49 CFR Figure 3 to Subpart E of... - Trailer Car End Structure Conceptual Implementation 1-to Subpart E

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Trailer Car End Structure Conceptual Implementation 1-to Subpart E 3 Figure 3 to Subpart E of Part 238 Transportation Other Regulations Relating to... to Subpart E of Part 238—Trailer Car End Structure Conceptual Implementation 1—to Subpart E ER12MY99...

49 CFR Figure 3 to Subpart E of... - Trailer Car End Structure Conceptual Implementation 1-to Subpart E

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Trailer Car End Structure Conceptual Implementation 1-to Subpart E 3 Figure 3 to Subpart E of Part 238 Transportation Other Regulations Relating to... to Subpart E of Part 238—Trailer Car End Structure Conceptual Implementation 1—to Subpart E ER12MY99...

TFDP3 was expressed in coordination with E2F1 to inhibit E2F1-mediated apoptosis in prostate cancer.

PubMed

Ma, Yueyun; Xin, Yijuan; Li, Rui; Wang, Zhe; Yue, Qiaohong; Xiao, Fengjing; Hao, Xiaoke

2014-03-10

TFDP3 has been previously identified as an inhibitor of E2F molecules. It has been shown to suppress E2F1-induced apoptosis dependent P53 and to play a potential role in carcinogenesis. However, whether it indeed helps cancer cells tolerate apoptosis stress in cancer tissues remains unknown. TFDP3 expression was assessed by RT-PCR, in situ hybridization and immunohistochemistry in normal human tissues, cancer tissues and prostate cancer tissues. The association between TFDP3 and E2F1 in prostate cancer development was analyzed in various stages. Apoptosis was evaluated with annexin-V and propidium iodide staining and flow-cytometry. The results show that, in 96 samples of normal human tissues, TFDP3 could be detected in the cerebrum, esophagus, stomach, small intestine, bronchus, breast, ovary, uterus, and skin, but seldom in the lung, muscles, prostate, and liver. In addition, TFDP3 was highly expressed in numerous cancer tissues, such as brain-keratinous, lung squamous cell carcinoma, testicular seminoma, cervical carcinoma, skin squamous cell carcinoma, gastric adenocarcinoma, liver cancer, and prostate cancer. Moreover, TFDP3 was positive in 23 (62.2%) of 37 prostate cancer samples regardless of stage. Furthermore, immunohistochemistry results show that TFDP3 was always expressed in coordination with E2F1 at equivalent expression levels in prostate cancer tissues, and was highly expressed particularly in samples of high stage. When E2F1 was extrogenously expressed in LNCap cells, TFDP3 could be induced, and the apoptosis induced by E2F1 was significantly decreased. It was demonstrated that TFDP3 was a broadly expressed protein corresponding to E2F1 in human tissues, and suggested that TFDP3 is involved in prostate cancer cell survival by suppressing apoptosis induced by E2F1. Copyright © 2013 Elsevier B.V. All rights reserved.

The adenovirus E4-ORF3 protein functions as a SUMO E3 ligase for TIF-1γ sumoylation and poly-SUMO chain elongation.

PubMed

Sohn, Sook-Young; Hearing, Patrick

2016-06-14

The adenovirus (Ad) early region 4 (E4)-ORF3 protein regulates diverse cellular processes to optimize the host environment for the establishment of Ad replication. E4-ORF3 self-assembles into multimers to form a nuclear scaffold in infected cells and creates distinct binding interfaces for different cellular target proteins. Previous studies have shown that the Ad5 E4-ORF3 protein induces sumoylation of multiple cellular proteins and subsequent proteasomal degradation of some of them, but the detailed mechanism of E4-ORF3 function remained unknown. Here, we investigate the role of E4-ORF3 in the sumoylation process by using transcription intermediary factor (TIF)-1γ as a substrate. Remarkably, we discovered that purified E4-ORF3 protein stimulates TIF-1γ sumoylation in vitro, demonstrating that E4-ORF3 acts as a small ubiquitin-like modifier (SUMO) E3 ligase. Furthermore, E4-ORF3 significantly increases poly-SUMO3 chain formation in vitro in the absence of substrate, showing that E4-ORF3 has SUMO E4 elongase activity. An E4-ORF3 mutant, which is defective in protein multimerization, exhibited severely decreased activity, demonstrating that E4-ORF3 self-assembly is required for these activities. Using a SUMO3 mutant, K11R, we found that E4-ORF3 facilitates the initial acceptor SUMO3 conjugation to TIF-1γ as well as poly-SUMO chain elongation. The E4-ORF3 protein displays no SUMO-targeted ubiquitin ligase activity in our assay system. These studies reveal the mechanism by which E4-ORF3 targets specific cellular proteins for sumoylation and proteasomal degradation and provide significant insight into how a small viral protein can play a role as a SUMO E3 ligase and E4-like SUMO elongase to impact a variety of cellular responses.

The E3Σ1+ (63S1) ← A3Π0+(53P1) transition in CdAr revisited: The spectrum and new analysis of the E3Σ1+ Rydberg state interatomic potential

NASA Astrophysics Data System (ADS)

Urbańczyk, T.; Krośnicki, M.; Kędziorski, A.; Koperski, J.

2018-05-01

Revisited study of the E3Σ1+ (63S1) ← A3Π0+(53P1) transition in CdAr using both theoretical and experimental approach is presented. Systematic detection of the E3Σ1+in,υ' ← A3Π0+,υ″ = 6 transition frequencies with higher accuracy and spectrally narrower laser extended and improved analysis and simulation of the LIF excitation spectrum. More consistent characterization of the E3Σ1+in-Rydberg state inner well using inversed perturbation approach methodology was achieved. Free ← bound transitions in the E3Σ1+in ← A3Π0+,υ″ = 6 excitation were taken into account in the analysis and simulation of the recorded spectrum. The updated spectroscopic characterization of the A3Π0+ state was also revisited.

The E3Σ1+ (63S1)←A3Π0+(53P1) transition in CdAr revisited: The spectrum and new analysis of the E3Σ1+ Rydberg state interatomic potential.

PubMed

Urbańczyk, T; Krośnicki, M; Kędziorski, A; Koperski, J

2018-05-05

Revisited study of the E 3 Σ 1 + (6 3 S 1 )←A 3 Π 0+ (5 3 P 1 ) transition in CdAr using both theoretical and experimental approach is presented. Systematic detection of the E 3 Σ 1 + in ,υ'←A 3 Π 0+ ,υ″=6 transition frequencies with higher accuracy and spectrally narrower laser extended and improved analysis and simulation of the LIF excitation spectrum. More consistent characterization of the E 3 Σ 1 + in -Rydberg state inner well using inversed perturbation approach methodology was achieved. Free←bound transitions in the E 3 Σ 1 + in ←A 3 Π 0+ ,υ″=6 excitation were taken into account in the analysis and simulation of the recorded spectrum. The updated spectroscopic characterization of the A 3 Π 0+ state was also revisited. Copyright © 2018 Elsevier B.V. All rights reserved.

Compressive force induces osteoclast differentiation via prostaglandin E(2) production in MC3T3-E1 cells.

PubMed

Sanuki, Rina; Shionome, Chieko; Kuwabara, Akiko; Mitsui, Narihiro; Koyama, Yuki; Suzuki, Naoto; Zhang, Fan; Shimizu, Noriyoshi; Maeno, Masao

2010-04-01

In orthodontic tooth movement, prostaglandin E(2) (PGE(2)) released from osteoblasts can alter the normal process of bone remodeling. We previously showed that compressive force (CF) controls bone formation by stimulating the production of PGE(2) and Ep2 and/or Ep4 receptors in osteoblasts. The present study was undertaken to examine the effect of CF on the production of PGE(2), cyclooxygenase-2 (COX-2), macrophage colony-stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) using osteoblastic MC3T3-E1 cells and to examine the indirect effect of CF on osteoclast differentiation using RAW264.7 cells as osteoclast precursors. MC3T3-E1 cells were cultured with or without continuous CF (1.0 or 3.0 g/cm(2)) for 24 hr, and PGE(2) production was determined using ELISA. The expression of COX-2, M-CSF, RANKL, and OPG genes and proteins was determined using real-time PCR and ELISA, respectively. Osteoclast differentiation was estimated using tartrate-resistant acid phosphatase (TRAP) staining of RAW 264.7 cells cultured for 10 days with conditioned medium from CF-treated MC3T3-E1 cells and soluble RANKL. As CF increased, PGE(2) production and the expression of COX-2, M-CSF, and RANKL increased, whereas OPG expression decreased. The number of TRAP-positive cells increased as CF increased. Celecoxib, a specific inhibitor of COX-2, blocked the stimulatory effect of CF on TRAP staining and the production of PGE(2), M-CSF, RANKL, and OPG. These results suggest that CF induces osteoclast differentiation by increasing M-CSF production and decreasing OPG production via PGE(2) in osteoblasts.

40 CFR 721.10171 - 1H-benz(e)indolium, 1,1,2,3-tetramethyl-, 4-methylbenzenesulfonic acid (1:1).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1H-benz(e)indolium, 1,1,2,3... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10171 1H-benz(e)indolium, 1,1,2,3... reporting. (1) The chemical substance identified as 1H-benz(e)indolium, 1,1,2,3-tetramethyl-, 4...

Indication of prenatal diagnosis in pregnancies complicated by undetectable second-trimester maternal serum estriol levels.

PubMed

Minsart, Anne-Frédérique; Van Onderbergen, Anne; Jacques, Francotte; Kurt, Crener; Gillerot, Yves

2008-07-01

Undetectable maternal serum unconjugated estriol levels in the second-trimester screening test have been associated with congenital pathology and an adverse pregnancy outcome. We reviewed outcomes of pregnancies with undetectable levels of estriol (<0.25 ng/ml) in the triple-marker screening test and assessed the clinical value of this finding. We studied estriol values in 6,018 pregnant patients who underwent a triple-marker screening test during a seven-year period. 26 women had estriol levels at or below the sensitivity of the assay. The most common explanations were dating errors, prematurity, growth restriction and X-linked ichthyosis. We also observed one fetal death at 16 weeks, one severe threatened fetal abortion, one case of multiple congenital anomalies and one case of isolated adrenocorticotropin hormone deficiency. There were 6 women remaining with unexplained undetectable estriol. Undetectable maternal estriol values may indicate a severe fetal pathology and should lead to further investigations.

Structure of a Glomulin-RBX1-CUL1 Complex: Inhibition of a RING E3 Ligase through Masking of Its E2-Binding Surface

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

Duda, David M.; Olszewski, Jennifer L.; Tron, Adriana E.

2012-11-01

The approximately 300 human cullin-RING ligases (CRLs) are multisubunit E3s in which a RING protein, either RBX1 or RBX2, recruits an E2 to catalyze ubiquitination. RBX1-containing CRLs also can bind Glomulin (GLMN), which binds RBX1's RING domain, regulates the RBX1-CUL1-containing SCF{sup FBW7} complex, and is disrupted in the disease Glomuvenous Malformation. Here we report the crystal structure of a complex between GLMN, RBX1, and a fragment of CUL1. Structural and biochemical analyses reveal that GLMN adopts a HEAT-like repeat fold that tightly binds the E2-interacting surface of RBX1, inhibiting CRL-mediated chain formation by the E2 CDC34. The structure explains themore » basis for GLMN's selectivity toward RBX1 over RBX2, and how disease-associated mutations disrupt GLMN-RBX1 interactions. Our study reveals a mechanism for RING E3 ligase regulation, whereby an inhibitor blocks E2 access, and raises the possibility that other E3s are likewise controlled by cellular proteins that mask E2-binding surfaces to mediate inhibition.« less

Structure of a Glomulin-RBX1-CUL1 complex: inhibition of a RING E3 ligase through masking of its E2-binding surface

PubMed Central

Duda, David M.; Olszewski, Jennifer L.; Tron, Adriana E.; Hammel, Michal; Lambert, Lester J.; Waddell, M. Brett; Mittag, Tanja; DeCaprio, James A.; Schulman, Brenda A.

2012-01-01

Summary The ~300 human Cullin-RING ligases (CRLs) are multisubunit E3s in which a RING protein, either RBX1 or RBX2, recruits an E2 to catalyze ubiquitination. RBX1-containing CRLs also can bind Glomulin (GLMN), which binds RBX1’s RING domain, regulates the RBX1-CUL1-containing SCFFBW7 complex, and is disrupted in the disease Glomuvenous Malformation. Here we report the crystal structure of a complex between GLMN, RBX1, and a fragment of CUL1. Structural and biochemical analyses reveal that GLMN adopts a HEAT-like repeat fold that tightly binds the E2-interacting surface of RBX1, inhibiting CRL-mediated chain formation by the E2 CDC34. The structure explains the basis for GLMN’s selectivity toward RBX1 over RBX2, and how disease-associated mutations disrupt GLMN-RBX1 interactions. Our study reveals a mechanism for RING E3 ligase regulation whereby an inhibitor blocks E2 access, and raises the possibility that other E3s are likewise controlled by cellular proteins that mask E2-binding surfaces to mediate inhibition. PMID:22748924

The zebrafish orphan nuclear receptor genes nr2e1 and nr2e3 are expressed in developing eye and forebrain.

PubMed

Kitambi, Satish Srinivas; Hauptmann, Giselbert

2007-02-01

Mammalian Nr2e1 (Tailless, Mtll or Tlx) and Nr2e3 (photoreceptor-specific nuclear receptor, Pnr) are highly related orphan nuclear receptors, that are expressed in eye and forebrain-derived structures. In this study, we analyzed the developmental expression patterns of zebrafish nr2e1 and nr2e3. RT-PCR analysis showed that nr2e1 and nr2e3 are both expressed during embryonic and post-embryonic development. To examine the spatial distribution of nr2e1 and nr2e3 during development whole-mount in situ hybridization was performed. At tailbud stage, initial nr2e1 expression was localized to the rostral brain rudiment anterior to pax2.1 and eng2 expression at the prospective midbrain-hindbrain boundary. During subsequent stages, nr2e1 became widely expressed in fore- and midbrain primordia, eye and olfactory placodes. At 24hpf, strong nr2e1 expression was detected in telencephalon, hypothalamus, dorsal thalamus, pretectum, midbrain tectum, and retina. At 2dpf, the initially widespread nr2e1 expression became more restricted to distinct regions within the fore- and midbrain and to the retinal ciliary margin, the germinal zone which gives rise to retina and presumptive iris. Expression of nr2e3 was exclusively found in the developing retina and epiphysis. In both structures, nr2e3 expression was found in photoreceptor cells. The developmental expression profile of zebrafish nr2e1 and nr2e3 is consistent with evolutionary conserved functions in eye and rostral brain structures.

Efficacy of Erbium:YAG laser treatment compared to topical estriol treatment for symptoms of genitourinary syndrome of menopause

PubMed Central

Brandi, Hugo; Gomez, Valentin; Luque, Daniel

2016-01-01

Objectives The objective of this prospective comparative cohort study was to establish the effectiveness and safety of Erbium:YAG (Er:YAG) laser treatment for genitourinary syndrome of menopause and to compare it with an established topical estriol treatment. Methods Fifty patients with genitourinary syndrome of menopause were divided into two groups. The estriol group received a treatment of 0.5 mg estriol ovules for 8 weeks and the laser group was first treated for 2 weeks with 0.5 mg estriol ovules 3 times per week to hydrate the mucosa and then received three sessions with 2,940 nm Er:YAG laser in non‐ablative mode. Biopsies were taken before and at 1, 3, 6, and 12 months post‐treatment. Maturation index, maturation value and pH where recorded up to 12‐months post‐treatment, while the VAS analysis of symptoms was recorded up to 18 months post‐treatment. Results Statistically significant (P < 0.05), reduction of all assessed symptoms was observed in the laser group at all follow‐ups up to 18 months post‐treatment. Significant improvement in maturation value and a decrease of pH in the laser group was detected up to 12 months after treatment. The improvement in all endpoints was more pronounced and longer lasting in the laser group. Histological examination showed changes in the tropism of the vaginal mucosa and also angiogenesis, congestion, and restructuring of the lamina propria in the laser group. Side effects were minimal and of transient nature in both groups, affecting 4% of patients in the laser group and 12% of patients in the estriol group. Conclusions Our results show that Er:YAG laser treatment successfully relieves symptoms of genitourinary syndrome of menopause and that the results are more pronounced and longer lasting compared to topical estriol treatment. Lasers Surg. Med. 49:160–168, 2017. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc. PMID:27546524

Efficacy of Erbium:YAG laser treatment compared to topical estriol treatment for symptoms of genitourinary syndrome of menopause.

PubMed

Gaspar, Adrian; Brandi, Hugo; Gomez, Valentin; Luque, Daniel

2017-02-01

The objective of this prospective comparative cohort study was to establish the effectiveness and safety of Erbium:YAG (Er:YAG) laser treatment for genitourinary syndrome of menopause and to compare it with an established topical estriol treatment. Fifty patients with genitourinary syndrome of menopause were divided into two groups. The estriol group received a treatment of 0.5 mg estriol ovules for 8 weeks and the laser group was first treated for 2 weeks with 0.5 mg estriol ovules 3 times per week to hydrate the mucosa and then received three sessions with 2,940 nm Er:YAG laser in non-ablative mode. Biopsies were taken before and at 1, 3, 6, and 12 months post-treatment. Maturation index, maturation value and pH where recorded up to 12-months post-treatment, while the VAS analysis of symptoms was recorded up to 18 months post-treatment. Statistically significant (P < 0.05), reduction of all assessed symptoms was observed in the laser group at all follow-ups up to 18 months post-treatment. Significant improvement in maturation value and a decrease of pH in the laser group was detected up to 12 months after treatment. The improvement in all endpoints was more pronounced and longer lasting in the laser group. Histological examination showed changes in the tropism of the vaginal mucosa and also angiogenesis, congestion, and restructuring of the lamina propria in the laser group. Side effects were minimal and of transient nature in both groups, affecting 4% of patients in the laser group and 12% of patients in the estriol group. Our results show that Er:YAG laser treatment successfully relieves symptoms of genitourinary syndrome of menopause and that the results are more pronounced and longer lasting compared to topical estriol treatment. Lasers Surg. Med. 49:160-168, 2017. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Search for 1/3e and 2/3e charged quarks in the cosmic radiation at 2750-m altitude.

NASA Technical Reports Server (NTRS)

Cox, A. J.; Beauchamp, W. T.; Bowen, T.; Kalbach, R. M.

1972-01-01

A scintillation counter telescope consisting of eight liquid scintillation counters and four wide-gap spark chambers was used to search for particles with electric charge 1/3e and 2/3e in cosmic rays at 2750 m above sea level. No such particles were detected during the 1500-hr experimental run. Upper limits on the vertical fluxes are established, and estimates of the corresponding sea-level fluxes are made for comparison with previous results.

Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells

NASA Technical Reports Server (NTRS)

Yamaguchi, T.; Chattopadhyay, N.; Kifor, O.; Butters, R. R. Jr; Sugimoto, T.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

1998-01-01

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Osteoblasts appear at sites of osteoclastic bone resorption during bone remodeling in the "reversal" phase following osteoclastic resorption and preceding bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for osteoblasts in the vicinity, leading us to determine whether such osteoblasts express the CaR. In this study, we used the mouse osteoblastic, clonal cell line MC3T3-E1. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in MC3T3-E1 cells. We also identified CaR transcripts in MC3T3-E1 cells by Northern analysis using a CaR-specific riboprobe and by reverse transcription-polymerase chain reaction with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of MC3T3-E1 cells to high Ca2+o (up to 4.8 mM) or the polycationic CaR agonists, neomycin and gadolinium (Gd3+), stimulated both chemotaxis and DNA synthesis in MC3T3-E1 cells. Therefore, taken together, our data strongly suggest that the osteoblastic cell line MC3T3-E1 possesses both CaR protein and mRNA very similar, if not identical, to those in parathyroid and kidney. Furthermore, the CaR in these osteoblasts could play a key role in regulating bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local release of Ca2+o.

Calcification of MC3T3-E1 cells on titanium and zirconium.

PubMed

Umezawa, Takayuki; Chen, Peng; Tsutsumi, Yusuke; Doi, Hisashi; Ashida, Maki; Suzuki, Shoichi; Moriyama, Keiji; Hanawa, Takao

2015-01-01

To confirm similarity of hard tissue compatibility between titanium and zirconium, calcification of MC3T3-E1 cells on titanium and zirconium was evaluated in this study. Mirror-polished titanium (Ti) and zirconium (Zr) disks and zirconium-sputter deposited titanium (Zr/Ti) were employed in this study. The surface of specimens were characterized using scanning electron microscopy and X-ray diffraction. Then, the cellular proliferation, differentiation and calcification of MC3T3-E1 cells on specimens were investigated. The surface of Zr/Ti was much smoother and cleaner than those of Ti and Zr. The proliferation of the cell was the same among three specimens, while the differentiation and calcification on Zr/Ti were faster than those on Ti and Zr. Therefore, Ti and Zr showed the identical hard tissue compatibility according to the evaluation with MC3T3-E1 cells. Sputter deposition may improve cytocompatibility.

Bioactive constituents from Chinese natural medicines. XXII. Absolute structures of new megastigmane glycosides, sedumosides E1, E2, E3, F1, F2, and G, from Sedum sarmentosum (Crassulaceae).

PubMed

Morikawa, Toshio; Zhang, Yi; Nakamura, Seikou; Matsuda, Hisashi; Muraoka, Osamu; Yoshikawa, Masayuki

2007-03-01

Six new megastigmane glycosides, sedumosides E1, E2, E3, F1, F2, and G, were isolated from the whole plant of Sedum sarmentosum (Crassulaceae). The structures of new constituents including the absolute configuration were elucidated on the basis of chemical and physicochemical evidence.

E3 Success Story - Accelerating Adoption of E3 Recommendations

EPA Pesticide Factsheets

The state of Michigan, along with numerous local and state partners, formed E3 Michigan in 2010. This partnership will allow for up to 10 E3 assessments in southeast Michigan and 10 E3 assessments in western Michigan.

The tripartite leader sequence is required for ectopic expression of HAdV-B and HAdV-E E3 CR1 genes.

PubMed

Bair, Camden R; Kotha Lakshmi Narayan, Poornima; Kajon, Adriana E

2017-05-01

The unique repertoire of genes that characterizes the early region 3 (E3) of the different species of human adenovirus (HAdV) likely contributes to their distinct pathogenic traits. The function of many E3 CR1 proteins remains unknown possibly due to unidentified intrinsic properties that make them difficult to express ectopically. This study shows that the species HAdV-B- and HAdV-E-specific E3 CR1 genes can be expressed from vectors carrying the HAdV tripartite leader (TPL) sequence but not from traditional mammalian expression vectors. Insertion of the TPL sequence upstream of the HAdV-B and HAdV-E E3 CR1 open reading frames was sufficient to rescue protein expression from pCI-neo constructs in transfected 293T cells. The detection of higher levels of HAdV-B and HAdV-E E3 CR1 transcripts suggests that the TPL sequence may enhance gene expression at both the transcriptional and translational levels. Our findings will facilitate the characterization of additional AdV E3 proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

The efficacy and safety of estriol to treat vulvovaginal atrophy in postmenopausal women: a systematic literature review.

PubMed

Rueda, C; Osorio, A M; Avellaneda, A C; Pinzón, C E; Restrepo, O I

2017-08-01

To evaluate the efficacy and safety of estriol for the treatment of vulvovaginal atrophy in postmenopausal women. A systematic literature review was performed. We searched the following electronic databases: Medline, Cochrane, Embase, Lilacs, CINHAL and Google Scholar. The studies selected included controlled clinical trials and quasi-experimental studies. Selections were made in pairs and independently, first by title and abstract and then complete texts. We identified 188 studies, 22 of which met the inclusion criteria; 13 were controlled clinical trials and nine were quasi-experimental, and 1217 women were included. These studies confirmed the efficacy of local estrogens to treat symptoms of vulvovaginal atrophy with few adverse effects reported. Following treatment, serum estriol levels rose, peaking at 1 h. At the 6-month follow-up, there was no increase in serum estriol in treated women. The available evidence (of low and moderate quality) shows that, when administered vaginally, estriol preparations appear to be safe for women who have risk factors related to systemic estrogen therapy.

26 CFR 1.367(e)-0 - Outline of §§ 1.367(e)-1 and 1.367(e)-2.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 4 2011-04-01 2011-04-01 false Outline of §§ 1.367(e)-1 and 1.367(e)-2. 1.367(e)-0 Section 1.367(e)-0 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Effects on Corporation § 1.367(e)-0 Outline of §§ 1.367(e)-1...

Divalent Metal Ions Induced Osteogenic Differentiation of MC3T3E1

NASA Astrophysics Data System (ADS)

Wang, Guoshou; Su, Wenta; Chen, Pohung; Huang, Teyang

2017-12-01

Biomaterial scaffolds blended with biochemical signal molecules with adequate osteoinductive and osteoconductive properties have attracted significant interest in bone tissue engineering regeneration. The divalent metal ions can gradually release from the scaffold into the culture medium and then induced osteoblastic differentiation of MC3T3E1. These MC3T3E1 cells expressed high activity of alkaline phosphatase, bone-related gene expression of collagen type I, Runx2, osteopontin, osteocalcin, and significantly enhanced deposited minerals on scaffold after 21 days of culture. This experiment provided a useful inducer for osteogenic differentiation in bone repair.

Quasifree (e,e'p) reaction on /sup 3/He

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

Jans, E.; Barreau, P.; Bernheim, M.

1982-10-04

The proton momentum distribution of /sup 3/He has been determined up to momenta of 310 MeV/c by use of the reaction /sup 3/He(e,e'p). The experimental missing energy resolution, deltaE/sub m/ = 1.2 MeV, was sufficient to separate the two- and three-body breakup channels. Results for the three-body disintegration have been obtained up to missing energy values of 80 MeV. The resulting spectral function is compared with the predictions of Faddeev and variational calculations.

OH + (E)- and (Z)-1-chloro-3,3,3-trifluoropropene-1 (CF3CH═CHCl) reaction rate coefficients: stereoisomer-dependent reactivity.

PubMed

Gierczak, Tomasz; Baasandorj, M; Burkholder, James B

2014-11-20

Rate coefficients for the gas-phase reaction of the OH radical with (E)- and (Z)-CF3CH═CHCl (1-chloro-3,3,3-trifluoropropene-1, HFO-1233zd) (k1(T) and k2(T), respectively) were measured under pseudo-first-order conditions in OH over the temperature range 213-376 K. OH was produced by pulsed laser photolysis, and its temporal profile was measured using laser-induced fluorescence. The obtained rate coefficients were independent of pressure between 25 and 100 Torr (He, N2) with k1(296 K) = (3.76 ± 0.35) × 10(-13) cm(3) molecule(-1) s(-1) and k2(296 K) = (9.46 ± 0.85) × 10(-13) cm(3) molecule(-1) s(-1) (quoted uncertainties are 2σ and include estimated systematic errors). k2(T) showed a weak non-Arrhenius behavior over this temperature range. The (E)- and (Z)- stereoisomer rate coefficients were found to have opposite temperature dependencies that are well represented by k1(T) = (1.14 ± 0.15) × 10(-12) exp[(-330 ± 10)/T] cm(3) molecule(-1) s(-1) and k2(T) = (7.22 ± 0.65) × 10(-19) × T(2) × exp[(800 ± 20)/T] cm(3) molecule(-1) s(-1). The present results are compared with a previous room temperature relative rate coefficient study of k1, and an explanation for the discrepancy is presented. CF3CHO, HC(O)Cl, and CF3CClO, were observed as stable end-products following the OH radical initiated degradation of (E)- and (Z)-CF3CH═CHCl in the presence of O2. In addition, chemically activated isomerization was also observed. Atmospheric local lifetimes of (E)- and (Z)-CF3CH═CHCl, due to OH reactive loss, were estimated to be ∼34 and ∼11 days, respectively. Infrared absorption spectra measured in this work were used to estimate radiative efficiencies and well-mixed global warming potentials of ∼10 and ∼3 for (E)- and (Z)-CF3CH═CHCl, respectively, on the 100-year time horizon.

Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor(®)) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study.

PubMed

Donders, Gilbert; Neven, Patrick; Moegele, Maximilian; Lintermans, Anneleen; Bellen, Gert; Prasauskas, Valdas; Grob, Philipp; Ortmann, Olaf; Buchholz, Stefan

2014-06-01

Phase I pharmacokinetic (PK) study assessed circulating estrogens in breast cancer (BC) patients on a non-steroidal aromatase inhibitor (NSAI) with vaginal atrophy using vaginal ultra-low-dose 0.03 mg estriol (E3) and Lactobacillus combination vaginal tablets (Gynoflor(®)). 16 women on NSAI with severe vaginal atrophy applied a daily vaginal tablet of Gynoflor(®) for 28 days followed by a maintenance therapy of 3 tablets weekly for 8 weeks. Primary outcomes were serum concentrations and PK of E3, estradiol (E2), and estrone (E1) using highly sensitive gas chromatography-mass spectrometry. Secondary outcomes were clinical measures for efficacy and side effects; microscopic changes in vaginal epithelium and microflora; and changes in serum FSH, LH, and sex hormone-binding globulin. Compared with baseline, serum E1 and E2 did not increase in any of the women at any time following vaginal application. Serum E3 transiently increased after the first application in 15 of 16 women, with a maximum of 168 pg/ml 2-3 h post-insertion. After 4 weeks, serum E3 was slightly increased in 8 women with a maximum of 44 pg/ml. The vaginal atrophy resolved or improved in all women. The product was well tolerated, and discontinuation of therapy was not observed. The low-dose 0.03 mg E3 and Lactobacillus acidophilus vaginal tablets application in postmenopausal BC patients during AI treatment suffering from vaginal atrophy lead to small and transient increases in serum E3, but not E1 or E2, and therefore can be considered as safe and efficacious for treatment of atrophic vaginitis in BC patients taking NSAIs.

Osteogenic gene expression of murine osteoblastic (MC3T3-E1) cells under cyclic tension

NASA Astrophysics Data System (ADS)

Kao, C. T.; Chen, C. C.; Cheong, U.-I.; Liu, S. L.; Huang, T. H.

2014-08-01

Low-level laser therapy (LLLT) can promote cell proliferation. The remodeling ability of the tension side of orthodontic teeth affects post-orthodontic stability. The purpose of the present study was to investigate the osteogenic effects of LLLT on osteoblast-like cells treated with a simulated tension system that provides a mechanical tension regimen. Murine osteoblastic (MC3T3-E1) cells were cultured in a Flexcell strain unit with programmed loads of 12% elongation at a frequency of 0.5 Hz for 24 and 48 h. The cultured cells were treated with a low-level diode laser using powers of 5 J and 10 J. The proliferation of MC3T3-E1 cells was determined using the Alamar Blue assay. The expression of osteogenic genes (type I collagen (Col-1), osteopontin (OPN), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), bone morphologic protein (BMP-2), and bone morphologic protein (BMP-4)) in MC3T3-E1 cells was analyzed using reverse transcription polymerase chain reaction (RT-PCR). The data were analyzed using one-way analysis of variance. The proliferation rate of tension-cultured MC3T3-E1 cells under 5 J and 10 J LLLT increased compared with that of the control group (p < 0.05). Prominent mineralization of the MC3T3-E1 cells was visible using a von Kossa stain in the 5 J LLLT group. Osteogenic genes (Col-1, OC, OPG and BMP-2) were significantly expressed in the MC3T3-E1 cells treated with 5 J and 10 J LLLT (p < 0.05). LLLT in tension-cultured MC3T3-E1 cells showed synergistic osteogenic effects, including increases in cell proliferation and Col-1, OPN, OC, OPG and BMP-2 gene expression. LLLT might be beneficial for bone remodeling on the tension side of orthodontics.

Role of SKP1-CUL1-F-Box-Protein (SCF) E3 Ubiquitin Ligases in Skin Cancer

PubMed Central

Xie, Chuan-Ming; Wei, Wenyi; Sun, Yi

2013-01-01

Many biological processes such as cell proliferation, differentiation, and cell death depend precisely on the timely synthesis and degradation of key regulatory proteins. While protein synthesis can be regulated at multiple levels, protein degradation is mainly controlled by the ubiquitin—proteasome system (UPS), which consists of two distinct steps: (1) ubiquitylation of targeted protein by E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and E3 ubiquitin ligase, and (2) subsequent degradation by the 26S proteasome. Among all E3 ubiquitin ligases, the SCF (SKP1-CUL1-F-box protein) E3 ligases are the largest family and are responsible for the turnover of many key regulatory proteins. Aberrant regulation of SCF E3 ligases is associated with various human diseases, such as cancers, including skin cancer. In this review, we provide a comprehensive overview of all currently published data to define a promoting role of SCF E3 ligases in the development of skin cancer. The future directions in this area of research are also discussed with an ultimate goal to develop small molecule inhibitors of SCF E3 ligases as a novel approach for the treatment of human skin cancer. Furthermore, altered components or substrates of SCF E3 ligases may also be developed as the biomarkers for early diagnosis or predicting prognosis. PMID:23522382

21 CFR 862.1265 - Estriol test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Estriol test system. 862.1265 Section 862.1265 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

21 CFR 862.1265 - Estriol test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Estriol test system. 862.1265 Section 862.1265 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

21 CFR 862.1265 - Estriol test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Estriol test system. 862.1265 Section 862.1265 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

21 CFR 862.1265 - Estriol test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Estriol test system. 862.1265 Section 862.1265 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

Mutation at Tyrosine in AMLRY (GILRY Like) Motif of Yeast eRF1 on Nonsense Codons Suppression and Binding Affinity to eRF3

PubMed Central

Akhmaloka; Susilowati, Prima Endang; Subandi; Madayanti, Fida

2008-01-01

Termination translation in Saccharomyces cerevisiae is controlled by two interacting polypeptide chain release factors, eRF1 and eRF3. Two regions in human eRF1, position at 281-305 and position at 411-415, were proposed to be involved on the interaction to eRF3. In this study we have constructed and characterized yeast eRF1 mutant at position 410 (correspond to 415 human eRF1) from tyrosine to serine residue resulting eRF1(Y410S). The mutations did not affect the viability and temperature sensitivity of the cell. The stop codons suppression of the mutant was analyzed in vivo using PGK-stop codon-LACZ gene fusion and showed that the suppression of the mutant was significantly increased in all of codon terminations. The suppression on UAG codon was the highest increased among the stop codons by comparing the suppression of the wild type respectively. In vitro interaction between eRF1 (mutant and wild type) to eRF3 were carried out using eRF1-(His)6 and eRF1(Y410S)-(His)6 expressed in Escherichia coli and indigenous Saccharomyces cerevisiae eRF3. The results showed that the binding affinity of eRF1(Y410S) to eRF3 was decreased up to 20% of the wild type binding affinity. Computer modeling analysis using Swiss-Prot and Amber version 9.0 programs revealed that the overall structure of eRF1(Y410S) has no significant different with the wild type. However, substitution of tyrosine to serine triggered the structural change on the other motif of C-terminal domain of eRF1. The data suggested that increasing stop codon suppression and decreasing of the binding affinity of eRF1(Y410S) were probably due to the slight modification on the structure of the C-terminal domain. PMID:18463713

Diagnosis of 25 genotypes of human papillomaviruses for their physical statuses in cervical precancerous/cancerous lesions: a comparison of E2/E6E7 ratio-based vs. multiple E1-L1/E6E7 ratio-based detection techniques.

PubMed

Zhang, Rong; He, Yi-feng; Chen, Mo; Chen, Chun-mei; Zhu, Qiu-jing; Lu, Huan; Wei, Zhen-hong; Li, Fang; Zhang, Xiao-xin; Xu, Cong-jian; Yu, Long

2014-10-02

Cervical lesions caused by integrated human papillomavirus (HPV) infection are highly dangerous because they can quickly develop into invasive cancers. However, clinicians are currently hampered by the lack of a quick, convenient and precise technique to detect integrated/mixed infections of various genotypes of HPVs in the cervix. This study aimed to develop a practical tool to determine the physical status of different HPVs and evaluate its clinical significance. The target population comprised 1162 women with an HPV infection history of > six months and an abnormal cervical cytological finding. The multiple E1-L1/E6E7 ratio analysis, a novel technique, was developed based on determining the ratios of E1/E6E7, E2/E6E7, E4E5/E6E7, L2/E6E7 and L1/E6E7 within the viral genome. Any imbalanced ratios indicate integration. Its diagnostic and predictive performances were compared with those of E2/E6E7 ratio analysis. The detection accuracy of both techniques was evaluated using the gold-standard technique "detection of integrated papillomavirus sequences" (DIPS). To realize a multigenotypic detection goal, a primer and probe library was established. The integration rate of a particular genotype of HPV was correlated with its tumorigenic potential and women with higher lesion grades often carried lower viral loads. The E1-L1/E6E7 ratio analysis achieved 92.7% sensitivity and 99.0% specificity in detecting HPV integration, while the E2/E6E7 ratio analysis showed a much lower sensitivity (75.6%) and a similar specificity (99.3%). Interference due to episomal copies was observed in both techniques, leading to false-negative results. However, some positive results of E1-L1/E6E7 ratio analysis were missed by DIPS due to its stochastic detection nature. The E1-L1/E6E7 ratio analysis is more efficient than E2/E6E7 ratio analysis and DIPS in predicting precancerous/cancerous lesions, in which both positive predictive values (36.7%-82.3%) and negative predictive values (75

Functional identification of MdSIZ1 as a SUMO E3 ligase in apple.

PubMed

Zhang, Rui-Fen; Guo, Ying; Li, Yuan-Yuan; Zhou, Li-Jie; Hao, Yu-Jin; You, Chun-Xiang

2016-07-01

SUMOylation, the conjugation of target proteins with SUMO (small ubiquitin-related modifier), is a type of post-translational modification in eukaryotes and involves the sequential action of activation (E1), conjugation (E2) and ligation (E3) enzymes. In Arabidopsis, the AtSIZ1 protein is a SUMO E3 ligase that promotes the conjugation of SUMO proteins to target substrates. Here, we isolated and identified a SUMO E3 ligase, MdSIZ1, in apple, which was similar to AtSIZ1. SUMOylation analysis showed that MdSIZ1 had SUMO E3 ligase activity in vitro and in vivo. SUMO conjugation was increased by high temperatures, low temperatures, and abscisic acid (ABA). The ectopic expression of MdSIZ1 in Arabidopsis siz1-2 mutant plants partially complemented the morphological mutant phenotype and enhanced the levels of SUMO conjugation. Taken together, these results suggest that MdSIZ1-mediated SUMO conjugation of target proteins is an important process that regulates the adaptation of apple plants to various environmental stresses. Copyright © 2016 Elsevier GmbH. All rights reserved.

miR-195 inhibited abnormal activation of osteoblast differentiation in MC3T3-E1 cells via targeting RAF-1.

PubMed

Chao, Chen; Li, Feng; Tan, Zhiping; Zhang, Weizhi; Yang, Yifeng; Luo, Cheng

2018-01-15

Recent reports have demonstrated that RAF-1 L613V (a mutant of RAF-1) mutant mice show bone deformities similar to Noonan syndrome. It has been suggested that RAF-1 L613V might abnormally activate osteoblast differentiation of MC3T3-E1 cells. To demonstrate that RAF-1 is associated with bone deformity and that RAF-1 L613V dependent bone deformity could be inhibited by microRNA-195 (miR-195), we first investigated the amplifying influence of wild-type RAF-1 (WT) or RAF-1 L613V (L613V) on the viability and differentiation of MC3T3-E1 cells induced by bone morphogenetic protein-2 (BMP-2) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. Subsequently, we investigated the blocking effect and its mechanism of miR-195 for abnormal activation of osteoblast differentiation of MC3T3-E1 cells via targeting RAF-1. RAF-1, especially RAF-1 L613V , abnormally activates osteoblast differentiation of MC3T3-E1 cells induced by BMP-2. Meanwhile, miR-195 could inhibit the cell viability and differentiation of MC3T3-E1 cells. Transfection of miR-195 largely suppressed the L613V-induced viability and osteoblast differentiation of MC3T3-E1 cells and attenuated the accelerative effect of L613V on runt-related transcription factor-2 (Runx2), Osterix (OSX), alkaline phosphatase (ALP), osteocalcin (OCN), and distal-less homeobox 5 (DLX5) osteogenic gene expressions. In addition, miR-195 decreased the expression of RAF-1 mRNA and protein by directly targeting the 3'-untranslated regions (3'-UTR) of RAF-1 mRNA in MC3T3-E1 cells. Our findings indicated that miR-195 inhibited WT and L613V RAF-1 induced hyperactive osteoblast differentiation in MC3T3-E1 cells by targeting RAF-1. miR-195 might be a novel therapeutic agent for the treatment of L613V-induced bone deformity in Noonan syndrome. Copyright © 2017. Published by

Lysophosphatidic acid induces chemotaxis in MC3T3-E1 osteoblastic cells

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

Masiello, Lisa M.; Fotos, Joseph S.; Galileo, Deni S.

2006-07-01

Lysophosphatidic acid (LPA) is a bioactive lipid that has pleiotropic effects on a variety of cell types and enhances the migration of endothelial and cancer cells, but it is not known if this lipid can alter osteoblast motility. We performed transwell migration assays using MC3T3-E1 osteoblastic cells and found LPA to be a potent chemotactic agent. Quantitative time-lapse video analysis of osteoblast migration after wounds were introduced into cell monolayers indicated that LPA stimulated both migration velocity and the average migration distance per cell. LPA also elicited substantial changes in cell shape and actin cytoskeletal structure; lipid-treated cells contained fewermore » stress fibers and displayed long membrane processes that were enriched in F-actin. Quantitative RT-PCR analysis showed that MC3T3-E1 cells express all four known LPA-specific G protein-coupled receptors (LPA1-LPA4) with a relative mRNA abundance of LPA1 > LPA4 > LPA2 >> LPA3. LPA-induced changes in osteoblast motility and morphology were antagonized by both pertussis toxin and Ki16425, a subtype-specific blocker of LPA1 and LPA3 receptor function. Cell migration in many cell types is linked to changes in intracellular Ca2+. Ki16425 also inhibited LPA-induced Ca2+ signaling in a dose-dependent manner, suggesting a link between LPA-induced Ca2+ transients and osteoblast chemotaxis. Our data show that LPA stimulates MC3T3-E1 osteoblast motility via a mechanism that is linked primarily to the G protein-coupled receptor LPA1.« less

Apolipoprotein E3 (ApoE3) but Not ApoE4 Protects against Synaptic Loss through Increased Expression of Protein Kinase Cϵ

PubMed Central

Sen, Abhik; Alkon, Daniel L.; Nelson, Thomas J.

2012-01-01

Synaptic loss is the earliest pathological change in Alzheimer disease (AD) and is the pathological change most directly correlated with the degree of dementia. ApoE4 is the major genetic risk factor for the age-dependent form of AD, which accounts for 95% of cases. Here we show that in synaptic networks formed from primary hippocampal neurons in culture, apoE3, but not apoE4, prevents the loss of synaptic networks produced by amyloid β oligomers (amylospheroids). Specific activators of PKCϵ, such as 8-(2-(2-pentyl-cyclopropylmethyl)-cyclopropyl)-octanoic acid methyl ester and bryostatin 1, protected against synaptic loss by amylospheroids, whereas PKCϵ inhibitors blocked this synaptic protection and also blocked the protection by apoE3. Blocking LRP1, an apoE receptor on the neuronal membrane, also blocked the protection by apoE. ApoE3, but not apoE4, induced the synthesis of PKCϵ mRNA and expression of the PKCϵ protein. Amyloid β specifically blocked the expression of PKCϵ but had no effect on other isoforms. These results suggest that protection against synaptic loss by apoE is mediated by a novel intracellular PKCϵ pathway. This apoE pathway may account for much of the protective effect of apoE and reduced risk for the age-dependent form of AD. This finding supports the potential efficacy of newly developed therapeutics for AD. PMID:22427674

A series of substituted (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-phenylprop-2-en-1-ones.

PubMed

Chopra, Deepak; Mohan, T P; Vishalakshi, B; Row, T N Guru

2007-12-01

In the molecular structures of a series of substituted chalcones, namely (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-phenylprop-2-en-1-one, C21H15FO2, (I), (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-(4-fluorophenyl)prop-2-en-1-one, C21H14F2O2, (II), (2E)-1-(4-chlorophenyl)-3-(2-fluoro-4-phenoxyphenyl)prop-2-en-1-one, C21H14ClFO2, (III), (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-(4-methylphenyl)prop-2-en-1-one, C22H17FO2, (IV), and (2E)-3-(2-fluoro-4-phenoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one, C22H17FO3, (V), the configuration of the keto group with respect to the olefinic double bond is s-cis. The molecules pack utilizing weak C-H...O and C-H...pi intermolecular contacts. Identical packing motifs involving C-H...O interactions, forming both chains and dimers, along with C-H...pi dimers and pi-pi aromatic interactions are observed in the fluoro, chloro and methyl derivatives.

Measurement of the e+e-→KSKLπ0 cross section in the energy range √{s }=1.3 -2.0 GeV

NASA Astrophysics Data System (ADS)

Achasov, M. N.; Aulchenko, V. M.; Barnyakov, A. Yu.; Beloborodov, K. I.; Berdyugin, A. V.; Berkaev, D. E.; Bogdanchikov, A. G.; Botov, A. A.; Dimova, T. V.; Druzhinin, V. P.; Golubev, V. B.; Kardapoltsev, L. V.; Kasaev, A. S.; Kharlamov, A. G.; Kirpotin, A. N.; Koop, I. A.; Korneev, L. A.; Korol, A. A.; Kovrizhin, D. P.; Koshuba, S. V.; Kupich, A. S.; Melnikova, N. A.; Martin, K. A.; Obrazovsky, A. E.; Otboev, A. V.; Pakhtusova, E. V.; Pugachev, K. V.; Rogovsky, Yu. A.; Senchenko, A. I.; Serednyakov, S. I.; Silagadze, Z. K.; Shatunov, Yu. M.; Shtol, D. A.; Shwartz, D. B.; Surin, I. K.; Usov, Yu. V.; Vasiljev, A. V.

2018-02-01

The e+e-→KSKLπ0 cross section is measured in the center-of-mass energy range √{s }=1.3 - 2.0 GeV . The analysis is based on the data sample with an integrated luminosity of 33.5 pb-1 collected with the SND detector at the VEPP-2000 e+e- collider.

Use of lactobacilli and estriol combination in the treatment of disturbed vaginal ecosystem: a review

PubMed Central

Ünlü, Cihat; Donders, Gilbert

2011-01-01

To maintain a healthy vaginal ecosystem or to restore any disturbance, sufficient estrogen levels, an intact mature vaginal epithelium, and physiological lactobacillary microflora are essential. Thus, a combination of beneficial lactobacilli and estrogen is an appealing treatment option. This article reviews the published data on the use of viable Lactobacillus acidophilus KS400 and a low dose of estriol (0.03 mg E3) in the form of vaginal tablets (Gynoflor®). In vitro studies demonstrated that L. acidophilus KS400 produces lactic acid and hydrogen peroxide (H2O2), inhibits the growth of relevant vaginal pathogens, and inhibits adherence of pathogens to epithelial cells. Topical administration of E3 for treatment of vaginal diseases is generally preferred, as this route of application of hormones produces a more significant local proliferative response and has no stimulating effect on the endometrium. Overall, 16 clinical studies have been published with the combination of L. acidophilus KS400 and 0.03 mg E3. The results of these trials have demonstrated that the combination improves the vaginal epithelium and the restoration of the lactobacillary microflora with an excellent safety profile, even during pregnancy. The combination can be used in pre- and postmenopausal women for the restoration of the vaginal flora after anti-infective therapy, for treatment of symptomatic vaginal atrophy, and for abnormal vaginal flora therapy. It can be also considered in repetitive therapy courses for the long-term prevention of recurrences of bacterial vaginosis, even though further clinical studies are needed to substantiate the benefit of this application. PMID:24592002

The Maize Gene terpene synthase 1 Encodes a Sesquiterpene Synthase Catalyzing the Formation of (E)-β-Farnesene, (E)-Nerolidol, and (E,E)-Farnesol after Herbivore Damage1

PubMed Central

Schnee, Christiane; Köllner, Tobias G.; Gershenzon, Jonathan; Degenhardt, Jörg

2002-01-01

Maize (Zea mays) emits a mixture of volatile compounds upon attack by the Egyptian cotton leafworm (Spodoptera littoralis). These substances, primarily mono- and sesquiterpenes, are used by parasitic wasps to locate the lepidopteran larvae, which are their natural hosts. This interaction among plant, lepidopteran larvae, and hymenopteran parasitoids benefits the plant and has been termed indirect defense. The committed step in the biosynthesis of the different skeletal types of mono- and sesquiterpenes is catalyzed by terpene synthases, a class of enzymes that forms a large variety of mono- and sesquiterpene products from prenyl diphosphate precursors. We isolated a terpene synthase gene, terpene synthase 1 (tps1), from maize that exhibits only a low degree of sequence identity to previously identified terpene synthases. Upon expression in a bacterial system, the encoded enzyme produced the acyclic sesquiterpenes, (E)-β-farnesene, (E,E)-farnesol, and (3R)-(E)-nerolidol, the last an intermediate in the formation of (3E)-4,8-dimethyl-1,3,7-nonatriene. Both (E)-β-farnesene and (3E)-4,8-dimethyl-1,3,7-nonatriene are prominent compounds of the maize volatile blend that is emitted after herbivore damage. The biochemical characteristics of the encoded enzyme are similar to those of terpene synthases from both gymnosperms and dicotyledonous angiosperms, suggesting that catalysis involves a similar electrophilic reaction mechanism. The transcript level of tps1 in the maize cv B73 was elevated after herbivory, mechanical damage, and treatment with elicitors. In contrast, the increase in the transcript level of the tps1 gene or gene homolog in the maize cv Delprim after herbivory was less pronounced, suggesting that the regulation of terpene synthase expression may vary among maize varieties. PMID:12481088

Collagen-derived dipeptide prolyl-hydroxyproline promotes differentiation of MC3T3-E1 osteoblastic cells

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

Kimira, Yoshifumi, E-mail: kimira@josai.ac.jp; Ogura, Kana; Taniuchi, Yuri

Highlights: • Pro-Hyp did not affect MC3T3-E1 cell proliferation and matrix mineralization. • Pro-Hyp significantly increased alkaline phosphatase activity. • Pro-Hyp significantly upregulated gene expression of Runx2, Osterix, and Col1α1. - Abstract: Prolyl-hydroxyproline (Pro-Hyp) is one of the major constituents of collagen-derived dipeptides. The objective of this study was to investigate the effects of Pro-Hyp on the proliferation and differentiation of MC3T3-E1 osteoblastic cells. Addition of Pro-Hyp did not affect MC3T3-E1 cell proliferation and matrix mineralization but alkaline phosphatase activity was significantly increased. Furthermore, cells treated with Pro-Hyp significantly upregulated gene expression of Runx2, Osterix, and Col1α1. These results indicatemore » that Pro-Hyp promotes osteoblast differentiation. This study demonstrates for the first time that Pro-Hyp has a positive effect on osteoblast differentiation with upregulation of Runx2, Osterix, and Collα1 gene expression.« less

Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1

DOE PAGES

Sekiyama, Naotaka; Arthanari, Haribabu; Papadopoulos, Evangelos; ...

2015-07-13

The eIF4E-binding protein (4E-BP) is a phosphorylation-dependent regulator of protein synthesis. The nonphosphorylated or minimally phosphorylated form binds translation initiation factor 4E (eIF4E), preventing binding of eIF4G and the recruitment of the small ribosomal subunit. Signaling events stimulate serial phosphorylation of 4E-BP, primarily by mammalian target of rapamycin complex 1 (mTORC1) at residues T 37/T 46, followed by T 70 and S 65. Hyperphosphorylated 4E-BP dissociates from eIF4E, allowing eIF4E to interact with eIF4G and translation initiation to resume. Because overexpression of eIF4E is linked to cellular transformation, 4E-BP is a tumor suppressor, and up-regulation of its activity is amore » goal of interest for cancer therapy. A recently discovered small molecule, eIF4E/eIF4G interaction inhibitor 1 (4EGI-1), disrupts the eIF4E/eIF4G interaction and promotes binding of 4E-BP1 to eIF4E. Structures of 14- to 16-residue 4E-BP fragments bound to eIF4E contain the eIF4E consensus binding motif, 54YXXXXLΦ 60 (motif 1) but lack known phosphorylation sites. We report in this paper a 2.1-Å crystal structure of mouse eIF4E in complex with m 7GTP and with a fragment of human 4E-BP1, extended C-terminally from the consensus-binding motif (4E-BP1 50–84). The extension, which includes a proline-turn-helix segment (motif 2) followed by a loop of irregular structure, reveals the location of two phosphorylation sites (S 65 and T 70). Our major finding is that the C-terminal extension (motif 3) is critical to 4E-BP1–mediated cell cycle arrest and that it partially overlaps with the binding site of 4EGI-1. Finally, the binding of 4E-BP1 and 4EGI-1 to eIF4E is therefore not mutually exclusive, and both ligands contribute to shift the equilibrium toward the inhibition of translation initiation.« less

MEASUREMENTS OF σ(e+e-→ μ±μ∓) IN THE ENERGY RANGE 1.2-3.0 GeV

NASA Astrophysics Data System (ADS)

Alles-Borelli, V.; Bernardini, M.; Bollini, D.; Giusti, P.; Massam, T.; Monari, L.; Palmonari, F.; Valenti, G.; Zichichi, A.

The analysis of 1466 events of the type e+e-→ μ±μ∓ in the time-like range from 1.44 to 9.00 GeV2, shows that the absolute value of the cross-section and its energy dependence follow QED expectations within (± 3.2%) and (± 1.2%), respectively.

Ultrafast transient photocarrier dynamics of the bulk-insulating topological insulator B i1.5S b0.5T e1.7S e1.3

NASA Astrophysics Data System (ADS)

Choi, Young Gwan; Zhung, Chan June; Park, Sun-Hee; Park, Joonbum; Kim, Jun Sung; Kim, Seongheun; Park, Jaehun; Lee, J. S.

2018-02-01

Using optical-pump terahertz-probe spectroscopy, we investigated an ultrafast photocarrier relaxation behavior in a B i1.5S b0.5T e1.7S e1.3 (BSTS) single crystal, which is one of the most bulk-insulating topological insulators. Compared to n -type bulk-metallic B i2S e3 , we found that BSTS endows distinct behaviors in its photocarrier dynamics; the relaxation time turns out to be an order of magnitude longer, and the transient conductance spectrum exhibits a nonlinear increase as a function of the pumping power. Also, we observed an abrupt reduction of the photocarrier scattering rate in several picoseconds after the initial photoexcitation. We discuss these intriguing experimental observations based on a bulk-to-surface carrier injection assisted by the built-in electric field near the surface and electron-phonon scattering.

E3Net: a system for exploring E3-mediated regulatory networks of cellular functions.

PubMed

Han, Youngwoong; Lee, Hodong; Park, Jong C; Yi, Gwan-Su

2012-04-01

Ubiquitin-protein ligase (E3) is a key enzyme targeting specific substrates in diverse cellular processes for ubiquitination and degradation. The existing findings of substrate specificity of E3 are, however, scattered over a number of resources, making it difficult to study them together with an integrative view. Here we present E3Net, a web-based system that provides a comprehensive collection of available E3-substrate specificities and a systematic framework for the analysis of E3-mediated regulatory networks of diverse cellular functions. Currently, E3Net contains 2201 E3s and 4896 substrates in 427 organisms and 1671 E3-substrate specific relations between 493 E3s and 1277 substrates in 42 organisms, extracted mainly from MEDLINE abstracts and UniProt comments with an automatic text mining method and additional manual inspection and partly from high throughput experiment data and public ubiquitination databases. The significant functions and pathways of the extracted E3-specific substrate groups were identified from a functional enrichment analysis with 12 functional category resources for molecular functions, protein families, protein complexes, pathways, cellular processes, cellular localization, and diseases. E3Net includes interactive analysis and navigation tools that make it possible to build an integrative view of E3-substrate networks and their correlated functions with graphical illustrations and summarized descriptions. As a result, E3Net provides a comprehensive resource of E3s, substrates, and their functional implications summarized from the regulatory network structures of E3-specific substrate groups and their correlated functions. This resource will facilitate further in-depth investigation of ubiquitination-dependent regulatory mechanisms. E3Net is freely available online at http://pnet.kaist.ac.kr/e3net.

Ubiquitination independent of E1 and E2 enzymes by bacterial effectors

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

Qiu, Jiazhang; Sheedlo, Michael J.; Yu, Kaiwen

Signaling by ubiquitination regulates virtually every cellular process in eukaryotes. Covalent attachment of ubiquitin to a substrate is catalyzed by the E1, E2 and E3 three-enzyme cascade 1, which links the C terminus of ubiquitin via an isopeptide bond mostly to the ε-amino group of a lysine of the substrate. Given the essential roles of ubiquitination in the regulation of the immune system, it is not surprising that the ubiquitination network is a common target for diverse infectious agents 2. For example, many bacterial pathogens exploit ubiquitin signaling using virulence factors that function as E3 ligases, deubiquitinases 3 or asmore » enzymes that directly attack ubiquitin 4. The bacterial pathogen Legionella pneumophila utilizes approximately 300 effectors that modulate diverse host processes to create a niche permissive for its replication in phagocytes 5. Here we demonstrate that members of the SidE effector family (SidEs) of L. pneumophila ubiquitinate multiple Rab small GTPases associated with the endoplasmic reticulum (ER). Moreover, we show that these proteins are capable of catalyzing ubiquitination without the need for the E1 and E2 enzymes. The E1/E2-independent ubiquitination catalyzed by these enzymes requires NAD but not ATP and Mg2+. A putative mono ADP-ribosyltransferase (mART) motif critical for the ubiquitination activity is also essential for the role of SidEs in intracellular bacterial replication in a protozoan host. These results establish that ubiquitination can be catalyzed by a single enzyme.« less

E&V Guidebook, Version 1.1

DTIC Science & Technology

1989-08-15

checklist 14.1] Chapter 3, Language-related issues, extracts from the Ada language reference manua! [,_D 1982] those features exp!icitly a!owcd to vay...welcome. Please send comments electronically (preferred) to szymansk~aja;po.sei.cmu.edu, or by regular mail to Mr. Raymond Szymanski , AFWAL/AAAF, Wright...of Tool Features for the Ada Programming Support Environment (APSE) 4-3 4.3 E&V Report: DoD APSE Analysis 4-4 4.4 Classification Schema/E&V Taxonomy

Three closely related (2E,2'E)-3,3'-(1,4-phenyl-ene)bis-[1-(meth-oxy-phen-yl)prop-2-en-1-ones]: supra-molecular assemblies in one dimension mediated by hydrogen bonding and C-H⋯π inter-actions.

PubMed

Sim, Aijia; Chidan Kumar, C S; Kwong, Huey Chong; Then, Li Yee; Win, Yip-Foo; Quah, Ching Kheng; Naveen, S; Chandraju, S; Lokanath, N K; Warad, Ismail

2017-06-01

In the title compounds, (2 E ,2' E )-3,3'-(1,4-phenyl-ene)bis-[1-(2-meth-oxy-phen-yl)prop-2-en-1-one], C 26 H 22 O 4 (I), (2 E ,2' E )-3,3'-(1,4-phenyl-ene)bis-[1-(3-meth-oxy-phen-yl)prop-2-en-1-one], C 26 H 22 O 4 (II) and (2 E ,2' E )-3,3'-(1,4-phenyl-ene)bis-[1-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one], C 28 H 26 O 6 (III), the asymmetric unit consists of a half-mol-ecule, completed by crystallographic inversion symmetry. The dihedral angles between the central and terminal benzene rings are 56.98 (8), 7.74 (7) and 7.73 (7)° for (I), (II) and (III), respectively. In the crystal of (I), mol-ecules are linked by pairs of C-H⋯π inter-actions into chains running parallel to [101]. The packing for (II) and (III), features inversion dimers linked by pairs of C-H⋯O hydrogen bonds, forming R 2 2 (16) and R 2 2 (14) ring motifs, respectively, as parts of [201] and [101] chains, respectively.

Efflux transport of estrogen glucuronides by human MRP2, MRP3, MRP4 and BCRP.

PubMed

Järvinen, Erkka; Deng, Feng; Kidron, Heidi; Finel, Moshe

2018-04-01

Estrone, estradiol and estriol are endogenous human estrogens that are rapidly conjugated with glucuronic acid in both intestinal and hepatic epithelial cells. The resulting glucuronides, estrone-3-glucuronide (E 1 -G), estradiol-3- and 17-glucuronides (E 2 -3G and E 2 -17G), as well as estriol-3- and 16-glucuronides (E 3 -3G and E 3 -16G) are found in human plasma and urine. Unlike E 2 -17G, the efflux transport of other estrogen glucuronides by human transporters has not yet been investigated comprehensively. We have studied the transport of E 1 -G, E 2 -3G, E 3 -3G, E 3 -16G and estrone-3-sulfate (E 1 -S), another important estrogen conjugate, using the vesicular transport assay with recombinant human MRP2, MRP3, MRP4, MDR1 and BCRP that were expressed in insect cells. The transport screening assays revealed that whereas E 1 -S was a good and specific substrate for BCRP, the less transporter-specific conjugates, E 1 -G and E 2 -3G, were still transported by BCRP at 10-fold higher rates than E 1 -S. BCRP also transported E 3 -16G at higher rates than the studied MRPs, while it transported E 3 -3G at lower rates than MRP3. MRP2 exhibited lower or equal transport rates of E 1 -G, E 2 -3G, E 3 -3G and E 3 -16G in comparison to MRP3 and BCRP in the screening assays, mainly due to its high K m values, between 180 and 790 μM. MRP3 transported all the tested glucuronides at rather similar rates, at K m values below 20 μM, but lower V max values than other transporters. In the case of E 3 -3G, MRP3 was the most active transporter in the screening assay. MRP4 transported only E 3 -16G at considerable rates, while none of the tested estrogen conjugates was transported by MDR1 at higher rates than control vesicles. These new results, in combination with previously reported in vivo human data, stimulate our understanding on the substrate specificity and role of efflux transporters in disposition of estrogen glucuronides in humans. Copyright © 2017 Elsevier Ltd. All

Highly efficient focus formation by Rous sarcoma virus on adenovirus type 12 E1A-transformed rat 3Y1 cells.

PubMed Central

Shiroki, K; Hamaguchi, M; Kawai, S

1992-01-01

When rat 3Y1 cells were infected with Rous sarcoma virus (RSV) variant SR-RSV-D(H), many 3Y1 cells acquired a stable provirus but only few of them formed transformed foci. In contrast, 12E1AY cells (3Y1 cells expressing the adenovirus type 12 [Ad12] E1A protein) formed transformed foci upon RSV infection with the same high frequency as did chicken embryo fibroblast cells. This enhancement of focus-forming efficiency was specifically observed in 3Y1 cells expressing Ad12 E1A protein but was not observed in 3Y1 cells expressing simian virus 40 T, c-myc, p53, c-fos, or v-fos protein. This enhancement was not evident in 5E1AY cells (3Y1 cells expressing the Ad5 E1A protein). Judging from the experiment using Ad12-Ad5 hybird E1A DNAs, the N-terminal half of the Ad12 E1A protein was responsible for this enhancement. The promoter activity of the RSV long terminal repeat measured by pLTR-CAT did not correlate to the efficiency of focus formation by RSV in these 3Y1 cells. Moreover, RSV containing the neo gene instead of the src gene produced G418-resistant cells equally efficiently among 3Y1, E1AY, and chicken embryo fibroblast cells. These results suggest that the enhancement of focus formation by RSV is not due to the increased expression of the src gene by the E1A protein. src mRNA and src protein were lower in RSV-transformed E1AY (RSVE1AY) cells than in RSV-transformed 3Y1 (RSV3Y1) cells. The phosphotyrosine-containing proteins were also less abundant in RSVE1AY cells than in RSV3Y1 cells, suggesting that E1AY cells require a lower threshold dose of p60v-src for transformation than do 3Y1 cells. E1AY cells were found to be more sensitive to lysis by detergents. The results suggest that the enhancement is due to changes in membrane structures in E1AY cells. Images PMID:1310757

Ghrelin inhibits the apoptosis of MC3T3-E1 cells through ERK and AKT signaling pathway

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

Liang, Qiu-Hua; Liu, Yuan; Wu, Shan-Shan

Ghrelin is a 28-amino-acid peptide that acts as a natural endogenous ligand of the growth hormone secretagogue receptor (GHSR) and strongly stimulates the release of growth hormone from the hypothalamus–pituitary axis. Previous studies have identified the important physiological effects of ghrelin on bone metabolism, such as regulating proliferation and differentiation of osteoblasts, independent of GH/IGF-1 axis. However, research on effects and mechanisms of ghrelin on osteoblast apoptosis is still rare. In this study, we identified expression of GHSR in MC3T3-E1 cells and determined the effects of ghrelin on the apoptosis of osteoblastic MC3T3-E1 cells and the mechanism involved. Our datamore » demonstrated that ghrelin inhibited the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, as determined by terminal deoxynucleotidyl transferase-mediated deoxyribonucleotide triphosphate nick end-labeling (TUNEL) and ELISA assays. Moreover, ghrelin upregulated Bcl-2 expression and downregulated Bax expression in a dose-dependent manner. Our study also showed decreased activated caspase-3 activity under the treatment of ghrelin. Further study suggested that ghrelin stimulated the phosphorylation of ERK and AKT. Pretreatment of cells with the ERK inhibitor PD98059, PI3K inhibitor LY294002, and GHSR-siRNA blocked the ghrelin-induced activation of ERK and AKT, respectively; however, ghrelin did not stimulate the phosphorylation of p38 or JNK. PD90859, LY294002 and GHSR-siRNA attenuated the anti-apoptosis effect of ghrelin in MC3T3-E1 cells. In conclusion, ghrelin inhibits the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, which may be mediated by activating the GHSR/ERK and GHSR/PI3K/AKT signaling pathways. - Highlights: • We explored the effects of ghrelin on serum deprivation-induced MC3T3-E1 cells apoptosis. • Both ELISA and TUNEL were used to detect the apoptosis. • The receptor of ghrelin, GHSR, was expressed in MC3T

Study of the decays D0-->pi{-}e{+}nu{e}, D{0}-->K{-}e{+}nu{e}, D{+}-->pi{0}e{+}nu{e}, and D{+}-->K0e{+}nu{e}.

PubMed

Cronin-Hennessy, D; Gao, K Y; Gong, D T; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Smith, A; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Ernst, J; Severini, H; Dytman, S A; Love, W; Savinov, V; Aquines, O; Li, Z; Lopez, A; Mehrabyan, S; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Coan, T E; Gao, Y S; Liu, F; Artuso, M; Blusk, S; Butt, J; Li, J; Menaa, N; Mountain, R; Nisar, S; Randrianarivony, K; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Asner, D M; Edwards, K W; Briere, R A; Brock, I; Chen, J; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Onyisi, P U E; Patterson, J R; Peterson, D; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Weinberger, M; Athar, S B; Patel, R; Potlia, V; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; White, E J; Wiss, J; Shepherd, M R; Besson, D; Pedlar, T K

2008-06-27

By using 1.8x10{6} DDpairs, we have measured B(D{0}-->pi{-}e{+}nu{e})=0.299(11)(9)%, B(D{+}-->pi{0}e{+}nu{e})=0.373(22)(13)%, B(D{0}-->K{-}e{+}nu{e})=3.56(3)(9)%, and B(D{+}-->K{0}e{+}nu{e})=8.53(13)(23)% and have studied the q;{2} dependence of the form factors. By combining our results with recent lattice calculations, we obtain |V{cd}|=0.217(9)(4)(23) and |V{cs}|=1.015(10)(11)(106).

Titan 3E/Centaur D-1T Systems Summary

NASA Technical Reports Server (NTRS)

1973-01-01

A systems and operational summary of the Titan 3E/Centaur D-1T program is presented which describes vehicle assembly facilities, launch facilities, and management responsibilities, and also provides detailed information on the following separate systems: (1) mechanical systems, including structural components, insulation, propulsion units, reaction control, thrust vector control, hydraulic systems, and pneumatic equipment; (2) astrionics systems, such as instrumentation and telemetry, navigation and guidance, C-Band tracking system, and range safety command system; (3) digital computer unit software; (4) flight control systems; (5) electrical/electronic systems; and (6) ground support equipment, including checkout equipment.

3. N ELEVATION OF BUILDING 1'S E WING, SHOWING THE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. N ELEVATION OF BUILDING 1'S E WING, SHOWING THE PILASTERS, TERRA COTTA PANELS, AND THE EGYPTIAN MOTIF DECORATIVE CORNICE ELEMENTS; LOOKING S. (Ryan) - Veterans Administration Medical Center, Building No. 1, Old State Route 13 West, Marion, Williamson County, IL

Synthesis and antimycobacterial and photosynthesis-inhibiting evaluation of 2-[(E)-2-substituted-ethenyl]-1,3-benzoxazoles.

PubMed

Imramovsky, Ales; Kozic, Jan; Pesko, Matus; Stolarikova, Jirina; Vinsova, Jarmila; Kralova, Katarina; Jampilek, Josef

2014-01-01

A series of twelve 2-[(E)-2-substituted-ethenyl]-1,3-benzoxazoles was designed. All the synthesized compounds were tested against three mycobacterial strains. The compounds were also evaluated for their ability to inhibit photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 2-[(E)-2-(4-Methoxyphenyl)ethenyl]-1,3-benzoxazole, 2-[(E)-2-(2,3-dihydro-1-benzofuran-5-yl)ethenyl]-1,3-benzoxazole and 2-{(E)-2-[4-(methylsulfanyl)phenyl]ethenyl}-1,3-benzoxazole showed the highest activity against M. tuberculosis, M. kansasii, and M. avium, and they demonstrated significantly higher activity against M. avium and M. kansasii than isoniazid. The PET-inhibiting activity of the most active ortho-substituted compound 2-[(E)-2-(2-methoxyphenyl)ethenyl]-1,3-benzoxazole was IC₅₀ = 76.3 μmol/L, while the PET-inhibiting activity of para-substituted compounds was significantly lower. The site of inhibitory action of tested compounds is situated on the donor side of photosystem II. The structure-activity relationships are discussed.

E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor

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

Turner, Roberta L.; Wilkinson, John C., E-mail: john.wilkinson@ndsu.edu; Ornelles, David A., E-mail: ornelles@wakehealth.edu

2014-05-15

Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4ORF3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose)more » polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4ORF3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins. - Highlights: • E1B-55K or E4orf3 prevents nuclear fragmentation. • Nuclear fragmentation requires AIF and PARP-1 activity. • Adenovirus DNA replication activates PARP-1. • E1B-55K or E4orf3 proteins alter the distribution of PAR.« less

Ghosts of Milky Way's past: the globular cluster ESO 37-1 (E 3)

NASA Astrophysics Data System (ADS)

de la Fuente Marcos, R.; de la Fuente Marcos, C.; Moni Bidin, C.; Ortolani, S.; Carraro, G.

2015-09-01

Context. In the Milky Way, most globular clusters are highly conspicuous objects that were found centuries ago. However, a few dozen of them are faint, sparsely populated systems that were identified largely during the second half of the past century. One of the faintest is ESO 37-1 (E 3) and as such it remains poorly studied, with no spectroscopic observations published so far although it was discovered in 1976. Aims: We investigate the globular cluster E 3 in an attempt to better constrain its fundamental parameters. Spectroscopy of stars in the field of E 3 is shown here for the first time. Methods: Deep, precise VI CCD photometry of E 3 down to V ~ 26 mag is presented and analysed. Low-resolution, medium signal-to-noise ratio spectra of nine candidate members are studied to derive radial velocity and metallicity. Proper motions from the UCAC4 catalogue are used to explore the kinematics of the bright members of E 3. Results: Isochrone fitting indicates that E 3 is probably very old, with an age of about 13 Gyr; its distance from the Sun is nearly 10 kpc. It is also somewhat metal rich with [Fe/H] = -0.7. Regarding its kinematics, our tentative estimate for the proper motions is (μα cosδ,μδ) = (-7.0 ± 0.8, 3.5 ± 0.3) mas yr-1 (or a tangential velocity of 382 ± 79 km s-1) and for the radial velocity 45 ± 5 km s-1 in the solar rest frame. Conclusions: E 3 is one of the most intriguing globular clusters in the Galaxy. Having an old age and being metal rich is clearly a peculiar combination, only seen in a handful of objects like the far more conspicuous NGC 104 (47 Tucanae). In addition, its low luminosity and sparse population make it a unique template for the study of the final evolutionary phases in the life of a star cluster. Unfortunately, E 3 is among the most elusive and challenging known globular clusters because field contamination severely hampers spectroscopic studies. This research note is based on observations made with the ESO VLT at the

Experiment E89-044 on the Quasielastic 3He(e,e'p) Reaction at Jefferson Laboratory

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

Penel-Nottaris, Emilie

The Jefferson Lab Hall A E89-044 experiment has measured the 3He(e,e'p) reaction cross-sections. The extraction of the longitudinal and transverse response functions for the two-body break-up 3He(e,e'p)d reaction in parallel kinematics allows the study of the bound proton electromagnetic properties inside the 3He nucleus and the involved nuclear mechanisms beyond plane wave approximations.

New strategies to inhibit KEAP1 and the Cul3-based E3 ubiquitin ligases

PubMed Central

Canning, Peter; Bullock, Alex N.

2014-01-01

E3 ubiquitin ligases that direct substrate proteins to the ubiquitin–proteasome system are promising, though largely unexplored drug targets both because of their function and their remarkable specificity. CRLs [Cullin–RING (really interesting new gene) ligases] are the largest group of E3 ligases and function as modular multisubunit complexes constructed around a Cullin-family scaffold protein. The Cul3-based CRLs uniquely assemble with BTB (broad complex/tramtrack/bric-à-brac) proteins that also homodimerize and perform the role of both the Cullin adapter and the substrate-recognition component of the E3. The most prominent member is the BTB–BACK (BTB and C-terminal Kelch)–Kelch protein KEAP1 (Kelch-like ECH-associated protein 1), a master regulator of the oxidative stress response and a potential drug target for common conditions such as diabetes, Alzheimer's disease and Parkinson's disease. Structural characterization of BTB–Cul3 complexes has revealed a number of critical assembly mechanisms, including the binding of an N-terminal Cullin extension to a bihelical ‘3-box’ at the C-terminus of the BTB domain. Improved understanding of the structure of these complexes should contribute significantly to the effort to develop novel therapeutics targeted to CRL3-regulated pathways. PMID:24450635

Abiotic Transformation Of Estrogens In Synthetic Municipal Wastewater: An Alternative For Treatment?

EPA Science Inventory

The abiotic transformation of estrogens, including estrone (E1), estradiol (E2), estriol (E3) and ethinylestradiol (EE2), in the presence of model vegetable matter was confirmed in this study. Batch experiments were performed to model the catalytic conversion of E1, E2, E3, and ...

Comparison of the Gyro C1E3 and BioMedicus centrifugal pump performances during cardiopulmonary bypass.

PubMed

Nakazawa, T; Takami, Y; Makinouchi, K; Gay, J; Taylor, D; Ueyama, K; Ohashi, Y; Kawahito, K; Tayama, E; Glueck, J; Nosé, Y

1997-07-01

The compact eccentric inlet port (C1E3) centrifugal blood pump was developed as a cardiopulmonary bypass (CPB) pump. The C1E3 pump incorporated a sealless design with a blood stagnation free structure. The pump impeller was magnetically coupled to the driver magnet in a sealless manner. To develop an atraumatic and antithrombogenic centrifugal pump without a shaft seal junction, a double pivot bearing system was introduced. Recently, a mass production model of the C1E3 was fabricated and evaluated. The ratio of the normalized index of hemolysis (NIH) of the C1E3 was 0.007 g/ 100 L, in comparison to the NIH of the BP-80, 0.018 g/ 100 L, each in a CPB condition of 5 L/min against 325 mm Hg. Both pumps were compared in identical in vitro circuits. To further evaluate the pumps during cardiopulmonary bypass for reliability and function, 6 h of CPB was performed on each of 8 bovines using either the C1E3 or BP-80 centrifugal pump. The BP-80 and C1E3 provided pump flows of 50-60 ml/kg/min without incident. The hemodynamics were stable, and the hematology and biochemistry data were within normal ranges. There were no statistically significant differences between the 2 groups. Concerning the plasma free hemoglobin values, a mass production model of the C1E3 pump had the same hemolysis levels as the BP-80. Our preliminary studies reveal that the C1E3 pump is reliable. Also, the C1E3 will satisfy clinical requirements as a cardiopulmonary bypass pump.

A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes

NASA Astrophysics Data System (ADS)

Lu, Xiaolong; Malley, Konstantin R.; Brenner, Caitlin C.; Koroleva, Olga; Korolev, Sergey; Downes, Brian P.

2016-08-01

Ubiquitin (Ub) is a protein modifier that controls processes ranging from protein degradation to endocytosis, but early-acting regulators of the three-enzyme ubiquitylation cascade are unknown. Here we report that the prenylated membrane-anchored ubiquitin-fold protein (MUB) is an early-acting regulator of subfamily-specific E2 activation. An AtMUB3:AtUBC8 co-crystal structure defines how MUBs inhibit E2~Ub formation using a combination of E2 backside binding and a MUB-unique lap-bar loop to block E1 access. Since MUBs tether Arabidopsis group VI E2 enzymes (related to HsUbe2D and ScUbc4/5) to the plasma membrane, and inhibit E2 activation at physiological concentrations, they should function as potent plasma membrane localized regulators of Ub chain synthesis in eukaryotes. Our findings define a biochemical function for MUB, a family of highly conserved Ub-fold proteins, and provide an example of selective activation between cognate Ub E2s, previously thought to be constitutively activated by E1s.

The E2F3—Oncomir 1 axis is activated in Wilms Tumor

PubMed Central

Kort, Eric J.; Farber, Leslie; Tretiakova, Maria; Petillo, David; Furge, Kyle A.; Yang, Ximing J.; Cornelius, Albert; Teh, Bin T.

2008-01-01

Oncomir-1 is an oncogenic cluster of microRNAs located on chromosome 13. Previous in vitro studies demonstrated that it is transcriptionally regulated by the transcription factor E2F3. In this report we combine expression profiling of both messenger RNA (mRNA) and micro RNAs (miRNA) in Wilms tumor (WT) samples to provide the first evidence that the E2F3—Oncomir 1 axis, previously identified in cell culture, is deregulated in primary human tumors. Analysis of RNA expression signatures demonstrated that an E2F3 gene signature was activated in all Wilms tumor samples analyzed, in contrast to other kidney tumors. This finding was validated by immunohistochemistry (IHC) on the protein level. Expression of E2F3 was lowest in early stage tumors, and highest in metastatic tissue. Expression profiling of miRNAs in WT showed that expression of each measured member of the Oncomir-1 family was highest in WT relative to other kidney tumor subtypes. Quantitative polymerase chain reaction (PCR) confirmed that these microRNAs were overexpressed in Wilms tumor relative to normal kidney tissue. These results suggest that the E2F3—Oncomir-1 axis is activated in Wilms tumor. Our study also demonstrates the utility of integrated genomics combining gene signature analysis with miRNA expression profiling to identify protein-miRNA interactions that are perturbed in disease states. PMID:18519660

Study of the Decays D0→π-e+νe, D0→K-e+νe, D+→π0e+νe, and D+→ Kmacr 0e+νe

NASA Astrophysics Data System (ADS)

Cronin-Hennessy, D.; Gao, K. Y.; Gong, D. T.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Smith, A.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Ernst, J.; Severini, H.; Dytman, S. A.; Love, W.; Savinov, V.; Aquines, O.; Li, Z.; Lopez, A.; Mehrabyan, S.; Mendez, H.; Ramirez, J.; Huang, G. S.; Miller, D. H.; Pavlunin, V.; Sanghi, B.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Coan, T. E.; Gao, Y. S.; Liu, F.; Artuso, M.; Blusk, S.; Butt, J.; Li, J.; Menaa, N.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Redjimi, R.; Sia, R.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Zhang, K.; Csorna, S. E.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Asner, D. M.; Edwards, K. W.; Briere, R. A.; Brock, I.; Chen, J.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Adam, N. E.; Alexander, J. P.; Berkelman, K.; Cassel, D. G.; Duboscq, J. E.; Ecklund, K. M.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Pivarski, J.; Riley, D.; Ryd, A.; Sadoff, A. J.; Schwarthoff, H.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Weinberger, M.; Athar, S. B.; Patel, R.; Potlia, V.; Yelton, J.; Rubin, P.; Cawlfield, C.; Eisenstein, B. I.; Karliner, I.; Kim, D.; Lowrey, N.; Naik, P.; Sedlack, C.; Selen, M.; White, E. J.; Wiss, J.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.

2008-06-01

By using 1.8×106 D Dmacr pairs, we have measured B(D0→π-e+νe)=0.299(11)(9)%, B(D+→π0e+νe)=0.373(22)(13)%, B(D0→K-e+νe)=3.56(3)(9)%, and B(D+→ Kmacr 0e+νe)=8.53(13)(23)% and have studied the q2 dependence of the form factors. By combining our results with recent lattice calculations, we obtain |Vcd|=0.217(9)(4)(23) and |Vcs|=1.015(10)(11)(106).

Protective effect of Edaravone against hypoxia-induced cytotoxicity in osteoblasts MC3T3-E1 cells.

PubMed

Cao, Bo; Chai, Chunxiang; Zhao, Sishun

2015-12-01

Edaravone is a newly developed clinical medicine for the treatment of acute cerebral infarction. Reduced blood supply to bones (hypoxia) has been involved in the pathological development of osteoporosis. In this study, we investigated the effect of Edaravone and its latent mechanism on hypoxia-induced cell toxicity in MC3T3-E1 cells. Cell viability was determined by the 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Intracellular reactive oxygen species (ROS) and nitric oxide (NO) were determined by the fluorescence dyes 2',7'-dichlorofluorescein diacetate (DCFH-DA) and 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA), respectively. mRNA and proteins were determined by real-time polymerase chain reaction and Western blot analysis, respectively. Edaravone significantly restored the hypoxia-induced reduction of MC3T3-E1 cell viability and inhibited lactate dehydrogenase release. In addition, we found that Edaravone inhibits the generation of ROS and NO. Hoechst staining results indicated that the nuclear condensation characteristic of apoptosis was increased in MC3T3-E1 cells after hypoxia exposure, which was significantly suppressed by Edaravone treatment. Mechanistically, we found that Edaravone markedly reduced the expression of cleaved caspase-3 and blunted the release of cytochrome c. These findings strongly suggested that Edaravone suppresses hypoxia-induced cytotoxicity in MC3T3-E1 cells. The pleiotropic effects of Edaravone on hypoxia exposure in osteoblasts suggest potential antiosteoporosis mechanisms of Edaravone. © 2015 International Union of Biochemistry and Molecular Biology.

Arginine methyltransferase inhibitor 1 inhibits gastric cancer by downregulating eIF4E and targeting PRMT5.

PubMed

Zhang, Baolai; Zhang, Su; Zhu, Lijuan; Chen, Xue; Zhao, Yunfeng; Chao, Li; Zhou, Juanping; Wang, Xing; Zhang, Xinyang; Ma, Nengqian

2017-12-01

Arginine methylation is carried out by protein arginine methyltransferase (PRMTs) family. Arginine methyltransferase inhibitor 1 (AMI-1) is mainly used to inhibit type I PRMT activity in vitro. However, the effects of AMI-1 on type II PRMT5 activity and gastric cancer (GC) remain unclear. In this study, we provided the first evidence that AMI-1 significantly inhibited GC cell proliferation and migration while induced GC cell apoptosis, and reduced the expression of PRMT5, eukaryotic translation initiation factor 4E (eIF4E), symmetric dimethylation of histone 3 (H3R8me2s) and histone 4 (H4R3me2s). In addition, AMI-1 inhibited tumor growth, downregulated eIF4E, H4R3me2s and H3R8me2s expression in mice xenografts model of GC. Collectively, our results suggest that AMI-1 inhibits GC by downregulating eIF4E and targeting type II PRMT5. Copyright © 2017 Elsevier Inc. All rights reserved.

Crystal structures of 3,5-bis-[(E)-3-hy-droxy-benzyl-idene]-1-methyl-piperidin-4-one and 3,5-bis-[(E)-2-chloro-benzyl-idene]-1-methyl-piperidin-4-one.

PubMed

Eryanti, Yum; Zamri, Adel; Herlina, Tati; Supratman, Unang; Rosli, Mohd Mustaqim; Fun, Hoong-Kun

2015-12-01

The title compounds, C20H19NO3, (1), and C20H17Cl2NO, (2), are the 3-hy-droxy-benzyl-idene and 2-chloro-benzyl-idene derivatives, respectively, of curcumin [systematic name: (1E,6E)-1,7-bis-(4-hy-droxy-3-meth-oxy-phen-yl)-1,6-hepta-diene-3,5-dione]. The dihedral angles between the benzene rings in each compound are 21.07 (6)° for (1) and 13.4 (3)° for (2). In both compounds, the piperidinone rings adopt a sofa confirmation and the methyl group attached to the N atom is in an equatorial position. In the crystal of (1), two pairs of O-H⋯N and O-H⋯O hydrogen bonds link the mol-ecules, forming chains along [10-1]. The chains are linked via C-H⋯O hydrogen bonds, forming undulating sheets parallel to the ac plane. In the crystal of (2), mol-ecules are linked by weak C-H⋯Cl hydrogen bonds, forming chains along the [204] direction. The chains are linked along the a-axis direction by π-π inter-actions [inter-centroid distance = 3.779 (4) Å]. For compound (2), the crystal studied was a non-merohedral twin with the refined ratio of the twin components being 0.116 (6):0.886 (6).

Decreased eIF3e/Int6 expression causes epithelial-to-mesenchymal transition in breast epithelial cells.

PubMed

Gillis, L D; Lewis, S M

2013-08-01

eIF3e/Int6 is a component of the multi-subunit eIF3 complex, which binds directly to the 40S ribosome to facilitate ribosome recruitment to mRNA and hence protein synthesis. Reduced expression of eIF3e/Int6 has been found in up to 37% of human breast cancers, and expression of a truncated mutant version of the mouse eIF3e/Int6 protein leads to malignant transformation of normal mammary cells. These findings suggest that eIF3e/Int6 is a tumor suppressor; however, a recent study has reported that a reduction of eIF3e/Int6 expression in breast cancer cells leads to reduced translation of oncogenes, suggesting that eIF3e/Int6 may in fact have an oncogenic role in breast cancer. To gain a better understanding of the role of eIF3e/Int6 in breast cancer, we have examined the effects of decreased eIF3e/Int6 expression in an immortalized breast epithelial cell line, MCF-10A. Surprisingly, we find that decreased expression of eIF3e/Int6 causes breast epithelial cells to undergo epithelial-to-mesenchymal transition (EMT). We show that EMT induced by a decrease in eIF3e/Int6 expression imparts invasive and migratory properties to breast epithelial cells, suggesting that regulation of EMT by eIF3e/Int6 may have an important role in breast cancer metastasis. Furthermore, we show that reduced eIF3e/Int6 expression in breast epithelial cells causes a specific increase in the expression of the key EMT regulators Snail1 and Zeb2, which occurs at both the transcriptional and post-transcriptional levels. Together, our data indicate a novel role of eIF3e/Int6 in the regulation of EMT in breast epithelial cells and support a tumor suppressor role of eIF3e/Int6.

Active sites prediction and binding analysis E1-E2 protein human papillomavirus with biphenylsulfonacetic acid

NASA Astrophysics Data System (ADS)

Iryani, I.; Amelia, F.; Iswendi, I.

2018-04-01

Cervix cancer triggered by Human papillomavirus infection is the second cause to woman death in worldwide. The binding site of E1-E2 protein of HPV 16 is not known from a 3-D structure yet, so in this study we address this issue to study the structure of E1-E2 protein from Human papillomavirus type 16 and to find its potential binding sites using biphenylsulfonacetic acid as inhibitor. Swiss model was used for 3D structure prediction and PDB: 2V9P (E1 protein) and 2NNU (E2 protein) having 52.32% and 100% identity respectively was selected as a template. The 3D model structure developed of E1 and E2 in the core and allowed regions were 99.2% and 99.5%. The ligand binding sites were predicted using online server meta pocket 2.0 and MOE 2009.10 was used for docking. E1-and E2 protein of HPV-16 has three potential binding site that can interact with the inhibitors. The Docking biphenylsulfonacetic acid using these binding sites shows that ligand interact with the protein through hydrogen bonds on Lys 403, Arg 410, His 551 in the first pocket, on Tyr 32, Leu 99 in the second pocket, and Lys 558m Lys 517 in the third pocket.

Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

PubMed

Genazzani, Alessandro D; Podfigurna-Stopa, Agnieszka; Czyzyk, Adam; Katulski, Krzysztof; Prati, Alessia; Despini, Giulia; Angioni, Stefano; Simoncini, Tommaso; Meczekalski, Blazej

2016-01-01

To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 μg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

40 CFR 721.4575 - L-aspartic acid, N,N′- [(1E) - 1,2 - ethenediylbis[(3-sulfo-4, 1-phenylene)imino [6-(phenylamino...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-aspartic acid, N,Nâ²- [(1E) - 1,2... Substances § 721.4575 L-aspartic acid, N,N′- [(1E) - 1,2 - ethenediylbis[(3-sulfo-4, 1-phenylene)imino [6... uses subject to reporting. (1) The chemical substance identified as l-aspartic acid, N,N′- [(1E) - 1,2...

Polarization transfer in the {sup 4}He(e(pol), e'p(pol)) {sup 3}He reaction at Q{sup 2} = 0.8 and 1.3 GeV/c){sup 2}.

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

Paolone, M.; Malace, S. P.; Strauch, S.

2010-08-12

Proton recoil polarization was measured in the quasielastic 4He(e(pol),e{prime}p(pol)){sup 3}H reaction at Q{sup 2}=0.8 and 1.3(GeV/c){sup 2} with unprecedented precision. The polarization-transfer coefficients are found to differ from those of the {sup 1}H(e(pol),e{prime}p(pol)) reaction, contradicting a relativistic distorted-wave approximation and favoring either the inclusion of medium-modified proton form factors predicted by the quark-meson coupling model or a spin-dependent charge-exchange final-state interaction. For the first time, the polarization-transfer ratio is studied as a function of the virtuality of the proton.

76 FR 78149 - Oral Dosage Form New Animal Drugs; Estriol

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Estriol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

Identifying the substrate proteins of U-box E3s E4B and CHIP by orthogonal ubiquitin transfer.

PubMed

Bhuripanyo, Karan; Wang, Yiyang; Liu, Xianpeng; Zhou, Li; Liu, Ruochuan; Duong, Duc; Zhao, Bo; Bi, Yingtao; Zhou, Han; Chen, Geng; Seyfried, Nicholas T; Chazin, Walter J; Kiyokawa, Hiroaki; Yin, Jun

2018-01-01

E3 ubiquitin (UB) ligases E4B and carboxyl terminus of Hsc70-interacting protein (CHIP) use a common U-box motif to transfer UB from E1 and E2 enzymes to their substrate proteins and regulate diverse cellular processes. To profile their ubiquitination targets in the cell, we used phage display to engineer E2-E4B and E2-CHIP pairs that were free of cross-reactivity with the native UB transfer cascades. We then used the engineered E2-E3 pairs to construct "orthogonal UB transfer (OUT)" cascades so that a mutant UB (xUB) could be exclusively used by the engineered E4B or CHIP to label their substrate proteins. Purification of xUB-conjugated proteins followed by proteomics analysis enabled the identification of hundreds of potential substrates of E4B and CHIP in human embryonic kidney 293 cells. Kinase MAPK3 (mitogen-activated protein kinase 3), methyltransferase PRMT1 (protein arginine N -methyltransferase 1), and phosphatase PPP3CA (protein phosphatase 3 catalytic subunit alpha) were identified as the shared substrates of the two E3s. Phosphatase PGAM5 (phosphoglycerate mutase 5) and deubiquitinase OTUB1 (ovarian tumor domain containing ubiquitin aldehyde binding protein 1) were confirmed as E4B substrates, and β-catenin and CDK4 (cyclin-dependent kinase 4) were confirmed as CHIP substrates. On the basis of the CHIP-CDK4 circuit identified by OUT, we revealed that CHIP signals CDK4 degradation in response to endoplasmic reticulum stress.

Identifying the substrate proteins of U-box E3s E4B and CHIP by orthogonal ubiquitin transfer

PubMed Central

Bhuripanyo, Karan; Wang, Yiyang; Liu, Xianpeng; Zhou, Li; Liu, Ruochuan; Duong, Duc; Zhao, Bo; Bi, Yingtao; Zhou, Han; Chen, Geng; Seyfried, Nicholas T.; Chazin, Walter J.; Kiyokawa, Hiroaki; Yin, Jun

2018-01-01

E3 ubiquitin (UB) ligases E4B and carboxyl terminus of Hsc70-interacting protein (CHIP) use a common U-box motif to transfer UB from E1 and E2 enzymes to their substrate proteins and regulate diverse cellular processes. To profile their ubiquitination targets in the cell, we used phage display to engineer E2-E4B and E2-CHIP pairs that were free of cross-reactivity with the native UB transfer cascades. We then used the engineered E2-E3 pairs to construct “orthogonal UB transfer (OUT)” cascades so that a mutant UB (xUB) could be exclusively used by the engineered E4B or CHIP to label their substrate proteins. Purification of xUB-conjugated proteins followed by proteomics analysis enabled the identification of hundreds of potential substrates of E4B and CHIP in human embryonic kidney 293 cells. Kinase MAPK3 (mitogen-activated protein kinase 3), methyltransferase PRMT1 (protein arginine N-methyltransferase 1), and phosphatase PPP3CA (protein phosphatase 3 catalytic subunit alpha) were identified as the shared substrates of the two E3s. Phosphatase PGAM5 (phosphoglycerate mutase 5) and deubiquitinase OTUB1 (ovarian tumor domain containing ubiquitin aldehyde binding protein 1) were confirmed as E4B substrates, and β-catenin and CDK4 (cyclin-dependent kinase 4) were confirmed as CHIP substrates. On the basis of the CHIP-CDK4 circuit identified by OUT, we revealed that CHIP signals CDK4 degradation in response to endoplasmic reticulum stress. PMID:29326975

Management of an eLearning Evaluation Project: The e3Learning Model

ERIC Educational Resources Information Center

Lam, Paul; McNaught, Carmel

2007-01-01

This article describes the evaluation of purpose-built course websites for university-level teaching and learning developed by a funded project (e3Learning, e3L) in Hong Kong, which was designed to support teachers in three universities to supplement classroom teaching with eLearning. Previous articles on the e3L project have described the…

E-3A EMP Evaluation Program.

DTIC Science & Technology

1980-01-01

34OGRAh~g"NT. PROJECT, TASI( AREA & YRIC UIT NUMBERS EG&G, Inc. 9733 Coors Road NW 67I/7Z~i Albuqueroue,_NM_87114 _____________ 11. CONTROLLING OFFICE...Report) III. SUPPLEMENTARY NOTES III. KCy WORDS (Centingnpo r. everse wooe Ii noeew ayE ~Eeatly by’ b1euk nuabr) E- 3A Airborne Warning and Control ... CONTROL PROCEDURE ANALYSIS . 73 1 L -.... TABLE OF CONTENTS (Continued) Page SECTION V TEST ACTIVITIES .... .............. . 81 1. PRE-PULSE

Smad Ubiquitylation Regulatory Factor 1/2 (Smurf1/2) Promotes p53 Degradation by Stabilizing the E3 Ligase MDM2*

PubMed Central

Nie, Jing; Xie, Ping; Liu, Lin; Xing, Guichun; Chang, Zhijie; Yin, Yuxin; Tian, Chunyan; He, Fuchu; Zhang, Lingqiang

2010-01-01

The tumor suppressor p53 protein is tightly regulated by a ubiquitin-proteasomal degradation mechanism. Several E3 ubiquitin ligases, including MDM2 (mouse double minute 2), have been reported to play an essential role in the regulation of p53 stability. However, it remains unclear how the activity of these E3 ligases is regulated. Here, we show that the HECT-type E3 ligase Smurf1/2 (Smad ubiquitylation regulatory factor 1/2) promotes p53 degradation by enhancing the activity of the E3 ligase MDM2. We provide evidence that the role of Smurf1/2 on the p53 stability is not dependent on the E3 activity of Smurf1/2 but rather is dependent on the activity of MDM2. We find that Smurf1/2 stabilizes MDM2 by enhancing the heterodimerization of MDM2 with MDMX, during which Smurf1/2 interacts with MDM2 and MDMX. We finally provide evidence that Smurf1/2 regulates apoptosis through p53. To our knowledge, this is the first report to demonstrate that Smurf1/2 functions as a factor to stabilize MDM2 protein rather than as a direct E3 ligase in regulation of p53 degradation. PMID:20484049

Human Placental Lactogen Induces CYP2E1 Expression via PI 3-Kinase Pathway in Female Human Hepatocytes

PubMed Central

Lee, Jin Kyung; Chung, Hye Jin; Fischer, Liam; Fischer, James; Gonzalez, Frank J.

2014-01-01

The state of pregnancy is known to alter hepatic drug metabolism. Hormones that rise during pregnancy are potentially responsible for the changes. Here we report the effects of prolactin (PRL), placental lactogen (PL), and growth hormone variant (GH-v) on expression of major hepatic cytochromes P450 expression and a potential molecular mechanism underlying CYP2E1 induction by PL. In female human hepatocytes, PRL and GH-v showed either no effect or small and variable effects on mRNA expression of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4, and 3A5. On the other hand, PL increased expression level of CYP2E1 mRNA with corresponding increases in CYP2E1 protein and activity levels. Results from hepatocytes and HepaRG cells indicate that PL does not affect the expression or activity of HNF1α, the known transcriptional activator of basal CYP2E1 expression. Furthermore, transient transfection studies and Western blot results showed that STAT signaling, the previously known mediator of PL actions in certain tissues, does not play a role in CYP2E1 induction by PL. A chemical inhibitor of PI3-kinase signaling significantly repressed the CYP2E1 induction by PL in human hepatocytes, suggesting involvement of PI3-kinase pathway in CYP2E1 regulation by PL. CYP2E1-humanized mice did not exhibit enhanced CYP2E1 expression during pregnancy, potentially because of interspecies differences in PL physiology. Taken together, these results indicate that PL induces CYP2E1 expression via PI3-kinase pathway in human hepatocytes. PMID:24408518

The plant homeodomain fingers of fission yeast Msc1 exhibit E3 ubiquitin ligase activity.

PubMed

Dul, Barbara E; Walworth, Nancy C

2007-06-22

The DNA damage checkpoint pathway governs how cells regulate cell cycle progression in response to DNA damage. A screen for suppressors of a fission yeast chk1 mutant defective in the checkpoint pathway identified a novel Schizosaccharomyces pombe protein, Msc1. Msc1 contains 3 plant homeodomain (PHD) finger motifs, characteristically defined by a C4HC3 consensus similar to RING finger domains. PHD finger domains in viral proteins and in the cellular protein kinase MEKK1 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1) have been implicated as ubiquitin E3 protein ligases that affect protein stability. The close structural relationship of PHD fingers to RING fingers suggests that other PHD domain-containing proteins might share this activity. We show that each of the three PHD fingers of Msc1 can act as ubiquitin E3 ligases, reporting for the first time that PHD fingers from a nuclear protein exhibit E3 ubiquitin ligase activity. The function of the PHD fingers of Msc1 is needed to rescue the DNA damage sensitivity of a chk1Delta strain. Msc1 co-precipitates Rhp6, the S. pombe homologue of the human ubiquitin-conjugating enzyme Ubc2. Strikingly, deletion of msc1 confers complete suppression of the slow growth phenotype, UV and hydroxyurea sensitivities of an rhp6 deletion strain and restores deficient histone H3 methylation observed in the rhp6Delta mutant. We speculate that the target of the E3 ubiquitin ligase activity of Msc1 is likely to be a chromatin-associated protein.

Observation of ψ(3686)→e^{+}e^{-}χ_{cJ} and χ_{cJ}→e^{+}e^{-}J/ψ.

PubMed

Ablikim, M; Achasov, M N; Ai, X C; Albayrak, O; Albrecht, M; Ambrose, D J; Amoroso, A; An, F F; An, Q; Bai, J Z; Baldini Ferroli, R; Ban, Y; Bennett, D W; Bennett, J V; Bertani, M; Bettoni, D; Bian, J M; Bianchi, F; Boger, E; Boyko, I; Briere, R A; Cai, H; Cai, X; Cakir, O; Calcaterra, A; Cao, G F; Cetin, S A; Chang, J F; Chelkov, G; Chen, G; Chen, H S; Chen, H Y; Chen, J C; Chen, M L; Chen, S; Chen, S J; Chen, X; Chen, X R; Chen, Y B; Cheng, H P; Chu, X K; Cibinetto, G; Dai, H L; Dai, J P; Dbeyssi, A; Dedovich, D; Deng, Z Y; Denig, A; Denysenko, I; Destefanis, M; De Mori, F; Ding, Y; Dong, C; Dong, J; Dong, L Y; Dong, M Y; Dou, Z L; Du, S X; Duan, P F; Fan, J Z; Fang, J; Fang, S S; Fang, X; Fang, Y; Farinelli, R; Fava, L; Fedorov, O; Feldbauer, F; Felici, G; Feng, C Q; Fioravanti, E; Fritsch, M; Fu, C D; Gao, Q; Gao, X L; Gao, X Y; Gao, Y; Gao, Z; Garzia, I; Goetzen, K; Gong, L; Gong, W X; Gradl, W; Greco, M; Gu, M H; Gu, Y T; Guan, Y H; Guo, A Q; Guo, L B; Guo, R P; Guo, Y; Guo, Y P; Haddadi, Z; Hafner, A; Han, S; Hao, X Q; Harris, F A; He, K L; Held, T; Heng, Y K; Hou, Z L; Hu, C; Hu, H M; Hu, J F; Hu, T; Hu, Y; Huang, G S; Huang, J S; Huang, X T; Huang, X Z; Huang, Y; Huang, Z L; Hussain, T; Ji, Q; Ji, Q P; Ji, X B; Ji, X L; Jiang, L W; Jiang, X S; Jiang, X Y; Jiao, J B; Jiao, Z; Jin, D P; Jin, S; Johansson, T; Julin, A; Kalantar-Nayestanaki, N; Kang, X L; Kang, X S; Kavatsyuk, M; Ke, B C; Kiese, P; Kliemt, R; Kloss, B; Kolcu, O B; Kopf, B; Kornicer, M; Kupsc, A; Kühn, W; Lange, J S; Lara, M; Larin, P; Leng, C; Li, C; Li, Cheng; Li, D M; Li, F; Li, F Y; Li, G; Li, H B; Li, H J; Li, J C; Li, Jin; Li, K; Li, K; Li, Lei; Li, P R; Li, Q Y; Li, T; Li, W D; Li, W G; Li, X L; Li, X N; Li, X Q; Li, Y B; Li, Z B; Liang, H; Liang, Y F; Liang, Y T; Liao, G R; Lin, D X; Liu, B; Liu, B J; Liu, C X; Liu, D; Liu, F H; Liu, Fang; Liu, Feng; Liu, H B; Liu, H H; Liu, H H; Liu, H M; Liu, J; Liu, J B; Liu, J P; Liu, J Y; Liu, K; Liu, K Y; Liu, L D; Liu, P L; Liu, Q; Liu, S B; Liu, X; Liu, Y B; Liu, Z A; Liu, Zhiqing; Loehner, H; Lou, X C; Lu, H J; Lu, J G; Lu, Y; Lu, Y P; Luo, C L; Luo, M X; Luo, T; Luo, X L; Lyu, X R; Ma, F C; Ma, H L; Ma, L L; Ma, M M; Ma, Q M; Ma, T; Ma, X N; Ma, X Y; Ma, Y M; Maas, F E; Maggiora, M; Mao, Y J; Mao, Z P; Marcello, S; Messchendorp, J G; Min, J; Mitchell, R E; Mo, X H; Mo, Y J; Morales Morales, C; Muchnoi, N Yu; Muramatsu, H; Nefedov, Y; Nerling, F; Nikolaev, I B; Ning, Z; Nisar, S; Niu, S L; Niu, X Y; Olsen, S L; Ouyang, Q; Pacetti, S; Pan, Y; Patteri, P; Pelizaeus, M; Peng, H P; Peters, K; Pettersson, J; Ping, J L; Ping, R G; Poling, R; Prasad, V; Qi, H R; Qi, M; Qian, S; Qiao, C F; Qin, L Q; Qin, N; Qin, X S; Qin, Z H; Qiu, J F; Rashid, K H; Redmer, C F; Ripka, M; Rong, G; Rosner, Ch; Ruan, X D; Sarantsev, A; Savrié, M; Schoenning, K; Schumann, S; Shan, W; Shao, M; Shen, C P; Shen, P X; Shen, X Y; Sheng, H Y; Shi, M; Song, W M; Song, X Y; Sosio, S; Spataro, S; Sun, G X; Sun, J F; Sun, S S; Sun, X H; Sun, Y J; Sun, Y Z; Sun, Z J; Sun, Z T; Tang, C J; Tang, X; Tapan, I; Thorndike, E H; Tiemens, M; Ullrich, M; Uman, I; Varner, G S; Wang, B; Wang, B L; Wang, D; Wang, D Y; Wang, K; Wang, L L; Wang, L S; Wang, M; Wang, P; Wang, P L; Wang, S G; Wang, W; Wang, W P; Wang, X F; Wang, Y; Wang, Y D; Wang, Y F; Wang, Y Q; Wang, Z; Wang, Z G; Wang, Z H; Wang, Z Y; Wang, Z Y; Weber, T; Wei, D H; Wei, J B; Weidenkaff, P; Wen, S P; Wiedner, U; Wolke, M; Wu, L H; Wu, L J; Wu, Z; Xia, L; Xia, L G; Xia, Y; Xiao, D; Xiao, H; Xiao, Z J; Xie, Y G; Xiu, Q L; Xu, G F; Xu, J J; Xu, L; Xu, Q J; Xu, Q N; Xu, X P; Yan, L; Yan, W B; Yan, W C; Yan, Y H; Yang, H J; Yang, H X; Yang, L; Yang, Y X; Ye, M; Ye, M H; Yin, J H; Yu, B X; Yu, C X; Yu, J S; Yuan, C Z; Yuan, W L; Yuan, Y; Yuncu, A; Zafar, A A; Zallo, A; Zeng, Y; Zeng, Z; Zhang, B X; Zhang, B Y; Zhang, C; Zhang, C C; Zhang, D H; Zhang, H H; Zhang, H Y; Zhang, J; Zhang, J J; Zhang, J L; Zhang, J Q; Zhang, J W; Zhang, J Y; Zhang, J Z; Zhang, K; Zhang, L; Zhang, S Q; Zhang, X Y; Zhang, Y; Zhang, Y H; Zhang, Y N; Zhang, Y T; Zhang, Yu; Zhang, Z H; Zhang, Z P; Zhang, Z Y; Zhao, G; Zhao, J W; Zhao, J Y; Zhao, J Z; Zhao, Lei; Zhao, Ling; Zhao, M G; Zhao, Q; Zhao, Q W; Zhao, S J; Zhao, T C; Zhao, Y B; Zhao, Z G; Zhemchugov, A; Zheng, B; Zheng, J P; Zheng, W J; Zheng, Y H; Zhong, B; Zhou, L; Zhou, X; Zhou, X K; Zhou, X R; Zhou, X Y; Zhu, K; Zhu, K J; Zhu, S; Zhu, S H; Zhu, X L; Zhu, Y C; Zhu, Y S; Zhu, Z A; Zhuang, J; Zotti, L; Zou, B S; Zou, J H

2017-06-02

Using 4.479×10^{8}  ψ(3686) events collected with the BESIII detector, we search for the decays ψ(3686)→e^{+}e^{-}χ_{cJ} and χ_{cJ}→e^{+}e^{-}J/ψ, where J=0, 1, 2. The decays ψ(3686)→e^{+}e^{-}χ_{cJ} and χ_{cJ}→e^{+}e^{-}J/ψ are observed for the first time. The measured branching fractions are B(ψ(3686)→e^{+}e^{-}χ_{cJ})=(11.7±2.5±1.0)×10^{-4}, (8.6±0.3±0.6)×10^{-4}, (6.9±0.5±0.6)×10^{-4} for J=0, 1, 2, and B(χ_{cJ}→e^{+}e^{-}J/ψ)=(1.51±0.30±0.13)×10^{-4}, (3.73±0.09±0.25)×10^{-3}, (2.48±0.08±0.16)×10^{-3} for J=0, 1, 2, respectively. The ratios of the branching fractions B(ψ(3686)→e^{+}e^{-}χ_{cJ})/B(ψ(3686)→γχ_{cJ}) and B(χ_{cJ}→e^{+}e^{-}J/ψ)/B(χ_{cJ}→γJ/ψ) are also reported. Also, the α values of helicity angular distributions of the e^{+}e^{-} pair are determined for ψ(3686)→e^{+}e^{-}χ_{c1,2} and χ_{c1,2}→e^{+}e^{-}J/ψ.

1,3-Butadiene-Induced Mitochondrial Dysfunction is Correlated with Mitochondrial CYP2E1 Activity in Collaborative Cross Mice

PubMed Central

Hartman, Jessica H.; Miller, Grover P.; Caro, Andres A.; Byrum, Stephanie D.; Orr, Lisa M.; Mackintosh, Samuel G.; Tackett, Alan J.; MacMillan-Crow, Lee Ann; Hallberg, Lance M.; Ameredes, Bill T.; Boysen, Gunnar

2017-01-01

Cytochrome P450 2E1 (CYP2E1) metabolizes low molecular weight hydrophobic compounds, including 1,3-butadiene, which is converted by CYP2E1 to electrophilic epoxide metabolites that covalently modify cellular proteins and DNA. Previous CYP2E1 studies have mainly focused on the enzyme localized in the endoplasmic reticulum (erCYP2E1); however, active CYP2E1 also localizes in mitochondria (mtCYP2E1) and the distribution of CYP2E1 between organelles can influence an individual's response to exposure. Relatively few studies have focused on the contribution of mtCYP2E1 to activation of chemical toxicants. We hypothesized that CYP2E1 bioactivation of butadiene within mitochondria adversely affects mitochondrial respiratory complexes I-IV. A population of Collaborative Cross mice were exposed to air (control) or 200 ppm butadiene. Subcellular fractions (mitochondria, DNA, and microsomes) were collected from frozen livers and CYP2E1 activity was measured in microsomes and mitochondria. Individual activities of mitochondrial respiratory complexes I-IV were measured using in vitro assays with purified mitochondrial fractions. In air- and butadiene-exposed mouse samples, mtDNA copy numbers were assessed by RT-PCR, and mtDNA integrity was assessed through a PCR-based assay. No significant change in mtDNA copy number or integrity were observed; however, there was a decrease in overall activity of mitochondrial respiratory complexes I, II, and IV after butadiene exposure. Additionally, higher mtCYP2E1 (but not erCYP2E1) activity was correlated with decreased mitochondrial respiratory complex activity (in complexes I-IV) in the butadiene-exposed (not control) animals. Together, these results represent the first in vivo link between mitochondrial CYP2E1 activity and mitochondrial toxicity. PMID:28082109

Depth Acuity Methodology for Electronic 3D Displays: eJames (eJ)

DTIC Science & Technology

2016-07-01

AFRL-RH-WP-TR-2016-0060 Depth Acuity Methodology for Electronic 3D Displays: eJames (eJ) Eric L. Heft, John McIntire...AND SUBTITLE Depth Acuity Methodology for Electronic 3D Displays: eJames (eJ) 5a. CONTRACT NUMBER FA8650-08-D-6801-0050 5b. GRANT NUMBER...of 3D electronic displays: one active-eyewear Stereo 3D (S3D) and two non-eyewear full parallax Field-of-Light Display (FoLD) systems. The two FoLD

THE E1 PROTEINS

PubMed Central

Bergvall, Monika; Melendy, Thomas; Archambault, Jacques

2013-01-01

E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of E1 at the origin and how the enzyme unwinds DNA using a spiral escalator mechanism. E1 is tightly regulated in vivo, in particular by post-translational modifications that restrict its accumulation in the nucleus. Here we review how different functional domains of E1 orchestrate viral DNA replication, with an emphasis on their interactions with substrate DNA, host DNA replication factors and modifying enzymes. These studies have made E1 one of the best characterized helicases and provided unique insights on how PVs usurp different host-cell machineries to replicate and amplify their genome in a tightly controlled manner. PMID:24029589

Genetically engineered mouse models for functional studies of SKP1-CUL1-F-box-protein (SCF) E3 ubiquitin ligases.

PubMed

Zhou, Weihua; Wei, Wenyi; Sun, Yi

2013-05-01

The SCF (SKP1 (S-phase-kinase-associated protein 1), Cullin-1, F-box protein) E3 ubiquitin ligases, the founding member of Cullin-RING ligases (CRLs), are the largest family of E3 ubiquitin ligases in mammals. Each individual SCF E3 ligase consists of one adaptor protein SKP1, one scaffold protein cullin-1 (the first family member of the eight cullins), one F-box protein out of 69 family members, and one out of two RING (Really Interesting New Gene) family proteins RBX1/ROC1 or RBX2/ROC2/SAG/RNF7. Various combinations of these four components construct a large number of SCF E3s that promote the degradation of many key regulatory proteins in cell-context, temporally, and spatially dependent manners, thus controlling precisely numerous important cellular processes, including cell cycle progression, apoptosis, gene transcription, signal transduction, DNA replication, maintenance of genome integrity, and tumorigenesis. To understand how the SCF E3 ligases regulate these cellular processes and embryonic development under in vivo physiological conditions, a number of mouse models with transgenic (Tg) expression or targeted deletion of components of SCF have been established and characterized. In this review, we will provide a brief introduction to the ubiquitin-proteasome system (UPS) and the SCF E3 ubiquitin ligases, followed by a comprehensive overview on the existing Tg and knockout (KO) mouse models of the SCF E3s, and discuss the role of each component in mouse embryogenesis, cell proliferation, apoptosis, carcinogenesis, as well as other pathogenic processes associated with human diseases. We will end with a brief discussion on the future directions of this research area and the potential applications of the knowledge gained to more effective therapeutic interventions of human diseases.

Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms.

PubMed

Dove, Katja K; Stieglitz, Benjamin; Duncan, Emily D; Rittinger, Katrin; Klevit, Rachel E

2016-08-01

RING-in-between-RING (RBR) ubiquitin (Ub) ligases are a distinct class of E3s, defined by a RING1 domain that binds E2 Ub-conjugating enzyme and a RING2 domain that contains an active site cysteine similar to HECT-type E3s. Proposed to function as RING/HECT hybrids, details regarding the Ub transfer mechanism used by RBRs have yet to be defined. When paired with RING-type E3s, E2s perform the final step of Ub ligation to a substrate. In contrast, when paired with RBR E3s, E2s must transfer Ub onto the E3 to generate a E3~Ub intermediate. We show that RBRs utilize two strategies to ensure transfer of Ub from the E2 onto the E3 active site. First, RING1 domains of HHARI and RNF144 promote open E2~Ubs. Second, we identify a Ub-binding site on HHARI RING2 important for its recruitment to RING1-bound E2~Ub. Mutations that ablate Ub binding to HHARI RING2 also decrease RBR ligase activity, consistent with RING2 recruitment being a critical step for the RBR Ub transfer mechanism. Finally, we demonstrate that the mechanism defined here is utilized by a variety of RBRs. © 2016 The Authors.

Functional expression of 5-HT{sub 2A} receptor in osteoblastic MC3T3-E1 cells

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

Hirai, Takao; Kaneshige, Kota; Kurosaki, Teruko

2010-05-28

In the previous study, we reported the gene expression for proteins related to the function of 5-hydroxytryptamine (5-HT, serotonin) and elucidated the expression patterns of 5-HT{sub 2} receptor subtypes in mouse osteoblasts. In the present study, we evaluated the possible involvement of 5-HT receptor subtypes and its inactivation system in MC3T3-E1 cells, an osteoblast cell line. DOI, a 5-HT{sub 2A} and 5-HT{sub 2C} receptor selective agonist, as well as 5-HT concentration-dependently increased proliferative activities of MC3T3-E1 cells in their premature period. This effect of 5-HT on cell proliferation were inhibited by ketanserin, a 5-HT{sub 2A} receptor specific antagonist. Moreover, bothmore » DOI-induced cell proliferation and phosphorylation of ERK1 and 2 proteins were inhibited by PD98059 and U0126, selective inhibitors of MEK in a concentration-dependent manner. Furthermore, treatment with fluoxetine, a 5-HT specific re-uptake inhibitor which inactivate the function of extracellular 5-HT, significantly increased the proliferative activities of MC3T3-E1 cells in a concentration-dependent manner. Our data indicate that 5-HT fill the role for proliferation of osteoblast cells in their premature period. Notably, 5-HT{sub 2A} receptor may be functionally expressed to regulate mechanisms underlying osteoblast cell proliferation, at least in part, through activation of ERK/MAPK pathways in MC3T3-E1 cells.« less

Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation

PubMed Central

Lechtenberg, Bernhard C.; Rajput, Akhil; Sanishvili, Ruslan; Dobaczewska, Małgorzata K.; Ware, Carl F.; Mace, Peter D.; Riedl, Stefan J.

2015-01-01

Ubiquitination is a central process affecting all facets of cellular signaling and function1. A critical step in ubiquitination is the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to a substrate or a growing ubiquitin chain, which is mediated by E3 ubiquitin ligases. RING-type E3 ligases typically facilitate the transfer of ubiquitin from the E2 directly to the substrate2,3. The RBR family of RING-type E3 ligases, however, breaks this paradigm by forming a covalent intermediate with ubiquitin similarly to HECT-type E3 ligases4–6. The RBR family includes Parkin4 and HOIP, the central catalytic factor of the linear ubiquitin chain assembly complex (LUBAC)7. While structural insights into the RBR E3 ligases Parkin and HHARI in their overall autoinhibited forms are available8–13, no structures exist of intact fully active RBR E3 ligases or any of their complexes. Thus, the RBR mechanism of action has remained largely enigmatic. Here we present the first structure of the fully active HOIP-RBR in its transfer complex with an E2~ubiquitin conjugate, which elucidates the intricate nature of RBR E3 ligases. The active HOIP-RBR adopts a conformation markedly different from that of autoinhibited RBRs. HOIP-RBR binds the E2~ubiquitin conjugate in an elongated fashion, with the E2 and E3 catalytic centers ideally aligned for ubiquitin transfer, which structurally both requires and enables a HECT-like mechanism. In addition, surprisingly, three distinct helix–IBR-fold motifs inherent to RBRs form ubiquitin-binding regions that engage the activated ubiquitin of the E2~Ub conjugate as well as an additional regulatory ubiquitin molecule. The features uncovered reveal critical states of the HOIP-RBR E3 ligase cycle, and comparison with Parkin and HHARI suggests a general mechanism for RBR E3 ligases. PMID:26789245

20 CFR 655.700 - What statutory provisions govern the employment of H-1B, H-1B1, and E-3 nonimmigrants and how do...

Code of Federal Regulations, 2012 CFR

2012-04-01

... employment of H-1B, H-1B1, and E-3 nonimmigrants and how do employers apply for H-1B, H-1B1, and E-3 visas... Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in...

20 CFR 655.700 - What statutory provisions govern the employment of H-1B, H-1B1, and E-3 nonimmigrants and how do...

Code of Federal Regulations, 2013 CFR

2013-04-01

... employment of H-1B, H-1B1, and E-3 nonimmigrants and how do employers apply for H-1B, H-1B1, and E-3 visas... Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in...

20 CFR 655.700 - What statutory provisions govern the employment of H-1B, H-1B1, and E-3 nonimmigrants and how do...

Code of Federal Regulations, 2014 CFR

2014-04-01

... employment of H-1B, H-1B1, and E-3 nonimmigrants and how do employers apply for H-1B, H-1B1, and E-3 visas... Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in...

20 CFR 655.700 - What statutory provisions govern the employment of H-1B, H-1B1, and E-3 nonimmigrants and how do...

Code of Federal Regulations, 2011 CFR

2011-04-01

... employment of H-1B, H-1B1, and E-3 nonimmigrants and how do employers apply for H-1B, H-1B1, and E-3 visas... Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in...

20 CFR 655.700 - What statutory provisions govern the employment of H-1B, H-1B1, and E-3 nonimmigrants and how do...

Code of Federal Regulations, 2010 CFR

2010-04-01

... employment of H-1B, H-1B1, and E-3 nonimmigrants and how do employers apply for H-1B, H-1B1, and E-3 visas... Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in...

Genetic polymorphism analysis of cytochrome P4502E1 (CYP2E1) in a Chinese Tibetan population

PubMed Central

Wang, Li; Ren, Guoxia; Li, Jingjie; Zhu, Linhao; Niu, Fanglin; Yan, Mengdan; Li, Jing; Yuan, Dongya; Jin, Tianbo

2017-01-01

Abstract Cytochrome P4502E1 (CYP2E1) gene genetic polymorphisms vary markedly in frequency among different ethnic and racial groups. We studied the genotype distributions and allele frequencies of 3 CYP2E1 polymorphisms: CYP2E1∗1A, CYP2E1∗7A, and CYP2E1∗7C by polymerase chain reaction technique in a sample of 100 healthy subjects representing Tibetan population. The frequencies of CYP2E1∗1A, ∗7A, and ∗7C alleles were 0.705, 0.125, and 0.170, respectively. Compared with other populations, we found that the allele frequencies of the variants −352A>G (rs2070672) and −333A>T (rs2070673) in this Tibetan population have significant differences compared with European-American, African-American, Japanese, Korean, and other different geographic areas in Chinese Han population. Furthermore, the results of protein prediction revealed that the variant 6397G>A (rs61710826) could influence the protein structure and function. These findings in this study would be valuable for pharmacogenetics for drug therapy and drug discovery. However, further studies in larger samples are warranted to confirm our results. PMID:29381998

Study of the semileptonic charm decays D0→π-e+νe, D+→π0e+νe, D0→K-e+νe, and D+→ Kmacr 0e+νe

NASA Astrophysics Data System (ADS)

Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Ernst, J.; Severini, H.; Dytman, S. A.; Love, W.; Savinov, V.; Aquines, O.; Li, Z.; Lopez, A.; Mehrabyan, S.; Mendez, H.; Ramirez, J.; Huang, G. S.; Miller, D. H.; Pavlunin, V.; Sanghi, B.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Coan, T. E.; Gao, Y. S.; Liu, F.; Artuso, M.; Blusk, S.; Butt, J.; Li, J.; Menaa, N.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Redjimi, R.; Sia, R.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Zhang, K.; Csorna, S. E.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Asner, D. M.; Edwards, K. W.; Briere, R. A.; Brock, I.; Chen, J.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Adam, N. E.; Alexander, J. P.; Berkelman, K.; Cassel, D. G.; Duboscq, J. E.; Ecklund, K. M.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Pivarski, J.; Riley, D.; Ryd, A.; Sadoff, A. J.; Schwarthoff, H.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Weinberger, M.; Athar, S. B.; Patel, R.; Potlia, V.; Yelton, J.; Rubin, P.; Cawlfield, C.; Eisenstein, B. I.; Karliner, I.; Kim, D.; Lowrey, N.; Naik, P.; Sedlack, C.; Selen, M.; White, E. J.; Wiss, J.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Gong, D. T.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Smith, A.; Zweber, P.

2008-06-01

Using a sample of 1.8 million D Dmacr mesons collected at the ψ(3770) with the CLEO-c detector, we study the semileptonic decays D0→π-e+νe, D+→π0e+νe, D0→K-e+νe, and D+→ Kmacr 0e+νe. For the total branching fractions we find B(D0→π-e+νe)=0.299(11)(9)%, B(D+→π0e+νe)=0.373(22)(13)%, B(D0→K-e+νe)=3.56(3)(9)%, and B(D+→ Kmacr 0e+νe)=8.53(13)(23)%, where the first error is statistical and the second systematic. In addition, form factors are studied through fits to the partial branching fractions obtained in five q2 ranges. By combining our results with recent unquenched lattice calculations, we obtain |Vcd|=0.217(9)(4)(23) and |Vcs|=1.015(10)(11)(106), where the final error is theoretical.

Specific IgE for Fag e 3 Predicts Oral Buckwheat Food Challenge Test Results and Anaphylaxis: A Pilot Study.

PubMed

Yanagida, Noriyuki; Sato, Sakura; Maruyama, Nobuyuki; Takahashi, Kyohei; Nagakura, Ken-Ichi; Ogura, Kiyotake; Asaumi, Tomoyuki; Ebisawa, Motohiro

2018-01-01

Buckwheat (BW) is the source of a life-threatening allergen. Fag e 3-specific serum IgE (sIgE) is more useful than BW-sIgE for diagnosis; however, it is unknown whether Fag e 3-sIgE can predict oral food challenge (OFC) results and anaphylaxis. This study aimed to clarify the efficacy of Fag e 3-sIgE in predicting OFC results and anaphylaxis. We conducted a retrospective review of BW- and Fag e 3-sIgE data obtained using the ImmunoCAP® assay system and fluorescent enzyme-linked immunosorbent assay from children who underwent OFC using 3,072 mg of BW protein between July 2006 and March 2014 at Sagamihara National Hospital, Kanagawa, Japan. We analyzed 60 patients aged 1.9-13.4 years (median 6.0 years); 20 (33%) showed objective symptoms upon BW OFC. The patients without symptoms had significantly lower Fag e 3-sIgE than those with non-anaphylactic (p < 0.001) and anaphylactic reactions to BW (p = 0.004). Fag e 3-sIgE was the only tested factor that significantly predicted positive OFC results (odds ratio 8.93, 95% confidence interval 3.10-25.73, p < 0.001) and OFC-induced anaphylaxis (2.67, 1.12-6.35, p = 0.027). We suggest that a threshold Fag e 3-sIgE level of 18.0 kUE/L has 95% probability of provoking a positive reaction to BW. Fag e 3-sIgE predicted OFC results and OFC-induced anaphylaxis. We further emphasize paying careful attention to the risk of BW OFC-induced anaphylaxis. © 2018 The Author(s) Published by S. Karger AG, Basel.

The association of GSK3 beta with E2F1 facilitates nerve growth factor-induced neural cell differentiation.

PubMed

Zhou, Fangfang; Zhang, Long; Wang, Aijun; Song, Bo; Gong, Kai; Zhang, Lihai; Hu, Min; Zhang, Xiufang; Zhao, Nanming; Gong, Yandao

2008-05-23

It is widely acknowledged that E2F1 and GSK3beta are both involved in the process of cell differentiation. However, the relationship between E2F1 and GSK3beta in cell differentiation has yet to be discovered. Here, we provide evidence that in the differentiation of PC12 cells induced by nerve growth factor (NGF), GSK3beta was increased at both the mRNA and protein levels, whereas E2F1 at these two levels was decreased. Both wild-type GSK3beta and its kinase-defective mutant GSK3beta KM can inhibit E2F1 by promoting its ubiquitination through physical interaction. In addition, the colocalization of GSK3beta and E2F1 and their subcellular distribution, regulated by NGF, were observed in the process of PC12 differentiation. At the tissue level, GSK3beta colocalized and interacted with E2F1 in mouse hippocampus. Furthermore, GSK3beta facilitated neurite outgrowth by rescuing the promoter activities of Cdk inhibitors p21 and p15 from the inhibition caused by E2F1. To summarize, our findings suggest that GSK3beta can promote the ubiquitination of E2F1 via physical interaction and thus inhibit its transcription activity in a kinase activity independent manner, which plays an important role in the NGF-induced PC12 differentiation.

E4orf1 Limits the Oncolytic Potential of the E1B-55K Deletion Mutant Adenovirus▿

PubMed Central

Thomas, Michael A.; Broughton, Robin S.; Goodrum, Felicia D.; Ornelles, David A.

2009-01-01

Clinical trials have shown oncolytic adenoviruses to be tumor selective with minimal toxicity toward normal tissue. The virus ONYX-015, in which the gene encoding the early region 1B 55-kDa (E1B-55K) protein is deleted, has been most effective when used in combination with either chemotherapy or radiation therapy. Therefore, improving the oncolytic nature of tumor-selective adenoviruses remains an important objective for improving this form of cancer therapy. Cells infected during the G1 phase of the cell cycle with the E1B-55K deletion mutant virus exhibit a reduced rate of viral late protein synthesis, produce fewer viral progeny, and are less efficiently killed than cells infected during the S phase. Here we demonstrate that the G1 restriction imposed on the E1B-55K deletion mutant virus is due to the viral oncogene encoded by open reading frame 1 of early region 4 (E4orf1). E4orf1 has been reported to signal through the phosphatidylinositol 3′-kinase pathway leading to the activation of Akt, mTOR, and p70 S6K. Evidence presented here shows that E4orf1 may also induce the phosphorylation of Akt and p70 S6K in a manner that depends on Rac1 and its guanine nucleotide exchange factor Tiam1. Accordingly, agents that have been reported to disrupt the Tiam1-Rac1 interaction or to prevent phosphorylation of the ribosomal S6 kinase partially alleviated the E4orf1 restriction to late viral protein synthesis and enhanced tumor cell killing by the E1B-55K mutant virus. These results demonstrate that E4orf1 limits the oncolytic nature of a conditionally replicating adenovirus such as ONYX-015. The therapeutic value of similar oncolytic adenoviruses may be improved by abrogating E4orf1 function. PMID:19129452

E4orf1 limits the oncolytic potential of the E1B-55K deletion mutant adenovirus.

PubMed

Thomas, Michael A; Broughton, Robin S; Goodrum, Felicia D; Ornelles, David A

2009-03-01

Clinical trials have shown oncolytic adenoviruses to be tumor selective with minimal toxicity toward normal tissue. The virus ONYX-015, in which the gene encoding the early region 1B 55-kDa (E1B-55K) protein is deleted, has been most effective when used in combination with either chemotherapy or radiation therapy. Therefore, improving the oncolytic nature of tumor-selective adenoviruses remains an important objective for improving this form of cancer therapy. Cells infected during the G(1) phase of the cell cycle with the E1B-55K deletion mutant virus exhibit a reduced rate of viral late protein synthesis, produce fewer viral progeny, and are less efficiently killed than cells infected during the S phase. Here we demonstrate that the G(1) restriction imposed on the E1B-55K deletion mutant virus is due to the viral oncogene encoded by open reading frame 1 of early region 4 (E4orf1). E4orf1 has been reported to signal through the phosphatidylinositol 3'-kinase pathway leading to the activation of Akt, mTOR, and p70 S6K. Evidence presented here shows that E4orf1 may also induce the phosphorylation of Akt and p70 S6K in a manner that depends on Rac1 and its guanine nucleotide exchange factor Tiam1. Accordingly, agents that have been reported to disrupt the Tiam1-Rac1 interaction or to prevent phosphorylation of the ribosomal S6 kinase partially alleviated the E4orf1 restriction to late viral protein synthesis and enhanced tumor cell killing by the E1B-55K mutant virus. These results demonstrate that E4orf1 limits the oncolytic nature of a conditionally replicating adenovirus such as ONYX-015. The therapeutic value of similar oncolytic adenoviruses may be improved by abrogating E4orf1 function.

A novel chimeric peptide binds MC3T3‑E1 cells to titanium and enhances their proliferation and differentiation.

PubMed

Wang, Dan; Liao, Xiaofu; Qin, Xu; Shi, Wei; Zhou, Bin

2013-05-01

Previous studies have demonstrated that the modification of the titanium (Ti) surface of an implant with RGD (Arg‑Gly‑Asp) promotes the activity of osteoblasts. A novel Ti‑binding peptide, minTBP‑1, and a chimeric peptide, minTBP‑1‑PRGDN, have been synthesized to assist the fixing of RGD to Ti. In our previous study, minTBP‑1‑PRGDN demonstrated favorable affinity for Ti surfaces and facilitated the adhesion of MC3T3‑E1 cells. The aim of the present study was to evaluate the effect of this chimeric peptide on the proliferation and differentiation of MC3T3‑E1 cells. For this purpose, MC3T3‑E1 cells were cultured and differentiation was induced on Ti discs precoated with minTBP‑1‑PRGDN, minTBP‑1 or PRGDN. The MC3T3‑E1 cells on the minTBP‑1‑PRGDN‑precoated Ti disc were observed to exhibit the highest cell number after 24 h and alkaline phosphatase levels in all groups increased in a time‑dependent manner. In addition, marked expression of osteogenic marker genes [osteopontin (OPN) and osteocalcin (OC)] was detected on minTBP‑1‑PRGDN/Ti at day 14. Mineralized deposits on minTBP‑1‑PRGDN/Ti presented the maximal average area and the highest number of deposits was observed on PRGDN/Ti. The present study indicates that minTBP‑1‑PRGDN may enhance and accelerate the activities of MC3T3‑E1 cells on Ti, however, its role in vivo must be determined by further studies.

Accessing heavy allyl-analogous [(TerN)2E](-) (E = Sb, Bi) ions and their reactivity towards ECl3.

PubMed

Hinz, Alexander; Schulz, Axel; Villinger, Alexander

2015-07-21

The attempted preparation of the biradicaloid [E(μ-NTer)]2 (E = Sb, Bi) yielded salts of the anion [(TerN)2E](-). These heteroatom allyl analogues could be further utilized in the reaction with pnictogen(III) chlorides to form the first 1,3-dichloro-1-bisma-3-stiba-2,4-diazane [ClSb(μ-NTer)2BiCl].

Susceptibility of northern corn rootworm Diabrotica barberi (Coleoptera: Chrysomelidae) to mCry3A and eCry3.1Ab Bacillus thuringiensis proteins.

PubMed

Oyediran, Isaac O; Matthews, Phillip; Palekar, Narendra; French, Wade; Conville, Jared; Burd, Tony

2016-12-01

The susceptibility of the northern corn rootworm Diabrotica barberi (Smith & Lawrence) to mCry3A and eCry3.1Ab proteins derived from Bacillus thuringiensis (Bt) was determined using a diet bioassay. Northern corn rootworm neonates were exposed to different concentrations of mCry3A and eCry3.1Ab, incorporated into artificial diet. Larval mortality was evaluated after 7 d. The mCry3A and eCry3.1Ab proteins were found to be toxic to the northern corn rootworm larvae. The LC 50 and LC 99 values for mCry3A were 5.13 and 2482.31 μg/mL, respectively. For eCry3.1Ab, the LC 50 and LC 99 values were 0.49 and 213.01 μg/mL. Based on the estimated lethal concentrations, eCry3.1Ab protein was more efficacious to northern corn rootworm larvae than mCry3A. These lethal concentration values will be used as diagnostic doses for routine annual monitoring for change in susceptibility of field collected northern corn rootworm to mCry3A, and eCry3.1Ab toxins. © 2015 Institute of Zoology, Chinese Academy of Sciences.

E3 ubiquitin ligase SP1 regulates peroxisome biogenesis in Arabidopsis

DOE PAGES

Pan, Ronghui; Satkovich, John; Hu, Jianping

2016-10-31

Peroxisomes are ubiquitous eukaryotic organelles that play pivotal roles in a suite of metabolic processes and often act coordinately with other organelles, such as chloroplasts and mitochondria. Peroxisomes import proteins to the peroxisome matrix by peroxins (PEX proteins), but how the function of the PEX proteins is regulated is poorly understood. In this study, we identified the Arabidopsis RING (really interesting new gene) type E3 ubiquitin ligase SP1 [suppressor of plastid protein import locus 1 (ppi1) 1] as a peroxisome membrane protein with a regulatory role in peroxisome protein import. SP1 interacts physically with the two components of the peroxisomemore » protein docking complex PEX13–PEX14 and the (RING)-finger peroxin PEX2. Loss of SP1 function suppresses defects of the pex14-2 and pex13-1 mutants, and SP1 is involved in the degradation of PEX13 and possibly PEX14 and all three RING peroxins. An in vivo ubiquitination assay showed that SP1 has the ability to promote PEX13 ubiquitination. Our study has revealed that, in addition to its previously reported function in chloroplast biogenesis, SP1 plays a role in peroxisome biogenesis. The same E3 ubiquitin ligase promotes the destabilization of components of two distinct protein-import machineries, indicating that degradation of organelle biogenesis factors by the ubiquitin–proteasome system may constitute an important regulatory mechanism in coordinating the biogenesis of metabolically linked organelles in eukaryotes.« less

26 CFR 1.503(e)-1 - Special rules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... adequate security and a reasonable rate of interest) the acquisition of a bond, debenture, note, or...) Section 503(e) does not affect the requirement in section 503(b)(1) of a reasonable rate of interest. Thus... indebtedness does not bear a reasonable rate of interest. (3) The provisions of section 503(e) do not limit the...

Crystal structures of three 1-[4-(4-bromo-but-oxy)-phen-yl] chalcone derivatives: (E)-1-[4-(4-bromo-but-oxy)-phen-yl]-3-phenyl-prop-2-en-1-one, (E)-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(4-meth-oxy-phen-yl)prop-2-en-1-one and (E)-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one.

PubMed

Maragatham, Gunasekaran; Selvarani, Sivasamy; Rajakumar, Perumal; Lakshmi, Srinivasakannan

2017-07-01

The crystal structures of three chalcones with a bromo-substituted but-oxy side chain, viz . ( E )-1-[4-(4-bromo-but-oxy)-phen-yl]-3-phenyl-prop-2-en-1-one, C 19 H 19 BrO 2 , (I), ( E )-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(4-meth-oxy-phen-yl)prop-2-en-1-one, C 20 H 21 BrO 3 , (II), and ( E )-1-[4-(4-bromo-but-oxy)-phen-yl]-3-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one, C 21 H 23 BrO 4 , (III), are reported. In all mol-ecules, the conformation of the keto group with respect to the olefinic bond is s - cis . Mol-ecules of (I) and (II) are nearly planar, while mol-ecule (III) is not planar. In the crystal of compounds (I) and (II), mol-ecules are linked into chains parallel to the c axis by C-H⋯π inter-actions. In the crystal of compound (III), mol-ecules are linked by a pairs of C-H⋯O hydrogen bonds, forming inversion dimers. Weak C-Br⋯π inter-actions are also observed in (III).

Crystal structures of (2E)-1-(3-bromo-thio-phen-2-yl)-3-(2-meth-oxy-phen-yl)prop-2-en-1-one and (2E)-1-(3-bromo-thio-phen-2-yl)-3-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one.

PubMed

Naik, Vasant S; Shettigar, Venkataraya; Berglin, Tyler S; Coburn, Jillian S; Jasinski, Jerry P; Yathirajan, Hemmige S

2015-08-01

In the mol-ecules of the title compounds, (2E)-1-(3-bromo-thio-phen-2-yl)-3-(2-meth-oxy-phen-yl)prop-2-en-1-one, C14H11BrO2S, (I), which crystallizes in the space group P-1 with four independent mol-ecules in the asymmetric unit (Z' = 8), and (2E)-1-(3-bromo-thio-phen-2-yl)-3-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one, C15H13BrO3S, (II), which crystallizes with Z' = 8 in the space group I2/a, the non-H atoms are nearly coplanar. The mol-ecules of (I) pack with inversion symmetry stacked diagonally along the a-axis direction. Weak C-H⋯Br intra-molecular inter-actions in each of the four mol-ecules in the asymmetric unit are observed. In (II), weak C-H⋯O, bifurcated three-center inter-molecular inter-actions forming dimers along with weak C-H⋯π and π-π stacking inter-actions are observed, linking the mol-ecules into sheets along [001]. A weak C-H⋯Br intra-molecular inter-action is also present. There are no classical hydrogen bonds present in either structure.

Resolvin E1 (Rv E1 ) attenuates LPS induced inflammation and subsequent atrophy in C2C12 myotubes.

PubMed

Baker, Luke A; Martin, Neil R W; Kimber, Marc C; Pritchard, Gareth J; Lindley, Martin R; Lewis, Mark P

2018-03-25

Resolution of inflammation is now known to be an active process which in part is instigated and controlled by specialized pro-resolving lipid mediators (SPM's) derived from dietary omega-3 fatty acids. Resolvin E1 (R v E 1 ) is one of these SPM's derived from the omega-3 fatty acid eicosapentaenoic acid. Using both molecular and phenotypic functional measures we report that in a model of Lipopolysaccharide (LPS) induced inflammation, R v E 1 attenuated mRNA levels of both interlukin-6 and monocyte chemoattractant protein-1 whilst having no effect on tumor necrosis factor-α or interlukin-1β in C2C12 skeletal muscle myotubes. Findings at the molecular level were transferred into similar changes in extracellular protein levels of the corresponding genes with the greatest attenuation being noted in IL-6 protein concentrations. R v E 1 instigated beneficial morphological changes through the prevention of LPS induced skeletal muscle atrophy, in tandem with attenuation of the LPS induced reduction in contractile force in tissue engineered skeletal muscle. These findings demonstrate, in our model of endotoxin induced inflammation in skeletal muscle, that R v E 1 has pro-resolving properties in this cell type. Our data provides rationale for further investigation into the mechanistic action of R v E 1 in skeletal muscle, with the vision of having potential benefits for the prevention/resolution of in-vivo skeletal muscle atrophy. © 2018 Wiley Periodicals, Inc.

Correlations for the Viscosity of 2,3,3,3-Tetrafluoroprop-1-ene (R1234yf) and trans-1,3,3,3-Tetrafluoropropene (R1234ze(E))†

PubMed Central

Huber, Marcia L.; Assael, Marc J.

2016-01-01

Due to concerns about global warming, there is interest in 2,3,3,3-Tetrafluoroprop-1-ene (R1234yf) and trans-1,3,3,3-Tetrafluoropropene (R1234ze(E)) as potential replacements for refrigerants with high global warming potential (GWP). In this manuscript we survey available data and provide viscosity correlations that cover the entire fluid range including vapor, liquid, and supercritical regions. The correlation for R1234yf is valid from the triple point (220 K) to 410 K at pressures up to 30 MPa, and the correlation for R1234ze(E) is valid from the triple point (169 K) to 420 K at pressures up to 100 MPa. The estimated uncertainty for both correlations at a 95 % confidence level is 2 % for the liquid phase over the temperature range 243 K to 363 K at pressures to 30 MPa, and 3 % for the gas phase at atmospheric pressure. PMID:27840461

Elimination of both E1 and E2 from adenovirus vectors further improves prospects for in vivo human gene therapy.

PubMed Central

Gorziglia, M I; Kadan, M J; Yei, S; Lim, J; Lee, G M; Luthra, R; Trapnell, B C

1996-01-01

A novel recombinant adenovirus vector, Av3nBg, was constructed with deletions in adenovirus E1, E2a, and E3 regions and expressing a beta-galactosidase reporter gene. Av3nBg can be propagated at a high titer in a corresponding A549-derived cell line, AE1-2a, which contains the adenovirus E1 and E2a region genes inducibly expressed from separate glucocorticoid-responsive promoters. Av3nBg demonstrated gene transfer and expression comparable to that of Av1nBg, a first-generation adenovirus vector with deletions in E1 and E3. Several lines of evidence suggest that this vector is significantly more attenuated than E1 and E3 deletion vectors. Metabolic DNA labeling studies showed no detectable de novo vector DNA synthesis or accumulation, and metabolic protein labeling demonstrated no detectable de novo hexon protein synthesis for Av3nBg in naive A549 cells even at a multiplicity of infection of up to 3,000 PFU per cell. Additionally, naive A549 cells infected by Av3nBg did not accumulate infectious virions. In contrast, both Av1nBg and Av2Lu vectors showed DNA replication and hexon protein synthesis at multiplicities of infection of 500 PFU per cell. Av2Lu has a deletion in E1 and also carries a temperature-sensitive mutation in E2a. Thus, molecular characterization has demonstrated that the Av3nBg vector is improved with respect to the potential for vector DNA replication and hexon protein expression compared with both first-generation (Av1nBg) and second-generation (Av2Lu) adenoviral vectors. These observations may have important implications for potential use of adenovirus vectors in human gene therapy. PMID:8648763

(e,2e) and (Î3,2e) Processes: Open and Closed Questions

NASA Astrophysics Data System (ADS)

An important breakthrough has been achieved recently in the description of (e,2e) and (Î3,2e) processes with the development of new ab-initio theories: the external complex scaling theory (ECS), the time dependent close coupling theory (TDCC), and the hyperspherical R-matrix theory with semiclassical outgoing waves (HRM-SOW). The principles of these various theories are summarized, their relations are considered, and their achievements are discussed with respect to the available experimental data regarding electron impact ionization of H and photo double ionization of He. Possible directions for future work are outlined.

Distinct transcriptomic changes in E14.5 mouse skeletal muscle lacking RYR1 or Cav1.1 converge at E18.5

PubMed Central

Henry, Margit; Rotshteyn, Tamara; Brunn, Anna; Carstov, Mariana; Deckert, Martina; Hescheler, Jürgen; Sachinidis, Agapios; Pfitzer, Gabriele

2018-01-01

In skeletal muscle the coordinated actions of two mechanically coupled Ca2+ channels—the 1,4-dihydropyridine receptor (Cav1.1) and the type 1 ryanodine receptor (RYR1)–underlie the molecular mechanism of rapid cytosolic [Ca2+] increase leading to contraction. While both [Ca2+]i and contractile activity have been implicated in the regulation of myogenesis, less is known about potential specific roles of Cav1.1 and RYR1 in skeletal muscle development. In this study, we analyzed the histology and the transcriptomic changes occurring at E14.5 –the end of primary myogenesis and around the onset of intrauterine limb movement, and at E18.5 –the end of secondary myogenesis, in WT, RYR1-/-, and Cav1.1-/- murine limb skeletal muscle. At E14.5 the muscle histology of both mutants exhibited initial alterations, which became much more severe at E18.5. Immunohistological analysis also revealed higher levels of activated caspase-3 in the Cav1.1-/- muscles at E14.5, indicating an increase in apoptosis. With WT littermates as controls, microarray analyses identified 61 and 97 differentially regulated genes (DEGs) at E14.5, and 493 and 1047 DEGs at E18.5, in RYR1-/- and Cav1.1-/- samples, respectively. Gene enrichment analysis detected no overlap in the affected biological processes and pathways in the two mutants at E14.5, whereas at E18.5 there was a significant overlap of DEGs in both mutants, affecting predominantly processes linked to muscle contraction. Moreover, the E18.5 vs. E14.5 comparison revealed multiple genotype-specific DEGs involved in contraction, cell cycle and miRNA-mediated signaling in WT, neuronal and bone development in RYR1-/-, and lipid metabolism in Cav1.1-/- samples. Taken together, our study reveals discrete changes in the global transcriptome occurring in limb skeletal muscle from E14.5 to E18.5 in WT, RYR1-/- and Cav1.1-/- mice. Our results suggest distinct functional roles for RYR1 and Cav1.1 in skeletal primary and secondary myogenesis. PMID

Osteoblast-like MC3T3-E1 Cells Prefer Glycolysis for ATP Production but Adipocyte-like 3T3-L1 Cells Prefer Oxidative Phosphorylation.

PubMed

Guntur, Anyonya R; Gerencser, Akos A; Le, Phuong T; DeMambro, Victoria E; Bornstein, Sheila A; Mookerjee, Shona A; Maridas, David E; Clemmons, David E; Brand, Martin D; Rosen, Clifford J

2018-06-01

Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate into osteoblasts, chondrocytes, and adipocytes. We hypothesized that osteoblasts and adipocytes utilize distinct bioenergetic pathways during MSC differentiation. To test this hypothesis, we compared the bioenergetic profiles of preosteoblast MC3T3-E1 cells and calvarial osteoblasts with preadipocyte 3T3L1 cells, before and after differentiation. Differentiated MC3T3-E1 osteoblasts met adenosine triphosphate (ATP) demand mainly by glycolysis with minimal reserve glycolytic capacity, whereas nondifferentiated cells generated ATP through oxidative phosphorylation. A marked Crabtree effect (acute suppression of respiration by addition of glucose, observed in both MC3T3-E1 and calvarial osteoblasts) and smaller mitochondrial membrane potential in the differentiated osteoblasts, particularly those incubated at high glucose concentrations, indicated a suppression of oxidative phosphorylation compared with nondifferentiated osteoblasts. In contrast, both nondifferentiated and differentiated 3T3-L1 adipocytes met ATP demand primarily by oxidative phosphorylation despite a large unused reserve glycolytic capacity. In sum, we show that nondifferentiated precursor cells prefer to use oxidative phosphorylation to generate ATP; when they differentiate to osteoblasts, they gain a strong preference for glycolytic ATP generation, but when they differentiate to adipocytes, they retain the strong preference for oxidative phosphorylation. Unique metabolic programming in mesenchymal progenitor cells may influence cell fate and ultimately determine the degree of bone formation and/or the development of marrow adiposity. © 2018 American Society for Bone and Mineral Research. © 2018 American Society for Bone and Mineral Research.

5,6-Dehydrokawain from Alpinia zerumbet promotes osteoblastic MC3T3-E1 cell differentiation.

PubMed

Kumagai, Momochika; Mishima, Takashi; Watanabe, Akio; Harada, Teppei; Yoshida, Izumi; Fujita, Kazuhiro; Watai, Masatoshi; Tawata, Shinkichi; Nishikawa, Keisuke; Morimoto, Yoshiki

2016-07-01

Bone homeostasis is maintained by balancing bone formation and bone resorption, but an imbalance between them is associated with various bone-related diseases such as osteoporosis and rheumatoid arthritis. We found that 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK), which were isolated as promising compounds from Alpinia zerumbet rhizomes, promote differentiation of osteoblastic MC3T3-E1 cells. DK and DDK increased the alkaline phosphatase activity and matrix mineralization of MC3T3-E1 cells. DK exerts larger effects than DDK. The gene expression of runt-related transcription factor 2 and osterix, which are essential transcription factors in the early period of osteoblast differentiation, was significantly increased by DK treatment. The mRNA level of distal-less homeobox 5 was also enhanced by DK treatment, and DK activated the p38 mitogen-activated protein kinase pathway. Therefore, DK may have clinical potential for preventing osteoporosis, and could be considered as a potential anabolic therapeutic agent.

Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome.

PubMed

Yaron, Y; Cherry, M; Kramer, R L; O'Brien, J E; Hallak, M; Johnson, M P; Evans, M I

1999-10-01

We evaluated the value of all 3 common biochemical serum markers, maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol, and combinations thereof as predictors of pregnancy outcome. A total of 60,040 patients underwent maternal serum screening. All patients had maternal serum alpha-fetoprotein measurements; beta-human chorionic gonadotropin was measured in 45,565 patients, and 24,504 patients had determination of all 3 markers, including unconjugated estriol. The incidences of various pregnancy outcomes were evaluated according to the serum marker levels by using clinically applied cutoff points. In confirmation of previous observations, increased maternal serum alpha-fetoprotein levels (>2.5 multiples of the median) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, intrauterine growth restriction, intrauterine fetal death, oligohydramnios, and abruptio placentae. Increased beta-human chorionic gonadotropin levels (>2.5 multiples of the median [MoM]) were significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, and intrauterine fetal death. Finally, decreased unconjugated estriol levels (<0.5 MoM) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, intrauterine growth restriction, and intrauterine fetal death. As with increased second-trimester maternal serum alpha-fetoprotein levels, increased serum beta-human chorionic gonadotropin and low unconjugated estriol levels are significantly associated with adverse pregnancy outcomes. These are most likely attributed to placental dysfunction. Multiple-marker screening can be used not only for the detection of fetal anomalies and aneu-ploidy but also for detection of high-risk pregnancies.

Molecular Structure of a 9-MDa Icosahedral Pyruvate Dehydrogenase Subcomplex Containing the E2 and E3 Enzymes Using Cryoelectron Microscopy*

PubMed Central

Milne, Jacqueline L. S.; Wu, Xiongwu; Borgnia, Mario J.; Lengyel, Jeffrey S.; Brooks, Bernard R.; Shi, Dan; Perham, Richard N.; Subramaniam, Sriram

2006-01-01

The pyruvate dehydrogenase multienzyme complexes are among the largest multifunctional catalytic machines in cells, catalyzing the production of acetyl CoA from pyruvate. We have previously reported the molecular architecture of an 11-MDa subcomplex comprising the 60-mer icosahedral dihydrolipoyl acetyltransferase (E2) decorated with 60 copies of the heterotetrameric (α2β2) 153-kDa pyruvate decarboxylase (E1) from Bacillus stearothermophilus (Milne, J. L. S., Shi, D., Rosenthal, P. B., Sunshine, J. S., Domingo, G. J., Wu, X., Brooks, B. R., Perham, R. N., Henderson, R., and Subramaniam, S. (2002) EMBO J. 21, 5587–5598). An annular gap of ~90 Å separates the acetyltransferase catalytic domains of the E2 from an outer shell formed of E1 tetramers. Using cryoelectron microscopy, we present here a three-dimensional reconstruction of the E2 core decorated with 60 copies of the homodimeric 100-kDa dihydrolipoyl dehydrogenase (E3). The E2E3 complex has a similar annular gap of ~75 Å between the inner icosahedral assembly of acetyltransferase domains and the outer shell of E3 homodimers. Automated fitting of the E3 coordinates into the map suggests excellent correspondence between the density of the outer shell map and the positions of the two best fitting orientations of E3. As in the case of E1 in the E1E2 complex, the central 2-fold axis of the E3 homodimer is roughly oriented along the periphery of the shell, making the active sites of the enzyme accessible from the annular gap between the E2 core and the outer shell. The similarities in architecture of the E1E2 and E2E3 complexes indicate fundamental similarities in the mechanism of active site coupling involved in the two key stages requiring motion of the swinging lipoyl domain across the annular gap, namely the synthesis of acetyl CoA and regeneration of the dithiolane ring of the lipoyl domain. PMID:16308322

mTORC1 signalling and eIF4E/4E-BP1 translation initiation factor stoichiometry influence recombinant protein productivity from GS-CHOK1 cells.

PubMed

Jossé, Lyne; Xie, Jianling; Proud, Christopher G; Smales, C Mark

2016-12-15

Many protein-based biotherapeutics are produced in cultured Chinese hamster ovary (CHO) cell lines. Recent reports have demonstrated that translation of recombinant mRNAs and global control of the translation machinery via mammalian target of rapamycin (mTOR) signalling are important determinants of the amount and quality of recombinant protein such cells can produce. mTOR complex 1 (mTORC1) is a master regulator of cell growth/division, ribosome biogenesis and protein synthesis, but the relationship between mTORC1 signalling, cell growth and proliferation and recombinant protein yields from mammalian cells, and whether this master regulating signalling pathway can be manipulated to enhance cell biomass and recombinant protein production (rPP) are not well explored. We have investigated mTORC1 signalling and activity throughout batch culture of a panel of sister recombinant glutamine synthetase-CHO cell lines expressing different amounts of a model monoclonal IgG4, to evaluate the links between mTORC1 signalling and cell proliferation, autophagy, recombinant protein expression, global protein synthesis and mRNA translation initiation. We find that the expression of the mTORC1 substrate 4E-binding protein 1 (4E-BP1) fluctuates throughout the course of cell culture and, as expected, that the 4E-BP1 phosphorylation profiles change across the culture. Importantly, we find that the eIF4E/4E-BP1 stoichiometry positively correlates with cell productivity. Furthermore, eIF4E amounts appear to be co-regulated with 4E-BP1 amounts. This may reflect a sensing of either change at the mRNA level as opposed to the protein level or the fact that the phosphorylation status, as well as the amount of 4E-BP1 present, is important in the co-regulation of eIF4E and 4E-BP1. © 2016 The Author(s).

FATE OF SEX HORMONES IN TWO PILOT-SCALE MUNICIPAL WASTEWATER TREATMENT PLANTS: CONVENTIONAL TREATMENT

EPA Science Inventory

The fate of seven sex hormones (estrone (E1), estradiol (E2), estriol (E3), ethinylestradiol (EE2), testosterone, androstenedione, and progesterone) was determined in two pilot-scale wastewater treatment plants operated under conventional loading conditions. The levels of hormon...

E 3 and M 2 transition strengths in Bi20983

NASA Astrophysics Data System (ADS)

Roberts, O. J.; NiÅ£ǎ, C. R.; Bruce, A. M.; Mǎrginean, N.; Bucurescu, D.; Deleanu, D.; Filipescu, D.; Florea, N. M.; Gheorghe, I.; GhiÅ£ǎ, D.; Glodariu, T.; Lica, R.; Mǎrginean, R.; Mihai, C.; Negret, A.; Sava, T.; Stroe, L.; Şuvǎilǎ, R.; Toma, S.; Alharbi, T.; Alexander, T.; Aydin, S.; Brown, B. A.; Browne, F.; Carroll, R. J.; Mulholland, K.; Podolyák, Zs.; Regan, P. H.; Smith, J. F.; Smolen, M.; Townsley, C. M.

2016-01-01

The 1 i13/2→1 h9/2 (M 2 ) and 3 s1/2→2 f7/2 (E 3 ) reduced proton transition probabilities in Bi20983 have been determined from the direct half-life measurements of the 13/21+ and 1/21+ states using the Romanian array for γ -ray SPectroscopy in HEavy ion REactions (RoSPHERE). The 13/21+ and 1/21+ states were found to have T1/2=0.120 (15 ) ns and T1/2=9.02 (24 ) ns respectively. Angular distribution measurements were used to determine an E 3 /M 2 mixing ratio of δ =-0.184 (13 ) for the 1609 keV γ -ray transition deexciting the 13/21+ state. This value for δ was combined with the measured half-life to give reduced transition probabilities of B (E 3 ,13/21+→9/21-) =12 (2 ) ×103 e2fm6 and B (M 2 ,13/21+→9/21-) =38 (5 ) μN2fm2 . These values are in good agreement with calculations within the finite Fermi system. The extracted value of B (E 3 ,1/21+→7/21-) =6.3 (2 ) ×103 e2fm6 can be explained by a small (˜6 % ) admixture in the wave function of the 1/21+ state.

Interaction of Adenovirus E1A with the HHV8 Promoter of Latent Genes: E1A Proteins are Able to Activate the HHV-8 LANAp in MV3 Reporter Cells

PubMed Central

Koehler-Hansner, Karin; Flore, Ornella; Opalka, Bertram; Hengge, Ulrich R

2008-01-01

Human herpesvirus 8 (HHV-8) is associated with Kaposi’s sarcoma, body cavity-based lymphoma, and Castleman’s disease. Adenoviral (Ad) E1A proteins regulate the activity of cellular and viral promoters/enhancers and transcription factors and can suppress tumorigenicity of human cancers. As (i) HHV-8 and Ad may co-exist in immunocompromised patients and (ii) E1A might be considered as therapeutic transgene for HHV-8-associated neoplasms we investigated whether the promoter of the latency-associated nuclear antigen (LANAp) controlling expression of vCyclin, vFLIP, and LANA proteins required for latent type infection is regulated by E1A. Transfection experiments in MV3 melanoma cells revealed activation of the LANAp by Ad5 E1A constructs containing an intact N terminus (aa 1-119). In particular, an Ad12 E1A mutant, Spm2, lacking six consecutive alanine residues in the “spacer” region activated the HHV-8 promoter about 15-fold compared to vector controls. In summary, we report the activation of the LANAp by E1A as a novel interaction of E1A with a viral promoter. These data may have relevance for the management of viral infections in immunocompromised patients. A role for E1A as a therapeutic in this context remains to be defined. PMID:19440465

Association of papillomavirus E6 proteins with either MAML1 or E6AP clusters E6 proteins by structure, function, and evolutionary relatedness

PubMed Central

Brimer, Nicole

2017-01-01

Papillomavirus E6 proteins bind to LXXLL peptide motifs displayed on targeted cellular proteins. Alpha genus HPV E6 proteins associate with the cellular ubiquitin ligase E6AP (UBE3A), by binding to an LXXLL peptide (ELTLQELLGEE) displayed by E6AP, thereby stimulating E6AP ubiquitin ligase activity. Beta, Gamma, and Delta genera E6 proteins bind a similar LXXLL peptide (WMSDLDDLLGS) on the cellular transcriptional co-activator MAML1 and thereby repress Notch signaling. We expressed 45 different animal and human E6 proteins from diverse papillomavirus genera to ascertain the overall preference of E6 proteins for E6AP or MAML1. E6 proteins from all HPV genera except Alpha preferentially interacted with MAML1 over E6AP. Among animal papillomaviruses, E6 proteins from certain ungulate (SsPV1 from pigs) and cetacean (porpoises and dolphins) hosts functionally resembled Alpha genus HPV by binding and targeting the degradation of E6AP. Beta genus HPV E6 proteins functionally clustered with Delta, Pi, Tau, Gamma, Chi, Mu, Lambda, Iota, Dyokappa, Rho, and Dyolambda E6 proteins to bind and repress MAML1. None of the tested E6 proteins physically and functionally interacted with both MAML1 and E6AP, indicating an evolutionary split. Further, interaction of an E6 protein was insufficient to activate degradation of E6AP, indicating that E6 proteins that target E6AP co-evolved to separately acquire both binding and triggering of ubiquitin ligase activation. E6 proteins with similar biological function clustered together in phylogenetic trees and shared structural features. This suggests that the divergence of E6 proteins from either MAML1 or E6AP binding preference is a major event in papillomavirus evolution. PMID:29281732

Activity‐Based Probes for HECT E3 Ubiquitin Ligases

PubMed Central

Byrne, Robert; Mund, Thomas

2017-01-01

Abstract Activity‐based probes (ABPs) have been used to dissect the biochemical/structural properties and cellular functions of deubiquitinases. However, their utility in studying cysteine‐based E3 ubiquitin ligases has been limited. In this study, we evaluate the use of ubiquitin‐ABPs (Ub‐VME and Ub‐PA) and a novel set of E2–Ub‐ABPs on a panel of HECT E3 ubiquitin ligases. Our in vitro data show that ubiquitin‐ABPs can label HECT domains. We also provide the first evidence that, in addition to the RBR E3 ubiquitin ligase Parkin, E2–Ub‐ABPs can also label the catalytic HECT domains of NEDD4, UBE3C, and HECTD1. Importantly, the endogenous proteasomal E3 ligase UBE3C was also successfully labelled by Ub‐PA and His‐UBE2D2–Ub‐ABP in lysate of cells grown under basal conditions. Our findings provide novel insights into the use of ABPs for the study of HECT E3 ubiquitin ligases. PMID:28425671

Antitumor properties of (5E,7E) analogs of vitamin D3.

PubMed

Filip, B; Milczarek, M; Wietrzyk, J; Chodyński, M; Kutner, A

2010-07-01

Geometric isomers (5E,7E) of major active metabolites of vitamin D3 [1alpha,25(OH)2D3 and (24R)-1,24(OH)2D3] were synthesized by a new convenient procedure. Vitamin D triene system of the metabolites was first derivatized as a Diels-Alder adduct. Removal of the triene protecting group, in a key synthetic step, yielded the title compounds PRI-2208 and PRI-2209, respectively. The analogs were examined for their antiproliferative activity in vitro against human breast cancer cells (MCF-7) and promyelocytic leukemia (HL-60) cells. The activity was compared with one of the parent compounds. Both analogs examined revealed similar or higher antiproliferative activity compared to 1alpha,25(OH)2D3 or to (24R)-1,24(OH)2D3. The studies of calcemic activity in vivo showed that analogs PRI-2208 and PRI-2209 did not influence the serum calcium level in doses, in which 1alpha,25(OH)2D3 or (24R)-1,24(OH)2D3 significantly increased this level. The antitumor activity of these analogs in the LLC mice tumor model was studied. Analog PRI-2208 was found to be more active in inhibiting LLC tumor growth than 1alpha,25(OH)2D3, as well as than PRI-2191 and PRI-2209. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment

DOE PAGES

Hodge, Curtis D.; Ismail, Ismail H.; Edwards, Ross A.; ...

2016-02-22

DNA double strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone Lys-63-linked ubiquitin chains in DSB signaling. In this paper, we defined the activated RNF8-Ubc13~ubiquitin complex by x-ray crystallography and its functional solution conformations by x-ray scattering, as tested by separation-of-function mutations imaged in cells by immunofluorescence. The collective results show that the RING E3 RNF8 targets E2 Ubc13 to DSB sites and plays a critical role in damage signaling by stimulating polyubiquitination through modulating conformations of ubiquitin covalently linked to the Ubc13more » active site. Structure-guided separation-of-function mutations show that the RNF8 E2 stimulating activity is essential for DSB signaling in mammalian cells and is necessary for downstream recruitment of 53BP1 and BRCA1. Chromatin-targeted RNF168 rescues 53BP1 recruitment involved in non-homologous end joining but not BRCA1 recruitment for homologous recombination. Finally, these findings suggest an allosteric approach to targeting the ubiquitin-docking cleft at the E2-E3 interface for possible interventions in cancer and chronic inflammation, and moreover, they establish an independent RNF8 role in BRCA1 recruitment.« less

Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes.

PubMed

Chaudhary, Natasha; Gonzalez, Eva; Chang, Sung-Hee; Geng, Fuqiang; Rafii, Shahin; Altorki, Nasser K; McGraw, Timothy E

2016-12-20

Insulin activation of phosphatidylinositol 3-kinase (PI3K) regulates metabolism, including the translocation of the Glut4 glucose transporter to the plasma membrane and inactivation of the FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth-factor activation of PI3K. We have used E4-ORF1 as a tool to dissect PI3K-mediated signaling in adipocytes. E4-ORF1 activation of PI3K in adipocytes recapitulates insulin regulation of FoxO1 but not regulation of Glut4. This uncoupling of PI3K effects occurs despite E4-ORF1 activating PI3K and downstream signaling to levels achieved by insulin. Although E4-ORF1 does not fully recapitulate insulin's effects on Glut4, it enhances insulin-stimulated insertion of Glut4-containing vesicles to the plasma membrane independent of Rab10, a key regulator of Glut4 trafficking. E4-ORF1 also stimulates plasma membrane translocation of ubiquitously expressed Glut1 glucose transporter, an effect that is likely essential for E4-ORF1 to promote an anabolic metabolism in a broad range of cell types. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

E2/E6 ratio and L1 immunoreactivity as biomarkers to determine HPV16-positive high-grade squamous intraepithelial lesions (CIN2 and 3) and cervical squamous cell carcinoma

PubMed Central

2018-01-01

Objective Human papillomavirus (HPV) 16 is the most carcinogenic HPV genotype. We investigated if HPV16 L1 capsid protein and E2/E6 ratio, evaluated by cervical cytology, may be used as biomarkers of ≥cervical intraepithelial neoplasia (CIN) 2 lesions. Methods Cervical specimens were obtained from 226 patients with HPV16 single infection. Using cytology specimen, L1 capsid protein and E2/E6 ratio were detected and the results were compared with those of the conventional histologic analysis of cervical tissues (CIN1–3 and squamous cell carcinoma [SCC]) to evaluate the association. Results The L1 positivity of CIN2/3 was significantly lower than that of normal cervical tissue (p<0.001) and SCC demonstrated significantly lower L1 positivity than CIN1 (p<0.001). The mean E2/E6 ratios of specimens graded as SCC (0.356) and CIN2/3 (0.483) were significantly lower than those of specimens graded as CIN1 (0.786) and normal (0.793) (p<0.05). We observed that area under the receiver operating characteristic curve (AUC) for E2/E6 ratio (0.844; 95% confidence interval [CI]=0.793–0.895) was higher than that for L1 immunochemistry (0.636; 95% CI=0.562–0.711). A combination of E2/E6 ratio and L1 immunocytochemistry analyses showed the highest AUC (0.871; 95% CI=0.826–0.917) for the prediction of ≥CIN2 lesions. Conclusion To our knowledge, this is the first study to validate HPV L1 capsid protein expression and decreased HPV E2/E6 ratio as valuable predictive markers of ≥CIN2 cervical lesions. Cervical cytology may be analyzed longitudinally on an outpatient basis with noninvasive procedures as against invasive conventional histologic analysis. PMID:29400024

Is e+e- pair emission important in the determination of the 3He+4He S factor?

NASA Astrophysics Data System (ADS)

Snover, K. A.; Hurd, A. E.

2003-05-01

We show that the cross section for direct E0 pair emission is related to the cross section for direct E2 photon emission, and is a negligible contribution to the total capture cross section for 3He+4He→7Be. E0 resonance emission, E1 pair emission, and internal conversion are also negligible. Thus there cannot be significant contributions to the 3He+4He→7Be capture cross section at low energies from electromagnetic emission processes other than single photon emission.

The crystal structures of six (2E)-3-aryl-1-(5-halogeno-thio-phen-2-yl)prop-2-en-1-ones.

PubMed

Naik, Vasant S; Yathirajan, Hemmige S; Jasinski, Jerry P; Smolenski, Victoria A; Glidewell, Christopher

2015-09-01

The structures of six chalcones containing 5-halogeno-thio-phen-2-yl substituents are reported: (2E)-1-(5-chloro-thio-phen-2-yl)-3-(4-ethyl-phen-yl)prop-2-en-1-one, C15H13ClOS, (I), and (2E)-1-(5-bromo-thio-phen-2-yl)-3-(4-ethyl-phen-yl)prop-2-en-1-one, C15H13BrOS, (II), are isostructural in space group P-1, while (2E)-1-(5-chloro-thio-phen-2-yl)-3-(4-eth-oxy-phen-yl)prop-2-en-1-one, C15H13ClO2S, (III), and (2E)-1-(5-bromo-thio-phen-2-yl)-3-(4-eth-oxy-phen-yl)prop-2-en-1-one C15H13BrO2S, (IV), are isostructural in space group P21/c. There are no hydrogen bonds of any kind in the structures of compounds (I) and (II), but in the structures of compounds (III) and (IV), the mol-ecules are linked into C(7) chains by means of C-H⋯O hydrogen bonds. In the structure of (2E)-3-(4-bromo-phen-yl)-1-(5-chloro-thio-phen-2-yl)prop-2-en-1-one, C13H8BrClOS, (V), there are again no hydrogen bonds nor π-π stacking inter-actions but in that of (2E)-1-(5-bromo-thio-phen-2-yl)-3-(3-meth-oxy-phen-yl)prop-2-en-1-one, C14H11BrO2S, (VI), the mol-ecules are linked into C(5) chains by C-H⋯O hydrogen bonds. In each of compounds (I)-(VI), the mol-ecular skeletons are close to planarity, and there are short halogen⋯halogen contacts in the structures of compounds (II) and (V) and a short Br⋯O contact in the structure of compound (VI). Comparisons are made with the structures of some similar compounds.

(2E)-1-(5-Chlorothiophen-2-yl)-3-{4-[(E)-2-phenylethenyl]phenyl}prop-2-en-1-one: Synthesis, XRD, FT-IR, Raman and DFT studies.

PubMed

Parlak, Cemal; Ramasami, Ponnadurai; Kumar, Chandraju Sadolalu Chidan; Tursun, Mahir; Quah, Ching Kheng; Rhyman, Lydia; Bilge, Metin; Fun, Hoong-Kun; Chandraju, Siddegowda

2015-01-01

A novel (2E)-1-(5-chlorothiophen-2-yl)-3-{4-[(E)-2-phenylethenyl]phenyl}prop-2-en-1-one [C21H15ClOS] compound has been synthesized and its structure has been characterized by FT-IR, Raman and single-crystal X-ray diffraction techniques. The conformational isomers, optimized geometric parameters, normal mode frequencies and corresponding vibrational assignments of the compound have been examined by means of HF, MP2, BP86, BLYP, BMK, B3LYP, B3PW91, B3P86 and M06-2X functionals. Reliable vibrational assignments and molecular orbitals have been investigated by the potential energy distribution and natural bonding orbital analyses, respectively. The compound crystallizes in the triclinic space group P-1 with the cis-trans-trans form. There is a good agreement between the experimentally determined structural parameters and vibrational frequencies of the compound and those predicted theoretically using the density functional theory with the BLYP and BP86 functionals. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis, spectroscopic characterization, theoretical study and anti-hepatic cancer activity study of 4-(1E,3Z,6E)-3-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,6-trien-1-yl)-2-methoxyphenyl 4-nitrobenzoate, a novel curcumin congener

NASA Astrophysics Data System (ADS)

Srivastava, Sangeeta; Gupta, Preeti; Singh, Ranvijay Pratap; Jafri, Asif; Arshad, M.; Banerjee, Monisha

2017-08-01

In the present work 4-(1E,3Z,6E)-3-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,6-trien-1-yl)-2-methoxyphenyl 4-nitrobenzoate (2), a novel curcumin ester was synthesized. The molecular structure and spectroscopic analysis were performed using experimental techniques like FT-IR, 1H,13C NMR, mass and UV-visible as well as theoretical calculations. The theoretical calculations were done by DFT level of theory using B3LYP/6-31G (d,p) basis set. The vibrational wavenumbers were calculated using DFT method and assigned with the help of potential energy distribution (PED). The electronic properties such as frontier orbitals and band gap energies have been calculated using time dependent density functional theory (TD-DFT). The strength and nature of weak intramolecular interactions have been studied by AIM approach. Global and local reactivity descriptors have been computed to predict reactivity and reactive sites in the molecule. First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compounds. Molecular electrostatic potential (MEP) analysis has also been carried out. The anti-hepatic cancer activity of compound 2 was also carried out.

eIF3a: A new anticancer drug target in the eIF family.

PubMed

Yin, Ji-Ye; Zhang, Jian-Ting; Zhang, Wei; Zhou, Hong-Hao; Liu, Zhao-Qian

2018-01-01

eIF3a is the largest subunit of eIF3, which is a key player in all steps of translation initiation. During the past years, eIF3a is recognized as a proto-oncogene, which is an important discovery in this field. It is widely reported to be correlated with cancer occurrence, metastasis, prognosis, and therapeutic response. Recently, the mechanisms of eIF3a action in the carcinogenesis are unveiled gradually. A number of cellular, physiological, and pathological processes involving eIF3a are identified. Most importantly, it is emerging as a new potential drug target in the eIF family, and some small molecule inhibitors are being developed. Thus, we perform a critical review of recent advances in understanding eIF3a physiological and pathological functions, with specific focus on its role in cancer and anticancer drug targets. Copyright © 2017 Elsevier B.V. All rights reserved.

Transport of the placental estriol precursor 16α-hydroxy-dehydroepiandrosterone sulfate (16α-OH-DHEAS) by stably transfected OAT4-, SOAT-, and NTCP-HEK293 cells.

PubMed

Schweigmann, H; Sánchez-Guijo, A; Ugele, B; Hartmann, K; Hartmann, M F; Bergmann, M; Pfarrer, C; Döring, B; Wudy, S A; Petzinger, E; Geyer, J; Grosser, G

2014-09-01

16α-Hydroxy-dehydroepiandrosterone sulfate (16α-OH-DHEAS) mainly originates from the fetus and serves as precursor for placental estriol biosynthesis. For conversion of 16α-OH-DHEAS to estriol several intracellular enzymes are required. However, prior to enzymatic conversion, 16α-OH-DHEAS must enter the cells by carrier mediated transport. To identify these carriers, uptake of 16α-OH-DHEAS by the candidate carriers organic anion transporter OAT4, sodium-dependent organic anion transporter SOAT, Na(+)-taurocholate cotransporting polypeptide NTCP, and organic anion transporting polypeptide OATP2B1 was measured in stably transfected HEK293 cells by LC-MS-MS. Furthermore, the study aimed to localize SOAT in the human placenta. Stably transfected OAT4-HEK293 cells revealed a partly sodium-dependent transport for 16α-OH-DHEAS with an apparent Km of 23.1 ± 5.1 μM and Vmax of 485.0 ± 39.1 pmol/mg protein/min, while stably transfected SOAT- and NTCP-HEK293 cells showed uptake only under sodium conditions with Km of 319.0 ± 59.5 μM and Vmax of 1465.8 ± 118.8 pmol/mg protein/min for SOAT and Km of 51.4 ± 9.9 μM and Vmax of 1423.3 ± 109.6 pmol/mg protein/min for NTCP. In contrast, stably transfected OATP2B1-HEK293 cells did not transport 16α-OH-DHEAS at all. Immunohistochemical studies and in situ hybridization of formalin fixed and paraffin embedded sections of human late term placenta showed expression of SOAT in syncytiotrophoblasts, predominantly at the apical membrane as well as in the vessel endothelium. In conclusion, OAT4, SOAT, and NTCP were identified as carriers for the estriol precursor 16α-OH-DHEAS. At least SOAT and OAT4 seem to play a functional role for the placental estriol synthesis as both are expressed in the syncytiotrophoblast of human placenta. Copyright © 2014 Elsevier Ltd. All rights reserved.

Unphosphorylated HSP27 (HSPB1) regulates the translation initiation process via a direct association with eIF4E in osteoblasts.

PubMed

Kuroyanagi, Gen; Tokuda, Haruhiko; Yamamoto, Naohiro; Matsushima-Nishiwaki, Rie; Kozawa, Osamu; Otsuka, Takanobu

2015-09-01

Heat-shock protein 27 (HSP27/HSPB1) and its phosphorylation are implicated in multiple physiological and pathophysiological cell functions. Our previous study reported that unphosphorylated HSP27 has an inhibitory role in triiodothyronine (T(3))‑induced osteocalcin (OC) synthesis in osteoblasts. However, the mechanisms behind the HSP27‑mediated effects on osteoblasts remain to be clarified. In the present study, to investigate the exact mechanism of HSP27 and its phosphorylation in osteoblasts, the molecular targets of HSP27 were explored using osteoblast‑like MC3T3‑E1 cells. The levels of OC mRNA induced by T(3) in the HSP27‑overexpressing cells did not show any significant differences compared with those in the control empty vector‑transfected cells. Therefore, the interactions between HSP27 and translational molecules were focused on, including eukaryotic translation initiation factor 4E (eIF4E), eIF4G and 4E‑binding protein 1 (4E‑BP1). The HSP27 protein in the unstimulated cells co‑immunoprecipitated with eIF4E, but not eIF4G or 4E‑BP1. In addition, the association of eIF4E with 4E‑BP1 was observed in the HSP27‑overexpressing cells, as well as in the control cells. Under T(3) stimulation, the binding of eIF4E to eIF4G was markedly attenuated in the HSP27‑overexpressing cells compared with the control cells. In addition, the binding of HSP27 to eIF4E in the unstimulated cells was diminished by the phosphorylation of HSP27. In response to T(3) stimulation, the association of eIF4E with eIF4G in the unphosphorylatable HSP27‑overexpressing cells was markedly reduced compared with the phospho‑mimic HSP27‑overexpressing cells. Taken together, these findings strongly suggest that unphosphorylated HSP27 associates with eIF4E in osteoblasts and suppresses the translation initiation process.

Three closely related (2E,2′E)-3,3′-(1,4-phenyl­ene)bis­[1-(meth­oxy­phen­yl)prop-2-en-1-ones]: supra­molecular assemblies in one dimension mediated by hydrogen bonding and C—H⋯π inter­actions

PubMed Central

Chidan Kumar, C. S.; Then, Li Yee; Win, Yip-Foo; Quah, Ching Kheng; Naveen, S.; Chandraju, S.; Lokanath, N. K.; Warad, Ismail

2017-01-01

In the title compounds, (2E,2′E)-3,3′-(1,4-phenyl­ene)bis­[1-(2-meth­oxy­phen­yl)prop-2-en-1-one], C26H22O4 (I), (2E,2′E)-3,3′-(1,4-phenyl­ene)bis­[1-(3-meth­oxy­phen­yl)prop-2-en-1-one], C26H22O4 (II) and (2E,2′E)-3,3′-(1,4-phenyl­ene)bis­[1-(3,4-di­meth­oxy­phen­yl)prop-2-en-1-one], C28H26O6 (III), the asymmetric unit consists of a half-mol­ecule, completed by crystallographic inversion symmetry. The dihedral angles between the central and terminal benzene rings are 56.98 (8), 7.74 (7) and 7.73 (7)° for (I), (II) and (III), respectively. In the crystal of (I), mol­ecules are linked by pairs of C—H⋯π inter­actions into chains running parallel to [101]. The packing for (II) and (III), features inversion dimers linked by pairs of C—H⋯O hydrogen bonds, forming R 2 2(16) and R 2 2(14) ring motifs, respectively, as parts of [201] and [101] chains, respectively. PMID:28638654

Sirtuin1 promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor γ in MC3T3-E1 cells

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

Qu, Bo; Ma, Yuan; Yan, Ming

Osteoporosis is a skeletal disorder characterized by bone loss, resulting in architectural deterioration of the skeleton, decreased bone strength and an increased risk of fragility fractures. Strengthening osteogenesis is an effective way to relieve osteoporosis. Sirtuin1 (Sirt1) is a nicotinamide adenine dinucleotide (NAD{sup +})-dependent deacetylase, which is reported to be involved in improving osteogenesis. Sirt1 targets peroxisome proliferator-activated receptor γ (PPARγ) in the regulation of adipose tissues; however, the molecular mechanism of Sirt1 in osteogenic differentiation is still unknown. PPARγ tends to induce more adipogenic differentiation rather than osteogenic differentiation. Hence, we hypothesized that Sirt1 facilitates osteogenic differentiation through downregulationmore » of PPARγ signaling. Mouse pre-osteoblastic MC3T3-E1 cells were cultured under osteogenic medium. Sirt1 was overexpressed through plasmid transfection. The results showed that high expression of Sirt1 was associated with increased osteogenic differentiation, as indicated by quantitative PCR and Western blot analysis of osteogenic markers, and Von Kossa staining. Sirt1 overexpression also directly and negatively regulated the expression of PPARγ and its downstream molecules. Use of the PPARγ agonist Rosiglitazone, reversed the effects of Sirt1 on osteogenic differentiation. Using constructed luciferase plasmids, we demonstrated a role of Sirt1 in inhibiting PPARγ–induced activity and expression of adipocyte–specific genes, including acetyl-coenzyme A carboxylase (Acc) and fatty acid binding protein 4 (Fabp4). The interaction between Sirt1 and PPARγ was further confirmed using co-immunoprecipitation analysis. Together, these results reveal a novel mechanism for Sirt1 in osteogenic differentiation through downregulation of PPARγ activity. These findings suggest that the Sirt1–PPARγ pathway may represent a potential target for enhancement of osteogenesis and

Cuscuta chinensis seeds water extraction protecting murine osteoblastic MC3T3-E1 cells against tertiary butyl hydroperoxide induced injury.

PubMed

Gao, Jian-mei; Li, Ran; Zhang, Lei; Jia, Li-long; Ying, Xi-xiang; Dou, De-qiang; Li, Jian-chun; Li, Hai-bo

2013-07-09

Cuscuta chinensis (C. chinensis) is a well-known traditional Chinese herb that has been used to treat heart disease, diabetes, liver injury, cancer, and aging. Murine osteoblastic MC3T3-E1 cells were treated with various concentrations of C. chinensis water extraction at different time intervals. The antioxidant effect of C. chinensis on MC3T3-E1 cells was evaluated using MTT and TUNEL assays. The effect of C. chinensis on cell cycle was analyzed by flow cytometry with propidium iodide. Lipid peroxidation was measured by the HPLC method. The cellular redox status was determined from the reduced glutathione to oxidized glutathione ratio (GSH/GSSG) and the enzymes involved in glutathione metabolism, including glutathione reductase (GR), Glutathione S-transferase (GST), and Glucose-6-phosphate dehydrogenase (G6PD). The changes in relative mitochondrial transmembrane potential (ΔΨm) in the MC3T3-E1 cells were analyzed with rhodamine 123 staining. Western blot analysis was used to evaluate the levels of cytochrome c (cyto c), Bax, Bcl-2, caspase 3, Sirt3, and IDH2 expressions. The C. chinensis water extraction protects tertiary butyl hydroperoxide (TBHP)-treated MC3T3-E1 cells from death in a dose-dependent manner. C. chinensis treatment significantly inhibited the reactive oxygen species (ROS) generation, malondialdehyde (MDA) production, and increased the activity of superoxide dismutase (SOD), GR, GST, and G6PD. The release of cyto c from mitochondria was reduced by C. chinensis, which increased the expression of antiapoptotic IDH2, Sirt3, and Bcl-2 and decreased the expression of Bax, cyto c, and caspase 3. C. chinensis modulated the oxidative stress-induced apoptosis in MC3T3-E1 cells, probably due to its antioxidant activity and functioning via mitochondria-dependent pathways. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

E&V (Evaluation and Validation) Reference Manual, Version 1.1

DTIC Science & Technology

1988-10-20

E&V. This model will allow the user to arrive at E&V techniques through many different paths, and provides a means to extract useful information...electronically (preferred) to szymansk@ajpo.sei.cmu.edu or by regular mail to Mr. Raymond Szymanski , AFWAL/AAAF, Wright Patterson AFB, OH 45433-6543. ES-2 E&V...1, 1-3 illustrate the types of infor- mation to be extracted from each document. Chapter 2 provides a more detailed description of the structure and

Occupational Analysis Products: Operations Management- AFSC 3E6X1 (CD-ROM)

DTIC Science & Technology

computer laser optical disc (CD-ROM); 4 3/4 in.; 23.4 MB. SYSTEMS DETAIL NOTE: ABSTRACT: This is a report of an occupational survey of the Operations ... Management (AFSC 3E6X1, OSSN 2560, Feb 04) career ladder, conducted by the Occupational Analysis Flight, AFOMS. The OSR reports the findings of current

A Cullin1-Based SCF E3 Ubiquitin Ligase Targets the InR/PI3K/TOR Pathway to Regulate Neuronal Pruning

PubMed Central

Wong, Jack Jing Lin; Wang, Cheng; Zhang, Heng; Kirilly, Daniel; Wu, Chunlai; Liou, Yih-Cherng; Wang, Hongyan; Yu, Fengwei

2013-01-01

Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroom body γ neurons specifically eliminate their axon branches within dorsal and medial lobes. However, it is unknown which E3 ligase directs these two modes of pruning. Here, we identified a conserved SCF E3 ubiquitin ligase that plays a critical role in pruning of both ddaC dendrites and mushroom body γ axons. The SCF E3 ligase consists of four core components Cullin1/Roc1a/SkpA/Slimb and promotes ddaC dendrite pruning downstream of EcR-B1 and Sox14, but independently of Mical. Moreover, we demonstrate that the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway. We show that the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination. Activation of the InR/PI3K/TOR pathway is sufficient to inhibit ddaC dendrite pruning. Thus, our findings provide a novel link between the E3 ligase and the InR/PI3K/TOR pathway during dendrite pruning. PMID:24068890

The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch

PubMed Central

Oberst, Andrew; Malatesta, Martina; Aqeilan, Rami I.; Rossi, Mario; Salomoni, Paolo; Murillas, Rodolfo; Sharma, Prashant; Kuehn, Michael R.; Oren, Moshe; Croce, Carlo M.; Bernassola, Francesca; Melino, Gerry

2007-01-01

Nedd4-binding partner-1 (N4BP1) has been identified as a protein interactor and a substrate of the homologous to E6AP C terminus (HECT) domain-containing E3 ubiquitin–protein ligase (E3), Nedd4. Here, we describe a previously unrecognized functional interaction between N4BP1 and Itch, a Nedd4 structurally related E3, which contains four WW domains, conferring substrate-binding activity. We show that N4BP1 association with the second WW domain (WW2) of Itch interferes with E3 binding to its substrates. In particular, we found that N4BP1 and p73α, a target of Itch-mediated ubiquitin/proteasome proteolysis, share the same binding site. By competing with p73α for binding to the WW2 domain, N4BP1 reduces the ability of Itch to recruit and ubiquitylate p73α and inhibits Itch autoubiquitylation activity both in in vitro and in vivo ubiquitylation assays. Similarly, both c-Jun and p63 polyubiquitylation by Itch are inhibited by N4BP1. As a consequence, genetic and RNAi knockdown of N4BP1 diminish the steady-state protein levels and significantly impair the transcriptional activity of Itch substrates. Notably, stress-induced induction of c-Jun was impaired in N4BP1−/− cells. These results demonstrate that N4BP1 functions as a negative regulator of Itch. In addition, because inhibition of Itch by N4BP1 results in the stabilization of crucial cell death regulators such as p73α and c-Jun, it is conceivable that N4BP1 may have a role in regulating tumor progression and the response of cancer cells to chemotherapy. PMID:17592138

The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch.

PubMed

Oberst, Andrew; Malatesta, Martina; Aqeilan, Rami I; Rossi, Mario; Salomoni, Paolo; Murillas, Rodolfo; Sharma, Prashant; Kuehn, Michael R; Oren, Moshe; Croce, Carlo M; Bernassola, Francesca; Melino, Gerry

2007-07-03

Nedd4-binding partner-1 (N4BP1) has been identified as a protein interactor and a substrate of the homologous to E6AP C terminus (HECT) domain-containing E3 ubiquitin-protein ligase (E3), Nedd4. Here, we describe a previously unrecognized functional interaction between N4BP1 and Itch, a Nedd4 structurally related E3, which contains four WW domains, conferring substrate-binding activity. We show that N4BP1 association with the second WW domain (WW2) of Itch interferes with E3 binding to its substrates. In particular, we found that N4BP1 and p73 alpha, a target of Itch-mediated ubiquitin/proteasome proteolysis, share the same binding site. By competing with p73 alpha for binding to the WW2 domain, N4BP1 reduces the ability of Itch to recruit and ubiquitylate p73 alpha and inhibits Itch autoubiquitylation activity both in in vitro and in vivo ubiquitylation assays. Similarly, both c-Jun and p63 polyubiquitylation by Itch are inhibited by N4BP1. As a consequence, genetic and RNAi knockdown of N4BP1 diminish the steady-state protein levels and significantly impair the transcriptional activity of Itch substrates. Notably, stress-induced induction of c-Jun was impaired in N4BP1(-/-) cells. These results demonstrate that N4BP1 functions as a negative regulator of Itch. In addition, because inhibition of Itch by N4BP1 results in the stabilization of crucial cell death regulators such as p73 alpha and c-Jun, it is conceivable that N4BP1 may have a role in regulating tumor progression and the response of cancer cells to chemotherapy.

Nano-hydroxyapatite particles induce apoptosis on MC3T3-E1 cells and tissue cells in SD rats

NASA Astrophysics Data System (ADS)

Wang, Liting; Zhou, Gang; Liu, Haifeng; Niu, Xufeng; Han, Jingyun; Zheng, Lisha; Fan, Yubo

2012-04-01

While the advantages of nanomaterials are being increasingly recognized, their potential toxicity is drawing more and more attention and concern. In this study, we explore the toxicity mechanism of 20-30 nm rod-shaped hydroxyapatite (HA) nanoparticles in vitro and in vivo. The nanoparticles were prepared by precipitation and characterized by IR, XRD and TEM. Concentrations of 0 μg mL-1, 10 μg mL-1, 100 μg mL-1, 1 mg mL-1, and 10 mg mL-1 were applied to the MC3T3-E1 cells for viability (MTT-test). Based on the characteristic differences of the two methods of cell death, the morphological features of the MC3T3-E1 cell line co-cultured with nano-hydroxyapatite (n-HA) (10 mg mL-1) for 24 h were also observed by TEM. Furthermore, important serum biochemical markers and histopathological examinations were used to evaluate the potential toxicological effect of n-HA on the major organs of SD rats injected intraperitoneally with n-HA (33.3 mg kg-1 body weight). In the results, we found cell growth inhibition and apoptosis in MC3T3-E1 cells co-cultured with n-HA. Moreover, apoptosis but not necrosis was illustrated in liver and renal tissue by using histopathology slices and serum biochemical markers. It suggests that apoptosis may be the possible mechanism of n-HA toxicity and provides a better understanding of the biocompatibility of nanomaterials applied in human bone repair.

THE INSTABILITY OF ESTROGENIC CHEMICALS DURING LABORATORY STATIC EXPOSURE CONDITIONS WITH MALE FATHEAD MINNOWS

EPA Science Inventory

Endocrine disrupting chemicals (EDCs) such as Para-nonylphenol (NP), estradiol (E2), estrone (E1), estriol (E3) and ethynylestradiol (EE2) are shown to be ubiquitous in surface waters, sediments and sludge. These EDCs are known to induce vitellogenin gene (Vg) expression in male...

Word Frequency Analysis. MOS: 62E. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

j., JtU I J ’I JT S EiM. ’J~VERSA. 5 *J (Jtl~iL I ’JSJP 1 J LUSE t J &USED 5 1 .3 u51’G 3 J .3 UTZLI ATEICN 2 J & VALVE 1 0 J3 EVISUAL I .3 fVj5JLY 2...ECOVERY I 7TI;1Irk 9 REVI1VE I RECTLY 2 PEO 4 i:’ 1 R.EC13CED ? Rr.~vl I IlFr~k 44 RcFFZ(E: ; I Ff ," TF1 ’. I 1 !E* ST EPS 4 1 RELL..SSD 7 PkLIF I RELI~E t

42 CFR 52e.3 - Who is eligible to apply?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Who is eligible to apply? 52e.3 Section 52e.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL HEART, LUNG, AND BLOOD INSTITUTE GRANTS FOR PREVENTION AND CONTROL PROJECTS § 52e.3 Who is eligible to apply? To be...

42 CFR 52e.3 - Who is eligible to apply?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Who is eligible to apply? 52e.3 Section 52e.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL HEART, LUNG, AND BLOOD INSTITUTE GRANTS FOR PREVENTION AND CONTROL PROJECTS § 52e.3 Who is eligible to apply? To be...

42 CFR 52e.3 - Who is eligible to apply?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Who is eligible to apply? 52e.3 Section 52e.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL HEART, LUNG, AND BLOOD INSTITUTE GRANTS FOR PREVENTION AND CONTROL PROJECTS § 52e.3 Who is eligible to apply? To be...

42 CFR 52e.3 - Who is eligible to apply?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Who is eligible to apply? 52e.3 Section 52e.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL HEART, LUNG, AND BLOOD INSTITUTE GRANTS FOR PREVENTION AND CONTROL PROJECTS § 52e.3 Who is eligible to apply? To be...

42 CFR 52e.3 - Who is eligible to apply?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Who is eligible to apply? 52e.3 Section 52e.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL HEART, LUNG, AND BLOOD INSTITUTE GRANTS FOR PREVENTION AND CONTROL PROJECTS § 52e.3 Who is eligible to apply? To be...

Mangiferin inhibits apoptosis and oxidative stress via BMP2/Smad-1 signaling in dexamethasone-induced MC3T3-E1 cells.

PubMed

Ding, Ling-Zhi; Teng, Xiao; Zhang, Zhao-Bo; Zheng, Chang-Jun; Chen, Shi-Hong

2018-05-01

Mangiferin is a xanthone glucoside, which possesses antioxidant, antiviral, antitumor and anti-inflammatory functions, and is associated with gene regulation. However, it remains unknown whether mangiferin protects osteoblasts, such as the MC3T3-E1 cell line, against glucocorticoid-induced damage. In the present study, MC3T3-E1 cells were treated with dexamethasone (Dex), which is a well-known synthetic glucocorticoid, in order to establish a glucocorticoid-induced cell injury model. After Dex and/or mangiferin treatment, cell viability, apoptosis and reactive oxygen species (ROS) production was measured by Cell Counting kit-8 (CCK-8) and flow cytometry, respectively, and the concentration of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and macrophage colony-stimulating factor (M-CSF) was measured by ELISA. The expression of bone morphogenetic protein 2 (BMP2), phosphorylated‑SMAD family member 1 (p-Smad-1), t-Smad-1, osterix (OSX), osteocalcin (OCN), osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), B‑cell lymphoma 2 (Bcl-2) and Bcl‑2‑associated X protein (Bax) was measured by real-time PCR and/or western blot analysis. The results indicated that pretreatment of MC3T3-E1 cells with mangiferin for 3 h prior to exposure to Dex for 48 h significantly attenuated Dex-induced injury and inflammation, as demonstrated by increased cell viability, and decreases in apoptosis, ROS generation, and the secretion of TNF-α, IL-6 and M-CSF. In addition, pretreatment with mangiferin markedly reduced Dex-induced BMP2 and p‑Smad-1 downregulation, and corrected the expression of differentiation‑ and apoptosis‑associated markers, including alkaline phosphatase, OSX, OCN, OPG, RANK, RANKL, Bcl-2 and Bax, which were altered by Dex treatment. Similar to the protective effects of mangiferin, overexpression of BMP2 suppressed not only Dex-induced cytotoxicity, but also ROS generation, and the secretion of TNF

RING-type E3 ligases: Master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination

PubMed Central

Metzger, Meredith B.; Pruneda, Jonathan N.; Klevit, Rachel E.; Weissman, Allan M.

2013-01-01

RING finger domain and RING finger-like ubiquitin ligases (E3s), such as U-box proteins, constitute the vast majority of known E3s. RING-type E3s function together with ubiquitin-conjugating enzymes (E2s) to mediate ubiquitination and are implicated in numerous cellular processes. In part because of their importance in human physiology and disease, these proteins and their cellular functions represent an intense area of study. Here we review recent advances in RING-type E3 recognition of substrates, their cellular regulation, and their varied architecture. Additionally, recent structural insights into RING-type E3 function, with a focus on important interactions with E2s and ubiquitin, are reviewed. This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. PMID:23747565

High-Throughput Screening of HECT E3 Ubiquitin Ligases Using UbFluor.

PubMed

Foote, Peter K; Krist, David T; Statsyuk, Alexander V

2017-09-14

HECT E3 ubiquitin ligases are responsible for many human disease phenotypes and are promising drug targets; however, screening assays for HECT E3 inhibitors are inherently complex, requiring upstream E1 and E2 enzymes as well as ubiquitin, ATP, and detection reagents. Intermediate ubiquitin thioesters and a complex mixture of polyubiquitin products provide further opportunities for off-target inhibition and increase the complexity of the assay. UbFluor is a novel ubiquitin thioester that bypasses the E1 and E2 enzymes and undergoes direct transthiolation with HECT E3 ligases. The release of fluorophore upon transthiolation allows fluorescence polarization detection of HECT E3 activity. In the presence of inhibitors, HECT E3 activity is ablated, and thus no reaction and no change in FP are observed. This assay has been adapted for high-throughput screening of small molecules against HECT E3 ligases, and its utility has been proven in the discovery of HECT E3 ligase inhibitors. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Influence of MC3T3-E1 preosteoblast culture on the corrosion of a T6-treated AZ91 alloy

PubMed Central

Brooks, Emily K.; Tobias, Menachem E.; Yang, Shuying; Bone, Lawrence B.; Ehrensberger, Mark T.

2015-01-01

This study investigated the corrosion of artificially aged T6 heat-treated Mg-9%Al-1%Zn (AZ91) for biomedical applications. Corrosion tests and surface analysis were completed both with and without a monolayer of mouse preosteoblast MC3T3-E1 cells cultured on the sample. Electrochemical impedance spectroscopy (EIS) and inductively coupled plasma mass spectroscopy (ICPMS) were used to explore the corrosion processes after either 3 or 21 days of AZ91 incubation in cell culture medium (CCM). The EIS showed both the inner layer resistance (Rin) and outer layer resistance (Rout) were lower for samples without cells cultured on the surface at 3 days (Rin = 2.64 e4 Ω/cm2, Rout = 140 Ω/cm2) compared to 21 days (Rin = 3.60 e4 Ω/cm2, Rout = 287 Ω/cm2) due to precipitation of magnesium and calcium phosphates over time. Samples with preosteoblasts cultured on the surface had a slower initial corrosion (3 day, Rin = 1.88 e5 Ω/cm2, Rout = 1060 Ω/cm2) which was observed to increase over time (21 day, Rin = 2.99 e4 Ω/cm2, Rout = 287 Ω/cm2). Changes in the corrosion processes were thought to be related to changes in the coverage provided by the cell layer. Our results reveal that the presence of cells and biological processes are able to significantly influence the corrosion rate of AZ91. PMID:25715925

26 CFR 1.514(e)-1 - Allocation rules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Allocation rules. 1.514(e)-1 Section 1.514(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations § 1.514(e)-1...

26 CFR 1.514(e)-1 - Allocation rules.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Allocation rules. 1.514(e)-1 Section 1.514(e)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations § 1.514(e)-1...

Glycogen Synthase Kinase 3 (GSK-3) influences epithelial barrier function by regulating Occludin, Claudin-1 and E-cadherin expression

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

Severson, Eric A.; Kwon, Mike; Hilgarth, Roland S.

2010-07-02

The Apical Junctional Complex (AJC) encompassing the tight junction (TJ) and adherens junction (AJ) plays a pivotal role in regulating epithelial barrier function and epithelial cell proliferative processes through signaling events that remain poorly characterized. A potential regulator of AJC protein expression is Glycogen Synthase Kinase-3 (GSK-3). GSK-3 is a constitutively active kinase that is repressed during epithelial-mesenchymal transition (EMT). In the present study, we report that GSK-3 activity regulates the structure and function of the AJC in polarized model intestinal (SK-CO15) and kidney (Madin-Darby Canine Kidney (MDCK)) epithelial cells. Reduction of GSK-3 activity, either by small molecule inhibitors ormore » siRNA targeting GSK-3 alpha and beta mRNA, resulted in increased permeability to both ions and bulk solutes. Immunofluorescence labeling and immunoblot analyses revealed that the barrier defects correlated with decreased protein expression of AJC transmembrane proteins Occludin, Claudin-1 and E-cadherin without influencing other TJ proteins, Zonula Occludens-1 (ZO-1) and Junctional Adhesion Molecule A (JAM-A). The decrease in Occludin and E-cadherin protein expression correlated with downregulation of the corresponding mRNA levels for these respective proteins following GSK-3 inhibition. These observations implicate an important role of GSK-3 in the regulation of the structure and function of the AJC that is mediated by differential modulation of mRNA transcription of key AJC proteins, Occludin, Claudin-1 and E-cadherin.« less

The clinical value of HPV E6/E7 and STAT3 mRNA detection in cervical cancer screening.

PubMed

Fan, Yibing; Shen, Zongji

2018-05-01

To explore the value of human papillomavirus (HPV) E6/E7 and signal transducer and activator of transcription 3 (STAT3) mRNA detection in the screening of cervical lesions. 192 patients with abnormal ThinPrep cytology test (TCT) results and/or high-risk HPV infection were screened to identify possible cervical lesions in cases. Diagnoses were confirmed by histopathology. Fluorescence in situ hybridization (FISH) was performed to detect and qualify the mRNAs of HPV E6/E7, STAT3, and Survivin in cervical exfoliated cells. In addition, the performance of separate and combined mRNA detection methods were compared with TCT, HR-HPV DNA schemes respectively. 1. Compared with HPVE6/E7 and STAT3 mRNA methods, Survivin mRNA assay had poor specificity (Sp), Youden index (YI) and concordance rate. 2. HPV E6/E7, STAT3, and STAT3 + HR-HPV methods had the best Sp, concordance rate and positive predictive value (PPV) for cervical lesions screening and atypical squamous cells of undetermined significance (ASCUS) triage. For screening of high grade squamous intraepithelial lesions or greater (HSILs+), no difference was observed in the Se of mRNA detection methods in comparison with that of TCT, HR-HPV and TCT + HR-HPV, whereas the false positive rate (FPR) decreased by 41.48%/55.99%/17.19% and the colposcopy referral rate reduced by about 20.00%/25.00%/11.17%. For triage of women with ASCUS, no difference was observed in the Se of mRNA detection methods as compared to that of HR-HPV (χ 2  = 1.05, P > 0.75), while the FPR decreased by 45.83%/37.50%/41.66% and the colposcopy referral rate reduced by 32.42%/22.60%/25.28%, respectively. The Se, YI, and PPV of the combined methods increased in comparison to each method alone. 3. Compared with the TCT + HR-HPV method, HPV E6/E7 + STAT3 method had perfect Sp (95.92%) and PPV (95.40%) for screening HSILs+, the FPR and colposcopy referral rate decreased by 31.06% and 22.48% respectively. 1. The expression of HPV E6/E

Degradation of human Lipin-1 by BTRC E3 ubiquitin ligase.

PubMed

Ishimoto, Kenji; Hayase, Ayaka; Kumagai, Fumiko; Kawai, Megumi; Okuno, Hiroko; Hino, Nobumasa; Okada, Yoshiaki; Kawamura, Takeshi; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Tachibana, Keisuke; Doi, Takefumi

2017-06-17

Lipin-1 has dual functions in the regulation of lipid and energy metabolism according to its subcellular localization, which is tightly controlled. However, it is unclear how Lipin-1 degradation is regulated. Here, we demonstrate that Lipin-1 is degraded through its DSGXXS motif. We show that Lipin-1 interacts with either of two E3 ubiquitin ligases, BTRC or FBXW11, and that this interaction is DSGXXS-dependent and mediates the attachment of polyubiquitin chains. Further, we demonstrate that degradation of Lipin-1 is regulated by BTRC in the cytoplasm and on membranes. These novel insights into the regulation of human Lipin-1 stability will be useful in planning further studies to elucidate its metabolic processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Loss of NR2E3 represses AHR by LSD1 reprogramming, is associated with poor prognosis in liver cancer.

PubMed

Khanal, Tilak; Choi, Kwangmin; Leung, Yuet-Kin; Wang, Jiang; Kim, Dasom; Janakiram, Vinothini; Cho, Sung-Gook; Puga, Alvaro; Ho, Shuk-Mei; Kim, Kyounghyun

2017-09-06

The aryl hydrocarbon receptor (AHR) plays crucial roles in inflammation, metabolic disorder, and cancer. However, the molecular mechanisms regulating AHR expression remain unknown. Here, we found that an orphan nuclear NR2E3 maintains AHR expression, and forms an active transcriptional complex with transcription factor Sp1 and coactivator GRIP1 in MCF-7 human breast and HepG2 liver cancer cell lines. NR2E3 loss promotes the recruitment of LSD1, a histone demethylase of histone 3 lysine 4 di-methylation (H3K4me2), to the AHR gene promoter region, resulting in repression of AHR expression. AHR expression and responsiveness along with H3K4me2 were significantly reduced in the livers of Nr2e3 rd7 (Rd7) mice that express low NR2E3 relative to the livers of wild-type mice. SP2509, an LSD1 inhibitor, fully restored AHR expression and H3K4me2 levels in Rd7 mice. Lastly, we demonstrated that both AHR and NR2E3 are significantly associated with good clinical outcomes in liver cancer. Together, our results reveal a novel link between NR2E3, AHR, and liver cancer via LSD1-mediated H3K4me2 histone modification in liver cancer development.

Observation of e + e → Φ χ c 1 and Φ χ c 2 at s = 4.600 GeV

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

Ablikim, M.; Achasov, M. N.; Ahmed, S.

Using a data sample collected with the BESIII detector operating at the BEPCII storage ring at a centerof- mass energy of √s = 4.600 GeV, we search for the production of e +e - → φχ c0,1,2. A search is also performed for the charmonium-like state X(4140) in the radiative transition e +e - → γX(4140) with X(4140) subsequently decaying into φJ/ψ. The processes e +e - → φχ c1 and φχ c2 are observed for the first time, each with a statistical significance ofmore than 10σ, and the Born cross sections are measuredmore » to be (4.2+1.7 -1.0±0.3) pb and (6.7+3.4 -1.7 ± 0.5) pb, respectively, where the first uncertainties are statistical and the second systematic. No significant signals are observed for e +e - → φχ c0 and e +e - → γX(4140) and upper limits on the Born cross sections at 90% confidence level are provided at √s = 4.600 GeV.« less

Observation of e + e → Φ χ c 1 and Φ χ c 2 at s = 4.600 GeV

DOE PAGES

Ablikim, M.; Achasov, M. N.; Ahmed, S.; ...

2018-02-12

Using a data sample collected with the BESIII detector operating at the BEPCII storage ring at a centerof- mass energy of √s = 4.600 GeV, we search for the production of e +e - → φχ c0,1,2. A search is also performed for the charmonium-like state X(4140) in the radiative transition e +e - → γX(4140) with X(4140) subsequently decaying into φJ/ψ. The processes e +e - → φχ c1 and φχ c2 are observed for the first time, each with a statistical significance ofmore than 10σ, and the Born cross sections are measuredmore » to be (4.2+1.7 -1.0±0.3) pb and (6.7+3.4 -1.7 ± 0.5) pb, respectively, where the first uncertainties are statistical and the second systematic. No significant signals are observed for e +e - → φχ c0 and e +e - → γX(4140) and upper limits on the Born cross sections at 90% confidence level are provided at √s = 4.600 GeV.« less

Functional characterization of DnSIZ1, a SIZ/PIAS-type SUMO E3 ligase from Dendrobium.

PubMed

Liu, Feng; Wang, Xiao; Su, Mengying; Yu, Mengyuan; Zhang, Shengchun; Lai, Jianbin; Yang, Chengwei; Wang, Yaqin

2015-09-17

SUMOylation is an important post-translational modification of eukaryotic proteins that involves the reversible conjugation of a small ubiquitin-related modifier (SUMO) polypeptide to its specific protein substrates, thereby regulating numerous complex cellular processes. The PIAS (protein inhibitor of activated signal transducers and activators of transcription [STAT]) and SIZ (scaffold attachment factor A/B/acinus/PIAS [SAP] and MIZ) proteins are SUMO E3 ligases that modulate SUMO conjugation. The characteristic features and SUMOylation mechanisms of SIZ1 protein in monocotyledon are poorly understood. Here, we examined the functions of a homolog of Arabidopsis SIZ1, a functional SIZ/PIAS-type SUMO E3 ligase from Dendrobium. In Dendrobium, the predicted DnSIZ1 protein has domains that are highly conserved among SIZ/PIAS-type proteins. DnSIZ1 is widely expressed in Dendrobium organs and has a up-regulated trend by treatment with cold, high temperature and wounding. The DnSIZ1 protein localizes to the nucleus and shows SUMO E3 ligase activity when expressed in an Escherichia coli reconstitution system. Moreover, ectopic expression of DnSIZ1 in the Arabidopsis siz1-2 mutant partially complements several phenotypes and results in enhanced levels of SUMO conjugates in plants exposed to heat shock conditions. We observed that DnSIZ1 acts as a negative regulator of flowering transition which may be via a vernalization-induced pathway. In addition, ABA-hypersensitivity of siz1-2 seed germination can be partially suppressed by DnSIZ1. Our results suggest that DnSIZ1 is a functional homolog of the Arabidopsis SIZ1 with SUMO E3 ligase activity and may play an important role in the regulation of Dendrobium stress responses, flowering and development.

Dual Roles of β-Oxodithioesters in the Copper-Catalyzed Synthesis of Benzo[e]pyrazolo[1,5-c][1,3]thiazine Derivatives.

PubMed

Wen, Li-Rong; Yuan, Wen-Kui; Li, Ming

2015-05-15

A facile and efficient method for the chemoselective synthesis of benzo[e]pyrazolo[1,5-c][1,3]thiazine derivatives has been developed by tandem Ullmann coupling reactions of β-oxodithioesters (ODEs) with 3-(2-bromoaryl)-1H-pyrazoles in C-S bond formation manner, in which ODEs play dual roles as both a substrate and a ligand. A series of benzo[e]pyrazolo[1,5-c][1,3]thiazine derivatives were provided in good to excellent yields with CuI as the copper source in the presence of NaOH in CH3CN at 80 °C under a N2 atmosphere.

Atmospheric volatilization and distribution of (Z)- and (E)-1,3-dichloropropene in field beds with and without plastic covers.

PubMed

Thomas, John E; Allen, L Hartwell; McCormack, Leslie A; Vu, Joseph C; Dickson, Donald W; Ou, Li-Tse

2004-01-01

The fumigant 1,3-dichloropropene (1,3-D) is considered to be a potential replacement for methyl bromide when methyl bromide is phased out in 2005. This study on surface emissions and subsurface diffusion of 1,3-D in a Florida sandy soil was conducted in field beds with or without plastic covers. After injection of the commercial fumigant Telone II by conventional chisels to field beds at 30cm depth which were covered with polyethylene film (PE), virtually impermeable film, or no cover (bare), (Z)- and (E)-1,3-D rapidly diffused upward. Twenty hours after injection, majority of (Z)- and (E)-1,3-D had moved upward from 30 cm depth to the layer of 5-20 cm depth. Downward movement of the two isomers in the beds with or without a plastic cover was not significant. (Z)-1,3-D diffused more rapidly than (E)-1,3-D. Virtually impermeable films (VIF) had a good capacity to retain (Z)- and (E)-1,3-D in soil pore air space. Vapor concentrations of the two isomers in the shallow subsurface of the field bed covered with VIF were greater than that in the two beds covered with polyethylene film (PE) or no cover (bare). In addition, VIF cover provided more uniform distribution of (Z)- and (E)-1,3-D in shallow subsurface than PE cover or no cover. Virtually impermeable film also had a better capability to retard surface emissions of the two isomers from soil in field beds than PE cover or no cover.

GENOTOXICITY OF 1,3-DICHLOROPROPANE, 2,2-DICHLOROPROPANE, AND L,1-DICHLOROPROPENE IN SALMONELLA AND E. COLI PROPHAGE-INDUCTION ASSAYS

EPA Science Inventory

Genotoxicity of 1,3-Dichloropropane, 2,2-Dichloropropane, and 1,1-Dichloropropene in
Salmonella and E. coli Prophage-Induction Assays

1,3-Dichloropropane (1,3-DCP), 2,2-dichloropropane (2,2-DCP), and 1,1- dichloropropene (I,I-DCP) have been detected in ground water i...

Rotenone Induction of Hydrogen Peroxide Inhibits mTOR-mediated S6K1 and 4E-BP1/eIF4E Pathways, Leading to Neuronal Apoptosis

PubMed Central

Zhou, Qian; Liu, Chunxiao; Liu, Wen; Zhang, Hai; Zhang, Ruijie; Liu, Jia; Zhang, Jinfei; Xu, Chong; Liu, Lei; Huang, Shile; Chen, Long

2015-01-01

Rotenone, a common pesticide and inhibitor of mitochondrial complex I, induces loss of dopaminergic neurons and consequential aspects of Parkinson’s disease (PD). However, the exact mechanism of rotenone neurotoxicity is not fully elucidated. Here, we show that rotenone induced reactive oxygen species (ROS), leading to apoptotic cell death in PC12 cells and primary neurons. Pretreatment with catalase (CAT), a hydrogen peroxide-scavenging enzyme, attenuated rotenone-induced ROS and neuronal apoptosis, implying hydrogen peroxide (H2O2) involved, which was further verified by imaging intracellular H2O2 using a peroxide-selective probe H2DCFDA. Using thenoyltrifluoroacetone (TTFA), antimycin A, or Mito-TEMPO, we further demonstrated rotenone-induced mitochondrial H2O2-dependent neuronal apoptosis. Rotenone dramatically inhibited mTOR-mediated phosphorylation of S6K1 and 4E-BP1, which was also attenuated by CAT in the neuronal cells. Of interest, ectopic expression of wild-type mTOR or constitutively active S6K1, or downregulation of 4E-BP1 partially prevented rotenone-induced H2O2 and cell apoptosis. Furthermore, we noticed that rotenone-induced H2O2 was linked to the activation of caspase-3 pathway. This was evidenced by the finding that pretreatment with CAT partially blocked rotenone-induced cleavages of caspase-3 and poly (ADP-ribose) polymerase. Of note, zVAD-fmk, a pan caspase inhibitor, only partially prevented rotenone-induced apoptosis in PC12 cells and primary neurons. Expression of mTOR-wt, S6K1-ca, or silencing 4E-BP1 potentiated zVAD-fmk protection against rotenone-induced apoptosis in the cells. The results indicate that rotenone induction of H2O2 inhibits mTOR-mediated S6K1 and 4E-BP1/eIF4E pathways, resulting in caspase-dependent and -independent apoptosis in neuronal cells. Our findings suggest that rotenone-induced neuronal loss in PD may be prevented by activating mTOR signaling and/or administering antioxidants. PMID:25304210

Influence of MC3T3-E1 preosteoblast culture on the corrosion of a T6-treated AZ91 alloy.

PubMed

Brooks, Emily K; Tobias, Menachem E; Yang, Shuying; Bone, Lawrence B; Ehrensberger, Mark T

2016-02-01

This study investigated the corrosion of artificially aged T6 heat-treated Mg-9%Al-1%Zn (AZ91) for biomedical applications. Corrosion tests and surface analysis were completed both with and without a monolayer of mouse preosteoblast MC3T3-E1 cells cultured on the sample. Electrochemical impedance spectroscopy (EIS) and inductively coupled plasma mass spectroscopy (ICPMS) were used to explore the corrosion processes after either 3 or 21 days of AZ91 incubation in cell culture medium (CCM). The EIS showed both the inner layer resistance (Rin ) and outer layer resistance (Rout ) were lower for samples without cells cultured on the surface at 3 days (Rin  = 2.64 e4 Ω/cm(2) , Rout  = 140 Ω/cm(2) ) compared to 21 days (Rin  = 3.60 e4 Ω/cm(2) , Rout  = 287 Ω/cm(2) ) due to precipitation of magnesium and calcium phosphates over time. Samples with preosteoblasts cultured on the surface had a slower initial corrosion (3 day, Rin  = 1.88 e5 Ω/cm(2) , Rout  = 1060 Ω/cm(2) ) which was observed to increase over time (21 day, Rin  = 2.99 e4 Ω/cm(2) , Rout  = 287 Ω/cm(2) ). Changes in the corrosion processes were thought to be related to changes in the coverage provided by the cell layer. Our results reveal that the presence of cells and biological processes are able to significantly influence the corrosion rate of AZ91. © 2015 Wiley Periodicals, Inc.

MC3T3-E1 cell response to stainless steel 316L with different surface treatments.

PubMed

Zhang, Hongyu; Han, Jianmin; Sun, Yulong; Huang, Yongling; Zhou, Ming

2015-11-01

In the present study, stainless steel 316L samples with polishing, aluminum oxide blasting, and hydroxyapatite (HA) coating were prepared and characterized through a scanning electron microscope (SEM), optical interferometer (surface roughness, Sq), contact angle, surface composition and phase composition analyses. Osteoblast-like MC3T3-E1 cell adhesion on the samples was investigated by cell morphology using a SEM (4h, 1d, 3d, 7d), and cell proliferation was assessed by MTT method at 1d, 3d, and 7d. In addition, adsorption of bovine serum albumin on the samples was evaluated at 1h. The polished sample was smooth (Sq: 1.8nm), and the blasted and HA coated samples were much rougher (Sq: 3.2μm and 7.8μm). Within 1d of incubation, the HA coated samples showed the best cell morphology (e.g., flattened shape and complete spread), but there was no significant difference after 3d and 7d of incubation for all the samples. The absorbance value for the HA coated samples was the highest after 1d and 3d of incubation, indicating better cell viability. However, it reduced to the lowest value at 7d. Protein adsorption on the HA coated samples was the highest at 1h. The results indicate that rough stainless steel surface improves cell adhesion and morphology, and HA coating contributes to superior cell adhesion, but inhibits cell proliferation. Copyright © 2015. Published by Elsevier B.V.

High glucose impaired estrogen receptor alpha signaling via β-catenin in osteoblastic MC3T3-E1.

PubMed

Wang, Rui; Gao, Dong; Zhou, Yin; Chen, Lu; Luo, Bin; Yu, Yanrong; Li, Hao; Hu, Jiawei; Huang, Qiren; He, Ming; Peng, Weijie; Luo, Dan

2017-11-01

Diabetic Mellitus is a risk factor for osteoporosis. It has been suggested that altered estrogen or estrogen receptor α/β (ERα/β) signaling may be involved in diabetic osteoporosis. The present study is to investigate the effects of high glucose on ERα/β signaling in osteoblastic MC3T3-E1 and how the altered signaling of ERα/β affect osteoblastic bone formation. ERα/β signaling was demonstrated as ERα/β protein expression (Western Blotting) and ER transcription activity (Luciferase Reporter assays). Proliferation (WSK-1 assaying), differentiation (ALP staining) and mineralization (Alizalard Red staining) of MC3T3-E1 were examined to evaluate bone formation function. It has been found that high glucose increased ERα/β expression dose-dependently and time-dependently, but high glucose (33mM) decreased ERα transcription activity. 17β-estradiol increased the ERα/β expression dose-dependently in normal medium, but decreased the ERα/β expression dose-dependently in medium with high glucose (33mM). High glucose decreased bone formation and also decreased the osteogenic effects of 17β-estradiol (10 -8 M). High glucose decreased β-catenin expression dose-dependently and time-dependently. LiCl, an inhibitor of β-catenin degradation, decreased ERα expression but increased ERα transcription activity. When compared with high glucose treatment, LiCl (5mM) increased ALP activity and calcified nodes. Besides, high glucose also decreased the protein expression PI-3K, pAKT/AKT, GSK-3β. In conclusion, the present study suggested that high glucose may impair ERα transcription activity by inhibiting β-catenin signaling in osteoblastic MC3T3-E1, leading decreased bone formation ligand-dependently or ligand-independently. Copyright © 2017 Elsevier Ltd. All rights reserved.

47 CFR 12.3 - 911 and E911 analyses and reports.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 1 2012-10-01 2012-10-01 false 911 and E911 analyses and reports. 12.3 Section 12.3 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL REDUNDANCY OF COMMUNICATIONS SYSTEMS § 12.3 911 and E911 analyses and reports. The following entities must analyze their 911 and E911...

Decoy Wnt receptor (sLRP6E1E2)-expressing adenovirus induces anti-fibrotic effect via inhibition of Wnt and TGF-β signaling.

PubMed

Lee, Won Jai; Lee, Jung-Sun; Ahn, Hyo Min; Na, Youjin; Yang, Chae Eun; Lee, Ju Hee; Hong, JinWoo; Yun, Chae-Ok

2017-11-08

Aberrant activation of the canonical Wingless type (Wnt) signaling pathway plays a key role in the development of hypertrophic scars and keloids, and this aberrant activation of Wnt pathway can be a potential target for the development of novel anti-fibrotic agents. In this study, we evaluated the anti-fibrotic potential of a soluble Wnt decoy receptor (sLRP6E1E2)-expressing non-replicating adenovirus (Ad; dE1-k35/sLRP6E1E2) on human dermal fibroblasts (HDFs), keloid fibroblasts (KFs), and keloid tissue explants. Higher Wnt3a and β-catenin expression was observed in the keloid region compared to the adjacent normal tissues. The activity of β-catenin and mRNA expression of type-I and -III collagen were significantly decreased following treatment with dE1-k35/sLRP6E1E2 in HDFs and KFs. The expression of LRP6, β-catenin, phosphorylated glycogen synthase kinase 3 beta, Smad 2/3 complex, and TGF-β1 were decreased in Wnt3a- or TGF-β1-activated HDFs, following administration of dE1-k35/sLRP6E1E2. Moreover, dE1-k35/sLRP6E1E2 markedly inhibited nuclear translocation of both β-catenin and Smad 2/3 complex. The expression levels of type-I and -III collagen, fibronectin, and elastin were also significantly reduced in keloid tissue explants after treatment with dE1-k35/sLRP6E1E2. These results indicate that Wnt decoy receptor-expressing Ad can degrade extracellular matrix in HDFs, KFs, and primary keloid tissue explants, and thus it may be beneficial for treatment of keloids.

Rates of E1, E2, M1, and M2 transitions in Ni II

NASA Astrophysics Data System (ADS)

Cassidy, C. M.; Hibbert, A.; Ramsbottom, C. A.

2016-03-01

Aims: We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive configuration interaction calculation. Methods: The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results: Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions: We believe that the present transition data are the best currently available. Full Table 4 and Tables 5-8 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/587/A107

Impact of e-liquid flavors on e-cigarette vaping behavior.

PubMed

St Helen, Gideon; Shahid, Marian; Chu, Sherman; Benowitz, Neal L

2018-05-31

The primary objective of this pilot study was to describe the impact of e-cigarette liquid flavors on experienced e-cigarette users' vaping behavior. 11 males and 3 females participated in a 3-day inpatient crossover study using e-cigarettes with strawberry, tobacco, and their usual brand e-liquid. Nicotine levels were nominally 18 mg/mL in the strawberry and tobacco e-liquids and ranged between 3-18 mg/mL in the usual brands. On each day, participants had access to the study e-cigarette (KangerTech mini ProTank 3, 1.5 Ohms, 3.7 V) and the assigned e-liquid during a 90-minute videotaped ad libitum session. Average puff duration was significantly longer when using the strawberry e-liquid (3.2 ± 1.3 s, mean ± SD) compared to the tobacco e-liquid (2.8 ± 1.1 s) but the average number of puffs was not significantly different (strawberry, 73 ± 35; tobacco, 69 ± 46). Compared to the strawberry- and tobacco-flavored e-liquids, average puff duration was significantly longer (4.3 ± 1.6 s) and the average number of puffs was significantly higher (106 ± 67 puffs) when participants used their usual brand of e-liquid. Participants generally puffed more frequently in small groups of puffs (1-5 puffs) with the strawberry compared to the tobacco e-liquid and more frequently in larger groups (>10 puffs) with their usual brand. The strength of the relationship between vaping topography and nicotine intake and exposure were not consistent across e-liquids. Vaping behavior changes across e-liquids and influences nicotine intake. Research is needed to understand the mechanisms that underlie these behavioral changes, including e-liquid pH and related sensory effects, subjective liking, and nicotine effects. Copyright © 2018. Published by Elsevier B.V.

Helicopter Flying Qualities Characteristics-CH-46E. Volume 1

DTIC Science & Technology

1983-10-03

STABILITY 54 6.0 CONTROL SENSITIVITY 61 . ° i CONTENTS (continued) Page 7.0 TIME HISTORY DATA 65 7.1 GENERAL 65 7.2 DYNAMIC STABILITY 65 7.3 CONTROL...The CH-46E meets these requirements by comfortable margins at the conditions tested. 61 NADC-81118-60 Volume 1 CH-46E (FRB, CONTROL IESPON!SE CH-46E...0 4.- ip L% t ,. _ 5" * ,.4 ••t, EFIGURE 7-5 I 7 ----- 1 FIU- - IA2 NADC-81118-6 Volume I-- .4 . > b in Zh. JI - ag4A 19-- O e t’ c 4 a I,- t

Functional Characterization of the Role of the N-terminal Domain of the c/Nip1 Subunit of Eukaryotic Initiation Factor 3 (eIF3) in AUG Recognition*

PubMed Central

Karásková, Martina; Gunišová, Stanislava; Herrmannová, Anna; Wagner, Susan; Munzarová, Vanda; Valášek, Leoš Shivaya

2012-01-01

In eukaryotes, for a protein to be synthesized, the 40 S subunit has to first scan the 5′-UTR of the mRNA until it has encountered the AUG start codon. Several initiation factors that ensure high fidelity of AUG recognition were identified previously, including eIF1A, eIF1, eIF2, and eIF5. In addition, eIF3 was proposed to coordinate their functions in this process as well as to promote their initial binding to 40 S subunits. Here we subjected several previously identified segments of the N-terminal domain (NTD) of the eIF3c/Nip1 subunit, which mediates eIF3 binding to eIF1 and eIF5, to semirandom mutagenesis to investigate the molecular mechanism of eIF3 involvement in these reactions. Three major classes of mutant substitutions or internal deletions were isolated that affect either the assembly of preinitiation complexes (PICs), scanning for AUG, or both. We show that eIF5 binds to the extreme c/Nip1-NTD (residues 1–45) and that impairing this interaction predominantly affects the PIC formation. eIF1 interacts with the region (60–137) that immediately follows, and altering this contact deregulates AUG recognition. Together, our data indicate that binding of eIF1 to the c/Nip1-NTD is equally important for its initial recruitment to PICs and for its proper functioning in selecting the translational start site. PMID:22718758

Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice.

PubMed

Rasmiena, Aliki A; Barlow, Christopher K; Stefanovic, Nada; Huynh, Kevin; Tan, Ricardo; Sharma, Arpeeta; Tull, Dedreia; de Haan, Judy B; Meikle, Peter J

2015-12-01

We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress. Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P = 5.69E-07) and 69% (P = 2.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P = 7.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P = 2.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P = 5.11E-06) in the aorta. Plasmalogen enrichment via batyl alcohol supplementation attenuated atherosclerosis in ApoE- and ApoE/GPx1-deficient mice, with a greater effect in the latter group. Plasmalogen enrichment may represent a viable therapeutic strategy to prevent atherosclerosis and reduce cardiovascular disease risk, particularly under conditions of elevated oxidative stress and inflammation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Anti-E1E2 antibodies status prior therapy favors direct-acting antiviral treatment efficacy.

PubMed

Virlogeux, Victor; Berthillon, Pascale; Bordes, Isabelle; Larrat, Sylvie; Crouy, Stéphanie; Scholtès, Caroline; Pradat, Pierre; Maynard, Marianne; Zoulim, Fabien; Leroy, Vincent; Chemin, Isabelle; Trépo, Christian; Petit, Marie-Anne

2018-03-15

Presence of anti-E1E2 antibodies was previously associated with spontaneous cure of hepatitis C virus (HCV) and predictive before treatment of a sustained virological response (SVR) to bi- or tri-therapy in naïve or experienced patients, regardless of HCV genotype. We investigated the impact of anti-E1E2 seroprevalence at baseline on treatment response in patients receiving direct-acting antiviral (DAA) therapy. We screened anti-E1E2 antibodies by ELISA in serum samples collected at treatment initiation for two groups of patients: 59 with SVR at the end of DAA treatment and 44 relapsers after DAA treatment. Nineteen patients received a combination of ribavirin (RBV) or PEG-interferon/ribavirin with sofosbuvir or daclatasvir and others received interferon-free treatment with DAA±RBV. HCV viral load was measured at different time points during treatment in a subgroup of patients. A significant association was observed between presence of anti-E1E2 and HCV viral load<6log10 prior treatment. Among patients with anti-E1E2 at baseline, 70% achieved SVR whereas among patients without anti-E1E2, only 45% achieved SVR. Conversely, 66% of patients experiencing DAA-failure were anti-E1E2 negative at baseline. In the multivariate analysis, presence of anti-E1E2 was significantly associated with SVR after adjustment on potential cofounders such as age, sex, fibrosis stage, prior HCV treatment and alanine aminotransferase (ALT) level. The presence of anti-E1E2 at treatment initiation is a predictive factor of SVR among patients treated with DAA and more likely among patients with low initial HCV viral load (<6log10). Absence of anti-E1E2 at baseline could predict DAA-treatment failure. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Cooperative transformation and coexpression of bovine papillomavirus type 1 E5 and E7 proteins.

PubMed

Bohl, J; Hull, B; Vande Pol, S B

2001-01-01

Productively infected bovine fibropapillomas were examined for bovine papillomavirus type 1 (BPV-1) E7 localization. BPV-1 E7 was observed in the cytoplasm of basal and lower spinous epithelial cells, coexpressed in the cytoplasm of basal cells with the E5 oncoprotein. E7 was also observed in nucleoli throughout the basal and spinous layers but not in the granular cell layer. Ectopic expression of E7 in cultured epithelial cells gave rise to localization similar to that seen in productive fibropapillomas, with cytoplasmic and nucleolar expression observed. Consistent with the coexpression of E7 and E5 in basal keratinocytes, BPV-1 E7 cooperated with E5 as well as E6 in an anchorage independence transformation assay. While E5 is expressed in both basal and superficial differentiating keratinocytes, BPV-1 E7 is only observed in basal and lower spinous epithelial cells. Therefore, BPV-1 E7 may serve to modulate the cellular response of basal epithelial cells to E5 expression.

Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases.

PubMed

Boomsma, Wouter; Nielsen, Sofie V; Lindorff-Larsen, Kresten; Hartmann-Petersen, Rasmus; Ellgaard, Lars

2016-01-01

The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2 ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology of their ordered regions, and did not capture the unique disorder patterns that encode the functional mechanism of San1. However, by searching specifically for key features of the San1 sequence, such as long regions of intrinsic disorder embedded with short stretches predicted to be suitable for substrate interaction, we identified several E3 ligases with these characteristics. Our initial analysis revealed that another remarkable trait of San1 is shared with several candidate E3 ligases: long stretches of complete lysine suppression, which in San1 limits auto-ubiquitination. We encode these characteristic features into a San1 similarity-score, and present a set of proteins that are plausible candidates as San1 counterparts in humans. In conclusion, our work indicates that San1 is

Word Frequency Analysis MOS: 15E. Skill Levels 1 and 2.

DTIC Science & Technology

1982-05-01

AR 34 ARE I I AREA1 L 5 15 ARM 1 .: 𔃻A’FNT 3 AROL D 25 AS 12 ASSEI 3LE 12 ASSEPALED11 iES b8 ASSEMBLY 4 ASSISTA CE27 ASSISTANT13 1’A T . SSISTED 29 ...CABLE31 CA3Lr.P 2, C.ABLES . . 1 L.BLI"IG I CAM C>; 4 CA’"UT 2 CANvA S 29 CAP2 CYPSCRE ,S 4 CAPTIVE A , L I AR o,7 CAREFiULLY .... CARRY IG 2 LA.TELL 1...1 (l. 5 1 jS I E (f r I FR I 5 IP E V PEET ~ (F I 4 3 E X P N A WL S q 6 XPL11S VE E EXPIUSIVS I z~ SE 17 *.!GU I 5 EXTE nrEC 3 WI’S1. lltj 3 29 ~Il

The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

PubMed Central

Marlowe, Jennifer L.; Fan, Yunxia; Chang, Xiaoqing; Peng, Li; Knudsen, Erik S.; Xia, Ying

2008-01-01

Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr−/− fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, γH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of E2F1 expression. In contrast, ligand-dependent AHR activation protects these cells from etoposide-induced cell death. In cells expressing both proteins, AHR and E2F1 interact independently of the retinoblastoma protein (RB), because AHR and E2F1 coimmunoprecipitate from extracts of RB-negative cells. Additionally, chromatin immunoprecipitation assays indicate that AHR and E2F1 bind to the Apaf1 promoter at a region containing a consensus E2F1 binding site but no AHR binding sites. AHR activation represses Apaf1 and TAp73 mRNA induction by a constitutively active CHK2 expression vector. Furthermore, AHR overexpression blocks the transcriptional induction of Apaf1 and p73 and the accumulation of sub-G0/G1 cells resulting from ectopic overexpression of E2F1. These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression. PMID:18524851

Process for Biotransformation of Androsta-4-ene-3, 17-Dione (4-AD) to Androsta-1,4-Diene-3,17-Dione (ADD).

PubMed

Prakash, Surya; Bajaj, Abhay

2017-01-01

Androsta-1,4-diene-3,17-dione (androstadienedione, ADD) is key intermediate for the organic synthesis of a variety of female sex hormones such as estrone, estradiol, estriol and other related derivatives. De novo synthesis of this molecule is not yet reported in any form of living system, i.e., microbial, plant, and animal. The structural complexities due to presence of several chiral carbon centers create significant hurdles in chemical synthesis of such molecules. Microbe-mediated biotransformation offer a highly reliable, cost-effective, and relatively non hazardous way for commercial manufacturing of steroidal key intermediates. Currently microbial biotransformations are extensively being exploited for large-scale production of basic intermediates such as androstenedione (AD), ADD, and several types of hydroxylated derivatives of androstane compounds. In this chapter several aspects of microbial biotransformation process of AD to ADD are discussed.

Maple syrup urine disease: The E1{beta} gene of human branched-chain {alpha}-ketoacid dehydrogenase complex has 11 rather than 10 exons, and the 3{prime} UTR in one of the two E1{beta} mRNAs arises from intronic sequences

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

Chuang, J.L.; Chuang, D.T.; Cox, R.P.

1996-06-01

Maple syrup urine disease (MSUD) or branched-chain ketoaciduria is caused by a deficiency in the mitochondrial branched-chain {alpha}-ketoacid dehydrogenase (BCKAD) complex. The clinical manifestations are characterized by accumulation of branched chain amino and {alpha}-ketoacids, which leads to severe cerebral edema with seizures, ketoacidosis, and mental retardation. The BCKAD complex comprises three catalytic components, i.e., a decarboxylase (E1) consisting of two E1{alpha} (M{sub r} = 46,000) and two E1{Beta} (M{sub r} = 37,500) subunits, a transacylase (E2) that contains 24 lipoic acid-bearing subunits, and a dehydrogenase (E3), which is a homodimeric flavoprotein. MSUD is genetically heterogeneous, since mutations in the E1{alpha}more » subunit (type IA MSUD), the E1{Beta} subunit (type IB), the E2 subunit (type II) and the E3 subunit (type III) have been described. The functional consequences of certain mutations in the BCKAD complex have been studied. 23 refs., 3 figs.« less

E3 Success Story - E3 Southwest Virginia: Economy, Energy and the Environment

EPA Pesticide Factsheets

E3 Southwest Virginia supports sustainable manufacturing in 17 counties in southwest Virginia. The MTC provides manufacturers with assessments of production processes to reduce their energy consumption and drive innovation.

Nuclear Receptor Rev-erb Alpha (Nr1d1) Functions in Concert with Nr2e3 to Regulate Transcriptional Networks in the Retina

PubMed Central

Mollema, Nissa J.; Yuan, Yang; Jelcick, Austin S.; Sachs, Andrew J.; von Alpen, Désirée; Schorderet, Daniel; Escher, Pascal; Haider, Neena B.

2011-01-01

The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated by genes such as nuclear hormone receptors. The nuclear hormone receptor gene Rev-erb alpha/Nr1d1 has been widely studied for its role in the circadian cycle and cell metabolism, however its role in the retina is unknown. In order to understand the role of Rev-erb alpha/Nr1d1 in the retina, we evaluated the effects of loss of Nr1d1 to the developing retina and its co-regulation with the photoreceptor-specific nuclear receptor gene Nr2e3 in the developing and mature retina. Knock-down of Nr1d1 expression in the developing retina results in pan-retinal spotting and reduced retinal function by electroretinogram. Our studies show that NR1D1 protein is co-expressed with NR2E3 in the outer neuroblastic layer of the developing mouse retina. In the adult retina, NR1D1 is expressed in the ganglion cell layer and is co-expressed with NR2E3 in the outer nuclear layer, within rods and cones. Several genes co-targeted by NR2E3 and NR1D1 were identified that include: Nr2c1, Recoverin, Rgr, Rarres2, Pde8a, and Nupr1. We examined the cyclic expression of Nr1d1 and Nr2e3 over a twenty-four hour period and observed that both nuclear receptors cycle in a similar manner. Taken together, these studies reveal a novel role for Nr1d1, in conjunction with its cofactor Nr2e3, in regulating transcriptional networks critical for photoreceptor development and function. PMID:21408158

Observation of e+e-→ϕ χc 1 and ϕ χc 2 at √{s }=4.600 GeV

NASA Astrophysics Data System (ADS)

Ablikim, M.; Achasov, M. N.; Ahmed, S.; Albrecht, M.; Amoroso, A.; An, F. F.; An, Q.; Bai, J. Z.; Bai, Y.; Bakina, O.; Baldini Ferroli, R.; Ban, Y.; Bennett, D. W.; Bennett, J. V.; Berger, N.; Bertani, M.; Bettoni, D.; Bian, J. M.; Bianchi, F.; Boger, E.; Boyko, I.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chai, J.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, P. L.; Chen, S. J.; Chen, X. R.; Chen, Y. B.; Chu, X. K.; Cibinetto, G.; Dai, H. L.; Dai, J. P.; Dbeyssi, A.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; de Mori, F.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Dou, Z. L.; Du, S. X.; Duan, P. F.; Fang, J.; Fang, S. S.; Fang, Y.; Farinelli, R.; Fava, L.; Fegan, S.; Feldbauer, F.; Felici, G.; Feng, C. Q.; Fioravanti, E.; Fritsch, M.; Fu, C. D.; Gao, Q.; Gao, X. L.; Gao, Y.; Gao, Y. G.; Gao, Z.; Garzia, I.; Goetzen, K.; Gong, L.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guo, A. Q.; Guo, R. P.; Guo, Y. P.; Haddadi, Z.; Han, S.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, X. Q.; Heinsius, F. H.; Held, T.; Heng, Y. K.; Holtmann, T.; Hou, Z. L.; Hu, H. M.; Hu, T.; Hu, Y.; Huang, G. S.; Huang, J. S.; Huang, X. T.; Huang, X. Z.; Huang, Z. L.; Hussain, T.; Ikegami Andersson, W.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, X. S.; Jiang, X. Y.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Jin, Y.; Johansson, T.; Julin, A.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Ke, B. C.; Khan, T.; Khoukaz, A.; Kiese, P.; Kliemt, R.; Koch, L.; Kolcu, O. B.; Kopf, B.; Kornicer, M.; Kuemmel, M.; Kuessner, M.; Kuhlmann, M.; Kupsc, A.; Kühn, W.; Lange, J. S.; Lara, M.; Larin, P.; Lavezzi, L.; Leithoff, H.; Leng, C.; Li, C.; Li, Cheng; Li, D. M.; Li, F.; Li, F. Y.; Li, G.; Li, H. B.; Li, H. J.; Li, J. C.; Li, Jin; Li, K. J.; Li, Kang; Li, Ke; Li, Lei; Li, P. L.; Li, P. R.; Li, Q. Y.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Lin, D. X.; Liu, B.; Liu, B. J.; Liu, C. X.; Liu, D.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. M.; Liu, Huanhuan; Liu, Huihui; Liu, J. B.; Liu, J. P.; Liu, J. Y.; Liu, K.; Liu, K. Y.; Liu, Ke; Liu, L. D.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqing; Long, Y. F.; Lou, X. C.; Lu, H. J.; Lu, J. G.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, X. L.; Lyu, X. R.; Ma, F. C.; Ma, H. L.; Ma, L. L.; Ma, M. M.; Ma, Q. M.; Ma, T.; Ma, X. N.; Ma, X. Y.; Ma, Y. M.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, Y. J.; Mao, Z. P.; Marcello, S.; Meng, Z. X.; Messchendorp, J. G.; Mezzadri, G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Morales Morales, C.; Muchnoi, N. Yu.; Muramatsu, H.; Musiol, P.; Mustafa, A.; Nefedov, Y.; Nerling, F.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, S. L.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Pan, Y.; Papenbrock, M.; Patteri, P.; Pelizaeus, M.; Pellegrino, J.; Peng, H. P.; Peters, K.; Pettersson, J.; Ping, J. L.; Ping, R. G.; Pitka, A.; Poling, R.; Prasad, V.; Qi, H. R.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, N.; Qin, X. S.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Richter, M.; Ripka, M.; Rolo, M.; Rong, G.; Rosner, Ch.; Sarantsev, A.; Savrié, M.; Schnier, C.; Schoenning, K.; Shan, W.; Shao, M.; Shen, C. P.; Shen, P. X.; Shen, X. Y.; Sheng, H. Y.; Song, J. J.; Song, W. M.; Song, X. Y.; Sosio, S.; Sowa, C.; Spataro, S.; Sun, G. X.; Sun, J. F.; Sun, L.; Sun, S. S.; Sun, X. H.; Sun, Y. J.; Sun, Y. K.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, G. Y.; Tang, X.; Tapan, I.; Tiemens, M.; Tsednee, B.; Uman, I.; Varner, G. S.; Wang, B.; Wang, B. L.; Wang, D.; Wang, D. Y.; Wang, Dan; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, Meng; Wang, P.; Wang, P. L.; Wang, W. P.; Wang, X. F.; Wang, Y.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. Y.; Wang, Zongyuan; Weber, T.; Wei, D. H.; Weidenkaff, P.; Wen, S. P.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, L. J.; Wu, Z.; Xia, L.; Xia, Y.; Xiao, D.; Xiao, H.; Xiao, Y. J.; Xiao, Z. J.; Xie, Y. G.; Xie, Y. H.; Xiong, X. A.; Xiu, Q. L.; Xu, G. F.; Xu, J. J.; Xu, L.; Xu, Q. J.; Xu, Q. N.; Xu, X. P.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, Y. H.; Yang, H. J.; Yang, H. X.; Yang, L.; Yang, Y. H.; Yang, Y. X.; Ye, M.; Ye, M. H.; Yin, J. H.; You, Z. Y.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yuan, C. Z.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zeng, Y.; Zeng, Z.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. L.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, K.; Zhang, L.; Zhang, S. Q.; Zhang, X. Y.; Zhang, Y. H.; Zhang, Y. T.; Zhang, Yang; Zhang, Yao; Zhang, Yu; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, J. Y.; Zhao, J. Z.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, W. J.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhou, Y. X.; Zhu, J.; Zhu, J.; Zhu, K.; Zhu, K. J.; Zhu, S.; Zhu, S. H.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zou, B. S.; Zou, J. H.; Besiii Collaboration

2018-02-01

Using a data sample collected with the BESIII detector operating at the BEPCII storage ring at a center-of-mass energy of √{s }=4.600 GeV , we search for the production of e+e-→ϕ χc 0 ,1 ,2 . A search is also performed for the charmonium-like state X (4140 ) in the radiative transition e+e-→γ X (4140 ) with X (4140 ) subsequently decaying into ϕ J /ψ . The processes e+e-→ϕ χc 1 and ϕ χc 2 are observed for the first time, each with a statistical significance of more than 10 σ , and the Born cross sections are measured to be (4. 2-1.0+1.7±0.3 ) and (6. 7-1.7+3.4±0.5 ) pb , respectively, where the first uncertainties are statistical and the second systematic. No significant signals are observed for e+e-→ϕ χc 0 and e+e-→γ X (4140 ) and upper limits on the Born cross sections at 90% C.L. are provided at √{s }=4.600 GeV .

Molecular structure and spectral properties of ethyl 3-quinolinecarboxylate (E3Q) and [Ag(E3Q)2(TCA)] complex (TCA = Trichloroacetate)

NASA Astrophysics Data System (ADS)

Soliman, Saied M.; Kassem, Taher S.; Badr, Ahmed M. A.; Abou Youssef, Morsy A.; Assem, Rania

2014-09-01

A new [Ag(E3Q)2(TCA)] complex; (E3Q = Ethyl 3-quinolinecarboxylate and TCA = Trichloroacetate) has been synthesized and characterized using elemental analysis, FTIR, NMR and mass spectroscopy. The molecular geometry and spectroscopic properties of the complex as well as the free ligand have been calculated using the hybrid B3LYP method. The calculations predicted a distorted tetrahedral arrangement around Ag(I) ion. The vibrational spectra of the studied compounds have been assigned using potential energy distribution (PED). TD-DFT method was used to predict the electronic absorption spectra. The most intense absorption band showed a bathochromic shift and lowering of intensity in case of the complex (233.7 nm, f = 0.5604) compared to E3Q (λmax = 228.0 nm, f = 0.9072). The calculated 1H NMR chemical shifts using GIAO method showed good correlations with the experimental data. The computed dipole moment, polarizability and HOMO-LUMO energy gap were used to predict the nonlinear optical (NLO) properties. It is found that Ag(I) enhances the NLO activity. The natural bond orbital (NBO) analyses were used to elucidate the intramolecular charge transfer interactions causing stabilization for the investigated systems.

Hepatitis E virus genotypes 1 and 3 in wastewater samples in Tunisia.

PubMed

Béji-Hamza, A; Hassine-Zaafrane, M; Khélifi-Gharbi, H; Della Libera, S; Iaconelli, M; Muscillo, M; Petricca, S; Ciccaglione, A R; Bruni, R; Taffon, S; Aouni, M; La Rosa, G

2015-01-01

Hepatitis E represents an important public-health concern throughout the world. It is one of the leading causes of hepatitis in North Africa, Asia and the Middle East. In Tunisia, the true burden of HEV infection is still unknown. The objectives of the present study were to assess the occurrence of hepatitis E virus in Tunisia through the monitoring of urban sewage and to characterize the strains identified using molecular assays. A total of 150 sewage samples (raw and treated) were collected from three wastewater treatment plants located in the regions of Monastir and Mahdia and analyzed by nested RT-PCR using a qualitative assay targeting the methyltransferase gene in ORF1. Of these, only three samples (2 %) were found to be positive for HEV, one belonging to genotype 1 and two to genotype 3. The results of the present study indicate a low level of virus excretion among the Tunisian population. Both genotypes 1 and 3 are circulating in this country, however, possibly causing sporadic infections. The presence of the zoonotic genotype 3, known to be transmitted to humans mainly by swine and demonstrated in Tunisia for the first time in this work, raises the question of possible reservoir species, since pork products are not consumed in this country, pigs are not bred, and wild boar is not endemic. Further studies will be needed to gather information on the occurrence and diversity of HEV strains circulating among humans and animals in Tunisia, and on possible animal reservoirs.

Evaluation of potential fitness costs associated with eCry3.1Ab resistance in Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae)

USDA-ARS?s Scientific Manuscript database

Both an eCry3.1Ab resistant and paired control western corn rootworm, Diabrotica virgifera virgifera colony were tested for adult longevity, egg oviposition, egg viability, and larval development in order to evaluate the potential fitness costs associated with eCry3.1Ab resistance in the western cor...

Doxycycline-Regulated 3T3-L1 Preadipocyte Cell Line with Inducible, Stable Expression of Adenoviral E4orf1 Gene: A Cell Model to Study Insulin-Independent Glucose Disposal

PubMed Central

Krishnapuram, Rashmi; Dhurandhar, Emily J.; Dubuisson, Olga; Hegde, Vijay; Dhurandhar, Nikhil V.

2013-01-01

Impaired glycemic control and excessive adiposity are major risk factors for Type 2 Diabetes mellitus. In rodent models, Ad36, a human adenovirus, improves glycemic control, independent of dietary fat intake or adiposity. It is impractical to use Ad36 for therapeutic action. Instead, we identified that E4orf1 protein of Ad36, mediates its anti-hyperglycemic action independent of insulin signaling. To further evaluate the therapeutic potential of E4orf1 to improve glycemic control, we established a stable 3T3-L1 cell system in which E4orf1 expression can be regulated. The development and characterization of this cell line is described here. Full-length adenoviral-36 E4orf1 cDNA obtained by PCR was cloned into a tetracycline responsive element containing vector (pTRE-Tight-E4orf1). Upon screening dozens of pTRE-Tight-E4orf1 clones, we identified the one with the highest expression of E4orf1 in response to doxycycline treatment. Furthermore, using this inducible system we characterized the ability of E4orf1 to improve glucose disposal in a time dependent manner. This stable cell line offers a valuable resource to carefully study the novel signaling pathways E4orf1 uses to enhance cellular glucose disposal independent of insulin. PMID:23544159

Doxycycline-regulated 3T3-L1 preadipocyte cell line with inducible, stable expression of adenoviral E4orf1 gene: a cell model to study insulin-independent glucose disposal.

PubMed

Krishnapuram, Rashmi; Dhurandhar, Emily J; Dubuisson, Olga; Hegde, Vijay; Dhurandhar, Nikhil V

2013-01-01

Impaired glycemic control and excessive adiposity are major risk factors for Type 2 Diabetes mellitus. In rodent models, Ad36, a human adenovirus, improves glycemic control, independent of dietary fat intake or adiposity. It is impractical to use Ad36 for therapeutic action. Instead, we identified that E4orf1 protein of Ad36, mediates its anti-hyperglycemic action independent of insulin signaling. To further evaluate the therapeutic potential of E4orf1 to improve glycemic control, we established a stable 3T3-L1 cell system in which E4orf1 expression can be regulated. The development and characterization of this cell line is described here. Full-length adenoviral-36 E4orf1 cDNA obtained by PCR was cloned into a tetracycline responsive element containing vector (pTRE-Tight-E4orf1). Upon screening dozens of pTRE-Tight-E4orf1 clones, we identified the one with the highest expression of E4orf1 in response to doxycycline treatment. Furthermore, using this inducible system we characterized the ability of E4orf1 to improve glucose disposal in a time dependent manner. This stable cell line offers a valuable resource to carefully study the novel signaling pathways E4orf1 uses to enhance cellular glucose disposal independent of insulin.

In-silico and in-vitro anti-cancer potential of a curcumin analogue (1E, 6E)-1, 7-di (1H-indol-3-yl) hepta-1, 6-diene-3, 5-dione.

PubMed

Sufi, Shamim Akhtar; Adigopula, Lakshmi Narayana; Syed, Safiulla Basha; Mukherjee, Victor; Coumar, Mohane S; Rao, H Surya Prakash; Rajagopalan, Rukkumani

2017-01-01

Previously we showed that BDMC, an analogue of curcumin suppresses growth of human breast and laryngeal cancer cell line by causing apoptosis. Here, we demonstrate the enhanced anti-cancer activity of a heterocyclic ring (indole) incorporated curcumin analogue ((1E, 6E)-1, 7-di (1H-indol-3-yl) hepta-1, 6-diene-3, 5-Dione), ICA in short, in comparison to curcumin. ICA was synthesized by a one pot condensation reaction. Anti-cancer potential of ICA was assessed in three human cancer cell lines of different origin (Lung adenocarcinoma (A549), leukemia (K562) and colon cancer (SW480)) by MTT assay. Mode of cell death was determined by acridine orange-ethidium bromide (Ao-Eb) staining. Putative cellular targets of ICA were investigated by molecular docking studies. Cell cycle analysis following curcumin or ICA treatment in SW480 cell line was carried out by flow cytometry. Expression levels of Cyclin D1 and apoptotic markers, such as Caspase 3, 8 and 9 were studied by western blot analysis in SW480 cell line treated with or without ICA and curcumin. The yield of ICA synthesis was found to be 69% with a purity of 98%. ICA demonstrated promising anti-cancer activity compared to curcumin alone, as discerned by MTT assay. ICA was non-toxic to the cell line of normal origin. We further observed that ICA is ∼2 fold more potent than curcumin in inhibiting the growth of SW480 cells. Ao-Eb staining revealed that ICA could induce apoptosis in all the cell lines tested. Molecular docking studies suggest that ICA may possibly exhibit its anticancer effect by inhibiting EGFR in A549, Bcr-Abl in K562 and GSK-3β kinase in SW480 cell line. Moreover, ICA showed strong binding avidity for Bcl-2 protein in silico, which could result in induction of apoptosis. Cell cycle analysis revealed that both curcumin and ICA induced concomitant cell cycle arrest at G0/G1 and G2/M phase. Western blot shows that ICA could effectively down regulate the expression of cell cycle protein cyclin D1

Picosecond excite-and-probe absorption measurement of the intra-2E(g)E(3/2)-state vibrational relaxation time in Ti(3+):Al2O3

NASA Technical Reports Server (NTRS)

Gayen, S. K.; Wang, W. B.; Petricevic, V.; Yoo, K. M.; Alfano, R. R.

1987-01-01

The Ti(3+)-doped Al2O3 has been recently demonstrated to be a tunable solid-state laser system with Ti(3+) as the laser-active ion. In this paper, the kinetics of vibrational transitions in the 2E(g)E(3/2) electronic state of Ti(3+):Al2O3a (crucial for characterizing new host materials for the Ti ion) was investigated. A 527-nm 5-ps pulse was used to excite a band of higher vibrational levels of the 2E(g)E(3/2) state, and the subsequent growth of population in the zero vibrational level and lower vibrational levels was monitored by a 3.9-micron picosecond probe pulse. The time evolution curve in the excited 2E(g)E(3/2) state at room temperature was found to be characterized by a sharp rise followed by a long decay, the long lifetime decay reflecting the depopulation of the zero and the lower vibrational levels of the 2E(g)E(3/2) state via radiative transitions. An upper limit of 3.5 ps was estimated for intra-2E(g)E(3/2)-state vibrational relaxation time.

Protein phosphatase PPM1G regulates protein translation and cell growth by dephosphorylating 4E binding protein 1 (4E-BP1).

PubMed

Liu, Jianyu; Stevens, Payton D; Eshleman, Nichole E; Gao, Tianyan

2013-08-09

Protein translation initiation is a tightly controlled process responding to nutrient availability and mitogen stimulation. Serving as one of the most important negative regulators of protein translation, 4E binding protein 1 (4E-BP1) binds to translation initiation factor 4E and inhibits cap-dependent translation in a phosphorylation-dependent manner. Although it has been demonstrated previously that the phosphorylation of 4E-BP1 is controlled by mammalian target of rapamycin in the mammalian target of rapamycin complex 1, the mechanism underlying the dephosphorylation of 4E-BP1 remains elusive. Here, we report the identification of PPM1G as the phosphatase of 4E-BP1. A coimmunoprecipitation experiment reveals that PPM1G binds to 4E-BP1 in cells and that purified PPM1G dephosphorylates 4E-BP1 in vitro. Knockdown of PPM1G in 293E and colon cancer HCT116 cells results in an increase in the phosphorylation of 4E-BP1 at both the Thr-37/46 and Ser-65 sites. Furthermore, the time course of 4E-BP1 dephosphorylation induced by amino acid starvation or mammalian target of rapamycin inhibition is slowed down significantly in PPM1G knockdown cells. Functionally, the amount of 4E-BP1 bound to the cap-dependent translation initiation complex is decreased when the expression of PPM1G is depleted. As a result, the rate of cap-dependent translation, cell size, and protein content are increased in PPM1G knockdown cells. Taken together, our study has identified protein phosphatase PPM1G as a novel regulator of cap-dependent protein translation by negatively controlling the phosphorylation of 4E-BP1.

Probability 1/e

ERIC Educational Resources Information Center

Koo, Reginald; Jones, Martin L.

2011-01-01

Quite a number of interesting problems in probability feature an event with probability equal to 1/e. This article discusses three such problems and attempts to explain why this probability occurs with such frequency.

Characterization of cytochrome P450 CYP109E1 from Bacillus megaterium as a novel vitamin D3 hydroxylase.

PubMed

Abdulmughni, Ammar; Jóźwik, Ilona K; Putkaradze, Natalia; Brill, Elisa; Zapp, Josef; Thunnissen, Andy-Mark W H; Hannemann, Frank; Bernhardt, Rita

2017-02-10

In this study the ability of CYP109E1 from Bacillus megaterium to metabolize vitamin D 3 (VD 3 ) was investigated. In an in vitro system using bovine adrenodoxin reductase (AdR) and adrenodoxin (Adx 4-108 ), VD 3 was converted by CYP109E1 into several products. Furthermore, a whole-cell system in B. megaterium MS941 was established. The new system showed a conversion of 95% after 24h. By NMR analysis it was found that CYP109E1 catalyzes hydroxylation of VD 3 at carbons C-24 and C-25, resulting in the formation of 24(S)-hydroxyvitamin D 3 (24S(OH)VD 3 ), 25-hydroxyvitamin D 3 (25(OH)VD 3 ) and 24S,25-dihydroxyvitamin D 3 (24S,25(OH) 2 VD 3 ). Through time dependent whole-cell conversion of VD 3 , we identified that the formation of 24S,25(OH) 2 VD 3 by CYP109E1 is derived from VD 3 via the intermediate 24S(OH)VD 3 . Moreover, using docking analysis and site-directed mutagenesis, we identified important active site residues capable of determining substrate specificity and regio-selectivity. HPLC analysis of the whole-cell conversion with the I85A-mutant revealed an increased selectivity towards 25-hydroxylation of VD 3 compared with the wild type activity, resulting in an approximately 2-fold increase of 25(OH)VD 3 production (45mgl -1 day -1 ) compared to wild type (24.5mgl -1 day -1 ). Copyright © 2017 Elsevier B.V. All rights reserved.

Physicochemical and biological characterization of 1E10 Anti-Idiotype vaccine

PubMed Central

2011-01-01

Background 1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH)3, in several clinical trials for melanoma, breast, and lung cancer. During early clinical development this mAb was obtained in vivo from mice ascites fluid. Currently, the production process of 1E10 is being transferred from the in vivo to a bioreactor-based method. Results Here, we present a comprehensive molecular and immunological characterization of 1E10 produced by the two different production processes in order to determine the impact of the manufacturing process in vaccine performance. We observed differences in glycosylation pattern, charge heterogeneity and structural stability between in vivo-produced 1E10 and bioreactor-obtained 1E10. Interestingly, these modifications had no significant impact on the immune responses elicited in two different animal models. Conclusions Changes in 1E10 primary structure like glycosylation; asparagine deamidation and oxidation affected 1E10 structural stability but did not affect the immune response elicited in mice and chickens when compared to 1E10 produced in mice. PMID:22108317

CYP2E1 Metabolism of Styrene Involves Allostery

PubMed Central

Hartman, Jessica H.; Boysen, Gunnar

2012-01-01

We are the first to report allosterism during styrene oxidation by recombinant CYP2E1 and human liver microsomes. At low styrene concentrations, oxidation is inefficient because of weak binding to CYP2E1 (Ks = 830 μM). A second styrene molecule then binds CYP2E1 with higher affinity (Kss = 110 μM) and significantly improves oxidation to achieve a kcat of 6.3 nmol · min−1 · nmol CYP2E1−1. The transition between these metabolic cycles coincides with reported styrene concentrations in blood from exposed workers; thus, this CYP2E1 mechanism may be relevant in vivo. Scaled modeling of the in vitro-positive allosteric mechanism for styrene metabolism to its in vivo clearance led to significant deviations from the traditional model based on Michaelis-Menten kinetics. Low styrene levels were notably much less toxic than generally assumed. We interrogated the allosteric mechanism using the CYP2E1-specific inhibitor and drug 4-methylpyrazole, which we have shown binds two CYP2E1 sites. From the current studies, styrene was a positive allosteric effector on 4-methylpyrazole binding, based on a 10-fold increase in 4-methylpyrazole binding affinity from Ki 0.51 to Ksi 0.043 μM. The inhibitor was a negative allosteric effector on styrene oxidation, because kcat decreased 6-fold to 0.98 nmol · min−1 · nmol CYP2E1−1. Consequently, mixtures of styrene and other molecules can induce allosteric effects on binding and metabolism by CYP2E1 and thus mitigate the efficiency of their metabolism and corresponding effects on human health. Taken together, our elucidation of mechanisms for these allosteric reactions provides a powerful tool for further investigating the complexities of CYP2E1 metabolism of drugs and pollutants. PMID:22807108

Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4DCAF5 ubiquitin ligase.

PubMed

Leng, Feng; Yu, Jiekai; Zhang, Chunxiao; Alejo, Salvador; Hoang, Nam; Sun, Hong; Lu, Fei; Zhang, Hui

2018-04-24

Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4 DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4 DCAF5 . Mouse L3MBTL3/MBT-1 deletion causes accumulation of DNMT1 protein, increased genomic DNA methylation, and late embryonic lethality. DNMT1 contains a consensus methylation motif shared by many non-histone proteins including E2F1, a key transcription factor for S phase. We show that the methylation-dependent E2F1 degradation is also controlled by L3MBTL3-CRL4 DCAF5 . Our studies elucidate for the first time a novel mechanism by which the stability of many methylated non-histone proteins are regulated.

Magnolol protects osteoblastic MC3T3-E1 cells against antimycin A-induced cytotoxicity through activation of mitochondrial function.

PubMed

Choi, Eun Mi

2012-06-01

Antimycin A treatment of cells blocks the mitochondrial electron transport chain and leads to elevated ROS generation. In the present study, we investigated the protective effects of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, on antimycin A-induced toxicity in osteoblastic MC3T3-E1 cells. Osteoblastic MC3T3-E1 cells were pre-incubated with magnolol before treatment with antimycin A. Cell viability and mineralization of osteoblasts were assessed by MTT assay and Alizarin Red staining, respectively. Mitochondrial dysfunction in cells was measured by mitochondrial membrane potential (MMP), complex IV activity, and ATP level. The cellular antioxidant effect of magnolol in osteoblastic MC3T3-E1 cells was assessed by measuring cardiolipin oxidation, mitochondrial superoxide levels, and nitrotyrosine content. Phosphorylated cAMP-response element-binding protein (CREB ) was evaluated using ELISA assay. Pretreatment with magnolol prior to antimycin A exposure significantly reduced antimycin A-induced osteoblast dysfunction by preventing MMP dissipation, ATP loss, and CREB inactivation. Magnolol also reduced cardiolipin peroxidation, mitochondrial superoxide, and nitrotyrosine production induced by antimycin A. These results suggest that magnolol has a protective effect against antimycin A-induced cell damage by its antioxidant effects and the attenuation of mitochondrial dysfunction. All these data indicate that magnolol may reduce or prevent osteoblast degeneration in osteoporosis or other degenerative disorders.

Chemical disorder and 207Pb hyperfine fields in the magnetoelectric multiferroic Pb (F e1 /2S b1 /2 ) O3 and its solid solution with Pb (F e1 /2N b1 /2) O3

NASA Astrophysics Data System (ADS)

Zagorodniy, Yu. O.; Kuzian, R. O.; Kondakova, I. V.; Maryško, M.; Chlan, V.; Štěpánková, H.; Olekhnovich, N. M.; Pushkarev, A. V.; Radyush, Yu. V.; Raevski, I. P.; Zalar, B.; Laguta, V. V.; Stephanovich, V. A.

2018-01-01

We report on the results of magnetic susceptibility, electron paramagnetic resonance, and 207Pb nuclear magnetic resonance (NMR) studies of the magnetoelectric multiferroic Pb (F e1 /2S b1 /2 ) O3 (PFS) ceramic, as well as its solid solution with Pb (F e1 /2N b1 /2) O3 (PFN) of different degrees of the 1:1 ordering of magnetic F e3 + and nonmagnetic S b5 + ions. The ordering has been studied by x-ray diffraction (XRD) and NMR methods. In particular, two spectral lines, originating from the ordered and disordered regions, respectively, are resolved in the 207Pb NMR spectra. This demonstrates the presence of spatially heterogeneous ordering where ordered regions are embedded into a disordered matrix. Combining XRD and NMR data, we have determined both the long-range order parameter s and the volume fraction of ordered regions s' for all investigated samples. The values vary in the range s =0 -0.93 and s'=0 -1 . We have found that the 207Pb Fermi contact interaction strongly depends on the disorder in the Fe/Sb positions: whereas it reaches 7.08 MHz in the ordered lattice, it is almost zero in the disordered environment. These results are further supported by the studies of PFS-PFN solid solutions. The analysis of experimental data in terms of density functional theory reveals a noticeably higher hybridization between Pb 6s and Fe 3d orbitals in the ordered case. The ordering of magnetic and nonmagnetic ions has a strong impact on the magnetic properties of PFS, leading to a transformation of the long-range ordered antiferromagnetic phase in chemically ordered samples to the spin glass state already in partially (s =0.35 ) disordered specimens. In our opinion, the difference in the magnetic properties of PFN and PFS is related to the fact that PFN is completely disordered, in contrast to PFS, which is only partially disordered, with small ordered regions existing in the disordered matrix that prevent the percolation of the nearest-neighbor Fe-Fe exchange interaction

Substitution of specific cysteine residues in E1 glycoprotein of classical swine fever virus strain Brescia affects formation of E1-E2 heterodimers and alters virulence in swine

USDA-ARS?s Scientific Manuscript database

E1, along with E^rns and E2, is one of the three envelope glycoproteins of Classical Swine Fever Virus (CSFV). E1 and E2 are anchored to the virus envelope at their carboxyl termini and E^rns loosely associates with the viral envelope. In infected cells, E2 forms homodimers and heterodimers with E1,...

The crystal structures of six (2E)-3-aryl-1-(5-halogeno­thio­phen-2-yl)prop-2-en-1-ones

PubMed Central

Naik, Vasant S.; Yathirajan, Hemmige S.; Jasinski, Jerry P.; Smolenski, Victoria A.; Glidewell, Christopher

2015-01-01

The structures of six chalcones containing 5-halogeno­thio­phen-2-yl substituents are reported: (2E)-1-(5-chloro­thio­phen-2-yl)-3-(4-ethyl­phen­yl)prop-2-en-1-one, C15H13ClOS, (I), and (2E)-1-(5-bromo­thio­phen-2-yl)-3-(4-ethyl­phen­yl)prop-2-en-1-one, C15H13BrOS, (II), are isostructural in space group P-1, while (2E)-1-(5-chloro­thio­phen-2-yl)-3-(4-eth­oxy­phen­yl)prop-2-en-1-one, C15H13ClO2S, (III), and (2E)-1-(5-bromo­thio­phen-2-yl)-3-(4-eth­oxy­phen­yl)prop-2-en-1-one C15H13BrO2S, (IV), are isostructural in space group P21/c. There are no hydrogen bonds of any kind in the structures of compounds (I) and (II), but in the structures of compounds (III) and (IV), the mol­ecules are linked into C(7) chains by means of C—H⋯O hydrogen bonds. In the structure of (2E)-3-(4-bromo­phen­yl)-1-(5-chloro­thio­phen-2-yl)prop-2-en-1-one, C13H8BrClOS, (V), there are again no hydrogen bonds nor π–π stacking inter­actions but in that of (2E)-1-(5-bromo­thio­phen-2-yl)-3-(3-meth­oxy­phen­yl)prop-2-en-1-one, C14H11BrO2S, (VI), the mol­ecules are linked into C(5) chains by C—H⋯O hydrogen bonds. In each of compounds (I)–(VI), the mol­ecular skeletons are close to planarity, and there are short halogen⋯halogen contacts in the structures of compounds (II) and (V) and a short Br⋯O contact in the structure of compound (VI). Comparisons are made with the structures of some similar compounds. PMID:26396857

Impotence evaluated by the use of prostaglandin E1

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

Hwang, T.I.; Yang, C.R.; Wang, S.J.

1989-06-01

We screened 80 patients at our hospital for the differential diagnosis of impotence using intracavernous injection of prostaglandin E1 (20 micrograms). The rate of positive response was 78.8 per cent (63 patients). Neither systemic reactions nor priapism occurred. However, a considerable incidence (23.8 per cent, 19 of 80 patients) of tolerable injection pain was encountered. The 133-xenon penile washout study was conducted routinely in impotent men for hemodynamic evaluation of penile vascularity. In 80 patients a positive correlation between the response of intracavernous prostaglandin E1 injection and the result of the washout study was found (r equals 0.381, p lessmore » than 0.0002). We selected 14 subjects randomly to receive additional intravenous infusions of prostaglandin E1 (6 ampules, 120 micrograms total) for 3 days, after which another 133-xenon washout study was done. The washout studies before and after intravenous prostaglandin E1 infusion were compared, and 10 patients (71.4 per cent) appeared to obtain improvement in half-time clearance and penile blood flow. However, only 3 patients noticed improvement subjectively. We suggest that prostaglandin E1 could be a desirable alternative for the diagnosis and treatment of impotence.« less

A multinuclear solid-state NMR study of the dimethyltin chalcogenides ((CH 3) 2SnE) 3, E  S,Se,Te

NASA Astrophysics Data System (ADS)

Gay, Ian D.; Jones, C. H. W.; Sharma, R. D.

The solid-state NMR spectra, measured using MAS, are reported for 13C, 119Sn, 77Se, and 125Te in the compounds (Me 2SnE) 3, E  S, Se, or Te. For ((CH 3) 2SnS) 3, tetragonal, three inequivalent carbons and two inequivalent tins are observed consistent with a reinterpretation of the crystal structure data of this compound which shows a twofold axis through opposing tin and sulfur atoms, the molecule being in a twisted-boat conformation. For the monoclinic form six inequivalent carbons and three inequivalent tins were observed. Chemical shifts for 13C and 119Sn and the magnitudes of the 2JSn Sn coupling constants are reported. The tetragonal forms of ((CH 3) 2SnSe) 3 and ((CH 3) 2SnTe) 3 show the presence of two inequivalent tin and chalcogen atoms and three inequivalent carbons, again consistent with a twofold axis. In these compounds it is possible to identify the three different observed single-bond coupling constants with the distinct crystallographically determined tin-chalcogen bonds. The 13C, 119Sn, 77Se, and 125Te chemical shifts are reported, together with the magnitude of 1JSn E (E  Se or Te). In addition to isotropic shifts and couplings, chemical-shift anisotropies are reported for Sn, Se, and Te.

UV-B induction of the E3 ligase ARIADNE12 depends on CONSTITUTIVELY PHOTOMORPHOGENIC 1

PubMed Central

Xie, Lisi; Lang-Mladek, Christina; Richter, Julia; Nigam, Neha; Hauser, Marie-Theres

2015-01-01

The UV-B inducible ARIADNE12 (ARI12) gene of Arabidopsis thaliana is a member of the RING-between-RING (RBR) family of E3 ubiquitin ligases for which a novel ubiquitination mechanism was identified in mammalian homologs. This RING-HECT hybrid mechanism needs a conserved cysteine which is replaced by serine in ARI12 and might affect the E3 ubiquitin ligase activity. We have shown that under photomorphogenic UV-B, ARI12 is a downstream target of the classical ultraviolet B (UV-B) UV RESISTANCE LOCUS 8 (UVR8) pathway. However, under high fluence rate of UV-B ARI12 was induced independently of UVR8 and the UV-A/blue light and red/far-red photoreceptors. A key component of several light signaling pathways is CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1). Upon UV-B COP1 is trapped in the nucleus through interaction with UVR8 permitting the activation of genes that regulate the biosynthesis of UV-B protective metabolites and growth adaptations. To clarify the role of COP1 in the regulation of ARI12 mRNA expression and ARI12 protein stability, localization and interaction with COP1 was assessed with and without UV-B. We found that COP1 controls ARI12 in white light, low and high fluence rate of UV-B. Furthermore we show that ARI12 is indeed an E3 ubiquitin ligase which is mono-ubiquitinated, a prerequisite for the RING-HECT hybrid mechanism. Finally, genetic analyses with transgenes expressing a genomic pmARI12:ARI12-GFP construct confirm the epistatic interaction between COP1 and ARI12 in growth responses to high fluence rate UV-B. PMID:25817546

47 CFR 12.3 - 911 and E911 analyses and reports.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 1 2014-10-01 2014-10-01 false 911 and E911 analyses and reports. 12.3 Section... RELIABILITY OF COMMUNICATIONS § 12.3 911 and E911 analyses and reports. The following entities must analyze their 911 and E911 networks and/or systems and provide a detailed report to the Commission on the...

Evidence for the decay D0-->K(-)pi(+)pi(-)e(+)nu(e).

PubMed

Artuso, M; Blusk, S; Butt, J; Li, J; Menaa, N; Mountain, R; Nisar, S; Randrianarivony, K; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Asner, D M; Edwards, K W; Naik, P; Briere, R A; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Cassel, D G; Duboscq, J E; Ehrlich, R; Fields, L; Galik, R S; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Mohapatra, D; Onyisi, P U E; Patterson, J R; Peterson, D; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Athar, S B; Patel, R; Potlia, V; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Karliner, I; Kim, D; Lowrey, N; Selen, M; White, E J; Wiss, J; Mitchell, R E; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Smith, A; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Ernst, J; Ecklund, K M; Severini, H; Love, W; Savinov, V; Aquines, O; Lopez, A; Mehrabyan, S; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Hu, D; Moziak, B; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F

2007-11-09

Using a 281 pb{-1} data sample collected at the psi(3770) with the CLEO-c detector, we present the first absolute branching fraction measurement of the decay D0-->K(-)pi(+)pi(-)e(+)nu(e) at a statistical significance of about 4.0 standard deviations. We find 10 candidates consistent with the decay D0-->K(-)pi(+)pi(-)e(+)nu(e). The probability that a background fluctuation accounts for this signal is less than 4.1 x 10{-5}. We find B(D0-->K(-)pi(+)pi(-)e(+)nu(e)) = [2.8{-1.1}{+1.4}(stat)+/-0.3(syst)]x10{-4}. By restricting the invariant mass of the hadronic system to be consistent with K1(1270), we obtain the product of branching fractions B(D{0}-->K{1}{-}(1270)e{+}nu{e})xB(K1-(1270)-->K{-}pi{+}pi{-})=[2.5{-1.0}{+1.3}(stat)+/-0.2(syst)]x10{-4}. Using B(K1-(1270)-->K{-}pi{+}pi{-})=(33+/-3)%, we obtain B(D{0}-->K{1}{-}(1270)e{+}nu{e})=[7.6{-3.0}{+4.1}(stat)+/-0.6(syst)+/-0.7]x10{-4}. The last error accounts for the uncertainties in the measured K1-(1270)-->K{-}pi{+}pi{-} branching fractions.

Theoretical Study of the Jahn-Teller effect in CH3CN+ (X2E) and CD3CN+ (X2E): multimode spin-vibronic energy level calculations.

PubMed

Zhang, Shiyang; Mo, Yuxiang

2009-10-15

The spin-vibronic energy levels for CH(3)CN(+)(X(2)E) and CD(3)CN(+)(X(2)E) have been calculated using a diabatic model including multimode vibronic couplings and spin-orbit interaction without adjusting any parameter. The diabatic potential energy surfaces are represented by the Taylor expansions including linear, quadratic and bilinear vibronic coupling terms. The normal coordinates used in the Taylor expansion were expressed by the mass-weighted Cartesian coordinates. The adiabatic potential energy surfaces for CH(3)CN(+) and CD(3)CN(+) were calculated at the level of CASPT2/cc-pvtz, and the spin-orbit coupling constant was calculated at the level of MRCI/CAS/cc-pvtz. The spin-orbit energy splittings for the ground vibrational states of CH(3)CN(+)(X(2)E) and CD(3)CN(+)(X(2)E) are 20 and 16 cm(-1), respectively, which are resulted from the quenching of the spin-orbit coupling strength of 51 cm(-1). The calculated spin-vibronic levels are in good agreement with the experimental data. The calculation results show that the Jahn-Teller effects in CH(3)CN(+)(X(2)E) and CD(3)CN(+)(X(2)E) are essential to understand their spin-vibronic energy structure.

Inhibitors of ubiquitin E3 ligase as potential new antimalarial drug leads.

PubMed

Jain, Jagrati; Jain, Surendra K; Walker, Larry A; Tekwani, Babu L

2017-06-02

Protein ubiquitylation is an important post-translational regulation, which has been shown to be necessary for life cycle progression and survival of Plasmodium falciparum. Ubiquitin is a highly conserved 76 amino acid polypeptide, which attaches covalently to target proteins through combined action of three classes of enzymes namely, the ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin-protein ligase (E3). Ubiquitin E1 and E2 are highly conserved within eukaryotes. However, the P. falciparum E3 ligase is substantially variable and divergent compared to the homologs from other eukaryotes, which make the E3 ligase a parasite-specific target. A set of selected E3 ubiquitin ligase inhibitors was tested in vitro against a chloroquine-sensitive P. falciparum D6 strain (PfD6) and a chloroquine-resistant P. falciparum W2 strain (PfW2). The inhibitors were also tested against Vero and transformed THP1 cells for cytotoxicity. The lead antimalarial E3 ubiquitin ligase inhibitors were further evaluated for the stage-specific antimalarial action and effects on cellular development of P. falciparum in vitro. Statistics analysis was done by two-way ANOVA followed by Tukey and Sidak multiple comparison test using GraphPad Prism 6. E3 ligase inhibitors namely, JNJ 26854165, HLI 373 and Nutlin 3 showed prominent antimalarial activity against PfD6 and PfW2. These inhibitors were considerably less cytotoxic to mammalian Vero cells. JNJ 26854165, HLI 373 and Nutlin 3 blocked the development of P. falciparum parasite at the trophozoite and schizont stages, resulting in accumulation of distorted trophozoites and immature schizonts. Interruption of trophozoites and schizont maturation by the antimalarial E3 ligase inhibitors suggest the role of ubiquitin/proteasome functions in the intraerythrocytic development of malaria parasite. The ubiquitin/proteasome functions may be critical for schizont maturation. Further investigations on the lead E3 ligase

High-accuracy calculations of the ground, 1 1A1', and the 2 1A1', 2 3A1', and 1 1E' excited states of H3+.

PubMed

Pavanello, Michele; Adamowicz, Ludwik

2009-01-21

Accurate variational Born-Oppenheimer calculations of the 1 (1)A(1) ('), 2 (1)A(1) ('), 2 (3)A(1) ('), and 1 (1)E(') states of the H(3) (+) ion at the ground-state equilibrium geometry are reported. The wave functions of the states are expanded in terms of explicitly correlated spherical Gaussian functions with shifted centers. In the variational optimization the analytical gradient of the energy with respect to the nonlinear exponential parameters of the Gaussians has been employed. The energies obtained in the calculations are the best variational estimates ever calculated for the four states. One-electron densities for the states, as well as a D(3h)-restricted potential energy surface of the ground state calculated around the equilibrium geometry, are also presented and discussed.

Role of Sandhika: a polyherbal formulation on MC3T3-E1 osteoblast-like cells.

PubMed

Tripathi, Yamini B; Tripathi, Pratibha; Korlagunta, Kiranmayi; Chai, Sheau Ching; Smith, Brenda J; Arjmandi, Bahram H

2008-02-01

Sandhika is a polyherbal formulation, (water soluble fraction of Commiphora mukul, Boswellia serrata, Semecarpus anacardium and Strychnos nux vomica), which has been in clinical use in India for last 20 years. Its modified formulation BHUx has shown specific inhibition of cyclooxygenase (COX)-2 and lipoxygenase (LOX)-15 and has prevented diet-induced atherosclerosis in rabbits. In order to explore the possibility of the use of Sandhika for the management of osteoporosis, we have examined its influence on MC3T3-E1 osteoblast-like cells in presence of lipopolysaccharide (1 microg/ml) in terms of calcium nodule formation and alkaline phosphatase activity. MC3T3-E1 osteoblast-like cells (80% confluence in 6-well plates) were treated with water extract of Sandhika, for 10 days, in the concentration range of 0.5 to 16 mg/ml final concentration, in presence of LPS. Media was changed on every third day and culture supernatant was collected after every change to assess the alkaline phosphatase activity and on the tenth day, cells were washed and stained with "Alizarin S" for visualization of calcium nodules by using Meta Morph software (Universal Imaging, Downingtown, PA). The results showed significant enhancement in calcium nodule formation in the dose dependent manner up to 2 mg/ml, followed by gradual decrease at higher concentrations. This change was accompanied with the increase in the alkaline phosphatase activity in these plates, indicating a potential anabolic effect of this polyherbal formulation on osteoblast-like cells under inflammatory conditions induced by LPS.

Perturbative QCD analysis of exclusive processes e+e-→V P and e+e-→T P

NASA Astrophysics Data System (ADS)

Lü, Cai-Dian; Wang, Wei; Xing, Ye; Zhang, Qi-An

2018-06-01

We study the e+e-→V P and e+e-→T P processes in the perturbative QCD approach based on kT factorization, where the P , V and T denotes a light pseudoscalar, vector, and tensor meson, respectively. We point out in the case of e+e-→T P transition due to charge conjugation invariance, only three channels are allowed: e+e-→a2±π∓ , e+e-→K2*±K∓ and the V-spin suppressed e+e-→K2*0K¯ 0+K¯2 *0K0 . Cross sections of e+e-→V P and e+e-→T P at √{s }=3.67 GeV and √{s }=10.58 GeV are calculated and the invariant mass dependence is found to favor the 1 /s4 power law. Most of our theoretical results are consistent with the available experimental data and other predictions can be tested at the ongoing BESIII and forthcoming Belle-II experiments.

PDC-E3BP is not a dominant T-cell autoantigen in primary biliary cirrhosis.

PubMed

McHugh, Anna; Robe, Amanda J; Palmer, Jeremy M; Jones, David E J

2006-05-01

Autoantibody responses reactive with the E2 and E3BP components of pyruvate dehydrogenase complex (PDC), which characterise primary biliary cirrhosis (PBC) crossreact, precluding the identification, from serological studies, of the antigen to which the principal breakdown of tolerance occurs. Although autoreactive T-cell responses to PDC-E2 have been well characterised it is, at present, unclear whether T-cell tolerance breakdown also occurs to PDC-E3BP. The aims of this study were to characterise autoreactive T-cell responses to PDC-E3BP in PBC and potential factors regulating their expression. Peripheral blood T-cell proliferative responses to purified recombinant human PDC-E2 and PDC-E3BP at a range of concentrations were characterised in PBC patients and control subjects. T-cell proliferative responses to both E2 and E3BP were absent from control subjects (median peak stimulation index (SI) to PDC-E2 1.2 [range 0.3-1.9], 0/10 positive (SI>2.32), median peak SI to PDC-E3BP 1.1 [0.7-2.1

Structure of an E3:E2~Ub Complex Reveals an Allosteric Mechanism Shared among RING/U-box Ligases

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

Pruneda, Jonathan N.; Littlefield, Peter J.; Soss, Sarah E.

2012-09-28

Despite the widespread importance of RING/U-box E3 ubiquitin ligases in ubiquitin (Ub) signaling, the mechanismby which this class of enzymes facilitates Ub transfer remains enigmatic. Here, we present a structural model for a RING/U-box E3:E2~Ub complex poised for Ub transfer. The model and additional analyses reveal that E3 binding biases dynamic E2~Ub ensembles toward closed conformations with enhanced reactivity for substrate lysines. We identify a key hydrogen bond between a highly conserved E3 side chain and an E2 backbone carbonyl, observed in all structures of active RING/ U-Box E3/E2 pairs, as the linchpin for allosteric activation of E2~Ub. The conformationalmore » biasing mechanism is generalizable across diverse E2s and RING/U-box E3s, but is not shared by HECT-type E3s. The results provide a structural model for a RING/ U-box E3:E2~Ub ligase complex and identify the long sought-after source of allostery for RING/UBox activation of E2~Ub conjugates.« less

TMEM129 is a Derlin-1 associated ERAD E3 ligase essential for virus-induced degradation of MHC-I.

PubMed

van den Boomen, Dick J H; Timms, Richard T; Grice, Guinevere L; Stagg, Helen R; Skødt, Karsten; Dougan, Gordon; Nathan, James A; Lehner, Paul J

2014-08-05

The US11 gene product of human cytomegalovirus promotes viral immune evasion by hijacking the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. US11 initiates dislocation of newly translocated MHC I from the ER to the cytosol for proteasome-mediated degradation. Despite the critical role for ubiquitin in this degradation pathway, the responsible E3 ligase is unknown. In a forward genetic screen for host ERAD components hijacked by US11 in near-haploid KBM7 cells, we identified TMEM129, an uncharacterized polytopic membrane protein. TMEM129 is essential and rate-limiting for US11-mediated MHC-I degradation and acts as a novel ER resident E3 ubiquitin ligase. TMEM129 contains an unusual cysteine-only RING with intrinsic E3 ligase activity and is recruited to US11 via Derlin-1. Together with its E2 conjugase Ube2J2, TMEM129 is responsible for the ubiquitination, dislocation, and subsequent degradation of US11-associated MHC-I. US11 engages two degradation pathways: a Derlin-1/TMEM129-dependent pathway required for MHC-I degradation and a SEL1L/HRD1-dependent pathway required for "free" US11 degradation. Our data show that TMEM129 is a novel ERAD E3 ligase and the central component of a novel mammalian ERAD complex.

Registration of DGE-3, a durum wheat disomic substitution line 1E(1B) involving a wheatgrass chromosome

USDA-ARS?s Scientific Manuscript database

Durum wheat (Triticum turgidum L., 2n = 4x = 28; AABB genomes) alien disomic substitution 1E(1B) line DGE-3 (PI 665473) was developed by the U.S. Department of Agriculture – Agricultural Research Service, Northern Crop Science Lab, Cereal Crops Research Unit, Fargo, ND and released in 2012. It was ...

Crystal structures of two bacterial HECT-like E3 ligases in complex with a human E2 reveal atomic details of pathogen-host interactions

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

Lin, David Yin-wei; Diao, Jianbo; Chen, Jue

2012-12-10

In eukaryotes, ubiquitination is an important posttranslational process achieved through a cascade of ubiquitin-activating (E1), conjugating (E2), and ligase (E3) enzymes. Many pathogenic bacteria deliver virulence factors into the host cell that function as E3 ligases. How these bacterial 'Trojan horses' integrate into the eukaryotic ubiquitin system has remained a mystery. Here we report crystal structures of two bacterial E3s, Salmonella SopA and Escherichia coli NleL, both in complex with human E2 UbcH7. These structures represent two distinct conformational states of the bacterial E3s, supporting the necessary structural rearrangements associated with ubiquitin transfer. The E2-interacting surface of SopA and NleLmore » has little similarity to those of eukaryotic E3s. However, both bacterial E3s bind to the canonical surface of E2 that normally interacts with eukaryotic E3s. Furthermore, we show that a glutamate residue on E3 is involved in catalyzing ubiquitin transfer from E3 to the substrate, but not from E2 to E3. Together, these results provide mechanistic insights into the ubiquitin pathway and a framework for understanding molecular mimicry in bacterial pathogenesis.« less

sIgE Ana o 1, 2 and 3 accurately distinguish tolerant from allergic children sensitized to cashew nuts.

PubMed

van der Valk, J P M; Gerth van Wijk, R; Vergouwe, Y; Steyerberg, E W; Reitsma, M; Wichers, H J; Savelkoul, H F J; Vlieg-Boerstra, B; de Groot, H; Dubois, A E J; de Jong, N W

2017-01-01

The double-blind, placebo-controlled food challenge test (DBPCFC) is the gold standard in cashew nut allergy. This test is costly, time consuming and not without side effects. Analysis of IgE reactivity to cashew nut components may reduce the need for food challenge tests. In a prospective and multicentre study, children with suspected cashew nut allergy underwent a DBPCFC with cashew nut. Specific IgE to cashew nut and to the components Ana o 1, 2 and 3 were determined. A skin prick test (SPT) with cashew nut extract was performed. The association between the outcome of the food challenge test and specific IgE to Ana o 1, 2 and 3 was assessed with logistic regression analyses, unadjusted and adjusted for other diagnostic variables. Discriminative ability was quantified with a concordance index (c). A total of 173 children (103 boys, 60%) with a median age of 9 years were included. About 79% had a positive challenge test outcome. A steep rise in the risk of a positive challenge was observed for specific IgE to each individual component Ana o 1, 2 and 3 with estimated risks up to approximately 100%. Median values of Ana o 1, 2, 3 were 1.29 kU/l (range 0-100 kU/l), 4.77 kU/l (range 0-100 kU/l) and 8.33 kU/l (range 0-100 kU/l) respectively and varied significantly (p < 0.001). Specific IgE to Ana o 1, 2 and 3 was better distinguished between cashew-allergic and tolerant children (c = 0.87, 0.85 and 0.89, respectively) than specific IgE to cashew nut or SPT (c = 0.76 and 0.83, respectively). The major cashew nut allergens Ana o 1, 2 and 3 are each individually predictive for the outcome of food challenge tests in cashew-allergic children. © 2016 John Wiley & Sons Ltd.

Functional synergy between DP-1 and E2F-1 in the cell cycle-regulating transcription factor DRTF1/E2F.

PubMed Central

Bandara, L R; Buck, V M; Zamanian, M; Johnston, L H; La Thangue, N B

1993-01-01

It is widely believed that the cellular transcription factor DRTF1/E2F integrates cell cycle events with the transcription apparatus because during cell cycle progression in mammalian cells it interacts with molecules that are important regulators of cellular proliferation, such as the retinoblastoma tumour suppressor gene product (pRb), p107, cyclins and cyclin-dependent kinases. Thus, pRb, which negatively regulates early cell cycle progression and is frequently mutated in tumour cells, and the Rb-related protein p107, bind to and repress the transcriptional activity of DRTF1/E2F. Viral oncoproteins, such as adenovirus E1a and SV40 large T antigen, overcome such repression by sequestering pRb and p107 and in so doing are likely to activate genes regulated by DRTF1/E2F, such as cdc2, c-myc and DHFR. Two sequence-specific DNA binding proteins, E2F-1 and DP-1, which bind to the E2F site, contain a small region of similarity. The functional relationship between them has, however, been unclear. We report here that DP-1 and E2F-1 exist in a DNA binding complex in vivo and that they bind efficiently and preferentially as a heterodimer to the E2F site. Moreover, studies in yeast and Drosophila cells indicate that DP-1 and E2F-1 interact synergistically in E2F site-dependent transcriptional activation. Images PMID:8223441

Low-intensity pulsed ultrasound (LIPUS) stimulates mineralization of MC3T3-E1 cells through calcium and phosphate uptake.

PubMed

Tassinary, João Alberto Fioravante; Lunardelli, Adroaldo; Basso, Bruno de Souza; Dias, Henrique Bregolin; Catarina, Anderson Velasque; Stülp, Simone; Haute, Gabriela Viegas; Martha, Bianca Andrade; Melo, Denizar Alberto da Silva; Nunes, Fernanda Bordignon; Donadio, Márcio Vinícius Fagundes; Oliveira, Jarbas Rodrigues de

2018-03-01

The present study aimed to evaluate the effect of low-intensity pulsed ultrasound (LIPUS) on pre-osteoblast mineralization using in vitro bioassays. Pre-osteoblastic MC3T3-E1 cells were exposed to LIPUS at 1 MHz frequency, 0.2 W/cm 2 intensity and 20% duty cycle for 30 min. The analyses were carried out up to 336 h (14 days) after exposure. The concentration of collagen, phosphate, alkaline phosphatase, calcium and transforming growth factor beta 1 (TGF-β1) in cell supernatant and the presence of calcium deposits in the cells were analyzed. Our results showed that LIPUS promotes mineralized nodules formation. Collagen, phosphate, and calcium levels were decreased in cell supernatant at 192 h after LIPUS exposure. However, alkaline phosphatase and TGF-β1 concentrations remained unchanged. Therapeutic pulsed ultrasound is capable of stimulating differentiation and mineralization of pre-osteoblastic MC3T3-E1 cells by calcium and phosphate uptake with consequent hydroxyapatite formation. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigation of the intermolecular recognition mechanism between the E3 ubiquitin ligase Keap1 and substrate based on multiple substrates analysis.

PubMed

Jiang, Zheng-Yu; Xu, Li-Li; Lu, Meng-Chen; Pan, Yang; Huang, Hao-Ze; Zhang, Xiao-Jin; Sun, Hao-Peng; You, Qi-Dong

2014-12-01

E3 ubiquitin ligases are attractive drug targets due to their specificity to the ubiquitin machinery. However, the development of E3 ligase inhibitors has proven challenging for the fact that they must disrupt protein-protein interactions (PPIs). The E3 ligase involved in interactome provide new hope for the discovery of the E3 ligase inhibitors. These currently known natural binding partners of the E3 ligase can benefit the discovery of other unknown substrates and also the E3 ligase inhibitors. Herein, we present a novel strategy that using multiple substrates to elucidate the molecular recognition mechanism of E3 ubiquitin ligase. Molecular dynamics simulation, molecular mechanics-generalized born surface area (MM-GBSA) binding energy calculation and energy decomposition scheme were incorporated to evaluate the quantitative contributions of sub-pocket and per-residue to binding. In this case, Kelch-like ECH-associated protein-1 (Keap1), a substrate adaptor component of the Cullin-RING ubiquitin ligases complex, is applied for the investigation of how it recognize its substrates, especially Nrf2, a master regulator of the antioxidant response. By analyzing multiple substrates binding determinants, we found that both the polar sub-pockets (P1 and P2) and the nonpolar sub-pockets (P4 and P5) of Keap1 can make remarkable contributions to intermolecular interactions. This finding stresses the requirement for substrates to interact with the polar and nonpolar sub-pockets simultaneously. The results discussed in this paper not only show the binding determinants of the Keap1 substrates but also provide valuable implications for both Keap1 substrate discovery and PPI inhibitor design.

Investigation of the intermolecular recognition mechanism between the E3 ubiquitin ligase Keap1 and substrate based on multiple substrates analysis

NASA Astrophysics Data System (ADS)

Jiang, Zheng-Yu; Xu, Li-Li; Lu, Meng-Chen; Pan, Yang; Huang, Hao-Ze; Zhang, Xiao-Jin; Sun, Hao-Peng; You, Qi-Dong

2014-12-01

E3 ubiquitin ligases are attractive drug targets due to their specificity to the ubiquitin machinery. However, the development of E3 ligase inhibitors has proven challenging for the fact that they must disrupt protein-protein interactions (PPIs). The E3 ligase involved in interactome provide new hope for the discovery of the E3 ligase inhibitors. These currently known natural binding partners of the E3 ligase can benefit the discovery of other unknown substrates and also the E3 ligase inhibitors. Herein, we present a novel strategy that using multiple substrates to elucidate the molecular recognition mechanism of E3 ubiquitin ligase. Molecular dynamics simulation, molecular mechanics-generalized born surface area (MM-GBSA) binding energy calculation and energy decomposition scheme were incorporated to evaluate the quantitative contributions of sub-pocket and per-residue to binding. In this case, Kelch-like ECH-associated protein-1 (Keap1), a substrate adaptor component of the Cullin-RING ubiquitin ligases complex, is applied for the investigation of how it recognize its substrates, especially Nrf2, a master regulator of the antioxidant response. By analyzing multiple substrates binding determinants, we found that both the polar sub-pockets (P1 and P2) and the nonpolar sub-pockets (P4 and P5) of Keap1 can make remarkable contributions to intermolecular interactions. This finding stresses the requirement for substrates to interact with the polar and nonpolar sub-pockets simultaneously. The results discussed in this paper not only show the binding determinants of the Keap1 substrates but also provide valuable implications for both Keap1 substrate discovery and PPI inhibitor design.

[Establishment of A1E3 and B1C4 monoclonal antibody-based ELISA for detecting circulating antigen of Schistosoma japonicum and its preliminary application].

PubMed

Cai, Yu-Chun; Chen, Shao-Hong; Tian, Li-Guang; Chu, Yan-Hong; Lu, Yan; Chen, Mu-Xin; Ai, Lin; Zhou, Yang; Chen, Jia-Xu

2014-02-01

To establish A1E3 and B1C4 monoclonal antibody-based ELISA for detecting circulating antigen of Schistosoma japonicum and explore its application value in the field. The characteristics of A1E3 and B1C4 monoclonal antibodies were analyzed by SDS-PAGE and Western blotting. The SEA-based ELISA was used to evaluate the titers of A1E3 and B1C4. The orthogonal test was used to determine the best concentration of coating antibody B1C4 and optimal working concentration of A1E3-HRP. Under the optimal conditions, the serum samples of 20 acute schistosomiasis cases, 46 chronic schistosomiasis cases, and 20 control sera were tested to evaluate its detection sensitivity and specificity. Seventy-two antibody positive serum samples from Jiangling County of Hubei Province were detected and compared to a commercially available ELISA kit, to evaluate the detection effects of this method. The results of SDS-PAGE demonstrated that the purified A1E3 and B1C4 contained a clear heavy chain with molecular weight of 88,000 and 52,000 respectively and had the same light chain with molecular weight of 20,000; while Western blotting demonstrated that A1E3 and B1C4 could be recognized by SEA and serum samples of acute schistosomiasis cases. The SEA-based ELISA demonstrated the titers of B1C4 and A1E3 were 1:10(5) and 1:30,000, respectively. The serum samples from all the acute cases and 86.9% of the chronic cases showed a positive reaction. All of the control sera from healthy persons gave a negative response. The positive rates of the double monoclonal antibody ELISA and commercial ELISA for detecting the circulating antigen were 45.8% and 43.1% respectively, and there was no significant difference between the results of the two methods. A1E3 and B1C4 monoclonal antibody-based ELISA is established successfully. It exhibits a high sensitivity and specificity in detecting circulating antigen of Schistosoma japonicum.

Enhanced osteogenic differentiation of MC3T3-E1 cells on grid-topographic surface and evidence for involvement of YAP mediator.

PubMed

Zhang, Yingying; Gong, He; Sun, Yan; Huang, Yan; Fan, Yubo

2016-05-01

Numerous studies have shown that surface topography can promote cell-substrate associations and deeply influence cell fate. The intracellular mechanism or how micro- or nano-patterned extracellular signal is ultimately linked to activity of nuclear transcription factors remains unknown. It has been reported that Yes-associated protein (YAP) can respond to extracellular matrix microenvironment signals, thus regulates stem cell differentiation process. We propose that YAP may play a role in mediating the topography induced cell differentiation. To this end, we fabricated polydimethylsiloxane (PDMS) micropatterns with grid topology (GT) (3 μm pattern width, 2 μm pattern interval length, 7 μm pattern height); nonpatterned PDMS substrates were used as the planar controls. The MC3T3-E1 cells were then cultured on these surfaces, respectively, in osteogenic inducing medium. Cell differentiation in terms of osteogenesis related gene expression, protein levels, alkaline phosphatase activity and extracellular matrix mineralization was assessed. It was shown that the cells on GT surfaces had stronger osteogenesis capacity. In addition, expression level of YAP was increased when MC3T3-E1 cells grew on GT substrates, which was similar to the levels of osteogenic differentiation markers. It was also shown that YAP knockdown attenuated GT substrates-induced MC3T3-E1 differentiation, which reduced the osteogenic differentiation effect of the GT substrates. Collectively, our findings indicate that GT substrates-induced MC3T3-E1 differentiation may be associated with YAP. This paper provides new target points for transcriptional mechanism research of microenvironment induced cell differentiation and a useful approach to obtain more biofunctionalization scaffolds for tissue engineering. © 2016 Wiley Periodicals, Inc.

Liraglutide attenuates the osteoblastic differentiation of MC3T3-E1 cells by modulating AMPK/mTOR signaling

PubMed Central

Hu, Xiong-Ke; Yin, Xin-Hua; Zhang, Hong-Qi; Guo, Chao-Feng; Tang, Ming-Xing

2016-01-01

Liraglutide, a synthetic analogue of glucagon-like peptide-1, is utilized in the treatment of type 2 diabetes and obesity. Liraglutide has been previously demonstrated to prevent osteoblastic differentiation of human vascular smooth muscle cells, resulting in the slowing of arterial calcification, however, its effect on bone formation remains unclear. The present study investigated the effect of liraglutide on osteoblastic differentiation using Alizarin Red S staining, and examined the molecular mechanisms underlying the regulatory effect by western blot analysis. The present study demonstrated that protein expression levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were downregulated in MC3T3-E1 cells during osteoblastic differentiation in commercial osteogenic differentiation medium, whereas protein expression levels of transforming growth factor-β (TGF-β) and phosphorylated mammalian target of rapamycin (p-mTOR) increased. Liraglutide was subsequently demonstrated to dose-dependently attenuate the osteoblastic differentiation of MC3T3-E1 cells, to upregulate p-AMPK, and downregulate p-mTOR and TGF-β protein expression levels. Treatment with an AMPK-specific inhibitor, Compound C, eradicated the effect of liraglutide on osteoblastic differentiation, and p-mTOR and TGF-β downregulation. An mTOR activator, MHY1485, also abolished the inhibitory effect of liraglutide on osteoblastic differentiation, and resulted in p-mTOR and TGF-β downregulation, but did not attenuate the liraglutide-induced increase in p-AMPK protein expression levels. The results of the present study demonstrate that liraglutide attenuates osteoblastic differentiation of MC3T3-E1 cells via modulation of AMPK/mTOR signaling. The present study revealed a novel function of liraglutide, which contributes to the understanding of its pharmacological and physiological effects in clinical settings. PMID:27600753

ITOS D AND E system design report, volume 1

NASA Technical Reports Server (NTRS)

1970-01-01

The configuration and functions of the ITOS D and E system are described. The system will expand the operational capability of the basic TIROS M/ITOS system. The ITOS D and E mission will utilize the capabilities of the two-stage DSV 3N-6 Delta launch vehicle to place the ITOS D and E spacecraft into a circular, near-polar, sun synchronous orbit at 790 nautical miles altitude. The ITOS D and E will provide the following primary data: (1) visible daytime observations of cloud cover, (2) daytime and nighttime observations of cloud cover as detected from radiance in infrared spectrum, and (3) vertical temperature profile of the atmosphere on a global basis for data processing. In addition, the ITOS D and E system will provide secondary data comprising solar proton density measurements obtained throughout the orbit.

Apple RING E3 ligase MdMIEL1 inhibits anthocyanin accumulation by ubiquitinating and degrading MdMYB1 protein.

PubMed

An, Jian-Ping; Liu, Xin; Li, Hao-Hao; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2017-11-01

MdMYB1 is an important regulator for anthocyanin accumulation in apple (Malus × domestica). Here, an apple RING E3 ligase, MdMIEL1, was screened out as a partner of MdMYB1 with a yeast two-hybrid approach. Pull-down, bimolecular fluorescence complementation and coimmunoprecipitation assays further verified the interaction between MdMIEL1 and MdMYB1 proteins. Subsequently, in vitro and in vivo experiments indicated that MdMIEL1 functioned as a ubiquitin E3 ligase to ubiquitinate MdMYB1 protein, followed by degradation through a 26S proteasome pathway. Furthermore, transgenic studies in apple calli and Arabidopsis demonstrated that MdMIEL1 negatively regulated anthocyanin accumulation by modulating the degradation of MdMYB1 protein. Taken together, our findings provide a new insight into the molecular mechanism by which MdMIEL1 negatively regulates anthocyanin biosynthesis by ubiquitinating and degrading MdMYB1 protein. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Structure of the Human FANCL RING-Ube2T Complex Reveals Determinants of Cognate E3-E2 Selection

PubMed Central

Hodson, Charlotte; Purkiss, Andrew; Miles, Jennifer Anne; Walden, Helen

2014-01-01

Summary The combination of an E2 ubiquitin-conjugating enzyme with an E3 ubiquitin-ligase is essential for ubiquitin modification of a substrate. Moreover, the pairing dictates both the substrate choice and the modification type. The molecular details of generic E3-E2 interactions are well established. Nevertheless, the determinants of selective, specific E3-E2 recognition are not understood. There are ∼40 E2s and ∼600 E3s giving rise to a possible ∼24,000 E3-E2 pairs. Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex, revealing a specific and extensive network of additional electrostatic and hydrophobic interactions. Furthermore, we show that these specific interactions are required for selection of Ube2T over other E2s by FANCL. PMID:24389026

Two Distinct Types of E3 Ligases Work in Unison to Regulate Substrate Ubiquitylation.

PubMed

Scott, Daniel C; Rhee, David Y; Duda, David M; Kelsall, Ian R; Olszewski, Jennifer L; Paulo, Joao A; de Jong, Annemieke; Ovaa, Huib; Alpi, Arno F; Harper, J Wade; Schulman, Brenda A

2016-08-25

Hundreds of human cullin-RING E3 ligases (CRLs) modify thousands of proteins with ubiquitin (UB) to achieve vast regulation. Current dogma posits that CRLs first catalyze UB transfer from an E2 to their client substrates and subsequent polyubiquitylation from various linkage-specific E2s. We report an alternative E3-E3 tagging cascade: many cellular NEDD8-modified CRLs associate with a mechanistically distinct thioester-forming RBR-type E3, ARIH1, and rely on ARIH1 to directly add the first UB and, in some cases, multiple additional individual monoubiquitin modifications onto CRL client substrates. Our data define ARIH1 as a component of the human CRL system, demonstrate that ARIH1 can efficiently and specifically mediate monoubiquitylation of several CRL substrates, and establish principles for how two distinctive E3s can reciprocally control each other for simultaneous and joint regulation of substrate ubiquitylation. These studies have broad implications for CRL-dependent proteostasis and mechanisms of E3-mediated UB ligation. Copyright © 2016 Elsevier Inc. All rights reserved.

Recall of E-cigarette Advertisements and Adolescent E-cigarette Use.

PubMed

Nicksic, Nicole E; Harrell, Melissa B; Pérez, Adriana; Pasch, Keryn E; Perry, Cheryl L

2017-04-01

We examined the impact of e-cigarette advertising on e-cigarette use behaviors among youth over time. At baseline, 3907 students participated in a youth tobacco surveillance study from 2014-2015 and 2488 students completed a 6-month follow-up. Weighted logistic regression models investigated the recall of e-cigarette advertisements (TV/radio/billboards/retail/Internet) as a risk factor for e-cigarette perceived harm, use, and susceptibility. The odds of ever e-cigarette use was 3 times higher (AOR=2.99; 95% CI, 1.50-5.97) at 6-month follow-up among e-cigarette never-users who recalled e-cigarette advertisements in retail stores at baseline, compared to those who did not. Likewise, the odds of current e-cigarette use and susceptibility to e-cigarette use at 6-month follow-up were 2.03 (95% CI, 1.11-3.72) and 1.77 (95% CI, 1.20-2.61), respectively. Additionally, recall of e-cigarette advertisements on the Internet at baseline was significantly related to current use (AOR=2.17; 95% CI, 1.05-4.48) and susceptibility to use e-cigarettes (AOR=1.72;95% CI, 1.15-2.58) at 6-month follow-up. Recall of e-cigarette advertisements at point-of-sale and on the Internet was significantly associated with adolescent e-cigarette susceptibility and use, which supports the need to minimize adolescent exposure to these advertisements.

Recall of E-cigarette Advertisements and Adolescent E-cigarette Use

PubMed Central

Nicksic, Nicole E.; Harrell, Melissa B.; Pérez, Adriana; Pasch, Keryn E.; Perry, Cheryl L.

2017-01-01

Objective We examined the impact of e-cigarette advertising on e-cigarette use behaviors among youth over time. Methods At baseline, 3907 students participated in a youth tobacco surveillance study from 2014–2015 and 2488 students completed a 6-month follow-up. Weighted logistic regression models investigated the recall of e-cigarette advertisements (TV/radio/billboards/retail/Internet) as a risk factor for e-cigarette perceived harm, use, and susceptibility. Results The odds of ever e-cigarette use was 3 times higher (AOR=2.99; 95% CI, 1.50–5.97) at 6-month follow-up among e-cigarette never-users who recalled e-cigarette advertisements in retail stores at baseline, compared to those who did not. Likewise, the odds of current e-cigarette use and susceptibility to e-cigarette use at 6-month follow-up were 2.03 (95% CI, 1.11–3.72) and 1.77 (95% CI, 1.20–2.61), respectively. Additionally, recall of e-cigarette advertisements on the Internet at baseline was significantly related to current use (AOR=2.17; 95% CI, 1.05–4.48) and susceptibility to use e-cigarettes (AOR=1.72;95% CI, 1.15–2.58) at 6-month follow-up. Conclusions Recall of e-cigarette advertisements at point-of-sale and on the Internet was significantly associated with adolescent e-cigarette susceptibility and use, which supports the need to minimize adolescent exposure to these advertisements. PMID:29104901

Regulation of collagenase-3 and osteocalcin gene expression by collagen and osteopontin in differentiating MC3T3-E1 cells

NASA Technical Reports Server (NTRS)

D'Alonzo, Richard C.; Kowalski, Aaron J.; Denhardt, David T.; Nickols, G. Allen; Partridge, Nicola C.

2002-01-01

Both collagenase-3 and osteocalcin mRNAs are expressed maximally during the later stages of osteoblast differentiation. Here, we demonstrate that collagenase-3 mRNA expression in differentiating MC3T3-E1 cells is dependent upon the presence of ascorbic acid, is inhibited in the presence of the collagen synthesis inhibitor, 3,4-dehydroproline, and is stimulated by growth on collagen in the absence of ascorbic acid. Transient transfection studies show that collagenase-3 promoter activity increases during cell differentiation and requires the presence of ascorbic acid. Additionally, we show that, in differentiating MC3T3-E1 cells, collagenase-3 gene expression increases in the presence of an anti-osteopontin monoclonal antibody that binds near the RGD motif of this protein, whereas osteocalcin expression is inhibited. Furthermore, an RGD peptidomimetic compound, designed to block interaction of ligands to the alpha(v) integrin subunit, increases osteocalcin expression and inhibits collagenase-3 expression, suggesting that the RGD peptidomimetic initiates certain alpha(v) integrin signaling in osteoblastic cells. Overall, these studies demonstrate that stimulation of collagenase-3 expression during osteoblast differentiation requires synthesis of a collagenous matrix and that osteopontin and alpha(v) integrins exert divergent regulation of collagenase-3 and osteocalcin expression during osteoblast differentiation.

Analysis of eIF4E and 4EBP1 mRNAs in head and neck cancer.

PubMed

Sunavala-Dossabhoy, Gulshan; Palaniyandi, Senthilnathan; Clark, Cheryl; Nathan, Cherie-Ann O; Abreo, Fleurette W; Caldito, Gloria

2011-10-01

The eukaryotic translation initiation factor 4E (eIF4E) in conjunction with its binding protein, 4EBP1, regulates the translation of cap-dependent mRNAs. An aberrant increase in eIF4E shifts the balance in favor of translation of transcripts that promote cell proliferation and malignancy. eIF4E protein is commonly elevated in head and neck squamous cell carcinomas (HNSCC), and its overexpression is associated with increased recurrence. An underlying mechanism for eIF4E overexpression is gene amplification, and we wanted to determine whether eIF4E mRNA could serve as a prognostic maker of HNSCC. Tumor specimens from 26 HNSCC patients and oral tissues from 17 control subjects were examined for eIF4E and 4EBP1 by semiquantitative RT-PCR and correlated with clinical and pathologic findings. Unlike eIF4E mRNA alone, expression of eIF4E relative to 4EBP1 was a more precise predictor of HNSCC and its progression (P < .01, Wilcoxon rank sum test). Eight of 26 patients (31%) had elevated eIF4E:4EBP1 (4E:4EBP1; >25), and 7 of these (87.5%) had recurrence. Alternately, from 18 patients with low 4E:4EBP1 (<25; 69%), only 5 patients had recurrence (30.1%). To determine the probability of no recurrence, Kaplan-Meier analysis showed significantly poor disease-free survival in patients with elevated 4E:4EBP1 than those with low ratios (P < .01, log rank test). Elevated 4E:4EBP1 significantly correlated with increased disease recurrence. Because 4EBP1 modulates eIF4E activity, our results highlight the importance of incorporating a joint analysis of eIF4E and 4EBP1 mRNAs in HNSCC patient care decisions. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

26 CFR 1.1402(e)-1A - Application of regulations under section 1402(e).

Code of Federal Regulations, 2010 CFR

2010-04-01

... relate to section 1402(e) as amended by section 115(b)(2) of the Social Security Amendments of 1967 (81 Stat. 839) and apply to taxable years ending after 1967. Section 1.1402(e)-5A reflects changes made by... effect prior to amendment by the Social Security Amendments of 1967) applicable to taxable years ending...

Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs.

PubMed