Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

International Nuclear Information System (INIS)

Park, In-Hyun; Erbay, Ebru; Nuzzi, Paul; Chen Jie

2005-01-01

The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector

USING THE 1.6 μm BUMP TO STUDY REST-FRAME NEAR-INFRARED-SELECTED GALAXIES AT REDSHIFT 2

International Nuclear Information System (INIS)

Sorba, Robert; Sawicki, Marcin

2010-01-01

We explore the feasibility and limitations of using the 1.6 μm bump as a photometric redshift indicator and selection technique, and use it to study the rest-frame H-band galaxy luminosity and stellar mass functions (SMFs) at redshift z ∼ 2. We use publicly available Spitzer/IRAC images in the GOODS fields and find that color selection in the IRAC bandpasses alone is comparable in completeness and contamination to BzK selection. We find that the shape of the 1.6 μm bump is robust, and photometric redshifts are not greatly affected by choice of model parameters. Comparison with spectroscopic redshifts shows photometric redshifts to be reliable. We create a rest-frame NIR-selected catalog of galaxies at z ∼ 2 and construct a galaxy SMF. Comparisons with other SMFs at approximately the same redshift but determined using shorter wavelengths show good agreement. This agreement suggests that selection at bluer wavelengths does not miss a significant amount of stellar mass in passive galaxies. Comparison with SMFs at other redshifts shows evidence for the downsizing scenario of galaxy evolution. We conclude by pointing out the potential for using the 1.6 μm bump technique to select high-redshift galaxies with the JWST, whose λ>0.6 μm coverage will not be well suited to selecting galaxies using techniques that require imaging at shorter wavelengths.

A 18 m 2 cylindrical tracking detector made of 2.6 m long, stereo mylar straw tubes with 100 μm resolution

Science.gov (United States)

Benussi, L.; Bertani, M.; Bianco, S.; Fabbri, F. L.; Gianotti, P.; Giardoni, M.; Ghezzo, A.; Guaraldo, C.; Lanaro, A.; Locchi, P.; Lu, J.; Lucherini, V.; Mecozzi, A.; Pace, E.; Passamonti, L.; Qaisar, N.; Ricciardi, A.; Sarwar, S.; Serdyouk, V.; Trasatti, L.; Volkov, A.; Zia, A.

1998-12-01

An array of 2424 2.6 m-long, 15 mm-diameter mylar straw tubes, arranged in two axial and four stereo layers, has been assembled. The array covers a cylindrical tracking surface of 18 m 2 and provides coordinate measurement in the drift direction and along the wire. A correction of the systematic effects which are introduced by gravitational sag and electrostatics, thus dominating the detector performance especially with long straws, allows to determine wire position from drift-time distribution. The correction has been applied to reach a space resolution of 40 μm with DME, 100 μm with Ar+C 2H 6, and 100-200 μm with CO 2. Such a resolution is the best ever obtained for straws of these dimensions. A study of the gas leakage for the straw system has been performed, and results are reported. The array is being commissioned as a subdetector of the FINUDA spectrometer, and tracking performances are being studied with cosmic rays.

Is a volume of 3.6 mL better than 1.8 mL for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis?

Science.gov (United States)

Fowler, Sara; Reader, Al

2013-08-01

The purpose of this retrospective study was to determine the success of the inferior alveolar nerve (IAN) block using either 3.6 mL or 1.8 mL 2% lidocaine with 1:100,000 epinephrine in patients presenting with symptomatic irreversible pulpitis. As part of 7 previously published studies, 319 emergency patients presenting with symptomatic irreversible pulpitis received either a 1.8-mL volume or 3.6-mL volume of 2% lidocaine with 1:100,000 epinephrine in an IAN block. One hundred ninety patients received a 1.8-mL volume, and 129 received a 3.6-mL volume. Endodontic emergency treatment was completed on each subject. Success was defined as the ability to access and instrument the tooth without pain (visual analog scale score of 0) or mild pain (VAS rating ≤54 mm). Success of the 1.8-mL volume was 28%, and for the 3.6-mL volume it was 39%. There was no statistically significant difference between the 2 volumes. In conclusion, for patients presenting with irreversible pulpitis, success was not significantly different between a 3.6-mL volume and a 1.8-mL volume of 2% lidocaine with 1:100,000 epinephrine. The success rates (28%-39%) with either volume were not high enough to ensure complete pulpal anesthesia. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

A 18 m2 cylindrical tracking detector made of 2,6 m long, stereo mylar straw tubes with 100 μm resolution

International Nuclear Information System (INIS)

Benussi, L.; Bertani, M.; Bianco, S.; Fabbri, F.L.; Gianotti, P.; Giardoni, M.; Ghezzo, A.; Guaraldo, C.; Lanaro, A.; Locchi, P.; Lu, J.; Lucherini, V.; Mecozzi, A.; Pace, E.; Passamonti, L.; Qaisar, N.; Ricciardi, A.; Sarwar, S.; Serdyouk, V.; Trasatti, L.; Volkov, A.; Zia, A.

1998-01-01

An array of 2424 2.6 m-long, 15 mm-diameter mylar straw tubes, arranged in two axial and four stereo layers, has been assembled. The array covers a cylindrical tracking surface of 18 m 2 and provides coordinate measurement in the drift direction and along the wire. An under-standing of the systematic effects which are introduced by gravitational sag and electrostatics, thus dominating the detector performance especially with long straws, allows to determine wire position from drift-time distribution. The correction has been applied to reach a space resolution of 40 μm with DME, 100 μm with Ar + C 2 H 6 , and 100-200 μm with CO 2 . Such a resolution is the best ever obtained for straws of these dimensions. A study of the gas leakage for the straw system has been performed, and results are reported. The array is being commissioned as a subdetector of the FINUDA spectrometer, and tracking performances are being studied with cosmic rays. (author)

Gastric cancer: the role of insulin-like growth factor 2 (IGF 2) and its receptors (IGF 1R and M6-P/IGF 2R).

Science.gov (United States)

Pavelić, Kresimir; Kolak, Toni; Kapitanović, Sanja; Radosević, Senka; Spaventi, Sime; Kruslin, Bozo; Pavelić, Jasminka

2003-11-01

Insulin-like growth factor 2 (IGF 2) appears to be involved in the progression of many tumours. It binds to at least two different types of receptor: IGF type 1 (IGF 1R) and mannose 6-phosphate/IGF type 2 (M6-P/IGF 2R). Ligand binding to IGF 1R provokes mitogenic and anti-apoptotic effects. M6-P/IGF 2R has a tumour suppressor function--it mediates IGF 2 degradation. Mutation of M6-P/IGF 2R causes both diminished growth suppression and augmented growth stimulation. The aim of this study was to investigate the role of IGF 2 and its receptors (IGF 1R and IGF 2R) in human gastric cancer. The expression of IGF 2 and its receptors was measured in order to analyse the possible correlation between the activity of these genes and cell proliferation in two different gastric tumour types: diffuse and intestinal. The effect of IGF 1 receptor blockage on cell proliferation and anchorage-independent cell growth was also examined. Increased expression of IGF 2 and IGF 1R genes (at the mRNA and protein level) was found in gastric cancer when compared with non-tumour tissue. Furthermore, there was a significant difference between IGF 2 expression in the more aggressive diffuse type and that in the intestinal type of gastric cancer. Moreover, the IGF 2 peptide level in the culture media obtained from the diffuse type of cancer cells was significantly higher when compared with the intestinal type. The level of IGF 2 peptide in the conditioned media strongly correlated with [3H]thymidine incorporation and cell proliferation. On the contrary, IGF 2R mRNA expression was much higher in the intestinal type of cancer than in the diffuse type. In addition, IGF 2R protein expression was substantially lower with progression of the diffuse cancer type to a higher stage. The alphaIR3 monoclonal antibody strongly inhibited [3H]thymidine incorporation and decreased the number of colonies in soft agar of cells overexpressing IGF 2. These findings suggest that members of the IGF family are involved

The Р60-S6K1 isoform of ribosomal protein S6 kinase 1 is a product of alternative mRNA translation

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I. V. Zaiets

2018-07-01

Full Text Available Ribosomal protein S6 kinase 1 (S6K1 is a well-known downstream effector of mTORC1 (mechanistic target of rapamycin complex 1 participating primarily in the regulation of cell growth and metabolism. Deregulation of mTOR/S6K1 signaling can promote numerous human pathologies, including cancer, neurodegeneration, cardiovascular disease, and metabolic disorders. As existing data suggest, the S6K1 gene encodes several protein isoforms, including p85-S6K1, p70-S6K1, and p60-S6K1. The two of these isoforms, p85-S6K1 and p70-S6K1, were extensively studied to date. The origin and functional significance of the p60-S6K1 isoform remains a mystery, however, it was suggested that the isoform could be a product of alternative S6K1 mRNA translation. Herein we report the generation of HEK-293 cells exclusively expressing p60-S6K1 as a result of CRISPR/Cas9-mediated inactivation of p85/p70-S6K1 translation. Moreover, the generated modified cells displayed the elevated level of p60-S6K1 expression compared to that in wild-type HEK-293 cells. Our data confirm an assumption that p60-S6K1 is alternatively translated, most probably, from the common for both p70- and p85-S6K1 mRNA transcript and reveal a link between p60-S6K1 expression and such cellular processes as cell proliferation and motility. In addition, our findings indicate that the p60-S6K1 isoform of S6K1 may undergo a mode of regulation distinct from p70- and p85-S6K1 due to the absence of mTOR-regulated p60-S6K1 phosphorylation at T389 that is important for S6K1 activation.

The monoclinic superstructure of the M2Pt6Al15 series (M=Ca, Sc, Y, La, Lu)

International Nuclear Information System (INIS)

Radzieowski, Mathis; Stegemann, Frank; Hoffmann, Rolf-Dieter; Janka, Oliver; Oldenburg Univ.

2017-01-01

The five ternary intermetallic compounds M 2 Pt 6 Al 15 (M=Ca, Sc, Y, La, Lu) were prepared from the elements by arc-melting. The crystal structure was determined via single crystal X-ray diffraction. The title compounds crystallize in a superstructure of the RE 0.67 Pt 2 Al 5 type structure (P6 3 /mmc) in the monoclinic crystal system with space group P12 1 /m1 (Sc 2 Pt 6 Al 15 : a=734.19(2), b=1628.96(10), c=734.19(2) pm, β=119.999(3) ; wR=0.0356, 3034 F 2 values, 68 variables). The superstructure can be derived by the superspace formalism using (3+2)D or (3+1)D interpretations of the diffraction data. The structural relation to the subcell structure is discussed on the basis of a group-subgroup scheme. In the crystal structure strongly bonded [Pt 2 Al 4 ] δ- slabs are alternatingly stacked with ordered layers containing M atoms and Al 3 triangles.

Thermoelectric properties of M{sub 2}Mo{sub 6}Se{sub 6} (M =Tl,In)

Energy Technology Data Exchange (ETDEWEB)

Verebelyi, D T; Payne, J E; Tessema, G X; Mengistu, E

1997-07-01

The authors have measured the thermal conductivity of Tl{sub 2}Mo{sub 6}Se{sub 6}, a quasi-one dimensional conductor which belongs to the family of M{sub 2}Mo{sub 6}X{sub 6} linear chain compounds. Using these results and the measurements of the Seebeck coefficient and the electrical conductivity the authors estimate the dimensionless figure of merit to be of the order of 0.08. This result suggest that this compound and other related compounds are good potential TE.

The singlet-triplet energy gap in divalent three, five and seven-membered cyclic C2H2M, C4H4M and C6H6M (M = C, Si, Ge, Sn AND Pb

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E. Vessally

2009-08-01

Full Text Available Total energy gaps, ∆Et–s, enthalpy gaps, ∆Ht–s, and Gibbs free energy gaps, ∆Gt–s, between singlet (s and triplet (t states were calculated for three, five and seven-membered cyclic C2H2M, C4H4M and C6H6M (M = C, Si, Ge, Sn and Pb at B3LYP/6-311++G**. The singlet-triplet free energy gaps, ∆Gt–s, for C2H2M (M = C, Si, Ge, Sn and Pb are found to be increased in the order: C2H2Si > C2H2C > C2H2Ge > C2H2Sn > C2H2Pb. The ∆Gt–s of C4H4M are found to be increased in the order: C4H4Pb > C4H4Sn > C4H4Ge > C4H4Si > C4H4C. Also, the ∆Gt–s of C6H6M are determined in the order: C6H6Pb > C6H6Ge ≥ C6H6Sn > C6H6Si > C6H6C. The most stable conformers of C2H2M, C4H4M and C6H6M are proposed for both the singlet and triplet states. Nuclear independent chemical shifts (NICS calculations were carried out for determination of aromatic character. The geometrical parameters are calculated and discussed.

Ground motion attenuation during M 7.1 Darfield and M 6.2 Christchurch, New Zealand, earthquakes and performance of global Ppedictive models

Science.gov (United States)

Segou, Margaret; Kalkan, Erol

2011-01-01

The M 7.1 Darfield earthquake occurred 40 km west of Christchurch (New Zealand) on 4 September 2010. Six months after, the city was struck again with an M 6.2 event on 22 February local time (21 February UTC). These events resulted in significant damage to infrastructure in the city and its suburbs. The purpose of this study is to evaluate the performance of global predictive models (GMPEs) using the strong motion data obtained from these two events to improve future seismic hazard assessment and building code provisions for the Canterbury region.The Canterbury region is located on the boundary between the Pacific and Australian plates; its surface expression is the active right lateral Alpine fault (Berryman et al. 1993). Beneath the North Island and the north South Island, the Pacific plate subducts obliquely under the Australian plate, while at the southwestern part of the South Island, a reverse process takes place. Although New Zealand has experienced several major earthquakes in the past as a result of its complex seismotectonic environment (e.g., M 7.1 1888 North Canterbury, M 7.0 1929 Arthur's Pass, and M 6.2 1995 Cass), there was no evidence of prior seismic activity in Christchurch and its surroundings before the September event. The Darfield and Christchurch earthquakes occurred along the previously unmapped Greendale fault in the Canterbury basin, which is covered by Quaternary alluvial deposits (Forsyth et al. 2008). In Figure 1, site conditions of the Canterbury epicentral area are depicted on a VS30 map. This map was determined on the basis of topographic slope calculated from a 1-km grid using the method of Allen and Wald (2007). Also shown are the locations of strong motion stations.The Darfield event was generated as a result of a complex rupture mechanism; the recordings and geodetic data reveal that earthquake consists of three sub-events (Barnhart et al. 2011, page 815 of this issue). The first event was due to rupturing of a blind reverse

N,N'-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1) suppresses the proliferation of PANC-1 pancreatic cancer cells via apoptosis and G2/M cell cycle arrest.

Science.gov (United States)

Chen, Su-Feng; Xia, Jun; Lv, Ya-Ping; Liu, Jin-Lin; Li, Wan-Xiang; Yu, Xi-Ping; Hu, Wei-Xiao; Zhou, Yong-Lie

2015-04-01

Pancreatic cancer is one of the human gastrointestinal malignancies with a high mortality and poor prognosis. Approximately eighty percent of patients are diagnosed with unresectable or metastatic disease. Thus, development of novel chemicals in the treatment of pancreatic cancer is imperative. This study aimed to investigate the anticancer effects of N,N'-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1), a new tetrazine derivative, on the PANC-1 pancreatic cancer cell line and clarify the underlying molecular mechanism. Using an MTT assay, we found that ZGDHu-1 significantly suppressed the proliferation of PANC-1 cells in a time- and dose-dependent manner. Moreover, according to the morphological and flow cytometric analysis, the results indicated that ZGDHu-1 induced PANC-1 cell apoptosis and G2/M cell cycle arrest in a dose-dependent manner. In the western blot analysis, expression of the pro-apoptotic Bax gene was upregulated while the anti-apoptotic Bcl-2 gene was downregulated following treatment with ZGDHu-1. ZGDHu-1 also activated pro-caspase-3 and PARP and increased the expression of NF-κB inhibitor IκB. Furthermore, the expression levels of G2/M regulatory molecules such as cyclin B1 and cdc2 were decreased while that of Chk1 was increased. These results suggested that ZGDHu-1 suppressed the proliferation of pancreatic cancer cells, rendering it a potential therapeutic drug for the treatment of pancreatic cancer.

Calculation of parity violating effects in the 62P/sub 1/2/-72P/sub 1/2/ forbidden M1 transition in thallium

International Nuclear Information System (INIS)

Neuffer, D.B.

1977-05-01

Calculations are presented of the E1 amplitude expected in forbidden M1 transitions of Tl and Cs if parity is violated in the neutral weak e-N interaction, as proposed in a number of gauge models, including that of Weinberg and Salam. Valence electron wave functions are generated as numerical solutions to the Dirac equation in a modified Tietz central potential. These wave functions are used to calculate allowed E1 transition rates, hfs splittings, and Stark E1 transition ampitudes. These results are compared with experiment and the agreement is generally good. The relativistic Tl 6 2 P/sub 1/2/-7 2 P/sub 1/2/ M1 transition amplitude M is also calculated, and corrections due to interconfiguration interaction, Breit interaction, and hfs mixing are included. The parity violating E1 amplitude E/sub PV/ is calculated and a value for the circular dichroism in the Weinberg model delta = -2.6 x 10 -3 is obtained. Parity violating effects in other Tl transitions are discussed. Contributions to the M1 amplitude for the forbidden Cs 6 2 S/sub 1/2/-7 2 S/sub 1/2/ and 6 2 S/sub 1/2/-8 2 S/sub 1/2/ transitions and to the Cs 6 2 S/sub 1/2/ g-factor anomaly from relativistic effects, Breit interaction, interconfiguration interaction, and hfs mixing are calculated, and it is found that this current theoretical description is not entirely adequate. The parity violating E1 amplitude E/sub PV/ for the 6S/sub 1/2/-7 2 S/sub 1/2/ and 6S/sub 1/2/-8 2 S/sub 1/2/ transitions is evaluated. With a measured value M/sub expt/ and the Weinberg value Q/sub W/ = -99, a circular dichroism delta = 1.64 x 10 -4 for the 6 2 S/sub 1/2/-7 2 S/sub 1/2/ transition is found

Annual carbon balance of a peatland 10 yr following restoration

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M. Strack

2013-05-01

Full Text Available Undisturbed peatlands represent long-term net sinks of carbon; however, peat extraction converts these systems into large and persistent sources of greenhouse gases. Although rewetting and restoration following peat extraction have taken place over the last several decades, very few studies have investigated the longer term impact of this restoration on peatland carbon balance. We determined the annual carbon balance of a former horticulturally-extracted peatland restored 10 yr prior to the study and compared these values to the carbon balance measured at neighboring unrestored and natural sites. Carbon dioxide (CO2 and methane (CH4 fluxes were measured using the chamber technique biweekly during the growing season from May to October 2010 and three times over the winter period. Dissolved organic carbon (DOC export was measured from remnant ditches in the unrestored and restored sites. During the growing season the restored site had greater uptake of CO2 than the natural site when photon flux density was greater than 1000 μmol m−2 s−1, while the unrestored site remained a source of CO2. Ecosystem respiration was similar between natural and restored sites, which were both significantly lower than the unrestored site. Methane flux remained low at the restored site except from open water pools, created as part of restoration, and remnant ditches. Export of DOC during the growing season was 5.0 and 28.8 g m−2 from the restored and unrestored sites, respectively. Due to dry conditions during the study year all sites acted as net carbon sources with annual balance of the natural, restored and unrestored sites of 250.7, 148.0 and 546.6 g C m−2, respectively. Although hydrological conditions and vegetation community at the restored site remained intermediate between natural and unrestored conditions, peatland restoration resulted in a large reduction in annual carbon loss from the system resulting in a carbon balance more similar to a natural

Cs_7Sm_1_1[TeO_3]_1_2Cl_1_6 and Rb_7Nd_1_1[TeO_3]_1_2Br_1_6, the new tellurite halides of the tetragonal Rb_6LiNd_1_1[SeO_3]_1_2Cl_1_6 structure type

International Nuclear Information System (INIS)

Charkin, Dmitri O.; Black, Cameron; Downie, Lewis J.; Sklovsky, Dmitry E.; Berdonosov, Peter S.; Olenev, Andrei V.; Zhou, Wuzong; Lightfoot, Philip; Dolgikh, Valery A.

2015-01-01

Two new rare-earth – alkali – tellurium oxide halides were synthesized by a salt flux technique and characterized by single-crystal X-ray diffraction. The structures of the new compounds Cs_7Sm_1_1[TeO_3]_1_2Cl_1_6 (I) and Rb_7Nd_1_1[TeO_3]_1_2Br_1_6 (II) (both tetragonal, space group I4/mcm) correspond to the sequence of [MLn_1_1(TeO_3)_1_2] and [M_6X_1_6] layers and bear very strong similarities to those of known selenite analogs. We discuss the trends in similarities and differences in compositions and structural details between the Se and Te compounds; more members of the family are predicted. - Graphical abstract: Two new rare-earth – alkali – tellurium oxide halides were predicted and synthesized. - Highlights: • Two new rare-earth – alkali – tellurium oxide halides were synthesized. • They adopt slab structure of rare earth-tellurium-oxygen and CsCl-like slabs. • The Br-based CsCl-like slabs have been observed first in this layered family.

Implication of Xenobiotic Metabolizing Enzyme gene (CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 Polymorphisms in Breast Carcinoma

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Gabbouj Sallouha

2008-04-01

Full Text Available Abstract Background Xenobiotic Metabolizing Enzymes (XMEs contribute to the detoxification of numerous cancer therapy-induced products. This study investigated the susceptibility and prognostic implications of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene polymorphisms in breast carcinoma patients. Methods The authors used polymerase chain reaction and restriction enzyme digestion to characterize the variation of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene in a total of 560 unrelated subjects (246 controls and 314 patients. Results The mEH (C/C mutant and the NAT2 slow acetylator genotypes were significantly associated with breast carcinoma risk (p = 0.02; p = 0.01, respectively. For NAT2 the association was more pronounced among postmenopausal patients (p = 0.006. A significant association was found between CYP2D6 (G/G wild type and breast carcinoma risk only in postmenopausal patients (p = 0.04. Association studies of genetic markers with the rates of breast carcinoma specific overall survival (OVS and the disease-free survival (DFS revealed among all breast carcinoma patients no association to DFS but significant differences in OVS only with the mEH gene polymorphisms (p = 0.02. In addition, the mEH wild genotype showed a significant association with decreased OVS in patients with axillary lymph node-negative patients (p = 0.03 and with decreasesd DFS in patients with axillary lymph node-positive patients (p = 0.001. However, the NAT2 intermediate acetylator genotype was associated with decreased DFS in axillary lymph node-negative patients. Conclusion The present study may prove that polymorphisms of some XME genes may predict the onset of breast carcinoma as well as survival after treatment.

M2 macrophages coexist with a Th1-driven profile in periapical cysts.

Science.gov (United States)

Ribeiro, C M; de Carli, M L; Nonogaki, S; Nogueira, D A; Pereira, A A C; Sperandio, F F; Hanemann, J A C

2018-02-01

To evaluate the participation of both Th1 and Th2 responses in periapical cysts by assessing the presence of M2 macrophages, as well as acute IL-1 β, TNF-α and IL-6 cytokines. Twenty-four cases of periapical cysts were selected. Immuno-expressions of IL-1 β, IL-6, TNF-α and CD163 were analysed in the cystic capsules in both superficial and deeper regions. Data were analysed with paired Wilcoxon test and Spearman correlation coefficient (P ≤ 0.05). There was a higher expression of IL-1β, IL-6, TNF-α and M2 macrophages in the superficial region (P periapical cysts and correlated with the expression of certain acute Th1-related cytokines. This illustrates the coexistence of an acute and chronic Th2-driven immune response in these lesions. Although M2 macrophages favour the healing process, their presence is not sufficient for periapical cyst regression, once an acute active response has occurred due to an infectious stimuli. © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver.

Science.gov (United States)

Nagashima, Kazuki; Sawa, Shinichiro; Nitta, Takeshi; Prados, Alejandro; Koliaraki, Vasiliki; Kollias, George; Nakashima, Tomoki; Takayanagi, Hiroshi

2017-11-04

The gut-associated lymphoid tissues (GALTs), including Peyer's patches (PPs), cryptopatches (CPs) and isolated lymphoid follicles (ILFs), establish a host-microbe symbiosis by the promotion of immune reactions against gut microbes. Microfold cell inducer (MCi) cells in GALTs are the recently identified mesenchymal cells that express the cytokine RANKL and initiate bacteria-specific immunoglobulin A (IgA) production via induction of microfold (M) cell differentiation. In the previous study, the Twist2-Cre driver was utilized for gene deletion in mesenchymal cells including MCi cells. In order to investigate MCi cells more extensively, it will be necessary to develop experimental tools in addition to the Twist2-Cre driver mice and characterize such drivers in specificity and efficiency. Here we show that M cell differentiation and IgA production are impaired in the targeted deletion of RANKL by the Col6a1-Cre driver. We compared Col6a1-Cre with Twist2-Cre in terms of the specificity for mesenchymal cells in GALTs. Col6a1-Cre CAG-CAT-EGFP mice exhibited EGFP expression in podoplanin + CD31 - cells including MCi cells, while Twist2-Cre mice were shown to target endothelial cells and podoplanin + CD31 - cells. Tnfsf11 fl/Δ Col6a1-Cre mice exhibited the absence of M cells and severe IgA reduction together with an alteration in gut microbial composition. Moreover, we analyzed germ free mice to test whether changes in the microbiota are the cause of M cell deficiency. M cell differentiation was normal in the CPs/ILFs of germ free mice, indicating that MCi cells induce M cells independently of microbial colonization. This study demonstrates that Col6a1-Cre driver mice are as useful as Twist2-Cre driver mice for functional analyses of GALT-resident mesenchymal cells, including MCi cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis and reactivity towards diiodine of palladium(II) and platinum(II) complexes with non-cyclic and cyclic ligands (C6H3{CH=NR1R2}2-2,6)-. End-on diiodine-platinum(II) bonding in macrocyclic [PtI(C6H3{CH2NMe(CH2)7MeNCH2}-2,6)(h1-I2)

NARCIS (Netherlands)

Koten, G. van; Beek, J.A.M. van; Dekker, G.P.C.M.; Wissing, E.; Zoutberg, M.C.; Stam, C.H.

1990-01-01

Several new organo-platinum(II) and -palladium(II) complexes [MX(C{6}H{3}{CH{2}NR}1{R}2{}{2}-2, 6)] (X = halide, M = Pt, Pd; R}1{ = R}2{ = Et; R}2{ = Me, R}1{ = }t{Bu, M = Pt: R}2{ = Me, R}1{ = Ph) have been synthesized from [PtCl{2}(SEt{2}){2}] or [PdCl{2}(COD)] (COD = 1, 5-cyclooctadiene) by

Specific heat and thermodynamic functions of uranovanadates of the M2+(VUO6)2 · nH2O series (M2+ = Mg, Ca, Sr, Ba, Pb)

International Nuclear Information System (INIS)

Karyakin, N.V.; Chernorukov, N.G.; Sulejmanov, E.V.; Trostin, V.L.; Alimzhanov, M.I.; Razuvaeva, E.A.

1999-01-01

Isobaric specific heat of crystal uranovanadates Ca(VUO 6 ) 2 · 8H 2 O, Ba(VUO 6 ) 2 · 4H 2 O in the temperature range of 10 - 300 K and of M 1 (VUO 6 ) 2 · 5H 2 O, (M 1 = Mg, Ca, Sr, Pb) at 80 -300 K are measured by the method of adiabatic vacuum calorimetry. The functions H 0 (T) - H 0 (0), S 0 (T), G 0 (T) - H 0 (T) for all the above-mentioned compounds in the range of 0 - 300 K have been calculated, the standard entropies and Gibbs functions of uranovanadates formation at 298.15 K being calculated as well [ru

Identification of 6H1 as a P2Y purinoceptor: P2Y5.

Science.gov (United States)

Webb, T E; Kaplan, M G; Barnard, E A

1996-02-06

We have determined the identity of the orphan G-protein coupled receptor cDNA, 6H1, present in activated chicken T cells, as a subtype of P2Y purinoceptor. This identification is based on first on the degree of sequence identity shared with recently cloned members of the P2Y receptor family and second on the pharmacological profile. Upon transient expression in COS-7 cells the 6H1 receptor bound the radiolabel [35S]dATP alpha S specifically and with high affinity (Kd, 10 nM). This specific binding could be competitively displaced by a range of ligands active at P2 purinoceptors, with ATP being the most active (K (i)), 116 nM). Such competition studies have established the following rank order of activity: ATP ADP 2-methylthioATP alpha, beta-methylene ATP, UTP, thus confirming 6H1 as a member of the growing family of P2Y purinoceptors. As the fifth receptor of this type to be identified we suggest that it be named P2Y5.

Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization1

Science.gov (United States)

Dale, Matthew A; Xiong, Wanfen; Carson, Jeffrey S; Suh, Melissa K; Karpisek, Andrew D.; Meisinger, Trevor M.; Casale, George P.; Baxter, B. Timothy

2016-01-01

Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Damage to elastin in the ECM results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Pro-inflammatory M1 macrophages initially are recruited to sites of injury but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. AAA tissue reveals a high M1/M2 ratio where pro-inflammatory cells and their associated markers dominate. In the present study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57Bl/6 mice, antibody-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and pro-inflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2 polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a pro-inflammatory environment in aortic tissue by inducing M1 polarization and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m6A/MYC/CEBPA Signaling.

Science.gov (United States)

Su, Rui; Dong, Lei; Li, Chenying; Nachtergaele, Sigrid; Wunderlich, Mark; Qing, Ying; Deng, Xiaolan; Wang, Yungui; Weng, Xiaocheng; Hu, Chao; Yu, Mengxia; Skibbe, Jennifer; Dai, Qing; Zou, Dongling; Wu, Tong; Yu, Kangkang; Weng, Hengyou; Huang, Huilin; Ferchen, Kyle; Qin, Xi; Zhang, Bin; Qi, Jun; Sasaki, Atsuo T; Plas, David R; Bradner, James E; Wei, Minjie; Marcucci, Guido; Jiang, Xi; Mulloy, James C; Jin, Jie; He, Chuan; Chen, Jianjun

2018-01-11

R-2-hydroxyglutarate (R-2HG), produced at high levels by mutant isocitrate dehydrogenase 1/2 (IDH1/2) enzymes, was reported as an oncometabolite. We show here that R-2HG also exerts a broad anti-leukemic activity in vitro and in vivo by inhibiting leukemia cell proliferation/viability and by promoting cell-cycle arrest and apoptosis. Mechanistically, R-2HG inhibits fat mass and obesity-associated protein (FTO) activity, thereby increasing global N 6 -methyladenosine (m 6 A) RNA modification in R-2HG-sensitive leukemia cells, which in turn decreases the stability of MYC/CEBPA transcripts, leading to the suppression of relevant pathways. Ectopically expressed mutant IDH1 and S-2HG recapitulate the effects of R-2HG. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. Collectively, while R-2HG accumulated in IDH1/2 mutant cancers contributes to cancer initiation, our work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m 6 A/MYC/CEBPA signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

Selective mGAT2 (BGT-1) GABA Uptake Inhibitor

DEFF Research Database (Denmark)

Vogensen, Stine Byskov; Jørgensen, Lars; Madsen, Karsten Kirkegaard

2013-01-01

β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1−4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compou...... 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors....

Leptin Stimulates Prolactin mRNA Expression in the Goldfish Pituitary through a Combination of the PI3K/Akt/mTOR, MKK3/6/p38MAPK and MEK1/2/ERK1/2 Signalling Pathways.

Science.gov (United States)

Yan, Aifen; Chen, Yanfeng; Chen, Shuang; Li, Shuisheng; Zhang, Yong; Jia, Jirong; Yu, Hui; Liu, Lian; Liu, Fang; Hu, Chaoqun; Tang, Dongsheng; Chen, Ting

2017-12-20

Leptin actions at the pituitary level have been extensively investigated in mammalian species, but remain insufficiently characterized in lower vertebrates, especially in teleost fish. Prolactin (PRL) is a pituitary hormone of central importance to osmoregulation in fish. Using goldfish as a model, we examined the global and brain-pituitary distribution of a leptin receptor (lepR) and examined the relationship between expression of lepR and major pituitary hormones in different pituitary regions. The effects of recombinant goldfish leptin-AI and leptin-AII on PRL mRNA expression in the pituitary were further analysed, and the mechanisms underlying signal transduction for leptin-induced PRL expression were determined by pharmacological approaches. Our results showed that goldfish lepR is abundantly expressed in the brain-pituitary regions, with highly overlapping PRL transcripts within the pituitary. Recombinant goldfish leptin-AI and leptin-AII proteins could stimulate PRL mRNA expression in dose- and time-dependent manners in the goldfish pituitary, by both intraperitoneal injection and primary cell incubation approaches. Moreover, the PI3K/Akt/mTOR, MKK 3/6 /p 38 MAPK, and MEK 1/2 /ERK 1/2 -but not JAK2/STAT 1, 3 and 5 cascades-were involved in leptin-induced PRL mRNA expression in the goldfish pituitary.

mPGES-1-derived PGE2 mediates dehydration natriuresis

Science.gov (United States)

Jia, Zhanjun; Liu, Gang; Sun, Ying; Kakizoe, Yutaka; Guan, Guangju; Zhang, Aihua; Zhou, Shu-Feng

2013-01-01

PGE2 is a natriuretic factor whose production is elevated after water deprivation (WD) but its role in dehydration natriuresis is not well-defined. The goal of the present study was to investigate the role of microsomal prostaglandin E synthase-1 (mPGES-1) in dehydration natriuresis. After 24-h WD, wild-type (WT) mice exhibited a significant increase in 24-h urinary Na+ excretion accompanied with normal plasma Na+ concentration and osmolality. In contrast, WD-induced elevation of urinary Na+ excretion was completely abolished in mPGES-1 knockout (KO) mice in parallel with increased plasma Na+ concentration and a trend increase in plasma osmolality. WD induced a 1.8-fold increase in urinary PGE2 output and a 1.6-fold increase in PGE2 content in the renal medulla of WT mice, both of which were completely abolished by mPGES-1 deletion. Similar patterns of changes were observed for urinary nitrate/nitrite and cGMP. The natriuresis in dehydrated WT mice was associated with a significant downregulation of renal medullary epithelial Na channel-α mRNA and protein, contrasting to unaltered expressions in dehydrated KO mice. By quantitative RT-PCR, WD increased the endothelial nitric oxide synthase (eNOS), inducible NOS, and neuronal NOS expressions in the renal medulla of WT mice by 3.9-, 1.48-, and 2.6-fold, respectively, all of which were significantly blocked in mPGES-1 KO mice. The regulation of eNOS expression was further confirmed by immunoblotting. Taken together, our results suggest that mPGES-1-derived PGE2 contributes to dehydration natriuresis likely via NO/cGMP. PMID:23171554

Study of the structural and thermal stability of Li0.3Co2/3Ni1/6Mn1/6O2

International Nuclear Information System (INIS)

Mahmoud, Abdelfattah; Saadoune, Ismael; Difi, Siham; Sougrati, Moulay Tahar; Lippens, Pierre-Emmanuel; Amarilla, José Manuel

2014-01-01

Thermal and structural stabilities of the delithiated positive electrode material Li x Co 2/3 Ni 1/6 Mn 1/6 O 2 were studied by X-ray diffraction, magnetic and thermogravimetric analysis. In the opposite to the classical electrode materials LiNiO 2 and LiCoO 2 , the structural symmetry (S.G. R-3 m) of the starting material LiCo 2/3 Ni 1/6 Mn 1/6 O 2 is preserved during the electrochemical cycling with a small variation of the unit cell parameters. Squid measurements evidenced that practically no Ni 2+ ions were present in the lithium slab even after the lithium extraction process. For the thermal stability, the highly oxidized phase Li 0.3 Co 2/3 Ni 1/6 Mn 1/6 O 2 was tested. This delithiated phase undergoes only 5.16% weight loss after heating up to 600 °C. This weight loss has no effect on the structure symmetry as the starting α-NaFeO 2 type structure was preserved during the thermal treatment. The obtained results coupled to the excellent electrochemical features of LiCo 2/3 Ni 1/6 Mn 1/6 O 2 clearly showits ability to compete with the commercialized cathode materials

Resveratrol regulates microglia M1/M2 polarization via PGC-1α in conditions of neuroinflammatory injury.

Science.gov (United States)

Yang, Xiaodong; Xu, Shaoqing; Qian, Yiwei; Xiao, Qin

2017-08-01

Microglia are the primary cells that exert immune function in the central nervous system (CNS), and accumulating evidence suggests that microglia act as key players in the initiation of neurodegenerative diseases. It is now well recognized that microglia have functional plasticity and dual phenotypes, proinflammatory M1 and anti-inflammatory M2 phenotypes. Inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for the treatment of neuroinflammation-related diseases. Resveratrol has been demonstrated to exert anti-inflammatory effects by suppressing M1 microglia activation. However, the role of resveratrol in regulating microglia polarization and the molecular mechanisms involved have not been fully clarified. In this study, we tested whether resveratrol could suppress microglia activation by promoting microglia polarization toward the M2 phenotype via PGC-1α by measuring M1 and M2 markers in vitro and in vivo. Our study demonstrated that resveratrol reduced inflammatory damage and promoted microglia polarization to the M2 phenotype in LPS-induced neuroinflammation. In addition, resveratrol ameliorated LPS-induced sickness behavior in mice. The promoting effects of resveratrol on M2 polarization were attenuated by knocking down PGC-1α. PGC-1α not only suppressed LPS-evoked M1 marker expression by inhibition of NF-κB activity but also increased M2 marker expression by coactivation of the STAT6 and STAT3 pathways. We propose that overexpression PGC-1α by resveratrol could be a potential therapeutic approach to suppress neuroinflammation by regulating microglia polarization. Copyright © 2017 Elsevier Inc. All rights reserved.

Revealing the effect of 6-gingerol, 6-shogaol and curcumin on mPGES-1, GSK-3β and β-catenin pathway in A549 cell line.

Science.gov (United States)

Eren, Demirpolat; Betul, Yerer Mukerrem

2016-10-25

In our study, anticancer effects of 6-gingerol, 6-shogaol from ginger and curcumin from turmeric were investigated and the results were compared with each other. We aimed to reveal their effects on microsomal prostaglandine E2 synthase 1 (mPGES-1) which is related with cancer progression and inflammation as well as β-catenin and glycogen synthase kinase 3β (GSK-3β) that are the main components of Wnt/GSK3 pathway. As it is known activation of GSK-3β and high levels of mPGES-1 pathway leads to cell proliferation and aggravates cancer progression. Therefore both of them are potential targets for cancer therapy. 6-shogaol and 6-gingerol' s effect on this pathway is not known very well up to now while curcumin that is known as an mPGES-1 inhibitor has anticancer properties via this pathway and many other pathways. Besides being in Zingiberaceae family, ginger's 6-gingerol and 6-shogaol have a molecular similarity with turmeric's curcumin. In our study we investigated their effects using a popular non small lung cancer cell line named A549 which expresses mPGES-1 and has active GSK3β pathway. IL-1β was used for inducing mPGES-1 and enabling the cancer characteristics such as cell proliferation. So compounds that inactivates or decreases the level of these components might be potential anticancer agents. A549 cells were incubated with interleukin 1β (IL-1β) for 24 h in order to maintain mPGES-1 enzyme induction. Experiments were performed both on IL-1β and non-IL-1β group. Real time cell analysis was performed to determine the cytotoxicity. Samples for western blotting and RT-PCR were collected after 24 h incubation with compounds to determine the amount of mPGES-1, GSK-3β, p-GSK-3β, β-catenin protein and mRNA. PGE2 which is the end product of mPGES-1 was measured by using ELISA kit. As a result of cell profile assay, cells exposed to IL-1β proliferate faster than non-IL-1β ones. This shows that induced mPGES-1 might play a role through GSK3β pathway

m6A-Driver: Identifying Context-Specific mRNA m6A Methylation-Driven Gene Interaction Networks

OpenAIRE

Zhang, Song-Yao; Zhang, Shao-Wu; Liu, Lian; Meng, Jia; Huang, Yufei

2016-01-01

As the most prevalent mammalian mRNA epigenetic modification, N6-methyladenosine (m6A) has been shown to possess important post-transcriptional regulatory functions. However, the regulatory mechanisms and functional circuits of m6A are still largely elusive. To help unveil the regulatory circuitry mediated by mRNA m6A methylation, we develop here m6A-Driver, an algorithm for predicting m6A-driven genes and associated networks, whose functional interactions are likely to be actively modulated ...

The Armys M-1 Abrams, M-2/M-3 Bradley, and M-1126 Stryker: Background and Issues for Congress

Science.gov (United States)

2016-04-05

the Army John McHugh , urging instead the limited production of 70 M-1A2SEPv2 tanks per year from FY2013 to FY2017. 32 Congress subsequently decided...House Members sent a letter to Secretary of the Army McHugh expressing concern over the Army’s failure to fund production of the M-1A2. Congress...John McHugh by Rep. Sander Levin and Rep. Mike Rogers, May 6, 2011. 33 See CRS Reports: CRS Report R43323, Defense: FY2014 Authorization and

Probing the electronic properties of ternary A n M3n-1B2n (n = 1: A = Ca, Sr; M = Rh, Ir and n = 3: A = Ca, Sr; M = Rh) phases: observation of superconductivity.

Science.gov (United States)

Takeya, Hiroyuki; ElMassalami, Mohammed; Terrazos, Luis A; Rapp, Raul E; Capaz, Rodrigo B; Fujii, Hiroki; Takano, Yoshihiko; Doerr, Mathias; Granovsky, Sergey A

2013-06-01

We follow the evolution of the electronic properties of the titled homologous series when n as well as the atomic type of A and M are varied where for n = 1, A = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal structure of n = 1 members is known to be CaRh 2 B 2 -type ( Fddd ), while that of n = 3 is Ca 3 Rh 8 B 6 -type ( Fmmm ); the latter can be visualized as a stacking of structural fragments from AM 3 B 2 ( P 6/ mmm ) and AM 2 B 2 . The metallic properties of the n = 1 and 3 members are distinctly different: on the one hand, the n = 1 members are characterized by a linear coefficient of the electronic specific heat γ ≈ 3 mJ mol -1 K -2 , a Debye temperature θ D ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe. The n = 3 family, on the other hand, exhibits γ ≈ 18 mJ mol -1 K -2 , θ D ≈ 330 K, a weak linear magnetoresistivity and an onset of superconductivity (for Ca 3 Rh 8 B 6 , T c = 4.0 K and H c2 = 14.5 kOe, while for Sr 3 Rh 8 B 6 , T c = 3.4 K and H c2 ≈ 4.0 kOe). These remarkable differences are consistent with the findings of the electronic band structures and density of state (DOS) calculations. In particular, satisfactory agreement between the measured and calculated γ was obtained. Furthermore, the Fermi level, E F , of Ca 3 Rh 8 B 6 lies at almost the top of a pronounced local DOS peak, while that of CaRh 2 B 2 lies at a local valley: this is the main reason behind the differences between the, e.g., superconducting properties. Finally, although all atoms contribute to the DOS at E F , the contribution of the Rh atoms is the strongest.

A study of magnetoplumbite-type (M-type) cobalt-titanium-substituted barium ferrite, BaCoxTixFe12-2xO19 (x = 1-6)

International Nuclear Information System (INIS)

Teh, G.B.; Saravanan, N.; Jefferson, D.A.

2007-01-01

Cobalt(II)-titanium(IV)-substituted barium ferrite forming the chemical formula of BaCo x Ti x Fe 12-2x O 19 (x = 1-6) have been investigated using X-ray diffraction spectroscopy (XRD), Superconducting Quantum Interference Device (SQUID) and high-resolution transmission electron microscopy (HRTEM). The specimen of magnetoplumbite (M-type) Co-Ti-substituted BaFe 12 O 19 were synthesised via sol-gel method using ethylene glycol as precursor. Significant increase in line broadening of the XRD patterns were observed indicating the decrease of particle sizes due to the Co(II)-Ti(IV) substitution. BaCo 3 Ti 3 Fe 6 O 19 showed the highest coercivity but moderate saturation and remnant magnetisations. HRTEM imaging showed that Co(II)-Ti(IV) substitution in the system of BaCo x Ti x Fe 12-2x O 19 (x = 1-6) produced no drastic change in the structure of the M-type ferrites. Most of the M-types crystals examined by HRTEM displayed a long axis perpendicular to the c-axis of the M-type structure. Disordered crystals showing the intergrowth between Co-Ti-substituted barium ferrite and the spinel-structured iron oxide were detected

E2F1 regulates cellular growth by mTORC1 signaling.

Directory of Open Access Journals (Sweden)

Sebastian Real

2011-01-01

Full Text Available During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.

Platinum complexes of 5,6-Dihydroacenaphtho[5,6-cd]-1,2-dichalcogenoles

OpenAIRE

Benson, Callum G. M.; Schofield, Catherine M.; Randall, Rebecca A. M.; Wakefield, Lucy; Knight, Fergus R.; Slawin, Alexandra M. Z.; Woollins, J. Derek

2013-01-01

Six bis(phosphane) platinum complexes bearing dichalcogen acenaphthene ligands have been prepared by metathesis from cis-[PtCl2(PR3)(2)] (R-3 = Ph-3, Ph2Me, PhMe2) and the dilithium salts of the parent 5,6-dihydroacenaphtho[5,6-cd]-1,2-dichalcogenoles (AcenapE(2), L1 E = S, L2 E = Se). For their synthesis, the appropriate disulfide or diselenide species was treated with super hydride [LiBEt3H] to afford the dilithium salt by in situ reduction of the AcenapE(2) E-E bond. Further reaction, by m...

m6A level and isoform characterization sequencing (m6A-LAIC-seq) reveals the census and complexity of the m6A epitranscriptome

OpenAIRE

Molinie, Benoit; Wang, Jinkai; Lim, Kok-Seong; Hillebrand, Roman; Lu, Zhi-xiang; Van Wittenberghe, Nicholas; Howard, Benjamin D.; Daneshvar, Kaveh; Mullen, Alan C.; Dedon, Peter; Xing, Yi; Giallourakis, Cosmas C.

2016-01-01

N6-Methyladenosine (m6A) is a widespread, reversible chemical modification of RNA molecules, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m6A modified (‘m6A levels’) or the relationship of m6A modification(s) to alternative RNA isoforms. To deconvolute the m6A epitranscriptome, we developed m6A-level and isoform-characterization sequencing (m6A-LAIC-seq). We found that cells exhibit a broad...

Dual mTORC1/C2 inhibitors suppress cellular geroconversion (a senescence program).

Science.gov (United States)

Leontieva, Olga V; Demidenko, Zoya N; Blagosklonny, Mikhail V

2015-09-15

In proliferating cells, mTOR is active and promotes cell growth. When the cell cycle is arrested, then mTOR converts reversible arrest to senescence (geroconversion). Rapamycin and other rapalogs suppress geroconversion, maintaining quiescence instead. Here we showed that ATP-competitive kinase inhibitors (Torin1 and PP242), which inhibit both mTORC1 and TORC2, also suppressed geroconversion. Despite inhibition of proliferation (in proliferating cells), mTOR inhibitors preserved re-proliferative potential (RP) in arrested cells. In p21-arrested cells, Torin 1 and PP242 detectably suppressed geroconversion at concentrations as low as 1-3 nM and 10-30 nM, reaching maximal gerosuppression at 30 nM and 300 nM, respectively. Near-maximal gerosuppression coincided with inhibition of p-S6K(T389) and p-S6(S235/236). Dual mTOR inhibitors prevented senescent morphology and hypertrophy. Our study warrants investigation into whether low doses of dual mTOR inhibitors will prolong animal life span and delay age-related diseases. A new class of potential anti-aging drugs can be envisioned.

Two hexagonal series of lanthanoid(III) oxide fluoride selenides.: M{sub 6}O{sub 2}F{sub 8}Se{sub 3} (M = La - Nd) and M{sub 2}OF{sub 2}Se (M = Nd, Sm, Gd - Ho)

Energy Technology Data Exchange (ETDEWEB)

Zimmermann, Dirk D.; Grossholz, Hagen; Wolf, Sarah; Schleid, Thomas [Institut fuer Anorganische Chemie, Universitaet Stuttgart (Germany); Janka, Oliver [Institut fuer Anorganische Chemie, Universitaet Stuttgart (Germany); Institut fuer Anorganische und Analytische Chemie, Westfaelische Wilhelms-Universitaet Muenster (Germany); Mueller, Alexander C. [Institut fuer Anorganische Chemie, Universitaet Stuttgart (Germany); Institut fuer Textilchemie und Chemiefasern, Denkendorf (Germany)

2015-09-15

Two hexagonal series of lanthanoid(III) oxide fluoride selenides with similar structure types can be obtained by the reaction of the components MF{sub 3}, M{sub 2}O{sub 3}, M, and Se in sealed niobium tubes at 850 C using CsI as fluxing agent. The compounds with the lighter and larger representatives (M = La - Nd) occur with the formula M{sub 6}O{sub 2}F{sub 8}Se{sub 3}, whereas with the heavier and smaller ones (M = Nd, Sm, Gd - Ho) their composition is M{sub 2}OF{sub 2}Se. For both systems single-crystal determinations were used in all cases. The compounds crystallize in the hexagonal crystal system (space group: P6{sub 3}/m) with lattice parameters of a = 1394-1331 pm and c = 403-372 pm (Z = 2 for M{sub 6}O{sub 2}F{sub 8}Se{sub 3} and Z = 6 for M{sub 2}OF{sub 2}Se). The (M1){sup 3+} cations show different square antiprismatic coordination spheres with or without an extra capping fluoride anion. All (M2){sup 3+} cations exhibit a ninefold coordination environment shaped as tricapped trigonal prism. In both structure types the Se{sup 2-} anions are sixfold coordinated as trigonal prisms of M{sup 3+} cations, being first condensed by edges to generate trimeric units and then via faces to form strands running along [001]. The light anions reside either in threefold triangular or in fourfold tetrahedral cationic coordination. For charge compensation, both structures have to contain a certain amount of oxide besides fluoride anions. Since F{sup -} and O{sup 2-} can not be distinguished by X-ray diffraction, bond-valence calculations were used to address the problem of their adjunction to the available crystallographic sites. (Copyright copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

m6ASNP: a tool for annotating genetic variants by m6A function.

Science.gov (United States)

Jiang, Shuai; Xie, Yubin; He, Zhihao; Zhang, Ya; Zhao, Yuli; Chen, Li; Zheng, Yueyuan; Miao, Yanyan; Zuo, Zhixiang; Ren, Jian

2018-04-02

Large-scale genome sequencing projects have identified many genetic variants for diverse diseases. A major goal of these projects is to characterize these genetic variants to provide insight into their function and roles in diseases. N6-methyladenosine (m6A) is one of the most abundant RNA modifications in eukaryotes. Recent studies have revealed that aberrant m6A modifications are involved in many diseases. In this study, we present a user-friendly web server called "m6ASNP" that is dedicated to the identification of genetic variants targeting m6A modification sites. A random forest model was implemented in m6ASNP to predict whether the methylation status of a m6A site is altered by the variants surrounding the site. In m6ASNP, genetic variants in a standard VCF format are accepted as the input data, and the output includes an interactive table containing the genetic variants annotated by m6A function. In addition, statistical diagrams and a genome browser are provided to visualize the characteristics and annotate the genetic variants. We believe that m6ASNP is a highly convenient tool that can be used to boost further functional studies investigating genetic variants. The web server "m6ASNP" is implemented in JAVA and PHP and is freely available at http://m6asnp.renlab.org.

Structure and expression of MHC class Ib genes of the central M region in rat and mouse: M4, M5, and M6.

Science.gov (United States)

Lambracht-Washington, Doris; Moore, Yuki F; Wonigeit, Kurt; Lindahl, Kirsten Fischer

2008-04-01

The M region at the telomeric end of the murine major histocompatibility complex (MHC) contains class I genes that are highly conserved in rat and mouse. We have sequenced a cosmid clone of the LEW rat strain (RT1 haplotype) containing three class I genes, RT1.M6-1, RT1.M4, and RT1.M5. The sequences of allelic genes of the BN strain (RT1n haplotype) were obtained either from cDNAs or genomic clones. For the coding parts of the genes few differences were found between the two RT1 haplotypes. In LEW, however, only RT1.M5 and RT1.M6 have open reading frames; whereas in BN all three genes were intact. In line with the findings in BN, transcription was found for all three rat genes in several tissues from strain Sprague Dawley. Protein expression in transfectants could be demonstrated for RT1.M6-1 using the monoclonal antibody OX18. By sequencing of transcripts obtained by RT-PCR, a second, transcribed M6 gene, RT1.M6-2, was discovered, which maps next to RT1.M6-1 outside of the region covered by the cosmid. In addition, alternatively spliced forms for RT1.M5 and RT1.M6 were detected. Of the orthologous mouse genes, H2-M4, H2-M5, and H2-M6, only H2-M5 has an open reading frame. Other important differences between the corresponding parts of the M region of the two species are insertion of long LINE repeats, duplication of RT1.M6, and the inversion of RT1.M5 in the rat. This demonstrates substantial evolutionary dynamics in this region despite conservation of the class I gene sequences themselves.

The human papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis.

Science.gov (United States)

Spangle, Jennifer M; Münger, Karl

2010-09-01

The mammalian target of rapamycin (mTOR) kinase acts as a cellular rheostat that integrates signals from a variety of cellular signal transduction pathways that sense growth factor and nutrient availability as well as intracellular energy status. It was previously reported that the human papillomavirus type 16 (HPV16) E6 oncoprotein may activate the S6 protein kinase (S6K) through binding and E6AP-mediated degradation of the mTOR inhibitor tuberous sclerosis complex 2 (TSC2) (Z. Lu, X. Hu, Y. Li, L. Zheng, Y. Zhou, H. Jiang, T. Ning, Z. Basang, C. Zhang, and Y. Ke, J. Biol. Chem. 279:35664-35670, 2004; L. Zheng, H. Ding, Z. Lu, Y. Li, Y. Pan, T. Ning, and Y. Ke, Genes Cells 13:285-294, 2008). Our results confirmed that HPV16 E6 expression causes an increase in mTORC1 activity through enhanced phosphorylation of mTOR and activation of downstream signaling pathways S6K and eukaryotic initiation factor binding protein 1 (4E-BP1). However, we did not detect a decrease in TSC2 levels in HPV16 E6-expressing cells. We discovered, however, that HPV16 E6 expression causes AKT activation through the upstream kinases PDK1 and mTORC2 under conditions of nutrient deprivation. We show that HPV16 E6 expression causes an increase in protein synthesis by enhancing translation initiation complex assembly at the 5' mRNA cap and an increase in cap-dependent translation. The increase in cap-dependent translation likely results from HPV16 E6-induced AKT/mTORC1 activation, as the assembly of the translation initiation complex and cap-dependent translation are rapamycin sensitive. Lastly, coexpression of the HPV16 E6 and E7 oncoproteins does not affect HPV16 E6-induced activation of mTORC1 and cap-dependent translation. HPV16 E6-mediated activation of mTORC1 signaling and cap-dependent translation may be a mechanism to promote viral replication under conditions of limited nutrient supply in differentiated, HPV oncoprotein-expressing proliferating cells.

Studies on solid solutions based on layered honeycomb-ordered phases P2-Na{sub 2}M{sub 2}TeO{sub 6} (M=Co, Ni, Zn)

Energy Technology Data Exchange (ETDEWEB)

Berthelot, Romain; Schmidt, Whitney; Sleight, A.W. [Department of Chemistry, Oregon State University, Corvallis, OR 97331 (United States); Subramanian, M.A., E-mail: mas.subramanian@oregonstate.edu [Department of Chemistry, Oregon State University, Corvallis, OR 97331 (United States)

2012-12-15

Three complete solid solutions between the layered phases P2-Na{sub 2}M{sub 2}TeO{sub 6} (M=Co, Ni, Zn) have been prepared by conventional solid state method and investigated through X-ray diffraction, magnetism and optical measurements. All compositions are characterized by a M{sup 2+}/X{sup 6+} honeycomb ordering within the slabs and crystallize in a hexagonal unit cell. However, a structural transition based on a different stacking is observed as nickel (space group P6{sub 3}/mcm) is substituted by zinc or cobalt (space group P6{sub 3}22). All compositions exhibit a paramagnetic Curie-Weiss behavior at high temperatures; and the magnetic moment values confirm the presence of Ni{sup 2+} and/or Co{sup 2+} cations. The low-temperature antiferromagnetic order of Na{sub 2}Ni{sub 2}TeO{sub 6} and Na{sub 2}Co{sub 2}TeO{sub 6} is suppressed by zinc substitution. The color of the obtained compositions varies from pink, to light green and white when M=Co, Ni, Zn, respectively. - Graphical abstract: The comparison between the structure of Na{sub 2}Ni{sub 2}TeO{sub 6} (left) and Na{sub 2}M{sub 2}TeO{sub 6} (M=Co, Zn) (right) evidences the stacking difference with distinct atom sequences along the hexagonal c-axis. Highlights: Black-Right-Pointing-Pointer Solid solutions between lamellar phases Na{sub 2}M{sub 2}TeO{sub 6} (M=Co, Ni, Zn) are investigated. Black-Right-Pointing-Pointer A M{sup 2+}/X{sup 6+} honeycomb ordering characterized all the compositions. Black-Right-Pointing-Pointer A structural transition is shown when Ni is replaced by Co or Zn. Black-Right-Pointing-Pointer The low-temperature AFM ordering of Na{sub 2}Ni{sub 2}TeO{sub 6} and Na{sub 2}Co{sub 2}TeO{sub 6} is suppressed by zinc substitution. Black-Right-Pointing-Pointer Color changes from pink to light green and white when M=Co, Ni, Zn, respectively.

Probing the electronic properties of ternary AnM3n−1B2n (n = 1: A = Ca, Sr; M = Rh, Ir and n = 3: A = Ca, Sr; M = Rh phases: observation of superconductivity

Directory of Open Access Journals (Sweden)

Hiroyuki Takeya, Mohammed ElMassalami, Luis A Terrazos, Raul E Rapp, Rodrigo B Capaz, Hiroki Fujii, Yoshihiko Takano, Mathias Doerr and Sergey A Granovsky

2013-01-01

Full Text Available We follow the evolution of the electronic properties of the titled homologous series when n as well as the atomic type of A and M are varied where for n = 1, A = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal structure of n = 1 members is known to be CaRh2B2-type (Fddd, while that of n = 3 is Ca3Rh8B6-type (Fmmm; the latter can be visualized as a stacking of structural fragments from AM3B2 (P6/mmm and AM2B2. The metallic properties of the n = 1 and 3 members are distinctly different: on the one hand, the n = 1 members are characterized by a linear coefficient of the electronic specific heat γ ≈ 3 mJ mol−1 K−2, a Debye temperature θD ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe. The n = 3 family, on the other hand, exhibits γ ≈ 18 mJ mol−1 K−2, θD ≈ 330 K, a weak linear magnetoresistivity and an onset of superconductivity (for Ca3Rh8B6, Tc = 4.0 K and Hc2 = 14.5 kOe, while for Sr3Rh8 B6, Tc = 3.4 K and Hc2 ≈ 4.0 kOe. These remarkable differences are consistent with the findings of the electronic band structures and density of state (DOS calculations. In particular, satisfactory agreement between the measured and calculated γ was obtained. Furthermore, the Fermi level, EF, of Ca3Rh8B6 lies at almost the top of a pronounced local DOS peak, while that of CaRh2B2 lies at a local valley: this is the main reason behind the differences between the, e.g., superconducting properties. Finally, although all atoms contribute to the DOS at EF, the contribution of the Rh atoms is the strongest.

Probing the electronic properties of ternary AnM3n−1B2n (n = 1: A = Ca, Sr; M = Rh, Ir and n = 3: A = Ca, Sr; M = Rh) phases: observation of superconductivity

Science.gov (United States)

Takeya, Hiroyuki; ElMassalami, Mohammed; Terrazos, Luis A; Rapp, Raul E; Capaz, Rodrigo B; Fujii, Hiroki; Takano, Yoshihiko; Doerr, Mathias; Granovsky, Sergey A

2013-01-01

We follow the evolution of the electronic properties of the titled homologous series when n as well as the atomic type of A and M are varied where for n = 1, A = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal structure of n = 1 members is known to be CaRh2B2-type (Fddd), while that of n = 3 is Ca3Rh8B6-type (Fmmm); the latter can be visualized as a stacking of structural fragments from AM3B2 (P6/mmm) and AM2B2. The metallic properties of the n = 1 and 3 members are distinctly different: on the one hand, the n = 1 members are characterized by a linear coefficient of the electronic specific heat γ ≈ 3 mJ mol−1 K−2, a Debye temperature θD ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe. The n = 3 family, on the other hand, exhibits γ ≈ 18 mJ mol−1 K−2, θD ≈ 330 K, a weak linear magnetoresistivity and an onset of superconductivity (for Ca3Rh8B6, Tc = 4.0 K and Hc2 = 14.5 kOe, while for Sr3Rh8 B6, Tc = 3.4 K and Hc2 ≈ 4.0 kOe). These remarkable differences are consistent with the findings of the electronic band structures and density of state (DOS) calculations. In particular, satisfactory agreement between the measured and calculated γ was obtained. Furthermore, the Fermi level, EF, of Ca3Rh8B6 lies at almost the top of a pronounced local DOS peak, while that of CaRh2B2 lies at a local valley: this is the main reason behind the differences between the, e.g., superconducting properties. Finally, although all atoms contribute to the DOS at EF, the contribution of the Rh atoms is the strongest. PMID:27877576

The monoclinic superstructure of the M{sub 2}Pt{sub 6}Al{sub 15} series (M=Ca, Sc, Y, La, Lu)

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Radzieowski, Mathis; Stegemann, Frank; Hoffmann, Rolf-Dieter [Muenster Univ. (Germany). Inst. fuer Anorganische und Analytische Chemie; Janka, Oliver [Muenster Univ. (Germany). Inst. fuer Anorganische und Analytische Chemie; Oldenburg Univ. (Germany). Inst. fuer Chemie

2017-07-01

The five ternary intermetallic compounds M{sub 2}Pt{sub 6}Al{sub 15} (M=Ca, Sc, Y, La, Lu) were prepared from the elements by arc-melting. The crystal structure was determined via single crystal X-ray diffraction. The title compounds crystallize in a superstructure of the RE{sub 0.67}Pt{sub 2}Al{sub 5} type structure (P6{sub 3}/mmc) in the monoclinic crystal system with space group P12{sub 1}/m1 (Sc{sub 2}Pt{sub 6}Al{sub 15}: a=734.19(2), b=1628.96(10), c=734.19(2) pm, β=119.999(3) ; wR=0.0356, 3034 F{sup 2} values, 68 variables). The superstructure can be derived by the superspace formalism using (3+2)D or (3+1)D interpretations of the diffraction data. The structural relation to the subcell structure is discussed on the basis of a group-subgroup scheme. In the crystal structure strongly bonded [Pt{sub 2}Al{sub 4}]{sup δ-} slabs are alternatingly stacked with ordered layers containing M atoms and Al{sub 3} triangles.

High Power OPO Laser and wavelength-controlled system for 1.6μm CO2-DIAL

Science.gov (United States)

Abo, M.; Nagasawa, C.; Shibata, Y.

2009-12-01

Unlike the existing 2.0μm CO2-DIAL, a high-energy pulse laser operating in the 1.6μm absorption band of CO2 has not been realized. Quasi phase matching (QPM) devices have high conversion efficiency and high beam quality due to their higher nonlinear optical coefficient. We adapt the PPMgLT crystal as the QPM device. The PPMgLT crystal had 3mm × 3mm apertures, and the periodically poled period was 30.9 μm, with the duty ratio close to the ideal value of 0.5. The beam quality of the pumping laser was exceed M2 ≥1.2. The repetition rate was 400 Hz and the energy was 35 mJ. The pumping laser pulse was injection-seeded by the continuous-wave (CW) fiber laser, which had a narrow spectrum. The pulse pumped the PPMgLT crystal in the ring cavity with a single pass through the dielectric mirror. The PPMgLT crystal was mounted on a copper holder, and the temperature was maintained at 40 °C using a Peltier module. The holder’s temperature was stabilized to within 0.01 °C when the copper holder was covered with a plastic case. The OPO ring cavity was a singly resonant oscillator optimized for the signal wave. Single-frequency oscillation of the PPMgLT OPO was achieved by injection seeding, as described in the following. The injection seeder was a DFB laser having a power of 30mW with a 1MHz oscillation spectrum. Their oscillation wavelength was coarse tuned by temperature and fine tuned by adjusting injection currents. The partial power of the online wavelength was split in the wavelength control unit. We locked the DFB laser as an injection seeder of the online wavelength onto the line center by referencing the fiber coupled multipath gas cell (path length 800mm) containing pure CO2 at a pressure of 700 Torr. Stabilization was estimated to within 1.8MHz rms of the line center of the CO2 absorption line by monitoring the feedback signal of a wavelength-controlled unit. Injection seeding of the PPMgLT OPO was performed by matching the cavity length to the seeder

Syntheses and structural characterization of non-centrosymmetric Na{sub 2}M{sub 2}M'S{sub 6} (M, M′=Ga, In, Si, Ge, Sn, Zn, Cd) sulfides

Energy Technology Data Exchange (ETDEWEB)

Yohannan, Jinu P.; Vidyasagar, Kanamaluru, E-mail: kvsagar@iitm.ac.in

2016-06-15

Seven new non-centrosymmetric Na{sub 2}M{sub 2}M’S{sub 6} sulfides, namely, Na{sub 2}Sn{sub 2}ZnS{sub 6}(1){sub ,} Na{sub 2}Ga{sub 2}GeS{sub 6}(2), Na{sub 2}Ga{sub 2}SnS{sub 6}(3-α), Na{sub 2}Ga{sub 2}SnS{sub 6}(3-β){sub ,} Na{sub 2}Ge{sub 2}ZnS{sub 6}(4){sub ,} Na{sub 2}Ge{sub 2}CdS{sub 6}(5){sub ,} Na{sub 2}In{sub 2}SiS{sub 6}(6) and Na{sub 2}In{sub 2}GeS{sub 6}(7), were synthesized by high temperature solid state reactions and structurally characterized by single crystal X-ray diffraction. They crystallize in non-centrosymmetric Fdd2 and Cc space groups and their three-dimensional [M{sub 2}M′S{sub 6}]{sup 2-}framework structures consist of MS{sub 4} and M′S{sub 4} tetrahedra corner-connected to one another in either orderly or disordered fashion. Sodium ions reside in the tunnels of the anionic framework. Compounds 1, 2 and 3-α have the structure of known Li{sub 2}Ga{sub 2}GeS{sub 6}, whereas compounds 6 and 7 are isostructural with known Li{sub 2}In{sub 2}GeS{sub 6} compound. Isostructural compounds 4 and 5 represent a new structural variant. Compounds 3-α and its new monoclinic structural variant 3-β have disordered structural framework. All of them are wide band gap semiconductors. Na{sub 2}Ga{sub 2}GeS{sub 6}(2), Na{sub 2}Ga{sub 2}SnS{sub 6}(3), Na{sub 2}Ge{sub 2}ZnS{sub 6}(4) and Na{sub 2}In{sub 2}GeS{sub 6}(7) compounds are found to be second-harmonic generation (SHG) active. Compounds 1, 2 and 3-α melt congruently. - Graphical abstract: Na{sub 2}Ga{sub 2}GeS{sub 6}, Na{sub 2}Ga{sub 2}SnS{sub 6}, Na{sub 2}Ge{sub 2}ZnS{sub 6}, Na{sub 2}In{sub 2}GeS{sub 6}, Na{sub 2}Sn{sub 2}ZnS{sub 6}, Na{sub 2}Ge{sub 2}CdS{sub 6} and Na{sub 2}In{sub 2}SiS{sub 6} have non-centrosymmetric structures and the first four compounds are SHG active. Display Omitted - Highlights: • Seven new Na{sub 2}M{sub 2}M′S{sub 6} compounds with non-centrosymmetric structures were synthesized. • They are wide band gap semiconductors. • Na{sub 2}Ga{sub 2}GeS{sub 6}, Na{sub 2

Properties of M1-M2-Si-Al-O-N glasses (M1 = La or Nd, M2 = Y or Er)

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Pomeroy, M.J.; Nestor, E.; Hampshire, S. [Limerick Univ. (Ireland). Materials and Surface Science Inst.; Ramesh, R. [Littelfuse Ireland, Dundalk, Co. Louth (Ireland)

2002-07-01

Mixed lanthanide cation oxynitride glasses have been prepared in the M1 - M2 - Si-Al-O-N systems where M1 = La or Nd and M2 = Y or Er. The densities ({rho}), Young's moduli (E), microhardnesses (H{sub v}), glass transition temperatures (T{sub g}), dilatometric softening temperatures (T{sub dil}) and coefficients of thermal expansion (CTE) of 13 glasses were determined. The molar volume values (MV) calculated from density data, E, H{sub v}, T{sub g}, T{sub dil} and CTE values were all found to vary linearly with the effective cation field strength arising from the M1 and M2 modifier cations. Least squares intercept and slope values are presented which correlate each property to effective cation field strength together with error values which arise from glass and specimen preparation and measurement inconsistencies. These linear correlations clearly indicate that the overall glass structure remains the same for each of the thirteen glasses with only the modifier cation(s) having any influence. This influence appears to be a cross-linking effect, the strength of which increases as the effective cation field strength of the M1, M2 modifiers increases. (orig.)

Effect of three 2-allyl-p-mentha-6,8-dien-2-ols on inhibition of mild steel corrosion in 1 M HCl

Directory of Open Access Journals (Sweden)

S. Kharchouf

2014-11-01

Full Text Available 2-Allyl-p-mentha-6,8-dien-2-ols P1−P3 synthesized from carvone P are tested as corrosion inhibitors of steel in 1 M HCl using weight loss measurements, potentiodynamic polarisation and impedance spectroscopy (EIS methods. The addition of 2-allyl-p-mentha-6,8-dien-2-ols reduced the corrosion rate. Potentiodynamic polarisation studies clearly reveal that the presence of inhibitors does not change the mechanism of hydrogen evolution and that they act essentially as cathodic inhibitors. 2-Allyl-p-mentha-6,8-dien-2-ols tested adsorb on the steel surface according to Langmuir isotherm. From the adsorption isotherm some thermodynamic data for the adsorption process are calculated and discussed. EIS measurements show the increase of the charge-transfer resistance with the inhibitor concentration. The highest inhibition efficiency (92% is obtained for P1 at 3 g/L. The corrosion rate decreases with the rise of temperature. The corresponding activation energies are determined.

Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration.

Science.gov (United States)

Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter; Schulze, Tobias

2017-01-01

Introduction . Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P 1-5 ) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods . Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results . All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P 1 . In contrast, M1-polarized macrophages significantly downregulated S1P 4 . The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion . The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.

6-Peroxo-6-zirconium crown and its hafnium analogue embedded in a triangular polyanion: [M6(O2)6(OH)6(gamma-SiW10O36)3]18- (M = Zr, Hf).

Science.gov (United States)

Bassil, Bassem S; Mal, Sib Sankar; Dickman, Michael H; Kortz, Ulrich; Oelrich, Holger; Walder, Lorenz

2008-05-28

We have synthesized and structurally characterized the unprecedented peroxo-zirconium(IV) containing [Zr6(O2)6(OH)6(gamma-SiW10O36)3]18- (1). Polyanion 1 comprises a cyclic 6-peroxo-6-zirconium core stabilized by three decatungstosilicate units. We have also prepared the isostructural hafnium(IV) analogue [Hf6(O2)6(OH)6(gamma-SiW10O36)3]18- (2). We investigated the acid/base and redox properties of 1 by UV-vis spectroscopy and electrochemistry studies. Polyanion 1 represents the first structurally characterized Zr-peroxo POM with side-on, bridging peroxo units. The simple, one-pot synthesis of 1 and 2 involving dropwise addition of aqueous hydrogen peroxide could represent a general procedure for incorporating peroxo groups into a large variety of transition metal and lanthanide containing POMs.

Thermodynamic study of (alkyl esters+{alpha},{omega}-alkyl dihalides) V. H{sub m}{sup E}andV{sub m}{sup E} for 25 binary mixtures {l_brace}xC{sub u-1}H{sub 2u-1}CO{sub 2}CH{sub 3}+(1-x){alpha},{omega}-ClCH{sub 2}(CH{sub 2}){sub v-2}CH{sub 2}Cl{r_brace}, where u=1 to 5, {alpha}=1 and v={omega}=2 to 6

Energy Technology Data Exchange (ETDEWEB)

Ortega, J. [Laboratorio de Termodinamica y Fisicoquimica de Fluidos, Parque Cientifico-Tecnologico, Campus Universitario de Tafira, Universidad de Las Palmas de Gran Canaria, 35071 Las Palmas de Gran Canaria, Canary Islands (Spain)]. E-mail: jortega@dip.ulpgc.es; Marrero, E. [Laboratorio de Termodinamica y Fisicoquimica de Fluidos, Parque Cientifico-Tecnologico, Campus Universitario de Tafira, Universidad de Las Palmas de Gran Canaria, 35071 Las Palmas de Gran Canaria, Canary Islands (Spain)

2007-05-15

The experimental data of excess molar enthalpies H{sub m}{sup E} and excess molar volumes V{sub m}{sup E} are presented for a set of 25 binary mixtures comprised of the first five methyl esters C{sub u-1}H{sub 2u-1}COOCH{sub 3} (u=1 to 5) and five {alpha},{omega}-dichloroalkanes, ClCH{sub 2}(CH{sub 2}){sub v-2}CH{sub 2}Cl (v=2 to 6), obtained at a temperature of 298.15K and atmospheric pressure. Except for the mixtures with u=1 and v=2 to 6, which are all endothermic and with u=5 and v=2 to 6, which are all exothermic, the others present net endo/exothermic effects and these mixing effects evolve quasiregularly, from endothermic to exothermic, depending on the dichloroalkane present. However, the V{sub m}{sup E} are positive in most mixtures except for those corresponding to u=4,5 and v=5,6, which present contraction effects. These results indicate a set of specific interactions with simultaneous effects for V{sub m}{sup E} of expansion/contraction and for exothermic/endothermic H{sub m}{sup E} for this set of mixtures. The change in V{sub m}{sup E} with the chain length of the compounds is irregular. To achieve a good application of the UNIFAC model using the version of Dang and Tassios, parameters of the ester (G)/dichloride (G') interaction were calculated again, making a distinction, during its application, dependent on the acid part of the ester u. Hence, interaction parameters are presented as a function of u, and of the dichloroalkane chain length v. The most appropriate general expression was of the type:a{sub G/G{sup '}}={phi}(u,v)={sigma}sub(i=0)sup(n)a{sub i-1}u{sup i-1}+{sigma}sub(i=0= )sup(n)b{sub i-1}v{sup i-1}and with this proposal good estimations of enthalpies were obtained with the UNIFAC model.

New metal-organic polygons involving MM quadruple bonds: M8(O2CtBu)4(mu-SC4H2-3,4-{CO2}2)6 (M=Mo, W).

Science.gov (United States)

Byrnes, Matthew J; Chisholm, Malcolm H; Patmore, Nathan J

2005-12-12

The reactions between M2(O2CtBu)4, where M=Mo or W, and thienyl-3,4-dicarboxylic acid (0.5-1.5 equiv) in toluene proceed via a series of detectable intermediates to the compounds M8(O2CtBu)4(mu-SC4H2-3,4-{CO2}2)6, which are isolated as air-sensitive yellow (M=Mo) or red (M=W) powders and show parent molecular ions in their mass spectra (MALDI). The structure of the molybdenum complex was determined by single-crystal X-ray crystallography and shown to contain an unusual M8 polygon involving four Mo2 quadruply bonded units linked via the agency of the six 3,4-thienylcarboxylate groups. The structure has crystallographically imposed S4 symmetry and may be described in terms of a highly distorted tetrahedron of Mo2 units or a bisphenoid in which two Mo2 units are linked by a thienyldicarboxylate such that intramolecular Mo2...O bonding is present, while the other thienylcarboxylate bridges merely serve to link these two [Mo2]...[Mo2] units together. The color of the compounds arises from intense M2 delta-to-thienyl pi transitions and, in THF, the complexes are redox-active and show four successive quasi-reversible oxidation waves. The [M8]+ radical cations, generated by one-electron oxidation with AgPF6, are shown to be valence-trapped (class II) by UV-vis-near-IR and electron paramagnetic resonance spectroscopy. These results are supported by the electronic structure calculations on model compounds M8(O2CH)4(mu-SC4H2-3,4-{CO}2)6 employing density functional theory that reveal only a small splitting of the M2 delta manifold via mixing with the 3,4-thienylcarboxylate pi system.

Infinitely many N=1 dualities from m+1−m=1

Energy Technology Data Exchange (ETDEWEB)

Agarwal, Prarit; Intriligator, Kenneth; Song, Jaewon [Department of Physics, University of California,San Diego, La Jolla, CA 92093 (United States)

2015-10-06

We discuss two infinite classes of 4d supersymmetric theories, T{sub N}{sup (m)} and U{sub N}{sup (m)}, labelled by an arbitrary non-negative integer, m. The T{sub N}{sup (m)} theory arises from the 6d, A{sub N−1} type N=(2,0) theory reduced on a 3-punctured sphere, with normal bundle given by line bundles of degree (m+1,−m); the m=0 case is the N=2 supersymmetric T{sub N} theory. The novelty is the negative-degree line bundle. The U{sub N}{sup (m)} theories likewise arise from the 6d N=(2,0) theory on a 4-punctured sphere, and can be regarded as gluing together two (partially Higgsed) T{sub N}{sup (m)} theories. The T{sub N}{sup (m)} and U{sub N}{sup (m)} theories can be represented, in various duality frames, as quiver gauge theories, built from T{sub N} components via gauging and nilpotent Higgsing. We analyze the RG flow of the U{sub N}{sup (m)} theories, and find that, for all integer m>0, they end up at the same IR SCFT as SU(N) SQCD with 2N flavors and quartic superpotential. The U{sub N}{sup (m)} theories can thus be regarded as an infinite set of UV completions, dual to SQCD with N{sub f}=2N{sub c}. The U{sub N}{sup (m)} duals have different duality frame quiver representations, with 2m+1 gauge nodes.

MASCARA-2 b. A hot Jupiter transiting the mV = 7.6 A-star HD 185603

Science.gov (United States)

Talens, G. J. J.; Justesen, A. B.; Albrecht, S.; McCormac, J.; Van Eylen, V.; Otten, G. P. P. L.; Murgas, F.; Palle, E.; Pollacco, D.; Stuik, R.; Spronck, J. F. P.; Lesage, A.-L.; Grundahl, F.; Fredslund Andersen, M.; Antoci, V.; Snellen, I. A. G.

2018-04-01

In this paper we present MASCARA-2 b, a hot Jupiter transiting the mV = 7.6 A2 star HD 185603. Since early 2015, MASCARA has taken more than 1.6 million flux measurements of the star, corresponding to a total of almost 3000 h of observations, revealing a periodic dimming in the flux with a depth of 1.3%. Photometric follow-up observations were performed with the NITES and IAC80 telescopes and spectroscopic measurements were obtained with the Hertzsprung SONG telescope. We find MASCARA-2 b orbits HD 185603 with a period of 3.4741119-0.000006+0.000005 at a distance of 0.057 ± 0.006 au, has a radius of 1.83 ± 0.07 RJ and place a 99% upper limit on the mass of http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/612/A57

Impact of peatland restoration on nutrient and carbon leaching from contrasting sites in southern Finland

Science.gov (United States)

Vasander, Harri; Sallantaus, Tapani; Koskinen, Markku

2010-05-01

with phosphorus. The reasons for the greater responses in Nuuksio are partly hydrological. The mires are minerogenic, catchment fed mires, and by restoration the peat layers regain their contact with the waters from the catchment. This is not the case with the bogs of Seitseminen and of less importance in the poor fens with a small catchment. Also biological reasons exist. The peat layers have changed much more in the fertile peatlands of Nuuksio. Moreover, the living biomass is much larger in Nuuksio, and due to restoration this biomass is inundated and consequently exposed to anaerobia. This has caused death of the forest species, release of bound nutrients, and gradual colonization by mires species leading to renewed bounding of nutrients. Restoration of drained peatlands is a positive action, but harmful water impacts should be avoided. This urges for hydrological knowledge in the planning and accomplishing phases. Table 1. Annual unrestored leaching rates of organic carbon, nitrogen and phosphorus in the study sites, and increase in leaching as a sum of 6 post-restoration years, calculated per restored mire area. Site Unrestored leaching g C m-2 a-1 Increase in leaching g C m-2 6a-1 Unrestored leaching g N m-2 a-1 Increase in leaching g N m-2 6a-1 Unrestored leaching g P m-2 a-1 Increase in leaching g P m-2 6a-1 Seitseminen 10.5 58 0.19 1.18 0.009 0.21 Nuuksio 5.3 107 0.13 2.54 0.004 0.18

TNP [N2-(m-Trifluorobenzyl, N6-(p-nitrobenzylpurine] ameliorates diet induced obesity and insulin resistance via inhibition of the IP6K1 pathway

Directory of Open Access Journals (Sweden)

Sarbani Ghoshal

2016-10-01

Full Text Available Objective: Obesity and type 2 diabetes (T2D lead to various life-threatening diseases such as coronary heart disease, stroke, osteoarthritis, asthma, and neurodegeneration. Therefore, extensive research is ongoing to identify novel pathways that can be targeted in obesity/T2D. Deletion of the inositol pyrophosphate (5-IP7 biosynthetic enzyme, inositol hexakisphosphate kinase-1 (IP6K1, protects mice from high fat diet (HFD induced obesity (DIO and insulin resistance. Yet, whether this pathway is a valid pharmacologic target in obesity/T2D is not known. Here, we demonstrate that TNP [N2-(m-Trifluorobenzyl, N6-(p-nitrobenzylpurine], a pan-IP6K inhibitor, has strong anti-obesity and anti-diabetic effects in DIO mice. Methods: Q-NMR, GTT, ITT, food intake, energy expenditure, QRT-PCR, ELISA, histology, and immunoblot studies were conducted in short (2.5-week- and long (10-week-term TNP treated DIO C57/BL6 WT and IP6K1-KO mice, under various diet and temperature conditions. Results: TNP, when injected at the onset of HFD-feeding, decelerates initiation of DIO and insulin resistance. Moreover, TNP facilitates weight loss and restores metabolic parameters, when given to DIO mice. However, TNP does not reduce weight gain in HFD-fed IP6K1-KO mice. TNP specifically enhances insulin sensitivity in DIO mice via Akt activation. TNP decelerates weight gain primarily by enhancing thermogenic energy expenditure in the adipose tissue. Accordingly, TNP's effect on body weight is partly abolished whereas its impact on glucose homeostasis is preserved at thermoneutral temperature. Conclusion: Pharmacologic inhibition of the inositol pyrophosphate pathway has strong therapeutic potential in obesity, T2D, and other metabolic diseases. Author Video: Author Video Watch what authors say about their articles Keywords: IP6K, Inositol pyrophosphate, Obesity, Energy expenditure, Diabetes, Akt

m6AVar: a database of functional variants involved in m6A modification

OpenAIRE

Zheng, Yueyuan; Nie, Peng; Peng, Di; He, Zhihao; Liu, Mengni; Xie, Yubin; Miao, Yanyan; Zuo, Zhixiang; Ren, Jian

2017-01-01

Abstract Identifying disease-causing variants among a large number of single nucleotide variants (SNVs) is still a major challenge. Recently, N 6-methyladenosine (m6A) has become a research hotspot because of its critical roles in many fundamental biological processes and a variety of diseases. Therefore, it is important to evaluate the effect of variants on m6A modification, in order to gain a better understanding of them. Here, we report m6AVar (http://m6avar.renlab.org), a comprehensive da...

Photochemistry of 1 and 2-(2-methylphenyl)-1,6-heptadiene

International Nuclear Information System (INIS)

Barrows, R.D.; Hornback, J.M.

1982-01-01

In an attempt to synthesize partially saturated phenanthrene derivatives by an intramolecular Diels-Alder reaction between a photochemically produced o-xylylene (diene) and a tethered dienophile, it was found that 1 and 2 underwent a photochemically allowed [2 + 2] cycloaddition. Irradiation of 1 gave 6-(2-methylphenyl)bicyclo[3.2.0]heptane in 86% yield. Upon irradiation of 2, a benzvalene rearrangement of 2 first took place, producing the meta isomer 2-(3-methylphenyl)-1,6-heptadiene, followed by a [2 + 2] photocycloaddition giving 1-(3-methylphenyl)bicyclo[3.2.0]heptane in 15% yield. Direct irradiation of 2-(3-methylphenyl)-1,6-heptadiene gave the same bicyclo derivative as 2 in 34% yield. Examination of the fluorescence spectra of 1 and 2 in comparison with 1-(2-methylphenyl)propene and 2-(2-methylphenyl)-1-butene, respectively, has shown that 1 may be biased toward [2 + 2] cycloaddition where 2 is not biased toward [2 + 2] photocycloization. Attempts to produce 4a-methyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene by an intramolecular Diels-Alder reaction of the o-xylylene produced by irradiation of 3 will also be described

CYP1A1 m1 and m2 polymorphisms: genetic susceptibility to lung cancer

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Paula Mota

2010-01-01

Full Text Available Lung cancer is considered an environment-related disease that develops as a consequence of exposure to mutagenic agents, namely those present in tobacco. The CYP1A1 gene codifies the phase I enzyme aryl hydrocarbon hydroxilase (AHH belonging to the cytochrome P450 system that plays a major role in the bio-activation of tobacco procarcinogenes. Two CYP1A1 polymorphisms, m1 (T6235C transition and m2 (A4889G transition, are associated with greater enzymatic activity and have been described as genetic susceptibility factors for lung cancer.The aim of this study was to verify if this association holds true in blood samples of 175 lung cancer patients and 217 non-cancer patients from Portugal's midlands region. The samples were studied by restriction fragment length polymorphism (RFLP assay.The allelic frequencies of the mutant alleles were 0.12 for allele C and 1.14 for allele G in the control population. The results were not statistically different from those alleles in the patient population. There was also no statistically significant difference in genotype distribution in lung cancer patients and controls even when combining high risk genotypes. In our control sample, as in other populations of different ethnic origin, both polymorphisms also seem to be in linkage disequilibrium. We conclude that in this sample of the Portuguese population, CYP1A1 m1 and m2 polymorphisms are too rare to be of clinical relevance, and do not seem to be associated with susceptibility to lung cancer. Resumo: O cancro do pulmão é considerado uma doença relacionada com o meio ambiente, consequência da exposição a agentes mutagénicos, nomeadamente os presentes no fumo do tabaco. O gene CYP1A1 codifica a enzima aril hidrocarboneto hidroxilase (AHH, da fase I, do sistema multienzimático do citocromo P450, que desempenha uma função preponderante na bioactivação dos procarcinogénios do tabaco. Dois polimorfismos do CYP1A1, m1 (transi

Determination of piperphentonamine and metabolites M1 and M6 in human plasma and urine by LC/MS/MS and its application in a pharmacokinetics study in Chinese healthy volunteers.

Science.gov (United States)

Shi, Aixin; Hu, Xin; Li, Kexin; Li, Jian; Han, Liping; Wan, Huayin; Li, Rubing

2012-11-01

Piperphentonamine hydrochloride (PPTA) is a new calcium sensitizer. A liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for determination of piperphentonamine and its metabolites M1 and M6 was developed for the first time and applied to a pharmacokinetics study. Protein precipitation was used for pre-treatment of plasma samples, and solid phase extraction method was used for pre-treatment of urine samples. The chromatographic separation was achieved on a C(18) column using gradient elution in this study: A: 1% acetic acid aqueous solution, and B: acetonitrile. The whole analysis lasted for 10.5min and the gradient flow rate was 0.25mL/min constantly. The detection was performed of a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via a positive electrospray ionization source. The results were that the m/z ratios of monitored precursor ions and product ions of PPTA, M1 and M6 were 354.0→191.8, 356.0→148.7 and 358.0→148.7, respectively. From the standard curve, the concentration ranges of both PPTA and M1 in blood and urine samples were 0.1-500ng/mL and 0.1-200ng/mL, respectively; the concentration ranges of M6 in blood sample and urine sample were 0.2-500ng/mL and 0.2-200ng/mL, respectively; and the correlation coefficient of standard curve was r>0.99. A total of 31 healthy Chinese subjects participated in the pharmacokinetic study of single bolus intravenous injection of piperphentonamine hydrochloride. They were divided into three dosage groups and given 0.2, 0.4 and 0.6mg/kg of PPTA. After drug administration, concentrations of PPTA, M1 and M6 in human plasma and urine samples were determined to evaluation the pharmacokinetic characteristics of PPTA and its metabolites M1 and M6. Copyright © 2012 Elsevier B.V. All rights reserved.

m6aViewer: software for the detection, analysis, and visualization of N6-methyladenosine peaks from m6A-seq/ME-RIP sequencing data.

Science.gov (United States)

Antanaviciute, Agne; Baquero-Perez, Belinda; Watson, Christopher M; Harrison, Sally M; Lascelles, Carolina; Crinnion, Laura; Markham, Alexander F; Bonthron, David T; Whitehouse, Adrian; Carr, Ian M

2017-10-01

Recent methods for transcriptome-wide N 6 -methyladenosine (m 6 A) profiling have facilitated investigations into the RNA methylome and established m 6 A as a dynamic modification that has critical regulatory roles in gene expression and may play a role in human disease. However, bioinformatics resources available for the analysis of m 6 A sequencing data are still limited. Here, we describe m6aViewer-a cross-platform application for analysis and visualization of m 6 A peaks from sequencing data. m6aViewer implements a novel m 6 A peak-calling algorithm that identifies high-confidence methylated residues with more precision than previously described approaches. The application enables data analysis through a graphical user interface, and thus, in contrast to other currently available tools, does not require the user to be skilled in computer programming. m6aViewer and test data can be downloaded here: http://dna2.leeds.ac.uk/m6a. © 2017 Antanaviciute et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Structural phase transition and magnetic properties of double perovskites Ba2CaMO6 (M=W, Re, Os)

International Nuclear Information System (INIS)

Yamamura, Kazuhiro; Wakeshima, Makoto; Hinatsu, Yukio

2006-01-01

Structures and magnetic properties for double perovskites Ba 2 CaMO 6 (M=W, Re, Os) were investigated. Both Ba 2 CaReO 6 and Ba 2 CaWO 6 show structural phase transitions at low temperatures. For Ba 2 CaReO 6 , the second order transition from cubic Fm3-bar m to tetragonal I4/m has been observed near 120K. For Ba 2 CaWO 6 , the space group of the crystal structure is I4/m at 295K and the transition to monoclinic I2/m has been observed between 220K. Magnetic susceptibility measurements show that Ba 2 CaReO 6 (S=1/2) and Ba 2 CaOsO 6 (S=1) transform to an antiferromagnetic state below 15.4 and 51K, respectively. Anomalies corresponding to their structural phase transition and magnetic transition have been also observed through specific heat measurements

mPW1PW91 Calculated Conformational Study of Calix[n]arene (n = 4,5,6): Hydrogen Bond

International Nuclear Information System (INIS)

Kim, Kwang Ho; Choe, Jong In

2009-01-01

We have performed mPW1PW91 calculations to investigate the conformational characteristics and hydrogen bonds of p-tert-butylcalix[4]arene, p-tert-butylcalix[5]arene, calix[6]arene and p-tertbutylcalix[ 6]arene. The structures of the different conformers of 1-3 were optimized by using mPW1PW91/ 6-31+G(d,p) method. The relative stability of the four conformers of 1 is in the following order: cone (most stable) > partial-cone > 1,2-alternate > 1,3-alternate. The relative stability of the conformers of 2 is in the following order: cone (most stable) > 1,2-alternate > partial-cone > 1,3-alternate. The relative stability of the various conformers of 3 is in the following order: cone (pinched: most stable) > partial-cone > cone (winged) ∼ 1,2-alternate ∼ 1,2,3-alternate > 1,4-alternate > 1,3-alternate > 1,3,5-alternate. The structures of the various conformers of 4 were optimized by using the mPW1PW91/6-31G(d,p) method followed by single point calculation of mPW1PW91/6-31+G(d,p). The relative stability of the conformers of 4 is in the following order: cone (pinched) > 1,2-alternate > cone (winged) > 1,4-alternate ∼ partial-cone > 1,2,3-alternate > 1,3,5-alternate > 1,3-alternate

Oxide fluoride sulfides of the lanthanoids with the formula M{sub 6}O{sub 2}F{sub 8}S{sub 3} (M = La-Nd, Sm, Gd); Oxidfluoridsulfide der Lanthanoide vom Formeltyp M{sub 6}O{sub 2}F{sub 8}S{sub 3} (M = La-Nd, Sm, Gd)

Energy Technology Data Exchange (ETDEWEB)

Grossholz, Hagen; Zimmermann, Dirk D.; Janka, Oliver; Schleid, Thomas [Stuttgart Univ. (Germany). Inst. fuer Anorganische Chemie

2013-07-15

The lanthanoid(III) oxide fluoride sulfides M{sub 6}O{sub 2}F{sub 8}S{sub 3} (M = La-Nd, Sm, Gd) can be obtained by reacting the rare-earth metals, their trifluorides and sesquioxides with elemental sulfur in appropriate molar ratios at 850 C flux-assisted by NaCl in gas-tightly sealed niobium or tantalum ampoules. All compounds are colorless, except for those containing M = Pr with green, M = Nd with lilac and M = Sm with yellow color. They form transparent single crystals as needles or rods. The M{sub 6}O{sub 2}F{sub 8}S{sub 3} representatives crystallize in a hexagonal structure (space group: P6{sub 3}/m; a {approx} 1382-1326, c {approx} 398-376 pm, c/a {approx} 0.288-0.284; Z = 2) with two different crystallographic M{sup 3+} positions. The (M2){sup 3+} cations reside in ninefold coordination of anions arranged as tricapped trigonal prisms formed by three F{sup -}, four mixed-occupied O{sup 2-}/F{sup -} and two S{sup 2-} anions, resembling the unique M{sup 3+} coordination sphere of the M{sub 3}OF{sub 5}S-type oxide fluoride sulfides. The (M1){sup 3+} cations are surrounded by square antiprisms built of four O{sup 2-}/F{sup -} and S{sup 2-} anions each, which are capped by one F{sup -} anion each, again resulting in a ninefold coordination similar to that of the A-MFS-type fluoride sulfides. While the crystallographically unique S{sup 2-} anions have six cationic neighbors arranged in trigonal prisms, there are four different light-anion positions. Two of them, representing only fluoride anions, are situated in a triangular environment of cations ((F1){sup -}: planar, (F2){sup -}: non-planar). The mixed-occupied light-anion positions (F3){sup -}/(O3){sup 2-} and (F4){sup -}/(O4){sup 2-} exhibit tetrahedral coordination spheres with a ratio F{sup -}: O{sup 2-} = 2:1. The M{sub 6}O{sub 2}F{sub 8}S{sub 3} arrangement is characterized by an empty hexagonal channel structure created by (F1){sup -} anions with a potential of accommodating alkali-metal cations like Na

Molecular magnetism of M6 hexagon ring in D(3d) symmetric [(MCl)6(XW9O33)2](12-) (M = Cu(II) and Mn(II), X = Sb(III) and As(III)).

Science.gov (United States)

Yamase, Toshihiro; Ishikawa, Hirofumi; Abe, Hiroko; Fukaya, Keisuke; Nojiri, Hiroyuki; Takeuchi, Hideo

2012-04-16

Ferromagnetic [n-BuNH(3)](12)[(CuCl)(6)(SbW(9)O(33))(2)]·6H(2)O (1) and antiferromagnetic [n-BuNH(3)](12)[(MnCl)(6)(AsW(9)O(33))(2)]·6H(2)O (4) have been synthesized and structurally and magnetically characterized. Two complexes are structural analogues of [n-BuNH(3)](12)[(CuCl)(6)(AsW(9)O(33))(2)]·6H(2)O (2) and [n-BuNH(3)](12)[(MnCl)(6)(SbW(9)O(33))(2)]·6H(2)O (3) with their ferromagnetic interactions, first reported by us in 2006. (1) When variable temperature (T) direct current (dc) magnetic susceptibility (χ(M)) data are analyzed with the isotropic exchange Hamiltonian for the magnetic exchange interactions, χ(M)T vs T curves fitted by a full matrix diagonalization (for 1) and by the Kambe vector coupling method/Van Vleck's approximation (for 4) yield J = +29.5 and -0.09 cm(-1) and g = 2.3 and 1.9, respectively. These J values were significantly distinguished from +61.0 and +0.14 cm(-1) for 2 and 3, respectively. The magnetization under the pulsed field (up to 10(3) T/s) at 0.5 K exhibits hysteresis loops in the adiabatic process, and the differential magnetization (dM/dB) plots against the pulsed field display peaks characteristic of resonant quantum tunneling of magnetization (QTM) at Zeeman crossed fields, indicating single-molecule magnets for 1-3. High-frequency ESR (HFESR) spectroscopy on polycrystalline samples provides g(∥) = 2.30, g(⊥) = 2.19, and D = -0.147 cm(-1) for 1 (S = 3 ground state), g(∥) = 2.29, g(⊥) = 2.20, and D = -0.145 cm(-1) for 2 (S = 3), and g(∥) = 2.03 and D = -0.007 cm(-1) for 3 (S = 15). An attempt to rationalize the magnetostructural correlation among 1-4, the structurally and magnetically modified D(3d)-symmetric M (=Cu(II) and Mn(II))(6) hexagons sandwiched by two diamagnetic α-B-[XW(9)O(33)](9-) (X = Sb(III) and As(III)) ligands through M-(μ(3)-O)-W linkages, is made. The strongest ferromagnetic coupling for the Cu(6) hexagon of 2, the structure of which approximately provides the Cu(6)(μ(3)-O)(12

2-Isobutyl-6-(4-methoxyphenylimidazo[2,1-b][1,3,4]thiadiazole

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Hoong-Kun Fun

2011-02-01

Full Text Available In the title compound, C15H17N3OS, the dihedral angle between the statistically planar imidazo[2,1-b][1,3,4]thiadiazole fused-ring system (r.m.s. deviation = 0.002 Å and the methyoxbenzene ring is 4.52 (6°. In the crystal, molecules are arranged into columns and stacked down the a axis. The crystal structure is stabilized by weak C—H...π and π–π interactions [centroid–centroid separations = 3.6053 (8 and 3.7088 (7 Å].

6,6'-(1E,1'E-((1R,2R-1,2-Diphenylethane-1,2-diylbis(azan-1-yl-1-ylidenebis(methan-1-yl-1-ylidenebis(2-tert-butyl-4-((trimethylsilylethynylphenol

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David Díaz Díaz

2013-03-01

Full Text Available Functionalizable salen derivative, 6,6'-(1E,1'E-((1R,2R-1,2-diphenylethane-1,2-diylbis(azan-1-yl-1-ylidenebis(methan-1-yl-1-ylidenebis(2-tert-butyl-4-((trimethylsilyl ethyn-ylphenol (3, was synthesized by condensation between (1R,2R-1,2-diphenylethane-1,2-diamine (2 and 3-tert-butyl-2-hydroxy-5-((trimethylsilylethynyl benzaldehyde (1 under refluxing conditions. The title compound was characterized by 1H-NMR, 13C-NMR, FT-IR, high-resolution mass spectrometry, optical rotation and melting point determination.

1,2-Bis(2-methoxy-6-formylphenoxyethane

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Hongqi Li

2011-02-01

Full Text Available In the title compound [systematic name: 3,3′-dimethoxy-2,2′-(ethane-1,2-diyldioxydibenzaldehyde], C18H18O6, prepared from 1,2-dibromoethane and ortho-vanillin in the presence of sodium carbonate, the two vanillin units are linked via a CH2–CH2 bridge. The two benzene rings are inclined at a dihedral angle of 41.6 (5°.

Role of loop L5-6 connecting transmembrane segments M5 and M6 in biogenesis and functioning of yeast Pma1 H+-ATPase.

Science.gov (United States)

Petrov, V V

2015-01-01

The L5-6 loop is a short extracytoplasmic stretch (714-DNSLDID) connecting transmembrane segments M5 and M6 and forming along with segments M4 and M8 the core through which cations are transported by H+-, Ca2+-, K+,Na+-, H+,K+-, and other P2-ATPases. To study structure-function relationships within this loop of the yeast plasma membrane Pma1 H+-ATPase, alanine- and cysteine-scanning mutagenesis has been employed. Ala and Cys substitutions for the most conserved residue (Leu717) led to complete block in biogenesis preventing the enzyme from reaching secretory vesicles. The Ala replacement at Asp714 led to five-fold decrease in the mutant expression and loss of its activity, while the Cys substitution blocked biogenesis completely. Replacements of other residues did not lead to loss of enzymatic activity. Additional replacements were made for Asp714 and Asp720 (Asp®Asn/Glu). Of the substitutions made at Asp714, only D714N partially restored the mutant enzyme biogenesis and functioning. However, all mutant enzymes with substituted Asp720 were active. The expressed mutants (34-95% of the wild-type level) showed activity high enough (35-108%) to be analyzed in detail. One of the mutants (I719A) had three-fold reduced coupling ratio between ATP hydrolysis and H+ transport; however, the I719C mutation was rather indistinguishable from the wild-type enzyme. Thus, substitutions at two of the seven positions seriously affected biogenesis and/or functioning of the enzyme. Taken together, these results suggest that the M5-M6 loop residues play an important role in protein stability and function, and they are probably responsible for proper arrangement of transmembrane segments M5 and M6 and other domains of the enzyme. This might also be important for the regulation of the enzyme.

Synthesis and characterization of 6,6'-(2,4,6-triisopropylphenyl)-2,2'-bipyridine (tripbipy) and its complexes of the late first row transition metals.

Science.gov (United States)

Benson, Eric E; Rheingold, Arnold L; Kubiak, Clifford P

2010-02-15

The synthesis of tripbipy, a new substituted bipyridine ligand (6,6'-(2,4,6-triisopropylphenyl)-2,2'-bipyridine), and the syntheses, structures, and magnetic properties of the first coordination compounds based on this ligand are described. Tripbipy was synthesized by the Suzuki coupling of 2,4,6-triisopropylphenyl boronic acid and 6,6'-dibromo-2,2'-bipyridine. Reported here are the tripbipy complexes of five late first row transition metal chlorides (MCl(2); M = Fe, Co, Ni, Cu, Zn). Four of the complexes MCl(2)tripbipy (M = Fe, Co, Ni, Zn) crystallize in the space group P2(1)/c and are isomorphous with one solvent molecule of crystallization. The complex CuCl(2)tripbipy crystallizes in the space group P2(1)2(1)2(1) with two solvent molecules of crystallization. All MCl(2)tripbipy complexes are four coordinate and contain distorted tetrahedral metal centers. CuCl(2)tripbipy shows a pseudo Jahn-Teller distortion, and X-band electron paramagnetic resonance (EPR) in a toluene glass gives approximate g( perpendicular, parallel) values of 2.2 and 2.1. Magnetic measurements (M = Fe, Co, Ni, Cu) are consistent with high spin d(n) configurations (n = 6-9, S = 2, 3/2, 1, 1/2) tetrahedral complexes and give chi(M)T values at 300 K of 3.56, 2.10, 1.01, and 0.37 cm(3) M(-1) K, respectively.

Stabilization of the H,K-ATPase M5M6 membrane hairpin by K+ ions. Mechanistic significance for p2-type atpases.

Science.gov (United States)

Gatto, C; Lutsenko, S; Shin, J M; Sachs, G; Kaplan, J H

1999-05-14

The integral membrane protein, the gastric H,K-ATPase, is an alpha-beta heterodimer, with 10 putative transmembrane segments in the alpha-subunit and one such segment in the beta-subunit. All transmembrane segments remain within the membrane domain following trypsinization of the intact gastric H,K-ATPase in the presence of K+ ions, identified as M1M2, M3M4, M5M6, and M7, M8, M9, and M10. Removal of K+ ions from this digested preparation results in the selective loss of the M5M6 hairpin from the membrane. The release of the M5M6 fragment is directed to the extracellular phase as evidenced by the accumulation of the released M5M6 hairpin inside the sealed inside out vesicles. The stabilization of the M5M6 hairpin in the membrane phase by the transported cation as well as loss to the aqueous phase in the absence of the transported cation has been previously observed for another P2-type ATPase, the Na, K-ATPase (Lutsenko, S., Anderko, R., and Kaplan, J. H. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 7936-7940). Thus, the effects of the counter-transported cation on retention of the M5M6 segment in the membrane as compared with the other membrane pairs may be a general feature of P2-ATPase ion pumps, reflecting a flexibility of this region that relates to the mechanism of transport.

Effect of Qingguang'an II on expression of PAX6, Ngn1 and Ngn2 mRNA of rats with chronic high intraocular pressure

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Ya-Sha Zhou

2017-09-01

Full Text Available AIM: To remark the effect of Qingguang'an II on expression of PAX6, Ngn1, and Ngn2 mRNA of rats with chronic high intraocular pressure. METHODS: Totally 40 male SD rats were randomly divided into 6 groups, that was: A: blank group, B: model group, C: Qingguang'an II low dose group, D: Qingguang'an II moderate dose group, E: Qingguang'an II high dose group, F: Yimaikang disket group. B, C, D, E, F groups of experimental rats were established the model of chronic high intraocular pressure(IOPby cauterizing of superficial scleral vein. Animal model was established successfully by using monitoring IOP consistently keep above 25mmHg for 8wk as cut-off criterion. Tissues of Eyes were obtained after intragastric administration for 2wk and 4wk. The expressions of PAX6, Ngn1, and Ngn2 mRNA were investigated by Real-time PCR. RESULTS: At the time-point of 2wk, PAX6, Ngn1, and Ngn2 mRNA in group B were statistically expressed in lower level comparing with other groups(PPPP>0.05. CONCLUSION: In summar, Qingguang'an II and Yimaikang disket can remarkably increase the expressions of PAX6, Ngn1, and Ngn2, which suggest protecting the optic nerve of rats caused by chronic high IOP. What's more, this study indicated that, in the protection of optic nerve of rats with chronic high IOP, the high dose of Qingguang'an II at the time-point of 4wk was the better choice.

Main: 1M2Q [RPSD[Archive

Lifescience Database Archive (English)

Full Text Available 1M2Q トウモロコシ Corn Zea mays L. Casein Kinase Ii, Alpha Chain Name=Ack2; Zea Mays Mole...cule: Casein Kinase Ii, Alpha Chain; Chain: A; Fragment: Catlytic Subunit; Synonym: Ckii; Engineered: Yes Tr...ansferase 2.7.1.37 (Casein Kinase Ii, Alpha Chain) E.De Moliner, S.Sarno, S.Moro, G.Zagotto, G.Zanotti, L.A....=2-326.|PDB; 1M2Q; X-ray; A=2-328.|PDB; 1M2R; X-ray; A=2-328.|PDB; 1OM1; X-ray; A=1-332.|Mai

Structural chemistry of the cation-ordered perovskites Sr2CaMo1-xTexO6 (0=1)

International Nuclear Information System (INIS)

Prior, Timothy J.; Couper, Victoria J.; Battle, Peter D.

2005-01-01

The crystal structures of Sr 2 CaMoO 6 and Sr 2 CaTeO 6 have been determined at room temperature by neutron powder diffraction. Both compounds crystallize in the perovskite structure with a rock-salt ordered array of Ca 2+ and M 6+ cations (M=Mo, Te) on the six-coordinate sites (space group P2 1 /n (no. 14); for M=Mo, a=5.76228(7), b=5.84790(7), c=8.18707(9)A, β=90.194(1) o , for M=Te, a=5.79919(9), b=5.83756(8), c=8.2175(1)A, β=90.194(1) o ). Compositions in the solid solution Sr 2 CaMo 1-x Te x O 6 have been synthesized and shown by X-ray diffraction to adopt the same ordered structure. The results are used in a discussion of the cation oxidation states in Ca 2 FeMoO 6 and to establish the similarity between the structural chemistry of hexavalent Mo and Te

EMMPRIN reduction via scFv-M6-1B9 intrabody affects α3β1-integrin and MCT1 functions and results in suppression of progressive phenotype in the colorectal cancer cell line Caco-2.

Science.gov (United States)

Sangboonruang, S; Thammasit, P; Intasai, N; Kasinrerk, W; Tayapiwatana, C; Tragoolpua, K

2014-06-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) exhibits overexpression in various cancers and promotes cancer progression and metastasis via the interaction with its associated molecules. The scFv-M6-1B9 intrabody has a potential ability to reduce EMMPRIN cell surface expression. However, the subsequent effect of scFv-M6-1B9 intrabody-mediated EMMPRIN abatement on its related molecules, α3β1-integrin, MCT1, MMP-2 and MMP-9, is undefined. Our results demonstrated that the scFv-M6-1B9 intrabody efficiently decreased α3β1-integrin cell surface expression levels. In addition, intracellular accumulation of MCT1 and lactate were increased. These results lead to suppression of features characteristic for tumor progression, including cell migration, proliferation and invasion, in a colorectal cancer cell line (Caco-2) although there was no difference in MMP expression. Thus, EMMPRIN represents an attractive target molecule for the disruption of cancer proliferation and metastasis. An scFv-M6-1B9 intrabody-based approach could be relevant for cancer gene therapy.

[H2en]2{La2M(SO4)6(H2O)2} (M=Co, Ni): First organically templated 3d-4f mixed metal sulfates

International Nuclear Information System (INIS)

Yuan Yanping; Wang Ruiyao; Kong Deyuan; Mao Jianggao; Clearfield, Abraham

2005-01-01

The first organically templated 3d-4f mixed metal sulfates, [H 2 en] 2 {La 2 M(SO 4 ) 6 (H 2 O) 2 } (M=Co 1, Ni 2) have been synthesized and structurally determined from non-merohedrally twinned crystals. The two compounds are isostructural and their structures feature a three-dimensional anionic network formed by the lanthanum(III) and nickel(II) ions bridged by sulfate anions. The La(III) ions in both compounds are 10-coordinated by four sulfate anions in bidentate chelating fashion, and two sulfate anions in a unidentate fashion. The transition metal(II) ion is octahedrally coordinated by six oxygens from four sulfate anions and two aqua ligands. The doubly protonated enthylenediamine cations are located at the tunnels formed by 8-membered rings (four La and four sulfate anions)

Studies on the Interaction of a Novel 6,6''-bis(1,2,4-triazin-3-yl)- 2,2':6',2''-terpyridine Ligand with Lanthanide(III) Ions and Americium(III)

International Nuclear Information System (INIS)

Lewis, Frank W.; Harwood, Laurence M.; Hudson, Michael J.; Drew, Michael G.B.; Modolo, Giuseppe; Sypula, Michal; Desreux, Jean F.; Bouslimani, Nouri; Vidick, Geoffrey

2010-01-01

The new solvent extraction reagent 6,6''-bis(5,5,8,8-tetramethyl- 5,6,7,8-tetrahydro-1,2,4-benzo-triazin-3-yl)-2,2':6',2''-terpyridine (CyMe 4 -BTTP) has been synthesized in 4 steps from 2,2':6',2''-terpyridine. Detailed NMR and mass spectrometry studies indicate that the ligand forms 1:2 complexes with lanthanide(III) perchlorates where the aliphatic rings are conformationally constrained whereas 1:1 complexes are formed with lanthanide(III) nitrates where the aliphatic rings are conformationally mobile. An optimized structure of the 1:2 solution complex with Yb(III) was obtained from the relative magnitude of the induced paramagnetic shifts. X-ray crystallographic structures of the ligand and of its 1:1 complex with Y(III) were also obtained. In the absence of a phase-modifier, CyMe 4 -BTTP in 1-octanol showed a maximum distribution coefficient of Am(III) of 0.039 (±20%) and a maximum separation factor of Am(III) over Eu(III) of 12.0 from nitric acid solution. The metal(III) cations are extracted as the 1:1 complex from nitric acid solutions. The generally low distribution coefficients observed compared with the BTBPs arise because the 1:1 complex of CyMe 4 -BTTP is considerably less hydrophobic than the 1:2 complexes formed by the BTBPs. In M(BTTP) 3+ complexes, there is a competition between the nitrate ions and the ligand for the complexation of the metal. (authors)

DFT study on oxidation of HS(CH2) m SH ( m = 1-8) in oxidative desulfurization

Science.gov (United States)

Song, Y. Z.; Song, J. J.; Zhao, T. T.; Chen, C. Y.; He, M.; Du, J.

2016-06-01

Density functional theory was employed for calculation of HS(CH2) m SH ( m = 1-8) and its derivatives at B3LYP method at 6-31++g ( d, p) level. Using eigenvalues of LUMO and HOMO for HS(CH2) m SH, the standard electrode potentials were estimated by a stepwise multiple regression techniques (MLR), and obtained as E° = 1.500 + 7.167 × 10-3 HOMO-0.229 LUMO with high correlation coefficients of 0.973 and F values of 43.973.

TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates diet induced obesity and insulin resistance via inhibition of the IP6K1 pathway.

Science.gov (United States)

Ghoshal, Sarbani; Zhu, Qingzhang; Asteian, Alice; Lin, Hua; Xu, Haifei; Ernst, Glen; Barrow, James C; Xu, Baoji; Cameron, Michael D; Kamenecka, Theodore M; Chakraborty, Anutosh

2016-10-01

Obesity and type 2 diabetes (T2D) lead to various life-threatening diseases such as coronary heart disease, stroke, osteoarthritis, asthma, and neurodegeneration. Therefore, extensive research is ongoing to identify novel pathways that can be targeted in obesity/T2D. Deletion of the inositol pyrophosphate (5-IP7) biosynthetic enzyme, inositol hexakisphosphate kinase-1 (IP6K1), protects mice from high fat diet (HFD) induced obesity (DIO) and insulin resistance. Yet, whether this pathway is a valid pharmacologic target in obesity/T2D is not known. Here, we demonstrate that TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine], a pan-IP6K inhibitor, has strong anti-obesity and anti-diabetic effects in DIO mice. Q-NMR, GTT, ITT, food intake, energy expenditure, QRT-PCR, ELISA, histology, and immunoblot studies were conducted in short (2.5-week)- and long (10-week)-term TNP treated DIO C57/BL6 WT and IP6K1-KO mice, under various diet and temperature conditions. TNP, when injected at the onset of HFD-feeding, decelerates initiation of DIO and insulin resistance. Moreover, TNP facilitates weight loss and restores metabolic parameters, when given to DIO mice. However, TNP does not reduce weight gain in HFD-fed IP6K1-KO mice. TNP specifically enhances insulin sensitivity in DIO mice via Akt activation. TNP decelerates weight gain primarily by enhancing thermogenic energy expenditure in the adipose tissue. Accordingly, TNP's effect on body weight is partly abolished whereas its impact on glucose homeostasis is preserved at thermoneutral temperature. Pharmacologic inhibition of the inositol pyrophosphate pathway has strong therapeutic potential in obesity, T2D, and other metabolic diseases.

The "1"2C("1"6O,γ"2"8Si) radiative capture reaction at sub-barrier energies

International Nuclear Information System (INIS)

Goasduff, A.; Courtin, S.; Haas, F.; Lebhertz, D.; Jenkins, D.G.; Fallis, J.; Ruiz, C.; Hutcheon, D.A.; Amandruz, P.A.; Davis, C.; Hager, U.; Ottewell, D.; Ruprecht, G.

2014-01-01

The heavy-ion radiative capture "1"2C("1"6O,γ"2"8Si) was measured at the sub-Coulomb barrier bombarding energy E(lab) = 15.7 MeV, which corresponds to the lowest important resonance observed in the "1"2C + "1"6O fusion excitation function. Thanks to combination of the bismuth germanate (BGO) γ-ray array and the 0 degree DRAGON electromagnetic spectrometer at TRIUMF, the γ-decay spectrum from the entrance channel down to the ground state of "2"8Si was measured. Comparisons of the experimental spectrum to γ spectrum extracted from Monte-Carlo simulations of the complete setup suggest a J"π = 2"+ spin-parity assignment to the entrance channel and yield the radiative capture cross section σ(RC) = 0.22 ± 0.04 μb. Combining this present spin assignment with previous data on radiative capture, a J (J + 1) systematics was constructed, and it indicated a moment of inertia commensurate with the "1"2C+"1"6O grazing angular momentum. Strong dipole transitions are observed from the entrance channel to T = 1 states around 11.5 MeV and are found to result from enhanced M1_I_V transitions to states exhausting a large part of the M1 sum rule built on the ground state of "2"8Si. This specific decay was also reported at bombarding energies close to the Coulomb barrier in our previous study of the "1"2C("1"2C,γ"2"4Mg) heavy-ion radiative capture reaction. Similarities between both systems are investigated. (authors)

6. Investigation of R2M17 compounds

International Nuclear Information System (INIS)

Elemans, J.B.A.A.; Buschow, K.H.J.

1975-01-01

A discussion is presented of the different crystallographic forms that arise in the parent RM 5 (R rare earth including yttrium or thorium; M = Fe, Co or Ni) with CaCu 5 structure in which every third R is replaced by a pair of M. This results in the stoichiometric composition R 2 M 17 . Metallographic studies of well annealed and quenched specimens of CeFesub(x), HoFesub(x) and TmFesub(x) with x varying from 8 to 9.5 showed that only those with x = 8.5 consisted of one phase. Similar experiments with ThNisub(x) and YNisub(x), x varying from 6.5 to 8.5 revealed that in these cases, single phases were obtained with x = 7.5

Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.

Science.gov (United States)

He, D; Kou, X; Luo, Q; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; Zeng, M; Gan, Y; Zhou, Y

2015-01-01

Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio. © International & American Associations for Dental Research 2014.

Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

Directory of Open Access Journals (Sweden)

Shweta Joshi

Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

Fragrance material review on 1-[5(or 6)-methyl-7(or 8)-1-(methylethyl)bicyclo[2.2.2]oct-5-en-2-yl]ethan-1-one.

Science.gov (United States)

Scognamiglio, J; Letizia, C S; Api, A M

2013-12-01

A toxicologic and dermatologic review of 1-[5(Or 6)-Methyl-7(or 8)-1-(methylethyl)bicyclo[2.2.2]oct-5-en-2-yl]ethan-1-one when used as a fragrance ingredient is presented. 1-[5(Or 6)-Methyl-7(or 8)-1-(methylethyl)bicyclo[2.2.2]oct-5-en-2-yl]ethan-1-one is a member of the fragrance structural group Alkyl Cyclic Ketones. These fragrances can be described as being composed of an alkyl, R1, and various substituted and bicyclic saturated or unsaturated cyclic hydrocarbons, R2, in which one of the rings may include up to 12 carbons. Alternatively, R2 may be a carbon bridge of C2-C4 carbon chain length between the ketone and cyclic hydrocarbon. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 1-[5(Or 6)-Methyl-7(or 8)-1-(methylethyl)bicyclo[2.2.2]oct-5-en-2-yl]ethan-1-one were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, phototoxicity, photoallergy, and genotoxicity, data. A safety assessment of the entire Alkyl Cyclic Ketones will be published simultaneously with this document; please refer to Belsito et al., Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2013. A Toxicologic and Dermatologic Assessment of Alkyl Cyclic Ketones When Used as Fragrance Ingredients. (submitted for publication)). for an overall assessment of the safe use of this material and all Alkyl Cyclic Ketones in fragrances. Copyright © 2013 Elsevier Ltd. All rights reserved.

A novel malic enzyme gene, Mime2, from Mortierella isabellina M6-22 contributes to lipid accumulation.

Science.gov (United States)

Li, Shan; Li, Lingyan; Xiong, Xiangfeng; Ji, Xiuling; Wei, Yunlin; Lin, Lianbing; Zhang, Qi

2018-05-18

This study was aimed at cloning and characterizing a novel malic enzyme (ME) gene of Mortierella isabellina M6-22 and identifying its relation with lipid accumulation. Mime2 was cloned from strain M6-22. Plasmid pET32aMIME2 was constructed to express ME of MIME2 in Escherichia coli BL21. After purification, the optimal pH and temperature of MIME2, as well as K m and V max for NADP + were determined. The effects of EDTA or metal ions (Mn 2+ , Mg 2+ , Co 2+ , Cu 2+ , Ca 2+ , or Zn 2+ ) on the enzymatic activity of MIME2 were evaluated. Besides, plasmid pRHMIME2 was created to express MIME2 in Rhodosporidium kratochvilovae YM25235, and its cell lipid content was measured by the acid-heating method. The optimal pH and temperature of MIME2 are 5.8 and 30 °C, respectively. The act ivity of MIME2 was significantly increased by Mg 2+ , Ca 2+ , or Mn 2+ at 0.5 mM but inhibited by Cu 2+ or Zn 2+ (p M6-22 contributes to lipid accumulation in strain YM25235.

Characterization of P1 promoter activity of the β-galactoside α2,6 ...

Indian Academy of Sciences (India)

2012-04-05

Apr 5, 2012 ... The level of β-galactoside α2,6-sialyltransferase I (ST6Gal I) mRNA, encoded by the gene siat1, is increased in malignant tissues. Expression is regulated by different promoters – P1, P2 and P3 – generating three mRNA isoforms. H, X and YZ. In cervical cancer tissue the mRNA isoform H, which results ...

Long non-coding RNA cox-2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization.

Science.gov (United States)

Ye, Yibiao; Xu, Yunxiuxiu; Lai, Yu; He, Wenguang; Li, Yanshan; Wang, Ruomei; Luo, Xinxi; Chen, Rufu; Chen, Tao

2018-03-01

Macrophages have been shown to demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. We investigate long non-coding RNA (lncRNA) cox-2 in macrophage polarization and the regulatory mechanism functions in hepatocellular carcinoma (HCC). Lipopolysaccharide (LPS) was used to induce RAW264.7 macrophages into M1 type, and IL-4 was to induce RAW264.7 macrophages into M2 type. We selected mouse hepatic cell line Hepal-6 and hepatoma cell line HepG2 for co-incubation with M1 or M2 macrophages. Quantitative real-time PCR was used to detect the expressions of lncRNA cox-2 and mRNAs. ELISA was conducted for testing IL-12 and IL-10 expressions; Western blotting for epithelial mesenchymal transition related factors (E-cadherin and Vimentin). An MTT, colony formation assay, flow cytometry, transwell assay, and stretch test were conducted to test cell abilities. The M1 macrophages had higher lncRNA cox-2 expression than that in the non-polarized macrophages and M2 macrophages. The lncRNA cox-2 siRNA decreased the expression levels of IL-12, iNOS, and TNF-α in M1 macrophages, increased the expression levels of IL-10, Arg-1, and Fizz-1 in M2 macrophages (all P evasion and tumor growth by inhibiting the polarization of M2 macrophages. © 2017 Wiley Periodicals, Inc.

The high affinity selectin glycan ligand C2-O-sLex and mRNA transcripts of the core 2 β-1,6-N-acetylglusaminyltransferase (C2GnT1) gene are highly expressed in human colorectal adenocarcinomas

International Nuclear Information System (INIS)

St Hill, Catherine A; Farooqui, Mariya; Mitcheltree, Gregory; Gulbahce, H Evin; Jessurun, Jose; Cao, Qing; Walcheck, Bruce

2009-01-01

The metastasis of cancer cells and leukocyte extravasation into inflamed tissues share common features. Specialized carbohydrates modified with sialyl Lewis x (sLe x ) antigens on leukocyte membranes are ligands for selectin adhesion molecules on activated vascular endothelial cells at inflammatory sites. The activity of the enzyme core 2 β1,6 N-acetylglucosaminyltransferase (C2GnT1) in leukocytes greatly increases their ability to bind to endothelial selectins. C2GnT1 is essential for the synthesis of core 2-branched O-linked carbohydrates terminated with sLe x (C2-O-sLe x ). Our goal was to determine the expression profiles of C2-O-sLe x in the malignant progression and metastasis of colorectal adenocarcinomas. The well characterized CHO-131 monoclonal antibody (mAb) specifically recognizes C2-O-sLe x present in human leukocytes and carcinoma cells. Using CHO-131 mAb, we investigated whether C2-O-sLe x was present in 113 human primary colorectal adenocarcinomas, 10 colorectal adenomas, 46 metastatic liver tumors, 28 normal colorectal tissues, and 5 normal liver tissues by immunohistochemistry. We also examined mRNA levels of the enzyme core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT1) in 20 well, 15 moderately, and 2 poorly differentiated colorectal adenocarcinomas, and in 5 normal colorectal tissues by using quantitative real-time polymerase chain reactions (RT-PCR). We observed high reactivity with CHO-131 mAb in approximately 70% of colorectal carcinomas and 87% of metastatic liver tumors but a lack of reactivity in colorectal adenomas and normal colonic and liver tissues. Positive reactivity with CHO-131 mAb was very prominent in neoplastic colorectal glands of well to moderately differentiated adenocarcinomas. The most intense staining with CHO-131 mAb was observed at the advancing edge of tumors with the deepest invasive components. Finally, we analyzed C2GnT1 mRNA levels in 37 colorectal adenocarcinomas and 5 normal colorectal tissues by RT

Photochemistry of 1 and 2-(2-methylphenyl)-1,6-heptadiene. [4a-methyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene

Energy Technology Data Exchange (ETDEWEB)

Barrows, R.D.; Hornback, J.M.

1982-01-01

In an attempt to synthesize partially saturated phenanthrene derivatives by an intramolecular Diels-Alder reaction between a photochemically produced o-xylylene (diene) and a tethered dienophile, it was found that 1 and 2 underwent a photochemically allowed (2 + 2) cycloaddition. Irradiation of 1 gave 6-(2-methylphenyl)bicyclo(3.2.0)heptane in 86% yield. Upon irradiation of 2, a benzvalene rearrangement of 2 first took place, producing the meta isomer 2-(3-methylphenyl)-1,6-heptadiene, followed by a (2 + 2) photocycloaddition giving 1-(3-methylphenyl)bicyclo(3.2.0)heptane in 15% yield. Direct irradiation of 2-(3-methylphenyl)-1,6-heptadiene gave the same bicyclo derivative as 2 in 34% yield. Examination of the fluorescence spectra of 1 and 2 in comparison with 1-(2-methylphenyl)propene and 2-(2-methylphenyl)-1-butene, respectively, has shown that 1 may be biased toward (2 + 2) cycloaddition where 2 is not biased toward (2 + 2) photocycloization. Attempts to produce 4a-methyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene by an intramolecular Diels-Alder reaction of the o-xylylene produced by irradiation of 3 will also be described.

PGE2-induced colon cancer growth is mediated by mTORC1

International Nuclear Information System (INIS)

Dufour, Marc; Faes, Seraina; Dormond-Meuwly, Anne; Demartines, Nicolas; Dormond, Olivier

2014-01-01

Highlights: • PGE 2 activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE 2 induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE 2 induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E 2 (PGE 2 ) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE 2 directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE 2 -induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE 2 increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE 2 EP 4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE 2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE 2 -induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE 2 increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE 2 mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth

Measurement of the figure of merit M for 1-C3F6/SF6 mixtures

DEFF Research Database (Denmark)

Christensen, Jørn Erik Berril; McAllister, Iain Wilson

1997-01-01

High precision measurements of the linear part of the Paschen curve are reported for 1-C3F6/SF6 mixtures. From these measurements, values for the pressure-reduced limiting electric field strength (E/p)lim and the associated figure of merit M are derived. These two parameters can be used to charac......High precision measurements of the linear part of the Paschen curve are reported for 1-C3F6/SF6 mixtures. From these measurements, values for the pressure-reduced limiting electric field strength (E/p)lim and the associated figure of merit M are derived. These two parameters can be used...

Evaluation of Ca3(Co,M2O6 (M=Co, Fe, Mn, Ni as new cathode materials for solid-oxide fuel cells

Directory of Open Access Journals (Sweden)

Fushao Li

2015-10-01

Full Text Available Series compounds Ca3(Co0.9M0.12O6 (M=Co, Fe, Mn, Ni with hexagonal crystal structure were prepared by sol–gel route as the cathode materials for solid oxide fuel cells (SOFCs. Effects of the varied atomic compositions on the structure, electrical conductivity, thermal expansion and electrochemical performance were systematically evaluated. Experimental results showed that the lattice parameters of Ca3(Co0.9Fe0.12O6 and Ca3(Co0.9Mn0.12O6 were both expanded to certain degree. Electron-doping and hole-doping effects were expected in Ca3(Co0.9Mn0.12O6 and Ca3(Co0.9Ni0.12O6 respectively according to the chemical states of constituent elements and thermal-activated behavior of electrical conductivity. Thermal expansion coefficients (TEC of Ca3(Co0.9M0.12O6 were measured to be distributed around 16×10−6 K−1, and compositional elements of Fe, Mn, and Ni were especially beneficial for alleviation of the thermal expansion problem of cathode materials. By using Ca3(Co0.9M0.12O6 as the cathodes operated at 800 °C, the interfacial area-specific resistance varied in the order of M=Co=Mn, and the over-potential increased in the order of M=Fe≈M=Co=Ni. Among all of these compounds, Ca3(Co0.9Fe0.12O6 showed the best electrochemical performance and the power density as high as ca. 500 mW cm−2 at 800 °C achieved in the single cell with La0.8Sr0.2Ga0.83Mg0.17O2.815 as electrolyte and Ni–Ce0.8Sm0.2O1.9 as anode. Ca3(Co0.9M0.12O6 (M=Co, Fe, Mn, Ni can be used as the cost-effective cathode materials for SOFCs.

Integral Representation of the Pictorial Proof of Sum of [superscript n][subscript k=1]k[superscript 2] = 1/6n(n+1)(2n+1)

Science.gov (United States)

Kobayashi, Yukio

2011-01-01

The pictorial proof of the sum of [superscript n][subscript k=1] k[superscript 2] = 1/6n(n+1)(2n+1) is represented in the form of an integral. The integral representations are also applicable to the sum of [superscript n][subscript k-1] k[superscript m] (m greater than or equal to 3). These representations reveal that the sum of [superscript…

Variations of force constants, M-O distances and bond order in solid solutions between Ba/sub 2/MgUO/sub 6/ and Ba/sub 2/MgWO/sub 6/

Energy Technology Data Exchange (ETDEWEB)

Kemmler-Sack, S; Fadini, A [Tuebingen Univ. (Germany, F.R.). Inst. fuer Chemie

1977-12-01

In solid solutions between the 1:1 ordered perovskites Ba/sub 2/MgUO/sub 6/ and Ba/sub 2/MgWO/sub 6/ (system Ba/sub 2/MgUsub(1-x)Wsub(x)O/sub 6/) the force constants of the UO/sub 6/ and WO/sub 6/ octahedras are variied. The valence force constants fsub(MO) tend to adjust for each x. The bond order and the M-O distances are reported as well.

Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

International Nuclear Information System (INIS)

Qin, Tian; Wang, Chenlong; Chen, Xuewei; Duan, Chenfan; Zhang, Xiaoyan; Zhang, Jing; Chai, Hongyan; Tang, Tian; Chen, Honglei; Yue, Jiang; Li, Ying; Yang, Jing

2015-01-01

Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing the coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor

Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

Energy Technology Data Exchange (ETDEWEB)

Qin, Tian; Wang, Chenlong; Chen, Xuewei; Duan, Chenfan; Zhang, Xiaoyan [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Chen, Honglei [Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yue, Jiang [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Li, Ying, E-mail: lyying0@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

2015-07-15

Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing the coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor

A new perylenequinone from a halotolerant fungus, Alternaria sp. M6.

Science.gov (United States)

Zhang, Song-Ya; Li, Zhan-Lin; Bai, Jiao; Wang, Yu; Zhang, Li-Min; Wu, Xin; Hua, Hui-Ming

2012-01-01

To study the metabolites of a halotolerant fungus Alternaria sp. M6. The metabolites were isolated and purified by various chromatographic techniques. Their structures were determined on the basis of physical properties and spectroscopic data. Nine compounds were isolated and identified as 8β-chloro-3, 6aα, 7β, 9β, 10-pentahydroxy-9, 8, 7, 6a-tetrahydroperylen-4(6aH)-one (1), alterperylenol (2), dihydroalterperylenol (3), adenine (4), adenosine (5), deoxyadenosine (6), guanosine (7), tryptophan (8), and hexadecanoic acid (9). Compound 1 is a new perylenequinone. Copyright © 2012 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Evaluation of autogenous tooth transplantation for replacement of the missing or unrestorable mandibular molar tooth

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Wahiduj Jaman

2017-06-01

Full Text Available This study was undertaken to evaluate the functional and occlusal stability of autogenous tooth transplantation. A total of 30 patients were included. Among them, 21 participants received transplanted first molar and the remaining 9 received transplanted second molar. In all the cases, donor tooth were third molar. In each participant, extraction of un-restorable first or second molar tooth was performed which was then replaced by atrumatic extracted third molar tooth. Each third molar tooth was placed in the recipient extracted socket, followed by the evaluation of the occlusion and then stabilized with arch bar and ligature wire. Clinical follow-up evaluation was performed at 15 days, 3 and 12 months in respect to occlusal stability, tooth mobility and periodontal status. It was found that 23 transplanted tooth were successful and the remaining 7 tooth need long-term observation for the final outcome, which was statistically significant. It can be concluded that the autogenous tooth transplantation can replace missing tooth to ensure the preservation of function, aesthetic and to prevent bone resorption of the missing area of the jaw, which can lead to exceptional esthetic and functional outcome.

Alfinated coating structure on HS6-5-2 (SW7M high speed steel

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T. Szymczak

2010-10-01

Full Text Available The paper presents the results of immersion alfinated coating structure in AlSi5 silumin on HS6-5-2 (SW7M high speed steel. Alfinating bath temperature was 750 ± 5 ° C, time of sample immersion was τ = 180s. Thickness of obtained coating under specified conditions was g = 150μm. Manufactured coating consists of three layers of different construction phase. The first layer from the substrate „g1`” constructed with a AlFe phase consist of alloy additives constituents of HS6-5-2 (SW7M steel: W, Mo, V, Cr and Si. On it crystallizes the second layer „g1``” of AlFeWMoCr intermetallic phases also containing Si and small amount of V. Last, the outer layer „g2” of the coating is composed with silumin including AlFeWMoCrVSi intermetallic phases. Within all layers of the coating occurs carbides. Penetration of carbides to individual coating layers is mainly due to steel surface partial melting and crystallizing layers „g1`” and „g1``” by alfinating liquid and shifting into her of carbides as well as partial carbides rejection by crystallization front of intermetallic phases occurs in coating.

Rac1 Regulates the Activity of mTORC1 and mTORC2 and Controls Cellular Size

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Saci, Abdelhafid; Cantley, Lewis C.; Carpenter, Christopher L.

2013-01-01

SUMMARY Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two separate complexes, mTORC1 and mTORC2, that function to control cell size and growth in response to growth factors, nutrients, and cellular energy levels. Low molecular weight GTP-binding proteins of the Rheb and Rag families are key regulators of the mTORC1 complex, but regulation of mTORC2 is poorly understood. Here, we report that Rac1, a member of the Rho family of GTPases, is a critical regulator of both mTORC1 and mTORC2 in response to growth-factor stimulation. Deletion of Rac1 in primary cells using an inducible-Cre/Lox approach inhibits basal and growth-factor activation of both mTORC1 and mTORC2. Rac1 appears to bind directly to mTOR and to mediate mTORC1 and mTORC2 localization at specific membranes. Binding of Rac1 to mTOR does not depend on the GTP-bound state of Rac1, but on the integrity of its C-terminal domain. This function of Rac1 provides a means to regulate mTORC1 and mTORC2 simultaneously. PMID:21474067

Chemistry and heat-treatment effects on mechanical and microstructural properties of heat-treated, beta-extruded Ti--6A1--6V--2Sn

International Nuclear Information System (INIS)

Ulitchny, M.G.; Rack, H.J.; Dawson, D.B.

1979-04-01

The mechanical behavior of beta-extruded Ti--6A1--6V--2Sn was examined after a variety of sub-transus heat treatments. The microstructural variations resulting from the range of heat treatments studied also were examined. A range of alloy chemistries, within commercial limits, was used to evaluate the effect of this variable on mechanical properties. The strength--toughness combinations obtained in beta-extruded Ti--6A1--6V--2Sn ranged from about 895 MPa and 82.5 MPa√m for duplex annealed material to 1200 MPa and 54.9 MPa√m for solution treated and peak aged material. Chemistry variations had less effect on mechanical properties than would have been the case with alpha--beta processing

Cubic Re6+ (5d1) Double Perovskites, Ba2MgReO6, Ba2ZnReO6, and Ba2Y2/3ReO6: Magnetism, Heat Capacity, μSR, and Neutron Scattering Studies and Comparison with Theory.

Science.gov (United States)

Marjerrison, Casey A; Thompson, Corey M; Sala, Gabrielle; Maharaj, Dalini D; Kermarrec, Edwin; Cai, Yipeng; Hallas, Alannah M; Wilson, Murray N; Munsie, Timothy J S; Granroth, Garrett E; Flacau, Roxana; Greedan, John E; Gaulin, Bruce D; Luke, Graeme M

2016-10-04

Double perovskites (DP) of the general formula Ba 2 MReO 6 , where M = Mg, Zn, and Y 2/3 , all based on Re 6+ (5d 1 , t 2g 1 ), were synthesized and studied using magnetization, heat capacity, muon spin relaxation, and neutron-scattering techniques. All are cubic, Fm3̅m, at ambient temperature to within the resolution of the X-ray and neutron diffraction data, although the muon data suggest the possibility of a local distortion for M = Mg. The M = Mg DP is a ferromagnet, T c = 18 K, with a saturation moment ∼0.3 bohr magnetons at 3 K. There are two anomalies in the heat capacity: a sharp feature at 18 K and a broad maximum centered near 33 K. The total entropy loss below 45 K is 9.68 e.u., which approaches R ln 4 (11.52 e.u.) supporting a j = 3/2 ground state. The unit cell constants of Ba 2 MgReO 6 and the isostructural, isoelectronic analogue, Ba 2 LiOsO 6 , differ by only 0.1%, yet the latter is an anti-ferromagnet. The M = Zn DP also appears to be a ferromagnet, T c = 11 K, μ sat (Re) = 0.1 μ B . In this case the heat capacity shows a somewhat broad peak near 10 K and a broader maximum at ∼33 K, behavior that can be traced to a smaller particle size, ∼30 nm, for this sample. For both M = Mg and Zn, the low-temperature magnetic heat capacity follows a T 3/2 behavior, consistent with a ferromagnetic spin wave. An attempt to attribute the broad 33 K heat capacity anomalies to a splitting of the j = 3/2 state by a crystal distortion is not supported by inelastic neutron scattering, which shows no transition at the expected energy of ∼7 meV nor any transition up to 100 meV. However, the results for the two ferromagnets are compared to the theory of Chen, Pereira, and Balents, and the computed heat capacity predicts the two maxima observed experimentally. The M = Y 2/3 DP, with a significantly larger cell constant (3%) than the ferromagnets, shows predominantly anti-ferromagnetic correlations, and the ground state is complex with a spin frozen component T

Direct Reduction of 1,2- and 1,6-Dibromohexane at Silver Cathodes in Dimethylformamide

International Nuclear Information System (INIS)

Martin, Erin T.; Strawsine, Lauren M.; Mubarak, Mohammad S.; Peters, Dennis G.

2015-01-01

Electrochemical reduction of 1,2-dibromohexane (1) and 1,6-dibromohexane (2) at silver cathodes in dimethylformamide (DMF) containing tetramethylammonium perchlorate (TMAP) has been investigated with the aid of cyclic voltammetry and controlled-potential electrolysis. Cyclic voltammograms for reduction of 1 and 2 both exhibit a single irreversible cathodic peak associated with reduction of carbon–bromine bonds; however, the cathodic peak potential (−0.33 V) for 1 is significantly less negative than that (−1.00 V) for 2, and the peak current for 1 is approximately half of that for 2. Cyclic voltammograms for 0.5–20.0 mM solutions of 1 and 2, separately, show that the parameter I pc /C* increases as the concentration (C*) decreases; this trend is likely due to a combination of adsorption phenomena and a potential-dependent transfer coefficient (α). Coulometric n values and product distributions arising from bulk electrolyses of 5.0 mM solutions of 1 and 2 depend on the positions of the bromine atoms: (a) for 1, n was 2.13 and 1-hexene was the only product; (b) for 2, n was 2.12 and a mixture of products was obtained [1-hexene (21%), n-hexane (37%), 1,5-hexadiene (22%), 5-hexen-1-ol (9%), and a trace of n-dodecane]. When 2 was electrolyzed in the presence of a proton or deuteron donor (2,2,2-trifluoroethanol or D 2 O), the n value and the amount of n-hexane increased, whereas 1-hexene and 1,5-hexadiene decreased in yield. We conclude that reduction of 1 follows a concerted mechanism, but that reduction of 2 proceeds via carbanionic intermediates.

Synthesis of 6-Substituted 2-Pyrones Starting from Renewable Resources: Total Synthesis of Sibirinone, (E)-6-(Pent-1-en-1-yl)-2H-pyran-2-one, and (E)-6-(Hept-1-en-1-yl)-2H-pyran-2-one.

Science.gov (United States)

Dobler, Daniel; Reiser, Oliver

2016-11-04

An atom-economic reaction sequence to 6-substituted 2-pyrones was developed starting from furfuryl alcohol, a renewable resource made from bran or bagasse, and aldehydes, utilizing a thermal rearrangement of cyclopentadienone epoxides as key step. Derivatives bearing a hydroxyalkyl side chain could be enzymatically resolved, providing access to enantiomerically pure 2-pyrones, or converted to alkenyl-substituted 2-pyrones such as naturally occurring sibirinone, (E)-6-(pent-1-en-1-yl)-2H-pyran-2-one, and (E)-6-(hept-1-en-1-yl)-2H-pyran-2-one.

Novel routes to 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines and 5,6,9,10,11,11a-hexahydro-8H-pyrido[1,2-a]pyrrolo[2,1-c]pyrazines.

Science.gov (United States)

Katritzky, Alan R; Jain, Ritu; Xu, Yong-Jiang; Steel, Peter J

2002-11-15

Condensation reactions of benzotriazole and 2-(pyrrol-1-yl)-1-ethylamine (1) with formaldehyde and glutaric dialdehyde, respectively, afforded intermediates 2 and 6. Subsequent nucleophilic substitutions of the benzotriazole group in 2 and 6 with Grignard reagents, sodium cyanide, and sodium borohydride gave 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines 3a-e, 4, 5 and 5,6,9,10,11,11a-hexahydro-8H-pyrido[1,2-a]pyrrolo[2,1-c]pyrazines 7a-c, 8, 9, respectively, in good yields.

Complex titanates Sr_1_-_xPb_xLi_2Ti_6O_1_4 (0≤x≤1) as anode materials for high-performance lithium-ion batteries

International Nuclear Information System (INIS)

Qian, Shangshu; Yu, Haoxiang; Yan, Lei; Li, Peng; Lin, Xiaoting; Wu, Yaoyao; Long, Nengbing; Shui, Miao; Shu, Jie

2016-01-01

Highlights: • Sr_1_-_xPb_xLi_2Ti_6O_1_4 (0≤x≤1) is prepared by a simple solid state reaction. • Sr_0_._5Pb_0_._5Li_2Ti_6O_1_4 exhibits enhanced lithium storage capability. • Sr_0_._5Pb_0_._5Li_2Ti_6O_1_4 can deliver a capacity of 141.8 mAh g"−"1 at 700 mA g"−"1. • In-situ XRD is performed to study the reversibility of Sr_1_-_xPb_xLi_2Ti_6O_1_4. - Abstract: With the Pb doping content at Sr-site increasing, a series of Sr_1_-_xPb_xLi_2Ti_6O_1_4 (x = 0, 0.25, 0.50, 0.75, 1.0) are synthesized by a simple solid-state reaction. It is found that the reversible capacity and rate capability experience a parabolic course from SrLi_2Ti_6O_1_4 to PbLi_2Ti_6O_1_4. Among all the as-prepared samples, Sr_0_._5Pb_0_._5Li_2Ti_6O_1_4 shows the best cycling and rate properties. It delivers an initial charge capacity of 163.2 mAh g"−"1 at 100 mA g"−"1 with the capacity retention of 96.08% after 100 cycles. In addition, it can also deliver a reversible capacity of 141.8 mAh g"−"1 at 700 mA g"−"1. The superior electrochemical properties of Sr_0_._5Pb_0_._5Li_2Ti_6O_1_4 are attributed to the reduced charge transfer resistance and increased lithium-ion diffusion coefficient after doping. Besides, in-situ X-ray diffraction is also performed to investigate the lithium-ion insertion/extraction behaviors of SrLi_2Ti_6O_1_4, Sr_0_._5Pb_0_._5Li_2Ti_6O_1_4 and PbLi_2Ti_6O_1_4. The observed results confirm that Sr_0_._5Pb_0_._5Li_2Ti_6O_1_4 has good structural stability and reversibility for repeated lithium storage.

No-carrier-added (NCA) synthesis of 6-[18F]fluoro-L-DOPA using 3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[6S-(6α, 8α, 8αβ)]-6,8-methano-2H-1,4-benzoxazin-2-one

International Nuclear Information System (INIS)

Horti, A.; Yale Univ., West Haven, CT; Redmond, D.E. Jr.; Soufer, R.

1995-01-01

3,5,6,7,8,8a-Hexahydro-7,7,8a-trimethyl-[6S-(6α,8α , 8αβ)]-6,8-methano-2H-1,4-benzoxazino-2-one (2) was investigated as chiral auxiliary for asymmetric NCA nucleophilic synthesis of 6-[ 18 F]Fluoro-L-DOPA. Direct condensation of 3,4-dimethoxy-2-[ 18 F]fluorobenzaldehyde (1a) or 6-[ 18 F]fluoro-piperonal (1b) in the presence of NaH with 2 gave the corresponding [ 18 F]-3-[(2-fluorophenyl)methylene]-3,5,6,7,8,8a-hexahydro-7,7,8 a-trimethyl-[6S-(3Z,3α,6α,8α,8αβ)]-6, 8-methano-2H-1,4-benzoxazin-2-one derivative 3a or 3b as a single stereoisomer. L-Selectride promoted hydrogenation of the olefinic double bond of these derivatives, in presence of tertbutyl alcohol, afforded the corresponding [ 18 F]-3-[(2-fluorophenyl) methyl]-3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[3S-(3α, 6α, 8α8αβ)]-6,8-methano-2H-1,4-benzoxazin-2-one derivatives (4a,b) without affecting the orientation of diasterofacial discrimination. Deprotection of the derivatives 4a,b yielded 6-[ 18 F]fluoro-L-DOPA (e.e. >90%, 3% radiochemical yield (EOB), total synthesis time 125 min, specific activity >2000 mCi/μmol). Direct deprotection/reduction of the compounds 3a,b provides the enantiomeric mixture of 6-[ 18 F]fluoro-D,L-DOPA (10-12% radiochemical yield) and, after chiral separation, 6-[ 18 F]fluoro-L-DOPA (e.e. 98%, 4-5% radiochemical yield). (author)

Isoliquiritigenin, a flavonoid from licorice, blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE{sub 2} and IL-6

Energy Technology Data Exchange (ETDEWEB)

Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Xinhua [Department of Liver, Biliary And Pancreatic Tumors, Hubei Cancer Hospital, Wuhan 430079 (China); Chen, Xuewei; Li, Ying; Ke, Zunqiong [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Guo, Austin M. [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Chen, Honglei, E-mail: hl-chen@whu.edu.cn [Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China)

2014-09-15

M2 macrophage polarization is implicated in colorectal cancer development. Isoliquiritigenin (ISL), a flavonoid from licorice, has been reported to prevent azoxymethane (AOM) induced colon carcinogenesis in animal models. Here, in a mouse model of colitis-associated tumorigenesis induced by AOM/dextran sodium sulfate (DSS), we investigated the chemopreventive effects of ISL and its mechanisms of action. Mice were treated with AOM/DSS and randomized to receive either vehicle or ISL (3, 15 and 75 mg/kg). Tumor load, histology, immunohistochemistry, and gene and protein expressions were determined. Intragastric administration of ISL for 12 weeks significantly decreased colon cancer incidence, multiplicity and tumor size by 60%, 55.4% and 42.6%, respectively. Moreover, ISL inhibited M2 macrophage polarization. Such changes were accompanied by downregulation of PGE{sub 2} and IL-6 signaling. Importantly, depletion of macrophages by clodronate (Clod) or zoledronic acid (ZA) reversed the effects of ISL. In parallel, in vitro studies also demonstrated that ISL limited the M2 polarization of RAW264.7 cells and mouse peritoneal macrophages with concomitant inactivation of PGE{sub 2}/PPARδ and IL-6/STAT3 signaling. Conversely, exogenous addition of PGE{sub 2} or IL-6, or overexpression of constitutively active STAT3 reversed ISL-mediated inhibition of M2 macrophage polarization. In summary, dietary flavonoid ISL effectively inhibits colitis-associated tumorigenesis through hampering M2 macrophage polarization mediated by the interplay between PGE{sub 2} and IL-6. Thus, inhibition of M2 macrophage polarization is likely to represent a promising strategy for chemoprevention of colorectal cancer. - Highlights: • Isoliquiritigenin (ISL) prevents colitis-associated tumorigenesis. • ISL inhibits M2 macrophage polarization in vivo and in vitro. • ISL inhibits PGE{sub 2} and IL-6 signaling in colitis-associated tumorigenesis. • ISL may be an attractive candidate agent for

ST6Gal1, Cox-2 and HB-EGF mRNA Expression in Breast Cancer

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Aliakbar Taherian

2015-01-01

Full Text Available Background: ST6Gal1, Cox-2 and HB-EGF genes are involved in different tumors and their enhanced expressions often correlate with poor prognosis. In this study we assay the expressions of these genes by reverse transcriptase-PCR in 54 breast cancer samples. Methods: Tissue samples were either formalin-fixed for histopathological examination or frozen for reverse transcriptase-PCR. Image program was used for the densitometry of the image of the gels and the expression of different genes was normalized with beta actin expression. The student's t-test and correlation matrix were used for data analyses. Results: We observed significantly higher expressions of ST6Gal1 (P= 0.040, Cox- 2 (P= 0.001 and HB-EGF (P= 0.009 in the tumor region compared to the margin samples. A significant correlation was found between HB-EGF and Cox-2 expression (P= 0.001. There was a positive correlation between total score, tumor size, histology grade and nuclear grade but there was a reverse correlation between age and tumor size, histology grade and total score. Conclusion: Expressions of ST6Gal1, Cox-2 and HB-EGF in breast tumor samples in this and a number of other studies emphasize their role as important markers in breast cancer. The use of medications to inhibit either their individual expressions or the possible inhibition of all three genes may improve patient survival and prevent metastasis.

Molecules based on M(v) (M=Mo, W) and Ni(II) ions: a new class of trigonal bipyramidal cluster and confirmation of SMM behavior for the pentadecanuclear molecule {NiII[NiII(tmphen)(MeOH)]6[Ni(H2O)3]2[micro-CN]30[WV(CN)3]6}.

Science.gov (United States)

Hilfiger, Matthew G; Zhao, Hanhua; Prosvirin, Andrey; Wernsdorfer, Wolfgang; Dunbar, Kim R

2009-07-14

The preparation, single crystal X-ray crystallography, and magnetic properties are reported for four new clusters based on [M'V(CN)8]3- octacyanometallates (M'=Mo, W). Reactions of [M'V(CN)8]3- with mononuclear NiII ions in the presence of the tmphen blocking ligand (tmphen=3,4,7,8-tetramethyl-1,10-phenanthroline) in a 2:3:6 ratio, respectively, lead to the formation of the trigonal bipyramidal clusters [NiII(tmphen)2]3[M'V(CN)8]2. Analogous reactions with the same starting materials performed in a 2:3:2 ratio, respectively, produce pentadecanuclear clusters of the type {NiII[NiII(tmphen)(MeOH)]6[Ni(H2O)3]2[micro-CN]30[WV(CN)3]6}. The W2Ni3 (1) and Mo2Ni3(2) pentanuclear clusters and the W6Ni9 (3) and Mo6Ni9 (4) pentadecanuclear molecules are isostructural to each other and crystallize in the space groups P2(1)/c and R3 respectively. Magnetic measurements indicate that the ground states for the trigonal bipyamidal clusters are S=4 as a consequence of ferromagnetic coupling with JW-Ni=9.5 cm(-1), JMo-Ni=10 cm(-1). The pentadecanuclear clusters exhibit ferromagnetic coupling as well, which leads to S=12 ground states (JW-Ni=12 cm(-1), JMo-Ni=12.2 cm(-1)). Reduced magnetization studies on the W-Ni analogues support the conclusion that they exhibit a negative axial anisotropy term; the fits give D values of -0.24 cm(-1) for the W2Ni3 cluster and D=-0.04 cm(-1)for the W6Ni9 cluster. AC susceptibility measurements indicate the beginning of an out-of-phase signal for the W2Ni3 and the W6Ni9 compounds, but detailed low temperature studies on small crystals by the microSQUID technique indicate that only the pentadecanuclear cluster exhibits hysteresis in accord with SMM behavior. Neither Mo cluster reveals any evidence for slow paramagnetic relaxation at low temperatures.

Design, synthesis and photoelectrochemical properties of hexagonal metallomacrocycles based on triphenylamine: [M6(4,4'-bis(2,2':6',2''-terpyridinyl)triphenylamine)6(X)12]; [M = Fe(II), PF6- and Zn(II), BF4-].

Science.gov (United States)

Hwang, Seok-Ho; Moorefield, Charles N; Wang, Pingshan; Fronczek, Frank R; Courtney, Brandy H; Newkome, George R

2006-08-07

Synthesis of a novel bis(terpyridine) ligand, 4,4'-bis(2,2':6',2''-terpyridinyl)triphenylamine, utilizing triphenylamine, as a specific angle controller, has led to the self-assembly of a unique hexagonal metallomacrocycle family, [Fe6(2)6(PF6)12] and [Zn6(2)6(BF4)12], utilizing terpyridine-metal(II)-terpyridine connectivity. The crystal structure of the novel ligand shows that the angle between the two terpyridinyl moieties is 119.69 degrees , which enabled the formation of the hexagonal-shaped macrocycles. The crystal packing architectures of this starting ligand revealed channels induced by solvent encapsulation. Following complexation of this ligand with transition metals [Fe(II) or Zn(II)] in a one-pot reaction, the resultant structures were characterized by (1)H and (13)C NMR, UV/Vis and mass spectroscopies. The expected metal-to-ligand charge transfer (MLCT; lambda(max) = 582 nm) and emission (lambda(em) = 575 nm) characteristics were exhibited by both [Fe6(2)6(PF6)12] and[Zn6(2)6(BF4)12]. The photoelectrochemical characteristics of these hexagonal metallomacrocycles demonstrate that they can be used as sensitizers in dye-sensitized solar cells.

26 CFR 1.401(m)-2 - ACP test.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 5 2010-04-01 2010-04-01 false ACP test. 1.401(m)-2 Section 1.401(m)-2 Internal... TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(m)-2 ACP test. (a) Actual contribution percentage (ACP) test—(1) In general—(i) ACP test formula. A plan satisfies the ACP test for a plan year only...

Phase stability, crystal structure and magnetism in (U1-xNbx)2 Ni21B6 and (UyNb1-y)3Ni20B6

Science.gov (United States)

Provino, Alessia; Bhattacharya, Amitava; Dhar, Sudesh K.; Pani, Marcella; Gatti, Flavio; Paudyal, Durga; Manfrinetti, Pietro

Ternary phases with composition T2M21X6 and T3M20X6 (T = transition metal; M = 3 d metal; X = B, C, P) are reported to crystallize with the W2Cr21C6-type and Mg3Ni20B6-type, respectively (ternary ordered derivatives of the cubic Cr23C6-type, cF116). They attract interest due to their refractory, mechanical, and peculiar magnetic properties. Literature data on these compounds only concern apparently stoichiometric 2:21:6 and 3:20:6 phases. Often only nominal composition has been reported, with few structural refinements and no measurements of physical properties. Lack of detailed stoichiometry and crystallographic data does not allow sufficient understanding of the crystal chemistry and properties of these compounds. We studied stability, crystal structure and magnetism of (U1-xNbx)2 Ni21B6 and (UyNb1-y)3Ni20B6; stable phases are U2Ni21B6 and Nb3Ni20B6, as also confirmed by theoretical calculations. The two pristine compounds solubilize Nb and U, respectively, up to a given extent. The substitution of U by Nb leads to a structural change from the W2Cr21C6- to the Mg3Ni20B6-type. While U2Ni21B6 is a Pauli paramagnet (itinerant non-magnetic state of U-5 f electrons), in agreement with literature, magnetization data for (UyNb1-y)3 Ni20B6 show itinerant ferromagnetism with TC >300 K.

Regulatory Role of N6 -methyladenosine (m6 A) Methylation in RNA Processing and Human Diseases.

Science.gov (United States)

Wei, Wenqiang; Ji, Xinying; Guo, Xiangqian; Ji, Shaoping

2017-09-01

N 6 -methyladenosine (m 6 A) modification is an abundant and conservative RNA modification in bacterial and eukaryotic cells. m 6 A modification mainly occurs in the 3' untranslated regions (UTRs) and near the stop codons of mRNA. Diverse strategies have been developed for identifying m 6 A sites in single nucleotide resolution. Dynamic regulation of m 6 A is found in metabolism, embryogenesis, and developmental processes, indicating a possible epigenetic regulation role along RNA processing and exerting biological functions. It has been known that m 6 A editing involves in nuclear RNA export, mRNA degradation, protein translation, and RNA splicing. Deficiency of m 6 A modification will lead to kinds of diseases, such as obesity, cancer, type 2 diabetes mellitus (T2DM), infertility, and developmental arrest. Some specific inhibitors against methyltransferase and demethylase have been developed to selectively regulate m 6 A modification, which may be advantageous for treatment of m 6 A related diseases. J. Cell. Biochem. 118: 2534-2543, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Synthesis and Screening of Modified 6,6'-Bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydrobenzo[e][1,2,4]triazin-3-yl)-2,2'-bipyridine Ligands for Actinide and Lanthanide Separation in Nuclear Waste Treatment.

Science.gov (United States)

Afsar, Ashfaq; Distler, Petr; Harwood, Laurence M; John, Jan; Westwood, James

2016-11-04

Effects of chloro and bromo substitution at the 4-position of the pyridine ring of 6,6'-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydrobenzo[e][1,2,4]triazin-3-yl)-2,2'-bipyridine (CyMe 4 -BTBP) have been studied with regard to the extraction of Am(III) from Eu(III) and Cm(III) from 0.1-3 M HNO 3 . Similarly to CyMe 4 -BTBP, a highly efficient (D Am > 10 at 3 M HNO 3 ) and selective (SF Am/Eu > 100 at 3 M HNO 3 ) extraction was observed for Cl-CyMe 4 -BTBP and Br-CyMe 4 -BTBP in 1-octanol but in the absence of a phase-transfer agent.

Separation of thorium, uranium and rare-earth elements with 2-[(2-arsenophenyl)-azo]-1,8-dihydroxy-7-[(2,4,6-tribromophenyl)azo]-naphthalene-3,6-disulfonic acid by capillary electrophoresis

International Nuclear Information System (INIS)

Liu, Bi-feng; Liu, Liang-bin; Cheng, Jie-ke

1998-01-01

The separation of thorium, uranium and rare-earth elements (RE) as their 2-[(2-arsenophenyl)-azo]-1,8-dihydroxy-7-[(2,4,6-tribromophenyl)azo]-naphthalene-3,6-disulfonic acid complexes by capillary electrophoresis with direct UV-Vis detection is presented in this paper. The influences of pH value and concentration of electrolyte, voltage and surfactant on separation were investigated and optimized. Under the selected conditions (30mM NaAc-HCl buffer containing 0.5mM cetyltrimethylammonium bromide and 0.2mM chelating reagent, pH 4.30, 12KV, 635nm as detection wavelength), the coexisted ions were separated within 4min, and limits of detection of 37, 39, 199μgl -1 for RE, thorium, uranium with a linear dynamic range of over 2 orders of magnitude were achieved, respectively

Inhibition of mild steel corrosion by 1,4,6-trimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile and synergistic effect of halide ion in 0.5 M H{sub 2}SO{sub 4}

Energy Technology Data Exchange (ETDEWEB)

Mourya, Punita, E-mail: mouryapunita025@gmail.com [Department of Chemistry, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005 (India); Singh, Praveen [Department of Chemistry, Banaras Hindu University, Varanasi 221005 (India); Rastogi, R.B.; Singh, M.M. [Department of Chemistry, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005 (India)

2016-09-01

Highlights: • TODPCN is a good corrosion inhibitor for mild steel in 0.5 M H{sub 2}SO{sub 4} solution. • Addition of iodide ion increases the inhibition efficiency of the studied nitrile derivative. • Inhibition efficiency successively increases with concentration. • XPS study has revealed the chemical composition of the protective film. - Abstract: The effect of iodide ions on inhibitive performance of 1,4,6-trimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (TODPCN) on mild steel (MS) corrosion in 0.5 M H{sub 2}SO{sub 4} was studied using gravimetric and electrochemical measurements. TODPCN inhibits the corrosion of MS to the extent of 62.3% at its lowest concentration (0.5 mM) and its inhibition efficiency (η) further increases on increasing concentration at 298 K. The adsorption of TODPCN on MS was found to follow the Langmuir adsorption isotherm. The value of η increased on the addition of 2.0 mM KI. The value of synergism parameter being more than unity indicates that the enhanced η value in the presence of iodide ions is only due to synergism. Thus, a cooperative mechanism of inhibition exists between the iodide anion and TODPCN cations. The increase in surface coverage in the presence of KI indicates that iodide ions enhance the adsorption of TODPCN. The surface morphology of corroded/inhibited MS was studied by atomic force microscopy. X-ray photoelectron spectroscopy of inhibited MS surface was carried out to determine the composition of the adsorbed film. Some quantum chemical parameters and the Mulliken charge densities for TODPCN calculated by density functional theory provided further insight into the mechanism of inhibition.

(2aR*,5S*,6aS*,8aS*,E-Ethyl 5-hydroxy-7,7,8a-trimethyl-8-oxo-2,2a,6,6a,7,8,8a,8b-octahydro-1H-pentaleno[1,6-bc]oxepine-4-carboxylate

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Goverdhan Mehta

2012-12-01

Full Text Available The title compound, C17H24O5, featuring a 2-carbethoxy-3-oxepanone unit in its intramolecularly O—H...O hydrogen-bonded enol form, was obtained via [(CF3CO22Rh]2-catalysed intramolecular O—H bond insertion in the α-diazo-ω-hydroxy-β-ketoester, ethyl 4-[(1S,3aS,6R,6aS-6-hydroxy-2,2,3a-trimethyl-3-oxo-octahydropentalen-1-yl]-2-diazo-3-oxobutanoate. The seven-membered oxacyclic ring, thus constructed on a cis-fused diquinane platform, was found to adopt a distorted boat–sofa conformation.

β-adrenergic-stimulated macrophages: Comprehensive localization in the M1–M2 spectrum

Science.gov (United States)

Lamkin, Donald M.; Ho, Hsin-Yun; Ong, Tiffany H.; Kawanishi, Carly K.; Stoffers, Victoria L.; Ahlawat, Nivedita; Ma, Jeffrey C.Y.; Arevalo, Jesusa M. G.; Cole, Steve W.; Sloan, Erica K.

2016-01-01

β-adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1–M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one predefined category of the M1–M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1–M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1–M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1–M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. PMID:27485040

Structure of Ga2O3(ZnO)6: a member of the homologous series Ga2O3(ZnO)m

International Nuclear Information System (INIS)

Michiue, Yuichi; Kanke, Yasushi; Kimizuka, Noboru

2008-01-01

The structure of Ga 2 O 3 (ZnO) 6 was determined using singlecrystal X-ray diffraction techniques in the space group Cmcm. The metal ion sublattice resembles some of the Zn ions in the wurtzite ZnO structure. The oxygen ion sublattice in Ga 2 O 3 (ZnO) 6 also resembles some of the O ions in ZnO. Structural relationships between Ga 2 O 3 (ZnO) 6 and ZnO are discussed, illustrating the process for obtaining the centrosymmetric Ga 2 O 3 (ZnO) 6 structure from the noncentrosymmetric ZnO. Structures of phases in the homologous series Ga 2 O 3 (ZnO) m are predicted on the basis of the structural data for Ga 2 O 3 (ZnO) 6 . The structures of even m are constructed by simply extending the structure units seen in Ga 2 O 3 (ZnO) 6 , while those of odd m consist of structure units which are of different types from those used for even m. (orig.)

Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin.

Science.gov (United States)

Bhagwat, Shripad V; Gokhale, Prafulla C; Crew, Andrew P; Cooke, Andy; Yao, Yan; Mantis, Christine; Kahler, Jennifer; Workman, Jennifer; Bittner, Mark; Dudkin, Lorina; Epstein, David M; Gibson, Neil W; Wild, Robert; Arnold, Lee D; Houghton, Peter J; Pachter, Jonathan A

2011-08-01

The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target. mTOR forms two distinct multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, metabolism, proliferation, and survival. Rapamycin and its analogues partially inhibit mTOR through allosteric binding to mTORC1, but not mTORC2, and have shown clinical utility in certain cancers. Here, we report the preclinical characterization of OSI-027, a selective and potent dual inhibitor of mTORC1 and mTORC2 with biochemical IC(50) values of 22 nmol/L and 65 nmol/L, respectively. OSI-027 shows more than 100-fold selectivity for mTOR relative to PI3Kα, PI3Kβ, PI3Kγ, and DNA-PK. OSI-027 inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 and OXA-01 (close analogue of OSI-027) potently inhibit proliferation of several rapamycin-sensitive and -insensitive nonengineered and engineered cancer cell lines and also, induce cell death in tumor cell lines with activated PI3K-AKT signaling. OSI-027 shows concentration-dependent pharmacodynamic effects on phosphorylation of 4E-BP1 and AKT in tumor tissue with resulting tumor growth inhibition. OSI-027 shows robust antitumor activity in several different human xenograft models representing various histologies. Furthermore, in COLO 205 and GEO colon cancer xenograft models, OSI-027 shows superior efficacy compared with rapamycin. Our results further support the important role of mTOR as a driver of tumor growth and establish OSI-027 as a potent anticancer agent. OSI-027 is currently in phase I clinical trials in cancer patients. ©2011 AACR

Dipropyl 3,6-diphenyl-1,2-dihydro-1,2,4,5-tetrazine-1,2-dicarboxylate.

Science.gov (United States)

Rao, Guo-Wu; Hu, Wei-Xiao

2003-05-01

The title compound, C(22)H(24)N(4)O(4), was prepared from propyl chloroformate and 3,6-diphenyl-1,2-dihydro-s-tetrazine. This reaction yields the title compound rather than dipropyl 3,6-diphenyl-1,4-dihydro-s-tetrazine-1,4-dicarboxylate. The 2,3-diazabutadiene group in the central six-membered ring is not planar; the C=N double-bond length is 1.285 (2) A, and the average N-N single-bond length is 1.401 (3) A, indicating a lack of conjugation. The ring has a twist conformation, in which adjacent N atoms lie +/- 0.3268 (17) A from the plane of the ring. The molecule has twofold crystallographic symmetry.

Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

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Chan Zhou

2017-08-01

Full Text Available N6-methyladenosine (m6A is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ RNAs. We developed a computational pipeline (AutoCirc that, together with depletion of ribosomal RNA and m6A immunoprecipitation, defined thousands of m6A circRNAs with cell-type-specific expression. The presence of m6A circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m6A sites in mRNAs, and by reduced m6A levels upon depletion of METTL3, the m6A writer. Despite sharing m6A readers and writers, m6A circRNAs are frequently derived from exons that are not methylated in mRNAs, whereas mRNAs that are methylated on the same exons that compose m6A circRNAs exhibit less stability in a process regulated by YTHDF2. These results expand our understanding of the breadth of m6A modifications and uncover regulation of circRNAs through m6A modification.

Cyclic AMP is a key regulator of M1 to M2a phenotypic conversion of microglia in the presence of Th2 cytokines.

Science.gov (United States)

Ghosh, Mousumi; Xu, Yong; Pearse, Damien D

2016-01-13

Microglia and macrophages play a central role in neuroinflammation. Pro-inflammatory cytokines trigger their conversion to a classically activated (M1) phenotype, sustaining inflammation and producing a cytotoxic environment. Conversely, anti-inflammatory cytokines polarize the cells towards an alternatively activated (M2), tissue reparative phenotype. Elucidation of the signal transduction pathways involved in M1 to M2 phenotypic conversion may provide insight into how the innate immune response can be harnessed during distinct phases of disease or injury to mediate neuroprotection and neurorepair. Microglial cells (cell line and primary) were subjected to combined cyclic adenosine monophosphate (cyclic AMP) and IL-4, or either alone, in the presence of pro-inflammatory mediators, lipopolysaccharide (LPS), or tumor necrosis factor-α (TNF-α). Their effects on the expression of characteristic markers for M1 and M2 microglia were assessed. Similarly, the M1 and M2 phenotypes of microglia and macrophages within the lesion site were then evaluated following a contusive spinal cord injury (SCI) to the thoracic (T8) spinal cord of rats and mice when the agents were administered systemically. It was demonstrated that cyclic AMP functions synergistically with IL-4 to promote M1 to M2 conversion of microglia in culture. The combination of cyclic AMP and IL-4, but neither alone, induced an Arg-1(+)/iNOS(-)cell phenotype with concomitant expression of other M2-specific markers including TG2 and RELM-α. M2-converted microglia showed ameliorated production of pro-inflammatory cytokines (TNF-α and IP-10) and reactive oxygen species, with no alteration in phagocytic properties. M2a conversion required protein kinase A (PKA), but not the exchange protein directly activated by cyclic AMP (EPAC). Systemic delivery of cyclic AMP and IL-4 after experimental SCI also promoted a significant M1 to M2a phenotypic change in microglia and macrophage population dynamics in the lesion

Transmembrane helix M6 in sarco(endo)plasmic reticulum Ca(2+)-ATPase forms a functional interaction site with phospholamban. Evidence for physical interactions at other sites.

Science.gov (United States)

Asahi, M; Kimura, Y; Kurzydlowski, K; Tada, M; MacLennan, D H

1999-11-12

In an earlier study (Kimura, Y., Kurzydlowski, K., Tada, M., and MacLennan, D. H. (1997) J. Biol. Chem. 272, 15061-15064), mutation of amino acids on one face of the phospholamban (PLN) transmembrane helix led to loss of PLN inhibition of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) molecules. This helical face was proposed to form a site of PLN interaction with a transmembrane helix in SERCA molecules. To determine whether predicted transmembrane helices M4, M5, M6, or M8 in SERCA1a interact with PLN, SERCA1a mutants were co-expressed with wild-type PLN and effects on Ca(2+) dependence of Ca(2+) transport were measured. Wild-type inhibitory interactions shifted apparent Ca(2+) affinity of SERCA1a by an average of -0.34 pCa units, but four of the seven mutations in M4 led to a more inhibitory shift in apparent Ca(2+) affinity, averaging -0.53 pCa units. Seven mutations in M5 led to an average shift of -0.32 pCa units and seven mutations in M8 led to an average shift of -0.30 pCa units. Among 11 mutations in M6, 1, Q791A, increased the inhibitory shift (-0.59 pCa units) and 5, V795A (-0.11), L802A (-0.07), L802V (-0.04), T805A (-0.11), and F809A (-0.12), reduced the inhibitory shift, consistent with the view that Val(795), Leu(802), Thr(805), and Phe(809), located on one face of a predicted M6 helix, form a site in SERCA1a for interaction with PLN. Those mutations in M4, M6, or M8 of SERCA1a that enhanced PLN inhibitory function did not enhance PLN physical association with SERCA1a, but mutants V795A and L802A in M6, which decreased PLN inhibitory function, decreased physical association, as measured by co-immunoprecipitation. In related studies, those PLN mutants that gained inhibitory function also increased levels of co-immunoprecipitation of wild-type SERCA1a and those that lost inhibitory function also reduced association, correlating functional interaction sites with physical interaction sites. Thus, both functional and physical data confirm that PLN

Combined adenovirus-mediated artificial microRNAs targeting mfgl2, mFas, and mTNFR1 protect against fulminant hepatic failure in mice.

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Dong Xi

Full Text Available Hepatitis B virus (HBV-related acute-on-chronic liver failure (ACLF has a poor prognosis with high in-hospital mortality. Hepatic and circulating inflammatory cytokines, such as fibrinogen like protein 2 (fgl2, FasL/Fas, and TNFα/TNFR1, play a significant role in the pathophysiology of ACLF. This study aimed to investigate the therapeutic effect of recombinant adenoviral vectors carrying constructed DNA code for non-native microRNA (miRNA targeting mouse fgl2 (mfgl2 or both mFas and mTNFR1 on murine hepatitis virus (MHV-3-induced fulminant hepatitis in BALB/cJ mice. Artificial miRNA eukaryotic expression plasmids against mfgl2, mFas, and mTNFR1 were constructed, and their inhibitory effects on the target genes were confirmed in vitro. pcDNA6.2-mFas-mTNFR1- miRNA，which expresses miRNA against both mFas and mTNFR1 simultaneously，was constructed. To construct a miRNA adenovirus expression vector against mfgl2, pcDNA6.2-mfgl2-miRNA was cloned using Gateway technology. Ad-mFas-mTNFR1- miRNA was also constructed by the same procedure. Adenovirus vectors were delivered by tail-vein injection into MHV-3-infected BALB/cJ mice to evaluate the therapeutic effect. 8 of 18 (44.4% mice recovered from fulminant viral hepatitis in the combined interference group treated with Ad-mfgl2-miRNA and Ad-mFas-mTNFR1-miRNA. But only 4 of 18 (22.2% mice receiving Ad-mfgl2-miRNA and 3 of 18 (16.7% mice receiving Ad-mFas-mTNFR1- miRNA survived. These adenovirus vectors significantly ameliorated inflammatory infiltration, fibrin deposition, hepatocyte necrosis and apoptosis, and prolonged survival time. Our data illustrated that combined interference using adenovirus-mediated artificial miRNAs targeting mfgl2, mFas, and mTNFR1 might have significant therapeutic potential for the treatment of fulminant hepatitis.

No-carrier-added (NCA) synthesis of 6-[{sup 18}F]fluoro-L-DOPA using 3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[6S-(6{alpha}, 8{alpha}, 8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazin-2-one

Energy Technology Data Exchange (ETDEWEB)

Horti, A. [Yale Univ., New Haven, CT (United States). School of Medicine]|[Yale Univ., West Haven, CT (United States). PET Center; Redmond, D.E. Jr. [Yale Univ., New Haven, CT (United States). School of Medicine; Soufer, R. [Yale Univ., West Haven, CT (United States). PET Center

1995-12-31

3,5,6,7,8,8a-Hexahydro-7,7,8a-trimethyl-[6S-(6{alpha},8{alpha} , 8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazino-2-one (2) was investigated as chiral auxiliary for asymmetric NCA nucleophilic synthesis of 6-[{sup 18}F]Fluoro-L-DOPA. Direct condensation of 3,4-dimethoxy-2-[{sup 18}F]fluorobenzaldehyde (1a) or 6-[{sup 18}F]fluoro-piperonal (1b) in the presence of NaH with 2 gave the corresponding [{sup 18}F]-3-[(2-fluorophenyl)methylene]-3,5,6,7,8,8a-hexahydro-7,7,8 a-trimethyl-[6S-(3Z,3{alpha},6{alpha},8{alpha},8{alpha}{beta})]-6, 8-methano-2H-1,4-benzoxazin-2-one derivative 3a or 3b as a single stereoisomer. L-Selectride promoted hydrogenation of the olefinic double bond of these derivatives, in presence of tertbutyl alcohol, afforded the corresponding [{sup 18}F]-3-[(2-fluorophenyl) methyl]-3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[3S-(3{alpha}, 6{alpha}, 8{alpha}8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazin-2-one derivatives (4a,b) without affecting the orientation of diasterofacial discrimination. Deprotection of the derivatives 4a,b yielded 6-[{sup 18}F]fluoro-L-DOPA (e.e. >90%, 3% radiochemical yield (EOB), total synthesis time 125 min, specific activity >2000 mCi/{mu}mol). Direct deprotection/reduction of the compounds 3a,b provides the enantiomeric mixture of 6-[{sup 18}F]fluoro-D,L-DOPA (10-12% radiochemical yield) and, after chiral separation, 6-[{sup 18}F]fluoro-L-DOPA (e.e. 98%, 4-5% radiochemical yield). (author).

DDX6 regulates sequestered nuclear CUG-expanded DMPK-mRNA in dystrophia myotonica type 1

DEFF Research Database (Denmark)

Pettersson, Olof Joakim; Aagaard, Lars; Andrejeva, Diana

2014-01-01

RNA to ‘sponge’ splicing factors of the muscleblind family. Although nuclear aggregation of CUG-containing mRNPs in distinct foci is a hallmark of DM1, the mechanisms of their homeostasis have not been completely elucidated. Here we show that a DEAD-box helicase, DDX6, interacts with CUG triplet-repeat m......RNA in primary fibroblasts from DM1 patients and with CUG–RNA in vitro. DDX6 overexpression relieves DM1 mis-splicing, and causes a significant reduction in nuclear DMPK-mRNA foci. Conversely, knockdown of endogenous DDX6 leads to a significant increase in DMPK-mRNA foci count and to increased sequestration...... in vitro in an adenosinetriphosphate-dependent manner, suggesting that DDX6 can remodel and release nuclear DMPK messenger ribonucleoprotein foci, leading to normalization of pathogenic alternative splicing events...

Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

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Mário Henrique M Barros

Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

Science.gov (United States)

Barros, Mário Henrique M; Hauck, Franziska; Dreyer, Johannes H; Kempkes, Bettina; Niedobitek, Gerald

2013-01-01

Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for

PGE{sub 2}-induced colon cancer growth is mediated by mTORC1

Energy Technology Data Exchange (ETDEWEB)

Dufour, Marc, E-mail: Marc.dufour@chuv.ch; Faes, Seraina, E-mail: Seraina.faes@chuv.ch; Dormond-Meuwly, Anne, E-mail: Anne.meuwly-Dormond@chuv.ch; Demartines, Nicolas, E-mail: Demartines@chuv.ch; Dormond, Olivier, E-mail: Olivier.dormond@chuv.ch

2014-09-05

Highlights: • PGE{sub 2} activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE{sub 2} induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE{sub 2} induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E{sub 2} (PGE{sub 2}) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE{sub 2} directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE{sub 2}-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE{sub 2} increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE{sub 2} EP{sub 4} receptor was responsible for transducing the signal to mTORC1. Moreover, PGE{sub 2} increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE{sub 2}-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE{sub 2} increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE{sub 2} mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth.

Discovery of a novel, CNS penetrant M4 PAM chemotype based on a 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core.

Science.gov (United States)

Bewley, Blake R; Spearing, Paul K; Weiner, Rebecca L; Luscombe, Vincent B; Zhan, Xiaoyan; Chang, Sichen; Cho, Hyekyung P; Rodriguez, Alice L; Niswender, Colleen M; Conn, P Jeffrey; Bridges, Thomas M; Engers, Darren W; Lindsley, Craig W

2017-09-15

This Letter details the discovery and subsequent optimization of a novel M 4 PAM scaffold based on an 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core, which represents a distinct departure from the classical M 4 PAM chemotypes. Optimized compounds in this series demonstrated improved M 4 PAM potency on both human and rat M 4 (4 to 5-fold relative to HTS hit), and displayed attractive physicochemical and DMPK profiles, including good CNS penetration (rat brain:plasma K p =5.3, K p,uu =2.4; MDCK-MDR1 (P-gp) ER=1.1). Copyright © 2017 Elsevier Ltd. All rights reserved.

Temperature-dependent Raman and ultraviolet photoelectron spectroscopy studies on phase transition behavior of VO{sub 2} films with M1 and M2 phases

Energy Technology Data Exchange (ETDEWEB)

Okimura, Kunio, E-mail: okifn@keyaki.cc.u-tokai.ac.jp; Hanis Azhan, Nurul [Graduate School of Engineering, Tokai University, Hiratsuka 259-1292 (Japan); Hajiri, Tetsuya [UVSOR Facility, Institute for Molecular Science, Okazaki 444-8585 (Japan); Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Kimura, Shin-ichi [UVSOR Facility, Institute for Molecular Science, Okazaki 444-8585 (Japan); Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871 (Japan); Zaghrioui, Mustapha; Sakai, Joe [GREMAN, UMR 7347 CNRS, Université François Rabelais de Tours, Parc de Grandmont, 37200 Tours (France)

2014-04-21

Structural and electronic phase transitions behavior of two polycrystalline VO{sub 2} films, one with pure M1 phase and the other with pure M2 phase at room temperature, were investigated by temperature-controlled Raman spectroscopy and ultraviolet photoelectron spectroscopy (UPS). We observed characteristic transient dynamics in which the Raman modes at 195 cm{sup −1} (V-V vibration) and 616 cm{sup −1} (V-O vibration) showed remarkable hardening along the temperature in M1 phase film, indicating the rearrangements of V-V pairs and VO{sub 6} octahedra. It was also shown that the M1 Raman mode frequency approached those of invariant M2 peaks before entering rutile phase. In UPS spectra with high energy resolution of 0.03 eV for the M2 phase film, narrower V{sub 3d} band was observed together with smaller gap compared to those of M1 phase film, supporting the nature of Mott insulator of M2 phase even in the polycrystalline film. Cooperative behavior of lattice rearrangements and electronic phase transition was suggested for M1 phase film.

Genetic and epigenetic inactivation of SESTRIN1 controls mTORC1 and response to EZH2 inhibition in follicular lymphoma.

Science.gov (United States)

Oricchio, Elisa; Katanayeva, Natalya; Donaldson, Maria Christine; Sungalee, Stephanie; Pasion, Joyce P; Béguelin, Wendy; Battistello, Elena; Sanghvi, Viraj R; Jiang, Man; Jiang, Yanwen; Teater, Matt; Parmigiani, Anita; Budanov, Andrei V; Chan, Fong Chun; Shah, Sohrab P; Kridel, Robert; Melnick, Ari M; Ciriello, Giovanni; Wendel, Hans-Guido

2017-06-28

Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as EZH2 Using a focused genetic screen, we identified SESTRIN1 as a relevant target of the 6q deletion and demonstrate tumor suppression by SESTRIN1 in vivo. Moreover, SESTRIN1 is a direct target of the lymphoma-specific EZH2 gain-of-function mutation ( EZH2 Y641X ). SESTRIN1 inactivation disrupts p53-mediated control of mammalian target of rapamycin complex 1 (mTORC1) and enables mRNA translation under genotoxic stress. SESTRIN1 loss represents an alternative to RRAGC mutations that maintain mTORC1 activity under nutrient starvation. The antitumor efficacy of pharmacological EZH2 inhibition depends on SESTRIN1, indicating that mTORC1 control is a critical function of EZH2 in lymphoma. Conversely, EZH2 Y641X mutant lymphomas show increased sensitivity to RapaLink-1, a bifunctional mTOR inhibitor. Hence, SESTRIN1 contributes to the genetic and epigenetic control of mTORC1 in lymphoma and influences responses to targeted therapies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

M2-F1 in flight being towed by a C-47

Science.gov (United States)

1964-01-01

The M2-F1 Lifting Body is seen here being towed behind a C-47 at the Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. In this rear view, the M2-F1 is flying above and to one side of the C-47. This was done to avoid wake turbulence from the towplane. Lacking wings, the M2-F1 used an unusual configuration for its control surfaces. It had two rudders on the fins, two elevons (called 'elephant ears') mounted on the outsides of the fins, and two body flaps on the upper rear fuselage. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind the C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and

Thermally induced A'-A site exchange in novel layered perovskites Ag2[Ca1.5M3O10] (M = Nb, Ta).

Science.gov (United States)

Bhuvanesh, Nattamai S P; Woodward, Patrick M

2002-12-04

We have synthesized and characterized new layered perovskites Ag2[A1.5M3O10] (A = Ca, M = Nb, Ta), from their lithium analogues, by soft-chemical ion exchange. These oxides show topotactic irreversible thermally induced A'-A site exchange, resulting in Ag1.1Ca0.9[Ca0.6Ag0.9M3O10], conferred from our high-temperature X-ray and ionic conductivity studies. The latter phases are the first compounds where Ag+ ions reside in both A' and A sites in layered perovskites. The absence of similar phase transition for A = Sr suggests that these transitions strongly depend on the size, charge, and the coordination preference of A' and A cations. This result provides a new synthetic tool for modifying the occupation of the 12-coordinate A site of layered perovskites using soft chemical routes.

SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride], a new nonpeptide antagonist of the bradykinin B1 receptor: biochemical and pharmacological characterization.

Science.gov (United States)

Gougat, Jean; Ferrari, Bernard; Sarran, Lionel; Planchenault, Claudine; Poncelet, Martine; Maruani, Jeanne; Alonso, Richard; Cudennec, Annie; Croci, Tiziano; Guagnini, Fabio; Urban-Szabo, Katalin; Martinolle, Jean-Pierre; Soubrié, Philippe; Finance, Olivier; Le Fur, Gérard

2004-05-01

The biochemical and pharmacological properties of a novel non-peptide antagonist of the bradykinin (BK) B(1) receptor, SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride] were evaluated. SSR240612 inhibited the binding of [(3)H]Lys(0)-des-Arg(9)-BK to the B(1) receptor in human fibroblast MRC5 and to recombinant human B(1) receptor expressed in human embryonic kidney cells with inhibition constants (K(i)) of 0.48 and 0.73 nM, respectively. The compound selectivity for B(1) versus B(2) receptors was in the range of 500- to 1000-fold. SSR240612 inhibited Lys(0)-desAr(9)-BK (10 nM)-induced inositol monophosphate formation in human fibroblast MRC5, with an IC(50) of 1.9 nM. It also antagonized des-Arg(9)-BK-induced contractions of isolated rabbit aorta and mesenteric plexus of rat ileum with a pA(2) of 8.9 and 9.4, respectively. Antagonistic properties of SSR240612 were also demonstrated in vivo. SSR240612 inhibited des-Arg(9)-BK-induced paw edema in mice (3 and 10 mg/kg p.o. and 0.3 and 1 mg/kg i.p.). Moreover, SSR240612 reduced capsaicin-induced ear edema in mice (0.3, 3 and 30 mg/kg p.o.) and tissue destruction and neutrophil accumulation in the rat intestine following splanchnic artery occlusion/reperfusion (0.3 mg/kg i.v.). The compound also inhibited thermal hyperalgesia induced by UV irradiation (1 and 3 mg/kg p.o.) and the late phase of nociceptive response to formalin in rats (10 and 30 mg/kg p.o.). Finally, SSR240612 (20 and 30 mg/kg p.o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat. In conclusion, SSR240612 is a new, potent, and orally active specific non-peptide bradykinin B(1) receptor antagonist.

Crystal structure of 2-amino-1,3-dibromo-6-oxo-5,6-dihydropyrido[1,2-a]quinoxalin-11-ium bromide monohydrate

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Md. Serajul Haque Faizi

2015-11-01

Full Text Available In the title hydrated salt, C12H8Br2N3O+·Br−·H2O, which was synthesized by the reaction of the pyridine derivative Schiff base N1,N4-bis(pyridine-2-ylmethylenebenzene-1,4-diamine with bromine, the asymmetric unit contains a 2-amino-1,3-dibromo-6-oxo-5,6-dihydropyrido[1,2-a]quinoxalin-11-ium cation, with a protonated pyridine moiety, a bromide anion and a water molecule of solvation. The cation is non-planar with the dibromo-substituted benzene ring, forming dihedral angles of 24.3 (4 and 11.5 (4° with the fused pyridine and pyrazine ring moieties, respectively. In the crystal, the cations are linked through a centrosymmetric hydrogen-bonded cyclic R42(8 Br2(H2O2 unit by N—H...Br, N—H...O and O—H...Br hydrogen bonds, forming one-dimensional ribbons extending along b, with the planes of the cations lying parallel to (100.

Cs2UPd3Se6

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George N. Oh

2011-02-01

Full Text Available Dicaesium uranium(IV tripalladium(II hexaselenide, Cs2UPd3Se6, crystallizes in the space group Fmmm in the Ba2NaCu3O6 structure type. The asymmetric unit comprises the following atoms with site symmetries as shown: U1 (mm2, Cs1 (222, Cs2 (m2m, Pd1 (.m., Pd2 (2mm, Se1 (m.., and Se2 (1. This layered structure contains six edge-sharing square-planar [PdSe4] units that form a hexagon. These, in turn, edge-share with [USe6] trigonal–prismatic units, forming an extended layer parallel to (010. The layers are stacked along [010]. They are staggered, and are separated by the Cs atoms. The Cs atoms are either coordinated in a square antiprism of Se atoms or are ten-coordinate, with one square face and the opposite face hexagonal.

K1-xMn1+x/2[Fe(CN)6]·yH2O Prussian blue analogues as an anode material for lithium-ion batteries

Science.gov (United States)

Zhou, Feng-Chen; Sun, Yan-Hui; Li, Jie-Qiong; Nan, Jun-Min

2018-06-01

Hexacyanoferrate, KMn[Fe(CN)6]·yH2O (KMnHCF), a Prussian blue analogue (PBA), is synthesized by a solution precipitation method under alkaline condition at room temperature. After treated with diluted hydrochloride acid, the KMnHCF is turned into Mn3[Fe(CN)6]2·yH2O (MnHCF). Then both synthesized KMnHCF and MnHCF are applied as anode material for lithium ion batteries (LIBs). The KMnHCF anode exhibits a super electrochemical performance than MnHCF. It shows a very low discharge voltage plateau of 0.6 V, an initial capacity of 777 mAh g-1, and a reversible capacity of 434 mAh g-1 after 50 cycles at a current density of 50 mA g-1. Furthermore, it keeps 425 mAh g-1 after 100 cycles at 100 mA g-1 and 215 mAh g-1 after 200 cycles even at 500 mA g-1. It is remarkable that the coulombic efficiency can be maintained larger than 98.4% from the 5th cycle at 50 mA g-1, 99.2% at 100 mA g-1, and 96.8% even at 500 mA g-1. In addition, the original structure of the KMnHCF has no obvious change after lithiation/de-lithiation based on the ex-situ X-ray powder diffraction (XRD) and Fourier transform infrared spectrometer (FT-IR) characterization, indicating large channels and interstitial sites in the open-framework can allow rapid insertion and extraction of Li+ and constrain volume expansion during charge/discharge process.

Crystal structures of KM(AsF6)3 (M2+ = Mg, Co, Mn, Zn), KCu(SbF6)3 and [Co(HF)2]Sr[Sr(HF)]2-[Sr(HF)2]2[AsF6]12

International Nuclear Information System (INIS)

Mazej, Zoran; Goreshnik, Evgeny

2015-01-01

The KM(AsF 6 ) 3 (M 2+ = Mg, Co, Mn, Zn) and KCu(SbF 6 ) 3 compounds crystallize isotypically to previously known KNi(AsF 6 ) 3 . The main features of the structure of these compounds are rings of MF 6 octahedra sharing apexes with AsF 6 octahedra connected into infinite tri-dimensional frameworks. In this arrangement cavities are formed where K + cations are placed. Single crystals of CoSr 5 (AsF 6 ) 12 .8HF were obtained as one of the products after the crystallization of 3KF/CoF 2 /SrF 2 mixture in the presence of AsF 5 in anhydrous HF. The CoSr 5 (AsF 6 ) 12 .8HF is monoclinic, C/2c (No.15), with a = 26.773(5) Aa, b = 10.087(2) Aa, c = 21.141(5) Aa, β = 93.296(13) circle , V = 5699.9(19) Aa 3 at 200 K, and Z = 4. There are three crystallographically non-equivalent Sr 2+ cations in the crystal structure of CoSr 5 (AsF 6 ) 12 .8HF. The Sr1 is coordinated by ten fluorine atoms from eight different [AsF 6 ]- anions, meanwhile Sr2 and Sr3 are bound to nine fluorine atoms provided by one HF and eight AsF 6 units or by two HF and six AsF 6 units, respectively. The Co 2+ is coordinated distorted-octahedrally by six fluorine atoms from two HF molecules and four different AsF 6 units. All those moieties in the crystal structure of [Co(HF) 2 ]Sr[Sr(HF)] 2 [Sr(HF) 2 ] 2 [AsF 6 ] 12 are connected into tridimensional framework. The CoSr 5 (AsF 6 ) 12 .8HF is a unique example of compound where HF molecules are directly bound via fluorine atoms to two different metal centres.

Draft Genome Sequence of Ezakiella peruensis Strain M6.X2, a Human Gut Gram-Positive Anaerobic Coccus.

Science.gov (United States)

Diop, Awa; Diop, Khoudia; Tomei, Enora; Raoult, Didier; Fenollar, Florence; Fournier, Pierre-Edouard

2018-03-01

We report here the draft genome sequence of Ezakiella peruensis strain M6.X2 T The draft genome is 1,672,788 bp long and harbors 1,589 predicted protein-encoding genes, including 26 antibiotic resistance genes with 1 gene encoding vancomycin resistance. The genome also exhibits 1 clustered regularly interspaced short palindromic repeat region and 333 genes acquired by horizontal gene transfer. Copyright © 2018 Diop et al.

Heterologous expression of Ralp3 in Streptococcus pyogenes M2 and M6 strains affects the virulence characteristics.

Science.gov (United States)

Siemens, Nikolai; Kreikemeyer, Bernd

2013-01-01

Ralp3 is a transcriptional regulator present in a serotype specific fashion on the chromosome of the human pathogen Streptococcus pyogenes (group A streptococci, GAS). In serotypes harbouring the ralp3 gene either positive or negative effects on important metabolic and virulence genes involved in colonization and immune evasion in the human host were observed. A previous study revealed that deletion of ralp3 in a GAS M49 serotype significantly attenuated many virulence traits and caused metabolic disadvantages. This leads to two questions: (i) which kind of consequences could Ralp3 expression have in GAS serotypes naturally lacking this gene, and (ii) is Ralp3 actively lost during evolution in these serotypes. We investigated the role of Ralp3 in GAS M2 and M6 pathogenesis. Both serotypes lack ralp3 on their chromosome. The heterologous expression of ralp3 in both serotypes resulted in reduced attachment to and internalization into the majority of tested epithelial cells. Both ralp3 expression strains showed a decreased ability to survive in human blood and exclusively M2::ralp3 showed decreased survival in human serum. Both mutants secreted more active SpeB in the supernatant, resulting in a higher activity compared to wild type strains. The respective M2 and M6 wild type strains outcompeted the ralp3 expression strains in direct metabolic competition assays. The phenotypic changes observed in the M2:ralp3 and M6:ralp3 were verified on the transcriptional level. Consistent with the virulence data, tested genes showed transcript level changes in the same direction. Together these data suggest that Ralp3 can take over transcriptional control of virulence genes in serotypes lacking the ralp3 gene. Those serotypes most likely lost Ralp3 during evolution since obviously expression of this gene is disadvantageous for metabolism and pathogenesis.

Amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole

International Nuclear Information System (INIS)

Saidov, D.K.; Rakhmonov, R.O.; Khodzhiboev, Yu.; Kukaniev, M.A.; Bandaev, S.

2015-01-01

Present article is devoted to amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole. The reaction of new modifications of derivatives of imidazo-[2.1-B]-1.3.4-thiadiazoles-2-bromine-6-p-bromophenyl and 2-alkyl alkylene sulfonyl-6-phenyl imidazo--[2.1-B]-1.3.4-thiadiazole on Mannich with secondary and heterocyclic amines was studied.

Sliding charge density wave in the monophosphate tungsten bronze (PO2)4(WO3)2m with alternate stacking of m=4 and m=6 WO3 layers

International Nuclear Information System (INIS)

Foury-Leylekian, P.; Sandre, E.; Ravy, S.; Pouget, J.-P.; Elkaim, E.; Roussel, P.; Groult, D.; Labbe, Ph.

2002-01-01

The monophosphate tungsten bronzes (PO 2 ) 4 (WO 3 ) 2m form family of two-dimensional metals which exhibit charge density wave (CDW) instabilities. These materials are generally built by the regular stacking of (a,b) layers in which chains made of segments of m WO 6 octahedra directed along the a and a±b directions are delimited. Their electronic structure thus originates from quasi-one-dimensional (1D) bands located on these chains. As a consequence their Fermi surface (FS) exhibits large flat portions whose nesting gives rise to successive CDW instabilities. Here we present a structural study of the CDW instability of the (PO 2 ) 4 (WO 3 ) 10 member formed by the alternate stacking of layers built with segments of m=4 and m=6 WO 6 octahedra. Its ab initio electronic structure calculation shows that the FS of this member exhibits large flat portions which can be extremely well nested. Its best nesting wave vector accounts for the modulation wave vector stabilized by the CDW transition which occurs at 156 K. Because of the regular stacking of layers of different m values the FS is slightly split. The unusual thermal dependence of the x-ray satellite intensity provides evidence that the two types of layers become modulated at different temperature. This also leads to a slight thermal sliding of the CDW-nesting modulation wave vector, which can be accounted for within the framework of a Landau-Ginzburg theory. In addition, the observation of a global hysteresis in the thermal cycling of the satellite intensity, as well as the degradation of the interlayer order upon cooling, suggest the formation of a disordered lattice of dilute solitons. Such solitons allow to accommodate the charge transferred between the two types of layer. Finally the relevance of local charge transfers, at intergrowth defects, for example, to create pinned discommensurations that break the CDW coherence is emphasized in this whole family of bronzes

Biphasic effect of duodenal ulcerogens cysteamine (C), mepirizole (M) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropryridine (MPTP) on gastric emptying in the rat

Energy Technology Data Exchange (ETDEWEB)

Pihan, G.; Kline, T.J.; Szabo, S.

1986-03-01

The effect of acute or chronic administration of duodenal ulcerogens on gastric emptying (GE) of a liquid meal was investigated. In Sprague-Dawley rats (150-200g) 2 ml of /sup 51/Cr in 2% dextrose (5000 CPM) was given intragastrically and the GE half life was established as 7.6 min (controls). In acute experiments, C (30mg/100g), M (40mg/100g) or MPTP (4mg/100g) injected subcutaneously all delayed GE at 1, 2, 4, 8 and 24 hr by 15-77%. Maximal GE delay (p<0.05) by 77, 48 or 71% was found 1, 1 or 2 hr after C, M or MPTP, respectively. In chronic experiments, C (22mg/100g) was given x3 on the first day and once daily (25mg/100g) for 3 or 10 additional days. M (20mg/100g) once daily and MPTP (4mg/100g) x3 daily were given for 4 or 11 days. GE was measured on the 5th and 12th day. Chronically, MPTP accelerated GE by 63 and 31% at 5 and 12 days (p<0.05) and C and M did not change GE. The severity of duodenal ulcers correlated (p<0.05) with the amount of /sup 51/Cr remaining in the stomach: r=-0.68, -0.74 and -0.70 after C, M and MPTP, respectively. Acute administration of duodenal ulcerogens delay GE in rats. Chronic treatment with duodenal ulcerogens either accelerates or does not change GE. The most severe chronic ulcers exhibit the most rapid emptying. The authors data suggest that rapid GE might be a secondary rather than a primary alteration in duodenal ulceration.

Highly Durable Na2V6O16·1.63H2O Nanowire Cathode for Aqueous Zinc-Ion Battery.

Science.gov (United States)

Hu, Ping; Zhu, Ting; Wang, Xuanpeng; Wei, Xiujuan; Yan, Mengyu; Li, Jiantao; Luo, Wen; Yang, Wei; Zhang, Wencui; Zhou, Liang; Zhou, Zhiqiang; Mai, Liqiang

2018-03-14

Rechargeable aqueous zinc-ion batteries are highly desirable for grid-scale applications due to their low cost and high safety; however, the poor cycling stability hinders their widespread application. Herein, a highly durable zinc-ion battery system with a Na 2 V 6 O 16 ·1.63H 2 O nanowire cathode and an aqueous Zn(CF 3 SO 3 ) 2 electrolyte has been developed. The Na 2 V 6 O 16 ·1.63H 2 O nanowires deliver a high specific capacity of 352 mAh g -1 at 50 mA g -1 and exhibit a capacity retention of 90% over 6000 cycles at 5000 mA g -1 , which represents the best cycling performance compared with all previous reports. In contrast, the NaV 3 O 8 nanowires maintain only 17% of the initial capacity after 4000 cycles at 5000 mA g -1 . A single-nanowire-based zinc-ion battery is assembled, which reveals the intrinsic Zn 2+ storage mechanism at nanoscale. The remarkable electrochemical performance especially the long-term cycling stability makes Na 2 V 6 O 16 ·1.63H 2 O a promising cathode for a low-cost and safe aqueous zinc-ion battery.

Radiative rates for E1, E2, M1, and M2 transitions in the Br-like ions Sr IV, Y V, Zr VI, Nb VII, and Mo VIII

International Nuclear Information System (INIS)

Aggarwal, Kanti M.; Keenan, Francis P.

2015-01-01

Energies and lifetimes are reported for the lowest 375 levels of five Br-like ions, namely Sr IV, Y V, Zr VI, Nb VII, and Mo VIII, mostly belonging to the 4s 2 4p 5 , 4s 2 4p 4 4ℓ, 4s4p 6 , 4s 2 4p 4 5ℓ, 4s 2 4p 3 4d 2 , 4s4p 5 4ℓ, and 4s4p 5 5ℓ configurations. Extensive configuration interaction has been included and the general-purpose relativistic atomic structure package (GRASP) has been adopted for the calculations. Additionally, radiative rates are listed among these levels for all E1, E2, M1, and M2 transitions. From a comparison with the measurements, the majority of our energy levels are assessed to be accurate to better than 2%, although discrepancies between theory and experiment for a few are up to 6%. An accuracy assessment of the calculated radiative rates (and lifetimes) is more difficult, because no prior results exist for these ions

[99mTc]Demotensin 5 and 6 in the NTS1-R-targeted imaging of tumours: synthesis and preclinical results

International Nuclear Information System (INIS)

Maina, Theodosia; Nikolopoulou, Anastasia; Stathopoulou, Eleni; Nock, Berthold A.; Galanis, Athanassios S.; Cordopatis, Paul

2007-01-01

The aim of this study was to evaluate the applicability of [ 99m Tc]Demotensin 5 and 6 ([ 99m Tc- N 0 4 ,(β)Ala 7 ,Dab 9 ,X 12 AA ]NT(7-13); X AA =Ile/5,Tle/6,NT=neurotensin) in the targeted diagnostic imaging of neurotensin subtype 1 receptor (NTS1-R)-expressing tumours. Labelling of Demotensin 5 and 6 with 99m Tc was conducted by brief incubation with 99m TcO 4 - , SnCl 2 and citrate anions in alkaline medium at ambient temperature. Affinities of conjugates for the NTS1-R were determined by competition binding experiments in WiDr cell membranes using [ 125 I-Tyr 3 ]NT as the radioligand. Saturation binding assays were conducted for [ 99m Tc/ 99g Tc]Demotensin 6 in WiDr cell membranes. Internalisation of [ 99m Tc]Demotensin 5 and 6 was studied at 37 C in WiDr cells. Biodistribution of [ 99m Tc]Demotensin 5 and 6 was performed in female Swiss nu/nu mice bearing human WiDr xenografts. Unlabelled conjugates showed a high affinity for the human NTS1-R (Demotensin 5 IC 50 =0.03±0.01 nM; Demotensin 6 IC 50 =0.08±0.02 nM), while high affinity was also exhibited by (radio)metallated [ 99m Tc/ 99g Tc]Demotensin 6 (K d =0.13±0.01 nM). [ 99m Tc]Demotensin 5 and 6 internalised rapidly and specifically in WiDr cells. After injection in WiDr tumour-bearing mice, radiopeptides, and especially the doubly stabilised [ 99m Tc]Demotensin 6, showed NTS1-R-mediated uptake in the intestines and in the implanted tumour (4.30±0.45%ID/g at 1 h post injection) and rapid renal excretion from non-target tissues into the urine. [ 99m Tc]Demotensin 6 shows a favourable preclinical profile and further testing in patients is warranted to monitor its eventual applicability as a radiotracer in the diagnostic imaging of NTS1-R-positive tumours. (orig.)

[Effects of lipopolysaccharides extracted from Porphyromonas endodontalis on the expression of IL-1beta mRNA and IL-6 mRNA in osteoblasts].

Science.gov (United States)

Yang, Di; Li, Ren; Qiu, Li-Hong; Li, Chen

2009-04-01

To quantify the IL-1 beta mRNA and IL-6 mRNA expression induced by lipopolysaccharides (LPS)extracted from Porphyromonas endodontalis(P.e) in osteoblasts, and to relate P.e-LPS to bone absorption pathogenesis in lesions of chronical apical periodontitis. MG63 was treated with different concentrations of P.e-LPS(0-50 microg/mL) for different hours(0-24h). The expression of IL-1 beta mRNA and IL-6 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR).Statistical analysis was performed using one- way ANOVA and Dunnett t test with SPSS11.0 software package. The level of IL-1 beta mRNA and IL-6 mRNA increased significantly after treatment with P.e-LPS at more than 5 microg/mL (P<0.01)and for more than 1 hour (P<0.01), which indicated that P.e-LPS induced osteoblasts to express IL-1 beta mRNA and IL-6 mRNA in dose and time dependent manners. P.e-LPS may promote bone resorption in lesions of chronical apical periodontitis by inducing IL-1 beta mRNA and IL-6 mRNA expression in osteoblasts.

A new and efficient culture method for porcine bone marrow-derived M1- and M2-polarized macrophages.

Science.gov (United States)

Gao, Jiye; Scheenstra, Maaike R; van Dijk, Albert; Veldhuizen, Edwin J A; Haagsman, Henk P

2018-06-01

Macrophages play an important role in the innate immune system as part of the mononuclear phagocyte system (MPS). They have a pro-inflammatory signature (M1-polarized macrophages) or anti-inflammatory signature (M2-polarized macrophages) based on expression of surface receptors and secretion of cytokines. However, very little is known about the culture of macrophages from pigs and more specific about the M1 and M2 polarization in vitro. Porcine monocytes or mononuclear bone marrow cells were used to culture M1- and M2-polarized macrophages in the presence of GM-CSF and M-CSF, respectively. Surface receptor expression was measured with flow cytometry and ELISA was used to quantify cytokine secretion in response to LPS and PAM 3 CSK 4 stimulation. Human monocyte-derived macrophages were used as control. Porcine M1- and M2-polarized macrophages were cultured best using porcine GM-CSF and murine M-CSF, respectively. Cultures from bone marrow cells resulted in a higher yield M1- and M2-polarized macrophages which were better comparable to human monocyte-derived macrophages than cultures from porcine monocytes. Porcine M1-polarized macrophages displayed the characteristic fried egg shape morphology, lower CD163 expression and low IL-10 production. Porcine M2-polarized macrophages contained the spindle-like morphology, higher CD163 expression and high IL-10 production. Porcine M1- and M2-polarized macrophages can be most efficiently cultured from mononuclear bone marrow cells using porcine GM-CSF and murine M-CSF. The new culture method facilitates more refined studies of porcine macrophages in vitro, important for both porcine and human health since pigs are increasingly used as model for translational research. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The BH3 α-Helical Mimic BH3-M6 Disrupts Bcl-XL, Bcl-2, and MCL-1 Protein-Protein Interactions with Bax, Bak, Bad, or Bim and Induces Apoptosis in a Bax- and Bim-dependent Manner*

Science.gov (United States)

Kazi, Aslamuzzaman; Sun, Jiazhi; Doi, Kenichiro; Sung, Shen-Shu; Takahashi, Yoshinori; Yin, Hang; Rodriguez, Johanna M.; Becerril, Jorge; Berndt, Norbert; Hamilton, Andrew D.; Wang, Hong-Gang; Sebti, Saïd M.

2011-01-01

A critical hallmark of cancer cell survival is evasion of apoptosis. This is commonly due to overexpression of anti-apoptotic proteins such as Bcl-2, Bcl-XL, and Mcl-1, which bind to the BH3 α-helical domain of pro-apoptotic proteins such as Bax, Bak, Bad, and Bim, and inhibit their function. We designed a BH3 α-helical mimetic BH3-M6 that binds to Bcl-XL and Mcl-1 and prevents their binding to fluorescently labeled Bak- or Bim-BH3 peptides in vitro. Using several approaches, we demonstrate that BH3-M6 is a pan-Bcl-2 antagonist that inhibits the binding of Bcl-XL, Bcl-2, and Mcl-1 to multi-domain Bax or Bak, or BH3-only Bim or Bad in cell-free systems and in intact human cancer cells, freeing up pro-apoptotic proteins to induce apoptosis. BH3-M6 disruption of these protein-protein interactions is associated with cytochrome c release from mitochondria, caspase-3 activation and PARP cleavage. Using caspase inhibitors and Bax and Bak siRNAs, we demonstrate that BH3-M6-induced apoptosis is caspase- and Bax-, but not Bak-dependent. Furthermore, BH3-M6 disrupts Bcl-XL/Bim, Bcl-2/Bim, and Mcl-1/Bim protein-protein interactions and frees up Bim to induce apoptosis in human cancer cells that depend for tumor survival on the neutralization of Bim with Bcl-XL, Bcl-2, or Mcl-1. Finally, BH3-M6 sensitizes cells to apoptosis induced by the proteasome inhibitor CEP-1612. PMID:21148306

Prognostic value of HPV E6/E7 mRNA assay in women with negative colposcopy or CIN1 histology result: a follow-up study.

Directory of Open Access Journals (Sweden)

Paolo Giorgi Rossi

Full Text Available Pap test, and especially HPV DNA test, identify a large group of women who do not have any clinically relevant lesions, i.e., CIN2+ (Cervical Intraepithelial Neoplasia grade 2 or worse, but who are at greater risk of getting lesions in the future. The follow up of these women needs new biomarkers with prognostic value. The objective of this study is to evaluate the prognostic value of E6/E7 mRNA over-expression assay (PreTect HPV-Proofer, Norchip for 5 HR-HPV types (16, 18, 31, 33, and 45 for progression to CIN2+ after a negative colposcopy. This prospective study, conducted at four Italian centres, enrolled 673 women with either a negative colposcopy or a negative or CIN1 histology. The clinical end-point was histological confirmation of CIN2+. Women were classified at baseline according to mRNA results and managed according to local colposcopy protocols. At least one conclusive follow-up test was obtained for 347 women (25 months average lapse since recruitment, range 5-74. Only seven CIN2+ were detected during follow up, three among the 82 women positive for mRNA at baseline, two among the 250 negative (Fisher exact test, p = 0.02, and two among the 12 with an invalid test. Absolute CIN2+ risk was 6.7/1,000 person/years in the whole cohort. The absolute CIN2+ risk was 18.4/1,000 person/years and 3.6/1,000 person/years in mRNA-positive and mRNA-negative women, respectively. In conclusion, E6/E7 mRNA over-expression appears to be a good candidate as a prognostic biomarker to manage HR-HPV DNA-positive women with negative colposcopy or histology, particularly in order to decrease follow-up intensity in those who are negative.

Crystal structures of the double perovskites Ba2Sr1-x Ca x WO6

International Nuclear Information System (INIS)

Fu, W.T.; Akerboom, S.; IJdo, D.J.W.

2007-01-01

Structures of the double perovskites Ba 2 Sr 1- x Ca x WO 6 have been studied by the profile analysis of X-ray diffraction data. The end members, Ba 2 SrWO 6 and Ba 2 CaWO 6 , have the space group I2/m (tilt system a 0 b - b - ) and Fm3-barm (tilt system a 0 a 0 a 0 ), respectively. By increasing the Ca concentration, the monoclinic structure transforms to the cubic one via the rhombohedral R3-bar phase (tilt system a - a - a - ) instead of the tetragonal I4/m phase (tilt system a 0 a 0 c - ). This observation supports the idea that the rhombohedral structure is favoured by increasing the covalency of the octahedral cations in Ba 2 MM'O 6 -type double perovskites, and disagrees with a recent proposal that the formation of the π-bonding, e.g., d 0 -ion, determines the tetragonal symmetry in preference to the rhombohedral one. - Graphical abstract: Enlarged sections showing the evolution of the basic (222) and (400) reflections in Ba 2 Sr 1- x Ca x WO 6 . Tick marks below are the positions of Bragg's reflections calculated using the space groups I2/m (x=0), R3-bar (x=0.25, 0.5 and 0.75) and Fm3-barm (x=1), respectively

A study of magnetoplumbite-type (M-type) cobalt-titanium-substituted barium ferrite, BaCo{sub x}Ti{sub x}Fe{sub 12-2x}O{sub 19} (x = 1-6)

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Teh, G.B. [Department of Bioscience and Chemistry, Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, 53300 Kuala Lumpur (Malaysia)], E-mail: tehgb@mail.utar.edu.my; Saravanan, N. [Department of Bioscience and Chemistry, Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, 53300 Kuala Lumpur (Malaysia); Jefferson, D.A. [Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (United Kingdom)

2007-10-15

Cobalt(II)-titanium(IV)-substituted barium ferrite forming the chemical formula of BaCo{sub x}Ti{sub x}Fe{sub 12-2x}O{sub 19} (x = 1-6) have been investigated using X-ray diffraction spectroscopy (XRD), Superconducting Quantum Interference Device (SQUID) and high-resolution transmission electron microscopy (HRTEM). The specimen of magnetoplumbite (M-type) Co-Ti-substituted BaFe{sub 12}O{sub 19} were synthesised via sol-gel method using ethylene glycol as precursor. Significant increase in line broadening of the XRD patterns were observed indicating the decrease of particle sizes due to the Co(II)-Ti(IV) substitution. BaCo{sub 3}Ti{sub 3}Fe{sub 6}O{sub 19} showed the highest coercivity but moderate saturation and remnant magnetisations. HRTEM imaging showed that Co(II)-Ti(IV) substitution in the system of BaCo{sub x}Ti{sub x}Fe{sub 12-2x}O{sub 19} (x = 1-6) produced no drastic change in the structure of the M-type ferrites. Most of the M-types crystals examined by HRTEM displayed a long axis perpendicular to the c-axis of the M-type structure. Disordered crystals showing the intergrowth between Co-Ti-substituted barium ferrite and the spinel-structured iron oxide were detected.

Thio-, selenido-, and telluridogermanates(III): K/sub 6/Ge/sub 2/S/sub 6/, K/sub 6/Ge/sub 2/Se/sub 6/, and Na/sub 6/Ge/sub 2/Te/sub 6/

Energy Technology Data Exchange (ETDEWEB)

Eisenmann, B; Kieselbach, E; Schaefer, H; Schrod, H [Technische Hochschule Darmstadt (Germany, F.R.). Fachbereich Anorganische Chemie und Kernchemie

1984-09-01

The new compounds K/sub 6/Ge/sub 2/S/sub 6/ and K/sub 6/Ge/sub 2/Se/sub 6/ crystallize in the monoclinic system, space group C2/m (No 12). The compounds are isotypic and form the K/sub 6/Si/sub 2/Te/sub 6/ structure. Na/sub 6/Ge/sub 2/Te/sub 6/ crystallizes in the K/sub 6/Sn/sub 2/Te/sub 6/ structure, monoclinic, space group P2/sub 1//c (No 14). The lattice constants are given.

mRNA Traffic Control Reviewed: N6-Methyladenosine (m6 A) Takes the Driver's Seat.

Science.gov (United States)

Visvanathan, Abhirami; Somasundaram, Kumaravel

2018-01-01

Messenger RNA is a flexible tool box that plays a key role in the dynamic regulation of gene expression. RNA modifications variegate the message conveyed by the mRNA. Similar to DNA and histone modifications, mRNA modifications are reversible and play a key role in the regulation of molecular events. Our understanding about the landscape of RNA modifications is still rudimentary in contrast to DNA and histone modifications. The major obstacle has been the lack of sensitive detection methods since they are non-editing events. However, with the advent of next-generation sequencing techniques, RNA modifications are being identified precisely at single nucleotide resolution. In recent years, methylation at the N6 position of adenine (m 6 A) has gained the attention of RNA biologists. The m 6 A modification has a set of writers (methylases), erasers (demethylases), and readers. Here, we provide a summary of interesting facts, conflicting findings, and recent advances in the technical and functional aspects of the m 6 A epitranscriptome. © 2017 WILEY Periodicals, Inc.

Bactericidal activity of an imidazo[1, 2-a]pyridine using a mouse M. tuberculosis infection model.

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Yong Cheng

Full Text Available Tuberculosis remains a global threat due in part to the long treatment regimen and the increased prevalence of drug resistant M. tuberculosis strains. Therefore, new drug regimens are urgently required to combat this deadly disease. We previously synthesized and evaluated a series of new anti-tuberculosis compounds which belong to the family of imidazo[1,2-a]pyridines. This family of compounds showed low nM MIC (minimal inhibitory concentration values against M. tuberculosis in vitro. In this study, a derivative of imidazo[1,2-a]pyridines, (N-(4-(4-chlorophenoxybenzyl-2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamide (ND-09759, was selected as a promising lead compound to determine its protective efficacy using a mouse infection model. Pharmacokinetic analysis of ND-09759 determined that at a dosage of 30 mg/kg mouse body weight (PO gave a maximum serum drug concentration (Cmax of 2.9 µg/ml and a half-life of 20.1 h. M. tuberculosis burden in the lungs and spleens was significantly decreased in mice treated once daily 6 days per week for 4-weeks with ND-09759 compared to untreated mice and this antibiotic activity was equivalent to isoniazid (INH and rifampicin (RMP, two first-line anti-TB drugs. We observed slightly higher efficacy when using a combination of ND-09759 with either INH or RMP. Finally, the histopathological analysis revealed that infected mice treated with ND-09759 had significantly reduced inflammation relative to untreated mice. In conclusion, our findings indicate ND-09759 might be a potent candidate for the treatment of active TB in combination with current standard anti-TB drugs.

Half-lives of isomeric levels of sup 1 sup 0 sup 7 sup m Ag, sup 1 sup 0 sup 9 sup m Ag and sup 1 sup 0 sup 3 sup m Rh photoactivated by sup 6 sup 0 Co gamma-ray irradiation

CERN Document Server

Yoshida, E; Kojima, Y; Shizuma, K

2000-01-01

Photoactivation by gamma-rays from sup 6 sup 0 Co of 10 kCi has been performed for isomers of sup 1 sup 0 sup 7 sup m Ag, sup 1 sup 0 sup 9 sup m Ag and sup 1 sup 0 sup 3 sup m Rh and half-lives of these isomers were determined. Gamma-rays emitted from sup 1 sup 0 sup 7 sup m Ag and sup 1 sup 0 sup 9 sup m Ag were measured with a low-background Ge detector and internal conversion electrons from sup 1 sup 0 sup 3 sup m Rh were measured with a 2 pi gas flow counter. The half-lives obtained are: sup 1 sup 0 sup 7 sup m Ag: 44.5+-0.8 s, sup 1 sup 0 sup 9 sup m Ag: 38.0+-1.2 s and sup 1 sup 0 sup 3 sup m Rh: 54.8+-3.8 min. The results are in agreement with previous values obtained by different excitation methods.

Electric conductivity of double fluorides in the systems M1F-Th(U)F4(M1=K, Tl) and M2F2-ThF4(M2=Ca, Sr, Ba)

International Nuclear Information System (INIS)

Murin, I.V.; Andreev, A.M.; Amelin, Yu.V.

1982-01-01

The temperature dependence of electric conductivity of some double fluorides formed in the systems M 1 F-Th(U)F 4 (M 1 =K, Tl) and M 2 F 2 -ThF 4 (M 2 =Ca, Sr, Ba) as well as UF 3 in a wide temperature range is studied. It is shown that the values of electric conductivity and activation energy of these fluorides depend on the compound structure and cation nature. The temperature electric conductivity dependence for double fluorides with the tysonite structure is close to the lanthanum fluoride dependence. Taking into account low electron electric conductivity component the conclusion is drawn that the investigated compounds can be used as solid electrolytes

5-[(3-Fluorophenyl(2-hydroxy-6-oxocyclohex-1-en-1-ylmethyl]-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H-dione

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Assem Barakat

2016-09-01

Full Text Available 5-[(3-Fluorophenyl(2-hydroxy-6-oxocyclohex-1-en-1-yl-methyl]-6-hydroxy-1,3-di-methylpyrimidine-2,4(1H,3H-dione 3 was synthesized via a multicomponent reaction. The Aldol–Michael addition reactions of N,N-dimethylbarbituric acid, cyclohexane-1,3-dione, and 3-fluorobenzaldehyde in aqueous solution gave the product in high yield. The molecular structure of the compound was confirmed by spectroscopic methods and X-ray crystallography. The title compound (C19H19FN2O5·H2O crystallizes in the Monoclinic form, P21/c, a = 7.8630 (5 Å, b = 20.0308 (13 Å, c = 11.3987 (8 Å, β = 104.274 (3°, V = 1739.9 (2° Å3, Z = 4, Rint = 0.117, wR(F2 = 0.124, T = 100 K.

Role of genetic polymorphisms of CYP1A1, CYP3A5, CYP2C9, CYP2D6, and PON1 in the modulation of DNA damage in workers occupationally exposed to organophosphate pesticides

International Nuclear Information System (INIS)

Singh, Satyender; Kumar, Vivek; Vashisht, Kapil; Singh, Priyanka; Banerjee, Basu Dev; Rautela, Rajender Singh; Grover, Shyam Sunder; Rawat, Devendra Singh; Pasha, Syed Tazeen; Jain, Sudhir Kumar; Rai, Arvind

2011-01-01

Organophosphate pesticides (OPs) are primarily metabolized by several xenobiotic metabolizing enzymes (XMEs). Very few studies have explored genetic polymorphisms of XMEs and their association with DNA damage in pesticide-exposed workers. The present study was designed to determine the role of genetic polymorphisms of CYP1A1, CYP3A5, CYP2C9, CYP2D6, and PON1 in the modulation of DNA damage in workers occupationally exposed to OPs. We examined 284 subjects including 150 workers occupationally exposed to OPs and 134 normal healthy controls. The DNA damage was evaluated using the alkaline comet assay and genotyping was done using PCR–RFLP. The results revealed that the PONase activity toward paraoxonase and AChE activity was found significantly lowered in workers as compared to control subjects (p < 0.001). Workers showed significantly higher DNA damage compared to control subjects (14.37 ± 2.15 vs. 6.24 ± 1.37 tail% DNA, p < 0.001). Further, the workers with CYP2D6*3 PM and PON1 (QQ and MM) genotypes were found to have significantly higher DNA damage when compared to other genotypes (p < 0.05). In addition, significant increase in DNA damage was also observed in workers with concomitant presence of certain CYP2D6 and PON1 (Q192R and L55M) genotypes which need further extensive studies. In conclusion, the results indicate that the PON1 and CYP2D6 genotypes can modulate DNA damage elicited by some OPs possibly through gene-environment interactions. -- Highlights: ► Role of CYP1A1, CYP3A5, CYP2C, CYP2D6 and PON1 genotypes on DNA damage. ► Workers exposed to some OPs demonstrated increased DNA damage. ► CYP2D6 *3 PM and PON1 (Q192R and L55M) genotypes are associated with DNA damage. ► Concomitant presence of certain CYP2D6 and PON1 genotypes can increase DNA damage.

Heterologous expression of Ralp3 in Streptococcus pyogenes M2 and M6 strains affects the virulence characteristics.

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Nikolai Siemens

Full Text Available BACKGROUND: Ralp3 is a transcriptional regulator present in a serotype specific fashion on the chromosome of the human pathogen Streptococcus pyogenes (group A streptococci, GAS. In serotypes harbouring the ralp3 gene either positive or negative effects on important metabolic and virulence genes involved in colonization and immune evasion in the human host were observed. A previous study revealed that deletion of ralp3 in a GAS M49 serotype significantly attenuated many virulence traits and caused metabolic disadvantages. This leads to two questions: (i which kind of consequences could Ralp3 expression have in GAS serotypes naturally lacking this gene, and (ii is Ralp3 actively lost during evolution in these serotypes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the role of Ralp3 in GAS M2 and M6 pathogenesis. Both serotypes lack ralp3 on their chromosome. The heterologous expression of ralp3 in both serotypes resulted in reduced attachment to and internalization into the majority of tested epithelial cells. Both ralp3 expression strains showed a decreased ability to survive in human blood and exclusively M2::ralp3 showed decreased survival in human serum. Both mutants secreted more active SpeB in the supernatant, resulting in a higher activity compared to wild type strains. The respective M2 and M6 wild type strains outcompeted the ralp3 expression strains in direct metabolic competition assays. The phenotypic changes observed in the M2:ralp3 and M6:ralp3 were verified on the transcriptional level. Consistent with the virulence data, tested genes showed transcript level changes in the same direction. CONCLUSIONS/SIGNIFICANCE: Together these data suggest that Ralp3 can take over transcriptional control of virulence genes in serotypes lacking the ralp3 gene. Those serotypes most likely lost Ralp3 during evolution since obviously expression of this gene is disadvantageous for metabolism and pathogenesis.

K2 Ultracool Dwarfs Survey. III. White Light Flares Are Ubiquitous in M6-L0 Dwarfs

Science.gov (United States)

Paudel, Rishi R.; Gizis, John E.; Mullan, D. J.; Schmidt, Sarah J.; Burgasser, Adam J.; Williams, Peter K. G.; Berger, Edo

2018-05-01

We report the white light flare rates for 10 ultracool dwarfs using Kepler K2 short-cadence data. Among our sample stars, two have spectral type M6, three are M7, three are M8, and two are L0. Most of our targets are old low-mass stars. We identify a total of 283 flares in all of the stars in our sample, with Kepler energies in the range log E Kp ∼ (29–33.5) erg. Using the maximum-likelihood method of line fitting, we find that the flare frequency distribution (FFD) for each star in our sample follows a power law with slope ‑α in the range ‑(1.3–2.0). We find that cooler objects tend to have shallower slopes. For some of our targets, the FFD follows either a broken power law, or a power law with an exponential cutoff. For the L0 dwarf 2MASS J12321827-0951502, we find a very shallow slope (‑α = ‑1.3) in the Kepler energy range (0.82–130) × 1030 erg: this L0 dwarf has flare rates which are comparable to those of high-energy flares in stars of earlier spectral types. In addition, we report photometry of two superflares: one on the L0 dwarf 2MASS J12321827-0951502 and another on the M7 dwarf 2MASS J08352366+1029318. In the case of 2MASS J12321827-0951502, we report a flare brightening by a factor of ∼144 relative to the quiescent photospheric level. Likewise, for 2MASS J08352366+1029318, we report a flare brightening by a factor of ∼60 relative to the quiescent photospheric level. These two superflares have bolometric (ultraviolet/optical/infrared) energies 3.6 × 1033 erg and 8.9 × 1033 erg respectively, while the full width half maximum timescales are very short, ∼2 min. We find that the M8 star TRAPPIST-1 is more active than the M8.5 dwarf 2M03264453+1919309, but less active than another M8 dwarf (2M12215066-0843197).

Point mutations in the extracytosolic loop between transmembrane segments M5 and M6 of the yeast Pma1 H+-ATPase: alanine-scanning mutagenesis.

Science.gov (United States)

Petrov, Valery V

2015-01-01

Membrane-spanning segments M4, M5, M6, and M8 of the H(+)-, Ca(2+)-, and K(+), Na(+)-ATPases, which belong to the P2-type pumps are the core through which cations are transported. M5 and M6 loop is a short extracytoplasmic stretch of the seven amino acid residues (714-DNSLDID) connecting two of these segments, M5 and M6, where residues involved in the formation of the proton-binding site(s) are located. In the present study, we have used alanine-scanning mutagenesis to explore the structural and functional relationships within this loop of the yeast plasma membrane Pma1 H(+)-ATPase. Of the 7 Ala mutants made, substitution for the most conserved residue (Leu-717) has led to a severe misfolding and complete block in biogenesis of the mutant enzyme. The replacement of Asp-714 has also caused misfolding leading to significant decrease in the expression of the mutant and loss of activity. The remaining mutants were expressed in secretory vesicles at 21-119% of the wild-type level and were active enough to be analyzed in detail. One of these mutants (I719A) showed five- to threefold decrease in both expression and ATP hydrolyzing and H(+) pumping activities and also threefold reduction in the coupling ratio between ATP hydrolysis and H(+) transport. Thus, Ala substitutions at three positions of the seven seriously affected biogenesis, folding, stability and/or functioning of the enzyme. Taken together, these results lead to suggestion that M5 and M6 loop play an important role in the protein stability and function and is responsible for proper arrangement of transmembrane segments M5 and M6 and probably other domains of the enzyme. Results for additional conserved substitutions (Asn and Glu) at Asp-714 and Asp-720 confirmed this suggestion.

Discovery of Clinical Candidate 2-((2S,6 S)-2-Phenyl-6-hydroxyadamantan-2-yl)-1-(3'-hydroxyazetidin-1-yl)ethanone [BMS-816336], an Orally Active Novel Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor

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Ye, Xiang-Yang; Chen, Stephanie Y.; Wu, Shung; Yoon, David S.; Wang, Haixia; Hong, Zhenqiu; O’Connor, Stephen P.; Li, Jun; Li, James J.; Kennedy, Lawrence J.; Walker, Steven J.; Nayeem, Akbar; Sheriff, Steven; Camac, Daniel M.; Ramamurthy, Vidyhashankar; Morin, Paul E.; Zebo, Rachel; Taylor, Joseph R.; Morgan, Nathan N.; Ponticiello, Randolph P.; Harrity, Thomas; Apedo, Atsu; Golla, Rajasree; Seethala, Ramakrishna; Wang, Mengmeng; Harper, Timothy W.; Sleczka, Bogdan G.; He, Bin; Kirby, Mark; Leahy, David K.; Li, Jianqing; Hanson, Ronald L.; Guo, Zhiwei; Li, Yi-Xin; DiMarco, John D.; Scaringe, Raymond; Maxwell, Brad; Moulin, Frederick; Barrish, Joel C.; Gordon, David A.; Robl, Jeffrey A.

2017-06-05

BMS-816336 (6n-2), a hydroxy-substituted adamantyl acetamide, has been identified as a novel, potent inhibitor against human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme (IC₅₀ 3.0 nM) with >10000-fold selectivity over human 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). 6n-2 exhibits a robust acute pharmacodynamic effect in cynomolgus monkeys (ED₅₀ 0.12 mg/kg) and in DIO mice. It is orally bioavailable (%F ranges from 20 to 72% in preclinical species) and has a predicted pharmacokinetic profile of a high peak to trough ratio and short half-life in humans. This ADME profile met our selection criteria for once daily administration, targeting robust inhibition of 11β-HSD1 enzyme for the first 12 h period after dosing followed by an “inhibition holiday” so that the potential for hypothalamic–pituitary–adrenal (HPA) axis activation might be mitigated. 6n-2 was found to be well-tolerated in phase 1 clinical studies and represents a potential new treatment for type 2 diabetes, metabolic syndrome, and other human diseases modulated by glucocorticoid control.

The electrically silent Kv6.4 subunit confers hyperpolarized gating charge movement in Kv2.1/Kv6.4 heterotetrameric channels.

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Elke Bocksteins

Full Text Available The voltage-gated K(+ (Kv channel subunit Kv6.4 does not form functional homotetrameric channels but co-assembles with Kv2.1 to form functional Kv2.1/Kv6.4 heterotetrameric channels. Compared to Kv2.1 homotetramers, Kv6.4 exerts a ~40 mV hyperpolarizing shift in the voltage-dependence of Kv2.1/Kv6.4 channel inactivation, without a significant effect on activation gating. However, the underlying mechanism of this Kv6.4-induced modulation of Kv2.1 channel inactivation, and whether the Kv6.4 subunit participates in the voltage-dependent gating of heterotetrameric channels is not well understood. Here we report distinct gating charge movement of Kv2.1/Kv6.4 heterotetrameric channels, compared to Kv2.1 homotetramers, as revealed by gating current recordings from mammalian cells expressing these channels. The gating charge movement of Kv2.1/Kv6.4 heterotetrameric channels displayed an extra component around the physiological K(+ equilibrium potential, characterized by a second sigmoidal relationship of the voltage-dependence of gating charge movement. This distinct gating charge displacement reflects movement of the Kv6.4 voltage-sensing domain and has a voltage-dependency that matches the hyperpolarizing shift in Kv2.1/Kv6.4 channel inactivation. These results provide a mechanistic basis for the modulation of Kv2.1 channel inactivation gating kinetics by silent Kv6.4 subunits.

Absorption by water vapour in the 1 to 2 μm region

International Nuclear Information System (INIS)

Smith, K.M.; Ptashnik, I.; Newnham, D.A.; Shine, K.P.

2004-01-01

The near-IR (in the range 5000-10 000 cm -1 , 1-2 μm) bands of water vapour have been measured in absorption in the laboratory at sub-Doppler spectral resolution (up to 0.0054 cm -1 after numerical apodisation) by Fourier transform spectroscopy. Measurements have been made at 296 K on pure water vapour (at pressures between 2 and 20 hPa) and mixtures of water and air (at total pressures of 100 and 1000 hPa), at optical path lengths in the range 0.26-9.75 m. Measured absorption intensities have been compared with values calculated using the HITRAN 2000 molecular database. These comparisons indicate that the intensities of the 2ν(1.4 μm) and 2ν+δ(1.14 μm) bands are underestimated in HITRAN 2000 by approximately 15% and 20%, respectively, for pure water vapour measurements, and 12% for both bands in the case of water-air mixtures. The ν+δ (1.86 μm) band is in good agreement (0.4% for pure water vapour and less than 6% for mixtures with air) with HITRAN 2000. For typical atmospheric conditions, these absorption bands are sufficiently strong that radiation is fully absorbed at wavelengths in the region of the band centres. Hence the extra absorption that has been identified has only a modest impact (0.16 W m -2 or about 0.2%) on the global-mean clear-sky absorption of solar radiation. The impact in the upper troposphere is several times larger