinopathy (20.9% vs 13.3%; p = 0.005) and thyroid dysfunction (34% vs 23.7%; p = 0.002). Vitamin B12 deficiency was also more frequent in patients treated with metformin (24.7% vs 15.8%; p = 0.017), antiplatelet agents (25.4% vs 16.2%, p < 0.001), and calcium channel blockers (26.8% vs 18.2%; p = 0.001). After adjustment for possible

Qubit and fermionic Fock spaces from type II superstring black holes

NASA Astrophysics Data System (ADS)

Belhaj, A.; Bensed, M.; Benslimane, Z.; Sedra, M. B.; Segui, A.

Using Hodge diagram combinatorial data, we study qubit and fermionic Fock spaces from the point of view of type II superstring black holes based on complex compactifications. Concretely, we establish a one-to-one correspondence between qubits, fermionic spaces and extremal black holes in maximally supersymmetric supergravity obtained from type II superstring on complex toroidal and Calabi-Yau compactifications. We interpret the differential forms of the n-dimensional complex toroidal compactification as states of n-qubits encoding information on extremal black hole charges. We show that there are 2n copies of n qubit systems which can be split as 2n = 2n-1 + 2n-1. More precisely, 2n-1 copies are associated with even D-brane charges in type IIA superstring and the other 2n-1 ones correspond to odd D-brane charges in IIB superstring. This correspondence is generalized to a class of Calabi-Yau manifolds. In connection with black hole charges in type IIA superstring, an n-qubit system has been obtained from a canonical line bundle of n factors of one-dimensional projective space ℂℙ1.

Tumor necrosis factor-α inhibits angiotensin II receptor type 1 expression in dorsal root ganglion neurons via β-catenin signaling.

PubMed

Yang, Y; Wu, H; Yan, J-Q; Song, Z-B; Guo, Q-L

2013-09-17

Both tumor necrosis factor (TNF)-α and the angiotensin (Ang) II/angiotensin II receptor type 1 (AT1) axis play important roles in neuropathic pain and nociception. In the present study, we explored the interaction between the two systems by examining the mutual effects between TNF-α and the Ang II/AT1 receptor axis in dorsal root ganglion (DRG) neurons. Rat DRG neurons were treated with TNF-α in different concentrations for different lengths of time in the presence or absence of transcription inhibitor actinomycin D, TNF receptor 1 (TNFR1) inhibitor SPD304, β-catenin signaling inhibitor CCT031374, or different kinase inhibitors. TNF-α decreased the AT1 receptor mRNA level as well as the AT1a receptor promoter activity in a dose-dependent manner within 30 h, which led to dose-dependent inhibition of Ang II-binding AT1 receptor level on the cell membrane. Actinomycin D (1 mg/ml), SPD304 (50 μM), p38 mitogen-activated protein kinase (MAPK) inhibitor PD169316 (25 μM), and CCT031374 (50 μM) completely abolished the inhibitory effect of TNF-α on AT1 receptor expression. TNF-α dose-dependently increased soluble β-catenin and phosphorylated GSK-3β levels, which was blocked by SPD304 and PD169316. In DRG neurons treated with AT2 receptor agonist CGP421140, or Ang II with or without AT1 receptor antagonist losartan or AT2 receptor antagonist PD123319 for 30 h, we found that Ang II and Ang II+PD123319 significantly decreased TNF-α expression, whereas CPG421140 and Ang II+losartan increased TNF-α expression. In conclusion, we demonstrate that TNF-α inhibits AT1 receptor expression at the transcription level via TNFR1 in rat DRG neurons by increasing the soluble β-catenin level through the p38 MAPK/GSK-3β pathway. In addition, Ang II appears to inhibit and induce TNF-α expression via the AT1 receptor and the AT2 receptor in DRG neurons, respectively. This is the first evidence of crosstalk between TNF-α and the Ang II/AT receptor axis in DRG neurons

Hedgehog inhibition promotes a switch from Type II to Type I cell death receptor signaling in cancer cells.

PubMed

Kurita, Satoshi; Mott, Justin L; Cazanave, Sophie C; Fingas, Christian D; Guicciardi, Maria E; Bronk, Steve F; Roberts, Lewis R; Fernandez-Zapico, Martin E; Gores, Gregory J

2011-03-31

TRAIL is a promising therapeutic agent for human malignancies. TRAIL often requires mitochondrial dysfunction, referred to as the Type II death receptor pathway, to promote cytotoxicity. However, numerous malignant cells are TRAIL resistant due to inhibition of this mitochondrial pathway. Using cholangiocarcinoma cells as a model of TRAIL resistance, we found that Hedgehog signaling blockade sensitized these cancer cells to TRAIL cytotoxicity independent of mitochondrial dysfunction, referred to as Type I death receptor signaling. This switch in TRAIL requirement from Type II to Type I death receptor signaling was demonstrated by the lack of functional dependence on Bid/Bim and Bax/Bak, proapoptotic components of the mitochondrial pathway. Hedgehog signaling modulated expression of X-linked inhibitor of apoptosis (XIAP), which serves to repress the Type I death receptor pathway. siRNA targeted knockdown of XIAP mimics sensitization to mitochondria-independent TRAIL killing achieved by Hedgehog inhibition. Regulation of XIAP expression by Hedgehog signaling is mediated by the glioma-associated oncogene 2 (GLI2), a downstream transcription factor of Hedgehog. In conclusion, these data provide additional mechanisms modulating cell death by TRAIL and suggest Hedgehog inhibition as a therapeutic approach for TRAIL-resistant neoplasms.

HCV proteins and immunoglobulin variable gene (IgV) subfamilies in HCV-induced type II mixed cryoglobulinemia: a concurrent pathogenetic role.

PubMed

Sautto, Giuseppe; Mancini, Nicasio; Solforosi, Laura; Diotti, Roberta A; Clementi, Massimo; Burioni, Roberto

2012-01-01

The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

Past and current perspective on new therapeutic targets for Type-II diabetes.

PubMed

Patil, Pradip D; Mahajan, Umesh B; Patil, Kalpesh R; Chaudhari, Sandip; Patil, Chandragouda R; Agrawal, Yogeeta O; Ojha, Shreesh; Goyal, Sameer N

2017-01-01

Loss of pancreatic β-cell function is a hallmark of Type-II diabetes mellitus (DM). It is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Recently, United Kingdom Prospective Diabetes Study reported that Type-II DM is a progressive disorder. Although, DM can be treated initially by monotherapy with oral agent; eventually, it may require multiple drugs. Additionally, insulin therapy is needed in many patients to achieve glycemic control. Pharmacological approaches are unsatisfactory in improving the consequences of insulin resistance. Single therapeutic approach in the treatment of Type-II DM is unsuccessful and usually a combination therapy is adopted. Increased understanding of biochemical, cellular and pathological alterations in Type-II DM has provided new insight in the management of Type-II DM. Knowledge of underlying mechanisms of Type-II DM development is essential for the exploration of novel therapeutic targets. Present review provides an insight into therapeutic targets of Type-II DM and their role in the development of insulin resistance. An overview of important signaling pathways and mechanisms in Type-II DM is provided for the better understanding of disease pathology. This review includes case studies of drugs that are withdrawn from the market. The experience gathered from previous studies and knowledge of Type-II DM pathways can guide the anti-diabetic drug development toward the discovery of clinically viable drugs that are useful in Type-II DM.

An interactive mutation database for human coagulation factor IX provides novel insights into the phenotypes and genetics of hemophilia B.

PubMed

Rallapalli, P M; Kemball-Cook, G; Tuddenham, E G; Gomez, K; Perkins, S J

2013-07-01

Factor IX (FIX) is important in the coagulation cascade, being activated to FIXa on cleavage. Defects in the human F9 gene frequently lead to hemophilia B. To assess 1113 unique F9 mutations corresponding to 3721 patient entries in a new and up-to-date interactive web database alongside the FIXa protein structure. The mutations database was built using MySQL and structural analyses were based on a homology model for the human FIXa structure based on closely-related crystal structures. Mutations have been found in 336 (73%) out of 461 residues in FIX. There were 812 unique point mutations, 182 deletions, 54 polymorphisms, 39 insertions and 26 others that together comprise a total of 1113 unique variants. The 64 unique mild severity mutations in the mature protein with known circulating protein phenotypes include 15 (23%) quantitative type I mutations and 41 (64%) predominantly qualitative type II mutations. Inhibitors were described in 59 reports (1.6%) corresponding to 25 unique mutations. The interactive database provides insights into mechanisms of hemophilia B. Type II mutations are deduced to disrupt predominantly those structural regions involved with functional interactions. The interactive features of the database will assist in making judgments about patient management. © 2013 International Society on Thrombosis and Haemostasis.

Correlating Type II and III Radio Bursts with Solar Energetic Particle Events

NASA Astrophysics Data System (ADS)

Ledbetter, K.; Winter, L. M.; Quinn, R. A.

2013-12-01

Solar energetic particles (SEPs) are high-energy particles, such as protons, which are accelerated at the Sun and speed outward into the solar system. If they reach Earth, they can be harmful to satellites, ionospheric communications, and humans in space or on polar airline routes. NOAA defines an SEP event as an occasion when the flux of protons with energies higher than 10 MeV exceeds 10 pfu (particle flux units) as measured by the GOES satellites in geosynchronous orbit. The most intense SEP events are associated with shocks, driven by coronal mass ejections (CMEs), which accelerate particles as they move through the corona. However, very few CMEs result in SEP events. To determine what factors are most important in distinguishing the shock waves that will result in SEP acceleration toward Earth, we take into account several variables and perform a principal component analysis (PCA) to examine their correlations. First, we examine Type II radio bursts, which are caused by electrons accelerating in the same CME-driven shocks that can accelerate SEPs. Using data from the WAVES instrument on the WIND satellite, these Type II radio bursts, as well as the Type III bursts that often accompany them, can be characterized by slope in 1/f space and by intensity. In addition, local Langmuir waves detected by WIND, which are caused by electrons speeding through the plasma surrounding the satellite, can be an indicator of the magnetic connectivity between the active region and Earth. Finally, X-ray flares directly preceding the Type II burst are also taken into consideration in the PCA analysis. The accompanying figure illustrates an example of the WAVES solar radio bursts along with the GOES solar proton flux >= 10 MeV during the SEP event on April 11, 2013. Using PCA to determine which of these factors are most relevant to the onset, intensity, and duration of SEP events will be valuable in future work to predict such events. In total, we present the analysis of all type

Human T-Cell Lymphotropic Virus Type 1 Open Reading Frame II-Encoded p30II Is Required for In Vivo Replication: Evidence of In Vivo Reversion

PubMed Central

Silverman, Lee R.; Phipps, Andrew J.; Montgomery, Andrew; Ratner, Lee; Lairmore, Michael D.

2004-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma and exhibits high genetic stability in vivo. HTLV-1 contains four open reading frames (ORFs) in its pX region. ORF II encodes two proteins, p30II and p13II, both of which are incompletely characterized. p30II localizes to the nucleus or nucleolus and has distant homology to the transcription factors Oct-1, Pit-1, and POU-M1. In vitro studies have demonstrated that at low concentrations, p30II differentially regulates cellular and viral promoters through an interaction with CREB binding protein/p300. To determine the in vivo significance of p30II, we inoculated rabbits with cell lines expressing either a wild-type clone of HTLV-1 (ACH.1) or a clone containing a mutation in ORF II, which eliminated wild-type p30II expression (ACH.30.1). ACH.1-inoculated rabbits maintained higher HTLV-1-specific antibody titers than ACH.30.1-inoculated rabbits, and all ACH.1-inoculated rabbits were seropositive for HTLV-1, whereas only two of six ACH.30.1-inoculated rabbits were seropositive. Provirus could be consistently PCR amplified from peripheral blood mononuclear cell (PBMC) DNA in all ACH.1-inoculated rabbits but in only three of six ACH.30.1-inoculated rabbits. Quantitative competitive PCR indicated higher PBMC proviral loads in ACH.1-inoculated rabbits. Interestingly, sequencing of ORF II from PBMC of provirus-positive ACH.30.1-inoculated rabbits revealed a reversion to wild-type sequence with evidence of early coexistence of mutant and wild-type sequence. Our data provide evidence that HTLV-1 must maintain its key accessory genes to survive in vivo and that in vivo pressures select for maintenance of wild-type ORF II gene products during the early course of infection. PMID:15047799

Factors Affecting Optimal Aortic Remodeling After Thoracic Endovascular Aortic Repair of Type B (IIIb) Aortic Dissection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, I-Ming; Chen, Po-Lin; Huang, Chun-Yang

PurposeThe purpose of this study was to determine factors associated with entire aortic remodeling after thoracic endovascular aortic repair (TEVAR) in patients with type B dissection.Materials and MethodsThe patients with type B (IIIb) dissections who underwent TEVAR from 2006 to 2013 with minimum of 2 years of follow-up computed tomography data were retrospectively reviewed. Based on the status of false lumen remodeling of entire aorta, patients were divided into three groups: complete regression, total thrombosis, and inadequate regression with patent abdominal false lumen.ResultsA total of 90 patients (72 males, 18 females; mean age 56.6 ± 16.4 years) were included and divided into the completemore » regression (n = 22), total thrombosis (n = 18), and inadequate regression (n = 50) groups. Multivariate logistic regression analysis indicated that dissection extension to iliac arteries, increased preoperative number of dissection tear over abdominal aorta, and decreased preoperative abdominal aorta bifurcation true lumen ratio, as compared between the inadequate and complete regression groups, were associated with a persistent false lumen (odds ratio = 33.33, 2.304, and 0.021; all, p ≤ 0.012). Comparison of 6, 12, and 24 months postoperative data revealed no significant differences at any level, suggesting that the true lumen area ratio might not change after 6 months postoperatively.ConclusionsIncreased preoperative numbers of dissection tear around the abdominal visceral branches, dissection extension to the iliac arteries, and decreased preoperative true lumen area ratio of abdominal aorta are predictive of entire aortic remodeling after TEVAR in patients with type B dissection.Level of EvidenceIII.« less

Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography

PubMed Central

Mousavi Hosseini, Kamran; Nasiri, Saleh

2015-01-01

Background: Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. Methods: PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Results: Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). Results of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). Conclusion: It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII. PMID:26034723

Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography.

PubMed

Mousavi Hosseini, Kamran; Nasiri, Saleh

2015-01-01

Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). RESULTS of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII.

Elevation of c-MYC Disrupts HLA Class II-mediated Immune Recognition of Human B-cell Tumors1

PubMed Central

God, Jason M.; Cameron, Christine; Figueroa, Janette; Amria, Shereen; Hossain, Azim; Kempkes, Bettina; Bornkamm, Georg W.; Stuart, Robert K.; Blum, Janice S.; Haque, Azizul

2014-01-01

Elevated levels of the transcription factor c-myc are strongly associated with various cancers, and in particular B-cell lymphomas. While many of c-MYC’s functions have been elucidated, its effect on the presentation of antigen (Ag) through the HLA class II pathway has not previously been reported. This is an issue of considerable importance, given the low immunogenicity of many c-MYC-positive tumors. We report here that increased c-MYC expression has a negative effect on the ability of B-cell lymphomas to functionally present Ags/peptides to CD4+ T cells. This defect was associated with alterations in the expression of distinct co-factors as well as interactions of antigenic peptides with class II molecules required for the presentation of class II-peptide complexes and T cell engagement. Using early passage Burkitt’s lymphoma (BL) tumors and transformed cells, we show that compared to B-lymphoblasts, BL cells express decreased levels of the class II editor HLA-DM, lysosomal thiol-reductase GILT, and a 47kDa enolase-like protein. Functional Ag presentation was partially restored in BL cells treated with a c-MYC inhibitor, demonstrating the impact of this oncogene on Ag recognition. This restoration of HLA class II-mediated Ag presentation in early passage BL tumors/cells was linked to enhanced HLA-DM expression and a concurrent decrease in HLA-DO in BL cells. Taken together, these results reveal c-MYC exerts suppressive effects at several critical checkpoints in Ag presentation which contribute to the immunoevasive properties of BL tumors. PMID:25595783

[Thrombocytopenia induced by type II heparin and myocardial infarct: 2 case reports].

PubMed

Antonijević, Nabojsa; Stanojević, Milica; Perunicić, Jovan; Djokić, Milan; Miković, Danijla; Kovac, Mirjana; Miljić, Predrag; Milosević, Rajko; Terzić, Branka; Vasiljević, Zorana

2004-01-01

Heparin-induced thrombocytopenia (HIT) type II is an acquired thrombophylic state and life-threatening immune complication of a heparin treatment mainly clinically manifested by marked thrombocytopenia, frequently by arterial and venous thrombosis, and sometimes by skin changes. Functional assay as heparin aggregation test and 14C-serotonin release assays are used in diagnostics as well as antigen assays of which detection tests for heparin-platelet factor 4 antibodies are most frequently used. Considering the fact that there is no single reliable assays for HIT II detection available, sometimes it is necessary to combine both of the above-mentioned types of assays. We present the case of a 57-year-old patient with an acute anterior myocardial infarction with cardiac insufficiency of III and IV degree according to Killip, recurrent ventricular fibrillation and diabetes mellitus type II developing thrombocytopenia to 37 x 10(9)/l accompanied with typical skin changes. The diagnosis was confirmed by the heparin aggregation test. The second patient aged 70 undergoing the treatment for anteroseptal myocardial infarction and reinfarction of the inferior wall complicated by a cardiogenic shock and acute right bundle branch block developed thrombocytopenia 59 x 10(9)/l on the third day of the heparin therapy, with the remark that he had received a heparin therapy during the first infarction as well. Antibodies against heparin-platelet factor 4 were detected by particle gel ID-HPF4 immuno-assay. In both patients, the disease had a lethal outcome despite all then available therapeutic measures applied. Further on we discuss advantages of certain types of tests, a therapy doctrine, need for urgent therapeutic measures, inclusive of the administration of antithrombins, avoidance of harmful procedures like low-molecular-weight heparins administration and prophylactic platelet transfusion as well as preventive measures.

Type-II Superlattice for High Performance LWIR Detectors

DTIC Science & Technology

2008-05-15

Superlattice for High Performance LWIR Detectors 5. FUNDING NUMBERS F49620-03-1-0436 6. AUTHOR(S) M. Razeghi 7. PERFORMING ORGANIZATION NAME(S...298 (Rcv.2-89) Prescribed by ANSI Std. 239-18 298-102 Final Technical Report Type-II Superlattice for High Performance LWIR Detectors Contract No...Short-period InAs/GaSb type-II superlattices for mid- infrared detectors . Physica E: Low- dimensional Systems and Nanostructures, 2006.

Solution structure of the chick TGFbeta type II receptor ligand-binding domain.

PubMed

Marlow, Michael S; Brown, Christopher B; Barnett, Joey V; Krezel, Andrzej M

2003-02-28

The transforming growth factor beta (TGFbeta) signaling pathway influences cell proliferation, immune responses, and extracellular matrix reorganization throughout the vertebrate life cycle. The signaling cascade is initiated by ligand-binding to its cognate type II receptor. Here, we present the structure of the chick type II TGFbeta receptor determined by solution NMR methods. Distance and angular constraints were derived from 15N and 13C edited NMR experiments. Torsion angle dynamics was used throughout the structure calculations and refinement. The 20 final structures were energy minimized using the generalized Born solvent model. For these 20 structures, the average backbone root-mean-square distance from the average structure is below 0.6A. The overall fold of this 109-residue domain is conserved within the superfamily of these receptors. Chick receptors fully recognize and respond to human TGFbeta ligands despite only 60% identity at the sequence level. Comparison with the human TGFbeta receptor determined by X-ray crystallography reveals different conformations in several regions. Sequence divergence and crystal packing interactions under low pH conditions are likely causes. This solution structure identifies regions were structural changes, however subtle, may occur upon ligand-binding. We also identified two very well conserved molecular surfaces. One was found to bind ligand in the crystallized human TGFbeta3:TGFbeta type II receptor complex. The other, newly identified area can be the interaction site with type I and/or type III receptors of the TGFbeta signaling complex.

Chiral anomaly and longitudinal magnetotransport in type-II Weyl semimetals

NASA Astrophysics Data System (ADS)

Sharma, Girish; Goswami, Pallab; Tewari, Sumanta

2017-07-01

In the presence of parallel electric and magnetic fields, the violation of a separate number conservation laws for the three-dimensional left- and right-handed Weyl fermions is known as the chiral anomaly. The recent discovery of Weyl and Dirac semimetals has paved the way for experimentally testing the effects of chiral anomaly via magnetotransport measurements, since chiral anomaly can lead to negative longitudinal magnetoresistance (LMR) while the transverse magnetoresistance remains positive. More recently, a type-II Weyl semimetal (WSM) phase has been proposed, where the nodal points possess a finite density of states due to the touching between electron and hole pockets. It has been suggested that the main difference between the two types of WSMs (type I and type II) is that in the latter, chiral-anomaly-induced negative LMR (positive longitudinal magnetoconductance) is strongly anisotropic, vanishing when the applied magnetic field is perpendicular to the direction of tilt of Weyl fermion cones in a type-II WSM. We analyze chiral anomaly in a type-II WSM in a quasiclassical Boltzmann framework, and find that the chiral-anomaly-induced positive longitudinal magnetoconductivity is present along any arbitrary direction. Thus, our results are pertinent for uncovering transport signatures of type-II WSMs in different candidate materials.

Modeling Type II-P/II-L Supernovae Interacting with Recent Episodic Mass Ejections from Their Presupernova Stars with MESA and SNEC

NASA Astrophysics Data System (ADS)

Das, Sanskriti; Ray, Alak

2017-12-01

We show how dense, compact, discrete shells of circumstellar gas immediately outside of red supergiants affect the optical light curves of Type II-P/II-L supernovae (SNe), using the example of SN 2013ej. Earlier efforts in the literature had used an artificial circumstellar medium (CSM) stitched to the surface of an evolved star that had not gone through a phase of late-stage heavy mass loss, which, in essence, is the original source of the CSM. In contrast, we allow enhanced mass-loss rate from the modeled star during the 16O and 28Si burning stages and construct the CSM from the resulting mass-loss history in a self-consistent way. Once such evolved pre-SN stars are exploded, we find that the models with early interaction between the shock and the dense CSM reproduce light curves far better than those without that mass loss and, hence, having no nearby dense CSM. The required explosion energy for the progenitors with a dense CSM is reduced by almost a factor of two compared to those without the CSM. Our model, with a more realistic CSM profile and presupernova and explosion parameters, fits observed data much better throughout the rise, plateau, and radioactive tail phases as compared to previous studies. This points to an intermediate class of supernovae between Type II-P/II-L and Type II-n SNe with the characteristics of simultaneous UV and optical peak, slow decline after peak, and a longer plateau.

Autopsy case of microcephalic osteodysplastic primordial "dwarfism" type II.

PubMed

Fukuzawa, Ryuji; Sato, Seiji; Sullivan, Michael J; Nishimura, Gen; Hasegawa, Tomonobu; Matsuo, Nobutake

2002-11-15

Microcephalic osteodysplastic primordial "dwarfism" (MOPD) is a group of disorders similar to Seckel syndrome. Three subtypes (types I-III) have been reported. We report here the first autopsy case of MOPD type II. The patient was a Japanese girl with typical clinical and radiological manifestations of MOPD type II. The manifestations included severe intrauterine and postnatal growth failure, microcephaly, a distinctive facial appearance, micromelia, brachytelephalangy, coxa vara, and V-shaped metaphyses of the distal femora. Other than small cerebral hemispheres, no neuropathological abnormalities were found. Chondro-osseous histology showed thinning of the growth plate, ballooned chondrocytes, reduced cellularity, lack of zonal and columnar formations, and poor formation of primary trabeculae. These findings suggest that impairment of chondrocytic formation and differentiation is the major pathogenesis of MOPD type II. Copyright 2002 Wiley-Liss, Inc.

Laboratory diagnosis of von Willebrand disease type 1/2E (2A subtype IIE), type 1 Vicenza and mild type 1 caused by mutations in the D3, D4, B1-B3 and C1-C2 domains of the von Willebrand factor gene. Role of von Willebrand factor multimers and the von Willebrand factor propeptide/antigen ratio.

PubMed

Gadisseur, Alain; Berneman, Zwi; Schroyens, Wilfried; Michiels, Jan Jacques

2009-01-01

Autosomal dominant von Willebrand disease (VWD) type 1/2E is a quantitative/qualitative defect in the von Willebrand factor (VWF) caused by heterozygous cysteine and non-cysteine mutations in the D3 domain of the VWF gene and results in a secretion-multimerization-clearance defect in mutant VWF with the loss of large VWF multimers not due to proteolysis. The multimers of patients with dominant VWD type 1/2E due to mutations in the D3 domain show an aberrant triplet structure with lack of outer bands but with pronounced inner bands of the triplet structure combined with a relative decrease in large multimers reflecting heterozygosity for multimerization defects. There is a good response to desmopressin (DDAVP) followed by rapid clearance of VWF:antigen (Ag), factor VIII coagulant activity (FVIII:C) and VWF:ristocetin cofactor activity (RCo) as the main cause of VWD type 1 or 2 with typical 2E multimeric pattern (VWD type 1/2E). Cysteine mutations in the D3 domains (C1130, C1149 and C1190) show pronounced features of VWD 1/2E with the relative loss of large and relative increase in small VWF multimers with abnormal triplet structure in heterozygotes. Such abnormalities are less pronounced in patients with a milder form of VWD type 1 due to non-cysteine mutations W1144G, T1156M and W1120S in the D3 domain. VWD type 1 Vicenza is caused by the R1205H mutation in the D3 domain and characterized by equally low levels of FVIII:C, VWF:Ag and VWF:RCo. The response to DDAVP in VWD Vicenza is good for FVIII:C, VWF:Ag and VWF:RCo, which is followed by a rapid clearance in less than a few hours of FVIII:C and VWF parameters. The ratios for FVIII:C/VWF:Ag, VWF:RCo/Ag and VWF:CB/Ag remain normal before and after DDAVP indicating that VWD Vicenza clearly differs from VWD type 1, 1/2E and 2M. A new set of missense mutations in D4, B1-B3 and C1-C2 domains has been discovered as the cause of a mild VWD type 1 secretion defect with normal VWF multimers or smeary VWF multimeric pattern

Management and classification of type II congenital portosystemic shunts.

PubMed

Lautz, Timothy B; Tantemsapya, Niramol; Rowell, Erin; Superina, Riccardo A

2011-02-01

Congenital portosystemic shunts (PSS) with preserved intrahepatic portal flow (type II) present with a range of clinical signs. The indications for and benefits of repair of PSS remain incompletely understood. A more comprehensive classification may also benefit comparative analyses from different institutions. All children treated at our institution for type II congenital PSS from 1999 through 2009 were reviewed for presentation, treatment, and outcome. Ten children (7 boys) with type II PSS were identified at a median age of 5.5 years. Hyperammonemia with varying degrees of neurocognitive dysfunction occurred in 80%. The shunt arose from a branch of the portal vein (type IIa; n = 2), from the main portal vein (type IIb; n = 7), or from a splenic or mesenteric vein (type IIc; n = 1). Management included operative ligation (n = 6), endovascular occlusion (n = 3), or a combined approach (n = 1). Shunt occlusion was successful in all cases. Serum ammonia decreased from 130 ± 115 μmol/L preoperatively to 31 ± 15 μmol/L postoperatively (P = .03). Additional benefits included resolution of neurocognitive dysfunction (n = 3), liver nodules (n = 1), and vaginal bleeding (n = 1). Correction of type II PSS relieves a wide array of symptoms. Surgery is indicated for patients with clinically significant shunting. A refined classification system will permit future comparison of patients with similar physiology. Copyright © 2011 Elsevier Inc. All rights reserved.

Plasma exchange in the treatment of thyroid storm secondary to type II amiodarone-induced thyrotoxicosis.

PubMed

Zhu, Ling; Zainudin, Sueziani Binte; Kaushik, Manish; Khor, Li Yan; Chng, Chiaw Ling

2016-01-01

Type II amiodarone-induced thyrotoxicosis (AIT) is an uncommon cause of thyroid storm. Due to the rarity of the condition, little is known about the role of plasma exchange in the treatment of severe AIT. A 56-year-old male presented with thyroid storm 2months following cessation of amiodarone. Despite conventional treatment, his condition deteriorated. He underwent two cycles of plasma exchange, which successfully controlled the severe hyperthyroidism. The thyroid hormone levels continued to fall up to 10h following plasma exchange. He subsequently underwent emergency total thyroidectomy and the histology of thyroid gland confirmed type II AIT. Management of thyroid storm secondary to type II AIT can be challenging as patients may not respond to conventional treatments, and thyroid storm may be more harmful in AIT patients owing to the underlying cardiac disease. If used appropriately, plasma exchange can effectively reduce circulating hormones, to allow stabilisation of patients in preparation for emergency thyroidectomy. Type II AIT is an uncommon cause of thyroid storm and may not respond well to conventional thyroid storm treatment.Prompt diagnosis and therapy are important, as patients may deteriorate rapidly.Plasma exchange can be used as an effective bridging therapy to emergency thyroidectomy.This case shows that in type II AIT, each cycle of plasma exchange can potentially lower free triiodothyronine levels for 10h.Important factors to consider when planning plasma exchange as a treatment for thyroid storm include timing of each session, type of exchange fluid to be used and timing of surgery.

Factors affecting marginal integrity of class II bulk-fill composite resin restorations

PubMed Central

Savadi Oskoee, Siavash; Bahari, Mahmoud; Jafari Navimipour, Elmira; Ajami, Amir Ahmad; Ghiasvand, Negar; Savadi Oskoee, Ayda

2017-01-01

Background. Bulk-fill composite resins are a new type of resin-based composite resins, claimed to have the capacity to be placed in thick layers, up to 4 mm. This study was carried out to evaluate factors affecting gap formation in Cl II cavities restored using the bulk-fill technique. Methods. A total of 60 third molars were used in this study. Two Cl II cavities were prepared in each tooth, one on the mesial aspect 1 mm coronal to the CEJ and one on the distal aspect 1 mm apical to the CEJ. The teeth were divided into 4 groups: A: The cavities were restored using the bulk-fill technique with Filtek P90 composite resin and its adhesive system and light-cured with quartz tungsten halogen (QTH) light-curing unit. B: The cavities were restored similar to that in group A but light-cured with an LED light-curing unit. C: The cavities were restored using the bulk-fill technique with X-tra Fil composite resin and Clearfil SE Bond adhesive system and light-cured with a QTH curing unit. D: The cavities were restored similar to that in group C but light-cured with an LED light-curing unit. The gaps were examined under a stereomicroscope at ×60. Data were analyzed with General Linear Model test. In cases of statistical significance (P<0.05), post hoc Bonferroni test was used for further analyses. Results. The light-curing unit type had no effect on gap formation. However, the results were significant in relation to the composite resin type and margin location (P<0.001). The cumulative effects of light-curing unit*gingival margin and light-curing unit*composite resin type were not significant; however, the cumulative effect of composite rein type*gingival margin was significant (P=0.04) Conclusion. X-tra Fil composite exhibited smaller gaps compared with Filtek P90 composite with both light-curing units. Both composite resins exhibited smaller gaps at enamel margins. PMID:28748051

Assessment of type II diabetes mellitus using irregularly sampled measurements with missing data.

PubMed

Barazandegan, Melissa; Ekram, Fatemeh; Kwok, Ezra; Gopaluni, Bhushan; Tulsyan, Aditya

2015-04-01

Diabetes mellitus is one of the leading diseases in the developed world. In order to better regulate blood glucose in a diabetic patient, improved modelling of insulin-glucose dynamics is a key factor in the treatment of diabetes mellitus. In the current work, the insulin-glucose dynamics in type II diabetes mellitus can be modelled by using a stochastic nonlinear state-space model. Estimating the parameters of such a model is difficult as only a few blood glucose and insulin measurements per day are available in a non-clinical setting. Therefore, developing a predictive model of the blood glucose of a person with type II diabetes mellitus is important when the glucose and insulin concentrations are only available at irregular intervals. To overcome these difficulties, we resort to online sequential Monte Carlo (SMC) estimation of states and parameters of the state-space model for type II diabetic patients under various levels of randomly missing clinical data. Our results show that this method is efficient in monitoring and estimating the dynamics of the peripheral glucose, insulin and incretins concentration when 10, 25 and 50% of the simulated clinical data were randomly removed.

Profiling of cardio-metabolic risk factors and medication utilisation among Type II diabetes patients in Ghana: a prospective cohort study.

PubMed

Adua, Eric; Roberts, Peter; Sakyi, Samuel Asamoah; Yeboah, Francis Agyemang; Dompreh, Albert; Frimpong, Kwasi; Anto, Enoch Odame; Wang, Wei

2017-09-07

Type II diabetes mellitus (T2DM) is complicated by multiple cardio-metabolic risk factors. Controlling these factors requires lifestyle modifications alongside utilisation of anti-diabetic medications. Different glucose lowering [(biguanides (BIGs), sulfonylureas (SUAs), thiazolidinediones (TNZ)], lipid lowering (statins), and anti-hypertensive medicines [angiotensin converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs) and central acting drugs (CADs)] have been approved for controlling hyperglycaemia, dyslipidaemia and hypertension respectively. Here, we examined factors that characterise T2DM and explored the response to medication therapy among T2DM patients. This prospective cohort study recruited 241 T2DM patients reporting at a clinic in Ghana, from January through to August, 2016. Each patient's demographic, medications and anthropometric data was obtained while information on medication adherence was captured using Morisky adherence scale-8 (MMAS-8). Fasting blood samples were collected for biochemical analysis. The mean age of participants was 57.82 years for baseline and six-month follow-up. Physical activity differed at baseline and follow up (p < 0.05) but not body mass index (BMI). BIG alone, or in combination with SUA and TNZ did not improve glycaemic status at follow up (p > 0.05). Many participants using either ACEI or ARB were able to control their blood pressures. Among dyslipidaemia patients under statin treatment, there was an improved lipid profile at follow-up. Statin medications are effective for reducing dyslipidaemia in T2DM patients. However, control of modifiable risk factors, particularly blood glucose and to a lesser degree blood pressure is suboptimal. Addressing these will require concomitant interventions including education on medication adherence and correct dietary plans, lifestyle modifications and physical activity.

Dynamic investigation of DNA bending and wrapping by type II topoisomerases

NASA Astrophysics Data System (ADS)

Shao, Qing; Finzi, Laura; Dunlap, David

2009-11-01

Type II topoisomerases catalyze DNA decatenation and unwinding which is crucial for cell division, and therefore type II topoisomerases are some of the main targets of anti-cancer drugs. A recent crystal structure shows that, during the catalytic cycle, a yeast type II topoimerase can bend a 10 base pair DNA segment by up to 150 degrees. Bacterial gyrase, another type II topoisomerase, can wrap DNA into a tight 180 degree turn. Bending a stiff polymer like DNA requires considerable energy and could represent the rate limiting step in the catalytic (topological) cycle. Using modified deoxyribonucleotides in PCR reactions, stiffer DNA fragments have been produced and used as substrates for topoisomerase II-mediated relaxation of plectonemes introduced in single molecules using magnetic tweezers. The wrapping ability of gyrase decreases for diamino-purine-substituted DNA in which every base pair has three hydrogen-bonds. The overall rate of relaxation of plectonemes by recombinant human topoisomerase II alpha also decreases. These results reveal the dynamic properties of DNA bending and wrapping by type II topisomerases and suggest that A:T base pair melting is a rate determining step for bending and wrapping.

In Situ D-periodic Molecular Structure of Type II Collagen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Antipova, Olga; Orgel, Joseph P.R.O.

Collagens are essential components of extracellular matrices in multicellular animals. Fibrillar type II collagen is the most prominent component of articular cartilage and other cartilage-like tissues such as notochord. Its in situ macromolecular and packing structures have not been fully characterized, but an understanding of these attributes may help reveal mechanisms of tissue assembly and degradation (as in osteo- and rheumatoid arthritis). In some tissues such as lamprey notochord, the collagen fibrillar organization is naturally crystalline and may be studied by x-ray diffraction. We used diffraction data from native and derivative notochord tissue samples to solve the axial, D-periodic structuremore » of type II collagen via multiple isomorphous replacement. The electron density maps and heavy atom data revealed the conformation of the nonhelical telopeptides and the overall D-periodic structure of collagen type II in native tissues, data that were further supported by structure prediction and transmission electron microscopy. These results help to explain the observed differences in collagen type I and type II fibrillar architecture and indicate the collagen type II cross-link organization, which is crucial for fibrillogenesis. Transmission electron microscopy data show the close relationship between lamprey and mammalian collagen fibrils, even though the respective larger scale tissue architecture differs.« less

Interaction between ROCK II and nucleophosmin/B23 in the regulation of centrosome duplication.

PubMed

Ma, Zhiyong; Kanai, Masayuki; Kawamura, Kenji; Kaibuchi, Kozo; Ye, Keqiang; Fukasawa, Kenji

2006-12-01

Nucleophosmin (NPM)/B23 has been implicated in the regulation of centrosome duplication. NPM/B23 localizes between two centrioles in the unduplicated centrosome. Upon phosphorylation on Thr(199) by cyclin-dependent kinase 2 (CDK2)/cyclin E, the majority of centrosomal NPM/B23 dissociates from centrosomes, but some NPM/B23 phosphorylated on Thr(199) remains at centrosomes. It has been shown that Thr(199) phosphorylation of NPM/B23 is critical for the physical separation of the paired centrioles, an initial event of the centrosome duplication process. Here, we identified ROCK II kinase, an effector of Rho small GTPase, as a protein that localizes to centrosomes and physically interacts with NPM/B23. Expression of the constitutively active form of ROCK II promotes centrosome duplication, while down-regulation of ROCK II expression results in the suppression of centrosome duplication, especially delaying the initiation of centrosome duplication during the cell cycle. Moreover, ROCK II regulates centrosome duplication in its kinase and centrosome localization activity-dependent manner. We further found that ROCK II kinase activity is significantly enhanced by binding to NPM/B23 and that NPM/B23 acquires a higher binding affinity to ROCK II upon phosphorylation on Thr(199). Moreover, physical interaction between ROCK II and NPM/B23 in vivo occurs in association with CDK2/cyclin E activation and the emergence of Thr(199)-phosphorylated NPM/B23. All these findings point to ROCK II as the effector of the CDK2/cyclin E-NPM/B23 pathway in the regulation of centrosome duplication.

Floquet Weyl semimetals in light-irradiated type-II and hybrid line-node semimetals

NASA Astrophysics Data System (ADS)

Chen, Rui; Zhou, Bin; Xu, Dong-Hui

2018-04-01

Type-II Weyl semimetals have recently attracted intensive research interest because they host Lorentz-violating Weyl fermions as quasiparticles. The discovery of type-II Weyl semimetals evokes the study of type-II line-node semimetals (LNSMs) whose linear dispersion is strongly tilted near the nodal ring. We present here a study on the circularly polarized light-induced Floquet states in type-II LNSMs, as well as those in hybrid LNSMs that have a partially overtilted linear dispersion in the vicinity of the nodal ring. We illustrate that two distinct types of Floquet Weyl semimetal (WSM) states can be induced in periodically driven type-II and hybrid LNSMs, and the type of Floquet WSMs can be tuned by the direction and intensity of the incident light. We construct phase diagrams of light-irradiated type-II and hybrid LNSMs which are quite distinct from those of light-irradiated type-I LNSMs. Moreover, we show that photoinduced Floquet type-I and type-II WSMs can be characterized by the emergence of different anomalous Hall conductivities.

Central IKKβ inhibition prevents air pollution mediated peripheral inflammation and exaggeration of type II diabetes.

PubMed

Liu, Cuiqing; Fonken, Laura K; Wang, Aixia; Maiseyeu, Andrei; Bai, Yuntao; Wang, Tse-Yao; Maurya, Santosh; Ko, Yi-An; Periasamy, Muthu; Dvonch, Timothy; Morishita, Masako; Brook, Robert D; Harkema, Jack; Ying, Zhekang; Mukherjee, Bhramar; Sun, Qinghua; Nelson, Randy J; Rajagopalan, Sanjay

2014-10-30

Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (<2.5 μm in aerodynamic diameter, PM2.5) and development of insulin resistance/Type II diabetes mellitus (Type II DM). We investigated the role of hypothalamic inflammation in PM2.5-mediated diabetes development. KKay mice, a genetically susceptible model of Type II DM, were assigned to either concentrated PM2.5 or filtered air (FA) for 4-8 weeks via a versatile aerosol concentrator and exposure system, or administered intra-cerebroventricular with either IKKβ inhibitor (IMD-0354) or TNFα antibody (infliximab) for 4-5 weeks simultaneously with PM2.5 exposure. Glucose tolerance, insulin sensitivity, oxygen consumption and heat production were evaluated. At euthanasia, blood, spleen, visceral adipose tissue and hypothalamus were collected to measure inflammatory cells using flow cytometry. Standard immunohistochemical methods and quantitative PCR were used to assess targets of interest. PM2.5 exposure led to hyperglycemia and insulin resistance, which was accompanied by increased hypothalamic IL-6, TNFα, and IKKβ mRNA expression and microglial/astrocyte reactivity. Targeting the NFκB pathway with intra-cerebroventricular administration of an IKKβ inhibitor [IMD-0354, n = 8 for each group)], but not TNFα blockade with infliximab [(n = 6 for each group], improved glucose tolerance, insulin sensitivity, rectified energy homeostasis (O2 consumption, CO2 production, respiratory exchange ratio and heat generation) and reduced peripheral inflammation in response to PM2.5. Central inhibition of IKKβ prevents PM2.5 mediated peripheral inflammation and exaggeration of type II diabetes. These results provide novel insights into how air pollution may mediate susceptibility to insulin resistance and Type II DM.

Experimental Observation of Anisotropic Adler-Bell-Jackiw Anomaly in Type-II Weyl Semimetal WTe1.98 Crystals at the Quasiclassical Regime

NASA Astrophysics Data System (ADS)

Lv, Yang-Yang; Li, Xiao; Zhang, Bin-Bin; Deng, W. Y.; Yao, Shu-Hua; Chen, Y. B.; Zhou, Jian; Zhang, Shan-Tao; Lu, Ming-Hui; Zhang, Lei; Tian, Mingliang; Sheng, L.; Chen, Yan-Feng

2017-03-01

The asymmetric electron dispersion in type-II Weyl semimetal theoretically hosts anisotropic transport properties. Here, we observe the significant anisotropic Adler-Bell-Jackiw (ABJ) anomaly in the Fermi-level delicately adjusted WTe1.98 crystals. Quantitatively, CW , a coefficient representing the intensity of the ABJ anomaly along the a and b axis of WTe1.98 are 0.030 and 0.051 T-2 at 2 K, respectively. We found that the temperature-sensitive ABJ anomaly is attributed to a topological phase transition from a type-II Weyl semimetal to a trivial semimetal, which is verified by a first-principles calculation using experimentally determined lattice parameters at different temperatures. Theoretical electrical transport study reveals that the observation of an anisotropic ABJ along both the a and b axes in WTe1.98 is attributed to electrical transport in the quasiclassical regime. Our work may suggest that electron-doped WTe2 is an ideal playground to explore the novel properties in type-II Weyl semimetals.

Leu7Pro polymorphism of PreproNPY associated with an increased risk for type II diabetes in middle-aged subjects.

PubMed

Ukkola, O; Kesäniemi, Y A

2007-09-01

Neuropeptide Y (NPY) plays a central in energy homeostasis and potentially in the development of obesity-related comorbidities, like type II diabetes. As the PreproNPY Leu7Pro polymorphism probably changes the intracellular processing of the synthesized preproNPY peptide, we assessed the hypothesis that PreproNPY Leu7Pro polymorphism is a risk factor for type II diabetes, impaired glucose tolerance and hypertension. Blood pressure recordings and oral glucose tolerance test were performed in the hypertensive (n=515) and control cohorts (n=525) of our well-defined Oulu Project Elucidating Risk of Atherosclerosis (OPERA) study. The prevalence of type II diabetes was 9% (n=93). The genotypes, insulin and glucose metabolism indexes and plasma ghrelin of the subjects were determined. Pro7 allele frequencies were 5.9, 5.3 and 11.3% in the total cohort, in subjects without and with type II diabetes, respectively. The PreproNPY Pro7 carrier status was a significant risk factor for type II diabetes, and the effect remained significant after adjustment for age, sex, waist circumference and study group (odds ratio=3.02, confidence interval: 1.67-5.44 and P<0.001). Pro7 carriers were more insulin resistant and showed lower ghrelin levels compared to non-carriers. The PreproNPY Pro7 allele is associated with an increased risk for type II diabetes. The risk seems to be associated with a higher insulin resistance among Pro7 carriers whereas low ghrelin concentrations in Pro7 carriers are possibly a consequence of high insulin levels.

A Statistical Study of Interplanetary Type II Bursts: STEREO Observations

NASA Astrophysics Data System (ADS)

Krupar, V.; Eastwood, J. P.; Magdalenic, J.; Gopalswamy, N.; Kruparova, O.; Szabo, A.

2017-12-01

Coronal mass ejections (CMEs) are the primary cause of the most severe and disruptive space weather events such as solar energetic particle (SEP) events and geomagnetic storms at Earth. Interplanetary type II bursts are generated via the plasma emission mechanism by energetic electrons accelerated at CME-driven shock waves and hence identify CMEs that potentially cause space weather impact. As CMEs propagate outward from the Sun, radio emissions are generated at progressively at lower frequencies corresponding to a decreasing ambient solar wind plasma density. We have performed a statistical study of 153 interplanetary type II bursts observed by the two STEREO spacecraft between March 2008 and August 2014. These events have been correlated with manually-identified CMEs contained in the Heliospheric Cataloguing, Analysis and Techniques Service (HELCATS) catalogue. Our results confirm that faster CMEs are more likely to produce interplanetary type II radio bursts. We have compared observed frequency drifts with white-light observations to estimate angular deviations of type II burst propagation directions from radial. We have found that interplanetary type II bursts preferably arise from CME flanks. Finally, we discuss a visibility of radio emissions in relation to the CME propagation direction.

Haemophilus influenzae type B meningitis in a previously healthy child.

PubMed

Horowitz, Ira N; Baorto, Elizabeth; Davis, Jennifer; Barisciano, Lisa

2010-10-01

Vaccines have proven successful in virtually eradicating certain infectious diseases that typically attack the pediatric population. Since 1988, when the conjugate vaccine was introduced, the incidence of invasive Haemophilus influenzae type B disease was reduced dramatically. However, immunization rates have decreased in certain parts of the country because of a combination of vaccine shortage and widespread parental perception that vaccines are harmful. We present the case of a previous healthy child, who ultimately succumbed to H. influenzae type B meningitis where multiple factors were likely responsible for his acquisition of the disease.

Relationship of microalbuminuria with the diabetic foot ulcers in type II diabetes.

PubMed

Guerrero-Romero, F; Rodríguez-Morán, M

1998-01-01

Microalbuminuria is a significant risk factor associated with nephropathy, retinopathy, and cardiovascular disease; however, there are no previous reports on the relationship of microalbuminuria with diabetic foot ulcers or stroke, despite the fact that microalbuminuria is a marker of vascular damage. The purpose of this study was to determine the relationship of microalbuminuria with diabetic foot ulcers in type II diabetes patients. In this, cross-sectional clinical study, outpatients of the offices at first level medical care in Durango, Mexico, were included in one of two groups; (a) patients with diabetic foot ulcers and (b) control of group patients without diabetic foot ulcers. Diabetic foot diagnosis was established on the basis of clinical criteria and pletismography. Patients diagnosed with renal disease, urinary tract infection, acute febrile illness, or heart failure and those receiving angiotensin-converting enzyme inhibitors were excluded from the study. Microalbuminuria was measured, on a 24-h urine collection, by precipitation with sulfasalicylic acid, and turbidity was determined by measuring absorbance with a spectrophotometer. The study included 670 diabetic patients. Using both odds ratio and logistic regression analyses, diabetes duration, cigarette smoking, aging, and microalbuminuria showed a strong relationship with diabetic foot ulcers. Microalbuminuria should be considered as an independent risk factor for diabetic foot ulcers.

Brucella abortus down-regulates MHC class II by the IL-6-dependent inhibition of CIITA through the downmodulation of IFN regulatory factor-1 (IRF-1).

PubMed

Velásquez, Lis N; Milillo, M Ayelén; Delpino, M Victoria; Trotta, Aldana; Fernández, Pablo; Pozner, Roberto G; Lang, Roland; Balboa, Luciana; Giambartolomei, Guillermo H; Barrionuevo, Paula

2017-03-01

Brucella abortus is an intracellular pathogen capable of surviving inside of macrophages. The success of B. abortus as a chronic pathogen relies on its ability to orchestrate different strategies to evade the adaptive CD4 + T cell responses that it elicits. Previously, we demonstrated that B. abortus inhibits the IFN-γ-induced surface expression of MHC class II (MHC-II) molecules on human monocytes, and this phenomenon correlated with a reduction in antigen presentation. However, the molecular mechanisms, whereby B. abortus is able to down-regulate the expression of MHC-II, remained to be elucidated. In this study, we demonstrated that B. abortus infection inhibits the IFN-γ-induced transcription of MHC-II, transactivator (CIITA) and MHC-II genes. Accordingly, we observed that the synthesis of MHC-II proteins was also diminished. B. abortus was not only able to reduce the expression of mature MHC-II, but it also inhibited the expression of invariant chain (Ii)-associated immature MHC-II molecules. Outer membrane protein 19 (Omp19), a prototypical B. abortus lipoprotein, diminished the expression of MHC-II and CIITA transcripts to the same extent as B. abortus infection. IL-6 contributes to these down-regulatory phenomena. In addition, B. abortus and its lipoproteins, through IL-6 secretion, induced the transcription of the negative regulators of IFN-γ signaling, suppressor of cytokine signaling (SOCS)-1 and -3, without interfering with STAT1 activation. Yet, B. abortus lipoproteins via IL-6 inhibit the expression of IFN regulatory factor 1 (IRF-1), a critical regulatory transcription factor for CIITA induction. Overall, these results indicate that B. abortus inhibits the expression of MHC-II molecules at very early points in their synthesis and in this way, may prevent recognition by T cells establishing a chronic infection. © Society for Leukocyte Biology.

HCV Proteins and Immunoglobulin Variable Gene (IgV) Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

PubMed Central

Sautto, Giuseppe; Mancini, Nicasio; Solforosi, Laura; Diotti, Roberta A.; Clementi, Massimo; Burioni, Roberto

2012-01-01

The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved. PMID:22690241

Neutral lipid trafficking regulates alveolar type II cell surfactant phospholipid and surfactant protein expression.

PubMed

Torday, John; Rehan, Virender

2011-08-01

Adipocyte differentiation-related protein (ADRP) is a critically important protein that mediates lipid uptake, and is highly expressed in lung lipofibroblasts (LIFs). Triacylglycerol secreted from the pulmonary circulation and stored in lipid storage droplets is a robust hormonal-, growth factor-, and stretch-regulated precursor for surfactant phospholipid synthesis by alveolar type II epithelial (ATII) cells. A549 lung epithelial cells rapidly take up green fluorescent protein (GFP)-ADRP fusion protein-associated lipid droplets (LDs) in a dose-dependent manner. The LDs initially localize to the perinuclear region of the cell, followed by localization in the cytoplasm. Uptake of ADRP-LDs causes a time- and dose-dependent increase in surfactant protein-B (SP-B) expression. This mechanism can be inhibited by either actinomycin D or cycloheximide, indicating that ADRP-LDs induce newly synthesized SP-B. ADRP-LDs concomitantly stimulate saturated phosphatidylcholine (satPC) synthesis by A549 cells, which is inhibited by ADRP antibody, indicating that this is a receptor-mediated mechanism. Intravenous administration of GFP-ADRP LDs to adult rats results in dose-dependent increases in lung ADRP and SP-B expression. These data indicate that lipofibroblast-derived ADRP coordinates ATII cells' synthesis of the surfactant phospholipid-protein complex by stimulating both satPC and SP-B. The authors propose, therefore, that ADRP is the physiologic determinant for the elusive coordinated, stoichiometric synthesis of surfactant phospholipid and protein by pulmonary ATII cells.

Receptor type I and type II binding regions and the peptidyl-prolyl isomerase site of cyclophilin B are required for enhancement of T-lymphocyte adhesion to fibronectin.

PubMed

Carpentier, Mathieu; Allain, Fabrice; Slomianny, Marie-Christine; Durieux, Sandrine; Vanpouille, Christophe; Haendler, Bernard; Spik, Geneviève

2002-04-23

Cyclophilin B (CyPB), a cyclosporin A (CsA) binding protein, interacts with two types of binding sites at the surface of T-lymphocytes. The type I sites correspond to functional receptors involved in endocytosis and the type II sites to sulfated glycosaminoglycans (GAGs). Mutational analysis of CyPB has revealed that W128, which is part of the CsA-binding pocket, is implicated in the binding to the functional type I receptors and that two amino acid clusters located in the N-terminus ensure the binding to GAGs. The peptidyl-prolyl isomerase activity of CyPB is not required for receptor binding. We have recently demonstrated that CyPB enhances adhesion of peripheral blood T-lymphocytes to fibronectin, a component of the extracellular matrix. We intended to identify additional amino acids involved in the binding of CyPB to its functional type I receptor and to determine regions responsible for the stimulation of peripheral blood T-lymphocyte adhesion. We determined that residues R76, G77, K132, D155, and D158 of the calcineurin (CN) interacting region were implicated in the recognition of type I receptor but not of GAGs. We also found that two different changes in the N-terminal extension that abated binding to GAGs prevented adhesion of peripheral blood T-lymphocytes to coated CyPB, whereas abbrogation of the PPIase activity had no effect. On the other hand, the adhesion of peripheral blood T-lymphocytes to coated fibronectin was not stimulated by CyPB mutants devoid of either type I receptor or GAGs binding activity or by mutants of the PPIase site. Altogether, the results demonstrate that different regions of CyPB are involved in peripheral blood T-lymphocyte activation and imply a novel important physiological function for peptidyl-prolyl isomerase activity.

Improvement in thermoelectric power factor of mechanically alloyed p-type SiGe by incorporation of TiB{sub 2}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmad, Sajid, E-mail: sajidahmadiitkgp@gmail.com; Dubey, K.; Bhattacharya, Shovit

2016-05-23

Nearly 60% of the world’s useful energy is wasted as heat and recovering a fraction of this waste heat by converting it as useful electrical power is an important area of research{sup [1]}. Thermoelectric power generators (TEG) are solid state devices which converts heat into electricity. TEG consists of n and p-type thermoelements connected electrically in series and thermally in parallel{sup [2]}. Silicon germanium (SiGe) alloy is one of the conventional high temperature thermoelectric materials and is being used in radio-isotopes based thermoelectric power generators for deep space exploration programs.Temperature (T) dependence of thermoelectric (TE) properties of p-type SiGe andmore » p-type SiGe-x wt.%TiB{sub 2} (x=6,8,10%) nanocomposite materials has been studied with in the temperature range of 300 K to 1100 K. It is observed that there is an improvement in the power factor (α{sup 2}/ρ) of SiGe alloy on addition of TiB{sub 2} upto 8 wt.% that is mainly due to increase in the Seebeck coefficient (α) and electrical conductivity (σ) of the alloy.« less

SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells

PubMed Central

Mossel, Eric C.; Wang, Jieru; Jeffers, Scott; Edeen, Karen E.; Wang, Shuanglin; Cosgrove, Gregory P.; Funk, C. Joel; Manzer, Rizwan; Miura, Tanya A.; Pearson, Leonard D.; Holmes, Kathryn V.; Mason, Robert J.

2008-01-01

Severe acute respiratory syndrome (SARS) is a disease characterized by diffuse alveolar damage. We isolated alveolar type II cells and maintained them in a highly differentiated state. Type II cell cultures supported SARS-CoV replication as evidenced by RT-PCR detection of viral subgenomic RNA and an increase in virus titer. Virus titers were maximal by 24 hours and peaked at approximately 105 pfu/mL. Two cell types within the cultures were infected. One cell type was type II cells, which were positive for SP-A, SP-C, cytokeratin, a type II cell-specific monoclonal antibody, and Ep-CAM. The other cell type was composed of spindle-shaped cells that were positive for vimentin and collagen III and likely fibroblasts. Viral replication was not detected in type I-like cells or macrophages. Hence, differentiated adult human alveolar type II cells were infectible but alveolar type I-like cells and alveolar macrophages did not support productive infection. PMID:18022664

Scaffold attachment factor B suppresses HIV-1 infection of CD4+ cells by preventing binding of RNA polymerase II to HIV-1's long terminal repeat.

PubMed

Ma, Li; Sun, Li; Jin, Xia; Xiong, Si-Dong; Wang, Jian-Hua

2018-06-10

The 5' end of HIV-1 long terminal repeat (LTR) promoter plays an essential role in driving viral transcription and productive infection. Multiple host and viral factors regulate LTR activity and modulate HIV-1 latency. Manipulation of the HIV-1 LTR provides a potential therapeutic strategy for combating HIV-1 persistence. In this study, we identified an RNA-/DNA-binding protein, Scaffold Attachment Factor B (SAFB1) as a host-cell factor that represses HIV-1 transcription. We found that SAFB1 bound to HIV-1 5`-LTR and significantly repressed 5`-LTR-driven-viral transcription and HIV-1 infection of CD4 + T cells. Mechanistically, SAFB1-mediated repression of HIV-1 transcription and infection was independent of its RNA- and DNA-binding capacities, instead, by binding to phosphorylated RNA polymerase II (RNA pol II), SAFB1 blocked its recruitment to the HIV-1 LTR. Of note, the SAFB1-mediated repression of HIV-1 transcription from proviral DNA maintained HIV-1 latency in CD4 + T cells. In summary, our findings reveal that SAFB1 binds to HIV-1-LTR and physically interacts with phosphorylated RNA pol II, repressing HIV-1 transcription initiation and elongation. Our findings improve the understanding of host modulation of HIV-1 transcription and latency and provide a new host-cell target for improved anti-HIV-1 therapies. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

ICC Type II large-format FPA detector assemblies

NASA Astrophysics Data System (ADS)

Clynne, Thomas H.; Powers, Thomas P.

1997-08-01

ICC presents a new addition to their integrated detector assembly product line with the announcement of their type II large format staring class FPA units. A result of internally funded research and development, the ICC type II detector assembly can accommodate all existing large format staring class PtSi, InSb and MCT focal planes, up to 640 by 480. Proprietary methodologies completely eliminate all FPA stresses to allow for maximum FPA survivability. Standard optical and cryocooler interfaces allow for the use of BEI, AEG, TI SADA Hughes/Magnavox and Joule Thompson coolers. This unit has been qualified to the current SADA II thermal environmental specifications and was tailored around ICC's worldwide industry standard type IV product. Assembled in a real world flexible manufacturing environment, this unit features a wide degree of adaptability and can be easily modified to a user's specifications via standard options and add-ons that include optical interfaces, electrical interfaces and window/filter material selections.

On the source conditions for herringbone structure in type II solar radio bursts

NASA Technical Reports Server (NTRS)

Cane, H. V.; White, S. M.

1989-01-01

An investigation is made of the correlation of the occurrence of the herringbone phenomenon in type II solar radio bursts with various flare properties. It is shown that herringbone is strongly correlated with the intensity of the type II burst: whereas about 21 percent of all type II bursts show herringbone, about 60 percent of the most intense bursts contain herringbone. This fact can explain most of the correlations between herringbone and other properties such as intense type III bursts, type IV emission, and high type II starting frequencies. It is also shown that when this is taken into account, there is no need to postulate two classes of type II burst in order to explain why there appears to be a difference in herringbone occurrence between the set of type II bursts associated with the leading edges of coronal mass ejections, and those not so associated. It is argued that the data are consistent with the idea that all coronal type II bursts are due to blast waves from flares.

Type II NKT Cells in Inflammation, Autoimmunity, Microbial Immunity, and Cancer

PubMed Central

Marrero, Idania; Ware, Randle; Kumar, Vipin

2015-01-01

Natural killer T cells (NKT) recognize self and microbial lipid antigens presented by non-polymorphic CD1d molecules. Two major NKT cell subsets, type I and II, express different types of antigen receptors (TCR) with distinct mode of CD1d/lipid recognition. Though type II NKT cells are less frequent in mice and difficult to study, they are predominant in human. One of the major subsets of type II NKT cells reactive to the self-glycolipid sulfatide is the best characterized and has been shown to induce a dominant immune regulatory mechanism that controls inflammation in autoimmunity and in anti-cancer immunity. Recently, type II NKT cells reactive to other self-glycolipids and phospholipids have been identified suggesting both promiscuous and specific TCR recognition in microbial immunity as well. Since the CD1d pathway is highly conserved, a detailed understanding of the biology and function of type II NKT cells as well as their interplay with type I NKT cells or other innate and adaptive T cells will have major implications for potential novel interventions in inflammatory and autoimmune diseases, microbial immunity, and cancer. PMID:26136748

Why is coronary collateral growth impaired in type II diabetes and the metabolic syndrome?

PubMed Central

Rocic, Petra

2012-01-01

Type II diabetes and the metabolic syndrome are strong predictors of severity of occlusive coronary disease and poorer outcomes of coronary revascularization therapies. Coronary collateral growth can provide an alternative or accessory pathway of revascularization. However, collateral growth is impaired in type II diabetes and the metabolic syndrome. Although many factors necessary for collateral growth are known and many interventions have shown promising results in animal studies, not a single attempt to induce coronary collateral growth in human clinical trials has led to satisfactory results. Accordingly, the first part of this review outlines the known deleterious effects of diabetes and the metabolic syndrome on factors necessary for collateral growth, including pro-angiogenic growth factors, endothelial function, the redox state of the coronary circulation, intracellular signaling, leukocytes and bone marrow-derived progenitors cells. The second section highlights the gaps in our current knowledge of how these factors interact with the radically altered environment of the coronary circulation in diabetes and the metabolic syndrome. The interplay between these pathologies and inadequately explored areas related to the temporal regulation of collateral remodeling and the roles of the extracellular matrix, vascular cell phenotype and pro-inflammatory cytokines are emphasized with implications to development of efficient therapies. PMID:22342811

Late-onset Bartter syndrome type II.

PubMed

Gollasch, Benjamin; Anistan, Yoland-Marie; Canaan-Kühl, Sima; Gollasch, Maik

2017-10-01

Mutations in the ROMK1 potassium channel gene ( KCNJ1 ) cause antenatal/neonatal Bartter syndrome type II (aBS II), a renal disorder that begins in utero , accounting for the polyhydramnios and premature delivery that is typical in affected infants, who develop massive renal salt wasting, hypokalaemic metabolic alkalosis, secondary hyperreninaemic hyperaldosteronism, hypercalciuria and nephrocalcinosis. This BS type is believed to represent a disorder of the infancy, but not in adulthood. We herein describe a female patient with a remarkably late-onset and mild clinical manifestation of BS II with compound heterozygous KCNJ1 missense mutations, consisting of a novel c.197T > A (p.I66N) and a previously reported c.875G > A (p.R292Q) KCNJ1 mutation. We implemented and evaluated the performance of two different bioinformatics-based approaches of targeted massively parallel sequencing [next generation sequencing (NGS)] in defining the molecular diagnosis. Our results demonstrate that aBS II may be suspected in patients with a late-onset phenotype. Our experimental approach of NGS-based mutation screening combined with Sanger sequencing proved to be a reliable molecular approach for defining the clinical diagnosis in our patient, and results in important differential diagnostic and therapeutic implications for patients with BS. Our results could have a significant impact on the diagnosis and methodological approaches of genetic testing in other patients with clinical unclassified phenotypes of nephrocalcinosis and congenital renal electrolyte abnormalities.

Phospholipase PlaB is a new virulence factor of Legionella pneumophila.

PubMed

Schunder, Eva; Adam, Patrick; Higa, Futoshi; Remer, Katharina A; Lorenz, Udo; Bender, Jennifer; Schulz, Tino; Flieger, Antje; Steinert, Michael; Heuner, Klaus

2010-06-01

We previously identified Legionella pneumophila PlaB as the major cell-associated phospholipase A/lysophospholipase A with contact-dependent hemolytic activity. In this study, we further characterized this protein and found it to be involved in the virulence of L. pneumophila. PlaB was mainly expressed and active during exponential growth. Active PlaB was outer membrane-associated and at least in parts surface-exposed. Transport to the outer membrane was not dependent on the type I (T1SS), II (T2SS), IVB (T4BSS) or Tat secretion pathways. Furthermore, PlaB activity was not dependent on the presence of the macrophage infectivity potentiator (Mip) or the major secreted zinc metalloproteinase A (MspA). Despite the fact that PlaB is not essential for replication in protozoa or macrophage cell lines, we found that plaB mutants were impaired for replication in the lungs and dissemination to the spleen in the guinea pig infection model. Histological sections monitored less inflammation and destruction of the lung tissue after infection with the plaB mutants compared to L. pneumophila wild type. Taken together, PlaB is the first phospholipase A/lysophospholipase A with a confirmed role in the establishment of Legionnaires' disease. Copyright 2010 Elsevier GmbH. All rights reserved.

High intensity focused ultrasound ablation for submucosal fibroids: A comparison between type I and type II.

PubMed

Xie, Bin; Zhang, Cai; Xiong, Chunyan; He, Jia; Huang, Guohua; Zhang, Lian

2015-01-01

The aim of this study was to compare high-intensity focused ultrasound (HIFU) treatment for type I and type II submucosal fibroids. From October 2011 to October 2013, 55 patients with submucosal fibroids were enrolled in this study. Based on submucosal fibroid classification, 27 patients were grouped as type I submucosal fibroids, and 28 patients were classified as type II submucosal fibroids. All patients received HIFU treatment and completed 1-, 6-, and 12-month follow-ups. Adverse effects were recorded. There were no significant differences in the baseline characteristics between the two groups (p > 0.05). Using similar sonication power, sonication time, and acoustic energy, the non-perfused volume (NPV) ratio was 83.0 ± 17.3% in the type I group, and 92.0 ± 9.5% in the type II group. All the patients tolerated the procedure well, and no serious adverse events occurred. During the follow-up intervals, the treated fibroids shrank and fibroid-related symptoms were relieved. No other reinterventional procedures were performed during the follow-up period. Based on our results with a small number of subjects, HIFU is suitable for both type I and type II submucosal fibroids. It seems that type II submucosal fibroids are more sensitive to HIFU ablation. Future studies with larger sample sizes and longer follow-up times to investigate the long-term results, including long-term symptom relief, pregnancy outcomes, and the recurrence rate as well as the reintervention rate are needed.

40 CFR Appendix B to Subpart A of... - Class II Controlled Substances a

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Class II Controlled Substances a B Appendix B to Subpart A of Part 82 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED..., Subpt. A, App. B Appendix B to Subpart A of Part 82—Class II Controlled Substances a Controlled...

Diffuse Interplanetary Radio Emission (DIRE) Accompanying Type II Radio Bursts

NASA Astrophysics Data System (ADS)

Teklu, T. B.; Gopalswamy, N.; Makela, P. A.; Yashiro, S.; Akiyama, S.; Xie, H.

2015-12-01

We report on an unusual drifting feature in the radio dynamic spectra at frequencies below 14 MHz observed by the Radio and Plasma Wave (WAVES) experiment on board the Wind spacecraft. We call this feature as "Diffuse Interplanetary Radio Emission (DIRE)". The DIRE events are generally associated with intense interplanetary type II radio bursts produced by shocks driven by coronal mass ejections (CMEs). DIREs drift like type II bursts in the dynamic spectra, but the drifting feature consist of a series of short-duration spikes (similar to a type I chain). DIREs occur at higher frequencies than the associated type II bursts, with no harmonic relationship with the type II burst. The onset of DIREs is delayed by several hours from the onset of the eruption. Comparing the radio dynamic spectra with white-light observations from the Solar and Heliospheric Observatory (SOHO) mission, we find that the CMEs are generally very energetic (fast and mostly halos). We suggest that the DIRE source is typically located at the flanks of the CME-driven shock that is still at lower heliocentric distances.

Effects of type II thyroplasty on adductor spasmodic dysphonia.

PubMed

Sanuki, Tetsuji; Yumoto, Eiji; Minoda, Ryosei; Kodama, Narihiro

2010-04-01

Type II thyroplasty, or laryngeal framework surgery, is based on the hypothesis that the effect of adductor spasmodic dysphonia (AdSD) on the voice is due to excessively tight closure of the glottis, hampering phonation. Most of the previous, partially effective treatments have aimed to relieve this tight closure, including recurrent laryngeal nerve section or avulsion, extirpation of the adductor muscle, and botulinum toxin injection, which is currently the most popular. The aim of this study was to assess the effects of type II thyroplasty on aerodynamic and acoustic findings in patients with AdSD. Case series. University hospital. Ten patients with AdSD underwent type II thyroplasty between August 2006 and December 2008. Aerodynamic and acoustic analyses were performed prior to and six months after surgery. Mean flow rates (MFRs) and voice efficiency were evaluated with a phonation analyzer. Jitter, shimmer, the harmonics-to-noise ratio (HNR), standard deviation of the fundamental frequency (SDF0), and degree of voice breaks (DVB) were measured from each subject's longest sustained phonation sample of the vowel /a/. Voice efficiency improved significantly after surgery. No significant difference was found in the MFRs between before and after surgery. Jitter, shimmer, HNR, SDF0, and DVB improved significantly after surgery. Treatment of AdSD with type II thyroplasty significantly improved aerodynamic and acoustic findings. The results of this study suggest that type II thyroplasty provides relief from voice strangulation in patients with AdSD. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Classification and Realizations of Type III Factor Representations of Cuntz-Krieger Algebras Associated with Quasi-Free States

NASA Astrophysics Data System (ADS)

Kawamura, Katsunori

2009-03-01

We completely classify type III factor representations of Cuntz-Krieger algebras associated with quasi-free states up to unitary equivalence. Furthermore, we realize these representations on concrete Hilbert spaces without using GNS construction. Free groups and their type II1 factor representations are used in these realizations.

Hearing loss in Usher syndrome type II is nonprogressive.

PubMed

Reisser, Christoph F V; Kimberling, William J; Otterstedde, Christian R

2002-12-01

Usher syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and progressive visual loss secondary to retinitis pigmentosa. In the literature, a possible progression of the moderate to severe hearing loss in Usher syndrome type II (Usher II) is controversial. We studied the development of the hearing loss of 125 patients with a clinical diagnosis of Usher syndrome type II intraindividually and interindividually by repeatedly performing complete audiological and neuro-otologic examinations. Our data show a very characteristic slope of the hearing curve in all Usher II patients and no clinically relevant progression of the hearing loss over up to 17 years. The subjective impression of a deterioration of the communicative abilities of Usher II patients must therefore be attributed to the progressive visual loss. The patients should be reassured that changes in their hearing abilities are unlikely and should be provided with optimally fitted modern hearing aids.

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.

Type II diabetes mellitus and the incidence of epithelial ovarian cancer in the cancer prevention study-II nutrition cohort.

PubMed

Gapstur, Susan M; Patel, Alpa V; Diver, W Ryan; Hildebrand, Janet S; Gaudet, Mia M; Jacobs, Eric J; Campbell, Peter T

2012-11-01

Despite consistent associations of type II diabetes mellitus with hormonally related cancers such as breast and endometrium, the relation between type II diabetes mellitus and ovarian cancer risk is unclear. Associations of type II diabetes mellitus status, duration, and insulin use with epithelial ovarian cancer overall, and with serous and nonserous histologic subtypes were examined in the Cancer Prevention Study-II Nutrition Cohort, a prospective study of U.S. men and women predominantly aged 50 years and older. Between 1992 and 2007, 524 incident epithelial ovarian cancer cases were identified among 63,440 postmenopausal women. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were computed using extended Cox regression to update diabetes status and bilateral oophorectomy status during follow-up. Type II diabetes mellitus status (RR = 1.05; 95% CI, 0.75-1.46) and duration were not associated with epithelial ovarian cancer risk. Although not statistically significantly different (P(difference) = 0.39), the RR was higher for type II diabetes mellitus with insulin use (RR = 1.28; 95% CI, 0.74-2.24) than for type II diabetes mellitus without insulin use (RR = 0.96; 95% CI, 0.64-1.43). Diabetes seemed to be more strongly associated with nonserous (RR = 1.41; 95% CI, 0.70-2.85) than serous (RR = 0.71; 95% CI, 0.41-1.23) histologic subtypes. Type II diabetes mellitus was not associated with risk of epithelial ovarian cancer, although higher risks with nonserous subtypes and among insulin users cannot be ruled out. Larger studies are needed to clarify associations of type II diabetes mellitus with or without insulin use with risk of ovarian cancer overall and by histologic subtypes. ©2012 AACR.

Generalized type II hybrid ARQ scheme using punctured convolutional coding

NASA Astrophysics Data System (ADS)

Kallel, Samir; Haccoun, David

1990-11-01

A method is presented to construct rate-compatible convolutional (RCC) codes from known high-rate punctured convolutional codes, obtained from best-rate 1/2 codes. The construction method is rather simple and straightforward, and still yields good codes. Moreover, low-rate codes can be obtained without any limit on the lowest achievable code rate. Based on the RCC codes, a generalized type-II hybrid ARQ scheme, which combines the benefits of the modified type-II hybrid ARQ strategy of Hagenauer (1988) with the code-combining ARQ strategy of Chase (1985), is proposed and analyzed. With the proposed generalized type-II hybrid ARQ strategy, the throughput increases as the starting coding rate increases, and as the channel degrades, it tends to merge with the throughput of rate 1/2 type-II hybrid ARQ schemes with code combining, thus allowing the system to be flexible and adaptive to channel conditions, even under wide noise variations and severe degradations.

[Metabolic surgery in treatment of diabetes mellitus of type II].

PubMed

Sedov, V M; Fishman, M B

2013-01-01

Nowadays, according to data of WHO, the diabetes mellitus was diagnosed in more than 280 million people. The diabetes mellitus type II had 90% patients. The applied methods of conservative therapy seldom lead to euglycemia condition of patients. Last years the treatment of diabetes mellitus was carried out by the method of different bariatic interventions. Good results was obtained, they should be analyzed and investigate. The results of treatment of 142 patients from 628 patients (with type II) were estimated. The patients were undergone by different bariatic interventions. Modern laparoscopic operations were performed on all the patients. Controlled bandage of stomach had 81 of patients. Gastric resection was performed in 28. Gastric bypass surgery was carried out in 22 of patients and biliopancreatic diversion - in 11. The improvement of control of leukemia level was obtained. Diabetes type II could be treated by surgical methods. The best results were obtained after combined operations, which potentially could present an alternative method of treatment of type II diabetes.

Type II Radio Bursts as Indicators of Space Weather Drivers

NASA Astrophysics Data System (ADS)

Gopalswamy, N.

2015-12-01

Interplanetary type II radio bursts are important indicators of shock-driving coronal mass ejections (CMEs). CME-driven shocks are responsible for large solar energetic particle (SEP) events and sudden commencement/sudden impulse events recorded by ground magnetometers. The excellent overlap of the spatial domains probed by SOHO/STEREO coronagraphs with the spectral domains of Wind/WAVES and STEREO/WAVES has contributed enormously in understanding CMEs and shocks as space weather drivers. This paper is concerned with type II bursts of solar cycle 23 and 24 that had emission components down to kilometric wavelengths. CMEs associated with these bursts seem to be the best indicators of large SEP events, better than the halo CMEs. However, there are some differences between the type II bursts of the two cycles, which are explained based on the different states of the heliosphere in the two cycles. Finally, the type II burst characteristics of some recent extreme events are discussed.

Type I and Type II error concerns in fMRI research: re-balancing the scale

PubMed Central

Cunningham, William A.

2009-01-01

Statistical thresholding (i.e. P-values) in fMRI research has become increasingly conservative over the past decade in an attempt to diminish Type I errors (i.e. false alarms) to a level traditionally allowed in behavioral science research. In this article, we examine the unintended negative consequences of this single-minded devotion to Type I errors: increased Type II errors (i.e. missing true effects), a bias toward studying large rather than small effects, a bias toward observing sensory and motor processes rather than complex cognitive and affective processes and deficient meta-analyses. Power analyses indicate that the reductions in acceptable P-values over time are producing dramatic increases in the Type II error rate. Moreover, the push for a mapwide false discovery rate (FDR) of 0.05 is based on the assumption that this is the FDR in most behavioral research; however, this is an inaccurate assessment of the conventions in actual behavioral research. We report simulations demonstrating that combined intensity and cluster size thresholds such as P < 0.005 with a 10 voxel extent produce a desirable balance between Types I and II error rates. This joint threshold produces high but acceptable Type II error rates and produces a FDR that is comparable to the effective FDR in typical behavioral science articles (while a 20 voxel extent threshold produces an actual FDR of 0.05 with relatively common imaging parameters). We recommend a greater focus on replication and meta-analysis rather than emphasizing single studies as the unit of analysis for establishing scientific truth. From this perspective, Type I errors are self-erasing because they will not replicate, thus allowing for more lenient thresholding to avoid Type II errors. PMID:20035017

B-type natriuretic peptide levels and continuous-flow left ventricular assist devices.

PubMed

Sareyyupoglu, Basar; Boilson, Barry A; Durham, Lucian A; McGregor, Christopher G A; Daly, Richard C; Redfield, Margaret M; Edwards, Brooks S; Frantz, Robert P; Pereira, Naveen L; Park, Soon J

2010-01-01

We postulated that postoperative B-type natriuretic peptide (BNP) levels would be reflective of the degree of hemodynamic support rendered by various pump speeds settings (RPM) of continuous-flow left ventricular assist devices (LVADs). Twenty LVAD patients were evaluated prospectively (Jarvik 2000: n = 9, HeartMate II: n = 11). The mean age was 57.7 ± 14.9 years, and 14 were male. B-type natriuretic peptide levels were drawn while the patients were supported on LVADs at variable RPM settings. The RPM settings were correlated with the changes in BNP levels. Eleven patients underwent LVAD implantation for a lifelong support while the rest were as a bridge therapy to transplantation. Four patients required LVAD change out for various causes of pump failure. Postoperative BNP levels decreased dramatically with the initiation of LVAD support. The levels correlated inversely with the degree of hemodynamic support rendered at various RPM settings of the HeartMate II (p < 0.001). Overall, BNP levels decreased significantly in 2 days after RPM increase. We observed a significant inverse correlation between the postoperative BNP levels and the degree of LVAD support. The effective LVAD support seems to result in a marked reduction in BNP levels, and monitoring serial BNP levels may be helpful in managing patients supported on continuous LVAD.

bHLH-O proteins balance the self-renewal and differentiation of Drosophila neural stem cells by regulating Earmuff expression.

PubMed

Li, Xiaosu; Chen, Rui; Zhu, Sijun

2017-11-15

Balancing self-renewal and differentiation of stem cells requires differential expression of self-renewing factors in two daughter cells generated from the asymmetric division of the stem cells. In Drosophila type II neural stem cell (or neuroblast, NB) lineages, the expression of the basic helix-loop-helix-Orange (bHLH-O) family proteins, including Deadpan (Dpn) and E(spl) proteins, is required for maintaining the self-renewal and identity of type II NBs, whereas the absence of these self-renewing factors is essential for the differentiation of intermediate neural progenitors (INPs) generated from type II NBs. Here, we demonstrate that Dpn maintains type II NBs by suppressing the expression of Earmuff (Erm). We provide evidence that Dpn and E(spl) proteins suppress Erm by directly binding to C-sites and N-boxes in the cis-regulatory region of erm. Conversely, the absence of bHLH-O proteins in INPs allows activation of erm and Erm-mediated maturation of INPs. Our results further suggest that Pointed P1 (PntP1) mediates the dedifferentiation of INPs resulting from the loss of Erm or overexpression of Dpn or E(spl) proteins. Taken together, these findings reveal mechanisms underlying the regulation of the maintenance of type II NBs and differentiation of INPs through the differential expression of bHLH-O family proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

B cell helper factors. II. Synergy among three helper factors in the response of T cell- and macrophage-depleted B cells.

PubMed

Liebson, H J; Marrack, P; Kappler, J

1982-10-01

The concanavalin A- (Con A) stimulated supernatant of normal spleen cells (normal Con A SN) was shown to contain a set of helper factors sufficient to allow T cell- and macrophage- (M phi) depleted murine splenic B cells to produce a plaque-forming cell response to the antigen sheep red blood cells (SRBC). The activity of normal Con A SN could be reconstituted by a mixture of three helper factor preparations. The first was the interleukin 2- (IL 2) containing Con A SN of the T cell hybridoma, FS6-14.13. The second was a normal Con A SN depleted of IL 2 by extended culture with T cell blasts from which the 30,000 to 50,000 m.w. factors were isolated (interleukin X, IL X). The third was a SN either from the M phi tumor cell line P388D1 or from normal M phi taken from Corynebacterium parvum-immune mice. The combination of all three helper factor preparations was required to equal the activity of normal Con A SN; however, the M phi SN had the least overall effect. The M phi SN and IL 2 had to be added at the initiation of the culture period for a maximal effect, but the IL X preparation was most effective when added 24 hr after the initiation of culture. These results indicate that at least three nonspecific helper factors contribute to the helper activity in normal Con A SN.

Space Density Of Optically-Selected Type II Quasars From The SDSS

NASA Astrophysics Data System (ADS)

Reyes, Reinabelle; Zakamska, N. L.; Strauss, M. A.; Green, J.; Krolik, J. H.; Shen, Y.; Richards, G. T.

2007-12-01

Type II quasars are luminous Active Galactic Nuclei (AGN) whose central regions are obscured by large amounts of gas and dust. In this poster, we present a catalog of 887 type II quasars with redshifts z<0.83 from the Sloan Digital Sky Survey (SDSS), selected based on their emission lines, and derive the 1/Vmax [OIII] 5007 luminosity function from this sample. Since some objects may not be included in the sample because they lack strong emission lines, the derived luminosity function is only a lower limit. We also derive the [OIII] 5007 luminosity function for a sample of type I (broad-line) quasars in the same redshift range. Taking [OIII] 5007 luminosity as a tracer of intrinsic luminosity in both type I and type II quasars, we obtain lower limits to the type II quasar fraction as a function of [OIII] 5007 luminosity, from L[OIII] = 108.3 to 1010 Lsun, which roughly correspond to bolometric luminosities of 1044 to 1046 erg/s.

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'. © 2014 Wiley Periodicals, Inc.

Polygalacturonase gene pgxB in Aspergillus niger is a virulence factor in apple fruit.

PubMed

Liu, Cheng-Qian; Hu, Kang-Di; Li, Ting-Ting; Yang, Ying; Yang, Feng; Li, Yan-Hong; Liu, He-Ping; Chen, Xiao-Yan; Zhang, Hua

2017-01-01

Aspergillus niger, a saprophytic fungus, is widely distributed in soil, air and cereals, and can cause postharvest diseases in fruit. Polygalacturonase (PG) is one of the main enzymes in fungal pathogens to degrade plant cell wall. To evaluate whether the deletion of an exo-polygalacturonase gene pgxB would influence fungal pathogenicity to fruit, pgxB gene was deleted in Aspergillus niger MA 70.15 (wild type) via homologous recombination. The ΔpgxB mutant showed similar growth behavior compared with the wild type. Pectin medium induced significant higher expression of all pectinase genes in both wild type and ΔpgxB in comparison to potato dextrose agar medium. However, the ΔpgxB mutant was less virulent on apple fruits as the necrosis diameter caused by ΔpgxB mutant was significantly smaller than that of wild type. Results of quantitive-PCR showed that, in the process of infection in apple fruit, gene expressions of polygalacturonase genes pgaI, pgaII, pgaA, pgaC, pgaD and pgaE were enhanced in ΔpgxB mutant in comparison to wild type. These results prove that, despite the increased gene expression of other polygalacturonase genes in ΔpgxB mutant, the lack of pgxB gene significantly reduced the virulence of A. niger on apple fruit, suggesting that pgxB plays an important role in the infection process on the apple fruit.

Polygalacturonase gene pgxB in Aspergillus niger is a virulence factor in apple fruit

PubMed Central

Yang, Ying; Yang, Feng; Li, Yan-Hong; Liu, He-Ping; Chen, Xiao-Yan

2017-01-01

Aspergillus niger, a saprophytic fungus, is widely distributed in soil, air and cereals, and can cause postharvest diseases in fruit. Polygalacturonase (PG) is one of the main enzymes in fungal pathogens to degrade plant cell wall. To evaluate whether the deletion of an exo-polygalacturonase gene pgxB would influence fungal pathogenicity to fruit, pgxB gene was deleted in Aspergillus niger MA 70.15 (wild type) via homologous recombination. The ΔpgxB mutant showed similar growth behavior compared with the wild type. Pectin medium induced significant higher expression of all pectinase genes in both wild type and ΔpgxB in comparison to potato dextrose agar medium. However, the ΔpgxB mutant was less virulent on apple fruits as the necrosis diameter caused by ΔpgxB mutant was significantly smaller than that of wild type. Results of quantitive-PCR showed that, in the process of infection in apple fruit, gene expressions of polygalacturonase genes pgaI, pgaII, pgaA, pgaC, pgaD and pgaE were enhanced in ΔpgxB mutant in comparison to wild type. These results prove that, despite the increased gene expression of other polygalacturonase genes in ΔpgxB mutant, the lack of pgxB gene significantly reduced the virulence of A. niger on apple fruit, suggesting that pgxB plays an important role in the infection process on the apple fruit. PMID:28257463

Type I and II β-turns prediction using NMR chemical shifts.

PubMed

Wang, Ching-Cheng; Lai, Wen-Chung; Chuang, Woei-Jer

2014-07-01

A method for predicting type I and II β-turns using nuclear magnetic resonance (NMR) chemical shifts is proposed. Isolated β-turn chemical-shift data were collected from 1,798 protein chains. One-dimensional statistical analyses on chemical-shift data of three classes β-turn (type I, II, and VIII) showed different distributions at four positions, (i) to (i + 3). Considering the central two residues of type I β-turns, the mean values of Cο, Cα, H(N), and N(H) chemical shifts were generally (i + 1) > (i + 2). The mean values of Cβ and Hα chemical shifts were (i + 1) < (i + 2). The distributions of the central two residues in type II and VIII β-turns were also distinguishable by trends of chemical shift values. Two-dimensional cluster analyses on chemical-shift data show positional distributions more clearly. Based on these propensities of chemical shift classified as a function of position, rules were derived using scoring matrices for four consecutive residues to predict type I and II β-turns. The proposed method achieves an overall prediction accuracy of 83.2 and 84.2% with the Matthews correlation coefficient values of 0.317 and 0.632 for type I and II β-turns, indicating that its higher accuracy for type II turn prediction. The results show that it is feasible to use NMR chemical shifts to predict the β-turn types in proteins. The proposed method can be incorporated into other chemical-shift based protein secondary structure prediction methods.

Endothelin-1 Expression Associated with Lipid Peroxidation and Nuclear Factor-κB Activation in Type 2 Diabetes Mellitus Patients with Angiopathy and Limb Amputation.

PubMed

Kuo, Yur-Ren; Chien, Ching-Ming; Kuo, Ming-Jen; Wang, Feng-Sheng; Huang, Eng-Yen; Wang, Ching-Jen

2016-01-01

It is unclear whether diabetic angiopathy is related to oxidative stress-associated endothelial dysfunction. The authors investigated whether alteration of endothelin-1 and lipid peroxide production and activation of nuclear factor-κB expression were involved in lower limb amputation in type 2 diabetes mellitus patients. A total of 135 subjects including 51 type 2 diabetes mellitus patients with major lower extremity amputations and 36 diabetes mellitus patients without limb and vascular complication and 48 normal controls were recruited for this study. The authors measured the plasma soluble endothelin-1 concentrations by a sandwich enzyme immunoassay, and measured oxidative stress as determined by the lipid peroxide byproduct malondialdehyde. Histologic staining and nuclear factor-κB activation determined by electrophoretic mobility shift assay of the amputated vessels were examined. Histologic staining revealed that severe arteriosclerosis with atheroma formation in the amputated diabetic arteries was significantly prominent compared with normal controls. Soluble endothelin-1 concentrations and malondialdehyde levels were increased significantly in diabetic amputation patients compared with other groups (p < 0.001). The nuclear factor-κB binding activity in amputated diabetic stump vessels was more prominent compared with healthy vessels without diabetes mellitus. There was a positive correlation between endothelin-1 and malondialdehyde in patients with diabetic amputation (r = 0.46, p = 0.001). These results suggest that elevation of endothelin-1 and lipid peroxide levels is involved in the pathogenesis of diabetic foot amputation. An increase of lipid peroxide and endothelin-1 associated with nuclear factor-κB activation plays an important role in the development of diabetic angiopathies.

Angiotensin II and the transcription factor Rel/NF-kappaB link environmental water shortage with memory improvement.

PubMed

Frenkel, L; Freudenthal, R; Romano, A; Nahmod, V E; Maldonado, H; Delorenzi, A

2002-01-01

One of the essential requirements even in the most ancient life forms is to be able to preserve body fluid medium. In line with such requirement, animals need to perform different behaviors to cope with water shortages. As angiotensin II (ANGII) is involved on a widespread range of functions in vertebrates, including memory modulation, an integrative role, in response to an environmental water shortage, has been envisioned. Previous work on the semi-terrestrial and brackish-water crab Chasmagnathus granulatus showed that endogenous ANGII enhanced an associative long-term memory and, in addition, that high salinity environment induces both an increase of brain ANGII levels and memory improvement. Here, we show that in the crab Chasmagnathus air exposure transiently increases blood sodium concentration, significantly increases brain ANGII immunoreactivity, and has a facilitatory effect on memory that is abolished by a non-selective ANGII receptor antagonist, saralasin. Furthermore, Rel/NF-kappaB, a transcription factor activated by ANGII in mammals and during memory consolidation in Chasmagnathus brain, is induced in the crab's brain by air exposure. Moreover, nuclear brain NF-kappaB is activated by ANGII, and this effect is reversed by saralasin. Our results constitute the first demonstration in an invertebrate that cognitive functions are modulated by an environmental stimulus through a neuropeptide and give evolutionary support to the role of angiotensins in memory processes. Moreover, these results suggest that angiotensinergic system is preserved across evolution not only in its structure and molecular mechanisms, but also in its capability of coordinating specific adaptative responses.

A new approach to the old problem: Inner filter effect type I and II in fluorescence.

PubMed

Kasparek, Adam; Smyk, Bogdan

2018-06-05

The fluorescence technique is very popular and has been used in many fields of research. It is simple in its assumptions but not very easy to use. One of the main problems is the inner filter effect (IF) I and II which takes place in the cuvette. IF type I is permanently present, but IF type II occurs only when absorption and fluorescence spectra overlap. To avoid IF type I, absorbencies in the cuvette should be smaller than 0.05, which is however very difficult to obtain in many experiments. In this work we propose a new method to solve these problems in the case of a Cary Eclipse fluorimeter, having horizontally-oriented slits, based on old equations developed in the middle of the last century. This method can be applied for other instruments, even these with vertically-oriented beams, because we share scripts written in MATLAB and GRAMS/AI environment. Calculations in our method enable specifying beam geometry parameters in the cuvette, which is necessary to obtain the correct shape and fluorescence intensity of emission and excitation spectra. Such a specific fluorescence intensity dependence on absorbance can, in many cases, afford possibilities to determine the quantum yield (QY) using slopes of the straight-lines, which was demonstrated with the use of Tryptophan (Trp), Tyrosine (Tyr), and Rhodamine B (RhB) solutions. For example, assuming that QY=0.14 for Tyr, the QY determined for RhB reached QY=0.71±0.05, although the measurement for Tyr and RhB was performed at a completely different spectral range. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Type II solar radio bursts, interplanetary shocks, and energetic particle events

NASA Technical Reports Server (NTRS)

Cane, H. V.; Stone, R. G.

1984-01-01

Using the ISEE-3 radio astronomy experiment data 37 interplanetary (IP) type II bursts have been identified in the period September 1978 to December 1981. These events and the associated phenomena are listed. The events are preceded by intense, soft X ray events with long decay times (LDEs) and type II and/or type IV bursts at meter wavelengths. The meter wavelength type II bursts are usually intense and exhibit herringbone structure. The extension of the herringbone structure into the kilometer wavelength range results in the occurrence of a shock accelerated (SA) event. The majority of the interplanetary type II bursts are associated with energetic particle events. These results support other studies awhich indicate that energetic solar particles detected at 1 A.U. are generated by shock acceleration. From a preliminary analysis of the available data there appears to be a high correlation with white light coronal transients.

Type B drum packages

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCoy, J.C.

1994-08-01

The Type B drum packages (TBD) are conceptualized as a family of containers in which a single 208 L or 114 L (55 gal or 30 gal) drum containing Type B quantities of radioactive material (RAM) can be packaged for shipment. The TBD containers are being developed to fill a void in the packaging and transportation capabilities of the U.S. Department of Energy as no container packaging single drums of Type B RAM exists offering double containment. Several multiple-drum containers currently exist, as well as a number of shielded casks, but the size and weight of these containers present manymore » operational challenges for single-drum shipments. As an alternative, the TBD containers will offer up to three shielded versions (light, medium, and heavy) and one unshielded version, each offering single or optional double containment for a single drum. To reduce operational complexity, all versions will share similar design and operational features where possible. The primary users of the TBD containers are envisioned to be any organization desiring to ship single drums of Type B RAM, such as laboratories, waste retrieval activities, emergency response teams, etc. Currently, the TBD conceptual design is being developed with the final design and analysis to be completed in 1995 to 1996. Testing and certification of the unshielded version are planned to be completed in 1996 to 1997 with production to begin in 1997 to 1998.« less

Treatment of distal-third clavicular fractures (Neer type ii-b) with a triple button device.

PubMed

Cano-Martínez, J A; Nicolás-Serrano, G; Andrés-Grau, J; Bento-Gerard, J

The purpose of this study is to describe the outcomes of using a triple button device for the treatment of displaced distal-third clavicle fractures (Neer, type ii-b). A retrospective review was conducted on a series of patients between November 2011 and December 2014. Fourteen patients initially met the inclusion criteria, but 2 were excluded, leaving 12 patients (83.3% male; mean age 32.2 years) for the final analysis at a mean follow-up of 26±11.24 months (range, 12-48). Post-operative follow-up was performed at 2 weeks (two first months), and monthly thereafter, until was achieving clinically and radiological healing. The functional outcome was evaluated using the Constant score, and DASH score in the last follow-up. The mean Constant Score was 95.5±5.2 points (range, 85-100), with a mean DASH score of 3.3±4.4 points (range, 0-12.5). The mean time to clinical healing was10.3±3.1 weeks (range, 8-16), and the mean time to radiological healing was 13.6±2.6 weeks (range, 12-20). There were no major complications. There were 5 minor complications without clinical impact: 2 coracoclavicular calcifications, 1 hypertrophic scar, 1 patient with discomfort due to the device, and 1 superficial wound infection. All patients returned their previous activity. Good clinical results can be achieved with the triple button device in unstable distal fractures of the clavicle, without the need to remove the hardware. Copyright © 2016 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

A new approach to the old problem: Inner filter effect type I and II in fluorescence

NASA Astrophysics Data System (ADS)

Kasparek, Adam; Smyk, Bogdan

2018-06-01

The fluorescence technique is very popular and has been used in many fields of research. It is simple in its assumptions but not very easy to use. One of the main problems is the inner filter effect (IF) I and II which takes place in the cuvette. IF type I is permanently present, but IF type II occurs only when absorption and fluorescence spectra overlap. To avoid IF type I, absorbencies in the cuvette should be smaller than 0.05, which is however very difficult to obtain in many experiments. In this work we propose a new method to solve these problems in the case of a Cary Eclipse fluorimeter, having horizontally-oriented slits, based on old equations developed in the middle of the last century. This method can be applied for other instruments, even these with vertically-oriented beams, because we share scripts written in MATLAB and GRAMS/AI environment. Calculations in our method enable specifying beam geometry parameters in the cuvette, which is necessary to obtain the correct shape and fluorescence intensity of emission and excitation spectra. Such a specific fluorescence intensity dependence on absorbance can, in many cases, afford possibilities to determine the quantum yield (QY) using slopes of the straight-lines, which was demonstrated with the use of Tryptophan (Trp), Tyrosine (Tyr), and Rhodamine B (RhB) solutions. For example, assuming that QY = 0.14 for Tyr, the QY determined for RhB reached QY = 0.71 ± 0.05, although the measurement for Tyr and RhB was performed at a completely different spectral range.

Usher syndrome clinical types I and II: could ocular symptoms and signs differentiate between the two types?

PubMed

Tsilou, Ekaterini T; Rubin, Benjamin I; Caruso, Rafael C; Reed, George F; Pikus, Anita; Hejtmancik, James F; Iwata, Fumino; Redman, Joy B; Kaiser-Kupfer, Muriel I

2002-04-01

Usher syndrome types I and II are clinical syndromes with substantial genetic and clinical heterogeneity. We undertook the current study in order to identify ocular symptoms and signs that could differentiate between the two types. Sixty-seven patients with Usher syndrome were evaluated. Based on audiologic and vestibular findings, patients were classified as either Usher type I or II. The severity of the ocular signs and symptoms present in each type were compared. Visual acuity, visual field area, electroretinographic amplitude, incidence of cataract and macular lesions were not significantly different between Usher types I and II. However, the ages when night blindness was perceived and retinitis pigmentosa was diagnosed differed significantly between the two types. There seems to be some overlap between types I and II of Usher syndrome in regard to the ophthalmologic findings. However, night blindness appears earlier in Usher type I (although the difference in age of appearance appears to be less dramatic than previously assumed). Molecular elucidation of Usher syndrome may serve as a key to understanding these differences and, perhaps, provide a better tool for use in clinical diagnosis, prognosis and genetic counseling.

Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients

PubMed Central

Delić, Denis; Eisele, Claudia; Schmid, Ramona; Baum, Patrick; Wiech, Franziska; Gerl, Martin; Zimdahl, Heike; Pullen, Steven S.; Urquhart, Richard

2016-01-01

MicroRNAs (miRNAs) are short non-coding RNA species which are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of diabetic nephropathy. miRNAs are present in urine in a remarkably stable form packaged in extracellular vesicles, predominantly exosomes. In the present study, urinary exosomal miRNA profiling was conducted in urinary exosomes obtained from 8 healthy controls (C), 8 patients with type II diabetes (T2D) and 8 patients with type II diabetic nephropathy (DN) using Agilent´s miRNA microarrays. In total, the expression of 16 miRNA species was deregulated (>2-fold) in DN patients compared to healthy donors and T2D patients: the expression of 14 miRNAs (miR-320c, miR-6068, miR-1234-5p, miR-6133, miR-4270, miR-4739, miR-371b-5p, miR-638, miR-572, miR-1227-5p, miR-6126, miR-1915-5p, miR-4778-5p and miR-2861) was up-regulated whereas the expression of 2 miRNAs (miR-30d-5p and miR-30e-5p) was down-regulated. Most of the deregulated miRNAs are involved in progression of renal diseases. Deregulation of urinary exosomal miRNAs occurred in micro-albuminuric DN patients but not in normo-albuminuric DN patients. We used qRT-PCR based analysis of the most strongly up-regulated miRNAs in urinary exosomes from DN patients, miRNAs miR-320c and miR-6068. The correlation of miRNA expression and micro-albuminuria levels could be replicated in a confirmation cohort. In conclusion, urinary exosomal miRNA content is altered in type II diabetic patients with DN. Deregulated miR-320c, which might have an impact on the TGF-β-signaling pathway via targeting thrombospondin 1 (TSP-1) shows promise as a novel candidate marker for disease progression in type II DN that should be evaluated in future studies. PMID:26930277

Predictors for switch from unipolar major depressive disorder to bipolar disorder type I or II: a 5-year prospective study.

PubMed

Holma, K Mikael; Melartin, Tarja K; Holma, Irina A K; Isometsä, Erkki T

2008-08-01

In this naturalistic study, we investigated the rate, time course, and predictors of a diagnostic switch from unipolar major depressive disorder (MDD) to bipolar disorder type I or II during a 5-year follow-up. The Vantaa Depression Study included at baseline 269 psychiatric outpatients (82.9%) and inpatients (17.1%) with DSM-IV MDD, diagnosed using structured and semi-structured interviews and followed up at 6 months, 18 months, and 5 years between February 1, 1997 and April 30, 2004. Information on 248 MDD patients (92.2%) was available for analyses of the risk of diagnostic switch. Cox proportional hazards models were used. Twenty-two subjects (8.9%) with previous unipolar MDD switched to bipolar disorder type II and 7 (2.8%) to type I. Median time for switch to bipolar type I was significantly shorter than to type II. In Cox proportional hazards analyses, severity of MDD (hazard ratio [HR] = 1.08, 95% CI = 1.00 to 1.15, p = .036), obsessive-compulsive disorder (OCD) (HR = 5.00, 95% CI = 2.04 to 12.5, p < .001), social phobia (HR = 2.33, 95% CI = 1.00 to 5.26, p = .050), and large number of cluster B personality disorder symptoms (HR = 1.10, 95% CI = 1.02 to 1.20, p = .022) predicted switch. Among outpatients with MDD in secondary level psychiatric settings, diagnostic switch to bipolar disorder usually refers to type II rather than type I. The few switching to bipolar type I do so relatively early. Predictors for diagnostic switch include not only features of mood disorder, such as severity, but may also include some features of psychiatric comorbidity, such as concurrent social phobia, OCD, and symptoms of cluster B personality disorders.

Treatment with salvianolic acid B restores endothelial function in angiotensin II-induced hypertensive mice.

PubMed

Ling, Wei Chih; Liu, Jian; Lau, Chi Wai; Murugan, Dharmani Devi; Mustafa, Mohd Rais; Huang, Yu

2017-07-15

Salvianolic acid B (Sal B) is one of the most abundant phenolic acids derived from the root of Danshen with potent anti-oxidative properties. The present study examined the vasoprotective effect of Sal B in hypertensive mice induced by angiotensin II (Ang II). Sal B (25mg/kg/day) was administered via oral gavage for 11days to Ang II (1.2mg/kg/day)-infused C57BL/6J mice (8-10weeks old). The vascular reactivity (both endothelium-dependent relaxations and contractions) in mouse arteries was examined by wire myography. The production of reactive oxygen species (ROS), protein level and localization of angiotensin AT 1 receptors and the proteins involved in ROS formation were evaluated using dihydroethidium (DHE) fluorescence, lucigenin-enhanced chemiluminescence, immunohistochemistry and Western blotting, respectively. The changes of ROS generating proteins were also assessed in vitro in human umbilical vein endothelial cells (HUVECs) exposed to Ang II with and without co-treatment with Sal B (0.1-10nM). Oral administration of Sal B reversed the Ang II-induced elevation of arterial systolic blood pressure in mice, augmented the impaired endothelium-dependent relaxations and attenuated the exaggerated endothelium-dependent contractions in both aortas and renal arteries of Ang II-infused mice. In addition, Sal B treatment normalized the elevated levels of AT 1 receptors, NADPH oxidase subunits (NOx-2 and NOx-4) and nitrotyrosine in arteries of Ang II-infused mice or in Ang II-treated HUVECs. In summary, the present study provided additional evidence demonstrating that Sal B treatment for 11days reverses the impaired endothelial function and with a marked inhibition of AT 1 receptor-dependent vascular oxidative stress. This vasoprotective and anti-oxidative action of Sal B most likely contributes to the anti-hypertensive action of the plant-derived compound. Copyright © 2017 Elsevier Inc. All rights reserved.

MicroRNA‑133b inhibits connective tissue growth factor in colorectal cancer and correlates with the clinical stage of the disease.

PubMed

Guo, Yihang; Li, Xiaorong; Lin, Changwei; Zhang, Yi; Hu, Gui; Zhou, Jianyu; Du, Juan; Gao, Kai; Gan, Yi; Deng, Hao

2015-04-01

Accumulating evidence indicates that dysregulation of microRNA‑133b (miR‑133b) is an important step in the development of certain types of human cancer and contributes to tumorigenesis. Altered expression of miR‑133b has been reported in colon carcinoma, but its association with clinical stage in colorectal cancer (CRC) has remained elusive. Connective tissue growth factor (CTGF), a potentially promising candidate gene for interaction with miR‑133b, was screened using microarray analysis. The expression of miR‑133b and CTGF was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The regulatory effects of miR‑133b on CTGF were evaluated using a dual‑luciferase reporter assay. CTGF was identified as a functional target of miR‑133b. The results demonstrated low expression of miR‑133b in CRC specimens with poor cell differentiation (P=0.011), lymph node metastasis (P=0.037) and advanced clinical stages (stage III or IV vs. I or II; P=0.036). Furthermore, there was a significant association between a high level of expression of CTGF mRNA and an advanced clinical stage (stage III or IV vs. I or II; P=0.015) and lymph node metastasis (P=0.034). CTGF expression was negatively regulated by miR‑133b in the human colorectum, suggesting that miR‑133b and CTGF may be candidate therapeutic targets in colorectal cancer.

Incidence, Progression, and Associated Risk Factors of Posterior Vitreous Detachment in Type 2 Diabetes Mellitus: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS II, Report No. 7).

PubMed

Gella, Laxmi; Raman, Rajiv; Pal, Swakshyar Saumya; Ganesan, Suganeswari; Sharma, Tarun

2017-01-01

To report the incidence and progression of posterior vitreous detachment (PVD) and factors influencing the same in a cohort of patients with type 2 diabetes in a South Indian population. A subset of 615 subjects from Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study II were included in this study. All of the subjects underwent detailed ophthalmic evaluation including stereo fundus photography. The status of PVD was assessed using B-scan ultrasonography. A p value of <0.05 was considered statistically significant. The incidence of either incomplete PVD (IPVD) or complete PVD (CPVD) from no PVD at baseline visit was 80.8%. Of them, 32.63% converted to CPVD from IPVD at baseline. High prevalence of emmetropia was observed in subjects with stable No PVD. Risk factors associated with the conversion of CPVD from no PVD and IPVD at baseline were age (OR: 1.04, p = 0.002), myopia (OR: 2.14, p = 0.009), and increase in axial length (OR: 1.35, p = 0.004). Subjects undergoing cataract surgery were at 2.32 times higher risk of converting to CPVD (p = 0.038). Independent risk factors for the progression of PVD were increase in age, myopia, increased axial length, and cataract surgery.

Observed Type II supernova colours from the Carnegie Supernova Project-I

NASA Astrophysics Data System (ADS)

de Jaeger, T.; Anderson, J. P.; Galbany, L.; González-Gaitán, S.; Hamuy, M.; Phillips, M. M.; Stritzinger, M. D.; Contreras, C.; Folatelli, G.; Gutiérrez, C. P.; Hsiao, E. Y.; Morrell, N.; Suntzeff, N. B.; Dessart, L.; Filippenko, A. V.

2018-06-01

We present a study of observed Type II supernova (SN II) colours using optical/near-infrared photometric data from the Carnegie Supernovae Project-I. We analyse four colours (B - V, u - g, g - r, and g - Y) and find that SN II colour curves can be described by two linear regimes during the photospheric phase. The first (s1, colour) is steeper and has a median duration of ˜40 d. The second, shallower slope (s2, colour) lasts until the end of the `plateau' (˜80 d). The two slopes correlate in the sense that steeper initial colour curves also imply steeper colour curves at later phases. As suggested by recent studies, SNe II form a continuous population of objects from the colour point of view as well. We investigate correlations between the observed colours and a range of photometric and spectroscopic parameters including the absolute magnitude, the V-band light-curve slopes, and metal-line strengths. We find that less luminous SNe II appear redder, a trend that we argue is not driven by uncorrected host-galaxy reddening. While there is significant dispersion, we find evidence that redder SNe II (mainly at early epochs) display stronger metal-line equivalent widths. Host-galaxy reddening does not appear to be a dominant parameter, neither driving observed trends nor dominating the dispersion in observed colours. Intrinsic SN II colours are most probably dominated by photospheric temperature differences, with progenitor metallicity possibly playing a minor role. Such temperature differences could be related to differences in progenitor radius, together with the presence or absence of circumstellar material close to the progenitor stars.

Intake of coffee, caffeine and other methylxanthines and risk of Type I vs Type II endometrial cancer.

PubMed

Uccella, S; Mariani, A; Wang, A H; Vierkant, R A; Cliby, W A; Robien, K; Anderson, K E; Cerhan, J R

2013-10-01

Coffee and other sources of methylxanthines and risk of Type I vs Type II endometrial cancer (EC) have not been evaluated previously. Prospective cohort of 23,356 postmenopausal women with 471 Type I and 71 Type II EC cases. Type I EC was statistically significantly associated with caffeinated (relative risk (RR)=0.65 for 4+ cups per day vs ≤1 cup per month: 95% confidence interval (CI): 0.47-0.89) but not decaffeinated (RR=0.76; 95% CI: 0.50-1.15) coffee intake; there were no associations with tea, cola or chocolate, or for Type II EC. The inverse association with caffeinated coffee intake was specific to women with a body mass index 30+ kg m(-2) (RR=0.56; 95% CI: 0.36-0.89). Coffee may protect against Type I EC in obese postmenopausal women.

Skeletal muscle insulin resistance in salt-sensitive hypertension: role of angiotensin II activation of NFκB.

PubMed

Zhou, Ming-Sheng; Liu, Chang; Tian, Runxia; Nishiyama, Akira; Raij, Leopoldo

2015-05-01

We have previously shown that in hypertensive Dahl salt-sensitive (DS) rats, impaired endothelium-dependent relaxation to acetylcholine and to insulin is mechanistically linked to up-regulation of angiotensin (Ang) II actions and the production of reactive oxygen species (ROS) and to activation of the proinflammatory transcription factor (NF)κB. Here we investigated whether Ang II activation of NFκB contributed to insulin resistance in the skeletal muscle of this animal model. DS rats were fed either a normal (NS, 0.5% NaCl) or high (HS, 4% NaCl) salt diet for 6 weeks. In addition, 3 separate groups of HS rats were given angiotensin receptor 1 blocker candesartan (ARB, 10 mg/kg/day in drinking water), antioxidant tempol (1 mmol/L in drinking water) or NFκB inhibitor PDTC (150 mg/kg in drinking water). DS rats manifested an increase in soleus muscle Ang II content, ROS production and phosopho-IκBα/IκBα ratio, ARB or tempol reduced ROS and phospho-IκBα/IκBα ratio. Hypertensive DS rats also manifested a reduction in glucose infusion rate, impaired insulin-induced Akt phosphorylation and Glut-4 translocation in the soleus muscle, which were prevented with treatment of either ARB, tempol, or PDTC. Data from the rat diabetes signaling pathway PCR array showed that 8 genes among 84 target genes were altered in the muscle of hypertensive rats with the increase in gene expression of ACE1 and 5 proinflammatory genes, and decrease of 2 glucose metabolic genes. Incubation of the muscle with NFκB SN50 (a specific peptide inhibitor of NFκB) ex vivo reversed changes in hypertension-induced gene expression. The current findings strongly suggest that the activation of NFκB inflammatory pathway by Ang II play a critical role in skeletal muscle insulin resistance in salt-sensitive hypertension.

A preliminary study of the effects of an extract of Ligularia fischeri leaves on type II collagen-induced arthritis in DBA/1J mice.

PubMed

Choi, Eun Mi; Kim, Young Ho

2008-01-01

The present study was undertaken to determine whether Ligularia fischeri leaf extract (LF) is efficacious against collagen-induced arthritis (CIA) in mice. DBA/1J mice were immunized with bovine type II collagen and treated with LF (100 and 200 mg/kg) for 49 days. Mice were assessed regularly for signs of arthritis and the levels of rheumatoid factor, anti-type II collagen antibody, cytokines, AST, ALT, and creatinine in serum were also examined after the animals were killed. The arthritis score and paw edema were markedly suppressed in the groups treated with LF. Moreover, levels of rheumatoid factor, anti-type II collagen antibody, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 in sera were reduced by LF administration. These data suggest that L. fischeri might be effective for the treatment of inflammatory arthritis like human rheumatoid arthritis.

The Major Histocompatibility Complex Class II Transactivator CIITA Inhibits the Persistent Activation of NF-κB by the Human T Cell Lymphotropic Virus Type 1 Tax-1 Oncoprotein

PubMed Central

Forlani, Greta; Abdallah, Rawan

2016-01-01

ABSTRACT Human T cell lymphotropic virus type 1 (HTLV-1) Tax-1, a key protein in HTLV-1-induced T cell transformation, deregulates diverse cell signaling pathways. Among them, the NF-κB pathway is constitutively activated by Tax-1, which binds to NF-κB proteins and activates the IκB kinase (IKK). Upon phosphorylation-dependent IκB degradation, NF-κB migrates into the nucleus, mediating Tax-1-stimulated gene expression. We show that the transcriptional regulator of major histocompatibility complex class II genes CIITA (class II transactivator), endogenously or ectopically expressed in different cells, inhibits the activation of the canonical NF-κB pathway by Tax-1 and map the region that mediates this effect. CIITA affects the subcellular localization of Tax-1, which is mostly retained in the cytoplasm, and this correlates with impaired migration of RelA into the nucleus. Cytoplasmic and nuclear mutant forms of CIITA reveal that CIITA exploits different strategies to suppress Tax-1-mediated NF-κB activation in both subcellular compartments. CIITA interacts with Tax-1 without preventing Tax-1 binding to both IKKγ and RelA. Nevertheless, CIITA affects Tax-1-induced IKK activity, causing retention of the inactive p50/RelA/IκB complex in the cytoplasm. Nuclear CIITA associates with Tax-1/RelA in nuclear bodies, blocking Tax-1-dependent activation of NF-κB-responsive genes. Thus, CIITA inhibits cytoplasmic and nuclear steps of Tax-1-mediated NF-κB activation. These results, together with our previous finding that CIITA acts as a restriction factor inhibiting Tax-1-promoted HTLV-1 gene expression and replication, indicate that CIITA is a versatile molecule that might also counteract Tax-1 transforming activity. Unveiling the molecular basis of CIITA-mediated inhibition of Tax-1 functions may be important in defining new strategies to control HTLV-1 spreading and oncogenic potential. IMPORTANCE HTLV-1 is the causative agent of human adult T cell leukemia

The Major Histocompatibility Complex Class II Transactivator CIITA Inhibits the Persistent Activation of NF-κB by the Human T Cell Lymphotropic Virus Type 1 Tax-1 Oncoprotein.

PubMed

Forlani, Greta; Abdallah, Rawan; Accolla, Roberto S; Tosi, Giovanna

2016-01-20

Human T cell lymphotropic virus type 1 (HTLV-1) Tax-1, a key protein in HTLV-1-induced T cell transformation, deregulates diverse cell signaling pathways. Among them, the NF-κB pathway is constitutively activated by Tax-1, which binds to NF-κB proteins and activates the IκB kinase (IKK). Upon phosphorylation-dependent IκB degradation, NF-κB migrates into the nucleus, mediating Tax-1-stimulated gene expression. We show that the transcriptional regulator of major histocompatibility complex class II genes CIITA (class II transactivator), endogenously or ectopically expressed in different cells, inhibits the activation of the canonical NF-κB pathway by Tax-1 and map the region that mediates this effect. CIITA affects the subcellular localization of Tax-1, which is mostly retained in the cytoplasm, and this correlates with impaired migration of RelA into the nucleus. Cytoplasmic and nuclear mutant forms of CIITA reveal that CIITA exploits different strategies to suppress Tax-1-mediated NF-κB activation in both subcellular compartments. CIITA interacts with Tax-1 without preventing Tax-1 binding to both IKKγ and RelA. Nevertheless, CIITA affects Tax-1-induced IKK activity, causing retention of the inactive p50/RelA/IκB complex in the cytoplasm. Nuclear CIITA associates with Tax-1/RelA in nuclear bodies, blocking Tax-1-dependent activation of NF-κB-responsive genes. Thus, CIITA inhibits cytoplasmic and nuclear steps of Tax-1-mediated NF-κB activation. These results, together with our previous finding that CIITA acts as a restriction factor inhibiting Tax-1-promoted HTLV-1 gene expression and replication, indicate that CIITA is a versatile molecule that might also counteract Tax-1 transforming activity. Unveiling the molecular basis of CIITA-mediated inhibition of Tax-1 functions may be important in defining new strategies to control HTLV-1 spreading and oncogenic potential. HTLV-1 is the causative agent of human adult T cell leukemia-lymphoma (ATLL). The viral

Crosslinked type II collagen matrices: preparation, characterization, and potential for cartilage engineering.

PubMed

Pieper, J S; van der Kraan, P M; Hafmans, T; Kamp, J; Buma, P; van Susante, J L C; van den Berg, W B; Veerkamp, J H; van Kuppevelt, T H

2002-08-01

The limited intrinsic repair capacity of articular cartilage has stimulated continuing efforts to develop tissue engineered analogues. Matrices composed of type II collagen and chondroitin sulfate (CS), the major constituents of hyaline cartilage, may create an appropriate environment for the generation of cartilage-like tissue. In this study, we prepared, characterized, and evaluated type 11 collagen matrices with and without CS. Type II collagen matrices were prepared using purified, pepsin-treated, type II collagen. Techniques applied to prepare type I collagen matrices were found unsuitable for type II collagen. Crosslinking of collagen and covalent attachment of CS was performed using 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide. Porous matrices were prepared by freezing and lyophilization, and their physico-chemical characteristics (degree of crosslinking, denaturing temperature, collagenase-resistance, amount of CS incorporated) established. Matrices were evaluated for their capacity to sustain chondrocyte proliferation and differentiation in vitro. After 7 d of culture, chondrocytes were mainly located at the periphery of the matrices. In contrast to type I collagen, type II collagen supported the distribution of cells throughout the matrix. After 14 d of culture, matrices were surfaced with a cartilagenous-like layer, and occasionally clusters of chondrocytes were present inside the matrix. Chondrocytes proliferated and differentiated as indicated by biochemical analyses, ultrastructural observations, and reverse transcriptase PCR for collagen types I, II and X. No major differences were observed with respect to the presence or absence of CS in the matrices.

Enhanced susceptibility to acute pneumococcal otitis media in mice deficient in complement C1qa, factor B, and factor B/C2.

PubMed

Tong, Hua Hua; Li, Yong Xing; Stahl, Gregory L; Thurman, Joshua M

2010-03-01

To define the roles of specific complement activation pathways in host defense against Streptococcus pneumoniae in acute otitis media (AOM), we investigated the susceptibility to AOM in mice deficient in complement factor B and C2 (Bf/C2(-/)(-)), C1qa (C1qa(-/)(-)), and factor B (Bf(-)(/)(-)). Bacterial titers of both S. pneumoniae serotype 6A and 14 in the middle ear lavage fluid samples from Bf/C2(-/)(-), Bf(-)(/)(-), and C1qa(-/)(-) mice were significantly higher than in samples from wild-type mice 24 h after transtympanical infection (P < 0.05) and remained persistently higher in samples from Bf/C2(-/)(-) mice than in samples from wild-type mice. Bacteremia occurred in Bf/C2(-/)(-), Bf(-)(/)(-), and C1qa(-/)(-) mice infected with both strains, but not in wild-type mice. Recruitment of inflammatory cells was paralleled by enhanced production of inflammatory mediators in the middle ear lavage samples from Bf/C2(-/)(-) mice. C3b deposition on both strains was greatest for sera obtained from wild-type mice, followed by C1qa(-)(/)(-) and Bf(-)(/)(-) mice, and least for Bf/C2(-)(/)(-) mice. Opsonophagocytosis and whole-blood killing capacity of both strains were significantly decreased in the presence of sera or whole blood from complement-deficient mice compared to wild-type mice. These findings indicate that both the classical and alternative complement pathways are critical for middle ear immune defense against S. pneumoniae. The reduced capacity of complement-mediated opsonization and phagocytosis in the complement-deficient mice appears to be responsible for the impaired clearance of S. pneumoniae from the middle ear and dissemination to the bloodstream during AOM.

Association between ApoA-II -265T/C polymorphism and oxidative stress in patients with type 2 diabetes mellitus.

PubMed

Koohdani, Fariba; Sadrzadeh-Yeganeh, Haleh; Djalali, Mahmoud; Eshraghian, Mohammadreza; Keramat, Laleh; Mansournia, Mohammad-Ali; Zamani, Elham

2015-01-01

Apolipoprotein A-II (ApoA-II) constitutes approximately 20% of the total HDL protein content. The results of various studies on the relationship between cardiovascular diseases (CVD) and the plasma ApoA-II level are contradictory. The aim of this study was to determine the relationship between ApoA-II polymorphism and oxidative stress (OS) as a risk factor for CVD. The present comparative study was carried out on 180 obese and non-obese patients with type 2 diabetes, with equal numbers of CC, TC, and TT genotypes of ApoA-II -265T/C gene. The ApoA-II genotype was determined by the TaqMan assay method. The anthropometric measurements and serum levels of lipid profile, superoxide dismutase activity (SOD), total antioxidant capacity (TAC), and 8-isoprostaneF2α were measured. After adjusting for confounding factors, in the total study population and in obese and non-obese groups, the subjects with CC genotype had a lower mean serum SOD activity (p=0.002, p=0.007 and p=0.005, respectively) and higher mean 8-isoprostaneF2α concentration (p<0.001, p=0.003 and p=0.004, respectively) than the T-allele carriers. In the TT/TC group, the mean 8-isoprostanF2α concentration was significantly higher in the obese subjects than the non-obese subjects (p=0.009). In the CC group, no significant differences were found in the OS factors between obese and non-obese groups. The T allele in patients with type 2 diabetes is a protective factor against OS; obesity inhibits this protective effect. The results of this study represent the anti-atherogenic properties of ApoA-II. However, further studies are needed in this field. Copyright © 2015 Elsevier Inc. All rights reserved.

VizieR Online Data Catalog: UBVRIz light curves of 51 Type II supernovae (Galbany+, 2016)

NASA Astrophysics Data System (ADS)

Galbany, L.; Hamuy, M.; Phillips, M. M.; Suntzeff, N. B.; Maza, J.; de Jaeger, T.; Moraga, T.; Gonzalez-Gaitan, S.; Krisciunas, K.; Morrell, N. I.; Thomas-Osip, J.; Krzeminski, W.; Gonzalez, L.; Antezana, R.; Wishnjewski, M.; McCarthy, P.; Anderson, J. P.; Gutierrez, C. P.; Stritzinger, M.; Folatelli, G.; Anguita, C.; Galaz, G.; Green, E. M.; Impey, C.; Kim, Y.-C.; Kirhakos, S.; Malkan, M. A.; Mulchaey, J. S.; Phillips, A. C.; Pizzella, A.; Prosser, C. F.; Schmidt, B. P.; Schommer, R. A.; Sherry, W.; Strolger, L.-G.; Wells, L. A.; Williger, G. M.

2016-08-01

This paper presents a sample of multi-band, visual-wavelength light curves of 51 type II supernovae (SNe II) observed from 1986 to 2003 in the course of four different surveys: the Cerro Tololo Supernova Survey, the Calan Tololo Supernova Program (C&T), the Supernova Optical and Infrared Survey (SOIRS), and the Carnegie Type II Supernovae Survey (CATS). Near-infrared photometry and optical spectroscopy of this set of SNe II will be published in two companion papers. A list of the SNe II used in this study is presented in Table1. The first object in our list is SN 1986L and it is the only SN observed with photoelectric techniques (by M.M.P and S.K., using the Cerro Tololo Inter-American Observatory (CTIO) 0.9m equipped with a photometer and B and V filters). The remaining SNe were observed using a variety of telescopes equipped with CCD detectors and UBV(RI)KCz filters (see Table5). The magnitudes for the photometric sequences of the 51 SNe II are listed in Table4. In every case, these sequences were derived from observations of Landolt standards (see Appendix D in Hamuy et al. 2001ApJ...558..615H for the definition of the z band and Stritzinger et al. 2002AJ....124.2100S for the description of the z-band standards). Table5 lists the resulting UBVRIz magnitudes for the 51 SNe. (3 data files).

Egg Yolk Factor of Staphylococcus aureus II. Characterization of the Lipase Activity

PubMed Central

Shah, D. B.; Wilson, J. B.

1965-01-01

Shah, D. B. (University of Wisconsin, Madison), and J. B. Wilson. Egg yolk factor of Staphylococcus aureus. II. Characterization of the lipase activity. J. Bacteriol. 89:949–953. 1965.—The staphylococcal egg yolk factor was characterized as a lipase. The enzyme had an optimal pH of 7.8, but the optimal pH of stability was 7. Substrate specificity data showed that the relative rate of hydrolysis was lowest with triacetin as substrate, was maximal with tributyrin, and decreased as the chain length of the acyl moieties increased. The enzyme showed an absolute requirement for a fatty acid acceptor like calcium, when the acyl moiety of triglyceride was water-insoluble. Magnesium, strontium, and barium functioned equally well as fatty acid acceptors. The enzyme was able to hydrolyze coconut oil, peanut oil, olive oil, and egg yolk oil. PMID:14276120

Binding Selectivity of Methanobactin from Methylosinus trichosporium OB3b for Copper(I), Silver(I), Zinc(II), Nickel(II), Cobalt(II), Manganese(II), Lead(II), and Iron(II).

PubMed

McCabe, Jacob W; Vangala, Rajpal; Angel, Laurence A

2017-12-01

Methanobactin (Mb) from Methylosinus trichosporium OB3b is a member of a class of metal binding peptides identified in methanotrophic bacteria. Mb will selectively bind and reduce Cu(II) to Cu(I), and is thought to mediate the acquisition of the copper cofactor for the enzyme methane monooxygenase. These copper chelating properties of Mb make it potentially useful as a chelating agent for treatment of diseases where copper plays a role including Wilson's disease, cancers, and neurodegenerative diseases. Utilizing traveling wave ion mobility-mass spectrometry (TWIMS), the competition for the Mb copper binding site from Ag(I), Pb(II), Co(II), Fe(II), Mn(II), Ni(II), and Zn(II) has been determined by a series of metal ion titrations, pH titrations, and metal ion displacement titrations. The TWIMS analyses allowed for the explicit identification and quantification of all the individual Mb species present during the titrations and measured their collision cross-sections and collision-induced dissociation patterns. The results showed Ag(I) and Ni(II) could irreversibly bind to Mb and not be effectively displaced by Cu(I), whereas Ag(I) could also partially displace Cu(I) from the Mb complex. At pH ≈ 6.5, the Mb binding selectivity follows the order Ag(I)≈Cu(I)>Ni(II)≈Zn(II)>Co(II)>Mn(II)≈Pb(II)>Fe(II), and at pH 7.5 to 10.4 the order is Ag(I)>Cu(I)>Ni(II)>Co(II)>Zn(II)>Mn(II)≈Pb(II)>Fe(II). Breakdown curves of the disulfide reduced Cu(I) and Ag(I) complexes showed a correlation existed between their relative stability and their compact folded structure indicated by their CCS. Fluorescence spectroscopy, which allowed the determination of the binding constant, compared well with the TWIMS analyses, with the exception of the Ni(II) complex. Graphical abstract ᅟ.

40 CFR Appendix B to Subpart A of... - Class II Controlled Substances a

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Class II Controlled Substances a B..., Subpt. A, App. B Appendix B to Subpart A of Part 82—Class II Controlled Substances a Controlled... the highest ODP, and the lower value is the estimate of the ODP of the isomer with the lowest ODP...

Alternatives to type II cement : final report.

DOT National Transportation Integrated Search

1978-01-01

Concrete mixtures incorporating fly ash were investigated as possible alternatives to mixtures utilizing Type II cements. The mixture characteristics considered were strength, resistance to freezing and thawing and sulfates, heat of hydration, and vo...

Management of Type II Odontoid Fracture for Osteoporotic Bone Structure: Preliminary Report.

PubMed

Cosar, Murat; Ozer, A Fahir; Alkan, Bahadır; Guven, Mustafa; Akman, Tarık; Aras, Adem Bozkurt; Ceylan, Davut; Tokmak, Mehmet

2015-01-01

Anterior transodontoid screw fixation technique is generally chosen for the management of type II odontoid fractures. The nonunion of type II odontoid fractures is still a major problem especially in elderly and osteoporotic patients. Eleven osteoporotic type II odontoid fracured patients were presented in this article. We have divided 11 patients in two groups as classical and Ozer's technique. We have also compared (radiologically and clinically) the classical anterior transodontoid screw fixation (group II: 6 cases) and Ozer's transodontoid screw fixation technique (group I: 5 cases) retrospectively. There was no difference regaring the clinical features of the groups. However, the radiological results showed 100% fusion for Ozer's screw fixation technique and 83% fusion for the classical screw fixation technique. In conclusion, we suggest that Ozer's technique may help to increase the fusion capacity for osteoporotic type II odontoid fractures.

Stronger enhancer II/core promoter activities of hepatitis B virus isolates of B2 subgenotype than those of C2 subgenotype

PubMed Central

Qin, Yanli; Zhou, Xueshi; Jia, Haodi; Chen, Chaoyang; Zhao, Weifeng; Zhang, Jiming; Tong, Shuping

2016-01-01

Hepatitis B virus (HBV) genotype C causes prolonged chronic infection and increased risk for liver cancer than genotype B. Our previous work revealed lower replication capacity of wild-type genotype C2 than B2 isolates. HBV DNA replication is driven by pregenomic RNA, which is controlled by core promoter (CP) and further augmented by enhancer I (ENI) and enhancer II (ENII). DNA fragments covering these regulatory elements were amplified from B2 and C2 isolates to generate luciferase reporter constructs. As ENII is fully embedded in CP, we inserted HBV DNA fragments in the sense orientation to determine their combined activities, and in the antisense orientation to measure enhancer activities alone. Genotype B2 isolates displayed higher ENI+ENII+CP, ENII+CP, and ENII activities, but not ENI or ENI+ENII activity, than C2 isolates. The higher ENII+CP activity was partly attributable to 4 positions displaying genotype-specific variability. Exchanging CP region was sufficient to revert the replication phenotypes of several B2 and C2 clones tested. These results suggest that a weaker ENII and/or CP at least partly accounts for the lower replication capacities of wild-type C2 isolates, which could drive the subsequent acquisition of CP mutations. Such mutations increase genome replication and are implicated in liver cancer development. PMID:27461034

Stronger enhancer II/core promoter activities of hepatitis B virus isolates of B2 subgenotype than those of C2 subgenotype.

PubMed

Qin, Yanli; Zhou, Xueshi; Jia, Haodi; Chen, Chaoyang; Zhao, Weifeng; Zhang, Jiming; Tong, Shuping

2016-07-27

Hepatitis B virus (HBV) genotype C causes prolonged chronic infection and increased risk for liver cancer than genotype B. Our previous work revealed lower replication capacity of wild-type genotype C2 than B2 isolates. HBV DNA replication is driven by pregenomic RNA, which is controlled by core promoter (CP) and further augmented by enhancer I (ENI) and enhancer II (ENII). DNA fragments covering these regulatory elements were amplified from B2 and C2 isolates to generate luciferase reporter constructs. As ENII is fully embedded in CP, we inserted HBV DNA fragments in the sense orientation to determine their combined activities, and in the antisense orientation to measure enhancer activities alone. Genotype B2 isolates displayed higher ENI+ENII+CP, ENII+CP, and ENII activities, but not ENI or ENI+ENII activity, than C2 isolates. The higher ENII+CP activity was partly attributable to 4 positions displaying genotype-specific variability. Exchanging CP region was sufficient to revert the replication phenotypes of several B2 and C2 clones tested. These results suggest that a weaker ENII and/or CP at least partly accounts for the lower replication capacities of wild-type C2 isolates, which could drive the subsequent acquisition of CP mutations. Such mutations increase genome replication and are implicated in liver cancer development.

Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway.

PubMed

Aoki, Hironori; Yamamoto, Eiichiro; Yamano, Hiro-O; Sugai, Tamotsu; Kimura, Tomoaki; Tanaka, Yoshihito; Matsushita, Hiro-O; Yoshikawa, Kenjiro; Takagi, Ryo; Harada, Eiji; Nakaoka, Michiko; Yoshida, Yuko; Harada, Taku; Sudo, Gota; Eizuka, Makoto; Yorozu, Akira; Kitajima, Hiroshi; Niinuma, Takeshi; Kai, Masahiro; Nojima, Masanori; Suzuki, Hiromu; Nakase, Hiroshi

2018-03-15

Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L). BRAF/KRAS mutations and DNA methylation of CpG island methylator phenotype (CIMP) markers (MINT1, - 2, - 12, - 31, p16, and MLH1) were analyzed through pyrosequencing. Type II-O was tightly associated with sessile serrated adenoma/polyps (SSA/Ps) with BRAF mutation and CIMP-high. Most lesions with simple Type II or Type II-L were hyperplastic polyps, while mixtures of Type II or Type II-L plus more advanced pit patterns (III/IV) were characteristic of traditional serrated adenomas (TSAs). Type II-positive TSAs frequently exhibited BRAF mutation and CIMP-low, while Type II-L-positive TSAs were tightly associated with KRAS mutation and CIMP-low. Analysis of lesions containing both premalignant and cancerous components suggested Type II-L-positive TSAs may develop into KRAS-mutated/CIMP-low/microsatellite stable cancers, while Type II-O-positive SSA/Ps develop into BRAF-mutated/CIMP-high/microsatellite unstable cancers. These results suggest that Type II subtypes reflect distinct molecular subclasses in the serrated neoplasia pathway and that they could be useful hallmarks for identifying SLs at high risk of developing into CRC.

Audiological findings in Usher syndrome types IIa and II (non-IIa).

PubMed

Sadeghi, Mehdi; Cohn, Edward S; Kelly, William J; Kimberling, William J; Tranebjoerg, Lisbeth; Möller, Claes

2004-03-01

The aim was to define the natural history of hearing loss in Usher syndrome type IIa compared to non-IIa. People with Usher syndrome type II show moderate-to-severe hearing loss, normal balance and retinitis pigmentosa. Several genes cause Usher syndrome type II. Our subjects formed two genetic groups: (1) subjects with Usher syndrome type IIa with a mutation and/or linkage to the Usher IIa gene; (2) subjects with the Usher II phenotype with no mutation and/or linkage to the Usher IIa gene. Four hundred and two audiograms of 80 Usher IIa subjects were compared with 435 audiograms of 87 non-IIa subjects. Serial audiograms with intervals of > or = 5 years were examined for progression in 109 individuals Those with Usher syndrome type IIa had significantly worse hearing thresholds than those with non-IIa Usher syndrome after the second decade. The hearing loss in Usher syndrome type IIa was found to be more progressive, and the progression started earlier than in non-IIa Usher syndrome. This suggests an auditory phenotype for Usher syndrome type IIa that is different from that of other types of Usher syndrome II. Thus, this is to our knowledge one of the first studies showing a genotype-phenotype auditory correlation.

Creation of a type IIS restriction endonuclease with a long recognition sequence

PubMed Central

Lippow, Shaun M.; Aha, Patti M.; Parker, Matthew H.; Blake, William J.; Baynes, Brian M.; Lipovšek, Daša

2009-01-01

Type IIS restriction endonucleases cleave DNA outside their recognition sequences, and are therefore particularly useful in the assembly of DNA from smaller fragments. A limitation of type IIS restriction endonucleases in assembly of long DNA sequences is the relative abundance of their target sites. To facilitate ligation-based assembly of extremely long pieces of DNA, we have engineered a new type IIS restriction endonuclease that combines the specificity of the homing endonuclease I-SceI with the type IIS cleavage pattern of FokI. We linked a non-cleaving mutant of I-SceI, which conveys to the chimeric enzyme its specificity for an 18-bp DNA sequence, to the catalytic domain of FokI, which cuts DNA at a defined site outside the target site. Whereas previously described chimeric endonucleases do not produce type IIS-like precise DNA overhangs suitable for ligation, our chimeric endonuclease cleaves double-stranded DNA exactly 2 and 6 nt from the target site to generate homogeneous, 5′, four-base overhangs, which can be ligated with 90% fidelity. We anticipate that these enzymes will be particularly useful in manipulation of DNA fragments larger than a thousand bases, which are very likely to contain target sites for all natural type IIS restriction endonucleases. PMID:19304757

Prevalence of health literacy and its correlates among patients with type II diabetes in Kuwait: A population based study.

PubMed

Hussein, Shaimaa H; Almajran, Abdullah; Albatineh, Ahmed N

2018-05-03

The purpose of this study is to estimate the prevalence of health literacy among patients with type II diabetes and investigate its association with several covariates. No studies were conducted in the Arabian Gulf region characterizing such factors for this population. A cross sectional study was implemented in which 359 type II diabetes patients were recruited from diabetes centers across Kuwait. Health literacy was measured by STOFHLA. Multivariate linear regression was applied to investigate the relationship between health literacy and several covariates. About 44.5% had inadequate, 19.5% marginal, and 35.5% adequate health literacy. Patients with inadequate health literacy were more likely to be older, females, widowed, low education, with income less than 500 KD/month. Multivariate linear regression indicated residence, nationality, education level, and age were significantly associated with health literacy. Adding marital status and gender, hierarchical linear regression revealed that 43.4% of the variability was accounted for. Inadequate health literacy is high in Kuwait. Interventions should be implemented to improve health literacy. This will reduce the prevalence of diabetes-related complications, produce better diabetes outcomes, and improve patients' quality-of-life. Health literacy should be an integral part to health promotion and chronic diseases' management programs in Kuwait. Copyright © 2018 Elsevier B.V. All rights reserved.

Structural study of Cu(II) complexes with benzo[b]furancarboxylic acids

NASA Astrophysics Data System (ADS)

Kalinowska, Diana; Klepka, Marcin T.; Wolska, Anna; Drzewiecka-Antonik, Aleksandra; Ostrowska, Kinga; Struga, Marta

2017-11-01

Four Cu(II) complexes with 2- and 3-benzo[b]furancarboxylic acids have been synthesized and characterized using combination of two spectroscopic techniques. These techniques were: (i) FTIR and (ii) XAFS. FTIR analysis confirmed that complexes were formed and gave insight into identification of possible coordinating groups to the metallic center. XANES analysis indicated that the oxidation state of Cu is +2. EXAFS analysis allowed to identify that the first coordination sphere is formed by 4-5 oxygen atoms with the Cu-O distances around 2 Å. Combining these techniques it was possible to structurally describe novel Cu(II) complexes with benzo[b]furancarboxylic acids.

Type II Heat-labile Enterotoxins: Structure, Function, and Immunomofdulatory Properties

PubMed Central

Hajishengallis, George; Connell, Terry D.

2012-01-01

The heat-labile enterotoxins (HLTs) of Escherichia coli and Vibrio cholerae are classified into two major types on the basis of genetic, biochemical, and immunological properties. Type I and Type II HLT have been intensively studied for their exceptionally strong adjuvant activities. Despite general structural similarities, these molecules, in intact or derivative (non-toxic) forms, display notable differences in their mode of immunomodulatory action. The molecular basis of these differences has remained largely uncharacterized until recently. This review focuses on the Type II HLTs and their immunomodulatory properties which depend largely on interactions with unique gangliosides and Toll-like receptors that are not utilized by the Type I HLTs. PMID:23137790

Mitomycin C induces apoptosis in cultured corneal fibroblasts derived from type II granular corneal dystrophy corneas.

PubMed

Kim, Tae-im; Choi, Seung-il; Lee, Hyung Keun; Cho, Young Jae; Kim, Eung Kweon

2008-06-30

The present study investigated the effect of mitomycin C (MMC) on cell viability, apoptosis, and transforming growth factor beta-induced protein (TGFBIp) expression in cultured normal corneal fibroblasts and heterozygote or homozygote granular corneal dystrophy type II (GCD II) corneal fibroblasts. Keratocytes were obtained from normal cornea or from heterozygote or homozygote GCD II patients after lamellar or penetrating keratoplasty. To measure cell viability, corneal fibroblasts were incubated with 0.02% MMC for 3 h, 6 h, and 24 h or with 0%, 0.01%, 0.02%, and 0.04% MMC for 24 h and then tested using lactate dehydrogenase (LDH) and 3-[4,5-demethylthiazol-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assays. To measure apoptosis, cells were analyzed by FACS analysis and annexin V staining. Bcl-xL, Bax, and TGFBI mRNA expression was measured using reverse transcription polymerase chain reaction (RT-PCR) assays. Cellular and media levels of TGFBIp protein were measured by immunoblotting. MTT and LDH assays showed that MMC reduced cell viability in all three cell types in a dose-dependent and time-dependent manner (p<0.05). FACS analysis and annexin V staining showed that MMC caused apoptosis with GCD II homozygote cells being most affected. RT-PCR analysis showed that MMC decreased Bcl-xL mRNA expression and increased Bax mRNA expression in all cell types. RT-PCR and immunoblotting analysis showed that MMC reduced TGFBI mRNA levels and cellular and media TGFBIp protein levels in all cell types. MMC induced apoptosis, and the effects of MMC were greatest in GCD II homozygote cells. MMC also reduced the production of TGFBIp in all three types of corneal fibroblasts. These findings may explain the additional therapeutic effect of MMC in GCD II patients.

Mitomycin C induces apoptosis in cultured corneal fibroblasts derived from type II granular corneal dystrophy corneas

PubMed Central

Choi, Seung-il; Lee, Hyung Keun; Cho, Young Jae

2008-01-01

Purpose The present study investigated the effect of mitomycin C (MMC) on cell viability, apoptosis, and transforming growth factor beta-induced protein (TGFBIp) expression in cultured normal corneal fibroblasts and heterozygote or homozygote granular corneal dystrophy type II (GCD II) corneal fibroblasts. Methods Keratocytes were obtained from normal cornea or from heterozygote or homozygote GCD II patients after lamellar or penetrating keratoplasty. To measure cell viability, corneal fibroblasts were incubated with 0.02% MMC for 3 h, 6 h, and 24 h or with 0%, 0.01%, 0.02%, and 0.04% MMC for 24 h and then tested using lactate dehydrogenase (LDH) and 3-[4,5-demethylthiazol-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assays. To measure apoptosis, cells were analyzed by FACS analysis and annexin V staining. Bcl-xL, Bax, and TGFBI mRNA expression was measured using reverse transcription polymerase chain reaction (RT–PCR) assays. Cellular and media levels of TGFBIp protein were measured by immunoblotting. Results MTT and LDH assays showed that MMC reduced cell viability in all three cell types in a dose-dependent and time-dependent manner (p<0.05). FACS analysis and annexin V staining showed that MMC caused apoptosis with GCD II homozygote cells being most affected. RT–PCR analysis showed that MMC decreased Bcl-xL mRNA expression and increased Bax mRNA expression in all cell types. RT–PCR and immunoblotting analysis showed that MMC reduced TGFBI mRNA levels and cellular and media TGFBIp protein levels in all cell types. Conclusions MMC induced apoptosis, and the effects of MMC were greatest in GCD II homozygote cells. MMC also reduced the production of TGFBIp in all three types of corneal fibroblasts. These findings may explain the additional therapeutic effect of MMC in GCD II patients. PMID:18615204

30 CFR 57.22222 - Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). 57.22222 Section 57.22222 Mineral Resources MINE SAFETY AND HEALTH....22222 Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). Brattice cloth and...

30 CFR 57.22222 - Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). 57.22222 Section 57.22222 Mineral Resources MINE SAFETY AND HEALTH....22222 Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). Brattice cloth and...

Types A and B Niemann-Pick Disease.

PubMed

Schuchman, Edward H; Wasserstein, Melissa P

2016-06-01

Two distinct metabolic abnormalities are included under the eponym Niemann-Pick disease (NPD). The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM). Patients with ASM deficiency are classified as having types A and B Niemann-Pick disease (NPD). Type A NPD patients exhibit hepatosplenomegaly, frequent pulmonary infections, and profound central nervous system involvement in infancy. They rarely survive beyond two years of age. Type B patients also have hepatosplenomegaly and progressive alterations of their lungs, but there are usually no central nervous system signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Recently, patients with phenotypes intermediate between types A and B NPD also have been identified. These individuals represent the expected continuum caused by inheriting different mutations in the ASM gene (SMPD1). Patients in the second category are designated as having type C NPD. Impaired intracellular trafficking of cholesterol causes type C NPD, and two distinct gene defects have been found. In this chapter only types A and B NPD will be discussed.

Contribution of the Nurses’ Health Studies to Uncovering Risk Factors for Type 2 Diabetes: Diet, Lifestyle, Biomarkers, and Genetics

PubMed Central

Ley, Sylvia H.; Ardisson Korat, Andres V.; Sun, Qi; Tobias, Deirdre K.; Zhang, Cuilin; Qi, Lu; Willett, Walter C.; Manson, JoAnn E.

2016-01-01

Objectives. To review the contribution of the Nurses’ Health Study (NHS) and the NHS II to addressing hypotheses regarding risk factors for type 2 diabetes. Methods. We carried out a narrative review of 1976 to 2016 NHS and NHS II publications. Results. The NHS and NHS II have uncovered important roles in type 2 diabetes for individual nutrients, foods, dietary patterns, and physical activity independent of excess body weight. Up to 90% of type 2 diabetes cases are potentially preventable if individuals follow a healthy diet and lifestyle. The NHS investigations have also identified novel biomarkers for diabetes, including adipokines, inflammatory cytokines, nutrition metabolites, and environmental pollutants, offering new insights into the pathophysiology of the disease. Global collaborative efforts have uncovered many common genetic variants associated with type 2 diabetes and improved our understanding of gene–environment interactions. Continued efforts to identify epigenetic, metagenomic, and metabolomic risk factors for type 2 diabetes have the potential to reveal new pathways and improve prediction and prevention. Conclusions. Over the past several decades, the NHS and NHS II have made major contributions to public health recommendations and strategies designed to reduce the global burden of diabetes. PMID:27459454

Contribution of the Nurses' Health Studies to Uncovering Risk Factors for Type 2 Diabetes: Diet, Lifestyle, Biomarkers, and Genetics.

PubMed

Ley, Sylvia H; Ardisson Korat, Andres V; Sun, Qi; Tobias, Deirdre K; Zhang, Cuilin; Qi, Lu; Willett, Walter C; Manson, JoAnn E; Hu, Frank B

2016-09-01

To review the contribution of the Nurses' Health Study (NHS) and the NHS II to addressing hypotheses regarding risk factors for type 2 diabetes. We carried out a narrative review of 1976 to 2016 NHS and NHS II publications. The NHS and NHS II have uncovered important roles in type 2 diabetes for individual nutrients, foods, dietary patterns, and physical activity independent of excess body weight. Up to 90% of type 2 diabetes cases are potentially preventable if individuals follow a healthy diet and lifestyle. The NHS investigations have also identified novel biomarkers for diabetes, including adipokines, inflammatory cytokines, nutrition metabolites, and environmental pollutants, offering new insights into the pathophysiology of the disease. Global collaborative efforts have uncovered many common genetic variants associated with type 2 diabetes and improved our understanding of gene-environment interactions. Continued efforts to identify epigenetic, metagenomic, and metabolomic risk factors for type 2 diabetes have the potential to reveal new pathways and improve prediction and prevention. Over the past several decades, the NHS and NHS II have made major contributions to public health recommendations and strategies designed to reduce the global burden of diabetes.

Evidence in Gabon for an intrafamilial clustering with mother-to-child and sexual transmission of a new molecular variant of human T-lymphotropic virus type-II subtype B.

PubMed

Tuppin, P; Gessain, A; Kazanji, M; Mahieux, R; Cosnefroy, J Y; Tekaia, F; Georges-Courbot, M C; Georges, A; de Thé, G

1996-01-01

Following the observation of an HTLV-II seropositive 60-year-old woman living in Gabon (Central Africa), a serologic and molecular study of her family members was conducted in an attempt to determine the duration of the HTLV-II infection and the modes of transmission of the virus. Among 41 family members, five were HTLV-I seropositive and 7 exhibited specific HTLV-II antibodies in their sera as demonstrated by high immunofluorescence titers on C19 cells and/or specific Western-blot pattern. The second husband of the index case and two of his sisters were infected by the virus, suggesting the presence of HTLV-II in this family over two generations. Sequence analysis of an amplified fragment of 172 nucleotides within the gp21 of the env region (6469-6640) of four HTLV-II infected individuals revealed a new HTLV-II molecular variant of the subtype b diverging from the prototypes NRA and G12 by seven (4.1%) and five (2.9%) bases substitutions, respectively. Molecular analysis of the total env gene (1462 bp) and fragments of the pol and pX regions confirmed that this new African variant was the most divergent HTLV-II subtype b yet described, exhibiting 2.3% of nucleotide substitutions in the env gene (33 bases) as compared to the two HTLV-II b prototypes. These data demonstrate, for the first time in Africa, intrafamilial both mother-to-child transmission and sexual transmission between spouses of an HTLV-II b molecular variant, and also suggest that this virus has been present in Gabon for a long period of time.

Cloning of the Lentinula edodes B mating-type locus and identification of the genetic structure controlling B mating.

PubMed

Wu, Lin; van Peer, Arend; Song, Wenhua; Wang, Hong; Chen, Mingjie; Tan, Qi; Song, Chunyan; Zhang, Meiyan; Bao, Dapeng

2013-12-01

During the life cycle of heterothallic tetrapolar Agaricomycetes such as Lentinula edodes (Berk.) Pegler, the mating type system, composed of unlinked A and B loci, plays a vital role in controlling sexual development and resulting formation of the fruit body. L. edodes is produced worldwide for consumption and medicinal purposes, and understanding its sexual development is therefore of great importance. A considerable amount of mating type factors has been indicated over the past decades but few genes have actually been identified, and no complete genetic structures of L. edodes B mating-type loci are available. In this study, we cloned the matB regions from two mating compatible L. edodes strains, 939P26 and 939P42. Four pheromone receptors were identified on each new matB region, together with three and four pheromone precursor genes in the respective strains. Gene polymorphism, phylogenetic analysis and distribution of pheromone receptors and pheromone precursors clearly indicate a bipartite matB locus, each sublocus containing a pheromone receptor and one or two pheromone precursors. Detailed sequence comparisons of genetic structures between the matB regions of strains 939P42, 939P26 and a previously reported strain SUP2 further supported this model and allowed identification of the B mating type subloci borders. Mating studies confirmed the control of B mating by the identified pheromone receptors and pheromones in L. edodes. © 2013 Elsevier B.V. All rights reserved.

Properties of Type-II ZnTe/ZnSe Submonolayer Quantum Dots Studied via Excitonic Aharonov- Bohm Effect and Polarized Optical Spectroscopy

NASA Astrophysics Data System (ADS)

Ji, Haojie

In this thesis I develop understanding of the fundamental physical and material properties of type-II ZnTe/ZnSe submonolayer quantum dots (QDs), grown via combination of molecular beam epitaxy (MBE) and migration enhanced epitaxy (MEE). I use magneto-photoluminescence, including excitonic Aharonov-Bohm (AB) effect and polarized optical spectroscopy as the primary tools in this work. I present previous studies as well as the background of optical and magneto-optical processes in semiconductor nanostructures and introduce the experimental methods in Chapters 1 - 3. In Chapter 4 I focus on the excitonic AB effect in the type-II QDs. I develop a lateral tightly-bound exciton model for ZnTe/ZnSe type-II QDs, using analytical methods and numerical calculations. This explained the magneto-PL observation and allowed for establishing the size and density of the QDs in each sample based on the results of PL and magneto-PL measurements. For samples with larger QDs, I observe behaviors that fall between properties of quantum-dot and quantum-well-like systems due to increased QD densities and their type-II nature. Finally, the decoherence mechanisms of the AB excitons are investigated via the temperature dependent studies of the magneto-PL. It is determined that the AB exciton decoherence is due to transport-like (acoustic phonon) scattering of the electrons moving in the ZnSe barriers, but with substantially smaller magnitude of electron-phonon coupling constant due to relatively strong electron-hole coupling within these type-II QDs. In Chapter 5 I discuss the results of circularly polarized magneto-PL measurements. A model with ultra-long spin-flip time of holes confined to submonolayer QDs is proposed. The g-factor of type-II excitons was extracted from the Zeeman splitting and the g-factor of electrons was obtained by fitting the temperature dependence of the degree of circular polarization (DCP), from which g-factor of holes confined within ZnTe QDs was found. It is shown

Hydrolytic stability of pneumococcal group 6 (type 6A and 6B) capsular polysaccharides.

PubMed Central

Zon, G; Szu, S C; Egan, W; Robbins, J D; Robbins, J B

1982-01-01

The hydrolyses of the immunologically cross-reactive and constitutionally isomeric group 6 pneumococcal polysaccharides, types 6A and 6B, were investigated by 31P nuclear magnetic resonance spectroscopy, gel filtration through Sepharose 4B, reducing-sugar analysis, and rocket immunoelectrophoresis. Phosphorus nuclear magnetic resonance spectroscopy showed that cleavage of the repeating-unit phosphodiester linkages at pH 10, 60 degrees C was considerably faster (greater than 10(3) ) for the type 6A than the type 6B polysaccharide. Under these reaction conditions, 31P nuclear magnetic resonance kinetic measurements showed that the Na+ form of the type 6A polysaccharide underwent phosphodiester-linkage hydrolysis two times slower than the corresponding Ca+2 form; a stoichiometrically excess amount of Ca+2 caused a 30-fold enhancement of the latter hydrolysis rate. The spectroscopic characterization of phosphorus-containing end groups resulting from hydrolysis of the type 6A polymer provided additional mechanistic information. Heating the type 6A and 6B polysaccharides at 56 degrees C for various times led to gel filtration coefficients of distribution (Kd values) which indicated that the type 6A material underwent size reductions considerably faster than did the type 6B antigen; these increased Kd values qualitatively correlated with the loss of immunochemical reactivity measured by rocket immunoelectrophoresis. The application of a statistical theory to the depolymerization of the type 6A and 6B polysaccharides was consistent with random bond cleavage, as evidenced by the calculated versus measured gel filtration patterns. Although the molecular changes causing the size reductions were not fully elaborated, it was established that the acetal linkages of the type 6A and 6B polysaccharides were comparatively resistant to hydrolysis and that depolymerization by hydrolysis of the phosphodiester linkage was a major factor only in the type 6A structure. It was concluded

Skeletal effects in Angle Class II/1 patients treated with the functional regulator type II : Cephalometric and tensor analysis.

PubMed

Schulz, Simone; Koos, Bernd; Duske, Kathrin; Stahl, Franka

2016-11-01

The purpose of this work was to employ both cephalometric and tensor analysis in characterizing the skeletal changes experienced by patients with Angle Class II/1 malocclusion during functional orthodontic treatment with the functional regulator type II. A total of 23 patients with Class II/1 malocclusion based on lateral cephalograms obtained before and after treatment with the functional regulator type II were analyzed. Another 23 patients with Angle Class II/1 malocclusion who had not undergone treatment were included as controls. Our cephalometric data attest to significant therapeutic effects of the functional regulator type II on the skeletal mandibular system, including significant advancement of the mandible, increases in effective mandibular length with enhancement of the chin profile, and reduction of growth-related bite deepening. No treatment-related effects were observed at the cranial-base and midface levels. In addition, tensor analysis revealed significant stimulation of mandibular growth in sagittal directions, without indications of growth effects on the maxilla. Its growth-pattern findings differed from those of cephalometric analysis by indicating that the appliance did promote horizontal development, which supports the functional orthodontic treatment effect in Angle Class II/1 cases. Tensor analysis yielded additional insights into sagittal and vertical growth changes not identifiable by strictly cephalometric means. The functional regulator type II was an effective treatment modality for Angle Class II/1 malocclusion and influenced the skeletal development of these patients in favorable ways.

Clinical and genetic investigation of families with type II Waardenburg syndrome

PubMed Central

CHEN, YONG; YANG, FUWEI; ZHENG, HEXIN; ZHOU, JIANDA; ZHU, GANGHUA; HU, PENG; WU, WEIJING

2016-01-01

The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia-associated transcription factor (MITF), sex-determining region Y-box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease-causing mutation in pedigree 1. However, there are novel disease-causing genes in Waardenburg syndrome type II, which require further research. PMID:26781036

Clinical and genetic investigation of families with type II Waardenburg syndrome.

PubMed

Chen, Yong; Yang, Fuwei; Zheng, Hexin; Zhou, Jianda; Zhu, Ganghua; Hu, Peng; Wu, Weijing

2016-03-01

The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia‑associated transcription factor (MITF), sex‑determining region Y‑box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease‑causing mutation in pedigree 1. However, there are novel disease‑causing genes in Waardenburg syndrome type II, which require further research.

Outcomes of endovascular interventions for TASC II B and C femoropopliteal lesions.

PubMed

Baril, Donald T; Marone, Luke K; Kim, Justine; Go, Michael R; Chaer, Rabih A; Rhee, Robert Y

2008-09-01

To evaluate outcomes of endovascular interventions on femoropopliteal occlusive disease and determine predictors of restenosis of Trans Atlantic Inter-Societal Consensus (TASC) II B and C lesions. All patients undergoing endovascular interventions for femoropopliteal occlusive disease between May 2003 and July 2007 were reviewed. Patient demographics, pre- and post-procedure ankle-brachial indices (ABI), and anatomic factors (including categorization by TASC II classification, lesion length, and runoff vessel status) were analyzed. Outcomes evaluated included freedom from restenoses, freedom from re-intervention, overall patency, and assisted-patency. A total of 237 total limbs were treated during the period reviewed. The study group included 108 TASC B and 32 TASC C limbs in 125 patients (mean age 73.1 +/- 10.4 years, male sex: 59%). Seventy-one percent of patients were Rutherford classification 2/3 while the remaining 29% were Rutherford classification 4/5. Mean follow-up period was 12.7 months (range, 1-52 m). Forty-one (41) limbs experienced restenosis or occlusion at a mean time of 8 months (range, 1-24 m). Freedom from restenosis/occlusion was 58.9% at 12 months and 47.9% at 24 months. Predictors of restenosis included a preoperative ABI <0.5 (hazard ratio [HR] 3.05, 95% confidence interval [CI] 1.36-6.86, P = .007) and hypercholesterolemia (HR 2.42, 95% CI 1.11-5.25, P = .025). Lesion length as a continuous variable (per centimeter) also correlated with a higher risk of restenosis (HR 1.06, 95% CI 1.00-1.12, P = .057). The overall assisted-primary and secondary-patency rates were 87% and 94% respectively at 3 years with no significant differences between TASC B and TASC C limbs. Endovascular interventions for TASC II B and C lesions are associated with restenosis/occlusion rates that are at least as good as those of open femoropopliteal bypass surgery from historical, previously published series. Furthermore, overall assisted-patency rates are excellent

Association of Neuropeptide-Y (NPY) and Interleukin-1beta (IL1B), Genotype-Phenotype Correlation and Plasma Lipids with Type-II Diabetes.

PubMed

Patel, Roma; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Ansarullah; Laddha, Naresh C; Thakker, Ami; Ramachandran, A V; Begum, Rasheedunnisa

2016-01-01

Neuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID). The present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B transcript levels. PCR-RFLP was used for genotyping these polymorphisms in a case-control study involving 558 TIID patients and 1085 healthy age-matched controls from Gujarat. Linkage disequilibrium and haplotype analysis of the NPY polymorphic sites were performed to assess their association with TIID. IL1B transcript levels in PBMCs were also assessed in 108 controls and 101 patients using real-time PCR. Our results show significant association of both structural and promoter polymorphisms of NPY (p<0.0001 and p<0.0001 respectively) in patients with TIID. However, the IL1B C/T polymorphism did not show any association (p = 0.3797) with TIID patients. Haplotype analysis revealed more frequent association of CC and CT haplotypes (p = 3.34 x 10-5, p = 6.04 x 10-9) in diabetics compared to controls and increased the risk of diabetes by 3.02 and 2.088 respectively. Transcript levels of IL1B were significantly higher (p<0.0001) in patients as compared to controls. Genotype-phenotype correlation of IL1B polymorphism did not show any association with its higher transcript levels. In addition, NPY +1128 T/C polymorphism was found to be associated with increased plasma LDL levels (p = 0.01). The present study provides an evidence for a strong correlation between structural and promoter polymorphisms of NPY gene and upregulation of IL1B transcript levels with susceptibility to TIID and altering the lipid metabolism in Gujarat population.

PSN J02455988-0734270 in NGC 1084 is a young type II-P SN

NASA Astrophysics Data System (ADS)

Childress, M.; Scalzo, R.; Yuan, F.; Schmidt, B.

2012-08-01

We report the spectroscopic classification of the optical transient PSN J02455988-0734270 in NGC 1084 (disc. 2012-08-11.039 by B. Monard) based on an optical spectrum taken with the Wide Field Spectrograph (WiFeS - Dopita et al., 2007, ApSS, 310, 255) on the ANU 2.3m telescope at Siding Spring Observatory, NSW Australia, using the B3000/R3000 gratings (3600-10000, 1A resolution). The transient spectrum was compared to supernova spectral templates using SNID (Blondin & Tonry, 2007, ApJ, 666, 1024) indicating it to be a supernova of type II-P at a very young age, perhaps only a few days after explosion.

Effects of Artesunate on the Expressions of Insulin-Like Growth Factor-1, Osteopontin and C-Telopeptides of Type II Collagen in a Rat Model of Osteoarthritis.

PubMed

Bai, Zhe; Guo, Xiao-Hui; Tang, Chi; Yue, Si-Tong; Shi, Long; Qiang, Bo

2018-01-01

The study aims to explore the effects of artesunate on insulin-like growth factor-1 (IGF-1), Osteopontin (OPN), and C-telopeptides of type II collagen (CTX-II) in serum, synovial fluid (SF), and cartilage tissues of rats with osteoarthritis (OA). OA models were established. Normal model, artesunate, and Viatril-S groups (20 rats respectively) were set. Enzyme-linked immunosorbent assay, IHC staining, and quantitative real-time polymerase chain reaction were conducted to calculate IGF-1, OPN, and CTX-II levels in serum, SF, and cartilage tissues of rats. The pathological changes in cartilage tissues were evaluated with Mankin score and Hematoxylin-Eosin staining. Compared with the normal group, the model group showed increased IGF-1 level; decreased OPN, CTX-II levels in the serum and SF; and contrary results were seen in the cartilage tissues. A gradual ascending IGF-1 level and descending OPN and CTX-II levels existed in the serum and SF in the artesunate and Viatril-S groups after 2 weeks. The model group showed the most obvious pathological changes and highest Mankin score compared with the other groups. Higher IGF-1 level and lower OPN, CTX-II levels were exhibited in the cartilage tissue in the artesunate and Viatril-S groups but not in the model group. Artesunate and Viatril-S inhibit OA development by elevating IGF-1 level and reducing OPN and CTX-II levels. © 2017 S. Karger AG, Basel.

Human transcription factor hTAF(II)150 (CIF150) is involved in transcriptional regulation of cell cycle progression.

PubMed

Martin, J; Halenbeck, R; Kaufmann, J

1999-08-01

Here we present evidence that CIF150 (hTAF(II)150), the human homolog of Drosophila TAF(II)150, plays an important and selective role in establishing gene expression patterns necessary for progression through the cell cycle. Gel filtration experiments demonstrate that CIF150 (hTAF(II)150) seems to be less tightly associated with human transcription factor IID than hTAF(II)130 is associated with hTAF(II)250. The transient functional knockout of CIF150 (hTAF(II)150) protein led to cell cycle arrest at the G(2)/M transition in mammalian cell lines. PCR display analysis with the RNA derived from CIF150-depleted cells indicated that CIF150 (hTAF(II)150) is required for the transcription of only a subset of RNA polymerase II genes. CIF150 (hTAF(II)150) directly stimulated cyclin B1 and cyclin A transcription in cotransfection assays and in vitro assays, suggesting that the expression of these genes is dependent on CIF150 (hTAF(II)150) function. We defined a CIF150 (hTAF(II)150) consensus binding site and demonstrated that a CIF150-responsive cis element is present in the cyclin B1 core promoter. These results suggest that one function of CIF150 (hTAF(II)150) is to select specific RNA polymerase II core promoter elements involved in cell cycle progression.

Identification of a high-virulence clone of type III Streptococcus agalactiae (group B Streptococcus) causing invasive neonatal disease.

PubMed

Musser, J M; Mattingly, S J; Quentin, R; Goudeau, A; Selander, R K

1989-06-01

Chromosomal genotypes of 128 isolates of six serotypes (Ia, Ib, Ic, II, Ic/II, and III) of Streptococcus agalactiae (group B Streptococcus) recovered predominantly from human infants in the United States were characterized by an analysis of electrophoretically demonstrable allelic profiles at 11 metabolic enzyme loci. Nineteen distinctive electrophoretic types (ETs), representing multilocus clonal genotypes, were identified. Mean genetic diversity per locus among ETs of isolates of the same serotype was, on average, nearly equal to that in all 19 ETs. Cluster analysis of the ETs revealed two primary phylogenetic divisions at a genetic distance of 0.65. A single clone (ET 1) represented by 40 isolates expressing type III antigen formed division I. Division II was composed of 18 ETs in three major lineages diverging from one another at distances greater than 0.35 and included strains of all six antigenic classes. The type III organisms in division I produce more extracellular neuraminidase and apparently are more virulent than the type III strains in division II, which are related to strains of other serotypes that cause disease much less frequently. The existence of this unusually virulent clone accounts, in major part, for the high morbidity and mortality associated with infection by type III organisms.

An increase in circulating B cell-activating factor in childhood-onset ocular myasthenia gravis.

PubMed

Motobayashi, Mitsuo; Inaba, Yuji; Nishimura, Takafumi; Kobayashi, Norimoto; Nakazawa, Yozo; Koike, Kenichi

2015-04-01

Myasthenia gravis is a B cell-mediated autoimmune disorder. The pathophysiology of childhood-onset ocular myasthenia gravis remains unclear. We investigated serum B cell-activating factor levels and other immunological parameters in child patients with ocular myasthenia gravis. Blood samples were obtained from 9 children with ocular myasthenia gravis and 20 age-matched controls. We assayed serum concentrations of B cell-activating factor, anti-acetylcholine receptor antibody titers, 7 types of cytokines (interleukins-2, -4, -6, -10, and -17A; interferon-γ; tumor necrosis factor-α) as well as the percentages of peripheral blood CD4+, CD8+, and CD19+ cells. Serum B cell-activating factor levels were significantly higher before immunosuppressive therapy in patients with childhood-onset ocular myasthenia gravis than in controls and decreased after immunosuppressive therapy. A significant positive correlation was observed between serum B cell-activating factor levels and anti-acetylcholine receptor antibody titers in patients with myasthenia gravis. Serum B cell-activating factor concentrations did not correlate with the percentages of CD4+, CD8+, and CD19+ cells or the CD4+/CD8+ ratio. No significant differences were observed in the levels of the 7 different types of cytokines examined, including interleukin-17A, between preimmunosuppressive therapy myasthenia gravis patients and controls. Circulating B cell-activating factor may play a key role in the pathophysiology of childhood-onset ocular myasthenia gravis. Copyright © 2015 Elsevier Inc. All rights reserved.

The role of intrinsic disorder and dynamics in the assembly and function of the type II secretion system.

PubMed

Gu, Shuang; Shevchik, Vladimir E; Shaw, Rosie; Pickersgill, Richard W; Garnett, James A

2017-10-01

Many Gram-negative commensal and pathogenic bacteria use a type II secretion system (T2SS) to transport proteins out of the cell. These exported proteins or substrates play a major role in toxin delivery, maintaining biofilms, replication in the host and subversion of host immune responses to infection. We review the current structural and functional work on this system and argue that intrinsically disordered regions and protein dynamics are central for assembly, exo-protein recognition, and secretion competence of the T2SS. The central role of intrinsic disorder-order transitions in these processes may be a particular feature of type II secretion. Copyright © 2017 Elsevier B.V. All rights reserved.

Association of Mannose-Binding Lectin rs1800450 and Tumor Necrotic Factor-α rs1800620 Polymorphism with Helicobacter pylori in Type II Diabetes Mellitus.

PubMed

Mortazavi, Elnaz; Eslami, Behnaz; Aghahosseini, Parisa; Ahron, Fatemeh; Amininejad, Armagan; Mahmoodi, Sepideh; Satarpour, Hadis; Radmanesh, Nilofar; Rassi, Hossein

2017-10-01

Type II diabetes mellitus (T2DM) is the prevalent type of diabetes, including 90% of the cases world-wide. Helicobacter pylori plays a pathogenic role in the development of T2DM. The host genetic factors have a significant impact on the clinical outcome and anatomical distribution of H. pylori infection and polymorphisms in several genes such as tumor necrotic factor (TNF)-α and mannose-binding lectin (MBL) and are considered to increase the risk for the development of T2DM. In this study, we investigate the prevalence rate of H. pylori infection and its relationship to MBL rs1800450 and TNF-α rs1800620 polymorphism in T2DM. In this case-control study, 174 patients with type II diabetes and 185 healthy controls were studied. Also, demographics, physical, and biochemical parameters were performed in all patients. The DNA extracted from blood specimens was amplified by H. pylori cagA-specific primers. The MBL rs1800450 and TNF-α rs1800620 genotyping were detected by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The results show that H. pylori cagA positivity was detected in 42.82% of the diabetic patients and in 22.16% of the control group, and H. pylori infection was closely correlated with MBL rs1800450 AA genotype and TNF-α rs1800620 GG genotype when compared with healthy controls. Furthermore, these two genotypes were strongly associated with H. pylori cagA(+) samples when compared with cagA(-) samples. In addition, the presence of H. pylori cagA(+) infection was significantly associated with the elevated serum levels of total cholesterol and low-density lipoprotein cholesterol. In general, it can be concluded that molecular analysis of MBL rs1800450 AA genotype and TNF-α rs1800620 AA genotype is important in the early detection and treatment of T2DM with H. pylori cagA(+) infection.

Antigen-B Cell Receptor Complexes Associate with Intracellular major histocompatibility complex (MHC) Class II Molecules*

PubMed Central

Barroso, Margarida; Tucker, Heidi; Drake, Lisa; Nichol, Kathleen; Drake, James R.

2015-01-01

Antigen processing and MHC class II-restricted antigen presentation by antigen-presenting cells such as dendritic cells and B cells allows the activation of naïve CD4+ T cells and cognate interactions between B cells and effector CD4+ T cells, respectively. B cells are unique among class II-restricted antigen-presenting cells in that they have a clonally restricted antigen-specific receptor, the B cell receptor (BCR), which allows the cell to recognize and respond to trace amounts of foreign antigen present in a sea of self-antigens. Moreover, engagement of peptide-class II complexes formed via BCR-mediated processing of cognate antigen has been shown to result in a unique pattern of B cell activation. Using a combined biochemical and imaging/FRET approach, we establish that internalized antigen-BCR complexes associate with intracellular class II molecules. We demonstrate that the M1-paired MHC class II conformer, shown previously to be critical for CD4 T cell activation, is incorporated selectively into these complexes and loaded selectively with peptide derived from BCR-internalized cognate antigen. These results demonstrate that, in B cells, internalized antigen-BCR complexes associate with intracellular MHC class II molecules, potentially defining a site of class II peptide acquisition, and reveal a selective role for the M1-paired class II conformer in the presentation of cognate antigen. These findings provide key insights into the molecular mechanisms used by B cells to control the source of peptides charged onto class II molecules, allowing the immune system to mount an antibody response focused on BCR-reactive cognate antigen. PMID:26400081

Neutrinoless double beta decay in type I+II seesaw models

NASA Astrophysics Data System (ADS)

Borah, Debasish; Dasgupta, Arnab

2015-11-01

We study neutrinoless double beta decay in left-right symmetric extension of the standard model with type I and type II seesaw origin of neutrino masses. Due to the enhanced gauge symmetry as well as extended scalar sector, there are several new physics sources of neutrinoless double beta decay in this model. Ignoring the left-right gauge boson mixing and heavy-light neutrino mixing, we first compute the contributions to neutrinoless double beta decay for type I and type II dominant seesaw separately and compare with the standard light neutrino contributions. We then repeat the exercise by considering the presence of both type I and type II seesaw, having non-negligible contributions to light neutrino masses and show the difference in results from individual seesaw cases. Assuming the new gauge bosons and scalars to be around a TeV, we constrain different parameters of the model including both heavy and light neutrino masses from the requirement of keeping the new physics contribution to neutrinoless double beta decay amplitude below the upper limit set by the GERDA experiment and also satisfying bounds from lepton flavor violation, cosmology and colliders.

Binding Selectivity of Methanobactin from Methylosinus trichosporium OB3b for Copper(I), Silver(I), Zinc(II), Nickel(II), Cobalt(II), Manganese(II), Lead(II), and Iron(II)

NASA Astrophysics Data System (ADS)

McCabe, Jacob W.; Vangala, Rajpal; Angel, Laurence A.

2017-12-01

Methanobactin (Mb) from Methylosinus trichosporium OB3b is a member of a class of metal binding peptides identified in methanotrophic bacteria. Mb will selectively bind and reduce Cu(II) to Cu(I), and is thought to mediate the acquisition of the copper cofactor for the enzyme methane monooxygenase. These copper chelating properties of Mb make it potentially useful as a chelating agent for treatment of diseases where copper plays a role including Wilson's disease, cancers, and neurodegenerative diseases. Utilizing traveling wave ion mobility-mass spectrometry (TWIMS), the competition for the Mb copper binding site from Ag(I), Pb(II), Co(II), Fe(II), Mn(II), Ni(II), and Zn(II) has been determined by a series of metal ion titrations, pH titrations, and metal ion displacement titrations. The TWIMS analyses allowed for the explicit identification and quantification of all the individual Mb species present during the titrations and measured their collision cross-sections and collision-induced dissociation patterns. The results showed Ag(I) and Ni(II) could irreversibly bind to Mb and not be effectively displaced by Cu(I), whereas Ag(I) could also partially displace Cu(I) from the Mb complex. At pH ≈ 6.5, the Mb binding selectivity follows the order Ag(I)≈Cu(I)>Ni(II)≈Zn(II)>Co(II)>>Mn(II)≈Pb(II)>Fe(II), and at pH 7.5 to 10.4 the order is Ag(I)>Cu(I)>Ni(II)>Co(II)>Zn(II)>Mn(II)≈Pb(II)>Fe(II). Breakdown curves of the disulfide reduced Cu(I) and Ag(I) complexes showed a correlation existed between their relative stability and their compact folded structure indicated by their CCS. Fluorescence spectroscopy, which allowed the determination of the binding constant, compared well with the TWIMS analyses, with the exception of the Ni(II) complex. [Figure not available: see fulltext.

Overlapping and lineage-specific roles for the type-B response regulators of monocots and dicots.

PubMed

Kim, Hyo Jung; Kieber, Joseph J; Schaller, G Eric

2012-09-01

Cytokinins are plant hormones with profound roles in growth and development. Cytokinin signaling is mediated through a 'two-component' signaling system composed of histidine kinases, histidine-containing phosphotransfer proteins, and response regulators. Phylogenetic analysis of two-component signaling elements from the monocot rice and the dicot Arabidopsis reveals lineage-specific expansions of the type-B response regulators, transcription factors that act as positive regulators for the cytokinin signal. We recently reported in Plant Physiology on a functional analysis of rice type-B response regulators. A type-B response regulator from a subfamily comprised of both monocot and dicot type-B response regulators complemented an Arabidopsis type-B response regulator mutant, but a type-B response regulator from a monocot-specific subfamily generally did not. Here, we extend this analysis to demonstrate that the promoter of an Arabidopsis cytokinin primary response gene is induced by type-B response regulators from a shared subfamily, but not by one from a lineage-specific subfamily. These results support a model in which the type-B response regulators of monocots and dicots share conserved roles in the cytokinin signaling pathway but have also diverged to take on lineage-specific roles.

Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs.

PubMed

Deparle, L A; Gupta, R C; Canerdy, T D; Goad, J T; D'Altilio, M; Bagchi, M; Bagchi, D

2005-08-01

DeParle L. A., Gupta R. C., Canerdy T. D., Goad J. T., D'Altilio M., Bagchi M., Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J. vet. Pharmacol. Therap.28, 385-390. In large breed dogs, arthritis is very common because of obesity, injury, aging, immune disorder, or genetic predispositions. This study was therefore undertaken to evaluate clinical efficacy and safety of undenatured type-II collagen (UC-II) in obese-arthritic dogs. Fifteen dogs in three groups received either no UC-II (Group I) or UC-II with 1 mg/day (Group II) or 10 mg/day (Group III) for 90 days. Lameness and pain were measured on a weekly basis for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were assayed for creatinine and blood urea nitrogen (markers of renal injury); and alanine aminotransferase and aspartate aminotransferase (evidence of hepatic injury). Dogs receiving 1 mg or 10 mg UC-II/day for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion, with 10 mg showed greater improvement. At either dose of UC-II, no adverse effects were noted and no significant changes were noted in serum chemistry, suggesting that UC-II was well tolerated. In addition, dogs receiving UC-II for 90 days showed increased physical activity level. Following UC-II withdrawal for a period of 30 days, all dogs experienced a relapse of overall pain, exercise-associated lameness, and pain upon limb manipulation. These results suggest that daily treatment of arthritic dogs with UC-II ameliorates signs and symptoms of arthritis, and UC-II is well tolerated as no adverse effects were noted.

Neurologic aspects of microcephalic osteodysplastic primordial dwarfism type II.

PubMed

Galasso, Cinzia; Lo-Castro, Adriana; Lalli, Cristina; Cerminara, Caterina; Curatolo, Paolo

2008-06-01

Microcephalic osteodysplastic primordial dwarfism type II is a specific disorder characterized by severe intrauterine and postnatal growth retardation, acquired microcephaly, cerebrovascular abnormalities, progressive bone dysplasia, and a characteristic face. Whereas the diagnostic features of this syndrome are well-recognized, the neurologic aspects have not been clearly defined. We report on a detailed neurodevelopmental follow-up study of a new case of microcephalic osteodysplastic primordial dwarfism type II, followed from the first years of life to adolescence, and we discuss the neurocognitive features of our patient. We also review the neurologic aspects of this disorder compared with syndromes with overlapping phenotypes, such as microcephalic osteodysplastic primordial dwarfism types I and III and Seckel syndrome.

A new method for correcting type I and type II constricted (cup and lop) ears.

PubMed

Xiaogeng, Hu; Hongxing, Zhuang; Qinghua, Yang; Haiyue, Jiang; Yanyong, Zhao

2006-01-01

Tanzer suggested the term "constricted ear," denoting a spectrum of deformities limited to the superior third of the ear. Tanzer classified the constricted ear into three types. Type I ears have involvement of the helix, which usually is flattened. Type II ears show involvement of both the helix and the scapha. With type III ears, the auricle is rolled into a nearly tubular form that some authors regard as a form of microtia. The authors' new method for correcting the constricted ear varies in accordance with the diverse degree of deformity. The new method was used to correct constricted ears through a one-stage operation in eight type I cases. For the remaining six type 2 cases, the methods were combined with composite grafting. Most of the patients were satisfied with the final results. Therefore, the authors conclude that their approach is suitable for the treatment of type I and type II constricted ears.

U10 : Trusted Truck(R) II (phase B).

DOT National Transportation Integrated Search

2009-01-01

Phase B of the Trusted Truck II project built on the system developed in Phase A (or Year 1). For the implementation portion of the project, systems were added to the trailer to provide additional diagnostic trailer data that can be sent to the TTM...

Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and lobule type in the Nurses' Health Study II.

PubMed

Rice, Megan S; Tamimi, Rulla M; Connolly, James L; Collins, Laura C; Shen, Dejun; Pollak, Michael N; Rosner, Bernard; Hankinson, Susan E; Tworoger, Shelley S

2012-03-13

Previous research in the Nurses' Health Study (NHS) and the NHSII observed that, among women diagnosed with benign breast disease (BBD), those with predominant type 1/no type 3 lobules (a marker of complete involution) versus other lobule types were at lower risk of subsequent breast cancer. Studies in animal models suggest that insulin-like growth factor-1 (IGF-1) may inhibit involution of lobules in the breast; however, this has not been studied in humans. We conducted a cross-sectional study among 472 women in the NHSII who were diagnosed with biopsy-confirmed proliferative BBD between 1991 and 2002 and provided blood samples between 1996 and 1999. A pathologist, blinded to exposure status, classified lobule type in normal adjacent tissue on available biopsy slides according to the number of acini per lobule. For each participant, the pathologist determined the predominant lobule type (that is, type 1, type 2, or type 3) and whether any type 1 or any type 3 lobules were present. Lobule type was then classified as: predominant type 1/no type 3 lobules, which is suggestive of complete involution; or other lobule types. Multivariate logistic models were used to assess the associations between plasma IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), and the ratio of IGF-1:IGFBP-3 levels with lobule type. In univariate analyses, greater age, higher body mass index, postmenopausal status, nulliparity, and lower IGF-1 levels were associated with predominant type 1/no type 3 lobules (P < 0.05). In multivariate models adjusting for age and assay batch, higher IGF-1 levels were associated with decreased odds of predominant type 1/no type 3 lobules (odds ratio quartile 4 vs. quartile 1 = 0.37, 95% confidence interval = 0.15 to 0.89). Greater ratios of IGF-1:IGFBP-3 levels were also associated with decreased odds of predominant type 1/no type 3 lobules (odds ratio quartile 4 vs. quartile 1 = 0.26, 95% confidence interval = 0.11 to 0.64). These results were

Switch from type II to I Fas/CD95 death signaling on in vitro culturing of primary hepatocytes.

PubMed

Walter, Dorothée; Schmich, Kathrin; Vogel, Sandra; Pick, Robert; Kaufmann, Thomas; Hochmuth, Florian Christoph; Haber, Angelika; Neubert, Karin; McNelly, Sabine; von Weizsäcker, Fritz; Merfort, Irmgard; Maurer, Ulrich; Strasser, Andreas; Borner, Christoph

2008-12-01

Fas/CD95-induced apoptosis of hepatocytes in vivo proceeds through the so-called type II pathway, requiring the proapoptotic BH3-only Bcl-2 family member Bid for mitochondrial death signaling. Consequently, Bid-deficient mice are protected from anti-Fas antibody injection induced fatal hepatitis. We report the unexpected finding that freshly isolated mouse hepatocytes, cultured on collagen or Matrigel, become independent of Bid for Fas-induced apoptosis, thereby switching death signaling from type II to type I. In such in vitro cultures, Fas ligand (FasL) activates caspase-3 without Bid cleavage, Bax/Bak activation or cytochrome c release, and neither Bid ablation nor Bcl-2 overexpression is protective. The type II to type I switch depends on extracellular matrix adhesion, as primary hepatocytes in suspension die in a Bid-dependent manner. Moreover, the switch is specific for FasL-induced apoptosis as collagen-plated Bid-deficient hepatocytes are protected from tumor necrosis factor alpha/actinomycin D (TNFalpha/ActD)-induced apoptosis. Our data suggest a selective crosstalk between extracellular matrix and Fas-mediated signaling that favors mitochondria-independent type I apoptosis induction.

SCF(KMD) controls cytokinin signaling by regulating the degradation of type-B response regulators.

PubMed

Kim, Hyo Jung; Chiang, Yi-Hsuan; Kieber, Joseph J; Schaller, G Eric

2013-06-11

Cytokinins are plant hormones that play critical roles in growth and development. In Arabidopsis, the transcriptional response to cytokinin is regulated by action of type-B Arabidopsis response regulators (ARRs). Although central elements in the cytokinin signal transduction pathway have been identified, mechanisms controlling output remain to be elucidated. Here we demonstrate that a family of F-box proteins, called the kiss me deadly (KMD) family, targets type-B ARR proteins for degradation. KMD proteins form an S-phase kinase-associated PROTEIN1 (SKP1)/Cullin/F-box protein (SCF) E3 ubiquitin ligase complex and directly interact with type-B ARR proteins. Loss-of-function KMD mutants stabilize type-B ARRs and exhibit an enhanced cytokinin response. In contrast, plants with elevated KMD expression destabilize type-B ARR proteins leading to cytokinin insensitivity. Our results support a model in which an SCF(KMD) complex negatively regulates cytokinin responses by controlling levels of a key family of transcription factors.

Preparation, structure, and digestibility of crystalline A- and B-type aggregates from debranched waxy starches.

PubMed

Cai, Liming; Shi, Yong-Cheng

2014-05-25

Highly crystalline A- and B-type aggregates were prepared from short linear α-1,4 glucans generated from completely debranched waxy maize and waxy potato starches by manipulating the chain length and crystallization conditions including starch solids concentration and crystallization temperature. The A-type crystalline products were more resistant to enzyme digestion than the B-type crystalline products, and the digestibility of the A- and B-type allomorphs was not correlated with the size of the aggregates formed. Annealing increased the peak melting temperature of the B-type crystallites, making it similar to that of the A-type crystallites, but did not improve the enzyme resistance of the B-type crystalline products. The possible reason for these results was due to the compact morphology as well as the denser packing pattern of double helices in A-type crystallites. Our observations counter the fact that most B-type native starches are more enzyme-resistant than A-type native starches. Crystalline type per se does not seem to be the key factor that controls the digestibility of native starch granules; the resistance of native starches with a B-type X-ray diffraction pattern is probably attributed to the other structural features in starch granules. Copyright © 2014 Elsevier Ltd. All rights reserved.

Type-I and type-II topological nodal superconductors with s -wave interaction

NASA Astrophysics Data System (ADS)

Huang, Beibing; Yang, Xiaosen; Xu, Ning; Gong, Ming

2018-01-01

Topological nodal superconductors with protected gapless points in momentum space are generally realized based on unconventional pairings. In this work we propose a minimal model to realize these topological nodal phases with only s -wave interaction. In our model the linear and quadratic spin-orbit couplings along the two orthogonal directions introduce anisotropic effective unconventional pairings in momentum space. This model may support different nodal superconducting phases characterized by either an integer winding number in BDI class or a Z2 index in D class at the particle-hole invariant axes. In the vicinity of the nodal points the effective Hamiltonian can be described by either type-I or type-II Dirac equations, and the Lifshitz transition from type-I nodal phases to type-II nodal phases can be driven by external in-plane magnetic fields. We show that these nodal phases are robust against weak impurities, which only slightly renormalizes the momentum-independent parameters in the impurity-averaged Hamiltonian, thus these phases are possible to be realized in experiments with real semi-Dirac materials. The smoking-gun evidences to verify these phases based on scanning tunneling spectroscopy method are also briefly discussed.

Pelagodinium gen. nov. and P. béii comb. nov., a dinoflagellate symbiont of planktonic foraminifera.

PubMed

Siano, Raffaele; Montresor, Marina; Probert, Ian; Not, Fabrice; de Vargas, Colomban

2010-07-01

The taxonomic status of the free-living stage of the dinoflagellate Gymnodinium béii, symbiont of the foraminifer Orbulina universa, was reassessed on the basis of detailed morpho-genetic analyses. Electron microscopy observations revealed previously undescribed morphological features of the cell that are important for species recognition. The presence of a single elongated apical vesicle (EAV) ornamented with a row of small knobs, absent in species of the genus Gymnodinium, calls into question the current taxonomic position of the symbiont. The presence of a type E extraplastidial eyespot, the arrangement of the amphiesmal vesicles in series and the absence of trichocysts confirm the affiliation with other symbiotic dinoflagellates and certain genetically related non-symbiotic genera, all belonging to the order Suessiales. The arrangement of the series of vesicles of the analyzed strain is unique within the Suessiales, and the ultrastructure of the pyrenoid is different from other symbiotic dinoflagellates. A large subunit (LSU) rDNA phylogenetic analysis confirmed that the analyzed pelagic symbiont clusters in an independent, well-supported clade within the Suessiales with other sequences of symbiotic dinoflagellates extracted from planktonic foraminifera. Hence a novel genus, Pelagodinium gen. nov., is erected for this pelagic, symbiotic dinoflagellate, and Gymnodinium béii is reclassified as Pelagodinium béii. 2010 Elsevier GmbH. All rights reserved.

Gene Scanning of an Internalin B Gene Fragment Using High-Resolution Melting Curve Analysis as a Tool for Rapid Typing of Listeria monocytogenes

PubMed Central

Pietzka, Ariane T.; Stöger, Anna; Huhulescu, Steliana; Allerberger, Franz; Ruppitsch, Werner

2011-01-01

The ability to accurately track Listeria monocytogenes strains involved in outbreaks is essential for control and prevention of listeriosis. Because current typing techniques are time-consuming, cost-intensive, technically demanding, and difficult to standardize, we developed a rapid and cost-effective method for typing of L. monocytogenes. In all, 172 clinical L. monocytogenes isolates and 20 isolates from culture collections were typed by high-resolution melting (HRM) curve analysis of a specific locus of the internalin B gene (inlB). All obtained HRM curve profiles were verified by sequence analysis. The 192 tested L. monocytogenes isolates yielded 15 specific HRM curve profiles. Sequence analysis revealed that these 15 HRM curve profiles correspond to 18 distinct inlB sequence types. The HRM curve profiles obtained correlated with the five phylogenetic groups I.1, I.2, II.1, II.2, and III. Thus, HRM curve analysis constitutes an inexpensive assay and represents an improvement in typing relative to classical serotyping or multiplex PCR typing protocols. This method provides a rapid and powerful screening tool for simultaneous preliminary typing of up to 384 samples in approximately 2 hours. PMID:21227395

Types A and B Niemann-Pick disease.

PubMed

Schuchman, Edward H; Wasserstein, Melissa P

2015-03-01

Two distinct metabolic abnormalities are encompassed under the eponym Niemann-Pick disease (NPD). The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM). Patients with ASM deficiency are classified as having types A and B Niemann-Pick disease (NPD). Type A NPD patients exhibit hepatosplenomegaly in infancy and profound central nervous system involvement. They rarely survive beyond two years of age. Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no central nervous system signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Recently, patients with phenotypes intermediate between types A and B NPD also have been identified. These individuals represent the expected continuum caused by inheriting different mutations in the ASM gene (SMPD1). Patients in the second NPD category are designated as having types C and D NPD. These patients may have mild hepatosplenomegaly, but the central nervous system is profoundly affected. Impaired intracellular trafficking of cholesterol causes types C and D NPD, and two distinct gene defects have been found. In this chapter only types A and B NPD will be discussed. Copyright © 2014. Published by Elsevier Ltd.

Endogenous and maximal sarcoplasmic reticulum calcium content and calsequestrin expression in type I and type II human skeletal muscle fibres.