Sample records for raske overvaegtige er

  1. Rab7a modulates ER stress and ER morphology.

    PubMed

    Mateus, Duarte; Marini, Elettra Sara; Progida, Cinzia; Bakke, Oddmund

    2018-05-01

    The Endoplasmic Reticulum (ER) is a membranous organelle with diverse structural and functional domains. Peripheral ER includes interconnected tubules, and dense tubular arrays called "ER matrices" together with bona fide flat cisternae. Transitions between these states are regulated by membrane-associated proteins and cytosolic factors. Recently, the small GTPases Rab10 and Rab18 were reported to control ER shape by regulating ER dynamics and fusion. Here, we present evidence that another Rab protein, Rab7a, modulates the ER morphology by controlling the ER homeostasis and ER stress. Indeed, inhibition of Rab7a expression by siRNA or expression of the dominant negative mutant Rab7aT22 N, leads to enlargement of sheet-like ER structures and spreading towards the cell periphery. Notably, such alterations are ascribable neither to a direct modulation of the ER shaping proteins Reticulon-4b and CLIMP63, nor to interactions with Protrudin, a Rab7a-binding protein known to affect the ER organization. Conversely, depletion of Rab7a leads to basal ER stress, in turn causing ER membrane expansion. Both ER enlargement and basal ER stress are reverted in rescue experiments by Rab7a re-expression, as well as by the ER chemical chaperone tauroursodeoxycholic acid (TUDCA). Collectively, these findings reveal a new role of Rab7a in ER homeostasis, and indicate that genetic and pharmacological ER stress manipulation may restore ER morphology in Rab7a silenced cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Eat it right: ER-phagy and recovER-phagy.

    PubMed

    Loi, Marisa; Fregno, Ilaria; Guerra, Concetta; Molinari, Maurizio

    2018-05-25

    The endoplasmic reticulum (ER) is the site of protein, lipid, phospholipid, steroid and oligosaccharide synthesis and modification, calcium ion storage, and detoxification of endogenous and exogenous products. Its volume (and activity) must be maintained under normal growth conditions, must be expanded in a controlled manner on activation of ER stress programs and must be reduced to pre-stress size during the recovery phase that follows ER stress termination. ER-phagy is the constitutive or regulated fragmentation and delivery of ER fragments to lysosomal compartments for clearance. It gives essential contribution to the maintenance of cellular homeostasis, proteostasis, lipidostasis and oligosaccharidostasis (i.e. the capacity to produce the proteome, lipidome and oligosaccharidome in appropriate quality and quantity). ER turnover is activated on ER stress, nutrient deprivation, accumulation of misfolded polypeptides, pathogen attack and by activators of macroautophagy. The selectivity of these poorly characterized catabolic pathways is ensured by proteins displayed at the limiting membrane of the ER subdomain to be removed from cells. These proteins are defined as ER-phagy receptors and engage the cytosolic macroautophagy machinery via specific modules that associate with ubiquitin-like, cytosolic proteins of the Atg8/LC3/GABARAP family. In this review, we give an overview on selective ER turnover and on the yeast and mammalian ER-phagy receptors identified so far. © 2018 The Author(s).

  3. Naltrexone ER/Bupropion ER: A Review in Obesity Management.

    PubMed

    Greig, Sarah L; Keating, Gillian M

    2015-07-01

    Oral naltrexone extended-release/bupropion extended-release (naltrexone ER/bupropion ER; Contrave(®), Mysimba(™)) is available as an adjunct to a reduced-calorie diet and increased physical activity in adults with an initial body mass index (BMI) of ≥ 30 kg/m(2) (i.e. obese) or a BMI of ≥ 27 kg/m(2) (i.e. overweight) in the presence of at least one bodyweight-related comorbidity, such as type 2 diabetes mellitus, hypertension or dyslipidaemia. In 56-week phase III trials in these patient populations, oral naltrexone ER/bupropion ER 32/360 mg/day was significantly more effective than placebo with regard to percentage bodyweight reductions from baseline and the proportion of patients who achieved bodyweight reductions of ≥ 5 and ≥ 10%. Significantly greater improvements in several cardiometabolic risk factors were also observed with naltrexone ER/bupropion ER versus placebo, as well as greater improvements in glycated haemoglobin levels in obese or overweight adults with type 2 diabetes. Naltrexone ER/bupropion ER was generally well tolerated in phase III trials, with nausea being the most common adverse event. Thus, naltrexone ER/bupropion ER 32/360 mg/day as an adjunct to a reduced-calorie diet and increased physical activity, is an effective and well tolerated option for chronic bodyweight management in obese adults or overweight adults with at least one bodyweight-related comorbidity.

  4. Low Estrogen Receptor (ER)-Positive Breast Cancer and Neoadjuvant Systemic Chemotherapy: Is Response Similar to Typical ER-Positive or ER-Negative Disease?

    PubMed

    Landmann, Alessandra; Farrugia, Daniel J; Zhu, Li; Diego, Emilia J; Johnson, Ronald R; Soran, Atilla; Dabbs, David J; Clark, Beth Z; Puhalla, Shannon L; Jankowitz, Rachel C; Brufsky, Adam M; Ahrendt, Gretchen M; McAuliffe, Priscilla F; Bhargava, Rohit

    2018-05-08

    Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors. Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded. The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases. Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy.

  5. ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology.

    PubMed

    Manford, Andrew G; Stefan, Christopher J; Yuan, Helen L; Macgurn, Jason A; Emr, Scott D

    2012-12-11

    Endoplasmic reticulum-plasma membrane (ER-PM) junctions are conserved structures defined as regions of the ER that tightly associate with the plasma membrane. However, little is known about the mechanisms that tether these organelles together and why such connections are maintained. Using a quantitative proteomic approach, we identified three families of ER-PM tethering proteins in yeast: Ist2 (related to mammalian TMEM16 ion channels), the tricalbins (Tcb1/2/3, orthologs of the extended synaptotagmins), and Scs2 and Scs22 (vesicle-associated membrane protein-associated proteins). Loss of all six tethering proteins results in the separation of the ER from the PM and the accumulation of cytoplasmic ER. Importantly, we find that phosphoinositide signaling is misregulated at the PM, and the unfolded protein response is constitutively activated in the ER in cells lacking ER-PM tether proteins. These results reveal critical roles for ER-PM contacts in cell signaling, organelle morphology, and ER function. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Comparison of Er:YAG and Er:YSGG laser ablation of dental hard tissues

    NASA Astrophysics Data System (ADS)

    Stock, Karl; Hibst, Raimund; Keller, Ulrich

    1997-12-01

    To compare ablation quality of Er:YAG and Er:YSGG laser the surface quality, crater shape, mass loss, and temperature development were determined using the same fiber transmission system and handpiece. Similar crater depths for both lasers but greater diameters for the Er:YAG laser were measured. Also mass loss per pulse of the Er:YAG laser exceeds that of the Er:YSGG laser. Temperature development while ablation of dentin is more pronounced for the Er:YSGG laser. The observed minor ablation quality of the Er:YSGG laser can be explained by the lower absorption coefficient of dental hard substances compared to the Er:YAG laser.

  7. Electronic state of Er in sputtered AlN:Er films determined by magnetic measurements

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

    Narang, V.; Seehra, M. S., E-mail: mseehra@wvu.edu; Korakakis, D.

    2014-12-07

    The optoelectronic and piezoelectric properties of AlN:Er thin films have been of great recent interest for potential device applications. In this work, the focus is on the electronic state of Er in AlN:Er thin films prepared by reactive magnetron sputtering on (001) p-type Si substrate. X-ray diffraction shows that Er doping expands the lattice and the AlN:Er film has preferential c-plane orientation. To determine whether Er in AlN:Er is present as Er metal, Er{sub 2}O{sub 3}, or Er{sup 3+} substituting for Al{sup 3+}, detailed measurements and analysis of the temperature dependence (2 K–300 K) of the magnetization M at a fixed magneticmore » field H along with the M vs. H data at 2 K up to H = 90 kOe are presented. The presence of Er{sub 2}O{sub 3} and Er metal is ruled out since their characteristic magnetic transitions are not observed in the AlN:Er sample. Instead, the observed M vs. T and M vs. H variations are consistent with Er present as Er{sup 3+} substituting for Al{sup 3+} in AlN:Er at a concentration x = 1.08% in agreement with x = 0.94% ± 0.20% determined using x-ray photoelectron spectroscopy (XPS). The larger size of Er{sup 3+} vs. Al{sup 3+}explains the observed lattice expansion of AlN:Er.« less

  8. Endoplasmic reticulum turnover: ER-phagy and other flavors in selective and non-selective ER clearance.

    PubMed

    Fregno, Ilaria; Molinari, Maurizio

    2018-01-01

    The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells. It is deputed to lipid and protein biosynthesis, calcium storage, and the detoxification of various exogenous and endogenous harmful compounds. ER activity and size must be adapted rapidly to environmental and developmental conditions or biosynthetic demand. This is achieved on induction of thoroughly studied transcriptional/translational programs defined as "unfolded protein responses" that increase the ER volume and the expression of ER-resident proteins regulating the numerous ER functions. Less understood are the lysosomal catabolic processes that maintain ER size at steady state, that prevent excessive ER expansion during ER stresses, or that ensure return to physiologic ER size during recovery from ER stresses. These catabolic processes may also be activated to remove ER subdomains where proteasome-resistant misfolded proteins or damaged lipids have been segregated. Insights into these catabolic mechanisms have only recently emerged with the identification of so-called ER-phagy receptors, which label specific ER subdomains for selective lysosomal delivery for clearance. Here, in eight chapters and one addendum, we comment on recent advances in ER turnover pathways induced by ER stress, nutrient deprivation, misfolded proteins, and live bacteria. We highlight the role of yeast (Atg39 and Atg40) and mammalian (FAM134B, SEC62, RTN3, and CCPG1) ER-phagy receptors and of autophagy genes in selective and non-selective catabolic processes that regulate cellular proteostasis by controlling ER size, turnover, and function.

  9. Minimising Immunohistochemical False Negative ER Classification Using a Complementary 23 Gene Expression Signature of ER Status

    PubMed Central

    Li, Qiyuan; Eklund, Aron C.; Juul, Nicolai; Haibe-Kains, Benjamin; Workman, Christopher T.; Richardson, Andrea L.; Szallasi, Zoltan; Swanton, Charles

    2010-01-01

    Background Expression of the oestrogen receptor (ER) in breast cancer predicts benefit from endocrine therapy. Minimising the frequency of false negative ER status classification is essential to identify all patients with ER positive breast cancers who should be offered endocrine therapies in order to improve clinical outcome. In routine oncological practice ER status is determined by semi-quantitative methods such as immunohistochemistry (IHC) or other immunoassays in which the ER expression level is compared to an empirical threshold[1], [2]. The clinical relevance of gene expression-based ER subtypes as compared to IHC-based determination has not been systematically evaluated. Here we attempt to reduce the frequency of false negative ER status classification using two gene expression approaches and compare these methods to IHC based ER status in terms of predictive and prognostic concordance with clinical outcome. Methodology/Principal Findings Firstly, ER status was discriminated by fitting the bimodal expression of ESR1 to a mixed Gaussian model. The discriminative power of ESR1 suggested bimodal expression as an efficient way to stratify breast cancer; therefore we identified a set of genes whose expression was both strongly bimodal, mimicking ESR expression status, and highly expressed in breast epithelial cell lines, to derive a 23-gene ER expression signature-based classifier. We assessed our classifiers in seven published breast cancer cohorts by comparing the gene expression-based ER status to IHC-based ER status as a predictor of clinical outcome in both untreated and tamoxifen treated cohorts. In untreated breast cancer cohorts, the 23 gene signature-based ER status provided significantly improved prognostic power compared to IHC-based ER status (P = 0.006). In tamoxifen-treated cohorts, the 23 gene ER expression signature predicted clinical outcome (HR = 2.20, P = 0.00035). These complementary ER signature-based strategies estimated that

  10. COPII-Dependent ER Export: A Critical Component of Insulin Biogenesis and β-Cell ER Homeostasis.

    PubMed

    Fang, Jingye; Liu, Ming; Zhang, Xuebao; Sakamoto, Takeshi; Taatjes, Douglas J; Jena, Bhanu P; Sun, Fei; Woods, James; Bryson, Tim; Kowluru, Anjaneyulu; Zhang, Kezhong; Chen, Xuequn

    2015-08-01

    Pancreatic β-cells possess a highly active protein synthetic and export machinery in the endoplasmic reticulum (ER) to accommodate the massive production of proinsulin. ER homeostasis is vital for β-cell functions and is maintained by the delicate balance between protein synthesis, folding, export, and degradation. Disruption of ER homeostasis by diabetes-causing factors leads to β-cell death. Among the 4 components to maintain ER homeostasis in β-cells, the role of ER export in insulin biogenesis is the least understood. To address this knowledge gap, the present study investigated the molecular mechanism of proinsulin ER export in MIN6 cells and primary islets. Two inhibitory mutants of the secretion-associated RAS-related protein (Sar)1 small GTPase, known to specifically block coat protein complex II (COPII)-dependent ER export, were overexpressed in β-cells using recombinant adenoviruses. Results from this approach, as well as small interfering RNA-mediated Sar1 knockdown, demonstrated that defective Sar1 function blocked proinsulin ER export and abolished its conversion to mature insulin in MIN6 cells, isolated mouse, and human islets. It is further revealed, using an in vitro vesicle formation assay, that proinsulin was packaged into COPII vesicles in a GTP- and Sar1-dependent manner. Blockage of COPII-dependent ER exit by Sar1 mutants strongly induced ER morphology change, ER stress response, and β-cell apoptosis. These responses were mediated by the PKR (double-stranded RNA-dependent kinase)-like ER kinase (PERK)/eukaryotic translation initiation factor 2α (p-eIF2α) and inositol-requiring protein 1 (IRE1)/x-box binding protein 1 (Xbp1) pathways but not via activating transcription factor 6 (ATF6). Collectively, results from the study demonstrate that COPII-dependent ER export plays a vital role in insulin biogenesis, ER homeostasis, and β-cell survival.

  11. YAG:Er3+, CaF2:Er3+, and Er2O3 Emission Spectra Under Laser and Laser Thermal Excitation

    NASA Astrophysics Data System (ADS)

    Marchenko, V. M.

    2018-05-01

    Experimental luminescence and selective-emission (SE) spectra of YAG:Er3+ (10 at.%) and CaF2:Er3+ (1 at.%) single crystals and Er2O3 polycrystal under laser and laser thermal excitation of the Er3+-ion multiplets are compared. Luminescence spectra under resonant excitation are determined by multiplet population relaxation with the corresponding radiative and nonradiative probabilities. The form of the SE spectra is determined by the thermal population of the multiplets and the probabilities of only radiative transitions. The SE band at 800 nm (4I9/2 → 4I15/2) is an indicator of high-temperature thermal emission of Er3+ ions. The absence of this band in luminescence spectra is explained by the short lifetime of the τ(4I9/2) level of 53 ns at T = 300 K.

  12. In Vitro Drug Release After Crushing: Evaluation of Xtampza® ER and Other ER Opioid Formulations.

    PubMed

    Mayock, Stephen P; Saim, Said; Fleming, Alison B

    2017-12-01

    Extended-release (ER) opioids are associated with high rates of abuse. Recreational opioid users often manipulate ER formulations to achieve a high plasma concentration in a short amount of time, resulting in a more rapid and intense high. Patients may also manipulate ER tablets to facilitate swallowing, without recognizing that manipulation could increase release rate. The goal of this study was to assess the ability of oxycodone DETERx (Xtampza ® ER, Collegium Pharmaceutical, Inc., Canton, MA, USA) and other commercially available ER opioid formulations with and without physicochemical abuse-deterrent characteristics to be manipulated by crushing in an in vitro setting. In vitro dissolution techniques were used to compare the opioid release from a variety of ER opioid formulations. Dissolution was assessed for intact and crushed dosage forms. Opioid release was quantified using high-performance liquid chromatography. Intact formulations exhibited drug release rates characteristic of 12- or 24-h dosage forms. After crushing using commonly available household tools, only Xtampza ER maintained ER of opioid. Xtampza ER maintained its ER characteristics after crushing, unlike many other commercially available opioid formulations, including some formulated with abuse-deterrent properties. As such, Xtampza ER may be less appealing to abusers and offer a margin of safety for patients who manipulate dosage forms to facilitate swallowing.

  13. ER-2 in flight

    NASA Technical Reports Server (NTRS)

    1996-01-01

    In this film clip, we see an ER-2 on its take off roll and climb as it departs from runway 22 at Edwards AFB, California. In 1981, NASA acquired its first ER-2 aircraft. The agency obtained a second ER-2 in 1989. These airplanes replaced two Lockheed U-2 aircraft, which NASA had used to collect scientific data since 1971. The U-2, and later the ER-2, were based at the Ames Research Center, Moffett Field, California, until 1997. In 1997, the ER-2 aircraft and their operations moved to NASA Dryden Flight Research Center, Edwards, California. Since the inaugural flight for this program, August 31, 1971, NASA U-2 and ER-2 aircraft have flown more than 4,000 data missions and test flights in support of scientific research conducted by scientists from NASA, other federal agencies, states, universities, and the private sector. NASA is currently using two ER-2 Airborne Science aircraft as flying laboratories. The aircraft, based at NASA Dryden, collect information about our surroundings, including Earth resources, celestial observations, atmospheric chemistry and dynamics, and oceanic processes. The aircraft also are used for electronic sensor research and development, satellite calibration, and satellite data validation. The ER-2 is a versatile aircraft well-suited to perform multiple mission tasks. It is 30 percent larger than the U-2 with a 20 feet longer wingspan and a considerably increased payload over the older airframe. The aircraft has four large pressurized experiment compartments and a high-capacity AC/DC electrical system, permitting it to carry a variety of payloads on a single mission. The modular design of the aircraft permits rapid installation or removal of payloads to meet changing mission requirements. The ER-2 has a range beyond 3,000 miles (4800 kilometers); is capable of long flight duration and can operate at altitudes up to 70,000 feet (21.3 kilometers) if required. Operating at an altitude of 65,000 feet (19.8 kilometers) the ER-2 acquires data

  14. Exciting transition metal doped dilute magnetic thin films: MgO:Er and ZnO:Er

    NASA Astrophysics Data System (ADS)

    Ćakıcı, T.; Sarıtaş, S.; Muǧlu, G. Merhan; Yıldırım, M.

    2017-02-01

    Erbium doped MgO and doped ZnO thin films have reasonably important properties applications in spintronic devices. These films were synthesized on glass substrates by Chemical Spray Pyrolysis (CSP) method. In the literature there has been almost no report on preparation of MgO:Er dilute magnetic thin films by means of CSP. Because doped thin films show different magnetic behaviors, depending upon the type of magnetic material ions, concentration of them, synthesis route and experimental conditions, synthesized MgO:Er and ZnO:Er films were compared to thin film properties. Optical analyses of the synthesized thin films were examined spectral absorption and transmittance measurements by UV-Vis double beam spectrophotometer technique. Structural analysis of the thin films was examined by using XRD, Raman Analysis, FE-SEM, EDX and AFM techniques. Also, magnetic properties of the MgO:Er and ZnO:Er films were investigated by vibrating sample magnetometer (VSM) which show that diamagnetic behavior of the MgO:Er thin film and ferromagnetic (FM) behavior of the ZnO:Er film were is formed.

  15. The role of the AR/ER ratio in ER-positive breast cancer patients.

    PubMed

    Rangel, Nelson; Rondon-Lagos, Milena; Annaratone, Laura; Osella-Abate, Simona; Metovic, Jasna; Mano, Maria Piera; Bertero, Luca; Cassoni, Paola; Sapino, Anna; Castellano, Isabella

    2018-03-01

    The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours. The aim of the present study was to analyse the prognostic impact of AR/ER ratio, evaluated by immunohistochemistry (IHC), correlating this value with clinical, pathological and molecular characteristics. We retrospectively selected a cohort of 402 ER+BC patients. On each tumour, IHC analyses for AR, ER, PgR, HER2 and Ki67 were performed and AR+ cases were used to calculate the AR/ER value. A cut-off of ≥2 was selected using receiver-operating characteristic (ROC) curve analyses. RNA from 19 cases with AR/ER≥2 was extracted and used for Prosigna-PAM50 assays. Tumours with AR/ER≥2 (6%) showed more frequent metastatic lymph nodes, larger size, higher histological grade and lower PgR levels than cases with AR/ER<2. Multivariate analysis confirmed that patients with AR/ER≥2 had worse disease-free interval (DFI) and disease-specific survival (DSS) (hazard ratios (HR) = 4.96 for DFI and HR = 8.69 for DSS, both P  ≤ 0.004). According to the Prosigna-PAM50 assay, 63% (12/19) of these cases resulted in intermediate or high risk of recurrence categories. Additionally, although all samples were positive for ER assessed by IHC, the molecular test assigned 47.4% (9/19) of BCs to intrinsic non-luminal subtypes. In conclusion, the AR/ER ratio ≥2 identifies a subgroup of patients with aggressive biological features and may represent an additional independent marker of worse BC prognosis. Moreover, the Prosigna-PAM50 results indicate that a significant number of cases with AR/ER≥2 could be non-luminal tumours. © 2018 Society for Endocrinology.

  16. ER trapping reveals Golgi enzymes continually revisit the ER through a recycling pathway that controls Golgi organization

    PubMed Central

    Sengupta, Prabuddha; Satpute-Krishnan, Prasanna; Seo, Arnold Y.; Burnette, Dylan T.; Patterson, George H.; Lippincott-Schwartz, Jennifer

    2015-01-01

    Whether Golgi enzymes remain localized within the Golgi or constitutively cycle through the endoplasmic reticulum (ER) is unclear, yet is important for understanding Golgi dependence on the ER. Here, we demonstrate that the previously reported inefficient ER trapping of Golgi enzymes in a rapamycin-based assay results from an artifact involving an endogenous ER-localized 13-kD FK506 binding protein (FKBP13) competing with the FKBP12-tagged Golgi enzyme for binding to an FKBP-rapamycin binding domain (FRB)-tagged ER trap. When we express an FKBP12-tagged ER trap and FRB-tagged Golgi enzymes, conditions precluding such competition, the Golgi enzymes completely redistribute to the ER upon rapamycin treatment. A photoactivatable FRB-Golgi enzyme, highlighted only in the Golgi, likewise redistributes to the ER. These data establish Golgi enzymes constitutively cycle through the ER. Using our trapping scheme, we identify roles of rab6a and calcium-independent phospholipase A2 (iPLA2) in Golgi enzyme recycling, and show that retrograde transport of Golgi membrane underlies Golgi dispersal during microtubule depolymerization and mitosis. PMID:26598700

  17. Effect of the unfolded protein response on ER protein export: a potential new mechanism to relieve ER stress.

    PubMed

    Shaheen, Alaa

    2018-05-05

    The unfolded protein response (UPR) is an adaptive cellular response that aims to relieve endoplasmic reticulum (ER) stress via several mechanisms, including inhibition of protein synthesis and enhancement of protein folding and degradation. There is a controversy over the effect of the UPR on ER protein export. While some investigators suggested that ER export is inhibited during ER stress, others suggested the opposite. In this article, their conflicting studies are analyzed and compared in attempt to solve this controversy. The UPR appears indeed to enhance ER export, possibly via multiple mechanisms. However, another factor, which is the integrity of the folding machinery/environment inside ER, determines whether ER export will appear increased or decreased during experimentation. Also, different methods of stress induction appear to have different effects on ER export. Thus, improvement of ER export may represent a new mechanism by which the UPR alleviates ER stress. This may help researchers to understand how the UPR works inside cells and how to manipulate it to alter cell fate during stress, either to promote cell survival or death. This may open up new approaches for the treatment of ER stress-related diseases.

  18. 20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. 228.10... component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. The...

  19. 20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. 228.10... component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. The...

  20. 20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. 228.10... component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. The...

  1. 20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. 228.10... component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. The...

  2. 20 CFR 228.10 - Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Computation of the tier I annuity component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. 228.10... component for a widow(er), disabled widow(er), remarried widow(er), and a surviving divorced spouse. The...

  3. 20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Adjustments to the widow(er)'s, disabled..., disabled widow(er)'s, surviving divorced spouse's, and remarried widow(er)'s tier I annuity amount. (a) If the employee died before attaining age 62 and after 1978 and the widow(er), disabled widow(er...

  4. 20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Adjustments to the widow(er)'s, disabled..., disabled widow(er)'s, surviving divorced spouse's, and remarried widow(er)'s tier I annuity amount. (a) If the employee died before attaining age 62 and after 1978 and the widow(er), disabled widow(er...

  5. 20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Adjustments to the widow(er)'s, disabled..., disabled widow(er)'s, surviving divorced spouse's, and remarried widow(er)'s tier I annuity amount. (a) If the employee died before attaining age 62 and after 1978 and the widow(er), disabled widow(er...

  6. Shear mode ER transfer function for robotic applications

    NASA Astrophysics Data System (ADS)

    Tan, K. P.; Stanway, R.; Bullough, W. A.

    2005-06-01

    Electro-rheological (ER) fluids are becoming popular in modern industrial applications. The advantage of employing ER devices is due to the ease of energizing the ER fluids at fast speeds of response. One innovation in ER applications could be in the positioning control of the robotic arm using an ER clutch. In order to actuate the manipulator, the ER output torque response is required. However, the behaviour of this ER torque response at different input conditions is not clearly understood. Therefore, in this paper, a sample study of the ER output torque is conducted. The ER output torque responses at different input parameters are studied carefully for the establishment of an appropriate ER transfer function in shear mode. This transfer function will serve as an important feature in future ER-actuated robot arm's control process.

  7. 20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Adjustments to the widow(er)'s, disabled widow..., disabled widow(er)'s, surviving divorced spouse's, and remarried widow(er)'s tier I annuity amount. (a) If the employee died before attaining age 62 and after 1978 and the widow(er), disabled widow(er...

  8. 20 CFR 228.17 - Adjustments to the widow(er)'s, disabled widow(er)'s, surviving divorced spouse's, and remarried...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Adjustments to the widow(er)'s, disabled widow..., disabled widow(er)'s, surviving divorced spouse's, and remarried widow(er)'s tier I annuity amount. (a) If the employee died before attaining age 62 and after 1978 and the widow(er), disabled widow(er...

  9. Endoplasmic Reticulum (ER) Stress and Endocrine Disorders

    PubMed Central

    Ariyasu, Daisuke; Yoshida, Hiderou; Hasegawa, Yukihiro

    2017-01-01

    The endoplasmic reticulum (ER) is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the “unfolded protein response” (UPR), which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI), Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2) are discussed in this article. PMID:28208663

  10. The structure of the 168Er nucleus and the 166Er(t,p) 168 Er reaction in terms of the sdg interacting boson model

    NASA Astrophysics Data System (ADS)

    Akiyama, Y.; Heyde, K.; Arima, A.; Yoshinaga, N.

    1986-05-01

    Extending the interacting boson model by incorporating besides s and d, also the g-boson, we can describe the population of positive parity states of 168Er in the 166Er(t,P) 168Er reaction rather well. In particular, the excitation of I,Kπi = 4,3 +1; 2,2 +2; 0,0 +3 and 0,0 +4 states is much improved over the sd-IBM approach.

  11. Functional characterization of estrogen receptor subtypes, ER{alpha} and ER{beta}, mediating vitellogenin production in the liver of rainbow trout

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

    Leanos-Castaneda, Olga; Kraak, Glen van der

    2007-10-15

    The estrogen-dependent process of vitellogenesis is a key function on oviparous fish reproduction and it has been widely used as an indicator of xenoestrogen exposure. The two estrogen receptor (ER) subtypes, ER{alpha} and ER{beta}, are often co-expressed in the liver of fish. The relative contribution of each ER subtype to modulate vitellogenin production by hepatocytes was studied using selected compounds known to preferentially interact with specific ER subtypes: propyl-pyrazole-triol (PPT) an ER{alpha} selective agonist, methyl-piperidino-pyrazole (MPP) an ER{alpha} selective antagonist, and diarylpropionitrile (DPN) an ER{beta} selective agonist. First, the relative binding affinity of the test compounds to estradiol for rainbowmore » trout hepatic nuclear ER was determined using a competitive ligand binding assay. All the test ligands achieved complete displacement of specific [{sup 3}H]-estradiol binding from the nuclear ER extract. This indicates that the test ligands have the potential to modify the ER function in the rainbow trout liver. Secondly, the ability of the test compounds to induce or inhibit vitellogenin production by primary cultures of rainbow trout hepatocytes was studied. Estradiol and DPN were the only compounds that induced a dose-dependent increase on vitellogenin synthesis. The lack of vitellogenin induction by PPT indicates that ER{alpha} could not have a role on this reproductive process whereas the ability of DPN to induce vitellogenin production supports the participation of ER{beta}. In addition, this hypothesis is reinforced by the results obtained from MPP plus estradiol. On one hand, the absence of suppressive activity of MPP in the estradiol-induced vitellogenin production does not support the participation of ER{alpha}. On the other hand, once blocked ER{alpha} with MPP, the only manifestation of agonist activity of estradiol would be achieved via ER{beta}. In conclusion, the present results indicate that vitellogenin

  12. Investigating the evolution of local structure around Er and Yb in ZnO:Er and ZnO:Er, Yb on annealing using X-ray absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Anjana, R.; Jayaraj, M. K.; Yadav, A. K.; Jha, S. N.; Bhattacharyya, D.

    2018-04-01

    The local structure around Er and Yb centre in ZnO favouring upconversion luminescence was studied using EXAFS (Extended X-ray absorption fine structure spectroscopy). Due to the ionic radii difference between Zn and Er, Yb ions, the dopants cannot replace Zn in the ZnO lattice properly. Er2O3 and Yb2O3 impurity phases are formed at the grain boundaries of ZnO. It is found that the local structure around the Er centre in ZnO is modified on annealing in air. The symmetry around both erbium and ytterbium reduces with increase in annealing temperature. Symmetry reduction will favour the intra-4f transition and the energy transitions causing upconversion luminescence. By fitting the EXAFS data with theoretically simulated data, it is found that the Er centre forms a local structure similar to C4ν symmetry which is a distorted octahedron. On annealing the sample to 1200 °C, all the erbium centres are transformed to C4ν symmetry causing enhanced upconversion emission. Yb centre has also been modified on annealing. The decrease in co-ordination number with annealing temperature will decrease the symmetry and increase the near infrared absorption cross section. The decrease in symmetry around both the erbium and ytterbium centre and formation of C4ν symmetry around Er centre is the reason behind the activation of upconversion luminescence with high temperature annealing in both Er doped and Er, Yb co-doped ZnO samples. The study will be useful for the synthesis of high efficiency upconversion materials.

  13. ER signaling is activated to protect human HaCaT keratinocytes from ER stress induced by environmental doses of UVB

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

    Mera, Kentaro; Kawahara, Ko-ichi; Tada, Ko-ichi

    Proteins are folded properly in the endoplasmic reticulum (ER). Various stress such as hypoxia, ischemia and starvation interfere with the ER function, causing ER stress, which is defined by the accumulation of unfolded protein (UP) in the ER. ER stress is prevented by the UP response (UPR) and ER-associated degradation (ERAD). These signaling pathways are activated by three major ER molecules, ATF6, IRE-1 and PERK. Using HaCaT cells, we investigated ER signaling in human keratinocytes irradiated by environmental doses of ultraviolet B (UVB). The expression of Ero1-L{alpha}, an upstream signaling molecule of ER stress, decreased at 1-4 h after 10more » mJ/cm{sup 2} irradiation, indicating that the environmental dose of UVB-induced ER stress in HaCaT cells, without growth retardation. Furthermore, expression of intact ATF6 was decreased and it was translocated to the nuclei. The expression of XBP-1, a downstream molecule of IRE-1, which is an ER chaperone whose expression is regulated by XBP-1, and UP ubiquitination were induced by 10 mJ/cm{sup 2} UVB at 4 h. PERK, which regulates apoptosis, was not phosphorylated. Our results demonstrate that UVB irradiation generates UP in HaCaT cells and that the UPR and ERAD systems are activated to protect cells from UVB-induced ER stress. This is the first report to show ER signaling in UVB-irradiated keratinocytes.« less

  14. Photoluminescence spectra of n-ZnO/p-GaN:(Er + Zn) and p-AlGaN:(Er + Zn) heterostructures

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

    Mezdrogina, M. M., E-mail: margaret.m@mail.ioffe.ru; Krivolapchuk, V. V., E-mail: vlad.krivol@mail.ioffe.ru; Feoktistov, N. A.

    2008-07-15

    Luminescence intensity of heterostructures based on n-ZnO/p-GaN:(Er + Zn) and n-ZnO/AlGaN:(Er + Zn) is higher by more than an order of magnitude than the corresponding intensity of separate n-ZnO, p-GaN:(Er + Zn), and AlGaN:(Er + Zn) layers. Most likely, this phenomenon is due to the effective tunneling recombination of charge carriers caused by a decrease in the concentration of the nonradiative recombination centers located between the n-ZnO/p-GaN:(Er + Zn) and n-ZnO/AlGaN:(Er + Zn) layers.

  15. Excited-state absorption in Er: BaY2F8 and Cs3Er2Br9 and comparison with Er: LiYF4

    NASA Astrophysics Data System (ADS)

    Pollnau, M.; Lüthy, W.; Weber, H. P.; Krämer, K.; Güdel, H. U.; McFarlane, R. A.

    1996-04-01

    The influence of Excited-State Absorption (ESA) on the green laser transition and the overlap of Ground-State Absorption (GSA) and ESA for 970 nm upconversion pumping in erbium is investigated in Er3+ : BaY2F8 and Cs3Er2Br9. Results are compared to Er3+ : LiYF4. In Er3+: BaY2F8, a good overlap between GSA and ESA is found at 969 nm in one polarization direction. The emission cross section at 550 nm is a factor of two smaller than in LiYF4. In Cs3Er2Br9, the smaller Stark splitting of the levels shifts the wavelengths of the green emission and ESA from4 I 1 3/2 off resonance. It enhances, however, ground-state reabsorption. The emission cross section at 550 nm is comparable to LiYF4. Upconversion leads to significant green fluorescence from2 H 9/2. A significant population of the4 I 11/2 level and ESA at 970 nm are not present under 800 nm pumping.

  16. ER Stress: A Therapeutic Target in Rheumatoid Arthritis?

    PubMed

    Rahmati, Marveh; Moosavi, Mohammad Amin; McDermott, Michael F

    2018-04-22

    Diverse physiological and pathological conditions that impact on protein folding of the endoplasmic reticulum (ER) cause ER stress. The unfolded protein response (UPR) and the ER-associated degradation (ERAD) pathway are activated to cope with ER stress. In rheumatoid arthritis (RA), inflammation and ER stress work in parallel by driving inflammatory cells to release cytokines that induce chronic ER stress pathways. This chronic ER stress may contribute to the pathogenesis of RA through synoviocyte proliferation and proinflammatory cytokine production. Therefore, ER stress pathways and their constituent elements are attractive targets for RA drug development. In this review, we integrate current knowledge of the contribution of ER stress to the overall pathogenesis of RA, and suggest some therapeutic implications of these discoveries. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats

    PubMed Central

    Chen, Xia; Fu, Xiang-Sheng; Li, Chang-Ping; Zhao, Hong-Xian

    2014-01-01

    AIM: To investigate the gastric muscle injury caused by endoplasmic reticulum (ER) stress in rats with diabetic gastroparesis. METHODS: Forty rats were randomly divided into two groups: a control group and a diabetic group. Diabetes was induced by intraperitoneal injection of 60 mg/kg of streptozotocin. Gastric emptying was determined at the 4th and 12th week. The ultrastructural changes in gastric smooth muscle cells (SMCs) were investigated by transmission electron microscopy. TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to assess apoptosis of SMCs. Expression of the ER stress marker, glucose-regulated protein 78 (GRP78), and the ER-specific apoptosis mediator, caspase-12 protein, was determined by immunohistochemistry. RESULTS: Gastric emptying was significantly lower in the diabetic rats than in the control rats at the 12th wk (40.71% ± 2.50%, control rats vs 54.65% ± 5.22%, diabetic rats; P < 0.05). Swollen and distended ER with an irregular shape was observed in gastric SMCs in diabetic rats. Apoptosis of gastric SMCs increased in the diabetic rats in addition to increased expression of GRP78 and caspase-12 proteins. CONCLUSION: ER stress and ER stress-mediated apoptosis are activated in gastric SMCs in diabetic rats with gastroparesis. PMID:25009401

  18. Bond strength of composites on Er:YAG and Er,Cr:YSGG laser-irradiated enamel

    NASA Astrophysics Data System (ADS)

    Apel, Christian; Gutknecht, Norbert

    1999-02-01

    In an in vitro study the bond strength of composite materials on Er:YAG and Er,Cr:YSGG laser-radiated enamel was examined. The results achieved on enamel surfaces conditioned conventionally using the acid etching method served as a control. On 80 extracted cariesfree third molars an enamel area of 4 X 4 mm was conditioned with three different systems. The Er:YAG laser was used at pulse frequencies of 8 Hz, 10 Hz, 12 Hz and 15 Hz using an energy of 120 mJ at each setting. The Er,Cr:YSGG laser was used at the settings of 20 Hz/50 mJ, 20 Hz/100 mJ and 20 Hz/150 mJ. The repetition rate for this device is constantly 20 Hz. In the reference group 10 teeth were etched with 37% phosphoric acid. In order to be able to perform the tensile tests under standard conditions metal brackets were placed on the conditioned surfaces. The 'Orthodontic-Bonding-System' was used as an adhesive system. The brackets were pulled off from the etched surfaces vertically to the tooth using a tensile testing machine. The results confirmed the highest bond strengths in the group of enamel surfaces which have been conditioned with acid etching gel. The bond strength of the Er:YAG laser (8, 10 and 12 Hz)- and Er,Cr:YSGG laser (20 Hz/150 mJ)-conditioned enamel surfaces was not significantly lower.

  19. Sigma-1 Receptor Chaperone at the ER-Mitochondrion Interface Mediates the Mitochondrion-ER-Nucleus Signaling for Cellular Survival

    PubMed Central

    Mori, Tomohisa; Hayashi, Teruo; Hayashi, Eri; Su, Tsung-Ping

    2013-01-01

    The membrane of the endoplasmic reticulum (ER) of a cell forms contacts directly with mitochondria whereby the contact is referred to as the mitochondrion-associated ER membrane or the MAM. Here we found that the MAM regulates cellular survival via an MAM-residing ER chaperone the sigma-1 receptor (Sig-1R) in that the Sig-1R chaperones the ER stress sensor IRE1 to facilitate inter-organelle signaling for survival. IRE1 is found in this study to be enriched at the MAM in CHO cells. We found that IRE1 is stabilized at the MAM by Sig-1Rs when cells are under ER stress. Sig-1Rs stabilize IRE1 and thus allow for conformationally correct IRE1 to dimerize into the long-lasting, activated endonuclease. The IRE1 at the MAM also responds to reactive oxygen species derived from mitochondria. Therefore, the ER-mitochondrion interface serves as an important subcellular entity in the regulation of cellular survival by enhancing the stress-responding signaling between mitochondria, ER, and nucleus. PMID:24204710

  20. Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival.

    PubMed

    Mori, Tomohisa; Hayashi, Teruo; Hayashi, Eri; Su, Tsung-Ping

    2013-01-01

    The membrane of the endoplasmic reticulum (ER) of a cell forms contacts directly with mitochondria whereby the contact is referred to as the mitochondrion-associated ER membrane or the MAM. Here we found that the MAM regulates cellular survival via an MAM-residing ER chaperone the sigma-1 receptor (Sig-1R) in that the Sig-1R chaperones the ER stress sensor IRE1 to facilitate inter-organelle signaling for survival. IRE1 is found in this study to be enriched at the MAM in CHO cells. We found that IRE1 is stabilized at the MAM by Sig-1Rs when cells are under ER stress. Sig-1Rs stabilize IRE1 and thus allow for conformationally correct IRE1 to dimerize into the long-lasting, activated endonuclease. The IRE1 at the MAM also responds to reactive oxygen species derived from mitochondria. Therefore, the ER-mitochondrion interface serves as an important subcellular entity in the regulation of cellular survival by enhancing the stress-responding signaling between mitochondria, ER, and nucleus.

  1. Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

    PubMed Central

    Bravo, Roberto; Gutierrez, Tomás; Paredes, Felipe; Gatica, Damián; Rodriguez, Andrea E.; Pedrozo, Zully; Chiong, Mario; Parra, Valentina; Quest, Andrew F.G.; Rothermel, Beverly A.; Lavandero, Sergio

    2014-01-01

    Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER–mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID:22064245

  2. FIRE_ACE_ER2_MAS

    Atmospheric Science Data Center

    2017-04-26

    ... Moderate Resolution Imaging Spectrometer (MODIS) Airborne Simulator (MAS) Data Project Title:  MAS ... IDL Code ER2 Flight Tracks Related Data:  MAS Additional Info:  ER-2 MODIS Airborne Simulator (MAS) Image Gallery:  ...

  3. Raman Spectrum of Er-Y-codoped ZrO2 and Fluorescence Properties of Er3+

    NASA Astrophysics Data System (ADS)

    He, Jun; Luo, Meng-fei; Jin, Ling-yun; He, Mai; Fang, Ping; Xie, Yun-long

    2007-02-01

    Er-Y-codoped ZrO2 mixed oxides with monoclinic, tetragonal and cubic structures were prepared by a sol-gel method. The crystal structure of ZrO2 matrix and the effect of the ZrO2 phases on the fluorescence properties of Er3+ were studied using Raman spectroscopy. The results indicated that the fluorescence properties of Er3+ depend on its local ZrO2 crystal structures. As ZrO2 matrix transferred from monoclinic to tetragonal and cubic phase, the Raman and fluorescence bands of Er3+ decreased in intensities and tended to form a single peak. With 632.8 nm excitation, the bands between 640 and 680 nm were attributed to the fluorescence of Er3+ in the ZrO2 environment. However, only the fluorescence was observed and no Raman spectra were seen under 514.5 nm excitation, while only Raman spectra were observed under 325 nm excitation. UV Raman spectroscopy was found to be more sensitive in the surface region while the information provided by XRD mainly came from the bulk. The phase with lower symmetry forms more easily on the surface than in the bulk.

  4. ER stress-induced protein, VIGG, disturbs plant cation homeostasis, which is correlated with growth retardation and robustness to ER stress

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

    Katoh, Hironori; Fujita, Keiko; Takuhara, Yuki

    2011-02-18

    Highlights: {yields} VIGG is an ER stress-induced protein in plant. {yields} We examine the characteristics of VIGG-overexpressing Arabidopsis plants. {yields} VIGG-overexpressing plants reveal growth retardation and robustness to ER stress. {yields} VIGG disturbs cation homeostasis in plant. -- Abstract: VIGG is a putative endoplasmic reticulum (ER) resident protein induced by virus infection and ER stress, and is correlated with fruit quality in grapevine. The present study was undertaken to determine the biological function of VIGG in grapevine. Experiments using fluorescent protein-VIGG fusion protein demonstrated that VIGG is localized in ER and the ER targeting sequence is in the N-terminus. Themore » overexpression of VIGG in Arabidopsis plant led to growth retardation. The rosette leaves of VIGG-overexpressing plants were smaller than those of the control plants and rolled at 42 days after seeding. VIGG-overexpressing plants revealed robustness to ER stress as well as the low expression of ER stress marker proteins, such as the luminal binding proteins. These characteristics of VIGG-overexpressing plants were supported by a microarray experiment that demonstrated the disruption of genes related to ER stress response and flowering, as well as cation mobility, in the plants. Finally, cation homeostasis in the plants was disturbed by the overexpression of VIGG. Taken together, these results suggest that VIGG may disturb cation homeostasis in plant, which is correlated with the robustness to ER stress and growth retardation.« less

  5. Laser performance of in-band pumped Er : LiYF4 and Er : LiLuF4 crystals

    NASA Astrophysics Data System (ADS)

    Gorbachenya, K. N.; Kurilchik, S. V.; Kisel, V. E.; Yasukevich, A. S.; Kuleshov, N. V.; Nizamutdinov, A. S.; Korableva, S. L.; Semashko, V. V.

    2016-02-01

    Spectroscopic properties of Er : LiLuF4 and Er : LiYF4 crystals in the spectral region near 1.5 μm and the lasing characteristics of these crystals under in-band pumping at a wavelength of 1522 nm are studied. With the Er : LiLuF4 crystal, the maximum slope efficiency with respect to the absorbed pump power was 44% at a wavelength of 1609 nm. Continuous-wave operation of an inband pumped Er : LiYF4 laser is obtained for the first time. The output power at a wavelength of 1606 nm was 58 mW with a slope efficiency of 21%.

  6. FIRE_AX_ER2_MAS

    Atmospheric Science Data Center

    2015-11-24

    ... Transition Experiment (ASTEX) ER-2 MODIS Airborne Simulator (MAS) Data Project Title:  MAS ... Temporal Resolution:  Each granule contains one flight track File Format:  HDF Tools:  ... Additional Info:  NASA ER-2 MODIS Airborne Simulator (MAS) SCAR-B Block:  SCAR-B ...

  7. Estrogen receptor (ER)-beta, but not ER-alpha, is present in thyroid vessels: immunohistochemical evaluations in multinodular goiter and papillary thyroid carcinoma.

    PubMed

    Ceresini, Graziano; Morganti, Simonetta; Graiani, Virna; Saccani, Maria; Milli, Bruna; Usberti, Elisa; Valenti, Giorgio; Ceda, Gian Paolo; Corcione, Luigi

    2006-12-01

    Estrogen receptors (ERs) have been demostrated in the vessel structures of several systems. Little is known on the presence of ERs in the thyroid vessels. We immunohistochemically evaluated both ER-alpha and ER-beta immunoreactivity (IR) in both vascular and follicular thyroid cells in tissue samples from 17 cases of multinodular goiter (MNG) and 17 cases of papillary thyroid carcinoma (PTC). ER-alpha IR was undetectable in either tissue examined. In 100% of MNG samples, nuclear ER-beta IR was detected in both endothelial and follicular cells. In PTC samples, endothelial nuclear ER-beta IR was found in 100% of cases, whereas the nuclear staining of follicular cells was found in 83% of cases. The intensity of staining of the endothelial ER-beta IR was comparable between MNG and PTC. However, when follicular cells were considered, a tendency toward a decrease in nuclear staining and a significant increase in cytoplasmic staining were found in PTC lesions as compared to MNG. This study demonstrated that ER-beta, but not ER-alpha, IR is present in the endothelium of thyroid vessels. Furthermore, although data need to be confirmed in larger observations, these results suggest the lack of differences in the pattern of vascular ER-beta IR between MNG and PTC.

  8. Electroreduction of Er 3+ in nonaqueous solvents

    DOE PAGES

    Small, Leo J.; Sears, Jeremiah M.; Lambert, Timothy N.; ...

    2016-09-15

    Here, the electroreduction of Er 3+ in propylene carbonate, N,N-dimethylformamide, or a variety of quaternary ammonium ionic liquids (ILs) was investigated using [Er(OTf) 3] and [Er(NTf 2) 3]. Systematic variation of the ILs' cation and anion, Er 3+ salt, and electrode material revealed a disparity in electrochemical interactions not previously seen. For most ILs at a platinum electrode, cyclic voltammetry exhibits irreversible interactions between Er 3+ salts and the electrode at potentials significantly less than the theoretical reduction potential for Er 3+. Throughout all solvent–salt systems tested, a deposit could be formed on the electrode, though obtaining a high purity,more » crystalline Er 0 deposit is challenging due to the extreme reactivity of the deposit and resulting chemical interactions, often resulting in the formation of a complex, amorphous solid–electrolyte interface that slowed deposition rates. Comparison of platinum, gold, nickel, and glassy carbon (GC) working electrodes revealed oxidation processes unique to the platinum surface. While no appreciable reduction current was observed on GC at the potentials investigated, deposits were seen on platinum, gold, and nickel electrodes.« less

  9. Hard tooth tissue removal by short and long Er:YAG or Er,Cr:YSGG mid-infrared laser radiation

    NASA Astrophysics Data System (ADS)

    Jelínková, H.; Dostálová, T.; Remeš, M.; Šulc, J.; Němec, M.; Fibrich, M.

    2017-02-01

    Hard dental tissue removal by laser radiation is an alternative treatment to conventional dental-drilling procedures. The advantages of this therapy are fast and localized treatment of hard dental tissue and painlessness. The most effective systems for those purposes are Er-lasers generating radiation at wavelengths of around 3 μm. The aim of this study was qualitative and quantitative examination of human dentin and ivory tissue removal by pulsed free-running (FR) and Q-switched (QSW) Er:YAG and Er,Cr:YSGG laser radiations. From the obtained results it follows that generally Er:YAG laser has lower threshold for the tissue removal in both FR and QSW regimes. Furthermore, the FR Er:YAG and Er,Cr:YSGG radiation can be effective for both dentin and ivory ablation and can prepare smooth cavities without side effects. The QSW regime is useful preferably for precise ablation of a starting tooth defect and for the part of the tooth very close to the gum. This regime is excellent for micro-preparation or for tooth treatment of children.

  10. An ER protein functionally couples neutral lipid metabolism on lipid droplets to membrane lipid synthesis in the ER.

    PubMed

    Markgraf, Daniel F; Klemm, Robin W; Junker, Mirco; Hannibal-Bach, Hans K; Ejsing, Christer S; Rapoport, Tom A

    2014-01-16

    Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Untangling the web: Mechanisms underlying ER network formation

    PubMed Central

    Goyal, Uma; Blackstone, Craig

    2013-01-01

    The ER is a continuous membrane system consisting of the nuclear envelope, flat sheets often studded with ribosomes, and a polygonal network of highly-curved tubules extending throughout the cell. Although protein and lipid biosynthesis, protein modification, vesicular transport, Ca2+dynamics, and protein quality control have been investigated in great detail, mechanisms that generate the distinctive architecture of the ER have been uncovered only recently. Several protein families including the reticulons and REEPs/DP1/Yop1p harbor hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1p family of dynamin-related GTPases interact with the ER-shaping proteins and mediate the formation of three-way junctions responsible for the polygonal structure of the tubular ER network, with Lunapark proteins acting antagonistically. Additional classes of tubular ER proteins including some REEPs and the M1 spastin ATPase interact with the microtubule cytoskeleton. Flat ER sheets possess a different complement of proteins such as p180, CLIMP-63 and kinectin implicated in shaping, cisternal stacking and cytoskeletal interactions. The ER is also in constant motion, and numerous signaling pathways as well as interactions among cytoskeletal elements, the plasma membrane, and organelles cooperate to position and shape the ER dynamically. Finally, many proteins involved in shaping the ER network are mutated in the most common forms of hereditary spastic paraplegia, indicating a particular importance for proper ER morphology and distribution in large, highly-polarized cells such as neurons. PMID:23602970

  12. Microtensile bond strength analysis of adhesive systems to Er:YAG and Er,Cr:YSGG laser-treated dentin.

    PubMed

    Ramos, Thaysa Monteiro; Ramos-Oliveira, Thayanne Monteiro; Moretto, Simone Gonçalves; de Freitas, Patricia Moreira; Esteves-Oliveira, Marcella; de Paula Eduardo, Carlos

    2014-03-01

    The aim of this in vitro study was to evaluate the effect of different surface treatments (control, diamond bur, erbium-doped yttrium aluminum garnet (Er:YAG) laser, and erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser) on sound dentin surface morphology and on microtensile bond strength (μTBS). Sixteen dentin fragments were randomly divided into four groups (n = 4), and different surface treatments were analyzed by scanning electron microscopy. Ninety-six third molars were randomly divided into eight groups (n = 12) according to type of surface treatment and adhesive system: G1 = Control + Clearfil SE Bond (SE); G2 = Control + Single Bond (SB); G3 = diamond bur (DB) + SE; G4 = DB + SB, G5 = Er:YAG laser (2.94 μm, 60 mJ, 2 Hz, 0.12 W, 19.3 J/cm(2)) + SE; G6 = Er:YAG + SB, G7 = Er,Cr:YSGG laser (2.78 μm, 50 mJ, 30 Hz, 1.5 W, 4.5 J/cm(2)) + SE; and G8 = Er,Cr:YSGG + SB. Composite blocks were bonded to the samples, and after 24-h storage in distilled/deionized water (37 °C), stick-shaped samples were obtained and submitted to μTBS test. Bond strength values (in megapascal) were analyzed by two-way ANOVA and Tukey tests (α = 0.05). G1 (54.69 ± 7.8 MPa) showed the highest mean, which was statistically significantly higher than all the other groups (p < 0.05). For all treatments, SE showed higher bond strength than SB, except only for Er,Cr:YSGG treatment, in which the systems did not differ statistically from each other. Based on the irradiation parameters considered in this study, it can be concluded that Er:YAG and Er,Cr:YSGG irradiation presented lower values than the control group; however, their association with self-etching adhesive does not have a significantly negative effect on sound dentin (μTBS values of >20 MPa).

  13. Arctigenin alleviates ER stress via activating AMPK

    PubMed Central

    Gu, Yuan; Sun, Xiao-xiao; Ye, Ji-ming; He, Li; Yan, Shou-sheng; Zhang, Hao-hao; Hu, Li-hong; Yuan, Jun-ying; Yu, Qiang

    2012-01-01

    Aim: To investigate the protective effects of arctigenin (ATG), a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L (Compositae), against ER stress in vitro and the underlying mechanisms. Methods: A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTT assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKKβ, LKB1, and AMPKα1 genes was achieved by RNA interference (RNAi). An ATP bioluminescent assay kit was employed to measure the intracellular ATP levels. Results: ATG (2.5, 5 and 10 μmol/L) inhibited cell death and unfolded protein response (UPR) in a concentration-dependent manner in cells treated with the ER stress inducer brefeldin A (100 nmol/L). ATG (1, 5 and 10 μmol/L) significantly attenuated protein synthesis in cells through inhibiting mTOR-p70S6K signaling and eEF2 activity, which were partially reversed by silencing AMPKα1 with RNAi. ATG (1-50 μmol/L) reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C (25 μmol/L) rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG (2.5 and 5 μmol/L) efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate (2 mmol/L) in INS-1 β cells. Conclusion: ATG is an effective ER stress alleviator, which protects cells against ER stress through activating AMPK, thus attenuating protein translation and reducing ER load. PMID:22705729

  14. Enhancement of endoplasmic reticulum (ER) degradation of misfolded Null Hong Kong alpha1-antitrypsin by human ER mannosidase I.

    PubMed

    Hosokawa, Nobuko; Tremblay, Linda O; You, Zhipeng; Herscovics, Annette; Wada, Ikuo; Nagata, Kazuhiro

    2003-07-11

    Misfolded glycoproteins synthesized in the endoplasmic reticulum (ER) are degraded by cytoplasmic proteasomes, a mechanism known as ERAD (ER-associated degradation). In the present study, we demonstrate that ERAD of the misfolded genetic variant-null Hong Kong alpha1-antitrypsin is enhanced by overexpression of the ER processing alpha1,2-mannosidase (ER ManI) in HEK 293 cells, indicating the importance of ER ManI in glycoprotein quality control. We showed previously that EDEM, an enzymatically inactive mannosidase homolog, interacts with misfolded alpha1-antitrypsin and accelerates its degradation (Hosokawa, N., Wada, I., Hasegawa, K., Yorihuzi, T., Tremblay, L. O., Herscovics, A., and Nagata, K. (2001) EMBO Rep. 2, 415-422). Herein we demonstrate a combined effect of ER ManI and EDEM on ERAD of misfolded alpha1-antitrypsin. We also show that misfolded alpha1-antitrypsin NHK contains labeled Glc1Man9GlcNAc and Man5-9GlcNAc released by endo-beta-N-acetylglucosaminidase H in pulse-chase experiments with [2-3H]mannose. Overexpression of ER ManI greatly increases the formation of Man8GlcNAc, induces the formation of Glc1Man8GlcNAc and increases trimming to Man5-7GlcNAc. We propose a model whereby the misfolded glycoprotein interacts with ER ManI and with EDEM, before being recognized by downstream ERAD components. This detailed characterization of oligosaccharides associated with a misfolded glycoprotein raises the possibility that the carbohydrate recognition determinant triggering ERAD may not be restricted to Man8GlcNAc2 isomer B as previous studies have suggested.

  15. Prevention of ER-Negative Breast Cancer

    PubMed Central

    Li, Yuxin

    2014-01-01

    The successful demonstration that the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene reduce the risk of breast cancer has stimulated great interest in using drugs to prevent breast cancer in high-risk women. In addition, recent results from breast cancer treatment trials suggest that aromatase inhibitors may be even more effective at preventing breast cancer than are SERMs. However, while SERMs and aromatase inhibitors do prevent the development of many estrogen-receptor (ER)-positive breast cancers, these drugs do not prevent the development of ER-negative breast cancer. Thus, there is an urgent need to identify agents that can prevent ER-negative breast cancer. We have studied the cancer preventative activity of several classes of drugs for their ability to prevent ER-negative breast cancer in preclinical models. Results from these studies demonstrate that rexinoids (analogs of retinoids that bind and activate RXR receptors), tyrosine kinase inhibitors (such as EGFR inhibitors and dual kinase inhibitors that block EGFR and HER2/neu signaling), and cyclo-oxygenase 2 (COX-2) inhibitors all prevent ER-negative breast cancer in transgenic mice that develop ER-negative breast cancer. Other promising agents now under investigation include vitamin D and vitamin D analogs, drugs that activate PPAR-gamma nuclear receptors, and statins. Many of these agents are now being tested in early phase cancer prevention clinical trials to determine whether they will show activity in breast tissue and whether they are safe for use in high-risk women without breast cancer. The current status of these studies will be reviewed. It is anticipated that in the future, drugs that effectively prevent ER-negative breast cancer will be used in combination with hormonal agents such SERMs or aromatase inhibitors to prevent all forms of breast cancer. PMID:19213564

  16. Characterization of patient-derived tumor xenografts (PDXs) as models for estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers.

    PubMed

    Kanaya, Noriko; Somlo, George; Wu, Jun; Frankel, Paul; Kai, Masaya; Liu, Xueli; Wu, Shang Victoria; Nguyen, Duc; Chan, Nymph; Hsieh, Meng-Yin; Kirschenbaum, Michele; Kruper, Laura; Vito, Courtney; Badie, Behnam; Yim, John H; Yuan, Yuan; Hurria, Arti; Peiguo, Chu; Mortimer, Joanne; Chen, Shiuan

    2017-06-01

    The research was to appraise the utility of the patient-derived tumor xenografts (PDXs) as models of estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers. We compared protein expression profiles by Reverse Phase Protein Array (RPPA) in tumors that resulted in PDXs compared to those that did not. Our overall PDX intake rate for ER+ breast cancer was 9% (9/97). The intake rate for ER+HER2+ tumors (3/16, 19%) was higher than for ER+HER2- tumors (6/81, 7%). Heat map analyses of RPPA data showed that ER+HER2- tumors were divided into 2 groups by luminal A/B signature [protein expression of ER, AR, Bcl-2, Bim (BCL2L11), GATA3 and INPP4b], and this expression signature was also associated with the rate of PDX intake. Cell survival pathways such as the PI3K/AKT signaling and RAS/ERK pathways were more activated in the specimens that could be established as PDX in both classes. Expression of the ER protein itself may have a bearing on the potential success of an ER+ PDX model. In addition, HER2 and its downstream protein expressions were up-regulated in the ER+HER2+ patient tumors that were successfully established as PDX models. Moreover, the comparison of RPPA data between original and PDX tumors suggested that the selection/adaptation process required to grow the tumors in mice is unavoidable for generation of ER+ PDX models, and we identified differences between patient tumor samples and paired PDX tumors. A better understanding of the biological characteristics of ER+PDX would be the key to using PDX models in assessing treatment strategies in a preclinical setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Growth, spectroscopic properties and laser output of Er : Ca 4YO(BO 3) 3 and Er : Yb : Ca 4YO(BO 3) 3 crystals

    NASA Astrophysics Data System (ADS)

    Zhang, Huaijin; Meng, Xianlin; Wang, Changqing; Wang, Pu; Zhu, Li; Liu, Xuesong; Dong, Chunming; Yang, Yuyong; Cheng, Ruiping; Dawes, Judith; Piper, Jim; Zhang, Shaojun; Sun, Lianke

    2000-09-01

    In this paper, Er : Ca 4YO(BO 3) 3 (Er : YCOB) and Er : Yb : Ca 4YO(BO 3) 3 (Er : Yb : YCOB) crystals with large size and excellent quality have been grown by the Czochralski method. The absorption and emission spectra of Er : YCOB and Er : Yb : YCOB crystals have been measured; the emission spectrum of Er : Yb : YCOB crystal shows that the strongest emission peak is located at 1537 nm. An output power of about 2 mW at the wavelength of 1553 nm has been obtained under the pumping power of a fiber-coupled laser diode (LD) of 1600 mW at 976 nm, using a Y direction cut 2.5 mm thick Er : Yb : YCOB crystal sample.

  18. The ERS Research Agency: the beginning.

    PubMed

    Soriano, Joan B; Paton, James; Martin Burrieza, Fernando; Bill, Werner; Pannetier, Carine; Aliberti, Stefano; Adcock, Ian M; Wagers, Scott; Migliori, Giovanni Battista

    2016-04-01

    There is at the current time a significant opportunity for the ERS to leverage its experience and reputation as an international umbrella organisation to promote high-quality, multinational respiratory research with the goal of improving the health of respiratory patients. This editorial proposes a model for the role and structure of an ERS Research Agency. It is based upon research, implicit knowledge and explicit feedback from ERS members and selected external individuals and organisations.As with any new endeavour there are challenges and threats. Building a Research Agency will be a major undertaking that will require significant organisational planning, resources, effort and commitment.Organisations with multiple stakeholders tend to have a status quo inertia that has to be overcome for any significant new endeavour. The ERS Research Agency could be an investment in the future of respiratory research.

  19. Laser performance of in-band pumped Er : LiYF{sub 4} and Er : LiLuF{sub 4} crystals

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

    Gorbachenya, K N; Kisel, V E; Yasukevich, A S

    2016-02-28

    Spectroscopic properties of Er : LiLuF{sub 4} and Er : LiYF{sub 4} crystals in the spectral region near 1.5 μm and the lasing characteristics of these crystals under in-band pumping at a wavelength of 1522 nm are studied. With the Er : LiLuF{sub 4} crystal, the maximum slope efficiency with respect to the absorbed pump power was 44% at a wavelength of 1609 nm. Continuous-wave operation of an inband pumped Er : LiYF{sub 4} laser is obtained for the first time. The output power at a wavelength of 1606 nm was 58 mW with a slope efficiency of 21%. (lasers)

  20. Dietary toxins, endoplasmic reticulum (ER) stress and diabetes.

    PubMed

    Hettiarachchi, Kalindi D; Zimmet, Paul Z; Myers, Mark A

    2008-05-01

    The incidence of Type 1 diabetes has been increasing at a rate too rapid to be due to changes in genetic risk. Instead changes in environmental factors are the likely culprit. The endoplasmic reticulum (ER) plays an important role in the production of newly synthesized proteins and interference with these processes leads to ER stress. The insulin-producing beta cells are particularly prone to ER stress as a result of their heavy engagement in insulin production. Increasing evidence suggests ER stress is central to initiation and progression of Type 1 diabetes. An early environmental exposure, such as toxins and viral infections, can impart a significant physiological load on beta cells to initiate abnormal processing of proinsulin, ER stress and insulin secretory defects. Release of altered proinsulin from the beta cells early in life may trigger autoimmunity in those with genetic susceptibility leading to cytokine-induced nitric oxide production and so exacerbating ER stress in beta cells, ultimately leading to apoptosis of beta cells and diabetes. Here we suggest that ER stress is an inherent cause of beta cell dysfunction and environmental factors, in particular dietary toxins derived from Streptomyces in infected root vegetables, can impart additional stress that aggravates beta cell death and progression to diabetes. Furthermore, we propose that the increasing incidence of Type 1 diabetes may be accounted for by increased dietary exposure to ER-stress-inducing Streptomyces toxins.

  1. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

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

    Yang, Ping; Fu, Shilong; Cao, Zhifei

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressivemore » ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice

  2. ER2OWL: Generating OWL Ontology from ER Diagram

    NASA Astrophysics Data System (ADS)

    Fahad, Muhammad

    Ontology is the fundamental part of Semantic Web. The goal of W3C is to bring the web into (its full potential) a semantic web with reusing previous systems and artifacts. Most legacy systems have been documented in structural analysis and structured design (SASD), especially in simple or Extended ER Diagram (ERD). Such systems need up-gradation to become the part of semantic web. In this paper, we present ERD to OWL-DL ontology transformation rules at concrete level. These rules facilitate an easy and understandable transformation from ERD to OWL. The set of rules for transformation is tested on a structured analysis and design example. The framework provides OWL ontology for semantic web fundamental. This framework helps software engineers in upgrading the structured analysis and design artifact ERD, to components of semantic web. Moreover our transformation tool, ER2OWL, reduces the cost and time for building OWL ontologies with the reuse of existing entity relationship models.

  3. Er 3+ Doping conditions of planar porous silicon waveguides

    NASA Astrophysics Data System (ADS)

    Najar, A.; Lorrain, N.; Ajlani, H.; Charrier, J.; Oueslati, M.; Haji, L.

    2009-11-01

    EDX and infrared photoluminescence (IR PL) analyses performed on erbium-doped porous silicon waveguides (PSWG) were studied using different doping conditions. Both parameters of the cathodisation electrochemical method used for Er incorporation and parameters of thermal treatments required for Er optical activation were taken into consideration. Firstly, by varying the current density and the time of cathodisation, we have shown that a current density of 0.1 mA/cm 2 for 10 min allows homogeneous Er doping to be achieved throughout the depth of the guiding layer. Then, the PL intensity at 1.53 μm was studied as a function of the oxidation time at 900 °C and Er diffusion temperature for 60 min. Increasing the oxidation time up to 1 h allows PL to be enhanced due to active Si-O-Er complex formation whereas an oxidation time of 2 h induces a decrease in PL because of Er segregation. Moreover, an increase in the diffusion temperature induces an optimal distribution of optically active Si-Er-O complexes inside the crystallites. When the temperature is too high, a PSWG densification and Er segregation occurs inducing a decrease in PL due to energy transfer phenomena.

  4. SR/ER-mitochondrial local communication: Calcium and ROS

    PubMed Central

    Csordás, György; Hajnóczky, György

    2009-01-01

    Mitochondria form junctions with the sarco/endoplasmic reticulum (SR/ER), which support signal transduction and biosynthetic pathways and affect organellar distribution. Recently, these junctions have received attention because of their pivotal role in mediating calcium signal propagation to the mitochondria, which is important for both ATP production and mitochondrial cell death. Many of the SR/ER-mitochondrial calcium transporters and signaling proteins are sensitive to redox regulation and are directly exposed to the reactive oxygen species (ROS) produced in the mitochondria and SR/ER. Although ROS has been emerging as a novel signaling entity, the redox signaling of the SR/ER-mitochondrial interface is yet to be elucidated. We describe here possible mechanisms of the mutual interaction between local Ca2+ and ROS signaling in the control of SR/ER-mitochondrial function. PMID:19527680

  5. MicroRNAs meet calcium: joint venture in ER proteostasis.

    PubMed

    Finger, Fabian; Hoppe, Thorsten

    2014-11-04

    The endoplasmic reticulum (ER) is a cellular compartment that has a key function in protein translation and folding. Maintaining its integrity is of fundamental importance for organism's physiology and viability. The dynamic regulation of intraluminal ER Ca(2+) concentration directly influences the activity of ER-resident chaperones and stress response pathways that balance protein load and folding capacity. We review the emerging evidence that microRNAs play important roles in adjusting these processes to frequently changing intracellular and environmental conditions to modify ER Ca(2+) handling and storage and maintain ER homeostasis. Copyright © 2014, American Association for the Advancement of Science.

  6. Integrated self-organization of transitional ER and early Golgi compartments.

    PubMed

    Glick, Benjamin S

    2014-02-01

    COPII coated vesicles bud from an ER domain termed the transitional ER (tER), but the mechanism that clusters COPII vesicles at tER sites is unknown. tER sites are closely associated with early Golgi or pre-Golgi structures, suggesting that the clustering of nascent COPII vesicles could be achieved by tethering to adjacent membranes. This model challenges the prevailing view that COPII vesicles are clustered by a scaffolding protein at the ER surface. Although Sec16 was proposed to serve as such a scaffolding protein, recent data suggest that rather than organizing COPII into higher-order structures, Sec16 acts at the level of individual COPII vesicles to regulate COPII turnover. A plausible synthesis is that tER sites are created by tethering to Golgi membranes and are regulated by Sec16. Meanwhile, the COPII vesicles that bud from tER sites are thought to nucleate new Golgi cisternae. Thus, an integrated self-organization process may generate tER-Golgi units. © 2014 WILEY Periodicals, Inc.

  7. Ternary Dy-Er-Al magnetic refrigerants

    DOEpatents

    Gschneidner, Jr., Karl A.; Takeya, Hiroyuki

    1995-07-25

    A ternary magnetic refrigerant material comprising (Dy.sub.1-x Er.sub.x)Al.sub.2 for a magnetic refrigerator using the Joule-Brayton thermodynamic cycle spanning a temperature range from about 60K to about 10K, which can be adjusted by changing the Dy to Er ratio of the refrigerant.

  8. [Development and medical application of Er-YAG laser].

    PubMed

    Okamoto, Y; Kobayashi, A; Awazu, A; Ogino, H; Ban, T

    1993-09-01

    Result of developments of Er-YAG laser and its delivery system were reported. Er-YAG laser's wavelength is 2.94 microns, the beam absorption rate by water is higher than other laser beam. Er-YAG laser has repeated pulse oscillation, pulse width is 400 mu, sec, the repeat frequency is between 5 to 10 pulse per second. The mean power is 4 W maximum, 10 pps. The fibers of laser are made of zirconium-F-glass. We carried out a study on the possible application of the Er-YAG laser on the rabbit arteries and myocardium and human arteries were examined in vitro. Very clear cuts were observed on the histological examination. There were no evidence of thermal damage, no carbonization on the sharp cutting surface. Experimental result showed that Er-YAG lasers had good potential for angioplastic laser.

  9. Comparative efficacy of Er,Cr:YSGG and Er:YAG lasers for etching of composite for orthodontic bracket bonding.

    PubMed

    Mirhashemi, Amir Hossein; Chiniforush, Nasim; Sharifi, Nastaran; Hosseini, Amir Mehdi

    2018-05-01

    Several techniques have been proposed to obtain a durable bond, and the efficacy of these techniques is assessed by measuring parameters such as bond strength. Laser has provided a bond strength as high as that of acid etching in vitro and has simpler use with shorter clinical time compared to acid etching. This study aimed to compare the efficacy of Er:YAG and Er,Cr:YSGG lasers for etching and bonding of composite to orthodontic brackets. No previous study has evaluated the effect of these particular types of laser. A total of 70 composite blocks were randomly divided into five groups (n = 14): group 1, etching with phosphoric acid for 20 s; group 2, Er:YAG laser irradiation with 2 W power for 10 s; group 3, Er:YAG laser with 3 W power for 10 s; group 4, Er,Cr:YSGG laser with 2 W power for 10 s; group 5, Er,Cr:YSGG laser with 3 W power for 10 s. Metal brackets were then bonded to composites, and after 5000 thermal cycles, they were subjected to shear bond strength test in a universal testing machine after 24 h of water storage. One sample of each group was evaluated under a scanning electron microscope (SEM) to assess changes in composite surface after etching. The adhesive remnant index (ARI) was calculated under a stereomicroscope. Data were statistically analyzed. The mean and standard deviation of shear bond strength were 18.65 ± 3.36, 19.68 ± 5.34, 21.31 ± 4.03, 17.38 ± 6.94, and 16.45 ± 4.26 MPa in groups 1-5, respectively. The ARI scores showed that the bond failure mode in all groups was mainly mixed. The groups were not significantly different in terms of shear bond strength. Er:YAG and Er,Cr:YSGG lasers with the mentioned parameters yield optimal shear bond strength and can be used as an alternative to acid etching for bracket bond to composite.

  10. Operational durability of a giant ER valve for Braille display

    NASA Astrophysics Data System (ADS)

    Luning, Xu; Han, Li; Yufei, Li; Shen, Rong; Kunquan, Lu

    2017-05-01

    The compact configuration of giant ER (electrorheological) valves provides the possibility of realizing a full-page Braille display. The operational durability of ER valves is a key issue in fulfilling a Braille display. A giant ER valve was used to investigate the variations in pressure drops and critical pressure drops of the valves over a long period under some typical operational parameters. The results indicate that neither the pressure drops nor critical pressure drops of giant ER valves show apparent deterioration over a long period. Without ER fluid exchange, a blockage appears in the channel of the valve because the ER structures induced by an external electric field cannot be broken by the Brownian motion of hydraulic oil molecules when the external electric field is removed. Forcing ER fluid flow is an effective and necessary method to keep the channel of the valve unblocked. Thus the operational durability of the valve using giant ER fluids is able to meet the demands of Braille display.

  11. Ternary Dy-Er-Al magnetic refrigerants

    DOEpatents

    Gschneidner, K.A. Jr.; Takeya, Hiroyuki

    1995-07-25

    A ternary magnetic refrigerant material comprising (Dy{sub 1{minus}x}Er{sub x})Al{sub 2} for a magnetic refrigerator using the Joule-Brayton thermodynamic cycle spanning a temperature range from about 60K to about 10K, which can be adjusted by changing the Dy to Er ratio of the refrigerant. 29 figs.

  12. Upconversion luminescence in Er3+ doped and Er3+/Yb3+ codoped zirconia and hafnia nanocrystals excited at 980 nm

    NASA Astrophysics Data System (ADS)

    Gómez, Luis A.; Menezes, Leonardo de S.; de Araújo, Cid B.; Gonçalves, Rogeria R.; Ribeiro, Sidney J. L.; Messaddeq, Younes

    2010-06-01

    Frequency upconversion (UC) luminescence in nanocrystalline zirconia (ZrO2) and hafnia (HfO2) doped with Er3+ and Yb3+ was studied under continuous-wave excitation at 980 nm. Samples of ZrO2:Er3+, ZrO2:Er3+/Yb3+, and HfO2:Er3+/Yb3+ were prepared by the sol-gel technique and characterized using x-ray diffraction and electron microscopy. A study of the infrared-to-green and infrared-to-red UC processes was performed including the analysis of the spectral and the temporal behavior. The mechanisms contributing to the UC luminescence were identified as excited state absorption and energy transfer among rare-earth ions.

  13. Cooperative Dynamics of AR and ER Activity in Breast Cancer

    PubMed Central

    D’Amato, Nicholas C.; Gordon, Michael A.; Babbs, Beatrice L.; Spoelstra, Nicole S.; Carson Butterfield, Kiel T.; Torkko, Kathleen C.; Phan, Vernon T.; Barton, Valerie N.; Rogers, Thomas J.; Sartorius, Carol A; Elias, Anthony D.; Gertz, Jason; Jacobsen, Britta M.; Richer, Jennifer K.

    2016-01-01

    Androgen receptor (AR) is expressed in 90% of estrogen receptor alpha positive (ER+) breast tumors, but its role in tumor growth and progression remains controversial. Use of two anti-androgens that inhibit AR nuclear localization, enzalutamide and MJC13, revealed that AR is required for maximum ER genomic binding. Here, a novel global examination of AR chromatin binding found that estradiol induced AR binding at unique sites compared to dihydrotestosterone (DHT). Estradiol-induced AR binding sites were enriched for estrogen response elements and had significant overlap with ER binding sites. Furthermore, AR inhibition reduced baseline and estradiol-mediated proliferation in multiple ER+/AR+ breast cancer cell lines, and synergized with tamoxifen and fulvestrant. In vivo, enzalutamide significantly reduced viability of tamoxifen-resistant MCF7 xenograft tumors and an ER+/AR+ patient-derived model. Enzalutamide also reduced metastatic burden following cardiac injection. Lastly, in a comparison of ER+/AR+ primary tumors versus patient-matched local recurrences or distant metastases, AR expression was often maintained even when ER was reduced or absent. These data provide pre-clinical evidence that anti-androgens that inhibit AR nuclear localization affect both AR and ER, and are effective in combination with current breast cancer therapies. In addition, single agent efficacy may be possible in tumors resistant to traditional endocrine therapy, since clinical specimens of recurrent disease demonstrate AR expression in tumors with absent or refractory ER. Implications This study suggests that AR plays a previously-unrecognized role in supporting E2-mediated ER activity in ER+/AR+ breast cancer cells, and that enzalutamide may be an effective therapeutic in ER+/AR+ breast cancers. PMID:27565181

  14. Er:YAG laser debonding of porcelain veneers

    NASA Astrophysics Data System (ADS)

    Buu, Natalie; Morford, Cynthia; Finzen, Frederick; Sharma, Arun; Rechmann, Peter

    2010-02-01

    The removal of porcelain veneers using Er:YAG lasers has not been previously described in the scientific literature. This study was designed to systematically investigate the efficacy of an Er:YAG laser on veneer debonding without damaging the underlying tooth structure, as well as preserving a new or misplaced veneer. Initially, Fourier Transform Infrared Spectroscopy (FTIR) was used on flat porcelain veneer samples (IPS Empress Esthetic; Ivoclar Vivadent, Amherst, NY) to assess which infrared laser wavelengths are transmitted through the veneer. Additionally, FTIR spectra from a veneer bonding cement (RelyX Veneer Cement A1; 3M ESPE, St. Paul, MN) were obtained. While the veneer material showed no characteristic water absorption bands in the FTIR, the bonding cement has a broad H2O/OH absorption band coinciding with the ER:YAG laser emission wavelength. Consequently Er:YAG laser energy transmission through different veneer thicknesses was measured. The porcelain veneers transmitted 11 - 18 % of the incident Er:YAG laser energy depending on their thicknesses (Er:YAG laser: LiteTouch by Syneron; wavelength 2,940 nm, 10 Hz repetition rate, pulse duration 100 μs at 133 mJ/pulse; straight sapphire tip 1,100 μm diameter; Syneron, Yokneam, Israel). Initial signs of cement ablation occurred at approximately 1.8 - 4.0 J/cm2. This can be achieved by irradiating through the veneer with the fiber tip positioned at a distance of 3-6 mm from the veneer surface, and operating the Er:YAG laser with 133 mJ output energy. All eleven veneers bonded on extracted anterior incisor teeth were easily removed using the Er:YAG laser. The removal occurred without damaging underlying tooth structure as verified by light microscopic investigation (Incident Light Microscope Olympus B 50, Micropublisher RTV 3.3 MP, Image Pro software, Olympus). The debonding mainly occurred at the cement/veneer interface. When the samples were stored in saline solution for 5 days and/or an air-waterspray was

  15. Two endoplasmic reticulum (ER) membrane proteins that facilitate ER-to-Golgi transport of glycosylphosphatidylinositol-anchored proteins.

    PubMed

    Barz, W P; Walter, P

    1999-04-01

    Many eukaryotic cell surface proteins are anchored in the lipid bilayer through glycosylphosphatidylinositol (GPI). GPI anchors are covalently attached in the endoplasmic reticulum (ER). The modified proteins are then transported through the secretory pathway to the cell surface. We have identified two genes in Saccharomyces cerevisiae, LAG1 and a novel gene termed DGT1 (for "delayed GPI-anchored protein transport"), encoding structurally related proteins with multiple membrane-spanning domains. Both proteins are localized to the ER, as demonstrated by immunofluorescence microscopy. Deletion of either gene caused no detectable phenotype, whereas lag1Delta dgt1Delta cells displayed growth defects and a significant delay in ER-to-Golgi transport of GPI-anchored proteins, suggesting that LAG1 and DGT1 encode functionally redundant or overlapping proteins. The rate of GPI anchor attachment was not affected, nor was the transport rate of several non-GPI-anchored proteins. Consistent with a role of Lag1p and Dgt1p in GPI-anchored protein transport, lag1Delta dgt1Delta cells deposit abnormal, multilayered cell walls. Both proteins have significant sequence similarity to TRAM, a mammalian membrane protein thought to be involved in protein translocation across the ER membrane. In vivo translocation studies, however, did not detect any defects in protein translocation in lag1Delta dgt1Delta cells, suggesting that neither yeast gene plays a role in this process. Instead, we propose that Lag1p and Dgt1p facilitate efficient ER-to-Golgi transport of GPI-anchored proteins.

  16. Two Endoplasmic Reticulum (ER) Membrane Proteins That Facilitate ER-to-Golgi Transport of Glycosylphosphatidylinositol-anchored Proteins

    PubMed Central

    Barz, Wolfgang P.; Walter, Peter

    1999-01-01

    Many eukaryotic cell surface proteins are anchored in the lipid bilayer through glycosylphosphatidylinositol (GPI). GPI anchors are covalently attached in the endoplasmic reticulum (ER). The modified proteins are then transported through the secretory pathway to the cell surface. We have identified two genes in Saccharomyces cerevisiae, LAG1 and a novel gene termed DGT1 (for “delayed GPI-anchored protein transport”), encoding structurally related proteins with multiple membrane-spanning domains. Both proteins are localized to the ER, as demonstrated by immunofluorescence microscopy. Deletion of either gene caused no detectable phenotype, whereas lag1Δ dgt1Δ cells displayed growth defects and a significant delay in ER-to-Golgi transport of GPI-anchored proteins, suggesting that LAG1 and DGT1 encode functionally redundant or overlapping proteins. The rate of GPI anchor attachment was not affected, nor was the transport rate of several non–GPI-anchored proteins. Consistent with a role of Lag1p and Dgt1p in GPI-anchored protein transport, lag1Δ dgt1Δ cells deposit abnormal, multilayered cell walls. Both proteins have significant sequence similarity to TRAM, a mammalian membrane protein thought to be involved in protein translocation across the ER membrane. In vivo translocation studies, however, did not detect any defects in protein translocation in lag1Δ dgt1Δ cells, suggesting that neither yeast gene plays a role in this process. Instead, we propose that Lag1p and Dgt1p facilitate efficient ER-to-Golgi transport of GPI-anchored proteins. PMID:10198056

  17. Oceanographic results from analysis of ERS-1 altimetry

    NASA Technical Reports Server (NTRS)

    Tapley, B. D.; Shum, C. K.; Chambers, D. P.; Peterson, G. E.; Ries, J. C.

    1994-01-01

    Large scale dynamic ocean topography and its variations were observed using ERS-1 radar altimeter measurements. The altimeter measurements analyzed are primarily from the ESA ocean product (OPR02) and from the Interim Geophysical Data Records (IGDR) generated by NOAA from the fast delivery (FD) data during the ERS-1 35 day repeat orbit phase. The precise orbits used for the dynamic topography solution are computed using dual satellite crossover measurements from ERS-1 and TOPEX (Topology Ocean Experiment)/Poseidon (T/P) as additional tracking data, and using improved models and constants which are consistent with T/P. Analysis of the ERS-1 dynamic topography solution indicates agreement with the T/P solution at the 5 cm root mean square level, with regional differences as large as 15 cm tide gauges at the 8 to 9 cm level. There are differences between the ERS-1 OPR02 and IGDR determined dynamic topography solutions on the order of 5 cm root mean square. Mesoscale oceanic variability time series obtained using collinear analysis of the ERS-1 altimeter data show good qualitative agreement when compared with the T/P results.

  18. Erbium induced magnetic properties of Er/ZnO nanoparticles

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

    Jayachandraiah, C.; Divya, A.; Sivakumar, K.

    Pure and Er (2, 3 and 4 at. %) doped ZnO nanoparticles have been synthesized by chemical co-precipitation method. EDS spectrum confirmed the presence of Zn, O and Er in the synthesized samples. The XRD measurements confirmed the hexagonal wurtzite structure of ZnO for all samples. The crystallite size of the samples decreases with increase in concentration and are compatible with the results that obtained from TEM analysis.EPR spectra exhibitedferromagnetic signals the substitution Er The possible ferromagnetic zinc interstials signal is appeared for 2 at. % of Er dopant. The room temperature ferromagnetic is observed only for 2 at. %more » of Er while all other samples exhibiting weak ferromagnetic nature.« less

  19. SNAREs support atlastin-mediated homotypic ER fusion in Saccharomyces cerevisiae

    PubMed Central

    Lee, Miriam; Ko, Young-Joon; Moon, Yeojin; Han, Minsoo; Kim, Hyung-Wook; Lee, Sung Haeng; Kang, KyeongJin

    2015-01-01

    Dynamin-like GTPases of the atlastin family are thought to mediate homotypic endoplasmic reticulum (ER) membrane fusion; however, the underlying mechanism remains largely unclear. Here, we developed a simple and quantitative in vitro assay using isolated yeast microsomes for measuring yeast atlastin Sey1p-dependent ER fusion. Using this assay, we found that the ER SNAREs Sec22p and Sec20p were required for Sey1p-mediated ER fusion. Consistently, ER fusion was significantly reduced by inhibition of Sec18p and Sec17p, which regulate SNARE-mediated membrane fusion. The involvement of SNAREs in Sey1p-dependent ER fusion was further supported by the physical interaction of Sey1p with Sec22p and Ufe1p, another ER SNARE. Furthermore, our estimation of the concentration of Sey1p on isolated microsomes, together with the lack of fusion between Sey1p proteoliposomes even with a 25-fold excess of the physiological concentration of Sey1p, suggests that Sey1p requires additional factors to support ER fusion in vivo. Collectively, our data strongly suggest that SNARE-mediated membrane fusion is involved in atlastin-initiated homotypic ER fusion. PMID:26216899

  20. ER-2: Flying Laboratory for Earth Science Studies

    NASA Technical Reports Server (NTRS)

    Navarro, Robert

    2007-01-01

    The National Aeronautics and Space Administration (NASA) Dryden Flight Research Center (DFRC), (Edwards, California, USA) has two Lockheed Martin Corporation (Bethesda, Maryland) Earth Research-2 (ER-2) aircraft that serve as high-altitude and long-range flying laboratories. The ER-2 has been utilized to conduct scientific studies of stratospheric and tropospheric chemistry, land-use mapping, disaster assessment, preliminary testing and calibration and validation of satellite sensors. The ER-2 aircraft provides experimenters with a wide array of payload accommodation areas with suitable environment control with required electrical and mechanical interfaces. Missions may be flown out of DFRC or from remote bases worldwide. The NASA ER-2 is utilized by a variety of customers, including U.S. Government agencies, civilian organizations, universities, and state governments. The combination of the ER-2 s range, endurance, altitude, payload power, payload volume and payload weight capabilities complemented by a trained maintenance and operations team provides an excellent and unique platform system to the science community.

  1. 20 CFR 222.24 - Relationship as remarried widow(er).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... FAMILY RELATIONSHIPS Relationship as Divorced Spouse, Surviving Divorced Spouse, or Remarried Widow(er) § 222.24 Relationship as remarried widow(er). (a) New eligibility. A claimant will have the relationship... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Relationship as remarried widow(er). 222.24...

  2. Etude des interdiffusions en phase solide dans le contact Er/GaAs

    NASA Astrophysics Data System (ADS)

    Députier, S.; Guivarc'h, A.; Caulet, J.; Minier, M.; Guérin, R.

    1994-05-01

    Solid state interdiffusions between a thin film of erbium deposited under vacuum conditions and (001) and (111) GaAs substrates were investigated in the temperature range 350-800 ^{circ}C. Complementary analysis methods (RBS, X-ray diffraction) allow us to point out, according to annealing temperatures, successives steps of the interaction corresponding to different mixtures of phases, essentially binaries. These steps are strongly depending on the GaAs substrate orientation, especially the final step of the interdiffusions. On (001) GaAs, only two steps have been observed : no visible interaction is noticed between erbium and GaAs before 600 ^{circ}C ; the interaction begins at 600 ^{circ}C, evolves slightly and leads at 800 ^{circ}C to the nominal composition " Er{10}GaAs " which corresponds to a mixture of several phases Er5Ga3, Er and ErAs. On (111) GaAs, several steps of interaction have been found ; first of all, erbium reacts with the substrate at 400 ^{circ}C (Er5Ga3 + Er mixture), then the reaction is continuing at 600 ^{circ}C (Er5Ga3 + Er + ErAs mixture) before reaching at 800 ^{circ}C the nominal composition " Er{1,5}GaAs ", which is in fact a mixture of the three binaries ErAs + ErGa2 + Er3Ga5. It can be noticed that the 800 ^{circ}C annealing is not sufficient to reach the mixture of the phases ErAs + Ga which, according to the ternary phase diagram, should be the final stage of the interaction Er/GaAs. The analysis of the Er/GaAs interdiffusions shows that ErAs is the " key " compound around which the interaction progresses. This compound appears as an ideal candidate to realize epitaxial ErAs/GaAs heterostructures. Les interdiffusions en phase solide entre une couche mince d'erbium déposée dans des conditions d'ultra-vide et des substrats de GaAs orientés (001) et (111) ont été étudiées après des traitements thermiques d'une heure entre 350 et 800 ^{circ}C. L'utilisation de techniques complémentaires d'analyse (RBS, diffraction X) a permis

  3. Gingival melanin depigmentation by Er:YAG laser: A literature review.

    PubMed

    Pavlic, Verica; Brkic, Zlata; Marin, Sasa; Cicmil, Smiljka; Gojkov-Vukelic, Mirjana; Aoki, Akira

    2018-04-01

    Laser ablation is recently suggested as a most effective and reliable technique for depigmentation of melanin hyperpigmented gingiva. To date, different lasers have been used for gingival depigmentation (CO 2 , diode, Nd:YAG, Er:YAG and Er,Cr:YSGG lasers). The use of Er:YAG laser for depigmentation of melanin hyperpigmented gingiva has gained increasing importance in recent years. The purpose of this study was to report removal of gingival melanin pigmentation using an Er:YAG laser in a literature review. The main outcomes, such as improvement of signs (clinical parameters of bleeding, erythema, swelling and wound healing), symptoms (pain) and melanin recurrence/repigmentation were measured. The literature demonstrated that depigmentation of gingival melanin pigmentation can be performed safely and effectively by Er:YAG laser resulting in healing and an esthetically significant improvement of gingival discoloration. Thus, Er:YAG laser seems to be safe and useful in melanin depigmentation procedure. However, the main issue in giving the final conclusion of the optimal Er:YAG laser use in melanin depigmentation is that, to date, studies are offering completely discrepant Er:YAG laser procedure protocols (complex settings of laser parameters), and different criteria for the assessment of depigmentation and repigmentation (recurrence), thus hampering the comparison of the results. Therefore, further studies are necessary to give an optimal recommendation on the use of Er:YAG laser in gingival melanin hyperpigmentation.

  4. Er-doped sesquioxides for 1.5-micron lasers - spectroscopic comparisons

    NASA Astrophysics Data System (ADS)

    Merkle, Larry D.; Ter-Gabrielyan, Nikolay

    2013-05-01

    Due to the favorable thermal properties of sesquioxides as hosts for rare earth laser ions, we have recently studied the spectroscopy of Er:Lu2O3 in the 1400-1700 nm wavelength range, and here report its comparison with our earlier results on Er:Y2O3 and Er:Sc2O3. These studies include absorption and fluorescence spectra, fluorescence lifetimes, and inference of absorption and stimulated emission cross sections, all as a function of temperature. At room temperature, optical absorption limits practical laser operation to wavelengths longer than about 1620 nm. In that spectral range, the strongest stimulated emission peak is that at 1665 nm in Er:Sc2O3, with an effective cross section considerably larger than those of Er:Y2O3 and Er:Lu2O3. At 77K, the absorption is weak enough for efficient laser operation at considerably shorter wavelengths, where there are peaks with much larger stimulated emission cross sections. The three hosts all have peaks near 1575-1580 nm with comparably strong cross sections. As we have reported earlier, it is possible to lase even shorter wavelengths efficiently at this temperature, in particular the line at 1558 nm in Er:Sc2O3. Our new spectroscopic studies of Er:Lu2O3 indicate that its corresponding peak, like that of Er:Sc2O3, has a less favorable ratio of stimulated emission to absorption cross sections. Reasons for the differences will be discussed. We conclude that for most operating scenarios, Er:Sc2O3 is the most promising of the Er-doped sesquioxides studied for laser operation around 1.5-1.6 microns.

  5. The widow(er)'s limit provision of Social Security.

    PubMed

    Weaver, D A

    Widow benefits have been a part of the Social Security program since the 1939 amendments to the Social Security Act (widower benefits were added later). For many years, the Social Security law called for paying a widow(er) a fraction of the deceased worker's primary insurance amount (PIA). However, the worker--while alive--may have received the full PIA as his or her retirement benefit. Over time, arguments were made that a widow(er) should be treated as generously as his or her spouse was. The 1972 amendments to the Social Security Act allowed for a widow(er) to receive a full PIA, subject to actuarial reductions if the widow(er) benefit was claimed before the normal retirement age (NRA) and subject to a new provision of the law commonly referred to as the widow(er)'s limit. Generally, the widow(er)'s limit specifies that if a worker received reduced retirement benefits (because the worker claimed benefits before the NRA), then the worker's widow(er) cannot receive a monthly benefit equal to the full PIA. Rather, the widow(er)'s benefit is generally limited to the amount the worker would receive if he or she was still alive. The limit provision appears to be motivated by the overall intent of the 1972 Congress to pay a benefit to a widow(er) that was comparable with what the worker received. A number of changes to the limit provision have been discussed. This article looks at the following options: Abolishing the limit, Raising the limit by requiring that it never be set below the average PIA among all retired-worker beneficiaries. Adjusting the limit for some widow(er)s--that is, only persons who are widowed before the NRA (the ARLA option), Making a simpler adjustment to the limit by abolishing it for persons who are widowed before age 62 (the SARLA option), and A proposal by Robert J. Myers that would make modest adjustments to the limit for cases in which the worker died before the NRA. The most fundamental change--abolishing the limit--would increase benefits

  6. Lace plant ethylene receptors, AmERS1a and AmERS1c, regulate ethylene-induced programmed cell death during leaf morphogenesis.

    PubMed

    Rantong, Gaolathe; Evans, Rodger; Gunawardena, Arunika H L A N

    2015-10-01

    The lace plant, Aponogeton madagascariensis, is an aquatic monocot that forms perforations in its leaves as part of normal leaf development. Perforation formation occurs through developmentally regulated programmed cell death (PCD). The molecular basis of PCD regulation in the lace plant is unknown, however ethylene has been shown to play a significant role. In this study, we examined the role of ethylene receptors during perforation formation. We isolated three lace plant ethylene receptors AmERS1a, AmERS1b and AmERS1c. Using quantitative PCR, we examined their transcript levels at seven stages of leaf development. Through laser-capture microscopy, transcript levels were also determined in cells undergoing PCD and cells not undergoing PCD (NPCD cells). AmERS1a transcript levels were significantly lower in window stage leaves (in which perforation formation and PCD are occurring) as compared to all other leaf developmental stages. AmERS1a and AmERS1c (the most abundant among the three receptors) had the highest transcript levels in mature stage leaves, where PCD is not occurring. Their transcript levels decreased significantly during senescence-associated PCD. AmERS1c had significantly higher transcript levels in NPCD compared to PCD cells. Despite being significantly low in window stage leaves, AmERS1a transcripts were not differentially expressed between PCD and NPCD cells. The results suggested that ethylene receptors negatively regulate ethylene-controlled PCD in the lace plant. A combination of ethylene and receptor levels determines cell fate during perforation formation and leaf senescence. A new model for ethylene emission and receptor expression during lace plant perforation formation and senescence is proposed.

  7. Evaluating the potential bioactivity of a novel compound ER1626.

    PubMed

    Wang, Lijun; Zeng, Yanyan; Wang, Tianling; Liu, Hongyi; Xiao, Hong; Xiang, Hua

    2014-01-01

    ER1626, a novel compound, is a derivate of indeno-isoquinoline ketone. This study was designed to evaluate the biological activity and potential anti-tumor mechanism of ER1626. MTT assay, scratch assay and flow cytometry were used to determine cell proliferation, cell migration and cell cycle distribution as well as cell apoptosis on human breast cancer MCF-7 cells and endometrial cancer Ishikawa cells. We also explored the antiangiogenic effect of ER1626 on HUVEC cells and chicken embryos. The expression of estrogen receptor protein was investigated with western-blot analysis. ER1626 down-regulated the expression of estrogen receptor α protein and up-regulated β protein in MCF-7 and Ishikawa cells. The value of IC50 of ER1626 on MCF-7 and Ishikawa cells were respectively 8.52 and 3.08 µmol/L. Meanwhile, ER1626 decreased VEGF secretion of MCF-7 and Ishikawa cells, disturbed the formation of VEGF-stimulated tubular structure in HUVEC cells, and inhibited the angiogenesis on the chicken chorioallantoic membrane. Scratch assay revealed that ER1626 suppressed the migration of MCF-7, Ishikawa and HUVEC cells. In addition to induction tumor cell apoptosis, ER1626 arrested cell cycle in G1/G0 phase in MCF-7 cells and G2/M phase in Ishikawa cells. In conclusion, our results demonstrated that ER1626 has favorable bioactivities to be a potential candidate against breast cancer and angiogenesis.

  8. Prohibitin promotes androgen receptor activation in ER-positive breast cancer

    PubMed Central

    Liu, Pengying; Xu, Yumei; Zhang, Wenwen; Li, Yan; Tang, Lin; Chen, Weiwei; Xu, Jing; Sun, Qian; Guan, Xiaoxiang

    2017-01-01

    ABSTRACT Prohibitin (PHB) is an evolutionarily conserved protein with multiple functions in both normal and cancer cells. Androgen receptor (AR) was reported to act as a different role in the ER-positive and ER-negative breast cancer. However, little is known about the role of PHB and whether PHB could regulate AR expression in the ER-positive breast cancer. Here, we determined the expression and clinical outcomes of PHB in breast cancer samples using 121 breast cancer tissues and published databases, and investigated the role of PHB in breast cancer cell growth, apoptosis and cell cycle arrest in the ER-positive breast cancer cells. We obtained the expression of PHB is significantly low in breast cancer samples, and low PHB expression positively correlated with poor prognosis of breast cancer. We detected that PHB could inhibit breast cancer cell proliferation, change cell cycle distribution and promote cell apoptosis in the ER-positive breast cancer cells. Moreover, we found PHB could significantly increase AR expression in both mRNA and protein levels in the ER-positive breast cancer cells. Additionally, a significant positive correlation between PHB and AR expression was identified in the 121 breast cancer tissues. PHB and AR expression are associated with prognosis in the ER-positive breast cancer patients. Our results indicate that PHB promotes AR activation in ER-positive breast cancer, making PHB and AR potential molecular targets for ER-positive breast cancer therapy. PMID:28272969

  9. Structure and radiation effect of Er-stuffed pyrochlore Er2(Ti2-xErx)O7-x/2 (x = 0-0.667)

    NASA Astrophysics Data System (ADS)

    Yang, D. Y.; Xu, C. P.; Fu, E. G.; Wen, J.; Liu, C. G.; Zhang, K. Q.; Wang, Y. Q.; Li, Y. H.

    2015-08-01

    Er-stuffed pyrochlore series Er2(Ti2-xErx)O7-x/2 (x = 0, 0.162, 0.286, 0.424 and 0.667) were synthesized using conventional ceramic processing procedures. The structure of Er2(Ti2-xErx)O7-x/2 is effectively tailored by the Er stuffing level (x). In order to study the radiation effect of Er-stuffed pyrochlores, irradiation experiments were performed with 400 keV Ne2+ ions to fluences ranging from 5 × 1014 to 3.0 × 1015 ions/cm2 at cryogenic condition. Irradiation induced microstructural evolution was examined using a grazing incidence X-ray diffraction technique. It is found that the irradiated layer of Er2(Ti2-xErx)O7-x/2 undergoes significant lattice disordering and swelling at fluences of ⩽1.5 × 1015 ions/cm2 and amorphization at fluences of ⩾1.5 × 1015 ions/cm2. The radiation effect depends strongly on the chemical compositions of the samples. Both the lattice swelling percentage and the amorphous fraction decrease with increasing x. The experimental results are discussed in the context of cation antisite defect. The defect formation energy which varies as a function of x is responsible for the difference in the structural behaviors of Er2(Ti2-xErx)O7-x/2 under 400 keV Ne2+ ion irradiation.

  10. Integration of ERS and ASAR Time Series for Differential Interferometric SAR Analysis

    NASA Astrophysics Data System (ADS)

    Werner, C. L.; Wegmüller, U.; Strozzi, T.; Wiesmann, A.

    2005-12-01

    Time series SAR interferometric analysis requires SAR data with good temporal sampling covering the time period of interest. The ERS satellites operated by ESA have acquired a large global archive of C-Band SAR data since 1991. The ASAR C-Band instrument aboard the ENVISAT platform launched in 2002 operates in the same orbit as ERS-1 and ERS-2 and has largely replaced the remaining operational ERS-2 satellite. However, interferometry between data acquired by ERS and ASAR is complicated by a 31 MHz offset in the radar center frequency between the instruments leading to decorrelation over distributed targets. Only in rare instances, when the baseline exceeds 1 km, can the spectral shift compensate for the difference in the frequencies of the SAR instruments to produce visible fringes. Conversely, point targets do not decorrelate due to the frequency offset making it possible to incorporate the ERS-ASAR phase information and obtain improved temporal coverage. We present an algorithm for interferometric point target analysis that integrates ERS-ERS, ASAR-ASAR and ERS-ASAR data. Initial analysis using the ERS-ERS data is used to identify the phase stable point-like scatterers within the scene. Height corrections relative to the initial DEM are derived by regression of the residual interferometric phases with respect to perpendicular baseline for a set of ERS-ERS interferograms. The ASAR images are coregistered with the ERS scenes and the point phase values are extracted. The different system pixel spacing values between ERS and ASAR requires additional refinement in the offset estimation and resampling procedure. Calculation of the ERS-ASAR simulated phase used to derive the differential interferometric phase must take into account the slightly different carrrier frequencies. Differential ERS-ASAR point phases contain an additional phase component related to the scatterer location within the resolution element. This additional phase varies over several cycles making the

  11. Longitudinal monitoring of Gaussia and Nano luciferase activities to concurrently assess ER calcium homeostasis and ER stress in vivo.

    PubMed

    Wires, Emily S; Henderson, Mark J; Yan, Xiaokang; Bäck, Susanne; Trychta, Kathleen A; Lutrey, Molly H; Harvey, Brandon K

    2017-01-01

    The endoplasmic reticulum (ER) is essential to many cellular processes including protein processing, lipid metabolism and calcium storage. The ability to longitudinally monitor ER homeostasis in the same organism would offer insight into progressive molecular and cellular adaptations to physiologic or pathologic states, but has been challenging. We recently described the creation of a Gaussia luciferase (GLuc)-based secreted ER calcium-modulated protein (SERCaMP or GLuc-SERCaMP) to longitudinally monitor ER calcium homeostasis. Here we describe a complementary tool to measure the unfolded protein response (UPR), utilizing a UPRE-driven secreted Nano luciferase (UPRE-secNLuc) to examine the activating transcription factor-6 (ATF6) and inositol-requiring enzyme 1 (IRE1) pathways of the UPR. We observed an upregulation of endogenous ATF6- and XBP1-regulated genes following pharmacologically-induced ER stress that was consistent with responsiveness of the UPRE sensor. Both GLuc and NLuc-based reporters have favorable properties for in vivo studies, however, they are not easily used in combination due to overlapping substrate activities. We describe a method to measure the enzymatic activities of both reporters from a single sample and validated the approach using culture medium and rat blood samples to measure GLuc-SERCaMP and UPRE-secNLuc. Measuring GLuc and NLuc activities from the same sample allows for the robust and quantitative measurement of two cellular events or cell populations from a single biological sample. This study is the first to describe the in vivo measurement of UPRE activation by sampling blood, using an approach that allows concurrent interrogation of two components of ER homeostasis.

  12. BOREAS Level-0 ER-2 Aerial Photography

    NASA Technical Reports Server (NTRS)

    Newcomer, Jeffrey A.; Dominquez, Roseanne; Hall, Forrest G. (Editor)

    2000-01-01

    For BOReal Ecosystem-Atmosphere Study (BOREAS), the ER-2 and other aerial photography was collected to provide finely detailed and spatially extensive documentation of the condition of the primary study sites. The ER-2 aerial photography consists of color-IR transparencies collected during flights in 1994 and 1996 over the study areas.

  13. Transitions of protein traffic from cardiac ER to junctional SR.

    PubMed

    Sleiman, Naama H; McFarland, Timothy P; Jones, Larry R; Cala, Steven E

    2015-04-01

    The junctional sarcoplasmic reticulum (jSR) is an important and unique ER subdomain in the adult myocyte that concentrates resident proteins to regulate Ca(2+) release. To investigate cellular mechanisms for sorting and trafficking proteins to jSR, we overexpressed canine forms of junctin (JCT) or triadin (TRD) in adult rat cardiomyocytes. Protein accumulation over time was visualized by confocal fluorescence microscopy using species-specific antibodies. Newly synthesized JCTdog and TRDdog appeared by 12-24h as bright fluorescent puncta close to the nuclear surface, decreasing in intensity with increasing radial distance. With increasing time (24-48h), fluorescent puncta appeared at further radial distances from the nuclear surface, eventually populating jSR similar to steady-state patterns. CSQ2-DsRed, a form of CSQ that polymerizes ectopically in rough ER, prevented anterograde traffic of newly made TRDdog and JCTdog, demonstrating common pathways of intracellular trafficking as well as in situ binding to CSQ2 in juxtanuclear rough ER. Reversal of CSQ-DsRed interactions occurred when a form of TRDdog was used in which CSQ2-binding sites are removed ((del)TRD). With increasing levels of expression, CSQ2-DsRed revealed a novel smooth ER network that surrounds nuclei and connects the nuclear axis. TRDdog was retained in smooth ER by binding to CSQ2-DsRed, but escaped to populate jSR puncta. TRDdog and (del)TRD were therefore able to elucidate areas of ER-SR transition. High levels of CSQ2-DsRed in the ER led to loss of jSR puncta labeling, suggesting a plasticity of ER-SR transition sites. We propose a model of ER and SR protein traffic along microtubules, with prominent transverse/radial ER trafficking of JCT and TRD along Z-lines to populate jSR, and an abundant longitudinal/axial smooth ER between and encircling myonuclei, from which jSR proteins traffic. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy

    PubMed Central

    Tan, S; Wei, X; Song, M; Tao, J; Yang, Y; Khatoon, S; Liu, H; Jiang, J; Wu, B

    2014-01-01

    Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG). p53-upregulated modulator of apoptosis (PUMA) was identified as a BH3-only Bcl-2 family protein that has an essential role in apoptosis induced by a variety of stimuli, including endoplasmic reticulum (ER) stress. However, whether PUMA is involved in mucosal apoptosis in PHG remains unclear, and whether PUMA induces PHG by mediating ER stress remains unknown. The aim of the study is to investigate whether PUMA is involved in PHG by mediating ER stress apoptotic signaling. To identify whether PUMA is involved in PHG by mediating ER stress, gastric mucosal injury and apoptosis were studied in both PHG patients and PHG animal models using PUMA knockout (PUMA-KO) and PUMA wild-type (PUMA-WT) mice. The induction of PUMA expression and ER stress signaling were investigated, and the mechanisms of PUMA-mediated apoptosis were analyzed. GES-1 and SGC7901 cell lines were used to further identify whether PUMA-mediated apoptosis was induced by ER stress in vitro. Epithelial apoptosis and PUMA were markedly induced in the gastric mucosa of PHG patients and mouse PHG models. ER stress had a potent role in the induction of PUMA and apoptosis in PHG models, and the apoptosis was obviously attenuated in PUMA-KO mice. Although the targeted deletion of PUMA did not affect ER stress, mitochondrial apoptotic signaling was downregulated in mice. Meanwhile, PUMA knockdown significantly ameliorated ER stress-induced mitochondria-dependent apoptosis in vitro. These results indicate that PUMA mediates ER stress-induced mucosal epithelial apoptosis through the mitochondrial apoptotic pathway in PHG, and that PUMA is a potentially therapeutic target for PHG. PMID:24625987

  15. Role of ERRF, a Novel ER-Related Nuclear Factor, in the Growth Control of ER-Positive Human Breast Cancer Cells

    PubMed Central

    Su, Dan; Fu, Xiaoying; Fan, Songqing; Wu, Xiao; Wang, Xin-Xin; Fu, Liya; Dong, Xue-Yuan; Ni, Jianping Jenny; Fu, Li; Zhu, Zhengmao; Dong, Jin-Tang

    2012-01-01

    Whereas estrogen–estrogen receptor α (ER) signaling plays an important role in breast cancer growth, it is also necessary for the differentiation of normal breast epithelial cells. How this functional conversion occurs, however, remains unknown. Based on a genome-wide sequencing study that identified mutations in several breast cancer genes, we examined some of the genes for mutations, expression levels, and functional effects on cell proliferation and tumorigenesis. We present the data for C1orf64 or ER-related factor (ERRF) from 31 cell lines and 367 primary breast cancer tumors. Whereas mutation of ERRF was infrequent (1 of 79 or 1.3%), its expression was up-regulated in breast cancer, and the up-regulation was more common in lower-stage tumors. In addition, increased ERRF expression was significantly associated with ER and/or progesterone receptor (PR) positivity, which was still valid in human epidermal growth factor receptor 2 (HER2)–negative tumors. In ER-positive tumors, ERRF expression was inversely correlated with HER2 status. Furthermore, higher ERRF protein expression was significantly associated with better disease-free survival and overall survival, particularly in ER- and/or PR-positive and HER2-negative tumors (luminal A subtype). Functionally, knockdown of ERRF in two ER-positive breast cancer cell lines, T-47D and MDA-MB-361, suppressed cell growth in vitro and tumorigenesis in xenograft models. These results suggest that ERRF plays a role in estrogen-ER–mediated growth of breast cancer cells and could, thus, be a potential therapeutic target. PMID:22341523

  16. ER-plasma membrane junctions: Why and how do we study them?

    PubMed

    Chang, Chi-Lun; Chen, Yu-Ju; Liou, Jen

    2017-09-01

    Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are membrane microdomains important for communication between the ER and the PM. ER-PM junctions were first reported in muscle cells in 1957, but mostly ignored in non-excitable cells due to their scarcity and lack of functional significance. In 2005, the discovery of stromal interaction molecule 1 (STIM1) mediating a universal Ca 2+ feedback mechanism at ER-PM junctions in mammalian cells led to a resurgence of research interests toward ER-PM junctions. In the past decade, several major advancements have been made in this emerging topic in cell biology, including the generation of tools for labeling ER-PM junctions and the unraveling of mechanisms underlying regulation and functions of ER-PM junctions. This review summarizes early studies, recently developed tools, and current advances in the characterization and understanding of ER-PM junctions. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Er{sub 1.33}Pt{sub 3}Ga{sub 8}: A modulated variant of the Er{sub 4}Pt{sub 9}Al{sub 24}-structure type

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

    Oswald, Iain W.H.; Gourdon, Olivier; Bekins, Amy

    Single crystals of Er{sub 1.33}Pt{sub 3}Ga{sub 8} were synthesized in a molten Ga flux. Er{sub 1.33}Pt{sub 3}Ga{sub 8} can be considered to be a modulated variant of the Er{sub 4}Pt{sub 9}Al{sub 24}-structure type, where the partial occupancies are ordered. Indeed, the presence of weak satellite reflections indicates a complex organization and distribution of the Er and Ga atoms within the [ErGa] slabs. The structure has been solved based on single crystal X-ray diffraction data in the monoclinic superspace group X2/m(0β0)00 with a commensurate modulated vector q=1/3b*. Precession images also indicate diffusion in the perpendicular direction indicating a partial disorder ofmore » this arrangement from layer to layer. In addition, Er{sub 1.33}Pt{sub 3}Ga{sub 8} shows antiferromagnetic ordering at T{sub N}~5 K. - Graphical abstract: A precession image of the hk0 zone showing weak, periodic, unindexed reflections indicating modulation and representation of the commensurate [ErGa] layer showing the waving modulated occupation. - Highlights: • Single crystals of Er{sub 1.33}Pt{sub 3}Ga{sub 8} were grown from gallium flux. • The structure of Er{sub 1.33}Pt{sub 3}Ga{sub 8} is compared to Er{sub 4}Pt{sub 9}Al{sub 24}. • Structure has been solved in the monoclinic superspace group X2/m(0β0)00 with a commensurate modulated vector q=1/3b*.« less

  18. ER-2 High Altitude Solar Cell Calibration Flights

    NASA Technical Reports Server (NTRS)

    Myers, Matthew G.; Piszczor, Michael F.

    2015-01-01

    The first flights of the ER-2 solar cell calibration demonstration were conducted during September-October of 2014. Three flights were performed that not only tested out the equipment and operational procedures, but also demonstrated the capability of this unique facility by conducting the first short-circuit measurements on a variety of test solar cells. Very preliminary results of these first flights were presented at the 2014 Space Photovoltaic Research and Technology (SPRAT) Conference in Cleveland, OH shortly following these first flights. At the 2015 Space Power Workshop, a more detailed description of these first ER-2 flights will be presented, along with the final flight data from some of the test cells that were flown and has now been reduced and corrected for ER-2 atmospheric flight conditions. Plans for ER-2 flights during the summer of 2015 will also be discussed.

  19. Electroluminescent Yb2O3:Er and Yb2Si2O7:Er nanolaminate films fabricated by atomic layer deposition on silicon

    NASA Astrophysics Data System (ADS)

    Ouyang, Zhongtao; Yang, Yang; Sun, Jiaming

    2018-06-01

    Atomic layer doped Yb2O3:Er and Yb2Si2O7:Er nanolaminate films are fabricated on silicon by atomic layer deposition, and ∼1530 nm electroluminescence (EL) is obtained from the metal-oxide-semiconductor light-emitting devices (MOSLEDs) based on these films. The Yb2O3 films transfer to Yb2Si2O7 phase after annealing above 1000 °C. Intense photoluminescence from Yb2Si2O7 film confirms high efficiency and energy transfer under optical excitation, but the limited electron conduction restricts the EL performance. EL from the Yb2O3:Er MOSLED outperforms, presenting an external quantum efficiency up to 8.5% and the power efficiency of 1 × 10-3. The EL is derived to result from the impact excitation of Er3+ ions by hot electrons, which stem from Fowler-Nordheim tunneling mechanism under sufficient bias voltage. The critical distance for the cross relaxation of doped Er3+ ions in nanolaminate Yb2O3 matrix is experimentally determined to be ∼3 nm. Such devices manifest the technological potential of Er-doped Yb-oxides for applications in silicon-based optoelectronics.

  20. ER-PM Contacts Define Actomyosin Kinetics for Proper Contractile Ring Assembly.

    PubMed

    Zhang, Dan; Bidone, Tamara C; Vavylonis, Dimitrios

    2016-03-07

    The cortical endoplasmic reticulum (ER), an elaborate network of tubules and cisternae [1], establishes contact sites with the plasma membrane (PM) through tethering machinery involving a set of conserved integral ER proteins [2]. The physiological consequences of forming ER-PM contacts are not fully understood. Here, we reveal a kinetic restriction role of ER-PM contacts over ring compaction process for proper actomyosin ring assembly in Schizosaccharomyces pombe. We show that fission yeast cells deficient in ER-PM contacts exhibit aberrant equatorial clustering of actin cables during ring assembly and are particularly susceptible to compromised actin filament crosslinking activity. Using quantitative image analyses and computer simulation, we demonstrate that ER-PM contacts function to modulate the distribution of ring components and to constrain their compaction kinetics. We propose that ER-PM contacts have evolved as important physical modulators to ensure robust ring assembly. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Lockheed ER-2 high altitude research aircraft

    NASA Image and Video Library

    1997-11-04

    ER-2 tail number 706, was one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft were platforms for a variety of high-altitude science missions flown over various parts of the world. They were also used for earth science and atmospheric sensor research and development, satellite calibration and data validation.

  2. Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor

    PubMed Central

    Omi, T; Tanimukai, H; Kanayama, D; Sakagami, Y; Tagami, S; Okochi, M; Morihara, T; Sato, M; Yanagida, K; Kitasyoji, A; Hara, H; Imaizumi, K; Maurice, T; Chevallier, N; Marchal, S; Takeda, M; Kudo, T

    2014-01-01

    We recently demonstrated that endoplasmic reticulum (ER) stress induces sigma-1 receptor (Sig-1R) expression through the PERK pathway, which is one of the cell's responses to ER stress. In addition, it has been demonstrated that induction of Sig-1R can repress cell death signaling. Fluvoxamine (Flv) is a selective serotonin reuptake inhibitor (SSRI) with a high affinity for Sig-1R. In the present study, we show that treatment of neuroblastoma cells with Flv induces Sig-1R expression by increasing ATF4 translation directly, through its own activation, without involvement of the PERK pathway. The Flv-mediated induction of Sig-1R prevents neuronal cell death resulting from ER stress. Moreover, Flv-induced ER stress resistance reduces the infarct area in mice after focal cerebral ischemia. Thus, Flv, which is used frequently in clinical practice, can alleviate ER stress. This suggests that Flv could be a feasible therapy for cerebral diseases caused by ER stress. PMID:25032855

  3. The ER in 3D: a multifunctional dynamic membrane network.

    PubMed

    Friedman, Jonathan R; Voeltz, Gia K

    2011-12-01

    The endoplasmic reticulum (ER) is a large, singular, membrane-bound organelle that has an elaborate 3D structure with a diversity of structural domains. It contains regions that are flat and cisternal, ones that are highly curved and tubular, and others adapted to form contacts with nearly every other organelle and with the plasma membrane. The 3D structure of the ER is determined by both integral ER membrane proteins and by interactions with the cytoskeleton. In this review, we describe some of the factors that are known to regulate ER structure and discuss how this structural organization and the dynamic nature of the ER membrane network allow it to perform its many different functions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Magnetocaloric effect in textured rare earth intermetallic compound ErNi

    NASA Astrophysics Data System (ADS)

    Sankar, Aparna; Chelvane, J. Arout; Morozkin, A. V.; Nigam, A. K.; Quezado, S.; Malik, S. K.; Nirmala, R.

    2018-05-01

    Melt-spun ErNi crystallizes in orthorhombic FeB-type structure (Space group Pnma, no. 62) similar to the arc-melted ErNi compound. Room temperature X-ray diffraction (XRD) experiments reveal the presence of texture and preferred crystal orientation in the melt-spun ErNi. The XRD data obtained from the free surface of the melt-spun ErNi show large intensity enhancement for (1 0 2) Bragg reflection. The scanning electron microscopy image of the free surface depicts a granular microstructure with grains of ˜1 μm size. The arc-melted and the melt-spun ErNi compounds order ferromagnetically at 11 K and 10 K (TC) respectively. Field dependent magnetization (M-H) at 2 K shows saturation behaviour and the saturation magnetization value is 7.2 μB/f.u. for the arc-melted ErNi and 7.4 μB/f.u. for the melt-spun ErNi. The isothermal magnetic entropy change (ΔSm) close to TC has been calculated from the M-H data. The maximum isothermal magnetic entropy change, -ΔSmmax, is ˜27 Jkg-1K-1 and ˜24 Jkg-1K-1 for the arc-melted and melt-spun ErNi for 50 kOe field change, near TC. The corresponding relative cooling power values are ˜440 J/kg and ˜432 J/kg respectively. Although a part of ΔSm is lost to crystalline electric field (CEF) effects, the magnetocaloric effect is substantially large at 10 K, thus rendering melt-spun ErNi to be useful in low temperature magnetic refrigeration applications such as helium gas liquefaction.

  5. Structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics for a-IGZO thin-film transistors

    PubMed Central

    2013-01-01

    In this letter, we investigated the structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics on the amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistor (TFT) devices. Compared with the Er2O3 dielectric, the a-IGZO TFT device incorporating an Er2TiO5 gate dielectric exhibited a low threshold voltage of 0.39 V, a high field-effect mobility of 8.8 cm2/Vs, a small subthreshold swing of 143 mV/decade, and a high Ion/Ioff current ratio of 4.23 × 107, presumably because of the reduction in the oxygen vacancies and the formation of the smooth surface roughness as a result of the incorporation of Ti into the Er2TiO5 film. Furthermore, the reliability of voltage stress can be improved using an Er2TiO5 gate dielectric. PMID:23294730

  6. Structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics for a-IGZO thin-film transistors.

    PubMed

    Chen, Fa-Hsyang; Her, Jim-Long; Shao, Yu-Hsuan; Matsuda, Yasuhiro H; Pan, Tung-Ming

    2013-01-08

    In this letter, we investigated the structural and electrical characteristics of high-κ Er2O3 and Er2TiO5 gate dielectrics on the amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistor (TFT) devices. Compared with the Er2O3 dielectric, the a-IGZO TFT device incorporating an Er2TiO5 gate dielectric exhibited a low threshold voltage of 0.39 V, a high field-effect mobility of 8.8 cm2/Vs, a small subthreshold swing of 143 mV/decade, and a high Ion/Ioff current ratio of 4.23 × 107, presumably because of the reduction in the oxygen vacancies and the formation of the smooth surface roughness as a result of the incorporation of Ti into the Er2TiO5 film. Furthermore, the reliability of voltage stress can be improved using an Er2TiO5 gate dielectric.

  7. Configuration Analysis of the ERS Points in Large-Volume Metrology System

    PubMed Central

    Jin, Zhangjun; Yu, Cijun; Li, Jiangxiong; Ke, Yinglin

    2015-01-01

    In aircraft assembly, multiple laser trackers are used simultaneously to measure large-scale aircraft components. To combine the independent measurements, the transformation matrices between the laser trackers’ coordinate systems and the assembly coordinate system are calculated, by measuring the enhanced referring system (ERS) points. This article aims to understand the influence of the configuration of the ERS points that affect the transformation matrix errors, and then optimize the deployment of the ERS points to reduce the transformation matrix errors. To optimize the deployment of the ERS points, an explicit model is derived to estimate the transformation matrix errors. The estimation model is verified by the experiment implemented in the factory floor. Based on the proposed model, a group of sensitivity coefficients are derived to evaluate the quality of the configuration of the ERS points, and then several typical configurations of the ERS points are analyzed in detail with the sensitivity coefficients. Finally general guidance is established to instruct the deployment of the ERS points in the aspects of the layout, the volume size and the number of the ERS points, as well as the position and orientation of the assembly coordinate system. PMID:26402685

  8. Spectroscopic characterisation of Er-doped LuVO4 single crystals

    NASA Astrophysics Data System (ADS)

    Lisiecki, R.; Dominiak-Dzik, G.; Solarz, P.; Strzęp, A.; Ryba-Romanowski, W.; Łukasiewicz, T.

    2010-12-01

    The LuVO4:Er single crystals were grown by the Czochralski technique. The crystal-field split energy levels of Er3+ ion were derived experimentally employing absorption and emission spectra measured at T=10 K. The Judd-Ofelt phenomenological method was used to estimate intensity parameters, radiative lifetimes and branching ratios of luminescence. The excited state dynamics of the LuVO4:Er systems was investigated and experimental lifetimes of emitting levels were measured. The emission cross section of the 4I13/2→4I15/2 transition in the infrared was calculated by the Füchtbauer-Ladenburg method. The gain cross section, estimated for several inverse-population parameters, allowed us to evaluate a potential laser activity of the LuVO4:Er system at 1.6 μm. Also, the potential range of the optical pumping was assessed based on absorption spectra achieved at the room temperature. The optical losses related to the green up-converted emission, encountered under the 978 nm excitation between 300 and 670 K were indicated and discussed. Spectroscopic peculiarities of the Er3+-doped LuVO4 crystal were discussed in relation to optical properties of the YVO4:Er and GdVO4:Er crystals. Taking into account the high quantum efficiency of the 4I13/2 level, and satisfactory absorption and emission features, the LuVO4:Er crystal can be considered as a promising active material for laser operation near 1.6 μm.

  9. Analysis of erythema after Er:YAG laser skin resurfacing.

    PubMed

    Ko, Na Young; Ahn, Hyo-Hyun; Kim, Soo-Nam; Kye, Young-Chul

    2007-11-01

    Postoperative erythema can be expected to occur in every patient after laser resurfacing, and pigmentary disturbances may be related to the intensity and the duration of erythema. This study was undertaken to assess the clinical features of erythema, the factors that influence its duration, and the relation between the duration of erythema and the incidence of hyperpigmentation and hypopigmentation in skin of Asian persons after Er:YAG laser resurfacing. A total of 218 patients (skin phototypes III to V) were recruited and treated with a short-pulsed Er:YAG laser, a variable-pulsed Er:YAG laser, or a dual-mode Er:YAG laser for skin resurfacing. Clinical assessments were performed retrospectively using medical charts and serial photographs. Postoperative erythema was observed in all patients after Er:YAG laser resurfacing with a mean duration of 4.72 months. In 98.2% of patients, erythema faded completely within 12 months. Postinflammatory hyperpigmentation was observed in 38.1% of patients after Er:YAG laser resurfacing. Skin phototype, level of ablation, and depth of thermal damage caused by a long-pulsed laser appear to be important factors that affect the duration of erythema. Moreover, prolonged erythema was related to the risk of postinflammatory hyperpigmentation.

  10. Initiation and execution of lipotoxic ER stress in pancreatic β-cells

    PubMed Central

    Cunha, Daniel A.; Hekerman, Paul; Ladrière, Laurence; Bazarra-Castro, Angie; Ortis, Fernanda; Wakeham, Marion C.; Moore, Fabrice; Rasschaert, Joanne; Cardozo, Alessandra K.; Bellomo, Elisa; Overbergh, Lutgart; Mathieu, Chantal; Lupi, Roberto; Hai, Tsonwin; Herchuelz, Andre; Marchetti, Piero; Rutter, Guy A.; Eizirik, Décio L.; Cnop, Miriam

    2013-01-01

    Summary Free fatty acids (FFA) cause apoptosis of pancreatic β-cells and might contribute to β-cell loss in type 2 diabetes via the induction of endoplasmic reticulum (ER) stress. We studied here the molecular mechanisms implicated in FFA-induced ER stress initiation and apoptosis in INS-1E cells, FACS-purified primary β-cells and human islets exposed to oleate and/or palmitate. Treatment with saturated and/or unsaturated FFA led to differential ER stress signaling. Palmitate induced more apoptosis and markedly activated the IRE1, PERK and ATF6 pathways, owing to a sustained depletion of ER Ca2+ stores, whereas the unsaturated FFA oleate led to milder PERK and IRE1 activation and comparable ATF6 signaling. Non-metabolizable methyl-FFA analogs induced neither ER stress nor β-cell apoptosis. The FFA-induced ER stress response was not modified by high glucose concentrations, suggesting that ER stress in primary β-cells is primarily lipotoxic, and not glucolipotoxic. Palmitate, but not oleate, activated JNK. JNK inhibitors reduced palmitate-mediated AP-1 activation and apoptosis. Blocking the transcription factor CHOP delayed palmitate-induced β-cell apoptosis. In conclusion, saturated FFA induce ER stress via ER Ca2+ depletion. The IRE1 and resulting JNK activation contribute to β-cell apoptosis. PERK activation by palmitate also contributes to β-cell apoptosis via CHOP. PMID:18559892

  11. Fluorescence lifetime imaging of microviscosity changes during ER autophagy in live cells

    NASA Astrophysics Data System (ADS)

    He, Ying; Samanta, Soham; Gong, Wanjun; Liu, Wufan; Pan, Wenhui; Yang, Zhigang; Qu, Junle

    2018-02-01

    Unfolded or misfolded protein accumulation inside Endoplasmic Reticulum (ER) will cause ER stress and subsequently will activate cellular autophagy to release ER stress, which would ultimately result in microviscosity changes. However, even though, it is highly significant to gain a quantitative assessment of microviscosity changes during ER autophagy to study ER stress and autophagy behaviors related diseases, it has rarely been reported yet. In this work, we have reported a BODIPY based fluorescent molecular rotor that can covalently bind with vicinal dithiols containing nascent proteins in ER and hence can result in ER stress through the inhibition of the folding of nascent proteins. The change in local viscosity, caused by the release of the stress in cells through autophagy, was quantified by the probe using fluorescence lifetime imaging. This work basically demonstrates the possibility of introducing synthetic chemical probe as a promising tool to diagnose ER-viscosity-related diseases.

  12. [Up-conversion luminescent materials of Y2O3: RE(RE=Er or Er/Yb) prepared by sol-gel combustion synthesis].

    PubMed

    Han, Peng-de; Zhang, Le; Huang, Xiao-gu; Wang, Li-xi; Zhang, Qi-tu

    2010-11-01

    Y2O3 powders doped with rare-earth ions were synthesized by sol-gel combustion synthesis. Effects of different calcinating temperatures, Er+ doping concentration and Yb3+ doping concentration were investigated. It was shown that the single well crystallized Y2O3 powders could be obtained at 800 degrees C; as the calcinating temperature increased, the crystallinity and upconversion luminescence intensity were higher; the particle size was uniform around 1 microm at 900 degrees C; when Er3+ doping concentration was 1 mol%, the green upconversion luminescence intensity reached the maximum, but for red upconversion luminescence, when Er3+ doping concentration was 4 mol%, its luminescence intensity reached the maximum; as the ratio of Yb3+ to Er3+ was 4:1, the green emission intensity reached the maximum, while the red emission intensity was always increasing as Yb3+ doping concentration increased.

  13. ER bodies in plants of the Brassicales order: biogenesis and association with innate immunity

    PubMed Central

    Nakano, Ryohei T.; Yamada, Kenji; Bednarek, Paweł; Nishimura, Mikio; Hara-Nishimura, Ikuko

    2014-01-01

    The endoplasmic reticulum (ER) forms highly organized network structures composed of tubules and cisternae. Many plant species develop additional ER-derived structures, most of which are specific for certain groups of species. In particular, a rod-shaped structure designated as the ER body is produced by plants of the Brassicales order, which includes Arabidopsis thaliana. Genetic analyses and characterization of A. thaliana mutants possessing a disorganized ER morphology or lacking ER bodies have provided insights into the highly organized mechanisms responsible for the formation of these unique ER structures. The accumulation of proteins specific for the ER body within the ER plays an important role in the formation of ER bodies. However, a mutant that exhibits morphological defects of both the ER and ER bodies has not been identified. This suggests that plants in the Brassicales order have evolved novel mechanisms for the development of this unique organelle, which are distinct from those used to maintain generic ER structures. In A. thaliana, ER bodies are ubiquitous in seedlings and roots, but rare in rosette leaves. Wounding of rosette leaves induces de novo formation of ER bodies, suggesting that these structures are associated with resistance against pathogens and/or herbivores. ER bodies accumulate a large amount of β-glucosidases, which can produce substances that potentially protect against invading pests. Biochemical studies have determined that the enzymatic activities of these β-glucosidases are enhanced during cell collapse. These results suggest that ER bodies are involved in plant immunity, although there is no direct evidence of this. In this review, we provide recent perspectives of ER and ER body formation in A. thaliana, and discuss clues for the functions of ER bodies. We highlight defense strategies against biotic stress that are unique for the Brassicales order, and discuss how ER structures could contribute to these strategies. PMID

  14. Transcriptional repression of ER through hMAPK dependent histone deacetylation by class I HDACs.

    PubMed

    Plotkin, Amy; Volmar, Claude-Henry; Wahlestedt, Claes; Ayad, Nagi; El-Ashry, Dorraya

    2014-09-01

    Anti-estrogen therapies are not effective in ER- breast cancers, thus identifying mechanisms underlying lack of ER expression in ER- breast cancers is imperative. We have previously demonstrated that hyperactivation of MAPK (hMAPK) downstream of overexpressed EGFR or overexpression/amplification of Her2 represses ER protein and mRNA expression. Abrogation of hMAPK in ER- breast cancer cell lines and primary cultures causes re-expression of ER and restoration of anti-estrogen responses. This study was performed to identify mechanisms of hMAPK-induced transcriptional repression of ER. We found that ER promoter activity is significantly reduced in the presence of hMAPK signaling, yet did not identify specific promoter sequences responsible for this repression. We performed an epigenetic compound screen in an ER- breast cancer cell line that expresses hMAPK yet does not exhibit ER promoter hypermethylation. A number of HDAC inhibitors were identified and confirmed to modulate ER expression and estrogen signaling in multiple ER- cell lines and tumor samples lacking ER promoter methylation. siRNA-mediated knockdown of HDACs 1, 2, and 3 reversed the mRNA repression in multiple breast cancer cell lines and primary cultures and ER promoter-associated histone acetylation increased following MAPK inhibition. These data implicate histone deacetylation downstream of hMAPK in the observed ER mRNA repression associated with hMAPK. Importantly, histone deacetylation appears to be a common mechanism in the transcriptional repression of ER between ER- breast cancers with or without ER promoter hypermethylation.

  15. Temperature Effects of Dielectric Properties of ER Fluids

    NASA Astrophysics Data System (ADS)

    Qiu, Z. Y.; Hu, L.; Liu, M. W.; Bao, H. X.; Jiang, Y. G.; Zhou, L. W.; Tang, Y.; Gao, Z.; Sun, M.; Korobko, E. V.

    Under the consideration of the role that energy transfer and dissipation play in ER effect, an improved theory frame for ER effects, polarization-dissipation-structure-rheology, is suggested. The theory frame is substantiated by the basic physical laws and certain critical experimental facts. The dielectric response of a diatomite ER fluid to temperature is measured in the temperature range of 140 K to 400 K. By comparison of the DC conductivity with the AC effective conductivity of the sample, we found that the AC dielectric loss consists of two parts. One part comes from the DC conductivity, the other from the response of the bound charges in scope of particle to AC field. It is suggested that the response of bound charges is very important to ER effects. Besides, the effect of temperature on shear stress is measured, and interpreted based on the dielectric measurements. The source of two loss peaks in the curve of the dielectric loss versus temperature is not clear.

  16. On the enhancement of Er{sup 3+} diffusion in LiNbO{sub 3} crystals by Er{sup 3+}/Ti{sup 4+} co-diffusion

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

    Almeida, José Manuel Marques Martins de, E-mail: jmmma@utad.pt; Department of Physics, School of Science and Technology, University of Trás-os-Montes e Alto Douro, PO. Box 1013, 5001-801 Vila Real; Sada, Cinzia

    2016-02-15

    Highlights: • Enhancement of the diffusion of erbium ions (Er{sup 3+}) in lithium niobate crystals. • Incoherence on published results lead to need for systematic revision of literature. • Further insight into the topic of co-diffusion of Er{sup 3+}/Ti{sup 4+} ions into LiNbO{sub 3}. - Abstract: After carrying out a revision of the literature on the enhancement of Er{sup 3+} diffusion in LiNbO{sub 3} crystals by Er{sup 3+}/Ti{sup 4+} co-diffusion and analyzing our own experimental results, we conclude that no reproducible results were reported, meaning that further research on this subject is necessary.

  17. Aging induced ER stress alters sleep and sleep homeostasis

    PubMed Central

    Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

    2014-01-01

    Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

  18. Getting ER into the Curriculum: No More Excuses!

    ERIC Educational Resources Information Center

    Ewert, Doreen

    2017-01-01

    Extensive reading (ER) is a research and theory-supported approach for language and reading development in an additional language, yet its implementation is limited, particularly in English-dominant contexts. This article addresses many of the uncertainties and perceived obstacles to adding ER to a language curriculum. After reviewing relevant…

  19. Clad-pumped Er-nanoparticle-doped fiber laser (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Baker, Colin C.; Friebele, E. Joseph; Rhonehouse, Daniel L.; Marcheschi, Barbara A.; Peele, John R.; Kim, Woohong; Sanghera, Jasbinder S.; Zhang, Jun; Chen, Youming; Pattnaik, Radha K.; Dubinskii, Mark

    2017-03-01

    Erbium-doped fiber lasers are attractive for directed energy weapons applications because they operate in a wavelength region that is both eye-safer and a window of high atmospheric transmission. For these applications a clad-pumped design is desirable, but the Er absorption must be high because of the areal dilution of the doped core vs. the pump cladding. High Er concentrations typically lead to Er ion clustering, resulting in quenching and upconversion. Nanoparticle (NP) doping of the core overcomes these problems by physically surrounding the Er ions with a cage of Al and O in the NP, which keeps them separated to minimize excited state energy transfer. A significant issue is obtaining high Er concentrations without the NP agglomeration that degrades the optical properties of the fiber core. We have developed the process for synthesizing stable Er-NP suspension which have been used to fabricate EDFs with Er concentrations >90 dB/m at 1532 nm. Matched clad fibers have been evaluated in a core-pumped MOPA with pump and signal wavelengths of 1475 and 1560 nm, respectively, and efficiencies of 72% with respect to absorbed pump have been obtained. We have fabricated both NP- and solution-doped double clad fibers, which have been measured in a clad-pumped laser testbed using a 1532 nm pump. The 1595 nm laser efficiency of the NP-doped fiber was 47.7%, which is high enough for what is believed to be the first laser experiment with the cladding pumped, NP-doped fiber. Further improvements are likely with a shaped cladding and new low-index polymer coatings with lower absorption in the 1500 - 1600 nm range.

  20. Harvard ER-2 OH laser-induced fluorescence instrument

    NASA Technical Reports Server (NTRS)

    Wennberg, Paul O.; Anderson, James G.

    1994-01-01

    The Harvard ER-2 OH instrument is scheduled to be integrated into the NASA ER-2 high altitude aircraft ozone payload in August 1992. Design and fabrication is presently underway. This experiment is a descendant of a balloon borne instrument designed and built in the mid-1980s. The ER-2 instrument is being designed to measure OH and HO2 as part of the NASA ozone payload for the investigation of processes controlling the concentration of stratospheric ozone. Although not specifically designed to do so, it is hoped that valid measurements of OH and HO2 can be made in the remote free troposphere with this instrument.

  1. Computational modelling of Er(3+): Garnet laser materials

    NASA Technical Reports Server (NTRS)

    Spangler, Lee H.

    1994-01-01

    The Er(3+) ion has attracted a lot of interest for four reasons: (1) Its (4)I(sub 13/2) yields (4)I(sub 15/2) transition lases in the eyesafe region near 1.5 micron; (2) the (4)I(sub 13/2) transition lases near 2.8 micron, an important wavelength for surgical purposes; (3) it displays surprisingly efficient upconversion with lasing observed at 1.7, 1.2, 0.85, 0.56, 0.55, and 0.47 micron following 1.5 micron pumping; and (4) it has absorption bands at 0.96 and 0.81 micron and thus can be diode pumped. However, properties desirable for upconversion reduce the efficiency of 1.5 and 3 micron laser operation and vice versa. Since all of the processes are influenced by the host via the crystal field induced stark splittings in the Er levels, this project undertook modelling of the host influence on the Er lasinng behavior. While growth and measurement of all ten Er(3+) doped garnets is the surest way of identifying hosts which maximize upconversion (or conversly, 1.5 and 3 micron performance), it is also expensive - costing approximately $10,000/material or approximately $100,000 for the materials computationally investigated here. The calculations were performed using a quantum mechanical point charge model developed by Clyde Morrison at Harry Diamond Laboratories. The programs were used to fit the Er:YAG experimental energy levels so that the crystal field parameters, B(sub nm) could be extracted. From these radial factors, rho (sub n) were determined for Er(3+) in garnets. These, in combination with crystal field components, Anm, available from X-ray data, were used to predict energy levels for Er in the other nine garnet hosts. The levels in Er:YAG were fit with an rms error of 12.2/cm over a 22,000/cm range. Predicted levels for two other garnets for which literature values were available had rms errors of less than 17/cm , showing the calculations to be reliable. Based on resonances between pairs of calculated stark levels, the model predicts GSGG as the best host

  2. Electrorheological (ER) Fluids: A Research Needs Assessment

    DTIC Science & Technology

    1993-05-01

    transmission, and to reduce energy loss and damage due to vibration and oscillation. A large number and variety of ER devices have been invented; they are...suspension must be stabilized to prevent settling. Separation could cause loss of fluid performance, plugging of flow paths, and other problems...performa.ice of ER fluids, especially those containing water, can change with time as a result of component loss through evaporation at elevated use

  3. ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER.

    PubMed

    Costello, Joseph L; Castro, Inês G; Hacker, Christian; Schrader, Tina A; Metz, Jeremy; Zeuschner, Dagmar; Azadi, Afsoon S; Godinho, Luis F; Costina, Victor; Findeisen, Peter; Manner, Andreas; Islinger, Markus; Schrader, Michael

    2017-02-01

    Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO-ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A-binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5-VAPB interaction regulates PO-ER associations. Moreover, we demonstrate that loss of PO-ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO-ER associations in mammalian cells and report a new function for ACBD5 in PO-ER tethering. © 2017 Costello et al.

  4. ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER

    PubMed Central

    Costello, Joseph L.; Hacker, Christian; Schrader, Tina A.; Zeuschner, Dagmar; Findeisen, Peter

    2017-01-01

    Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO–ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A–binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5–VAPB interaction regulates PO–ER associations. Moreover, we demonstrate that loss of PO–ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO–ER associations in mammalian cells and report a new function for ACBD5 in PO–ER tethering. PMID:28108524

  5. Interleukin 17A exacerbates ER-stress-mediated inflammation of macrophages following ICH.

    PubMed

    Yang, Zhao; Liu, Qingjun; Shi, Hui; Jiang, Xuheng; Wang, Song; Lu, Yuanlan; Zhang, Ji; Huang, Xiaofei; Yu, Anyong

    2018-05-30

    IL-17A contributes to the initiation of inflammation following intracerebral hemorrhage (ICH). Endoplasmic reticulum (ER) stress acts on protein folding and contributes to inflammatory diseases. The role of IL-17A in the regulation of ER stress following ICH has not been well characterized. In this study, macrophages were stimulated with IL-17A, and then, ER stress and downstream pro-inflammatory factors were measured in vitro. In addition, brain edema and brain injury in ICH mice were assessed in vivo. We demonstrated that IL-17A induced ER stress in macrophages and thus promoted inflammation in vitro. Conversely, IL-17A inhibition attenuated ER stress and neuroinflammation. Furthermore, ERK 1/2 and p38 MAPK pathways mediated IL-17A-induced ER stress in macrophages. We also showed that IL-17A inhibition significantly attenuated ER stress and brain injury in ICH mice. In conclusion, our results demonstrate that IL 17A increases ER stress in macrophages and represents a novel mechanism in ICH. Copyright © 2018. Published by Elsevier Ltd.

  6. Enhancement of Er optical efficiency through bismuth sensitization in yttrium oxide

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

    Scarangella, Adriana; Dipartimento di Fisica e Astronomia, Università di Catania, Via S. Sofia 64, 95123 Catania; Reitano, Riccardo

    2015-07-27

    The process of energy transfer (ET) between optically active ions has been widely studied to improve the optical efficiency of a system for different applications, from lighting and photovoltaics to silicon microphotonics. In this work, we report the influence of Bi on the Er optical emission in erbium-yttrium oxide thin films synthesized by magnetron co-sputtering. We demonstrate that this host permits to well dissolve Er and Bi ions, avoiding their clustering, and thus to stabilize the optically active Er{sup 3+} and Bi{sup 3+} valence states. In addition, we establish the ET occurrence from Bi{sup 3+} to Er{sup 3+} by themore » observed Bi{sup 3+} PL emission decrease and the simultaneous Er{sup 3+} photoluminescence (PL) emission increase. This was further confirmed by the coincidence of the Er{sup 3+} and Bi{sup 3+} excitation bands, analyzed by PL excitation spectroscopy. By increasing the Bi content of two orders of magnitude inside the host, though the occurrence of Bi-Bi interactions becomes deleterious for Bi{sup 3+} optical efficiency, the ET process between Bi{sup 3+} and Er{sup 3+} is still prevalent. We estimate ET efficiency of 70% for the optimized Bi:Er ratio equal to 1:3. Moreover, we have demonstrated to enhance the Er{sup 3+} effective excitation cross section by more than three orders of magnitude with respect to the direct one, estimating a value of 5.3 × 10{sup −18} cm{sup 2}, similar to the expected Bi{sup 3+} excitation cross section. This value is one of the highest obtained for Er in Si compatible hosts. These results make this material very promising as an efficient emitter for Si-compatible photonics devices.« less

  7. Visible upconversion emission and non-radiative direct Yb 3+ to Er 3+ energy transfer processes in nanocrystalline ZrO 2:Yb 3+,Er 3+

    NASA Astrophysics Data System (ADS)

    Diaz-Torres, L. A.; Meza, O.; Solis, D.; Salas, P.; De la Rosa, E.

    2011-06-01

    Wide band gap Yb 3+ and Er 3+ codoped ZrO 2 nanocrystals have been synthesized by a modified sol-gel method. Under 967 nm excitation strong green and red upconversion emission is observed for several Er 3+ to Yb 3+ ions concentration ratios. A simple microscopic rate equation model is used to study the effects of non-radiative direct Yb 3+ to Er 3+ energy transfer processes on the visible and near infrared fluorescence decay trends of both Er 3+ and Yb 3+ ions. The microscopic rate equation model takes into account the crystalline phase as well as the size of nanocrystals. Nanocrystals phase and size were estimated from XRD patterns. The rate equation model succeeds to fit simultaneously all visible and near infrared fluorescence decay profiles. The dipole-dipole interaction parameters that drive the non-radiative energy transfer processes depend on doping concentration due to crystallite phase changes. In addition the non-radiative relaxation rate ( 4I11/2→ 4I13/2) is found to be greater than that estimated by the Judd-Ofelt parameters due to the action of surface impurities. Results suggest that non-radiative direct Yb 3+ to Er 3+ energy transfer processes in ZrO 2:Yb,Er are extremely efficient.

  8. ER Consolidated Qtrly Rpt_April thru June 2015_October 2015

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

    Cochran, John

    2015-10-01

    This Sandia National Laboratories, New Mexico Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) fulfills all quarterly reporting requirements set forth in the Resource Conservation and Recovery Act Facility Operating Permit, and the Compliance Order on Consent. The 13 sites in the Corrective Action process are listed in Table I-1. Because the status of any Long-Term Stewardship (LTS) activity is detailed in other reports, Section I.3.0 (titled Long-Term Stewardship Work Completed) will not be presented in future ER Quarterly Reports. Section I.3.0 of this ER Quarterly Report identifies the other reports that detail LTS activities.

  9. Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

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

    Friedrich, Stephan; Boyd, Stephen; Cantor, Robin

    2016-05-06

    This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

  10. Fabrication of Gamma Detectors Based on Magnetic Ag:Er Microcalorimeters

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

    Friedrich, Stephan; Boyd, Stephen; Cantor, Robin

    2015-11-25

    This report discusses the photolithographic fabrication of ultra-high resolution gamma-ray detectors based on magnetic microcalorimeters (MMCs). The MMC uses a novel Er-doped silver sensor (Ag:Er) that is expected to have higher sensitivity than the Er-doped gold (Au:Er) sensors currently in use. The MMC also integrates the first-stage SQUID preamplifier on the same chip as the MMC gamma detector to increase its signal-to-noise ratio. In addition, the MMC uses a passive Ta-Nb heat switch to replace one of the common long-term failure points in earlier detectors. This report discusses the fabrication process we have developed to implement the proposed improvements.

  11. Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

    PubMed

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-04-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

  12. Evaluation of the bactericidal effect of Nd:YAG, Er:YAG, Er,Cr:YSGG laser radiation, and antimicrobial photodynamic therapy (aPDT) in experimentally infected root canals.

    PubMed

    Cheng, Xiaogang; Guan, Sumin; Lu, Hong; Zhao, Chunmiao; Chen, Xingxing; Li, Na; Bai, Qian; Tian, Yu; Yu, Qing

    2012-12-01

    In recent years, various laser systems have been introduced into the field of laser-assisted endodontic therapy. The aim of this study was to evaluate the bactericidal effect of Nd:YAG, Er:YAG, Er,Cr:YSGG laser radiation, and antimicrobial photodynamic therapy (aPDT) in experimentally infected root canals compared with standard endodontic treatment of 5.25% sodium hypochlorite (NaClO) irrigation. Two hundred and twenty infected root canals from extracted human teeth (contaminated with Enterococcus faecalis ATCC 4083 for 4 weeks) were randomly divided into five experimental groups (Nd:YAG, Er:YAG + 5.25% NaClO + 0.9% normal saline + distilled water (Er:YAG/NaClO/NS/DW), Er:YAG + 0.9% normal saline + distilled water (Er:YAG/NS/DW), Er,Cr:YSGG, and aPDT) and two control groups (5.25% NaClO as positive control and 0.9% normal saline (NS) as negative control). The numbers of bacteria on the surface of root canal walls and at different depths inside dentinal tubules before and after treatment were analyzed by means of one-way analysis of variance (one-way ANOVA). The morphology of bacterial cells before and after treatment was examined by scanning electron microscopy (SEM). After treatment, the bacterial reductions in the experimental groups and the positive control group were significantly greater than that of the negative control group (P < 0.001). However, only Er:YAG/NaClO/NS/DW group showed no bacterial growth (the bacterial reduction reached up to 100%) on the surface of root canal walls or at 100/200 µm inside the dentinal tubules. All the laser radiation protocols tested, especially Er:YAG/NaClO/NS/DW, have effective bactericidal effect in experimentally infected root canals. Er:YAG/NaClO/NS/DW seems to be an ideal protocol for root canal disinfection during endodontic therapy. Copyright © 2012 Wiley Periodicals, Inc.

  13. An ab initio-based Er–He interatomic potential in hcp Er

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

    Yang, Li; ye, Yeting; Fan, K. M.

    2014-09-01

    We have developed an empirical erbium-helium (Er-He) potential by fitting to the results calculated from ab initio method. Based on the electronic hybridization between Er and He atoms, an s-band model, along with a repulsive pair potential, has been derived to describe the Er-He interaction. The atomic configurations and the formation energies of single He defects, small He interstitial clusters (Hen) and He-vacancy (HenV ) clusters obtained by ab initio calculations are used as the fitting database. The binding energies and relative stabilities of the HnVm clusters are studied by the present potential and compared with the ab initio calculations.more » The Er-He potential is also applied to study the migration of He in hcp-Er at different temperatures, and He clustering is found to occur at 600 K in hcp Er crystal, which may be due to the anisotropic migration behavior of He interstitials.« less

  14. Structural Analysis of the QCM Aboard the ER-2

    NASA Technical Reports Server (NTRS)

    Jones, Phyllis D.; Bainum, Peter M.; Xing, Guangqian

    1997-01-01

    As a result of recent supersonic transport (SST) studies on the effect they may have on the atmosphere, several experiments have been proposed to capture and evaluate samples of the stratosphere where SST's travel. One means to achieve this is to utilize the quartz crystal microbalance (QCM) installed aboard the ER-2, formerly the U-2 reconnaissance aircraft. The QCM is a cascade impactor designed to perform in-situ, real-time measurements of aerosols and chemical vapors at an altitude of 60,000 - 70,000 feet. The ER-2 is primarily used by NASA for Earth resources to test new sensor systems before they are placed aboard satellites. One of the main reasons the ER-2 is used for this flight experiment is its capability to fly approximately twelve miles above sea level (can reach an altitude of 78,000 feet). Because the ER-2 operates at such a high altitude, it is of special interest to scientists interested in space exploration or supersonic aircraft. Some of the experiments are designed to extract data from the atmosphere around the ER-2. For the current flight experiment, the QCM is housed in a frame that is connected to an outer pod that is attached to the fuselage of the ER-2. Due to the location of the QCM within the housing frame and the location of the pod on the ER-2, the pod and its contents are subject to structural loads. In addition to structural loads, structural vibrations are also of importance because the QCM is a frequency induced instrument. Therefore, a structural analysis of the instrument within the frame is imperative to determine if resonance and/or undesirable deformations occur.

  15. Emerging themes of ER organization in the development and maintenance of axons

    PubMed Central

    Renvoisé, Benoît; Blackstone, Craig

    2010-01-01

    The endoplasmic reticulum (ER) is a continuous membrane system comprising the nuclear envelope, polyribosome-studded peripheral sheets, and a polygonal network of smooth tubules extending throughout the cell. Though protein biosynthesis, transport, and quality control in the ER have been extensively studied, mechanisms underlying the heterogeneous architecture of the ER have been clarified more recently. These insights have increased interest in ER morphology changes associated with the development of neuronal axons and dendrites as well as their integration with pre- and postsynaptic signaling pathways. A number of proteins involved in shaping and distributing the ER network are mutated in neurological disorders, particularly the hereditary spastic paraplegias, emphasizing the importance of proper ER morphology for the establishment and maintenance of highly-polarized neurons. PMID:20678923

  16. Gene therapy to target ER stress in brain diseases.

    PubMed

    Valenzuela, Vicente; Martínez, Gabriela; Duran-Aniotz, Claudia; Hetz, Claudio

    2016-10-01

    Gene therapy based on the use of Adeno-associated viruses (AAVs) is emerging as a safe and stable strategy to target molecular pathways involved in a variety of brain diseases. Endoplasmic reticulum (ER) stress is proposed as a transversal feature of most animal models and clinical samples from patients affected with neurodegenerative diseases. Manipulation of the unfolded protein response (UPR), a major homeostatic reaction under ER stress conditions, had proved beneficial in diverse models of neurodegeneration. Although increasing number of drugs are available to target ER stress, the use of small molecules to treat chronic brain diseases is challenging because of poor blood brain barrier permeability and undesirable side effects due to the role of the UPR in the physiology of peripheral organs. Gene therapy is currently considered a possible future alternative to circumvent these problems by the delivery of therapeutic agents to selective regions and cell types of the nervous system. Here we discuss current efforts to design gene therapy strategies to alleviate ER stress on a disease context. This article is part of a Special Issue entitled SI:ER stress. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Electrical properties of Er-doped CdS thin films

    NASA Astrophysics Data System (ADS)

    Dávila-Pintle, J. A.; Lozada-Morales, R.; Palomino-Merino, M. R.; Rivera-Márquez, J. A.; Portillo-Moreno, O.; Zelaya-Angel, O.

    2007-01-01

    Cadmium sulfide thin films were prepared by chemical bath on glass substrates at 80°C. CdS was Er-doped during the growth process by adding water-diluted Er(NO3)33•H2O to the CdS aqueous growing solution. The relative volume of the doping solution was varied in order to obtain different doping levels. The crystalline structure of CdS:Er films was cubic zinc blende for all the doped layers prepared. The (111) interplanar distance has an irregular variation with the Er doping level. Consequently, the band gap energy (Eg) firstly increases and afterward diminishes becoming, at last, approximately constant at around Eg=2.37eV. For higher doping levels, in the as-grown films, dark electrical conductivity (σ ) values reach 1.8×10-2Ω-1cm-1 at room temperature. The logarithm of σ vs 1/kT plot, where k is Boltzmann's constant and T the absolute temperature, indicates an effective doping of CdS as a result of the Er introduction into the lattice of the material. Hall effect measurements reveal a n-type doping with 2.8×1019cm-3 as maximum carrier density.

  18. Natural products targeting ER stress pathway for the treatment of cardiovascular diseases.

    PubMed

    Choy, Ker Woon; Murugan, Dharmani; Mustafa, Mohd Rais

    2018-04-21

    Endoplasmic reticulum (ER) is the main organelle for the synthesis, folding, and processing of secretory and transmembrane proteins. Pathological stimuli including hypoxia, ischaemia, inflammation and oxidative stress interrupt the homeostatic function of ER, leading to accumulation of unfolded proteins, a condition referred to as ER stress. ER stress triggers a complex signalling network referred as the unfolded protein response (UPR). Extensive studies have demonstrated that ER stress plays an important role in the pathogenesis of various cardiovascular diseases such as heart failure, ischemic heart disease and atherosclerosis. The importance of natural products in modern medicine are well recognized and continues to be of interests as a source of novel lead compounds. Natural products targeting components of UPR and reducing ER stress offers an innovative strategic approach to treat cardiovascular diseases. In this review, we discussed several therapeutic interventions using natural products with potential cardiovascular protective properties targeting ER stress signalling pathways. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. ER Consolidated Qtrly Rpt_April-June 2016_October 2016

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

    Cochran, John R.

    2016-10-01

    This Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) provides the status of ongoing corrective action activities being implemented by Sandia National Laboratories, New Mexico (SNL/NM) for the April, May, and June 2016 quarterly reporting period.

  20. Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis.

    PubMed

    Schneeberger, Marc; Gómez-Valadés, Alicia G; Altirriba, Jordi; Sebastián, David; Ramírez, Sara; Garcia, Ainhoa; Esteban, Yaiza; Drougard, Anne; Ferrés-Coy, Albert; Bortolozzi, Analía; Garcia-Roves, Pablo M; Jones, John G; Manadas, Bruno; Zorzano, Antonio; Gomis, Ramon; Claret, Marc

    2015-07-21

    Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Hereditary Spastic Paraplegia-Linked REEP1 Modulates ER-Mitochondria Contacts

    PubMed Central

    Lim, Youngshin; Cho, Il-Taeg; Schoel, Leah J.; Cho, Ginam; Golden, Jeffrey A.

    2015-01-01

    Objective Mutations in receptor expression enhancing protein 1 (REEP1) are associated with hereditary spastic paraplegias (HSPs). Although axonal degeneration is thought to be a predominant feature in HSP, the role of REEP1 mutations in degeneration is largely unknown. Previous studies have implicated a role for REEP1 in the ER, whereas others localized REEP1 with mitochondria. We sought to resolve the cellular localization of REEP1 and to further elucidate the pathobiology underlying REEP1 mutations in patients. Methods A combination of cellular imaging and biochemical approaches was used to refine the cellular localization of REEP1. Next, Reep1 mutations associated with HSP were functionally tested in neuritic growth and degeneration assays using mouse cortical culture. Finally, a novel assay was developed and used with wild type and mutant Reep1s to measure the interactions between the ER and mitochondria. Results We found that REEP1 is present at the ER-mitochondria interface, and it contains subdomains for mitochondrial as well as ER localization. Knockdown of Reep1 and the expression of pathological Reep1 mutations resulted in neuritic growth defects and degeneration. Finally, using our novel split-RLuc8 assay, we show REEP1 facilitates ER-mitochondria interactions, a function diminished by disease-associated mutations. Interpretation Our data potentially reconcile the current conflicting reports regarding REEP1 being either an ER or a mitochondrial protein. Furthermore, our results connect, for the first time, the disrupted ER-mitochondria interactions to a failure in maintaining health of long axons in HSPs. Finally, the split-RLuc8 assay offers a new tool to identify potential drugs for multiple neurodegenerative diseases with ER-mitochondria interaction defects. PMID:26201691

  2. CW YVO4:Er Laser with Resonant Pumping

    NASA Astrophysics Data System (ADS)

    Gorbachenya, K. N.; Kisel, V. E.; Yasukevich, A. S.; Matrosov, V. N.; Tolstik, N. A.; Kuleshov, N. V.

    2015-05-01

    The lasing characteristics of a YVO4:Er laser with resonant pumping in the 1.5-1.6 μm range are studied. Lasing is obtained at λ = 1603 nm with a differential efficiency of up to 61%. YVO4:Er crystals are found to offer promise for use in efficient resonantly (in-band) pumped lasers.

  3. Genome-wide association studies identify four ER negative–specific breast cancer risk loci

    PubMed Central

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

  4. ER/Golgi trafficking is facilitated by unbranched actin filaments containing Tpm4.2.

    PubMed

    Kee, Anthony J; Bryce, Nicole S; Yang, Lingyan; Polishchuk, Elena; Schevzov, Galina; Weigert, Roberto; Polishchuk, Roman; Gunning, Peter W; Hardeman, Edna C

    2017-10-01

    We have identified novel actin filaments defined by tropomyosin Tpm4.2 at the ER. EM analysis of mouse embryo fibroblasts (MEFs) isolated from mice expressing a mutant Tpm4.2 (Tpm4 Plt53/Plt53 ), incapable of incorporating into actin filaments, revealed swollen ER structures compared with wild-type (WT) MEFs (Tpm4 +/+ ). ER-to-Golgi, but not Golgi-to-ER trafficking was altered in the Tpm4 Plt53/Plt53 MEFs following the transfection of the temperature sensitive ER-associated ts045-VSVg construct. Exogenous Tpm4.2 was able to rescue the ER-to-Golgi trafficking defect in the Tpm4 Plt53/Plt53 cells. The treatment of WT MEFs with the myosin II inhibitor, blebbistatin, blocked the Tpm4.2-dependent ER-to-Golgi trafficking. The lack of an effect on ER-to-Golgi trafficking following treatment of MEFs with CK666 indicates that branched Arp2/3-containing actin filaments are not involved in anterograde vesicle trafficking. We propose that unbranched, Tpm4.2-containing filaments have an important role in maintaining ER/Golgi structure and that these structures, in conjunction with myosin II motors, mediate ER-to-Golgi trafficking. © 2017 Wiley Periodicals, Inc.

  5. Lockheed ER-2 #806 high altitude research aircraft in flight

    NASA Image and Video Library

    1998-11-17

    ER-2 tail number 806, is one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft are platforms for a variety of high-altitude science missions flown over various parts of the world. They are also used for earth science and atmospheric sensor research and development, satellite calibration and data validation. The ER-2s are capable of carrying a maximum payload of 2,600 pounds of experiments in a nose bay, the main equipment bay behind the cockpit, two wing-mounted superpods and small underbody and trailing edges. Most ER-2 missions last about six hours with ranges of about 2,200 nautical miles. The aircraft typically fly at altitudes above 65,000 feet. On November 19, 1998, the ER-2 set a world record for medium weight aircraft reaching an altitude of 68,700 feet. The aircraft is 63 feet long, with a wingspan of 104 feet. The top of the vertical tail is 16 feet above ground when the aircraft is on the bicycle-type landing gear. Cruising speeds are 410 knots, or 467 miles per hour, at altitude. A single General Electric F-118 turbofan engine rated at 17,000 pounds thrust powers the ER-2.

  6. Lockheed ER-2 #809 high altitude research aircraft in flight

    NASA Image and Video Library

    2001-08-01

    ER-2 tail number 809, is one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft are platforms for a variety of high-altitude science missions flown over various parts of the world. They are also used for earth science and atmospheric sensor research and development, satellite calibration and data validation. The ER-2s are capable of carrying a maximum payload of 2,600 pounds of experiments in a nose bay, the main equipment bay behind the cockpit, two wing-mounted superpods and small underbody and trailing edges. Most ER-2 missions last about six hours with ranges of about 2,200 nautical miles. The aircraft typically fly at altitudes above 65,000 feet. On November 19, 1998, the ER-2 set a world record for medium weight aircraft reaching an altitude of 68,700 feet. The aircraft is 63 feet long, with a wingspan of 104 feet. The top of the vertical tail is 16 feet above ground when the aircraft is on the bicycle-type landing gear. Cruising speeds are 410 knots, or 467 miles per hour, at altitude. A single General Electric F118 turbofan engine rated at 17,000 pounds thrust powers the ER-2.

  7. Lockheed ER-2 #806 high altitude research aircraft during landing

    NASA Image and Video Library

    1998-12-18

    ER-2 tail number 806, is one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft are platforms for a variety of high-altitude science missions flown over various parts of the world. They are also used for earth science and atmospheric sensor research and development, satellite calibration and data validation. The ER-2s are capable of carrying a maximum payload of 2,600 pounds of experiments in a nose bay, the main equipment bay behind the cockpit, two wing-mounted superpods and small underbody and trailing edges. Most ER-2 missions last about six hours with ranges of about 2,200 nautical miles. The aircraft typically fly at altitudes above 65,000 feet. On November 19, 1998, the ER-2 set a world record for medium weight aircraft reaching an altitude of 68,700 feet. The aircraft is 63 feet long, with a wingspan of 104 feet. The top of the vertical tail is 16 feet above ground when the aircraft is on the bicycle-type landing gear. Cruising speeds are 410 knots, or 467 miles per hour, at altitude. A single General Electric F-118 turbofan engine rated at 17,000 pounds thrust powers the ER-2.

  8. TaER Expression Is Associated with Transpiration Efficiency Traits and Yield in Bread Wheat

    PubMed Central

    Zheng, Jiacheng; Yang, Zhiyuan; Madgwick, Pippa J.; Carmo-Silva, Elizabete; Parry, Martin A. J.; Hu, Yin-Gang

    2015-01-01

    ERECTA encodes a receptor-like kinase and is proposed as a candidate for determining transpiration efficiency of plants. Two genes homologous to ERECTA in Arabidopsis were identified on chromosomes 6 (TaER2) and 7 (TaER1) of bread wheat (Triticum aestivum L.), with copies of each gene on the A, B and D genomes of wheat. Similar expression patterns were observed for TaER1 and TaER2 with relatively higher expression of TaER1 in flag leaves of wheat at heading (Z55) and grain-filling (Z73) stages. Significant variations were found in the expression levels of both TaER1 and TaER2 in the flag leaves at both growth stages among 48 diverse bread wheat varieties. Based on the expression of TaER1 and TaER2, the 48 wheat varieties could be classified into three groups having high (5 varieties), medium (27 varieties) and low (16 varieties) levels of TaER expression. Significant differences were also observed between the three groups varying for TaER expression for several transpiration efficiency (TE)- related traits, including stomatal density (SD), transpiration rate, photosynthetic rate (A), instant water use efficiency (WUEi) and carbon isotope discrimination (CID), and yield traits of biomass production plant-1 (BYPP) and grain yield plant-1 (GYPP). Correlation analysis revealed that the expression of TaER1 and TaER2 at the two growth stages was significantly and negatively associated with SD (P<0.01), transpiration rate (P<0.05) and CID (P<0.01), while significantly and positively correlated with flag leaf area (FLA, P<0.01), A (P<0.05), WUEi (P<0.05), BYPP (P<0.01) and GYPP (P<0.01), with stronger correlations for TaER1 than TaER2 and at grain-filling stage than at heading stage. These combined results suggested that TaER involved in development of transpiration efficiency -related traits and yield in bread wheat, implying a function for TaER in regulating leaf development of bread wheat and contributing to expression of these traits. Moreover, the results indicate

  9. TaER Expression Is Associated with Transpiration Efficiency Traits and Yield in Bread Wheat.

    PubMed

    Zheng, Jiacheng; Yang, Zhiyuan; Madgwick, Pippa J; Carmo-Silva, Elizabete; Parry, Martin A J; Hu, Yin-Gang

    2015-01-01

    ERECTA encodes a receptor-like kinase and is proposed as a candidate for determining transpiration efficiency of plants. Two genes homologous to ERECTA in Arabidopsis were identified on chromosomes 6 (TaER2) and 7 (TaER1) of bread wheat (Triticum aestivum L.), with copies of each gene on the A, B and D genomes of wheat. Similar expression patterns were observed for TaER1 and TaER2 with relatively higher expression of TaER1 in flag leaves of wheat at heading (Z55) and grain-filling (Z73) stages. Significant variations were found in the expression levels of both TaER1 and TaER2 in the flag leaves at both growth stages among 48 diverse bread wheat varieties. Based on the expression of TaER1 and TaER2, the 48 wheat varieties could be classified into three groups having high (5 varieties), medium (27 varieties) and low (16 varieties) levels of TaER expression. Significant differences were also observed between the three groups varying for TaER expression for several transpiration efficiency (TE)- related traits, including stomatal density (SD), transpiration rate, photosynthetic rate (A), instant water use efficiency (WUEi) and carbon isotope discrimination (CID), and yield traits of biomass production plant-1 (BYPP) and grain yield plant-1 (GYPP). Correlation analysis revealed that the expression of TaER1 and TaER2 at the two growth stages was significantly and negatively associated with SD (P<0.01), transpiration rate (P<0.05) and CID (P<0.01), while significantly and positively correlated with flag leaf area (FLA, P<0.01), A (P<0.05), WUEi (P<0.05), BYPP (P<0.01) and GYPP (P<0.01), with stronger correlations for TaER1 than TaER2 and at grain-filling stage than at heading stage. These combined results suggested that TaER involved in development of transpiration efficiency -related traits and yield in bread wheat, implying a function for TaER in regulating leaf development of bread wheat and contributing to expression of these traits. Moreover, the results indicate

  10. Interfacial structure of two-dimensional epitaxial Er silicide on Si(111)

    NASA Astrophysics Data System (ADS)

    Tuilier, M. H.; Wetzel, P.; Pirri, C.; Bolmont, D.; Gewinner, G.

    1994-07-01

    Auger-electron diffraction (AED) and surface-extended x-ray-absorption fine structure (SEXAFS) have been used to obtain a complete description of the atomic structure of a two-dimensional epitaxial Er silicide layer on Si(111). AED reveals that a monolayer of Er is located underneath a buckled Si double layer. The relevant Er-Si interlayer spacings are determined by means of single scattering cluster simulations and a R-factor analysis to be 1.92+/-0.05 Å to the first and 2.70+/-0.05 Å to the second Si top layer. Er near-neighbor bond lengths and coordination numbers are obtained independently from polarization-dependent SEXAFS. The SEXAFS data, when combined with the Si top-layer geometry inferred from AED, permit the determination of the atomic positions at the silicide/Si(111) interface. The Er is found to reside in relaxed T4 sites of Si(111) with a single Er-Si distance of 3.09+/-0.04 Å to the first- and second-layer Si atoms of the substrate.

  11. IRE1: ER stress sensor and cell fate executor

    PubMed Central

    Chen, Yani; Brandizzi, Federica

    2013-01-01

    Cells operate a signaling network termed unfolded protein response (UPR) to monitor protein-folding capacity in the endoplasmic reticulum (ER). IRE1 is an ER transmembrane sensor that activates UPR to maintain ER and cellular function. While mammalian IRE1 promotes cell survive, it can initiate apoptosis via decay of anti-apoptotic microRNAs. Convergent and divergent IRE1 characteristics between plants and animals underscore its significance in cellular homeostasis. This review provides an updated scenario of IRE1 signaling model, discusses emerging IRE1 sensing mechanisms, compares IRE1 features among species, and outlines exciting future directions in UPR research. PMID:23880584

  12. Overexpressed cyclophilin B suppresses apoptosis associated with ROS and Ca2+ homeostasis after ER stress.

    PubMed

    Kim, Jinhwan; Choi, Tae Gyu; Ding, Yan; Kim, Yeonghwan; Ha, Kwon Soo; Lee, Kyung Ho; Kang, Insug; Ha, Joohun; Kaufman, Randal J; Lee, Jinhwa; Choe, Wonchae; Kim, Sung Soo

    2008-11-01

    Prolonged accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in ER stress-mediated apoptosis. Cyclophilins are protein chaperones that accelerate the rate of protein folding through their peptidyl-prolyl cis-trans isomerase (PPIase) activity. In this study, we demonstrated that ER stress activates the expression of the ER-localized cyclophilin B (CypB) gene through a novel ER stress response element. Overexpression of wild-type CypB attenuated ER stress-induced cell death, whereas overexpression of an isomerase activity-defective mutant, CypB/R62A, not only increased Ca(2+) leakage from the ER and ROS generation, but also decreased mitochondrial membrane potential, resulting in cell death following exposure to ER stress-inducing agents. siRNA-mediated inhibition of CypB expression rendered cells more vulnerable to ER stress. Finally, CypB interacted with the ER stress-related chaperones, Bip and Grp94. Taken together, we concluded that CypB performs a crucial function in protecting cells against ER stress via its PPIase activity.

  13. Er:YAG laser dentistry in special needs patients

    PubMed Central

    Fornaini, Carlo; Clini, Fabio; Fontana, Matteo; Cella, Luigi; Oppici, Aldo

    2015-01-01

    Objective: Between a quarter and a third of adults with intellectual disability is estimated to have dental anxiety. Unpleasant stimuli, such as the injection of local anaesthesia or the noise and vibration of rotary instruments, may provoke anxiety and subsequent low compliance until the opposition to the treatment. The use of Er:YAG laser in conservative dentistry had a great development in these last years thank to new devices and also to their advantages when compared to the conventional instruments. The aim of this clinical study was to show the advantages of the Er:YAG laser in the conservative treatment of Special Care patients. Methods: Four cases are here described to show the Er:YAG laser use in our Unit on special needs patients. Results and conclusions: Based on the experience gained on conservative laser-assisted treatments performed in a time of 5 years at our Dentistry, Special Needs and Maxillo-Facial Surgery Unit we may affirm that Er:YAG laser may be considered as a good way to improve the cooperation, to reduce anxiety related to rotating instruments and to reach better results with equal or shorter operating times. PMID:26557733

  14. Golgi-to-Endoplasmic Reticulum (ER) Retrograde Traffic in Yeast Requires Dsl1p, a Component of the ER Target Site that Interacts with a COPI Coat Subunit

    PubMed Central

    Reilly, Barbara A.; Kraynack, Bryan A.; VanRheenen, Susan M.; Waters, M. Gerard

    2001-01-01

    DSL1 was identified through its genetic interaction with SLY1, which encodes a t-SNARE-interacting protein that functions in endoplasmic reticulum (ER)-to-Golgi traffic. Conditional dsl1 mutants exhibit a block in ER-to-Golgi traffic at the restrictive temperature. Here, we show that dsl1 mutants are defective for retrograde Golgi-to-ER traffic, even under conditions where no anterograde transport block is evident. These results suggest that the primary function of Dsl1p may be in retrograde traffic, and that retrograde defects can lead to secondary defects in anterograde traffic. Dsl1p is an ER-localized peripheral membrane protein that can be extracted from the membrane in a multiprotein complex. Immunoisolation of the complex yielded Dsl1p and proteins of ∼80 and ∼55 kDa. The ∼80-kDa protein has been identified as Tip20p, a protein that others have shown to exist in a tight complex with Sec20p, which is ∼50 kDa. Both Sec20p and Tip20p function in retrograde Golgi-to-ER traffic, are ER-localized, and bind to the ER t-SNARE Ufe1p. These findings suggest that an ER-localized complex of Dsl1p, Sec20p, and Tip20p functions in retrograde traffic, perhaps upstream of a Sly1p/Ufe1p complex. Last, we show that Dsl1p interacts with the δ-subunit of the retrograde COPI coat, Ret2p, and discuss possible roles for this interaction. PMID:11739780

  15. Mitochondrial pleomorphy in plant cells is driven by contiguous ER dynamics

    PubMed Central

    Jaipargas, Erica-Ashley; Barton, Kiah A.; Mathur, Neeta; Mathur, Jaideep

    2015-01-01

    Mitochondria are pleomorphic, double membrane-bound organelles involved in cellular energetics in all eukaryotes. Mitochondria in animal and yeast cells are typically tubular-reticulate structures and several micro-meters long but in green plants they are predominantly observed as 0.2–1.5 μm punctae. While fission and fusion, through the coordinated activity of several conserved proteins, shapes mitochondria, the endoplasmic reticulum (ER) has recently been identified as an additional player in this process in yeast and mammalian cells. The mitochondria-ER relationship in plant cells remains largely uncharacterized. Here, through live-imaging of the entire range of mitochondria pleomorphy we uncover the underlying basis for the predominantly punctate mitochondrial form in plants. We demonstrate that mitochondrial morphology changes in response to light and cytosolic sugar levels in an ER mediated manner. Whereas, large ER polygons and low dynamics under dark conditions favor mitochondrial fusion and elongation, small ER polygons result in increased fission and predominantly small mitochondria. Hypoxia also reduces ER dynamics and increases mitochondrial fusion to produce giant mitochondria. By observing elongated mitochondria in normal plants and fission-impaired Arabidopsis nmt1-2 and drp3a mutants we also establish that thin extensions called matrixules and a beads-on-a-string mitochondrial phenotype are direct consequences of mitochondria-ER interactions. PMID:26442089

  16. ER sheet persistence is coupled to myosin 1c-regulated dynamic actin filament arrays.

    PubMed

    Joensuu, Merja; Belevich, Ilya; Rämö, Olli; Nevzorov, Ilya; Vihinen, Helena; Puhka, Maija; Witkos, Tomasz M; Lowe, Martin; Vartiainen, Maria K; Jokitalo, Eija

    2014-04-01

    The endoplasmic reticulum (ER) comprises a dynamic three-dimensional (3D) network with diverse structural and functional domains. Proper ER operation requires an intricate balance within and between dynamics, morphology, and functions, but how these processes are coupled in cells has been unclear. Using live-cell imaging and 3D electron microscopy, we identify a specific subset of actin filaments localizing to polygons defined by ER sheets and tubules and describe a role for these actin arrays in ER sheet persistence and, thereby, in maintenance of the characteristic network architecture by showing that actin depolymerization leads to increased sheet fluctuation and transformations and results in small and less abundant sheet remnants and a defective ER network distribution. Furthermore, we identify myosin 1c localizing to the ER-associated actin filament arrays and reveal a novel role for myosin 1c in regulating these actin structures, as myosin 1c manipulations lead to loss of the actin filaments and to similar ER phenotype as observed after actin depolymerization. We propose that ER-associated actin filaments have a role in ER sheet persistence regulation and thus support the maintenance of sheets as a stationary subdomain of the dynamic ER network.

  17. Surfing the Sec61 channel: bidirectional protein translocation across the ER membrane.

    PubMed

    Römisch, K

    1999-12-01

    Misfolded secretory and transmembrane proteins are retained in the endoplasmic reticulum (ER) and subsequently degraded. Degradation is primarily mediated by cytosolic proteasomes and thus requires retrograde transport out of the ER back to the cytosol. The available evidence suggests that the protein-conducting channel formed by the Sec61 complex is responsible for both forward and retrograde transport of proteins across the ER membrane. For transmembrane proteins, retrograde transport can be viewed as a reversal of integration of membrane proteins into the ER membrane. Retrograde transport of soluble proteins through the Sec61 channel after signal-peptide cleavage, however, must be mechanistically distinct from signal-peptide-mediated import into the ER through the same channel.

  18. Neurotrophins regulate ApoER2 proteolysis through activation of the Trk signaling pathway.

    PubMed

    Larios, Jorge A; Jausoro, Ignacio; Benitez, Maria-Luisa; Bronfman, Francisca C; Marzolo, Maria-Paz

    2014-09-19

    ApoER2 and the neurotrophin receptors Trk and p75(NTR) are expressed in the CNS and regulate key functional aspects of neurons, including development, survival, and neuronal function. It is known that both ApoER2 and p75(NTR) are processed by metalloproteinases, followed by regulated intramembrane proteolysis. TrkA activation by nerve growth factor (NGF) increases the proteolytic processing of p75(NTR) mediated by ADAM17. Reelin induces the sheeding of ApoER2 ectodomain depending on metalloproteinase activity. However, it is not known if there is a common regulation mechanism for processing these receptors. We found that TrkA activation by NGF in PC12 cells induced ApoER2 processing, which was dependent on TrkA activation and metalloproteinases. NGF-induced ApoER2 proteolysis was independent of mitogen activated protein kinase activity and of phosphatidylinositol-3 kinase activity. In contrast, the basal proteolysis of ApoER2 increased when both kinases were pharmacologically inhibited. The ApoER2 ligand reelin regulated the proteolytic processing of its own receptor but not of p75(NTR). Finally, in primary cortical neurons, which express both ApoER2 and TrkB, we found that the proteolysis of ApoER2 was also regulated by brain-derived growth factor (BDNF). Our results highlight a novel relationship between neurotrophins and the reelin-ApoER2 system, suggesting that these two pathways might be linked to regulate brain development, neuronal survival, and some pathological conditions.

  19. Pilot James Barrilleaux with ER-2 aircraft on ramp

    NASA Technical Reports Server (NTRS)

    1998-01-01

    James Barrilleaux is the assistant chief pilot for ER-2s in the Flight Crew Branch of NASA's Dryden Flight Research Center, Edwards, California. The ER-2s--civilian variants of the military U-2S reconnaissance aircraft--are part of NASA's Airborne Science program. The ER-2s can carry airborne scientific payloads of up to 2,600 pounds to altitudes of about 70,000 feet to investigate such matters as earth resources, celestial phenomena, atmospheric chemistry and dynamics, and oceanic processes. Barrilleaux has held his current position since February 1998. Barrilleaux joined NASA in 1986 as a U-2/ER-2 pilot with NASA's Airborne Science program at Ames Research Center, Moffett Field, California. He flew both the U-2C (until 1989) and the ER-2 on a wide variety of missions both domestic and international. Barrilleaux flew high-altitude operations over Antarctica in which scientific instruments aboard the ER-2 defined the cause of ozone depletion over the continent, known as the ozone hole. He has also flown the ER-2 over the North Pole. Barrilleaux served for 20 years in the U.S. Air Force before he joined NASA. He completed pilot training at Reese Air Force Base, Lubbock, Texas, in 1966. He flew 120 combat missions as a F-4 fighter pilot over Laos and North Vietnam in 1970 and 1971. He joined the U-2 program in 1974, becoming the commander of an overseas U-2 operation in 1982. In 1983, he became commander of the squadron responsible for training all U-2 pilots and SR-71 crews located at Beale Air Force Base, Marysville, California. He retired from the Air Force as a lieutenant colonel in 1986. On active duty, he flew the U-2, F-4 Phantom, the T-38, T-37, and the T-33. His decorations included two Distinguished Flying Crosses, 12 Air Medals, two Meritorious Service Medals, and other Air Force and South Vietnamese awards. Barrilleaux earned a bachelor of science degree in chemical engineering from Texas A&M University, College Station, in 1964 and a master of science

  20. Role of ER Export Signals in Controlling Surface Potassium Channel Numbers

    NASA Astrophysics Data System (ADS)

    Ma, Dzwokai; Zerangue, Noa; Lin, Yu-Fung; Collins, Anthony; Yu, Mei; Jan, Yuh Nung; Yeh Jan, Lily

    2001-01-01

    Little is known about the identity of endoplasmic reticulum (ER) export signals and how they are used to regulate the number of proteins on the cell surface. Here, we describe two ER export signals that profoundly altered the steady-state distribution of potassium channels and were required for channel localization to the plasma membrane. When transferred to other potassium channels or a G protein-coupled receptor, these ER export signals increased the number of functional proteins on the cell surface. Thus, ER export of membrane proteins is not necessarily limited by folding or assembly, but may be under the control of specific export signals.

  1. A family of membrane-shaping proteins at ER subdomains regulates pre-peroxisomal vesicle biogenesis.

    PubMed

    Joshi, Amit S; Huang, Xiaofang; Choudhary, Vineet; Levine, Tim P; Hu, Junjie; Prinz, William A

    2016-11-21

    Saccharomyces cerevisiae contains three conserved reticulon and reticulon-like proteins that help maintain ER structure by stabilizing high membrane curvature in ER tubules and the edges of ER sheets. A mutant lacking all three proteins has dramatically altered ER morphology. We found that ER shape is restored in this mutant when Pex30p or its homologue Pex31p is overexpressed. Pex30p can tubulate membranes both in cells and when reconstituted into proteoliposomes, indicating that Pex30p is a novel ER-shaping protein. In contrast to the reticulons, Pex30p is low abundance, and we found that it localizes to subdomains in the ER. We show that these ER subdomains are the sites where most preperoxisomal vesicles (PPVs) are generated. In addition, overproduction or deletion of Pex30p or Pex31p alters the size, shape, and number of PPVs. Our findings suggest that Pex30p and Pex31p help shape and generate regions of the ER where PPV biogenesis occurs.

  2. Targeting the hallmarks of cancer with therapy-induced endoplasmic reticulum (ER) stress

    PubMed Central

    Garg, Abhishek D; Maes, Hannelore; van Vliet, Alexander R; Agostinis, Patrizia

    2015-01-01

    The endoplasmic reticulum (ER) is at the center of a number of vital cellular processes such as cell growth, death, and differentiation, crosstalk with immune or stromal cells, and maintenance of proteostasis or homeostasis, and ER functions have implications for various pathologies including cancer. Recently, a number of major hallmarks of cancer have been delineated that are expected to facilitate the development of anticancer therapies. However, therapeutic induction of ER stress as a strategy to broadly target multiple hallmarks of cancer has been seldom discussed despite the fact that several primary or secondary ER stress-inducing therapies have been found to exhibit positive clinical activity in cancer patients. In the present review we provide a brief historical overview of the major discoveries and milestones in the field of ER stress biology with important implications for anticancer therapy. Furthermore, we comprehensively discuss possible strategies enabling the targeting of multiple hallmarks of cancer with therapy-induced ER stress. PMID:27308392

  3. ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells.

    PubMed

    Arduino, Daniela M; Esteves, A Raquel; Domingues, A Filipa; Pereira, Claudia M F; Cardoso, Sandra M; Oliveira, Catarina R

    2009-11-30

    Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

  4. ER sheet persistence is coupled to myosin 1c–regulated dynamic actin filament arrays

    PubMed Central

    Joensuu, Merja; Belevich, Ilya; Rämö, Olli; Nevzorov, Ilya; Vihinen, Helena; Puhka, Maija; Witkos, Tomasz M.; Lowe, Martin; Vartiainen, Maria K.; Jokitalo, Eija

    2014-01-01

    The endoplasmic reticulum (ER) comprises a dynamic three-dimensional (3D) network with diverse structural and functional domains. Proper ER operation requires an intricate balance within and between dynamics, morphology, and functions, but how these processes are coupled in cells has been unclear. Using live-cell imaging and 3D electron microscopy, we identify a specific subset of actin filaments localizing to polygons defined by ER sheets and tubules and describe a role for these actin arrays in ER sheet persistence and, thereby, in maintenance of the characteristic network architecture by showing that actin depolymerization leads to increased sheet fluctuation and transformations and results in small and less abundant sheet remnants and a defective ER network distribution. Furthermore, we identify myosin 1c localizing to the ER-associated actin filament arrays and reveal a novel role for myosin 1c in regulating these actin structures, as myosin 1c manipulations lead to loss of the actin filaments and to similar ER phenotype as observed after actin depolymerization. We propose that ER-associated actin filaments have a role in ER sheet persistence regulation and thus support the maintenance of sheets as a stationary subdomain of the dynamic ER network. PMID:24523293

  5. ER phospholipid composition modulates lipogenesis during feeding and in obesity.

    PubMed

    Rong, Xin; Wang, Bo; Palladino, Elisa Nd; de Aguiar Vallim, Thomas Q; Ford, David A; Tontonoz, Peter

    2017-10-02

    Sterol regulatory element-binding protein 1c (SREBP-1c) is a central regulator of lipogenesis whose activity is controlled by proteolytic cleavage. The metabolic factors that affect its processing are incompletely understood. Here, we show that dynamic changes in the acyl chain composition of ER phospholipids affect SREBP-1c maturation in physiology and disease. The abundance of polyunsaturated phosphatidylcholine in liver ER is selectively increased in response to feeding and in the setting of obesity-linked insulin resistance. Exogenous delivery of polyunsaturated phosphatidylcholine to ER accelerated SREBP-1c processing through a mechanism that required an intact SREBP cleavage-activating protein (SCAP) pathway. Furthermore, induction of the phospholipid-remodeling enzyme LPCAT3 in response to liver X receptor (LXR) activation promoted SREBP-1c processing by driving the incorporation of polyunsaturated fatty acids into ER. Conversely, LPCAT3 deficiency increased membrane saturation, reduced nuclear SREBP-1c abundance, and blunted the lipogenic response to feeding, LXR agonist treatment, or obesity-linked insulin resistance. Desaturation of the ER membrane may serve as an auxiliary signal of the fed state that promotes lipid synthesis in response to nutrient availability.

  6. Excitation mechanisms of Er optical centers in GaN epilayers

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

    George, D. K.; Hawkins, M. D.; McLaren, M.

    2015-10-26

    We report direct evidence of two mechanisms responsible for the excitation of optically active Er{sup 3+} ions in GaN epilayers grown by metal-organic chemical vapor deposition. These mechanisms, resonant excitation via the higher-lying inner 4f shell transitions and band-to-band excitation of the semiconductor host, lead to narrow emission lines from isolated and the defect-related Er optical centers. However, these centers have different photoluminescence spectra, local defect environments, decay dynamics, and excitation cross sections. The photoluminescence at 1.54 μm from the isolated Er optical center which can be excited by either mechanism has the same decay dynamics, but possesses a much highermore » excitation cross-section under band-to-band excitation. In contrast, the photoluminescence at 1.54 μm from the defect-related Er optical center can only be observed through band-to-band excitation but has the largest excitation cross-section. These results explain the difficulty in achieving gain in Er doped GaN and indicate approaches for realization of optical amplification, and possibly lasing, at room temperature.« less

  7. The Grand Banks ERS-1 SAR wave spectra validation experiment

    NASA Technical Reports Server (NTRS)

    Vachon, P. W.; Dobson, F. W.; Smith, S. D.; Anderson, R. J.; Buckley, J. R.; Allingham, M.; Vandemark, D.; Walsh, E. J.; Khandekar, M.; Lalbeharry, R.

    1993-01-01

    As part of the ERS-1 validation program, the ERS-1 Synthetic Aperture Radar (SAR) wave spectra validation experiment was carried out over the Grand Banks of Newfoundland (Canada) in Nov. 1991. The principal objective of the experiment was to obtain complete sets of wind and wave data from a variety of calibrated instruments to validate SAR measurements of ocean wave spectra. The field program activities are described and the rather complex wind and wave conditions which were observed are summarized. Spectral comparisons with ERS-1 SAR image spectra are provided. The ERS-1 SAR is shown to have measured swell and range traveling wind seas, but did not measure azimuth traveling wind seas at any time during the experiment. Results of velocity bunching forward mapping and new measurements of the relationship between wind stress and sea state are also shown.

  8. Spectral properties of Er3+/Yb3+ codoped tungsten-tellurite glasses.

    PubMed

    Shen, Xiang; Nie, QiuHua; Xu, TieFeng; Gao, Yuan

    2005-07-01

    The spectral properties of Er3+/Yb3+ codoped tungsten-tellurite (WT) glasses have been investigated. The measured absorption spectra are analyzed by Judd-Ofelt theory. The compositional change of intensity parameter omega2 is attributed to the change in the covalency between the Er3+ and oxygen ions, the asymmetry in the local structures around the Er3+ ions can be neglected. The lifetimes of 4I(13/2) level of Er3+ in WT glasses are measured and comparable with other TeO2-based glasses. The stimulated emission cross-section is calculated based on McCumber theory. The fluorescence full width at half maximum (FWHM) and the emission cross-section (sigma(peak)) of the 4I(13/2) --> 4I(15/2) transition of Er3+ in different glass hosts have been compared. The suitability of such WT glasses as host materials for 1.5 microm broadband amplification is discussed.

  9. Single drug biomarker prediction for ER- breast cancer outcome from chemotherapy.

    PubMed

    Chen, Yong-Zi; Kim, Youngchul; Soliman, Hatem H; Ying, GuoGuang; Lee, Jae K

    2018-06-01

    ER-negative breast cancer includes most aggressive subtypes of breast cancer such as triple negative (TN) breast cancer. Excluded from hormonal and targeted therapies effectively used for other subtypes of breast cancer, standard chemotherapy is one of the primary treatment options for these patients. However, as ER- patients have shown highly heterogeneous responses to different chemotherapies, it has been difficult to select most beneficial chemotherapy treatments for them. In this study, we have simultaneously developed single drug biomarker models for four standard chemotherapy agents: paclitaxel (T), 5-fluorouracil (F), doxorubicin (A) and cyclophosphamide (C) to predict responses and survival of ER- breast cancer patients treated with combination chemotherapies. We then flexibly combined these individual drug biomarkers for predicting patient outcomes of two independent cohorts of ER- breast cancer patients who were treated with different drug combinations of neoadjuvant chemotherapy. These individual and combined drug biomarker models significantly predicted chemotherapy response for 197 ER- patients in the Hatzis cohort (AUC = 0.637, P  = 0.002) and 69 ER- patients in the Hess cohort (AUC = 0.635, P  = 0.056). The prediction was also significant for the TN subgroup of both cohorts (AUC = 0.60, 0.72, P  = 0.043, 0.009). In survival analysis, our predicted responder patients showed significantly improved survival with a >17 months longer median PFS than the predicted non-responder patients for both ER- and TN subgroups (log-rank test P -value = 0.018 and 0.044). This flexible prediction capability based on single drug biomarkers may allow us to even select new drug combinations most beneficial to individual patients with ER- breast cancer. © 2018 The authors.

  10. Innate Sensing of Influenza A Virus Hemagglutinin Glycoproteins by the Host Endoplasmic Reticulum (ER) Stress Pathway Triggers a Potent Antiviral Response via ER-Associated Protein Degradation.

    PubMed

    Frabutt, Dylan A; Wang, Bin; Riaz, Sana; Schwartz, Richard C; Zheng, Yong-Hui

    2018-01-01

    Innate immunity provides an immediate defense against infection after host cells sense danger signals from microbes. Endoplasmic reticulum (ER) stress arises from accumulation of misfolded/unfolded proteins when protein load overwhelms the ER folding capacity, which activates the unfolded protein response (UPR) to restore ER homeostasis. Here, we show that a mechanism for antiviral innate immunity is triggered after the ER stress pathway senses viral glycoproteins. When hemagglutinin (HA) glycoproteins from influenza A virus (IAV) are expressed in cells, ER stress is induced, resulting in rapid HA degradation via proteasomes. The ER-associated protein degradation (ERAD) pathway, an important UPR function for destruction of aberrant proteins, mediates HA degradation. Three class I α-mannosidases were identified to play a critical role in the degradation process, including EDEM1, EDEM2, and ERManI. HA degradation requires either ERManI enzymatic activity or EDEM1/EDEM2 enzymatic activity when ERManI is not expressed, indicating that demannosylation is a critical step for HA degradation. Silencing of EDEM1, EDEM2, and ERManI strongly increases HA expression and promotes IAV replication. Thus, the ER stress pathway senses influenza HA as "nonself" or misfolded protein and sorts HA to ERAD for degradation, resulting in inhibition of IAV replication. IMPORTANCE Viral nucleic acids are recognized as important inducers of innate antiviral immune responses that are sensed by multiple classes of sensors, but other inducers and sensors of viral innate immunity need to be identified and characterized. Here, we used IAV to investigate how host innate immunity is activated. We found that IAV HA glycoproteins induce ER stress, resulting in HA degradation via ERAD and consequent inhibition of IAV replication. In addition, we have identified three class I α-mannosidases, EDEM1, EDEM2, and ERManI, which play a critical role in initiating HA degradation. Knockdown of these proteins

  11. Development of a stable ERroGFP variant suitable for monitoring redox dynamics in the ER.

    PubMed

    Hoseki, Jun; Oishi, Asami; Fujimura, Takaaki; Sakai, Yasuyoshi

    2016-01-01

    The endoplasmic reticulum (ER) is an essential organelle for cellular metabolic homeostasis including folding and maturation of secretory and membrane proteins. Disruption of ER proteostasis has been implicated in the pathogenesis of various diseases such as diabetes and neurodegenerative diseases. The ER redox state, which is an oxidative environment suitable for disulfide-bond formation, is essential for ER protein quality control. Hence, detection of the ER redox state, especially in living cells, is essential to understand the mechanism by which the redox state of the ER is maintained. However, methods to detect the redox state of the ER have not been well-established because of inefficient folding and stability of roGFP variants with oxidative redox potential like roGFP-iL. Here we have improved the folding efficiency of ER-targeted roGFP-iL (ERroGFP-iL) in cells by introducing superfolder GFP (sfGFP) mutations. Four specific amino acid substitutions (S30R, Y39N, T105N and I171V) greatly improved folding efficiency in Escherichia coli and in the ER of HeLa cells, as well as the thermostability of the purified proteins. Introduction of these mutations also enhanced the dynamic range for redox change both in vitro and in the ER of living cells. ER-targeted roGFP-S4 (ERroGFP-S4) possessing these four mutations could detect physiological redox changes within the ER. ERroGFP-S4 is therefore a novel probe suitable for monitoring redox change in the ER. ERroGFP-S4 can be applied to detect aberrant ER redox states associated with various pathological conditions and to identify the mechanisms used to maintain the redox state of the ER. © 2016 The Author(s).

  12. IRE1: ER stress sensor and cell fate executor.

    PubMed

    Chen, Yani; Brandizzi, Federica

    2013-11-01

    Cells operate a signaling network termed the unfolded protein response (UPR) to monitor protein-folding capacity in the endoplasmic reticulum (ER). Inositol-requiring enzyme 1 (IRE1) is an ER transmembrane sensor that activates the UPR to maintain the ER and cellular function. Although mammalian IRE1 promotes cell survival, it can initiate apoptosis via decay of antiapoptotic miRNAs. Convergent and divergent IRE1 characteristics between plants and animals underscore its significance in cellular homeostasis. This review provides an updated scenario of the IRE1 signaling model, discusses emerging IRE1 sensing mechanisms, compares IRE1 features among species, and outlines exciting future directions in UPR research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Prevention and Treatment of ER-Negative Breast Cancer

    DTIC Science & Technology

    2005-10-01

    human breast epithelial cell lines that express several levels of P13 kinase and AKT activity. These lines will be characterized with respect to...cancer. (4)Defined a putative role for psoriasin in breast tumor progression. (5) Progress in the analysis of the role of NFkappaB signaling in ER...press.. 9 PREVENTION AND TREATMENT OF ER-NEGATIVE BREAST CANCERPrincipal Investigator: Brown, Mvles A. 4) IGF-1 Receptor and the Akt protein kinase Akt

  14. Lockheed ER-2C #809 high altitude research aircraft in flight

    NASA Image and Video Library

    1998-04-29

    ER-2C tail number 809, was one of two Airborne Science ER-2Cs used as science platforms by Dryden. The aircraft were platforms for a variety of high-altitude science missions flown over various parts of the world. They were also used for earth science and atmospheric sensor research and development, satellite calibration and data validation. The ER-2Cs were capable of carrying a maximum payload of 2,600 pounds of experiments in a nose bay, the main equipment bay behind the cockpit, two wing-mounted superpods and small underbody and trailing edges. Most ER-2C missions lasted about six hours with ranges of about 2,200 nautical miles. The aircraft typically flew at altitudes above 65,000 feet. On November 19, 1998, the ER-2C set a world record for medium weight aircraft reaching an altitude of 68,700 feet. The aircraft was 63 feet long, with a wingspan of 104 feet. The top of the vertical tail was 16 feet above ground when the aircraft was on the bicycle-type landing gear. Cruising speeds were 410 knots, or 467 miles per hour, at altitude. A single General Electric F-118 turbofan engine rated at 17,000 pounds thrust powers the ER-2C.

  15. Present statue of Japanese ERS-1 Project

    NASA Technical Reports Server (NTRS)

    Ishiwada, Yasufumi; Nemoto, Yoshiaki

    1986-01-01

    Earth Resources Satellite 1 (ERS-1) will be launched in the FY 1990 with the H-1 rocket from Tanegashima Space Center. ERS-1 will seek to firmly establish remote sensing technologies from space by using synthetic aperture radar and optical sensors, as well as primarily exploring for non-renewable resources and also monitoring for land use, agriculture, forestry, fishery, conservation of environment, prevention of disasters, and surveillance of coastal regions. ERS-1 is a joint project in which the main responsibility for the development of the mission equipment is assumed by the Agency of Industrial Science and Technology, MITI, and the Technology Research Association of Resources Remote Sensing System, while that for the satellite itself and launching rocket is assumed by the Science and Technology Agency (STA) and the National Space Development Agency (NASDA). In relation to this project, users have maintained a close working relationship with the manufacturers after submitting their requirements in 1984 on the specifications of the mission equipments. This missions parameters are outlined.

  16. Apoptosis Induced by the UV Filter Benzophenone-3 in Mouse Neuronal Cells Is Mediated via Attenuation of Erα/Pparγ and Stimulation of Erβ/Gpr30 Signaling.

    PubMed

    Wnuk, A; Rzemieniec, J; Lasoń, W; Krzeptowski, W; Kajta, M

    2018-03-01

    Although benzophenone-3 (BP-3) has frequently been reported to play a role in endocrine disruption, there is insufficient data regarding the impact of BP-3 on the nervous system, including its possible adverse effects on the developing brain. Our study demonstrated that BP-3 caused neurotoxicity and activated apoptosis via an intrinsic pathway involving the loss of mitochondrial membrane potential and the activation of caspases-9 and -3 and kinases p38/MAPK and Gsk3β. These biochemical alterations were accompanied by ROS production, increased apoptotic body formation and impaired cell survival, and by an upregulation of the genes involved in apoptosis. The BP-3-induced effects were tissue-specific and age-dependent with the most pronounced effects observed in neocortical cells at 7 days in vitro. BP-3 changed the messenger RNA (mRNA) expression levels of Erα, Erβ, Gpr30, and Pparγ in a time-dependent manner. At 3 h of exposure, BP-3 downregulated estrogen receptor mRNAs but upregulated Pparγ mRNA. After prolonged exposures, BP-3 downregulated the receptor mRNAs except for Erβ mRNA that was upregulated. The BP-3-induced patterns of mRNA expression measured at 6 and 24 h of exposure reflected alterations in the protein levels of the receptors and paralleled their immunofluorescent labeling. Erα and Pparγ agonists diminished, but Erβ and Gpr30 agonists stimulated the BP-3-induced apoptotic and neurotoxic effects. Receptor antagonists caused the opposite effects, except for ICI 182,780. This is in line with a substantial reduction in the effects of BP-3 in cells with siRNA-silenced Erβ/Gpr30 and the maintenance of BP-3 effects in Erα- and Pparγ siRNA-transfected cells. We showed for the first time that BP-3-affected mRNA and protein expression levels of Erα, Erβ, Gpr30, and Pparγ, paralleled BP-3-induced apoptosis and neurotoxicity. Therefore, we suggest that BP-3-evoked apoptosis of neuronal cells is mediated via attenuation of Erα/Pparγ and

  17. Lockheed ER-2 high altitude research aircraft in flight

    NASA Image and Video Library

    1997-11-04

    ER-2 tail number 706, was one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft were platforms for a variety of high-altitude science missions flown over various parts of the world. They were also used for earth science and atmospheric sensor research and development, satellite calibration and data validation.

  18. Pilot James Barrilleaux with ER-2 aircraft on ramp

    NASA Image and Video Library

    1998-03-18

    James Barrilleaux is the assistant chief pilot for ER-2s in the Flight Crew Branch of NASA's Dryden Flight Research Center, Edwards, California. The ER-2s--civilian variants of the military U-2S reconnaissance aircraft--are part of NASA's Airborne Science program. The ER-2s can carry airborne scientific payloads of up to 2,600 pounds to altitudes of about 70,000 feet to investigate such matters as earth resources, celestial phenomena, atmospheric chemistry and dynamics, and oceanic processes. Barrilleaux has held his current position since February 1998. Barrilleaux joined NASA in 1986 as a U-2/ER-2 pilot with NASA's Airborne Science program at Ames Research Center, Moffett Field, California. He flew both the U-2C (until 1989) and the ER-2 on a wide variety of missions both domestic and international. Barrilleaux flew high-altitude operations over Antarctica in which scientific instruments aboard the ER-2 defined the cause of ozone depletion over the continent, known as the ozone hole. He has also flown the ER-2 over the North Pole. Barrilleaux served for 20 years in the U.S. Air Force before he joined NASA. He completed pilot training at Reese Air Force Base, Lubbock, Texas, in 1966. He flew 120 combat missions as a F-4 fighter pilot over Laos and North Vietnam in 1970 and 1971. He joined the U-2 program in 1974, becoming the commander of an overseas U-2 operation in 1982. In 1983, he became commander of the squadron responsible for training all U-2 pilots and SR-71 crews located at Beale Air Force Base, Marysville, California. He retired from the Air Force as a lieutenant colonel in 1986. On active duty, he flew the U-2, F-4 Phantom, the T-38, T-37, and the T-33. His decorations included two Distinguished Flying Crosses, 12 Air Medals, two Meritorious Service Medals, and other Air Force and South Vietnamese awards. Barrilleaux earned a bachelor of science degree in chemical engineering from Texas A&M University, College Station, in 1964 and a master of science

  19. 4-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress.

    PubMed

    Zheng, Peili; Lin, Yu; Wang, Feifei; Luo, Renfei; Zhang, Tiezheng; Hu, Shan; Feng, Pinning; Liang, Xinling; Li, Chunling; Wang, Weidong

    2016-10-01

    Endoplasmic reticulum (ER) stress has been implicated in some types of glomerular and tubular disorders. The objectives of this study were to elucidate the role of ER stress in lithium-induced nephrogenic diabetes insipidus (NDI) and to investigate whether attenuation of ER stress by 4-phenylbutyric acid (4-PBA) improves urinary concentrating defect in lithium-treated rats. Wistar rats received lithium (40 mmol/kg food), 4-PBA (320 mg/kg body wt by gavage every day), or no treatment (control) for 2 wk, and they were dehydrated for 24 h before euthanasia. Lithium treatment resulted in increased urine output and decreased urinary osmolality, which was significantly improved by 4-PBA. 4-PBA also prevented reduced protein expression of aquaporin-2 (AQP2), pS256-AQP2, and pS261-AQP2 in the inner medulla of kidneys from lithium-treated rats after 24-h dehydration. Lithium treatment resulted in increased expression of ER stress markers in the inner medulla, which was associated with dilated cisternae and expansion of ER in the inner medullary collecting duct (IMCD) principal cells. Confocal immunofluorescence studies showed colocalization of a molecular chaperone, binding IgG protein (BiP), with AQP2 in principal cells. Immunohistochemistry demonstrated increased intracellular expression of BiP and decreased AQP2 expression in IMCD principal cells of kidneys from lithium-treated rats. 4-PBA attenuated expression of ER stress markers and recovered ER morphology. In IMCD suspensions isolated from lithium-treated rats, 4-PBA incubation was also associated with increased AQP2 expression and ameliorated ER stress. In conclusion, in experimental lithium-induced NDI, 4-PBA improved the urinary concentrating defect and increased AQP2 expression, likely via attenuating ER stress in IMCD principal cells. Copyright © 2016 the American Physiological Society.

  20. Phosphatidylserine synthesis at membrane contact sites promotes its transport out of the ER.

    PubMed

    Kannan, Muthukumar; Lahiri, Sujoy; Liu, Li-Ka; Choudhary, Vineet; Prinz, William A

    2017-03-01

    Close contacts between organelles, often called membrane contact sites (MCSs), are regions where lipids are exchanged between organelles. Here, we identify a novel mechanism by which cells promote phospholipid exchange at MCSs. Previous studies have shown that phosphatidylserine (PS) synthase activity is highly enriched in portions of the endoplasmic reticulum (ER) in contact with mitochondria. The objective of this study was to determine whether this enrichment promotes PS transport out of the ER. We found that PS transport to mitochondria was more efficient when PS synthase was fused to a protein in the ER at ER-mitochondria contacts than when it was fused to a protein in all portions of the ER. Inefficient PS transport to mitochondria was corrected by increasing tethering between these organelles. PS transport to endosomes was similarly enhanced by PS production in regions of the ER in contact with endosomes. Together, these findings indicate that PS production at MCSs promotes PS transport out of the ER and suggest that phospholipid production at MCSs may be a general mechanism of channeling lipids to specific cellular compartments.

  1. Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation

    PubMed Central

    Plate, Lars; Cooley, Christina B; Chen, John J; Paxman, Ryan J; Gallagher, Ciara M; Madoux, Franck; Genereux, Joseph C; Dobbs, Wesley; Garza, Dan; Spicer, Timothy P; Scampavia, Louis; Brown, Steven J; Rosen, Hugh; Powers, Evan T; Walter, Peter; Hodder, Peter; Wiseman, R Luke; Kelly, Jeffery W

    2016-01-01

    Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases. DOI: http://dx.doi.org/10.7554/eLife.15550.001 PMID:27435961

  2. Optical activity and defect/dopant evolution in ZnO implanted with Er

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

    Azarov, Alexander; Galeckas, Augustinas; Kuznetsov, Andrej

    2015-09-28

    The effects of annealing on the optical properties and defect/dopant evolution in wurtzite (0001) ZnO single crystals implanted with Er ions are studied using a combination of Rutherford backscattering/channeling spectrometry and photoluminescence measurements. The results suggest a lattice recovery behavior dependent on ion dose and involving formation/evolution of an anomalous multipeak defect distribution, thermal stability of optically active Er complexes, and Er outdiffusion. An intermediate defect band occurring between the surface and ion-induced defects in the bulk is stable up to 900 °C and has a photoluminescence signature around 420 nm well corresponding to Zn interstitials. The optical activity of the Ermore » atoms reaches a maximum after annealing at 700 °C but is not directly associated to the ideal Zn site configuration, since the Er substitutional fraction is maximal already in the as-implanted state. In its turn, annealing at temperatures above 700 °C leads to dissociation of the optically active Er complexes with subsequent outdiffusion of Er accompanied by the efficient lattice recovery.« less

  3. IMG ER: a system for microbial genome annotation expert review and curation.

    PubMed

    Markowitz, Victor M; Mavromatis, Konstantinos; Ivanova, Natalia N; Chen, I-Min A; Chu, Ken; Kyrpides, Nikos C

    2009-09-01

    A rapidly increasing number of microbial genomes are sequenced by organizations worldwide and are eventually included into various public genome data resources. The quality of the annotations depends largely on the original dataset providers, with erroneous or incomplete annotations often carried over into the public resources and difficult to correct. We have developed an Expert Review (ER) version of the Integrated Microbial Genomes (IMG) system, with the goal of supporting systematic and efficient revision of microbial genome annotations. IMG ER provides tools for the review and curation of annotations of both new and publicly available microbial genomes within IMG's rich integrated genome framework. New genome datasets are included into IMG ER prior to their public release either with their native annotations or with annotations generated by IMG ER's annotation pipeline. IMG ER tools allow addressing annotation problems detected with IMG's comparative analysis tools, such as genes missed by gene prediction pipelines or genes without an associated function. Over the past year, IMG ER was used for improving the annotations of about 150 microbial genomes.

  4. Generation of ER{alpha}-floxed and knockout mice using the Cre/LoxP system

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

    Antonson, P., E-mail: per.antonson@ki.se; Omoto, Y.; Humire, P.

    2012-08-10

    Highlights: Black-Right-Pointing-Pointer ER{alpha} floxed and knockout mice were generated. Black-Right-Pointing-Pointer Disruption of the ER{alpha} gene results in sterility in both male and female mice. Black-Right-Pointing-Pointer ER{alpha}{sup -/-} mice have ovaries with hemorrhagic follicles and hypoplastic uterus. Black-Right-Pointing-Pointer Female ER{alpha}{sup -/-} mice develop obesity. -- Abstract: Estrogen receptor alpha (ER{alpha}) is a nuclear receptor that regulates a range of physiological processes in response to estrogens. In order to study its biological role, we generated a floxed ER{alpha} mouse line that can be used to knock out ER{alpha} in selected tissues by using the Cre/LoxP system. In this study, we established amore » new ER{alpha} knockout mouse line by crossing the floxed ER{alpha} mice with Cre deleter mice. Here we show that genetic disruption of the ER{alpha} gene in all tissues results in sterility in both male and female mice. Histological examination of uterus and ovaries revealed a dramatically atrophic uterus and hemorrhagic cysts in the ovary. These results suggest that infertility in female mice is the result of functional defects of the reproductive tract. Moreover, female knockout mice are hyperglycemic, develop obesity and at the age of 4 months the body weight of these mice was more than 20% higher compared to wild type littermates and this difference increased over time. Our results demonstrate that ER{alpha} is necessary for reproductive tract development and has important functions as a regulator of metabolism in females.« less

  5. Gabapentin Extended-Release - Depomed: Gabapentin ER, Gabapentin Gastric Retention, Gabapentin GR.

    PubMed

    2007-01-01

    Depomed is developing an extended-release (ER) oral formulation of gabapentin, a GABA receptor agonist commonly used for the treatment of epilepsy and seizures, neuropathic pain and hot flushes. Gabapentin ER is based on the company's proprietary AcuForm drug delivery technology, which is part of the Gastric Retention (GR) family of technologies; this offers improved drug absorption and bioavailability compared with the existing immediate-release formulation of gabapentin (Neurontin), making gabapentin ER suitable for twice-daily dosing. The product is in clinical development for the treatment of postherpetic neuralgia and diabetic neuropathies in the US. Additionally, Depomed has commenced a phase II trial of gabapentin ER in postmenopausal patients with hot flushes. Depomed's AcuForm platform is based on polymer technology that provides targeted drug delivery for a variety of compounds. Following ingestion, AcuForm tablets swell and are retained for 6-8 hours in the stomach, enabling controlled and prolonged release of gabapentin to the upper intestinal tract; this extends the time of drug delivery to the small intestine for complete and safe elimination via the lower intestinal track. Gabapentin ER is available for licensing. Depomed acquired exclusive development and commercialisation rights to gabapentin ER in September 2003 via its subsidiary, Depomed Development Ltd (DDL). Depomed is not required to pay upfront license fees, but will make royalty and milestone payments to DDL upon successful commercialisation of gabapentin ER. Gabapentin ER was originally developed by DDL, a joint venture between Depomed and Elan established in January 2000 to design products using the GR family of technologies. However, in efforts to restructure joint venture relationships, Elan withdrew from operational involvement of DDL in September 2003, and Depomed has gained full ownership of DDL. Depomed sublicensed exclusive rights to a US patent (held by the University of Rochester

  6. The effects of energy transfer on the Er3+ 1.54 μm luminescence in nanostructured Y2O3 thin films with heterogeneously distributed Yb3+ and Er3+ codopants

    NASA Astrophysics Data System (ADS)

    Hoang, J.; Schwartz, Robert N.; Wang, Kang L.; Chang, J. P.

    2012-09-01

    We report the effects of heterogeneous Yb3+ and Er3+ codoping in Y2O3 thin films on the 1535 nm luminescence. Yb3+:Er3+:Y2O3 thin films were deposited using sequential radical enhanced atomic layer deposition. The Yb3+ energy transfer was investigated for indirect and direct excitation of the Yb 2F7/2 state using 488 nm and 976 nm sources, respectively, and the trends were described in terms of Forster and Dexter's resonant energy transfer theory and a macroscopic rate equation formalism. The addition of 11 at. % Yb resulted in an increase in the effective Er3+ photoluminescence (PL) yield at 1535 nm by a factor of 14 and 42 under 488 nm and 976 nm excitations, respectively. As the Er2O3 local thickness was increased to greater than 1.1 Å, PL quenching occurred due to strong local Er3+ ↔ Er3+ excitation migration leading to impurity quenching centers. In contrast, an increase in the local Yb2O3 thickness generally resulted in an increase in the effective Er3+ PL yield, except when the Er2O3 and Yb2O3 layers were separated by more than 2.3 Å or were adjacent, where weak Yb3+ ↔ Er3+ coupling or strong Yb3+ ↔ Yb3+ interlayer migration occurred, respectively. Finally, it is suggested that enhanced luminescence at steady state was observed under 488 nm excitation as a result of Er3+ → Yb3+ energy back transfer coupled with strong Yb3+ ↔ Yb3+ energy migration.

  7. Effects of Screening and Systemic Adjuvant Therapy on ER-Specific US Breast Cancer Mortality

    PubMed Central

    Munoz, Diego; Near, Aimee M.; van Ravesteyn, Nicolien T.; Lee, Sandra J.; Schechter, Clyde B.; Alagoz, Oguzhan; Berry, Donald A.; Burnside, Elizabeth S.; Chang, Yaojen; Chisholm, Gary; de Koning, Harry J.; Ali Ergun, Mehmet; Heijnsdijk, Eveline A. M.; Huang, Hui; Stout, Natasha K.; Sprague, Brian L.; Trentham-Dietz, Amy; Mandelblatt, Jeanne S.

    2014-01-01

    Background Molecular characterization of breast cancer allows subtype-directed interventions. Estrogen receptor (ER) is the longest-established molecular marker. Methods We used six established population models with ER-specific input parameters on age-specific incidence, disease natural history, mammography characteristics, and treatment effects to quantify the impact of screening and adjuvant therapy on age-adjusted US breast cancer mortality by ER status from 1975 to 2000. Outcomes included stage-shifts and absolute and relative reductions in mortality; sensitivity analyses evaluated the impact of varying screening frequency or accuracy. Results In the year 2000, actual screening and adjuvant treatment reduced breast cancer mortality by a median of 17 per 100000 women (model range = 13–21) and 5 per 100000 women (model range = 3–6) for ER-positive and ER-negative cases, respectively, relative to no screening and no adjuvant treatment. For ER-positive cases, adjuvant treatment made a higher relative contribution to breast cancer mortality reduction than screening, whereas for ER-negative cases the relative contributions were similar for screening and adjuvant treatment. ER-negative cases were less likely to be screen-detected than ER-positive cases (35.1% vs 51.2%), but when screen-detected yielded a greater survival gain (five-year breast cancer survival = 35.6% vs 30.7%). Screening biennially would have captured a lower proportion of mortality reduction than annual screening for ER-negative vs ER-positive cases (model range = 80.2%–87.8% vs 85.7%–96.5%). Conclusion As advances in risk assessment facilitate identification of women with increased risk of ER-negative breast cancer, additional mortality reductions could be realized through more frequent targeted screening, provided these benefits are balanced against screening harms. PMID:25255803

  8. ApoER2 and VLDLR in the developing human telencephalon.

    PubMed

    Cheng, Lin; Tian, Zhiliang; Sun, Ruizhen; Wang, Zhendong; Shen, Jingling; Shan, Zhiyan; Jin, Lianhong; Lei, Lei

    2011-07-01

    The Reelin-Dab1 signaling pathway plays a crucial role in regulating the migration and position of cortical neurons during the development of the cerebral cortex. Mutation in Reelin may result in severe developmental disorders such as autosomal recessive lissencephaly. Apolipoprotein E receptor type-2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) are canonical receptors of Reelin, through which extracellular Reelin activates the intracellular adapter, Disabled1(Dab1), and subsequently interacts with other molecules. Although it is widely accepted that ApoER2 and VLDLR are indispensable components of the Reelin signaling pathway, little is known of their expression pattern in the laminated developing human brain. Here, we collected 18 cases of human fetal brains of 6-18 gestational weeks (GW) old and examined the expression of ApoER2 and VLDLR in the their telencephalon using immunocytochemical staining. We found that both receptors were absent in the preplate (PP) and the earliest stage of the cortical plate (CP). In later stages of CP development, ApoER2 was expressed earlier than VLDLR in the migrating neurons. Thus, the Reelin-Dab1 signaling pathway may not be involved in the formation of the preplate and deep layers of the CP. Instead, the pathway may act on neurons that are destined to form the more superficial layers of the CP. In addition, the pathway required ApoER2 only rather than both ApoER2 and VLDLR at the initiation of activity. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  9. Fractionated Er:YAG laser versus fully ablative Er:YAG laser for scar revision: Results of a split scar, double blinded, prospective trial.

    PubMed

    Tidwell, W James; Owen, Cindy E; Kulp-Shorten, Carol; Maity, Abhishek; McCall, Michael; Brown, Timothy S

    2016-11-01

    Ablative laser resurfacing is a common treatment for post-surgical scars. Fractional ablative laser resurfacing has been an emerging treatment option that is replacing fully ablative lasers in many applications. Data comparing fractionated and fully ablative lasers in treating post-operative scars are lacking. Twenty patients were enrolled in a split scar study following excisions from dermatologic surgery. Wounds had to be older than 8 weeks but less than 1 year. The scars were randomly divided into two halves. One half of the scar was treated with fully ablative erbium-doped yttrium aluminum garnet (Er:YAG) and the other was treated with fractionated Er:YAG. The scars were treated at monthly intervals for 3 months, then followed up at months 1 and 2 after the last treatment. POSAS was used to evaluate the scars by a panel of dermatologists blinded to the lasers in conjunction with the patients, who were also blinded. Physicians and patients both observed a superior outcome of 32.5% (P = 0.019) and 58.1% (P = 0.001), respectively, using the POSAS. There was no trend in difference in pain reported by the patient between the two lasers. Patients overwhelmingly preferred the fractionated Er:YAG laser (94%) to the fully ablative laser when asked at the end of the study. Although this study is limited by a short follow-up period, it shows a statistically significant superior outcome in fractionated Er:YAG over fully ablative Er:YAG for scar revision. It also adds quantitative values to the assessment of scar appearance when treated with fractionated lasers compared to fully ablative lasers. It was also found that the fractionated Er:YAG had increased patient satisfaction, but there was no difference in reported pain scores. These data are useful when counseling patients undergoing laser surgery. Lasers Surg. Med. 48:837-843, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. ADMiER-ing thin but complex fluids

    NASA Astrophysics Data System (ADS)

    McDonnell, Amarin G.; Bhattacharjee, Pradipto K.; Pan, Sharadwata; Hill, David; Danquah, Michael K.; Friend, James R.; Yeo, Leslie Y.; Prabhakar, Ranganathan

    2011-12-01

    The Acoustics Driven Microfluidic Extensional Rheometer (ADMiER) utilises micro litre volumes of liquid, with viscosities as low as that of water, to create valid and observable extensional flows, liquid bridges that pinch off due to capillary forces in this case. ADMiER allows the study fluids that have been beyond conventional methods and also study more subtle fluid properties. We can observe polymeric fluids with solvent viscosities far below those previously testable, accentuating elastic effects. Also, it has enabled the testing of aqueous solutions of living motile particles, which significantly change fluid properties, opening up the potential for diagnostic applications.

  11. Next generation Er:YAG fractional ablative laser

    NASA Astrophysics Data System (ADS)

    Heinrich, A.; Vizhanyo, A.; Krammer, P.; Summer, S.; Gross, S.; Bragagna, T.; Böhler, C.

    2011-03-01

    Pantec Biosolutions AG presents a portable fractional ablative laser system based on a miniaturized diode pumped Er:YAG laser. The system can operate at repetition rates up to 500 Hz and has an incorporated beam deflection unit. It is smaller, lighter and cost efficient compared to systems based on lamp pumped Er:YAG lasers and incorporates a skin layer detection to guarantee precise control of the microporation process. The pulse parameters enable a variety of applications in dermatology and in general medicine, as demonstrated by first results on transdermal drug delivery of FSH (follicle stimulating hormone).

  12. Involvement of estrogen receptor variant ER-alpha36, not GPR30, in nongenomic estrogen signaling.

    PubMed

    Kang, Lianguo; Zhang, Xintian; Xie, Yan; Tu, Yaping; Wang, Dong; Liu, Zhenming; Wang, Zhao-Yi

    2010-04-01

    Accumulating evidence suggested that an orphan G protein-coupled receptor (GPR)30, mediates nongenomic responses to estrogen. The present study was performed to investigate the molecular mechanisms underlying GPR30 function. We found that knockdown of GPR30 expression in breast cancer SK-BR-3 cells down-regulated the expression levels of estrogen receptor (ER)-alpha36, a variant of ER-alpha. Introduction of a GPR30 expression vector into GPR30 nonexpressing cells induced endogenous ER-alpha36 expression, and cotransfection assay demonstrated that GPR30 activated the promoter activity of ER-alpha36 via an activator protein 1 binding site. Both 17beta-estradiol (E2) and G1, a compound reported to be a selective GPR30 agonist, increased the phosphorylation levels of the MAPK/ERK1/2 in SK-BR-3 cells, which could be blocked by an anti-ER-alpha36-specific antibody against its ligand-binding domain. G1 induced activities mediated by ER-alpha36, such as transcription activation activity of a VP16-ER-alpha36 fusion protein and activation of the MAPK/ERK1/2 in ER-alpha36-expressing cells. ER-alpha36-expressing cells, but not the nonexpressing cells, displayed high-affinity, specific E2 and G1 binding, and E2- and G1-induced intracellular Ca(2+) mobilization only in ER-alpha36 expressing cells. Taken together, our results demonstrated that previously reported activities of GPR30 in response to estrogen were through its ability to induce ER-alpha36 expression. The selective G protein-coupled receptor (GPR)30 agonist G1 actually interacts with ER-alpha36. Thus, the ER-alpha variant ER-alpha36, not GPR30, is involved in nongenomic estrogen signaling.

  13. Structural, optical and dielectric studies of Er substituted zinc ferrite nanospheres

    NASA Astrophysics Data System (ADS)

    Shoba, M.; Kaleemulla, S.

    2017-12-01

    The cationic distributions among tetrahedral and octahedral sites in spinel ferrites have a profound influence on their properties. Many studies were reported with various transition metal (TM) and rare earth (RE) cations distribution. We report the synthesis, structural, morphology, lattice vibrational, optical and dielectric properties of heavy RE cation (Er) substituted ZnFe2O4 as a function of different experimental parameters. The coprecipitated and calcined ZnFe2-xErxO4 (x = 0, 0.2, 0.4, 0.6 & 0.8) compounds crystallizes in cubic spinel structure and show narrow particle size distribution due to surfactant PEG. Particle size reduces (27-16 nm) with enhance of Er concentration (x = 0 to 0.8) in the compounds. The EDAX spectra of the samples incorporation Er3+ ions into the lattice and the cubic lattice parameter enhances with Er3+ concentration. The lattice vibrational spectra reveal that the particles surface were free from surfactant PEG. Optical excitation studies show that energy band gap (Eg) of compounds reduces (1.85-2.00 eV) with enhance of Er concentration. The temperature, as well as frequency dependent dielectric constant (εrʹ) of ZnFe2-xErxO4, shows enhanced εrʹ with Er concentration up to x = 0.4 and then reduces with further enhancing of Er concentration. The dielectric loss factor (εrʹʹ) show similar variation with Er concentration. Further, both εrʹ and εrʹʹ were reduced with enhancing of field frequency. In addition, both εrʹ and εrʹʹ were enhanced with temperature and showed exponential change at low frequencies and high temperature and is attributed magnetic transition at around 525 K. The interface polarization mechanism is the predominant one in the present samples. The ac impedance spectra show two semicircles and each semicircle results from dielectric relaxation due to either particle (grain) or particles interface (grain boundary) polarization. The ac impedance reduces with enhancing of temperature. From the above

  14. Coordination of Endoplasmic Reticulum (ER) Signaling During Maize Seed Development

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

    Boston, Rebecca S.

    2010-11-20

    Seed storage reserves represent one of the most important sources of renewable fixed carbon and nitrogen found in nature. Seeds are well-adapted for diverting metabolic resources to synthesize storage proteins as well as enzymes and structural proteins needed for their transport and packaging into membrane bound storage protein bodies. Our underlying hypothesis is that the endoplasmic reticulum (ER) stress response provides the critical cellular control of metabolic flux required for optimal accumulation of storage reserves in seeds. This highly conserved response is a cellular mechanism to monitor the protein folding environment of the ER and restore homeostasis in the presencemore » of unfolded or misfolded proteins. In seeds, deposition of storage proteins in protein bodies is a highly specialized process that takes place even in the presence of mutant proteins that no longer fold and package properly. The capacity of the ER to deposit these aberrant proteins in protein bodies during a period that extends several weeks provides an excellent model for deconvoluting the ER stress response of plants. We have focused in this project on the means by which the ER senses and responds to functional perturbations and the underlying intracellular communication that occurs among biosynthetic, trafficking and degradative pathways for proteins during seed development.« less

  15. The ER-mitochondria interface: the social network of cell death.

    PubMed

    Grimm, Stefan

    2012-02-01

    When cellular organelles communicate bad things can happen. Recent findings uncovered that the junction between the endoplasmic reticulum (ER) and the mitochondria holds a crucial role for cell death regulation. Not only does this locale connect the two best-known organelles in apoptosis, numerous regulators of cell death are concentrated at this spot, providing a terrain for intense signal transfers. Ca2+ is the most prominent signalling factor that is released from the ER and, at high concentration, mediates the transfer of an apoptosis signal to mitochondria as the executioner organelle for cell death. An elaborate array of checks and balances is fine-tuning this process including Bcl-2 family members. Moreover, MAMs, "mitochondria-associated membranes", are distinct membrane sections at the ER that are in close contact with mitochondria and have been found to exchange lipids and lipid-derived molecules such as ceramide for apoptosis induction. Recent work has also described a reverse transfer of apoptosis signals, from mitochondria to the ER, via cytochrome c release and prolonged IP3R opening or through the mitochondrial fission factor Fis1 and Bap31 at the ER, which form the ARCosome, a novel caspase-activation complex. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma

    PubMed Central

    Zode, Gulab S.; Sharma, Arti B.; Lin, Xiaolei; Searby, Charles C.; Bugge, Kevin; Kim, Gun Hee; Clark, Abbot F.; Sheffield, Val C.

    2014-01-01

    Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open-angle glaucoma (POAG). The underlying pathology of glucocorticoid-induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid-induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0.1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid-induced glaucoma in human patients. Furthermore, dexamethasone-induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma. PMID:24691439

  17. Ga flux dependence of Er-doped GaN luminescent thin films

    NASA Astrophysics Data System (ADS)

    Lee, D. S.; Steckl, A. J.

    2002-02-01

    Er-doped GaN thin films have been grown on (111) Si substrates with various Ga fluxes in a radio frequency plasma molecular beam epitaxy system. Visible photoluminescence (PL) and electroluminescence (EL) emission at 537/558 nm and infrared (IR) PL emission at 1.5 μm from GaN:Er films exhibited strong dependence on the Ga flux. Both visible and IR PL and visible EL increase with the Ga flux up to the stoichiometric growth condition, as determined by growth rate saturation. Beyond this condition, all luminescence levels abruptly dropped to the detection limit with increasing Ga flux. The Er concentration, measured by secondary ion mass spectroscopy and Rutherford backscattering, decreases with increasing Ga flux under N-rich growth conditions and remains constant above the stoichiometric growth condition. X-ray diffraction indicated that the crystalline quality of the GaN:Er film was improved with increasing Ga flux up to stoichiometric growth condition and then saturated. Er ions in the films grown under N-rich conditions appear much more optically active than those in the films grown under Ga-rich conditions.

  18. Exocrine pancreas ER stress is differentially induced by different fatty acids.

    PubMed

    Danino, Hila; Ben-Dror, Karin; Birk, Ruth

    2015-12-10

    Exocrine pancreas acinar cells have a highly developed endoplasmic reticulum (ER), accommodating their high protein production rate. Overload of dietary fat (typical to obesity) is a recognized risk factor in pancreatitis and pancreatic cancer. Dietary fat, especially saturated fat, has been suggested by others and us to induce an acinar lipotoxic effect. The effect of different dietary fatty acids on the ER stress response is unknown. We studied the effect of acute (24h) challenge with different fatty acids (saturated, mono and poly-unsaturated) at different concentrations (between 200 and 500µM, typical to normal and obese states, respectively), testing fat accumulation, ER stress indicators, X-box binding protein 1 (Xbp1) splicing and nuclear translocation, as well as unfolded protein response (UPR) transcripts and protein levels using exocrine pancreas acinar AR42J and primary cells. Acute exposure of AR42J cells to different fatty acids caused increased accumulation of triglycerides, dependent on the type of fat. Different FAs had different effects on ER stress: most notably, saturated palmitic acid significantly affected the UPR response, as demonstrated by altered Xbp1 splicing, elevation in transcript levels of UPR (Xbp, CHOP, Bip) and immune factors (Tnfα, Tgfβ), and enhanced Xbp1 protein levels and Xbp1 time-dependent nuclear translocation. Poly-unsaturated FAs caused milder elevation of ER stress markers, while mono-unsaturated oleic acid attenuated the ER stress response. Thus, various fatty acids differentially affect acinar cell fat accumulation and, apart from oleic acid, induce ER stress. The differential effect of the various fatty acids could have potential nutritional and therapeutic implications. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Carboxymethyl- and carboxyl-catechins from ripe Pu-er tea.

    PubMed

    Tian, Li-Wen; Tao, Mu-Ke; Xu, Min; Hu, Jing; Zhu, Hong-Tao; Xiong, Wen-Yong; Wang, Dong; Yang, Chong-Ren; Zhang, Ying-Jun

    2014-12-17

    Ripe Pu-er tea, a special microbial postfermented tea originated from Yunnan Province, China, since ancient times, is made from green Pu-er tea prepared from the leaves of Camellia sinensis var. assamica (Theaceae). Chemical investigation on thearubigin (n-BuOH-soluble) fraction of the commercial ripe Pu-er tea, led to the identification of four new flavan-3-ol derivatives, 8-carboxymethyl-(+)-catechin (1), 8-carboxymethyl-(+)-catechin methyl ester (2), 6-carboxymethyl-(+)-catechin (3), and 6-carboxyl-(-)-gallocatechin (4), together with 18 known compounds, including other three flavan-3-ol derivatives (5-7), 10 flavonoid glycosides (8-17), two hydrolyzable tannins (18 and 19), two quinic acid derivatives (20-21), and a purine alkaloid (22). Flavonoid glycosides 8-11 are reported from tea plants for the first time. The thearubigin fraction of ripe Pu-er tea was qualitatively analyzed by HPLC, and gallic acid was found to be the major component. Compounds 4, 6-17, 21 and 22 were tested for their acute activities on insulin sensitivity in differentiated 3T3-L1 adipocytes, but none of them showed significant bioactivity at a concentration of 10 μM.

  20. Structural and Functional Impacts of ER Coactivator Sequential Recruitment.

    PubMed

    Yi, Ping; Wang, Zhao; Feng, Qin; Chou, Chao-Kai; Pintilie, Grigore D; Shen, Hong; Foulds, Charles E; Fan, Guizhen; Serysheva, Irina; Ludtke, Steven J; Schmid, Michael F; Hung, Mien-Chie; Chiu, Wah; O'Malley, Bert W

    2017-09-07

    Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1. CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER. Combining cryo-electron microscopy (cryo-EM) structure analysis and biochemical approaches, we demonstrate that there is a close crosstalk between early- and late-recruited coactivators. The sequential recruitment of CARM1 not only adds a protein arginine methyltransferase activity to the ER-coactivator complex, it also alters the structural organization of the pre-existing ERE/ERα/SRC-3/p300 complex. It induces a p300 conformational change and significantly increases p300 HAT activity on histone H3K18 residues, which, in turn, promotes CARM1 methylation activity on H3R17 residues to enhance transcriptional activity. This study reveals a structural role for a coactivator sequential recruitment and biochemical process in ER-mediated transcription. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity.

    PubMed

    Henis-Korenblit, Sivan; Zhang, Peichuan; Hansen, Malene; McCormick, Mark; Lee, Seung-Jae; Cary, Michael; Kenyon, Cynthia

    2010-05-25

    When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

  2. Growth of semimetallic ErAs films epitaxially embedded in GaAs

    NASA Astrophysics Data System (ADS)

    Crook, Adam M.; Nair, Hari P.; Lee, Jong H.; Ferrer, Domingo A.; Akinwande, Deji; Bank, Seth R.

    2011-10-01

    We present models for the growth and electrical conductivity of ErAs films grown with the nanoparticle-seeded film growth technique. This growth mode overcomes the mismatch in rotational symmetry between the rocksalt ErAs crystal structure and the zincblende GaAs crystal structure. This results in films of ErAs grown through a thin film of GaAs that preserves the symmetry of the substrate. The conductivity of the films, as a function of film thickness, are investigated and a surface roughness model is used to explain observed trends. Transmission electron micrographs confirm the suppression of anti-phase domains. A simple diffusion model is developed to describe the diffusion and incorporation of surface erbium into subsurface ErAs layers and predict potential failure mechanisms of the growth method.

  3. On the accuracy of ERS-1 orbit predictions

    NASA Technical Reports Server (NTRS)

    Koenig, Rolf; Li, H.; Massmann, Franz-Heinrich; Raimondo, J. C.; Rajasenan, C.; Reigber, C.

    1993-01-01

    Since the launch of ERS-1, the D-PAF (German Processing and Archiving Facility) provides regularly orbit predictions for the worldwide SLR (Satellite Laser Ranging) tracking network. The weekly distributed orbital elements are so called tuned IRV's and tuned SAO-elements. The tuning procedure, designed to improve the accuracy of the recovery of the orbit at the stations, is discussed based on numerical results. This shows that tuning of elements is essential for ERS-1 with the currently applied tracking procedures. The orbital elements are updated by daily distributed time bias functions. The generation of the time bias function is explained. Problems and numerical results are presented. The time bias function increases the prediction accuracy considerably. Finally, the quality assessment of ERS-1 orbit predictions is described. The accuracy is compiled for about 250 days since launch. The average accuracy lies in the range of 50-100 ms and has considerably improved.

  4. Heat effect of pulsed Er:YAG laser radiation

    NASA Astrophysics Data System (ADS)

    Hibst, Raimund; Keller, Ulrich

    1990-06-01

    Pulsed Er:YAG laser radiation has been found to be effective for dental enamel and dentin removal. Damage to the surrounding hard tissue is little, but before testing the Er:YAG laser clinically for the preparation of cavities, possible effects on the soft tissue of the pulp must be known. In order to estimate pulp damage , temperature rise in dentin caused by the laser radiation was measured by a thermocouple. Additionally, temperature distributions were observed by means of a thermal imaging system. The heat effect of a single Er:YAG laser pulse is little and limited to the vicinity of the impact side. Because heat energy is added with each additional pulse , the temperature distribution depends not only on the radiant energy, but also on the number of pulses and the repetition rate. Both irradiation conditions can be found , making irreversible pulp damage either likely or unlikely. The experimental observations can be explained qualitatively by a simple model of the ablation process.

  5. Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading (TED)

    PubMed Central

    Samtleben, Samira; Jaepel, Juliane; Fecher, Caroline; Andreska, Thomas; Rehberg, Markus; Blum, Robert

    2013-01-01

    Visualization of calcium dynamics is important to understand the role of calcium in cell physiology. To examine calcium dynamics, synthetic fluorescent Ca2+ indictors have become popular. Here we demonstrate TED (= targeted-esterase induced dye loading), a method to improve the release of Ca2+ indicator dyes in the ER lumen of different cell types. To date, TED was used in cell lines, glial cells, and neurons in vitro. TED bases on efficient, recombinant targeting of a high carboxylesterase activity to the ER lumen using vector-constructs that express Carboxylesterases (CES). The latest TED vectors contain a core element of CES2 fused to a red fluorescent protein, thus enabling simultaneous two-color imaging. The dynamics of free calcium in the ER are imaged in one color, while the corresponding ER structure appears in red. At the beginning of the procedure, cells are transduced with a lentivirus. Subsequently, the infected cells are seeded on coverslips to finally enable live cell imaging. Then, living cells are incubated with the acetoxymethyl ester (AM-ester) form of low-affinity Ca2+ indicators, for instance Fluo5N-AM, Mag-Fluo4-AM, or Mag-Fura2-AM. The esterase activity in the ER cleaves off hydrophobic side chains from the AM form of the Ca2+ indicator and a hydrophilic fluorescent dye/Ca2+ complex is formed and trapped in the ER lumen. After dye loading, the cells are analyzed at an inverted confocal laser scanning microscope. Cells are continuously perfused with Ringer-like solutions and the ER calcium dynamics are directly visualized by time-lapse imaging. Calcium release from the ER is identified by a decrease in fluorescence intensity in regions of interest, whereas the refilling of the ER calcium store produces an increase in fluorescence intensity. Finally, the change in fluorescent intensity over time is determined by calculation of ΔF/F0. PMID:23685703

  6. Direct imaging of ER calcium with targeted-esterase induced dye loading (TED).

    PubMed

    Samtleben, Samira; Jaepel, Juliane; Fecher, Caroline; Andreska, Thomas; Rehberg, Markus; Blum, Robert

    2013-05-07

    Visualization of calcium dynamics is important to understand the role of calcium in cell physiology. To examine calcium dynamics, synthetic fluorescent Ca(2+) indictors have become popular. Here we demonstrate TED (= targeted-esterase induced dye loading), a method to improve the release of Ca(2+) indicator dyes in the ER lumen of different cell types. To date, TED was used in cell lines, glial cells, and neurons in vitro. TED bases on efficient, recombinant targeting of a high carboxylesterase activity to the ER lumen using vector-constructs that express Carboxylesterases (CES). The latest TED vectors contain a core element of CES2 fused to a red fluorescent protein, thus enabling simultaneous two-color imaging. The dynamics of free calcium in the ER are imaged in one color, while the corresponding ER structure appears in red. At the beginning of the procedure, cells are transduced with a lentivirus. Subsequently, the infected cells are seeded on coverslips to finally enable live cell imaging. Then, living cells are incubated with the acetoxymethyl ester (AM-ester) form of low-affinity Ca(2+) indicators, for instance Fluo5N-AM, Mag-Fluo4-AM, or Mag-Fura2-AM. The esterase activity in the ER cleaves off hydrophobic side chains from the AM form of the Ca(2+) indicator and a hydrophilic fluorescent dye/Ca(2+) complex is formed and trapped in the ER lumen. After dye loading, the cells are analyzed at an inverted confocal laser scanning microscope. Cells are continuously perfused with Ringer-like solutions and the ER calcium dynamics are directly visualized by time-lapse imaging. Calcium release from the ER is identified by a decrease in fluorescence intensity in regions of interest, whereas the refilling of the ER calcium store produces an increase in fluorescence intensity. Finally, the change in fluorescent intensity over time is determined by calculation of ΔF/F0.

  7. DoSSiER: Database of scientific simulation and experimental results

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

    Wenzel, Hans; Yarba, Julia; Genser, Krzystof

    The Geant4, GeantV and GENIE collaborations regularly perform validation and regression tests for simulation results. DoSSiER (Database of Scientific Simulation and Experimental Results) is being developed as a central repository to store the simulation results as well as the experimental data used for validation. DoSSiER can be easily accessed via a web application. In addition, a web service allows for programmatic access to the repository to extract records in json or xml exchange formats. In this paper, we describe the functionality and the current status of various components of DoSSiER as well as the technology choices we made.

  8. DoSSiER: Database of scientific simulation and experimental results

    DOE PAGES

    Wenzel, Hans; Yarba, Julia; Genser, Krzystof; ...

    2016-08-01

    The Geant4, GeantV and GENIE collaborations regularly perform validation and regression tests for simulation results. DoSSiER (Database of Scientific Simulation and Experimental Results) is being developed as a central repository to store the simulation results as well as the experimental data used for validation. DoSSiER can be easily accessed via a web application. In addition, a web service allows for programmatic access to the repository to extract records in json or xml exchange formats. In this paper, we describe the functionality and the current status of various components of DoSSiER as well as the technology choices we made.

  9. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival.

    PubMed

    Hayashi, Teruo; Su, Tsung-Ping

    2007-11-02

    Communication between the endoplasmic reticulum (ER) and mitochondrion is important for bioenergetics and cellular survival. The ER supplies Ca(2+) directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). We found here that the ER protein sigma-1 receptor (Sig-1R), which is implicated in neuroprotection, carcinogenesis, and neuroplasticity, is a Ca(2+)-sensitive and ligand-operated receptor chaperone at MAM. Normally, Sig-1Rs form a complex at MAM with another chaperone, BiP. Upon ER Ca(2+) depletion or via ligand stimulation, Sig-1Rs dissociate from BiP, leading to a prolonged Ca(2+) signaling into mitochondria via IP3Rs. Sig-1Rs can translocate under chronic ER stress. Increasing Sig-1Rs in cells counteracts ER stress response, whereas decreasing them enhances apoptosis. These results reveal that the orchestrated ER chaperone machinery at MAM, by sensing ER Ca(2+) concentrations, regulates ER-mitochondrial interorganellar Ca(2+) signaling and cell survival.

  10. ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer.

    PubMed

    Pinhel, Isabel; Hills, Margaret; Drury, Suzanne; Salter, Janine; Sumo, Georges; A'Hern, Roger; Bliss, Judith M; Sestak, Ivana; Cuzick, Jack; Barrett-Lee, Peter; Harris, Adrian; Dowsett, Mitch

    2012-03-14

    Estrogen receptor-α (ER) and human epidermal growth factor receptor 2 (HER2) positivity are inversely correlated by standard criteria. However, we investigated the quantitative relation between ER and HER2 expression at both RNA and protein levels in HER2+ve and HER2-ve breast carcinomas. ER and HER2 levels were assessed with immunohistochemistry (IHC) and (for HER2) fluorescent in situ hybridization (FISH) and by quantitative reverse transcription-polymerase chain reaction (q-RT-PCR) in formalin-fixed primary breast cancers from 448 patients in the National Cancer Research Institute (NCRI) Adjuvant Breast Cancer Trial (ABC) tamoxifen-only arm. Relations at the RNA level were assessed in 1,139 TransATAC tumors. ER and HER2 RNA levels were negatively correlated as expected in HER2+ve (IHC 3+ and/or FISH-amplified) tumors (r = -0.45; P = 0.0028). However, in HER2-ve tumors (ER+ve and ER-ve combined), a significant positive correlation was found (r = 0.43; P < 0.0001), HER2 RNA levels being 1.74-fold higher in ER+ve versus ER-ve tumors. This correlation was maintained in the ER+veHER2-ve subgroup (r = 0.24; P = 0.0023) and confirmed in this subgroup in 1,139 TransATAC tumours (r = 0.25; P < 0.0001). The positive relation extended to IHC-detected ER in ABC: mean ± 95% confidence interval (CI) H-scores were 90 ± 19 and 134 ± 19 for 0 and 1+ HER2 IHC categories, respectively (P = 0.0013). A trend toward lower relapse-free survival (RFS) was observed in patients with the lowest levels of ER and HER2 RNA levels within the ER+veHER2-ve subgroup both for ABC and TransATAC cohorts. ER and HER2 expression is positively correlated in HER2-ve tumors. The distinction between HER2+ve and HER2-ve is greater in ER-ve than in ER+ve tumors. These findings are important to consider in clinical trials of anti-HER2 and anti-endocrine therapy in HER2-ve disease. Clinical trial identifier: ISRCTN31514446.

  11. ER-2 High Altitude Solar Cell Calibration Flights

    NASA Technical Reports Server (NTRS)

    Piszczor, Michael F.

    2017-01-01

    ER-2 Capability: Flights can be conducted once every one to two days during a campaign. Flight season runs from April through September. Twelve 2x2cm cells can be flown per flight, or any other configuration that fits inside of the 14.2x14.2cm illuminated area. This capacity could be doubled if the second ER-2 pod is used. Data supplied includes Isc, Voc, IV curve, and cell temperature. Other optical or atmospheric sensors can be flown as able.

  12. 20 CFR 228.50 - Tier II annuity component widow(er), child, or parent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., or parent. 228.50 Section 228.50 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... annuity component widow(er), child, or parent. (a) General. The tier II annuity component is an additional amount payable to a widow(er), disabled widow(er), child, or parent, but not to a surviving divorced...

  13. ApoER2 Function in the Establishment and Maintenance of Retinal Synaptic Connectivity

    PubMed Central

    Trotter, Justin H.; Klein, Martin; Jinwal, Umesh K.; Abisambra, Jose F.; Dickey, Chad A.; Tharkur, Jeremy; Masiulis, Irene; Ding, Jindong; Locke, Kirstin G.; Rickman, Catherine Bowes; Birch, David G.; Weeber, Edwin J.; Herz, Joachim

    2011-01-01

    The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoprotein E (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and degeneration, respectively. Here we describe the function of ApoER2 in the developing and adult retina. ApoER2 expression was highest during postnatal inner retinal synaptic development and was considerably lower in the mature retina. Both during development and in the adult ApoER2 was expressed by A-II amacrine cells. ApoER2 knockout (KO) mice had rod bipolar morphogenic defects, altered A-II amacrine dendritic development, and impaired rod-driven retinal responses. The presence of an intact ApoER2 NPxY motif, necessary for binding disabled-1 (Dab1) and transducing the Reelin signal, was also necessary for development of the rod bipolar pathway while the alternatively-spliced exon19 was not. Mice deficient in another Reelin receptor, very low-density lipoprotein receptor (VLDLR), had normal rod bipolar morphology but altered A-II amacrine dendritic development. VLDLR KO mice also had reductions in oscillatory potentials and delayed synaptic response intervals. Interestingly, age-related reductions in rod and cone function were observed in both ApoER2 and VLDLR KOs. These results support a pivotal role for ApoER2 in the establishment and maintenance of normal retinal synaptic connectivity. PMID:21976526

  14. Novel Aspects of Degradation of T Cell Receptor Subunits from the Endoplasmic Reticulum (ER) in T Cells: Importance of Oligosaccharide Processing, Ubiquitination, and Proteasome-dependent Removal from ER Membranes

    PubMed Central

    Yang, Mei; Omura, Satoshi; Bonifacino, Juan S.; Weissman, Allan M.

    1998-01-01

    Expression of the T cell antigen receptor (TCR) on the surface of thymocytes and mature T cells is dependent on the assembly of receptor subunits into TCRs in the endoplasmic reticulum (ER) and their successful traversal of the secretory pathway to the plasma membrane. TCR subunits that fail to exit the ER for the Golgi complex are degraded by nonlysosomal processes that have been referred to as “ER degradation”. The molecular basis for the loss of the TCR CD3-δ and TCR-α subunits from the ER was investigated in lymphocytes. For CD3-δ, we describe a process leading to its degradation that includes trimming of mannose residues from asparagine-linked (N-linked) oligosaccharides, generation of ubiquitinated membrane-bound intermediates, and proteasome-dependent removal from the ER membrane. When either mannosidase activity or the catalytic activity of proteasomes was inhibited, loss of CD3-δ was markedly curtailed and CD3-δ remained membrane bound in a complex with CD3-ε. TCR-α was also found to be degraded in a proteasome-dependent manner with ubiquitinated intermediates. However, no evidence of a role for mannosidases was found for TCR-α, and significant retrograde movement through the ER membrane took place even when proteasome function was inhibited. These findings provide new insights into mechanisms employed to regulate levels of TCRs, and underscore that cells use multiple mechanisms to target proteins from the ER to the cytosol for degradation. PMID:9500786

  15. Optical properties of Er 3+/Yb 3+-codoped transparent PLZT ceramic

    NASA Astrophysics Data System (ADS)

    Zheng, Zhiqiang; Li, Xiaoyan; Liu, Jing; Feng, Zhuohong; Li, Baozeng; Yang, Jiwen; Li, Kewen; Jiang, Hua; Chen, Xuesheng; Xie, Jianping; Ming, Hai

    2008-01-01

    Optical absorption and emission spectra of Er 3+/Yb 3+ ions in PLZT (Pb 1-xLa xZr yTi 1-yO 3) ceramic have been studied. Based on the Judd-Ofelt (J-O) theory, the J-O intensity parameters were calculated to be Ω2=2.021×10 -20 cm 2, Ω4=0.423×10 -20 cm 2, Ω6=0.051×10 -20 cm 2 from the absorption spectrum of Er 3+/Yb 3+-codoped PLZT. The J-O intensity parameters have been used to calculate the radiative lifetimes and the branching ratios for some excited 4I 13/2, 4I 11/2, 4I 9/24F 9/2, and 4S 3/2 levels of Er 3+ ion. The stimulated emission cross-section (8.24×10 -21 cm 2) was evaluated for the 4I 13/2→ 4I 15/2 transition of Er 3+. The upconversion emissions at 538, 564, and 666 nm have been observed in Er 3+/Yb 3+-codoped PLZT by exciting at 980 nm, and their origins were identified and analyzed.

  16. Er-doped YVO4 amplifier diode pumped at 976 nm

    NASA Astrophysics Data System (ADS)

    Newburgh, G. A.; Dubinskii, Mark

    2016-05-01

    We report on the use of a 976 nm diode pumped Er:YVO4 slab for the amplification of 1603 nm laser radiation with a small signal gain of 2.1. To the best of our knowledge, this represents the first use of Er:YVO4 as a non-resonantly pumped amplifier.

  17. Hormonal Resistance And Metastasis ER-Coregulartor-Src Signaling Targeted Therapy

    DTIC Science & Technology

    2011-09-01

    with STAT3 and cross-talk between ER~ and STAT3 play an important role in leptin -in- duced STAT3 activation’’ The II.Kl axis is the major signaling...cancer. These patients could be treated with an aromatase inhibitor (Letrozole) that ablates peripheral estrogen synthesis and ER degraders /signaling

  18. 20 CFR 228.50 - Tier II annuity component widow(er), child, or parent.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... annuity component widow(er), child, or parent. (a) General. The tier II annuity component is an additional amount payable to a widow(er), disabled widow(er), child, or parent, but not to a surviving divorced... annuity component, the parent tier II annuity component is zero. (3) Child. The amount of each child's...

  19. 20 CFR 228.50 - Tier II annuity component widow(er), child, or parent.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... annuity component widow(er), child, or parent. (a) General. The tier II annuity component is an additional amount payable to a widow(er), disabled widow(er), child, or parent, but not to a surviving divorced... annuity component, the parent tier II annuity component is zero. (3) Child. The amount of each child's...

  20. 20 CFR 228.50 - Tier II annuity component widow(er), child, or parent.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... annuity component widow(er), child, or parent. (a) General. The tier II annuity component is an additional amount payable to a widow(er), disabled widow(er), child, or parent, but not to a surviving divorced... annuity component, the parent tier II annuity component is zero. (3) Child. The amount of each child's...

  1. 20 CFR 228.50 - Tier II annuity component widow(er), child, or parent.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... annuity component widow(er), child, or parent. (a) General. The tier II annuity component is an additional amount payable to a widow(er), disabled widow(er), child, or parent, but not to a surviving divorced... annuity component, the parent tier II annuity component is zero. (3) Child. The amount of each child's...

  2. Highly scalable, resonantly cladding-pumped, Er-doped fiber laser with record efficiency.

    PubMed

    Dubinskii, M; Zhang, J; Ter-Mikirtychev, V

    2009-05-15

    We report the performance of a resonantly cladding-pumped, Yb-free, Er-doped fiber laser. We believe this is the first reported resonantly cladding-pumped fiber-Bragg-grating-based, Er-doped, large-mode-area (LMA) fiber laser. The laser, pumped by fiber-coupled InGaAsP/InP laser diode modules at 1,532.5 nm, delivers approximately 48 W of cw output at 1,590 nm. It is believed to be the highest power ever reported from a Yb-free Er-doped LMA fiber. This fully integrated laser also has the optical-to-optical efficiency of approximately 57%, to the best of our knowledge, the highest efficiency reported for cladding-pumped unidirectionally emitting Er-doped laser.

  3. Antigen Retrieval to Improve the Immunocytochemistry Detection of Sigma-1 Receptors and ER Chaperones

    PubMed Central

    Hayashi, Teruo; Lewis, Abasha; Hayashi, Eri; Betenbaugh, Michael J.; Su, Tsung-Ping

    2011-01-01

    Molecular chaperones localized at the endoplasmic reticulum (ER) lumen constitutively or cellular stress-dependently associate with a variety of proteins to promote their proper folding or to inhibit protein misfolding. ER chaperones preferentially form large complexes with co-chaperones and/or misfolded proteins in a highly crowded cellular environment that often hampers their detection by immunocytochemistry (ICC). This study establishes an antigen retrieval (AR) protocol to improve the ICC detection of ER chaperones in cultured cells using widely available antibodies against synthetic peptides. Among ten different antigen retrieval/fixation conditions, only the AR with Tris-HCl (pH 9.5) containing 6 M urea (80 °C for 10 min) significantly improved the ICC detection of the novel ER chaperone sigma-1 receptor (Sig-1R) in Chinese hamster ovary cells. Extended fixation with 4% paraformaldehyde for 1 hr effectively preserved the morphology of the ER under the AR condition. This method greatly enhanced the signal-to-noise ratio in Sig-1R ICC, thus allowing for semi-quantitative detection of protein upregulation under ER stress. The AR similarly improved the ICC detection of a series of other major ER chaperones, including BiP/GRP78, GRP94, calnexin, calreticulin, ERp57, protein disulfide isomerase, and cyclophilin B. The improved ICC methodology using the urea AR at 80°C may improve ICC of ER molecules as well as visualization of ER structure and substructures. PMID:21573736

  4. ER stress response mechanisms in the pathogenic yeast Candida glabrata and their roles in virulence

    PubMed Central

    Miyazaki, Taiga; Kohno, Shigeru

    2014-01-01

    The maintenance of endoplasmic reticulum (ER) homeostasis is critical for numerous aspects of cell physiology. Eukaryotic cells respond to the accumulation of misfolded proteins in the ER (ER stress) by activating the unfolded protein response (UPR), an intracellular signaling pathway that adjusts the folding capacity of the ER. Recent studies of several pathogenic fungi have revealed that the UPR is important for antifungal resistance and virulence; therefore, the pathway has attracted much attention as a potential therapeutic target. While the UPR is highly conserved among eukaryotes, our group recently discovered that the pathogenic yeast Candida glabrata lacks the typical fungal UPR, but possesses alternative mechanisms to cope with ER stress. This review summarizes how C. glabrata responds to ER stress and discusses the impacts of ER quality control systems on antifungal resistance and virulence. PMID:24335436

  5. Irreversibility and critical current density of FeSr2ErCu2O6+y

    NASA Astrophysics Data System (ADS)

    Hata, Y.; Iida, I.; Mochiku, T.; Yasuoka, H.

    2018-03-01

    FeSr2ErCu2O6+y (ErFe1212) and non-superconducting FeSr2ErCu1.9Zn0.1O6+y were synthesized to study the property of the superconductivity and the irreversibility of ErFe1212. A large irreversibility in the temperature dependence of magnetization and a hysteresis in the magnetization curve were observed in ErFe1212. By comparison with non-superconducting FeSr2ErCu1.9Zn0.1O6+y, it was found that the most part of the hysteresis at high magnetic eld originates from the magnetism of Fe ion and some part of the hysteresis at low magnetic eld originates from the superconductivity. Using the magnetization curve of ErFe1212 and FeSr2ErCu1.9Zn0.1O6+y, the J c of ErFe1212 in individual grains at 10 K under 0.1 T was estimated by the Bean model and {J}\\text{c}\\text{intra} was 2.6 × 109 A/m2. The critical current density across inter-grain boundaries at 10 K estimated by V ‑ I measurement was {J}\\text{c}\\text{intra} = 5.7 × 104 A/m2. A large difference between {J}\\text{c}\\text{intra} and {J}\\text{c}\\text{intra} was observed in ErFe1212. {J}\\text{c}\\text{intra} and {J}\\text{c}\\text{intra} of ErFe1212 are 2.2 and 5.2 times larger than these of YFe1212, respectively.

  6. Analysis of the Glass-Forming Ability of Fe-Er Alloys, Based on Thermodynamic Modeling

    NASA Astrophysics Data System (ADS)

    Arutyunyan, N. A.; Zaitsev, A. I.; Dunaev, S. F.; Kalmykov, K. B.; El'nyakov, D. D.; Shaposhnikov, N. G.

    2018-05-01

    The Fe-Er phase diagram and thermodynamic properties of all its phases are assessed by means of self-consistent analysis. To refine the data on phase equilibria in the Fe-Er system, an investigation is performed in the 10-40 at % range of Er concentrations. The temperature-concentration dependences of the thermodynamic properties of a melt are presented using the model of ideal associated solutions. Thermodynamic parameters of each phase are obtained, and the calculated results are in agreement with available experimental data. The correlation between the thermodynamic properties of liquid Fe-Er alloys and their tendency toward amorphization are studied. It is shown that compositions of amorphous alloys prepared by melt quenching coincide with the ranges of concentration with the predominance of Fe3Er and FeEr2 associative groups that have large negative entropies of formation.

  7. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

    PubMed Central

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-01-01

    ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297

  8. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy.

    PubMed

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-08-02

    Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation.

  9. MappERS-C and MappERS-V. The crowd source for prevention and crisis support

    NASA Astrophysics Data System (ADS)

    Frigerio, Simone; Schenato, Luca; Bianchizza, Chiara; Del Bianco, Daniele

    2015-04-01

    The responsibilities within natural hazards at local/regional levels involve citizens and volunteers as first actors of civil protection and territorial management. The prevention implicates the capacities of professional operators and technical volunteers, but the priority implies now the involvement and awareness of the citizens over the territory they inhabit. The involvement of population creates context-specific strategies of territorial surveillance and management, skipping the limit to face risks only when they have to bear impacts on their lives. MAppERS (Mobile Application for Emergency Response and Support) is a EU project (funded under programme 2013-2015 Humanitarian Aid and Civil Protection, ECHO A5) which empowers "crowd-sourced mappers" through smart phone applications and sensors, with geo-tagged information, detailed gathered parameters, field-check survey in a contest of geospatial response. The process of development includes feedback from citizens, involving them in training courses on the monitoring as long term objective (raising public awareness and participation). The project deals with the development and testing of the smart phone applications (module MAppERS-V for volunteers, module MAppERS-C for citizens) according to Android SDK environment. A first research described a desk-based investigation on consequences of disasters impacts and costs of prevention strategies in pilot countries. Furthermore a review of state-of-the-art of database management systems (DBMS) in pilot countries and involvement of volunteers/citizens in data collection/monitoring collected basic info on data structure for the development. A desk-based research proposed communication methods/graphic solutions within mobile technologies for disaster management in pilot countries and available smartphone applications linked to centralized web/server database. A technical review is compulsory for a useful design-line for MappERS development, and it is linked with on

  10. Fracture Forces of Dentin after Surface Treatment with High Speed Drill Compared to Er:YAG and Er,Cr:YSGG Laser Irradiation

    PubMed Central

    Franzen, Rene; Kianimanesh, Nasrin; Marx, Rudolf; Ahmed, Asma; Gutknecht, Norbert

    2016-01-01

    Dental tooth restorative procedures may weaken the structural integrity of the tooth, with the possibility of leading to fracture. In this study we present findings of coronal dentin strength after different techniques of surface modification. The fracture strength of dentin beams after superficial material removal with a fine diamond bur high speed drill hand piece, Er:YAG (2.94 μm, 8 J/cm2), and Er,Cr:YSGG (2.78 μm, 7.8 J/cm2) laser irradiation slightly above the ablation threshold was measured by a four-point bending apparatus. Untreated dentin beams served as a control. A total of 58 dentin beams were manufactured from sterilized human extracted molars using the coronal part of the available dentin. Mean values of fracture strength were calculated as 82.0 ± 27.3 MPa for the control group (n = 10), 104.5 ± 26.3 MPa for high speed drill treatment (n = 10), 96.1 ± 28.1 MPa for Er,Cr:YSGG laser irradiation (n = 20), and 89.1 ± 36.3 MPa for Er:YAG laser irradiation (n = 18). Independent Student's t-tests showed no significant difference between each two groups (p > 0.05). Within the parameter settings and the limits of the experimental setup used in this study, both lasers systems as well as the high speed drill do not significantly weaken coronal dentin after surface treatment. PMID:26962473

  11. Lockheed ER-2 #709 high altitude research aircraft in flight

    NASA Image and Video Library

    1998-03-02

    ER-2 tail number 709, was one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft were platforms for a variety of high-altitude science missions flown over various parts of the world. They were also used for earth science and atmospheric sensor research and development, satellite calibration and data validation.

  12. COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport

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

    Wang, Ying-Nai; Wang, Hongmei; Yamaguchi, Hirohito

    2010-09-03

    Research highlights: {yields} ARF1 activation is involved in the EGFR transport to the ER and the nucleus. {yields} Assembly of {gamma}-COP coatomer mediates EGFR transport to the ER and the nucleus. {yields} Golgi-to-ER retrograde trafficking regulates nuclear transport of EGFR. -- Abstract: Emerging evidence indicates that cell surface receptors, such as the entire epidermal growth factor receptor (EGFR) family, have been shown to localize in the nucleus. A retrograde route from the Golgi to the endoplasmic reticulum (ER) is postulated to be involved in the EGFR trafficking to the nucleus; however, the molecular mechanism in this proposed model remains unexplored.more » Here, we demonstrate that membrane-embedded vesicular trafficking is involved in the nuclear transport of EGFR. Confocal immunofluorescence reveals that in response to EGF, a portion of EGFR redistributes to the Golgi and the ER, where its NH{sub 2}-terminus resides within the lumen of Golgi/ER and COOH-terminus is exposed to the cytoplasm. Blockage of the Golgi-to-ER retrograde trafficking by brefeldin A or dominant mutants of the small GTPase ADP-ribosylation factor, which both resulted in the disassembly of the coat protein complex I (COPI) coat to the Golgi, inhibit EGFR transport to the ER and the nucleus. We further find that EGF-dependent nuclear transport of EGFR is regulated by retrograde trafficking from the Golgi to the ER involving an association of EGFR with {gamma}-COP, one of the subunits of the COPI coatomer. Our findings experimentally provide a comprehensive pathway that nuclear transport of EGFR is regulated by COPI-mediated vesicular trafficking from the Golgi to the ER, and may serve as a general mechanism in regulating the nuclear transport of other cell surface receptors.« less

  13. The Entangled ER-Mitochondrial axis as a potential therapeutic strategy in Neurodegeneration: A Tangled Duo Unchained

    PubMed Central

    Joshi, Amit U.; Kornfeld, Opher S.; Mochly-Rosen, Daria

    2016-01-01

    Endoplasmic reticulum (ER) and mitochondrial function have both been shown to be critical events in neurodegenerative diseases. The ER mediates protein folding, maturation, sorting as well acts as calcium storage. The unfolded protein response (UPR) is a stress response of the ER that is activated by the accumulation of misfolded proteins within the ER lumen. Although the molecular mechanisms underlying ER stress-induced apoptosis are not completely understood, increasing evidence suggests that ER and mitochondria cooperate to signal cell death. Similarly, calcium-mediated mitochondrial function and dynamics not only contribute to ATP generation and calcium buffering but are also a linchpin in mediating cell fate. Mitochondria and ER form structural and functional networks (mitochondria-associated ER membranes [MAMs]) essential to maintaining cellular homeostasis and determining cell fate under various pathophysiological conditions. Regulated Ca2+ transfer from the ER to the mitochondria is important in maintaining control of pro-survival/pro-death pathways. In this review, we summarize the latest therapeutic strategies that target these essential organelles in the context of neurodegenerative diseases. PMID:27212603

  14. Effect of water on dental material ablation of the Er:YAG laser

    NASA Astrophysics Data System (ADS)

    Wigdor, Harvey A.; Visuri, Steven R.; Walsh, Joseph T., Jr.

    1994-09-01

    It is understood that if a laser is to replace the dental high speed handpiece it must be able to ablate dental materials which are present in teeth being treated with the laser. It is the intent of this paper to evaluate the effects of the Er:YAG laser on dental composite restorative material concentrating on the etch rate with and without waterspray. Composite dental material is used to form plugs of known thickness and the etch rate of the Er:YAG laser on this material is determined. The results are compared with those obtained from studies of the Er:YAG on dentin and enamel. In these studies the water reduced the efficiency of the Er:YAG laser 15 - 20% on these tissues.

  15. Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer

    DTIC Science & Technology

    2012-03-01

    patients with early stage ErbB2-overexpressing biopsies and ER- atypia . 13 REFERENCES: 1. Jordan VC. Tamoxifen for breast cancer prevention. Proc Soc...Summary01-03-2012 Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer Shalini Jain University of Texas M.D. Anderson Cancer Center Houston...SUBTITLE “Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer” 5a. CONTRACT NUMBER W81XWH-11-1-0004 5b. GRANT NUMBER

  16. Disulfide bonds in ER protein folding and homeostasis

    PubMed Central

    Feige, Matthias J.; Hendershot, Linda M.

    2010-01-01

    Proteins that are expressed outside the cell must be synthesized, folded and assembled in a way that ensures they can function in their designate location. Accordingly these proteins are primarily synthesized in the endoplasmic reticulum (ER), which has developed a chemical environment more similar to that outside the cell. This organelle is equipped with a variety of molecular chaperones and folding enzymes that both assist the folding process, while at the same time exerting tight quality control measures that are largely absent outside the cell. A major post-translational modification of ER-synthesized proteins is disulfide bridge formation, which is catalyzed by the family of protein disulfide isomerases. As this covalent modification provides unique structural advantages to extracellular proteins, multiple pathways to their formation have evolved. However, the advantages that disulfide bonds impart to these proteins come at a high cost to the cell. Very recent reports have shed light on how the cell can deal with or even exploit the side reactions of disulfide bond formation to maintain homeostasis of the ER and its folding machinery. PMID:21144725

  17. PREDICTING ER BINDING AFFINITY FOR EDC RANKING AND PRIORITIZATION: A COMPARISON OF THREE MODELS

    EPA Science Inventory

    A comparative analysis of how three COREPA models for ER binding affinity performed when used to predict potential estrogen receptor (ER) ligands is presented. Models I and II were developed based on training sets of 232 and 279 rat ER binding affinity measurements, respectively....

  18. Synergism between a half-site and an imperfect estrogen-responsive element, and cooperation with COUP-TFI are required for estrogen receptor (ER) to achieve a maximal estrogen-stimulation of rainbow trout ER gene.

    PubMed

    Petit, F G; Métivier, R; Valotaire, Y; Pakdel, F

    1999-01-01

    In all oviparous, liver represents one of the main E2-target tissues where estrogen receptor (ER) constitutes the key mediator of estrogen action. The rainbow trout estrogen receptor (rtER) gene expression is markedly up-regulated by estrogens and the sequences responsible for this autoregulation have been located in a 0.2 kb upstream transcription start site within - 40/- 248 enhancer region. Absence of interference with steroid hormone receptors and tissue-specific factors and a conserved basal transcriptional machinery between yeast and higher eukaryotes, make yeast a simple assay system that will enable determination of important cis-acting regulatory sequences within rtER gene promoter and identification of transcription factors implicated in the regulation of this gene. Deletion analysis allowed to show a synergistic effect between an imperfect estrogen-responsive element (ERE) and a consensus half-ERE to achieve a high hormone-dependent transcriptional activation of the rtER gene promoter in the presence of stably expressed rtER. As in mammalian cells, here we observed a positive regulation of the rtER gene promoter by the chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) through enhancing autoregulation. Using a point mutation COUP-TFI mutant unable to bind DNA demonstrates that enhancement of rtER gene autoregulation requires the interaction of COUP-TFI to the DNA. Moreover, this enhancement of transcriptional activation by COUP-TFI requires specifically the AF-1 transactivation function of ER and can be observed in the presence of E2 or 4-hydroxytamoxifen but not ICI 164384. Thus, this paper describes the reconstitution of a hormone-responsive transcription unit in yeast in which the regulation of rtER gene promoter could be enhanced by the participation of cis-elements and/or trans-acting factors, such as ER itself or COUP-TF.

  19. Galantamine-ER for the treatment of mild-to-moderate Alzheimer’s disease

    PubMed Central

    Seltzer, Ben

    2010-01-01

    An extended release form of the cholinesterase inhibitor (ChEI) drug galantamine (galantamine-ER) was developed, chiefly to increase adherence to medication regimes in patients with mild-to-moderate Alzheimer’s disease (AD). Except for predicted differences in (Cmax) and tmax, comparable doses of once daily galantamine-ER and regular, immediate release galantamine, (galantamine-IR), are pharmacologically equivalent. A 24-week randomized, double-blind, placebo-and active-controlled, multicenter phase III trial, which compared galantamine-IR, galantamine-ER and placebo in subjects with mild to moderate AD (mini-mental state examination [MMSE] score range, 10 to 24) showed that both formulations of galantamine were significantly better than placebo in terms of cognition, although not with regard to global change. There was no difference in drug-related adverse events between galantamine-ER and galantamine-IR. Since its release onto the market galantamine-ER has enjoyed wide popularity and a recent surveillance study suggests that it has the highest 1-year persistence rate of all the ChEIs. PMID:20169037

  20. Sensory-Neuropathy-Causing Mutations in ATL3 Cause Aberrant ER Membrane Tethering.

    PubMed

    Krols, Michiel; Detry, Sammy; Asselbergh, Bob; Almeida-Souza, Leonardo; Kremer, Anna; Lippens, Saskia; De Rycke, Riet; De Winter, Vicky; Müller, Franz-Josef; Kurth, Ingo; McMahon, Harvey T; Savvides, Savvas N; Timmerman, Vincent; Janssens, Sophie

    2018-05-15

    The endoplasmic reticulum (ER) is a complex network of sheets and tubules that is continuously remodeled. The relevance of this membrane dynamics is underscored by the fact that mutations in atlastins (ATLs), the ER fusion proteins in mammals, cause neurodegeneration. How defects in this process disrupt neuronal homeostasis is unclear. Using electron microscopy (EM) volume reconstruction of transfected cells, neurons, and patient fibroblasts, we show that hereditary sensory and autonomic neuropathy (HSAN)-causing ATL3 mutants promote aberrant ER tethering hallmarked by bundles of laterally attached ER tubules. In vitro, these mutants cause excessive liposome tethering, recapitulating the results in cells. Moreover, ATL3 variants retain their dimerization-dependent GTPase activity but are unable to promote membrane fusion, suggesting a defect in an intermediate step of the ATL3 functional cycle. Our data show that the effects of ATL3 mutations on ER network organization go beyond a loss of fusion and shed light on neuropathies caused by atlastin defects. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Optimization of loading ratio of ErN as regenerator of 4K-GM cryocooler

    NASA Astrophysics Data System (ADS)

    Nakagawa, T.; Miyauchi, T.; Shiraishi, T.; Seino, S.; Yamamoto, T. A.; Fujimoto, Y.; Masuyama, S.

    2017-09-01

    High purity erbium nitride (ErN) spheres with the size range of 150-180 µm and 180-212 µm were prepared by nitriding Er metal spheres with low oxygen content. The initial regenerator material of HoCu2 on the cold end of the second regenerator column in 4K-GM cryocooler with nominal cooling power of 0.1 W at 4.2 K was replaced by ErN with different sizes. Higher cooling power was obtained when ErN of smaller size with lower oxygen content was used. We investigated the effect of partial replacement of HoCu2 by ErN in the cold end side of second stage regenerator column on cooling power of 4K-GM cryocoolers. When ErN were substituted for 20 % of HoCu2, the cooling power at 4.2 K reached 0.318 W. This value was 1.36 times as high as that of the cooling power of the GM cryocooler with commercially available regenerator arrangement. Therefore, use of ErN regenerator materials leads to the energy-saving and downsizing of 4K-GM cryocoolers.

  2. Efficient protein targeting to the inner nuclear membrane requires Atlastin-dependent maintenance of ER topology

    PubMed Central

    Pawar, Sumit; Ungricht, Rosemarie; Tiefenboeck, Peter; Leroux, Jean-Christophe

    2017-01-01

    Newly synthesized membrane proteins are targeted to the inner nuclear membrane (INM) by diffusion within the membrane system of the endoplasmic reticulum (ER), translocation through nuclear pore complexes (NPCs) and retention on nuclear partners. Using a visual in vitro assay we previously showed that efficient protein targeting to the INM depends on nucleotide hydrolysis. We now reveal that INM targeting is GTP-dependent. Exploiting in vitro reconstitution and in vivo analysis of INM targeting, we establish that Atlastins, membrane-bound GTPases of the ER, sustain the efficient targeting of proteins to the INM by their continued activity in preserving ER topology. When ER topology is altered, the long-range diffusional exchange of proteins in the ER network and targeting efficiency to the INM are diminished. Highlighting the general importance of proper ER topology, we show that Atlastins also influence NPC biogenesis and timely exit of secretory cargo from the ER. PMID:28826471

  3. Lycopene Protects against Hypoxia/Reoxygenation Injury by Alleviating ER Stress Induced Apoptosis in Neonatal Mouse Cardiomyocytes

    PubMed Central

    Xu, Jiqian; Hu, Houxiang; Chen, Bin; Yue, Rongchuan; Zhou, Zhou; Liu, Yin; Zhang, Shuang; Xu, Lei; Wang, Huan; Yu, Zhengping

    2015-01-01

    Endoplasmic reticulum (ER) stress induced apoptosis plays a pivotal role in myocardial ischemia/reperfusion (I/R)-injury. Inhibiting ER stress is a major therapeutic target/strategy in treating cardiovascular diseases. Our previous studies revealed that lycopene exhibits great pharmacological potential in protecting against the I/R-injury in vitro and vivo, but whether attenuation of ER stress (and) or ER stress-induced apoptosis contributes to the effects remains unclear. In the present study, using neonatal mouse cardiomyocytes to establish an in vitro model of hypoxia/reoxygenation (H/R) to mimic myocardium I/R in vivo, we aimed to explore the hypothesis that lycopene could alleviate the ER stress and ER stress-induced apoptosis in H/R-injury. We observed that lycopene alleviated the H/R injury as revealed by improving cell viability and reducing apoptosis, suppressed reactive oxygen species (ROS) generation and improved the phosphorylated AMPK expression, attenuated ER stress as evidenced by decreasing the expression of GRP78, ATF6 mRNA, sXbp-1 mRNA, eIF2α mRNA and eIF2α phosphorylation, alleviated ER stress-induced apoptosis as manifested by reducing CHOP/GADD153 expression, the ratio of Bax/Bcl-2, caspase-12 and caspase-3 activity in H/R-treated cardiomyocytes. Thapsigargin (TG) is a potent ER stress inducer and used to elicit ER stress of cardiomyocytes. Our results showed that lycopene was able to prevent TG-induced ER stress as reflected by attenuating the protein expression of GRP78 and CHOP/GADD153 compared to TG group, significantly improve TG-caused a loss of cell viability and decrease apoptosis in TG-treated cardiomyocytes. These results suggest that the protective effects of lycopene on H/R-injury are, at least in part, through alleviating ER stress and ER stress-induced apoptosis in neonatal mouse cardiomyocytes. PMID:26291709

  4. INTRAPUPAL TEMPERATURE VARIATION DURING ER,CR:YSGG ENAMEL IRRADIATION ON CARIES PREVENTION

    PubMed Central

    de Freitas, Patrícia Moreira; Soares-Geraldo, Débora; Biella-Silva, Ana Cristina; Silva, Amanda Verna; da Silveira, Bruno Lopes; Eduardo, Carlos de Paula

    2008-01-01

    Studies have shown the cariostatic effect of Er,Cr:YSGG (2.78 μm) laser irradiation on human enamel and have suggested its use on caries prevention. However there are still no reports on the intrapulpal temperature increase during enamel irradiation using parameters for caries prevention. The aim of this in vitro study was to evaluate the temperature variation in the pulp chamber during human enamel irradiation with Er,Cr:YSGG laser at different energy densities. Fifteen enamel blocks obtained from third molars (3 x 3 x 3 mm) were randomly assigned to 3 groups (n=5): G1 – Er,Cr:YSGG laser 0.25 W, 20 Hz, 2.84 J/cm2, G2 – Er,Cr:YSGG laser 0.50 W, 20 Hz, 5.68 J/cm2, G3 – Er,Cr:YSGG laser 0.75 W, 20 Hz, 8.52 J/cm2. During enamel irradiation, two thermocouples were fixed in the inner surface of the specimens and a thermal conducting paste was used. One-way ANOVA did not show statistically significant difference among the experimental groups (α=0.05). There was intrapulpal temperature variation ≤0.1°C for all irradiation parameters. In conclusion, under the tested conditions, the use of Er,Cr:YSGG laser with parameters set for caries prevention lead to an acceptable temperature increase in the pulp chamber. PMID:19089198

  5. ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

    PubMed

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-09-15

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

  6. ER-driven membrane contact sites: Evolutionary conserved machineries for stress response and autophagy regulation?

    PubMed Central

    Molino, Diana; Nascimbeni, Anna Chiara; Giordano, Francesca; Codogno, Patrice

    2017-01-01

    ABSTRACT Endoplasmic Reticulum (ER), spreading in the whole cell cytoplasm, is a central player in eukaryotic cell homeostasis, from plants to mammals. Beside crucial functions, such as membrane lipids and proteins synthesis and outward transport, the ER is able to connect to virtually every endomembrane compartment by specific tethering molecular machineries, which enables the establishment of membrane-membrane contact sites. ER-mitochondria contact sites have been shown to be involved in autophagosome biogenesis, the main organelle of the autophagy degradation pathway. More recently we demonstrated that also ER-plasma membrane contact sites are sites for autophagosomes assembly, suggesting that more generally ER-organelles contacts are involved in autophagy and organelle biogenesis. Here we aim to discuss the functioning of ER-driven contact sites in mammals and plants and more in particular emphasize on their recently highlighted function in autophagy to finally conclude on some key questions that may be useful for further research in the field. PMID:29259731

  7. Familial CJD Associated PrP Mutants within Transmembrane Region Induced Ctm-PrP Retention in ER and Triggered Apoptosis by ER Stress in SH-SY5Y Cells

    PubMed Central

    Wang, Xin; Shi, Qi; Xu, Kun; Gao, Chen; Chen, Cao; Li, Xiao-Li; Wang, Gui-Rong; Tian, Chan; Han, Jun; Dong, Xiao-Ping

    2011-01-01

    Background Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrPC) to the pathogenic one (PrPSc). The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K) into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. Methodology/Principal Findings To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER), the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL) and PrP with three amino acids exchange in transmembrane region (PrP-3AV) were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP) were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and capase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V) induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K) failed. Conclusions/Significance The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them the mutants

  8. Hydrogeology of the Umm Er Radhuma Aquifer (Arabian peninsula)

    NASA Astrophysics Data System (ADS)

    Dirks, Heiko; Al Ajmi, Hussain; Kienast, Peter; Rausch, Randolf

    2018-03-01

    The aim of this article is to enhance the understanding of the Umm Er Radhuma aquifer's genesis, and its hydraulic and hydrochemical development over time. This is a prerequisite for wise use of the fossil groundwater resources contained within. The Umm Er Radhuma is a karstified limestone aquifer, extending over 1.6 Mio. km2 in the eastern part of the Arabian Peninsula. Both epigene and hypogene karstification contributed to the genesis of what is today the most prolific aquifer in the region. Besides man-made abstractions, even the natural outflows are higher than the small recharge (natural storage depletion). The Umm Er Radhuma shows that large aquifers in arid regions are never in "steady state" (where inflows equal outflows), considering Quaternary climate history. The aquifer's adaption to climate changes (precipitation, sea level) can be traced even after thousands of years, and is slower than the climate changes themselves.

  9. The ER Contact Proteins VAPA/B Interact with Multiple Autophagy Proteins to Modulate Autophagosome Biogenesis.

    PubMed

    Zhao, Yan G; Liu, Nan; Miao, Guangyan; Chen, Yong; Zhao, Hongyu; Zhang, Hong

    2018-04-23

    The endoplasmic reticulum (ER) is the site of biogenesis of the isolation membrane (IM, autophagosome precursor) and forms extensive contacts with IMs during their expansion into double-membrane autophagosomes. Little is known about the molecular mechanism underlying the formation and/or maintenance of the ER/IM contact. The integral ER proteins VAPA and VAPB (VAPs) participate in establishing ER contacts with multiple membranes by interacting with different tethers. Here, we demonstrate that VAPs also modulate ER/IM contact formation. Depletion of VAPs impairs progression of IMs into autophagosomes. Upon autophagy induction, VAPs are recruited to autophagosome formation sites on the ER, a process mediated by their interactions with FIP200 and PI(3)P. VAPs directly interact with FIP200 and ULK1 through their conserved FFAT motifs and stabilize the ULK1/FIP200 complex at the autophagosome formation sites on the ER. The formation of ULK1 puncta is significantly reduced by VAPA/B depletion. VAPs also interact with WIPI2 and enhance the formation of the WIPI2/FIP200 ER/IM tethering complex. Depletion of VMP1, which increases the ER/IM contact, greatly elevates the interaction of VAPs with these autophagy proteins. The VAPB P56S mutation, which is associated with amyotrophic lateral sclerosis, reduces the ULK1/FIP200 interaction and impairs autophagy at an early step, similar to the effect seen in VAPA/B-depleted cells. Our study reveals that VAPs directly interact with multiple ATG proteins, thereby contributing to ER/IM contact formation for autophagosome biogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. PREDICTING ER BINDING AFFINITY FOR EDC RANKING AND PRIORITIZATION: MODEL II

    EPA Science Inventory

    The training set used to derive a common reactivity pattern (COREPA) model for estrogen receptor (ER) binding affinity in Model I (see Abstract I in this series) was extended to include 47 rat estrogen receptor (rER) relative binding affinity (RBA) measurements in addition to the...

  11. New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases.

    PubMed

    Ji, Cheng

    2014-01-01

    Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also  in vivo  in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.

  12. Unusual hafnium-pyridylamido/ER(n) heterobimetallic adducts (ER(n) = ZnR2 or AlR3).

    PubMed

    Rocchigiani, Luca; Busico, Vincenzo; Pastore, Antonello; Talarico, Giovanni; Macchioni, Alceo

    2014-02-17

    NMR spectroscopy and DFT studies indicate that the Symyx/Dow Hf(IV)-pyridylamido catalytic system for olefin polymerization, [{N(-),N,CNph(-)}HfMe][B(C6F5)4] (1, Nph = naphthyl), interacts with ER(n) (E = Al or Zn, R = alkyl group) to afford unusual heterobimetallic adducts [{N(-),N}HfMe(μ-CNph)(μ-R)ER(n-1)][B(C6F5)4 in which the cyclometalated Nph acts as a bridge between Hf and E. (1)H VT (variable-temperature) EXSY NMR spectroscopy provides direct evidence of reversible alkyl exchanges in heterobimetallic adducts, with ZnR2 showing a higher tendency to participate in this exchange than AlR3. 1-Hexene/ERn competitive reactions with 1 at 240 K reveal that the formation of adducts is strongly favored over 1-hexene polymerization. Nevertheless, a slight increase in the temperature (to >265 K) initiates 1-hexene polymerization. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Photoluminescence of Er-doped silicon-rich oxide thin films with high Al concentrations

    NASA Astrophysics Data System (ADS)

    Rozo, Carlos; Fonseca, Luis F.; Jaque, Daniel; García Solé, José

    Er-doped silicon-rich oxide (SRO) thin films co-doped with Al in high concentrations were prepared by sputtering. Some films were deposited using a substrate heater (150 °CEr ion emission presents variations as the O content decreases and the Al content increases. The dependence of the Er ion 980 nm peak PL with respect to the Er ion 1525 nm peak PL indicates that the first emission depends less on energy transfer upconversion (ETU) processes as the O content decreases and the Al content increases. Broadband excitable Er3+ infrared (IR) emission with less loss due to ETU processes is important for applications in photonics.

  14. Silicide formation process of Er films with Ta and TaN capping layers.

    PubMed

    Choi, Juyun; Choi, Seongheum; Kim, Jungwoo; Na, Sekwon; Lee, Hoo-Jeong; Lee, Seok-Hee; Kim, Hyoungsub

    2013-12-11

    The phase development and defect formation during the silicidation reaction of sputter-deposited Er films on Si with ∼20-nm-thick Ta and TaN capping layers were examined. TaN capping effectively prevented the oxygen incorporation from the annealing atmosphere, which resulted in complete conversion to the ErSi2-x phase. However, significant oxygen penetration through the Ta capping layer inhibited the ErSi2-x formation, and incurred the growth of several Er-Si-O phases, even consuming the ErSi2-x layer formed earlier. Both samples produced a number of small recessed defects at an early silicidation stage. However, large rectangular or square-shaped surface defects, which were either pitlike or pyramidal depending on the capping layer identity, were developed as the annealing temperature increased. The origin of different defect generation mechanisms was suggested based on the capping layer-dependent silicidation kinetics.

  15. Verification and Improvement of ERS-1/2 Altimeter Geophysical Data Records for Global Change Studies

    NASA Technical Reports Server (NTRS)

    Shum, C. K.

    2000-01-01

    This Final Technical Report summarizes the research work conducted under NASA's Physical Oceanography Program entitled, Verification And Improvement Of ERS-112 Altimeter Geophysical Data Recorders For Global Change Studies, for the time period from January 1, 2000 through June 30, 2000. This report also provides a summary of the investigation from July 1, 1997 - June 30, 2000. The primary objectives of this investigation include verification and improvement of the ERS-1 and ERS-2 radar altimeter geophysical data records for distribution of the data to the ESA-approved U.S. ERS-1/-2 investigators for global climate change studies. Specifically, the investigation is to verify and improve the ERS geophysical data record products by calibrating the instrument and assessing accuracy for the ERS-1/-2 orbital, geophysical, media, and instrument corrections. The purpose is to ensure that the consistency of constants, standards and algorithms with TOPEX/POSEIDON radar altimeter for global climate change studies such as the monitoring and interpretation of long-term sea level change. This investigation has provided the current best precise orbits, with the radial orbit accuracy for ERS-1 (Phases C-G) and ERS-2 estimated at the 3-5 cm rms level, an 30-fold improvement compared to the 1993 accuracy. We have finalized the production and verification of the value-added ERS-1 mission (Phases A, B, C, D, E, F, and G), in collaboration with JPL PODAAC and the University of Texas. Orbit and data verification and improvement of algorithms led to the best data product available to-date. ERS-2 altimeter data have been improved and we have been active on Envisat (2001 launch) GDR algorithm review and improvement. The data improvement of ERS-1 and ERS-2 led to improvement in the global mean sea surface, marine gravity anomaly and bathymetry models, and a study of Antarctica mass balance, which was published in Science in 1998.

  16. Study of 162Er via the (p , t) and (p ,p') reactions

    NASA Astrophysics Data System (ADS)

    Kisliuk, D.; Garrett, P. E.; Finlay, A.; Bianco, L.; Bildstein, V.; Burbadge, C.; Chagnon-Lessard, S.; Diaz Varela, A.; Dunlop, M. R.; Dunlop, R.; Finlay, P.; Jamieson, D.; Jigmeddorj, B.; Maclean, A. D.; Michetti-Wilson, J.; Leach, K. G.; Radich, A. J.; Rand, E.; Svensson, C. E.; Wong, J.; Ball, G. C.; Triambak, S.; Faestermann, T.; Hertenberger, R.; Wirth, H.-F.

    2015-10-01

    The nature of excited states in well-deformed nuclei pose a challenge in nuclear structure. In light of this, the study of 162Er via the 164Er (p , t) and 162Er (p ,p') reactions has been initiated to shed light on the structure of these excited states. The experiments were performed at the Maier-Leibnitz Laboratory using a 22 MeV proton beam on highly-enriched targets of 162,164Er and the reaction was analyzed with the Q3D spectrograph. Strong population in the (p , t) reaction of the 02+ state, far greater than other 0+ states, has been observed. Transition matrix elements for population of low-lying states in the (p ,p') reaction have also been extracted. Initial results from these experiments will be presented.

  17. The interaction between ER and NFκB in resistance to endocrine therapy

    PubMed Central

    2012-01-01

    Endocrine therapy is a commonly used treatment for estrogen receptor (ER)-positive breast cancer. Although endocrine therapy has a favorable outcome in many patients, development of resistance is common. Recent studies have shown that NFκB, a transcription factor regulating a wide variety of cellular processes, might play a role in the development of endocrine resistance. The precise interaction between ER and NFκB and how this contributes to the attenuated responsiveness of ER-positive breast cancer cells to hormonal treatment remains unclear. This review provides an overview of the mechanisms of action for both transcription factors and focuses on the current knowledge explaining how ER and NFκB affect each other's activity and how this cross-talk might contribute to the development of an endocrine resistance phenotype in breast cancer cells. PMID:22963717

  18. 33 CFR 222.5 - Water control management (ER 1110-2-240).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Water control management (ER 1110... ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a... Engineers in carrying out water control management activities, including establishment of water control...

  19. 33 CFR 222.5 - Water control management (ER 1110-2-240).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Water control management (ER 1110... ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a... Engineers in carrying out water control management activities, including establishment of water control...

  20. 33 CFR 222.5 - Water control management (ER 1110-2-240).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Water control management (ER 1110... ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a... Engineers in carrying out water control management activities, including establishment of water control...

  1. 33 CFR 222.5 - Water control management (ER 1110-2-240).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Water control management (ER 1110... ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a... Engineers in carrying out water control management activities, including establishment of water control...

  2. 33 CFR 222.5 - Water control management (ER 1110-2-240).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Water control management (ER 1110... ARMY, DEPARTMENT OF DEFENSE ENGINEERING AND DESIGN § 222.5 Water control management (ER 1110-2-240). (a... Engineers in carrying out water control management activities, including establishment of water control...

  3. Systemic effects of AGEs in ER stress induction in vivo.

    PubMed

    Adamopoulos, Christos; Mihailidou, Chrysovalantou; Grivaki, Christofora; Papavassiliou, Kostas A; Kiaris, Hippokratis; Piperi, Christina; Papavassiliou, Athanasios G

    2016-08-01

    Emerging evidence indicates that accumulation of advanced glycation end products (AGEs) in human tissues may contribute to cell injury, inflammation and apoptosis through induction of endoplasmic reticulum (ER) stress. Human metabolism relies on ER homeostasis for the coordinated response of all metabolic organs by controlling the synthesis and catabolism of various nutrients. In vitro studies have demonstrated AGE-induced enhancement of unfolded protein response (UPR) in different cell types including endothelial, neuronal, pancreatic cells and podocytes, suggesting this crosstalk as an underlying pathological mechanism that contributes to metabolic diseases. In this minireview, we describe in vivo studies undertaken by our group and others that demonstrate the diverse systemic effects of AGEs in ER stress induction in major metabolic tissues such as brain, kidney, liver and pancreas of normal mice. Administration of high-AGEs content diet to normal mice for the period of 4 weeks upergulates the mRNA and protein levels of ER chaperone Bip (GRP78) indicative of UPR initiation in all major metabolic organs and induces activation of the pivotal transcription factor XBP1 that regulates glucose and lipid metabolism. Furthermore, animals with genetic ablation of UPR-activated transcription factor C/EBP homologous protein CHOP allocated in high-AGEs diet, exhibited relative resistance to UPR induction (BiP levels) and XBP1 activation in major metabolic organs. Since CHOP presents a critical mediator that links accumulation and aggregation of unfolded proteins with induction of oxidative stress and ER stress-related apoptosis, it is revealed as an important molecular target for the management of metabolic diseases.

  4. Mouse Stbd1 is N-myristoylated and affects ER-mitochondria association and mitochondrial morphology.

    PubMed

    Demetriadou, Anthi; Morales-Sanfrutos, Julia; Nearchou, Marianna; Baba, Otto; Kyriacou, Kyriacos; Tate, Edward W; Drousiotou, Anthi; Petrou, Petros P

    2017-03-01

    Starch binding domain-containing protein 1 (Stbd1) is a carbohydrate-binding protein that has been proposed to be a selective autophagy receptor for glycogen. Here, we show that mouse Stbd1 is a transmembrane endoplasmic reticulum (ER)-resident protein with the capacity to induce the formation of organized ER structures in HeLa cells. In addition to bulk ER, Stbd1 was found to localize to mitochondria-associated membranes (MAMs), which represent regions of close apposition between the ER and mitochondria. We demonstrate that N -myristoylation and binding of Stbd1 to glycogen act as major determinants of its subcellular targeting. Moreover, overexpression of non-myristoylated Stbd1 enhanced the association between ER and mitochondria, and further induced prominent mitochondrial fragmentation and clustering. Conversely, shRNA-mediated Stbd1 silencing resulted in an increase in the spacing between ER and mitochondria, and an altered morphology of the mitochondrial network, suggesting elevated fusion and interconnectivity of mitochondria. Our data unravel the molecular mechanism underlying Stbd1 subcellular targeting, support and expand its proposed function as a selective autophagy receptor for glycogen and uncover a new role for the protein in the physical association between ER and mitochondria. © 2017. Published by The Company of Biologists Ltd.

  5. Coxsackievirus A16 infection triggers apoptosis in RD cells by inducing ER stress.

    PubMed

    Zhu, Guoguo; Zheng, Yingcheng; Zhang, Lianglu; Shi, Yingying; Li, Wenhua; Liu, Zhongchun; Peng, Biwen; Yin, Jun; Liu, Wanhong; He, Xiaohua

    2013-11-29

    Coxsackievirus A16 (CA16) infection, which is responsible for hand, foot and mouth disease (HFMD), has become a common health problem in Asia due to the prevalence of the virus. Thus, it is important to understand the pathogenesis of CA16 infection. Viruses that induce endoplasmic reticulum (ER) stress are confronted with the unfolded protein response (UPR), which may lead to apoptotic cell death and influence viral replication. In this study, we found that CA16 infection could induce apoptosis and ER stress in RD cells. Interestingly, apoptosis via the activation of caspase-3, -8 and -9 in the extrinsic or intrinsic apoptotic pathways in RD cells was inhibited by 4-phenyl butyric acid (4PBA), a chemical chaperone that reduces ER stress. These results suggest that CA16 infection leads to ER stress, which in turn results in prolonged ER stress-induced apoptosis. This study provides a new basis for understanding CA16 infection and host responses. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Therapeutic correction of ApoER2 splicing in Alzheimer's disease mice using antisense oligonucleotides.

    PubMed

    Hinrich, Anthony J; Jodelka, Francine M; Chang, Jennifer L; Brutman, Daniella; Bruno, Angela M; Briggs, Clark A; James, Bryan D; Stutzmann, Grace E; Bennett, David A; Miller, Steven A; Rigo, Frank; Marr, Robert A; Hastings, Michelle L

    2016-04-01

    Apolipoprotein E receptor 2 (ApoER2) is an apolipoprotein E receptor involved in long-term potentiation, learning, and memory. Given its role in cognition and its association with the Alzheimer's disease (AD) risk gene, apoE, ApoER2 has been proposed to be involved in AD, though a role for the receptor in the disease is not clear. ApoER2 signaling requires amino acids encoded by alternatively spliced exon 19. Here, we report that the balance of ApoER2 exon 19 splicing is deregulated in postmortem brain tissue from AD patients and in a transgenic mouse model of AD To test the role of deregulated ApoER2 splicing in AD, we designed an antisense oligonucleotide (ASO) that increases exon 19 splicing. Treatment of AD mice with a single dose of ASO corrected ApoER2 splicing for up to 6 months and improved synaptic function and learning and memory. These results reveal an association between ApoER2 isoform expression and AD, and provide preclinical evidence for the utility of ASOs as a therapeutic approach to mitigate Alzheimer's disease symptoms by improving ApoER2 exon 19 splicing. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  7. Emerging features of ER resident J-proteins in plants

    PubMed Central

    Ohta, Masaru; Takaiwa, Fumio

    2014-01-01

    J-proteins are co-chaperone components of the HSP70 system. J-proteins stimulate Hsp70ATPase activity, which is responsible for stabilizing the interaction of Hsp70 with client proteins. J-proteins are localized in various intracellular compartments including the cytoplasm, mitochondria and endoplasmic reticulum (ER). Five types of ER resident J-proteins (ERdjs) have been found in plants (P58, ERdj2, ERdj2A, ERdj3B and ERdj7). Rice OsERdj3A is located in the vacuole and protein storage vacuoles (PSV, PB-II) under conditions of ER stress. J-proteins that are localized to the vacuole or lysosome are not found in mammals and yeast, suggesting that the presence of OsERdj3A in the vacuole is plant-specific and one of the features unique to plant ERdjs. In this review, we summarize the current state of knowledge and recent research advancements regarding plant ERdjs, and compare mammalian and yeast ERdjs with plant ERdjs. PMID:24614601

  8. Tunable, diode side-pumped Er: YAG laser

    DOEpatents

    Hamilton, Charles E.; Furu, Laurence H.

    1997-01-01

    A discrete-element Er:YAG laser, side pumped by a 220 Watt peak-power InGaAs diode array, generates >500 mWatts at 2.94 .mu.m, and is tunable over a 6 nm range near about 2.936 .mu.m. The oscillator is a plano-concave resonator consisting of a concave high reflector, a flat output coupler, a Er:YAG crystal and a YAG intracavity etalon, which serves as the tuning element. The cavity length is variable from 3 cm to 4 cm. The oscillator uses total internal reflection in the Er:YAG crystal to allow efficient coupling of the diode emission into the resonating modes of the oscillator. With the tuning element removed, the oscillator produces up to 1.3 Watts of average power at 2.94 .mu.m. The duty factor of the laser is 6.5% and the repetition rate is variable up to 1 kHz. This laser is useful for tuning to an atmospheric transmission window at 2.935 .mu.m (air wavelength). The laser is also useful as a spectroscopic tool because it can access several infrared water vapor transitions, as well as transitions in organic compounds. Other uses include medical applications (e.g., for tissue ablation and uses with fiber optic laser scalpels) and as part of industrial effluent monitoring systems.

  9. Tunable, diode side-pumped Er:YAG laser

    DOEpatents

    Hamilton, C.E.; Furu, L.H.

    1997-04-22

    A discrete-element Er:YAG laser, side pumped by a 220 Watt peak-power InGaAs diode array, generates >500 mWatts at 2.94 {micro}m, and is tunable over a 6 nm range near about 2.936 {micro}m. The oscillator is a plano-concave resonator consisting of a concave high reflector, a flat output coupler, a Er:YAG crystal and a YAG intracavity etalon, which serves as the tuning element. The cavity length is variable from 3 cm to 4 cm. The oscillator uses total internal reflection in the Er:YAG crystal to allow efficient coupling of the diode emission into the resonating modes of the oscillator. With the tuning element removed, the oscillator produces up to 1.3 Watts of average power at 2.94 {micro}m. The duty factor of the laser is 6.5% and the repetition rate is variable up to 1 kHz. This laser is useful for tuning to an atmospheric transmission window at 2.935 {micro}m (air wavelength). The laser is also useful as a spectroscopic tool because it can access several infrared water vapor transitions, as well as transitions in organic compounds. Other uses include medical applications (e.g., for tissue ablation and uses with fiber optic laser scalpels) and as part of industrial effluent monitoring systems. 4 figs.

  10. [Preparation and photoluminescence study of Er3+ : Y2O3 transparent ceramics].

    PubMed

    Luo, Jun-ming; Li, Yong-xiu; Deng, Li-ping

    2008-10-01

    Y2O3 acted as the matrix material, which was doped with different concentrations of Er3+, Er3+ : Y2O3 nanocrystalline powder was prepared by co-precipitation method, and Er3+ : Y2O3 transparent ceramics was fabricated by vacuum sintering at 1700 degrees C, 1 x 10(-3) Pa for 8 h. By using the X-ray diffraction (D/MAX-RB), transmission electron microscopy(Philips EM420), automatic logging spectrophotometer(DMR-22), fluorescence analyzer (F-4500) and 980 nm diode laser, the structural, morphological and luminescence properties of the sample were investigated. The results show that Er3+ dissolved completely in the Y2O3 cubic phase, the precursor was amorphous, weak diffraction peaks appeared after calcination at 400 degrees C, and if calcined at 700 degrees C, the precursor turned to pure cubic phase. With increasing the calcining temperature, the diffraction peaks became sharp quickly, and when the calcining temperature reached 1100 degrees C, the diffraction peaks became very sharp, indicating that the grains were very large. The particles of Er+ : Y2O3 is homogeneous and nearly spherical, the average diameter of the particles is in the range of 40-60 nm after being calcined at 1000 degrees C for 2 h. The relative density of Er3+ : Y2O3 transparent ceramics is 99.8%, the transmittance of the Er2+ : Y2O3 transparent ceramics is markedly lower than the single crystal at the short wavelength, but the transmittance is improved noticeably with increasing the wavelength, and the transmittance exceeds 60% at the wavelength of 1200 nm. Excited under the 980 nm diode laser, there are two main up-conversion emission bands, green emission centers at 562 nm and red emission centers at 660 nm, which correspond to (4)S(3/2) / (2)H(11/2) - (4)I(15/2) and (4)F(9/2) - (4)I(15/2) radiative transitions respectively. By changing the doping concentrations of Er3+, the color of up-conversion luminescence can be tuned from green to red gradually. The luminescence intensity is not reinforce

  11. Selective emission and luminescence of Er{sub 2}O{sub 3} under intense laser excitation

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

    Marchenko, V M; Studenikin, M I; Iskhakova, L D

    2013-09-30

    The microstructure of Er{sub 2}O{sub 3} polycrystals synthesised by laser heating is studied. The synthesis of erbium silicate (Er{sub 2}SiO{sub 5}) layers was observed upon interaction of Er{sub 2}O{sub 3} and SiO{sub 2} melts. The dependences of the selective emission (SE) and luminescence spectra of Er{sub 2}O{sub 3} polycrystals in the range 200 – 1700 nm on the intensity of laser-thermal (at the wavelength λ = 10.6 μm) and resonant laser (λ ≈ 975 nm) excitation are investigated. The emission of heated Er{sub 2}O{sub 3} polycrystals arises as a result of multiphonon relaxation of absorbed energy and is a superpositionmore » of the SE at the electronic-vibrational transitions of Er{sup 3+} ions and the thermal radiation of the crystal lattice. The shape of the SE spectra of Er{sub 2}O{sub 3} polycrystals in the range 400 – 1700 nm almost does not change upon laser-thermal heating from 300 to 1500 K and subsequent cooling and corresponds to the absorption spectra of Er{sup 3+} ions. With increasing temperature, the thermal radiation intensity increases faster than the SE intensity, and the shape of the Er{sub 2}O{sub 3} spectrum becomes closer to the calculated spectrum of a blackbody. The anti-Stokes luminescence spectra of Er{sup 3+} ions formed under intense laser excitation of the {sup 4}I{sub 11/2} level are explained by additional SE caused by heating of the crystal matrix due to the Stokes losses. A difference between the SE and luminescence spectra is observed at low intensities of resonant laser excitation and low temperatures, when only the Stokes luminescence occurs. The temperature dependences of the SE and luminescence spectra of Er{sub 2}O{sub 3} upon laser excitation testify to the fundamental role played by the interaction of the electronic f-shell of Er{sup 3+} ions with crystal lattice vibrations in the processes of multiphonon radiative and nonradiative relaxation. The laser-thermal synthesis is promising for inprocess variation of

  12. Cell biology. ER-to-Golgi traffic--this bud's for you.

    PubMed

    Brittle, E E; Waters, M G

    2000-07-21

    How do protein-transporting vesicles, which bud from the endoplasmic reticulum (ER), specifically dock to, and fuse with, the Golgi apparatus? In their Perspective, Brittle and Waters discuss new work (Allan et al.) suggesting that some vesicle-associated docking and fusion proteins are "programmed" during vesicle budding from the ER and direct downstream events that occur during fusion of these transport vesicles with the membranes of the Golgi.

  13. Performance Analysis of AN Engine Mount Featuring ER Fluids and Piezoactuators

    NASA Astrophysics Data System (ADS)

    Choi, S. H.; Choi, Y. T.; Choi, S. B.; Cheong, C. C.

    Conventional rubber mounts and various types of passive or semi-active hydraulic engine mounts for a passenger vehicle have their own functional aims on the limited frequency band in the broad engine operating frequency range. In order to achieve high system performance over all frequency ranges of the engine operation, a new type of engine mount featuring electro-rheological(ER) fluids and piezoactuators is proposed in this study. A mathematical model of the proposed engine mount is derived using the bond graph method which is inherently adequate to model the interconnected hydromechanical system. In the low frequency domain, the ER fluid is activated upon imposing an electric field for vibration isolation while the piezoactuator is activated in the high frequency domain. A neuro-control algorithm is utilized to determine control electric field for the ER fluid, and H∞ control technique is adopted for the piezoactuator Comparative works between the proposed and single-actuating(ER fluid only or piezoactuator only) engine mounts are undertaken by evaluating force transmissibility over a wide operating frequency range.

  14. Presenilin 1 mutations influence processing and trafficking of the ApoE receptor apoER2.

    PubMed

    Wang, Wei; Moerman-Herzog, Andrea M; Slaton, Arthur; Barger, Steven W

    2017-01-01

    Presenilin (PS)-1 is an intramembrane protease serving as the catalytic component of γ-secretase. Mutations in the PS1 gene are the most common cause of familial Alzheimer's disease (FAD). The low-density lipoprotein (LDL)-receptor family member apoER2 is a γ-secretase substrate that has been associated with AD in several ways, including acting as a receptor for apolipoprotein E (ApoE). ApoER2 is processed by γ-secretase into a C-terminal fragment (γ-CTF) that appears to regulate gene expression. FAD PS1 mutations were tested for effects on apoER2. PS1 mutation R278I showed impaired γ-secretase activity for apoER2 in the basal state or after exposure to Reelin. PS1 M146V mutation permitted accumulation of apoER2 CTFs after Reelin treatment, whereas no difference was seen between wild-type (WT) and M146V in the basal state. PS1 L282V mutation, combined with the γ-secretase inhibitor N-(N-[3,5-Difluorophenacetyl]-L-alanyl)-S-phenylglycine t-butyl ester, greatly reduced the cell-surface levels of apoER2 without affecting total apoER2 levels, suggesting a defect in receptor trafficking. These findings indicate that impaired processing or localization of apoER2 may contribute to the pathogenic effects of FAD mutations in PS1. Published by Elsevier Inc.

  15. New Er3+-doped phosphate glass for ion-exchanged waveguide amplifiers

    NASA Astrophysics Data System (ADS)

    Jiang, Shibin; Luo, Tao; Hwang, Bor-Chyuan; Nunzi Conti, Gualtiero; Myers, Michael J.; Rhonehouse, Daniel L.; Honkanen, Seppo; Peyghambarian, Nasser

    1998-12-01

    A new Er(superscript 3+)-doped phosphate glass exhibiting an excellent durability in both boiling water and NaNO(subscript 3) molten salt is developed. The ion-exchange process of this glass is investigated by treating glass samples in a variety of salt baths with various exposure times. A planar waveguide with one mode at 1.54 micrometers and three modes at 632.8 nm is demonstrated. The spectral properties of Er(superscript 3+) in this glass are characterized by measuring absorption and emission spectra and fluorescence lifetimes. The emission cross section of Er(superscript 3+) in this glass is calculated to be 0.76 X 10(superscript 20) cm(superscript 2) using McCumber theory.

  16. ER stress in Alzheimer's disease: a novel neuronal trigger for inflammation and Alzheimer's pathology

    PubMed Central

    2009-01-01

    The endoplasmic reticulum (ER) is involved in several crucial cellular functions, e.g. protein folding and quality control, maintenance of Ca2+ balance, and cholesterol synthesis. Many genetic and environmental insults can disturb the function of ER and induce ER stress. ER contains three branches of stress sensors, i.e. IRE1, PERK and ATF6 transducers, which recognize the misfolding of proteins in ER and activate a complex signaling network to generate the unfolded protein response (UPR). Alzheimer's disease (AD) is a progressive neurodegenerative disorder involving misfolding and aggregation of proteins in conjunction with prolonged cellular stress, e.g. in redox regulation and Ca2+ homeostasis. Emerging evidence indicates that the UPR is activated in neurons but not in glial cells in AD brains. Neurons display pPERK, peIF2α and pIRE1α immunostaining along with abundant diffuse staining of phosphorylated tau protein. Recent studies have demonstrated that ER stress can also induce an inflammatory response via different UPR transducers. The most potent pathways are IRE1-TRAF2, PERK-eIF2α, PERK-GSK-3, ATF6-CREBH, as well as inflammatory caspase-induced signaling pathways. We will describe the mechanisms which could link the ER stress of neurons to the activation of the inflammatory response and the evolution of pathological changes in AD. PMID:20035627

  17. STIM1L traps and gates Orai1 channels without remodeling the cortical ER

    PubMed Central

    Saüc, Sophie; Bulla, Monica; Nunes, Paula; Orci, Lelio; Marchetti, Anna; Antigny, Fabrice; Bernheim, Laurent; Cosson, Pierre; Frieden, Maud; Demaurex, Nicolas

    2015-01-01

    STIM proteins populate and expand cortical endoplasmic reticulum (ER) sheets to mediate store-operated Ca2+ entry (SOCE) by trapping and gating Orai channels in ER-plasma membrane clusters. A longer splice variant, STIM1L, forms permanent ER-plasma membrane clusters and mediates rapid Ca2+ influx in muscle. Here, we used electron microscopy, total internal reflection fluorescence (TIRF) microscopy and Ca2+ imaging to establish the trafficking and signaling properties of the two STIM1 isoforms in Stim1−/−/Stim2−/− fibroblasts. Unlike STIM1, STIM1L was poorly recruited into ER-plasma membrane clusters and did not mediate store-dependent expansion of cortical ER cisternae. Removal of the STIM1 lysine-rich tail prevented store-dependent cluster enlargement, whereas inhibition of cytosolic Ca2+ elevations or removal of the STIM1L actin-binding domain had no impact on cluster expansion. Finally, STIM1L restored robust but not accelerated SOCE and clustered with Orai1 channels more slowly than STIM1 following store depletion. These results indicate that STIM1L does not mediate rapid SOCE but can trap and gate Orai1 channels efficiently without remodeling cortical ER cisternae. The ability of STIM proteins to induce cortical ER formation is dispensable for SOCE and requires the lysine-rich tail of STIM1 involved in binding to phosphoinositides. PMID:25736291

  18. 184AA3: a xenograft model of ER+ breast adenocarcinoma

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

    Hines, William C.; Kuhn, Irene; Thi, Kate

    Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER +) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Xenografts of one cell line, 184AA3, consistently formed ER + adenocarcinomas that had a high proliferative rate and other features consistentmore » with “luminal B” intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44 High  subpopulation was discovered, yet their tumor forming ability was far less than CD44 Low  cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER +  cancers. In conclusion, this model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing, and drug development.« less

  19. 184AA3: a xenograft model of ER+ breast adenocarcinoma

    DOE PAGES

    Hines, William C.; Kuhn, Irene; Thi, Kate; ...

    2015-12-12

    Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER +) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Xenografts of one cell line, 184AA3, consistently formed ER + adenocarcinomas that had a high proliferative rate and other features consistentmore » with “luminal B” intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44 High  subpopulation was discovered, yet their tumor forming ability was far less than CD44 Low  cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER +  cancers. In conclusion, this model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing, and drug development.« less

  20. The APP intracellular domain (AICD) potentiates ER stress-induced apoptosis.

    PubMed

    Kögel, Donat; Concannon, Caoimhín G; Müller, Thorsten; König, Hildegard; Bonner, Caroline; Poeschel, Simone; Chang, Steffi; Egensperger, Rupert; Prehn, Jochen H M

    2012-09-01

    Here we employed human SHEP neuroblastoma cells either stably or inducibly expressing the amyloid precursor protein (APP) intracellular domain (AICD) to investigate its ability to modulate stress-induced cell death. Analysis of effector caspase activation revealed that AICD overexpression was specifically associated with an increased sensitivity to apoptosis induced by the 2 endoplasmic reticulum (ER) stressors thapsigargin and tunicamycin, but not by staurosporine (STS). Basal and ER stress-induced expression of Bip/Grp78 and C/EBP-homologous protein/GADD153 were not altered by AICD implying that AICD potentiated cell death downstream or independent of the conserved unfolded protein response (UPR). Interestingly, quantitative polymerase chain reaction analysis and reporter gene assays revealed that AICD significantly downregulated messenger RNA levels of the Alzheimer's disease susceptibility gene ApoJ/clusterin, indicating transcriptional repression. Knockdown of ApoJ/clusterin mimicked the effect of AICD on ER stress-induced apoptosis, but had no discernible effect on staurosporine-induced cell death. Our data suggest that altered levels of AICD may abolish the prosurvival function of ApoJ/clusterin and increase the susceptibility of neurons to ER stress-mediated cell death, a pathway that may contribute to the pathogenesis of Alzheimer's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. [Receptor status (ER and PgR) determined with histochemical and biochemical methods in breast carcinoma].

    PubMed

    Simone, G; Paradiso, A; Cirillo, R; Mangia, A; Rella, G; Wiesel, S; Petroni, S; De Benedictis, G; De Lena, M

    1991-01-01

    Recently, a method similar to ER.ICA has been proposed for the progesterone receptor (PgR) using two monoclonal antibodies, JZB39 and KD68, specific for human PgR and characterized by a molecular weight of 95 and 120 Kd, respectively. A series of 73 breast cancer patients was studied with regards to ER and PgR using both immunocytochemical (ICA) and biochemical (DCC) assays. Results showed no substantial differences between the two methods when considering common clinical-pathological parameters. Overall agreement between ICA and DCC methods was found: 79% for PgR and 78% for ER. A slight quantitative correlation was also observed between the "score values" of the ICA method and the Fmol content of ER and PgR using the Brave-Pearson test (r = 0.49 for PgR; r = 0.43 for ER). Specificity of PgR.ICA method was 77% for PgR and 72% for ER; sensitivity was 82% and 83%, respectively. The ICA method is a reliable technique to assess PgR presence as well as ER. Further studies are necessary to evaluate the prognostic role of nuclear PgR.

  2. Lockheed ER-2 #709 high altitude research aircraft during take off

    NASA Image and Video Library

    1998-02-18

    ER-2 tail number 709, was one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft were platforms for a variety of high-altitude science missions flown over various parts of the world. They were also used for earth science and atmospheric sensor research and development, satellite calibration and data validation.

  3. Lockheed ER-2 #709 high altitude research aircraft during take off

    NASA Image and Video Library

    1998-03-02

    ER-2 tail number 709, was one of two Airborne Science ER-2s used as science platforms by Dryden. The aircraft were platforms for a variety of high-altitude science missions flown over various parts of the world. They were also used for earth science and atmospheric sensor research and development, satellite calibration and data validation.

  4. Wormhole and entanglement (non-)detection in the ER=EPR correspondence

    DOE PAGES

    Bao, Ning; Pollack, Jason; Remmen, Grant N.

    2015-11-19

    The recently proposed ER=EPR correspondence postulates the existence of wormholes (Einstein-Rosen bridges) between entangled states (such as EPR pairs). Entanglement is famously known to be unobservable in quantum mechanics, in that there exists no observable (or, equivalently, projector) that can accurately pick out whether a generic state is entangled. Many features of the geometry of spacetime, however, are observables, so one might worry that the presence or absence of a wormhole could identify an entangled state in ER=EPR, violating quantum mechanics, specifically, the property of state-independence of observables. In this note, we establish that this cannot occur: there is nomore » measurement in general relativity that unambiguously detects the presence of a generic wormhole geometry. Furthermore, this statement is the ER=EPR dual of the undetectability of entanglement.« less

  5. 20 CFR 234.47 - Election of the RLS by a widow(er) or parent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Election of the RLS by a widow(er) or parent... parent. (a) An RLS cannot be paid if it appears that there are immediate or future monthly survivor benefits payable to anyone other than a widow(er) or parent. A widow(er) or parent can elect to have the...

  6. Hepatitis C Virus Lipoviroparticles Assemble in the Endoplasmic Reticulum (ER) and Bud off from the ER to the Golgi Compartment in COPII Vesicles.

    PubMed

    Syed, Gulam H; Khan, Mohsin; Yang, Song; Siddiqui, Aleem

    2017-08-01

    Hepatitis C virus (HCV) exists as a lipoprotein-virus hybrid lipoviroparticle (LVP). In vitro studies have demonstrated the importance of apolipoproteins in HCV secretion and infectivity, leading to the notion that HCV coopts the secretion of very-low-density lipoprotein (VLDL) for its egress. However, the mechanisms involved in virus particle assembly and egress are still elusive. The biogenesis of VLDL particles occurs in the endoplasmic reticulum (ER), followed by subsequent lipidation in the ER and Golgi compartment. The secretion of mature VLDL particles occurs through the Golgi secretory pathway. HCV virions are believed to latch onto or fuse with the nascent VLDL particle in either the ER or the Golgi compartment, resulting in the generation of LVPs. In our attempt to unravel the collaboration between HCV and VLDL secretion, we studied HCV particles budding from the ER en route to the Golgi compartment in COPII vesicles. Biophysical characterization of COPII vesicles fractionated on an iodixanol gradient revealed that HCV RNA is enriched in the highly buoyant COPII vesicle fractions and cofractionates with apolipoprotein B (ApoB), ApoE, and the HCV core and envelope proteins. Electron microscopy of immunogold-labeled microsections revealed that the HCV envelope and core proteins colocalize with apolipoproteins and HCV RNA in Sec31-coated COPII vesicles. Ultrastructural analysis also revealed the presence of HCV structural proteins, RNA, and apolipoproteins in the Golgi stacks. These findings support the hypothesis that HCV LVPs assemble in the ER and are transported to the Golgi compartment in COPII vesicles to embark on the Golgi secretory route. IMPORTANCE HCV assembly and release accompany the formation of LVPs that circulate in the sera of HCV patients and are also produced in an in vitro culture system. The pathway of HCV morphogenesis and secretion has not been fully understood. This study investigates the exact site where the association of HCV

  7. Hepatitis C Virus Lipoviroparticles Assemble in the Endoplasmic Reticulum (ER) and Bud off from the ER to the Golgi Compartment in COPII Vesicles

    PubMed Central

    Khan, Mohsin; Yang, Song

    2017-01-01

    ABSTRACT Hepatitis C virus (HCV) exists as a lipoprotein-virus hybrid lipoviroparticle (LVP). In vitro studies have demonstrated the importance of apolipoproteins in HCV secretion and infectivity, leading to the notion that HCV coopts the secretion of very-low-density lipoprotein (VLDL) for its egress. However, the mechanisms involved in virus particle assembly and egress are still elusive. The biogenesis of VLDL particles occurs in the endoplasmic reticulum (ER), followed by subsequent lipidation in the ER and Golgi compartment. The secretion of mature VLDL particles occurs through the Golgi secretory pathway. HCV virions are believed to latch onto or fuse with the nascent VLDL particle in either the ER or the Golgi compartment, resulting in the generation of LVPs. In our attempt to unravel the collaboration between HCV and VLDL secretion, we studied HCV particles budding from the ER en route to the Golgi compartment in COPII vesicles. Biophysical characterization of COPII vesicles fractionated on an iodixanol gradient revealed that HCV RNA is enriched in the highly buoyant COPII vesicle fractions and cofractionates with apolipoprotein B (ApoB), ApoE, and the HCV core and envelope proteins. Electron microscopy of immunogold-labeled microsections revealed that the HCV envelope and core proteins colocalize with apolipoproteins and HCV RNA in Sec31-coated COPII vesicles. Ultrastructural analysis also revealed the presence of HCV structural proteins, RNA, and apolipoproteins in the Golgi stacks. These findings support the hypothesis that HCV LVPs assemble in the ER and are transported to the Golgi compartment in COPII vesicles to embark on the Golgi secretory route. IMPORTANCE HCV assembly and release accompany the formation of LVPs that circulate in the sera of HCV patients and are also produced in an in vitro culture system. The pathway of HCV morphogenesis and secretion has not been fully understood. This study investigates the exact site where the association of

  8. Near Infrared Quantum Cutting Luminescence of Er3+/Tm3+ Ion Pairs in a Telluride Glass.

    PubMed

    Chen, Xiaobo; Li, Song; Hu, Lili; Wang, Kezhi; Zhao, Guoying; He, Lizhu; Liu, Jinying; Yu, Chunlei; Tao, Jingfu; Lin, Wei; Yang, Guojian; Salamo, Gregory J

    2017-05-16

    The multiphoton near-infrared, quantum cutting luminescence in Er 3+ /Tm 3+ co-doped telluride glass was studied. We found that the near-infrared 1800-nm luminescence intensity of (A) Er 3+ (8%)Tm 3+ (0.5%):telluride glass was approximately 4.4 to 19.5 times larger than that of (B) Tm 3+ (0.5%):telluride glass, and approximately 5.0 times larger than that of (C) Er 3+ (0.5%):telluride glass. Additionally, the infrared excitation spectra of the 1800 nm luminescence, as well as the visible excitation spectra of the 522 nm and 652 nm luminescence, of (A) Er 3+ (8%)Tm 3+ (0.5%):telluride glass are very similar to those of Er 3+ ions in (C) Er 3+ (0.5%):telluride glass, with respect to the shapes of their excitation spectral waveforms and peak wavelengths. Moreover, we found that there is a strong spectral overlap and energy transfer between the infrared luminescence of Er 3+ donor ions and the infrared absorption of Tm 3+ acceptor ions. The efficiency of this energy transfer { 4 I 13/2 (Er 3+ ) →  4 I 15/2 (Er 3+ ), 3 H 6 (Tm 3+ ) →  3 F 4 (Tm 3+ )} between the Er 3+ and Tm 3+ ions is approximately 69.8%. Therefore, we can conclude that the observed behaviour is an interesting multiphoton, near-infrared, quantum cutting luminescence phenomenon that occurs in novel Er 3+ -Tm 3+ ion pairs. These findings are significant for the development of next-generation environmentally friendly germanium solar cells, and near-to-mid infrared (1.8-2.0 μm) lasers pumped by GaN light emitting diodes.

  9. NRF1 Is an ER Membrane Sensor that Is Central to Cholesterol Homeostasis.

    PubMed

    Widenmaier, Scott B; Snyder, Nicole A; Nguyen, Truc B; Arduini, Alessandro; Lee, Grace Y; Arruda, Ana Paula; Saksi, Jani; Bartelt, Alexander; Hotamisligil, Gökhan S

    2017-11-16

    Cholesterol is a critical nutrient requiring tight constraint in the endoplasmic reticulum (ER) due to its uniquely challenging biophysical properties. While the mechanisms by which the ER defends against cholesterol insufficiency are well described, it remains unclear how the ER senses and effectively defends against cholesterol excess. Here, we identify the ER-bound transcription factor nuclear factor erythroid 2 related factor-1, Nrf1/Nfe2L1, as a critical mediator of this process. We show that Nrf1 directly binds to and specifically senses cholesterol in the ER through a defined domain and that cholesterol regulates Nrf1 turnover, processing, localization, and activity. In Nrf1 deficiency, in vivo cholesterol challenges induce massive hepatic cholesterol accumulation and damage, which is rescued by replacing Nrf1 exogenously. This Nrf1-mediated mechanism involves the suppression of CD36-driven inflammatory signaling and derepression of liver X receptor activity. These findings reveal Nrf1 as a guardian of cholesterol homeostasis and a core component of adaptive responses to excess cellular cholesterol. Copyright © 2017. Published by Elsevier Inc.

  10. A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell

    PubMed Central

    Clay, Lori; Caudron, Fabrice; Denoth-Lippuner, Annina; Boettcher, Barbara; Buvelot Frei, Stéphanie; Snapp, Erik Lee; Barral, Yves

    2014-01-01

    In many cell types, lateral diffusion barriers compartmentalize the plasma membrane and, at least in budding yeast, the endoplasmic reticulum (ER). However, the molecular nature of these barriers, their mode of action and their cellular functions are unclear. Here, we show that misfolded proteins of the ER remain confined into the mother compartment of budding yeast cells. Confinement required the formation of a lateral diffusion barrier in the form of a distinct domain of the ER-membrane at the bud neck, in a septin-, Bud1 GTPase- and sphingolipid-dependent manner. The sphingolipids, but not Bud1, also contributed to barrier formation in the outer membrane of the dividing nucleus. Barrier-dependent confinement of ER stress into the mother cell promoted aging. Together, our data clarify the physical nature of lateral diffusion barriers in the ER and establish the role of such barriers in the asymmetric segregation of proteotoxic misfolded proteins during cell division and aging. DOI: http://dx.doi.org/10.7554/eLife.01883.001 PMID:24843009

  11. Performance of the BG1Luc ER TA method in a qHTS format.

    PubMed

    Ceger, Patricia; Allen, David; Huang, Ruili; Xia, Menghang; Casey, Warren

    2015-01-01

    In 2012, the BG1Luc4E2 estrogen receptor (ER) transactivation (TA) method (BG1Luc ER TA) was accepted by U.S. regulatory agencies and the Organisation for Economic Co-operation and Development to detect substances with ER agonist activity. The method is now part of the Tier 1 testing battery in the Environmental Protection Agency's Endocrine Disruptor Screening Program. The BG1Luc ER TA method uses the BG1 ovarian cell line that endogenously expresses full-length ER (α and β) and is stably transfected with a plasmid containing four estrogen responsive elements upstream of a luciferase reporter gene. To allow increased throughput and testing efficiency, the BG1Luc ER TA ("BG1 manual") method was adapted for quantitative high-throughput screening (BG1 qHTS) in the U.S. Tox21 testing program. The BG1 qHTS test method was used to test approximately 10,000 chemicals three times each, and concentration-response data (n=15) were analyzed to evaluate test method performance. The balanced accuracy of the BG1 qHTS test method (97% [32/33]) was determined by comparing results to ER TA performance standards for the BG1 manual method. Concordance between the BG1 manual and qHTS methods was 92% (57/62) when calculated for a larger set of non-reference chemicals tested in both methods. These data demonstrate that the performance of the BG1 qHTS is similar to the currently accepted BG1 manual method, thereby establishing the utility of the BG1 qHTS method for identifying ER active environmental chemicals.

  12. Energy transfer upconversion in Er3+-Tm3+ codoped sodium silicate glass

    NASA Astrophysics Data System (ADS)

    Kumar, Vinod; Pandey, Anurag; Ntwaeaborwa, O. M.; Swart, H. C.

    2018-04-01

    Er3+/Tm3+ doped and codoped Na2O-SiO2-ZnO (NSZO) glasses were prepared by the conventional melt-quenching method. The amorphous nature of the prepared glasses was confirmed by the X-ray diffraction analysis. The optical absorption spectrum displayed several peaks, which correspond to Er3+ and Tm3+ dopant ions embedded into the NSZO glass. Both dopants experienced upconversion emission under 980 nm excitation. Efficient energy transfer from Er3+ to Tm3+ was observed in the co-doped samples to enhance the near infrared emission of the Tm3+ ions.

  13. Evidence that endoplasmic reticulum (ER) stress and caspase-4 activation occur in human neutrophils

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

    Binet, Francois; Chiasson, Sonia; Girard, Denis, E-mail: denis.girard@iaf.inrs.ca

    2010-01-01

    Apoptosis can result from activation of three major pathways: the extrinsic, the intrinsic, and the most recently identified endoplasmic reticulum (ER) stress-mediated pathway. While the two former pathways are known to be operational in human polymorphonuclear neutrophils (PMNs), the existence of the ER stress-mediated pathway, generally involving caspase-4, has never been reported in these cells. Recently, we have documented that arsenic trioxide (ATO) induced apoptosis in human PMNs by a mechanism that needs to be further investigated. In this study, using immunofluorescence and electron microscopy, we present evidence of ER alterations in PMNs activated by the ER stress inducer arsenicmore » trioxide (ATO). Several key players of the unfolded protein response, including GRP78, GADD153, ATF6, XBP1 and eIF2{alpha} are expressed and activated in PMNs treated with ATO or other ER stress inducers. Although caspase-4 is expressed and activated in neutrophils, treatment with a caspase-4 inhibitor did not attenuate the pro-apoptotic effect of ATO at a concentration that reverses caspase-4 processing and activation. Our results demonstrate for the first time that the ER stress-mediated apoptotic pathway operates in human neutrophils.« less

  14. Platinum assisted vapor-liquid-solid growth of er-si nanowires and their optical properties.

    PubMed

    Kim, Myoung-Ha; Kim, Il-Soo; Park, Yong-Hee; Park, Tae-Eon; Shin, Jung H; Choi, Heon-Jin

    2009-11-14

    We report the optical activation of erbium coated silicon nanowires (Er-SiNWs) grown with the assist of platinum (Pt) and gold (Au), respectively. The NWs were grown on Si substrates by using a chemical vapor transport process using SiCl4 and ErCl4 as precursors. Pt as well as Au worked successfully as vapor-liquid-solid (VLS) catalysts for growing SiNWs with diameters of ~100 nm and length of several micrometers, respectively. The SiNWs have core-shell structures where the Er-crystalline layer is sandwiched between silica layers. Photoluminescence spectra analyses showed the optical activity of SiNWs from both Pt and Au. A stronger Er3+ luminescence of 1,534 nm was observed from the SiNWs with Pt at room- and low-temperature (25 K) using the 488- and/or 477-nm line of an Ar laser that may be due to the uniform incorporation of more Er ions into NWs with the exclusion of the formation of catalyst-induced deep levels in the band-gap. Pt would be used as a VLS catalyst for high performance optically active Er-SiNWs.

  15. Platinum Assisted Vapor-Liquid-Solid Growth of Er-Si Nanowires and Their Optical Properties

    NASA Astrophysics Data System (ADS)

    Kim, Myoung-Ha; Kim, Il-Soo; Park, Yong-Hee; Park, Tae-Eon; Shin, Jung H.; Choi, Heon-Jin

    2010-02-01

    We report the optical activation of erbium coated silicon nanowires (Er-SiNWs) grown with the assist of platinum (Pt) and gold (Au), respectively. The NWs were grown on Si substrates by using a chemical vapor transport process using SiCl4 and ErCl4 as precursors. Pt as well as Au worked successfully as vapor-liquid-solid (VLS) catalysts for growing SiNWs with diameters of ~100 nm and length of several micrometers, respectively. The SiNWs have core-shell structures where the Er-crystalline layer is sandwiched between silica layers. Photoluminescence spectra analyses showed the optical activity of SiNWs from both Pt and Au. A stronger Er3+ luminescence of 1,534 nm was observed from the SiNWs with Pt at room- and low-temperature (25 K) using the 488- and/or 477-nm line of an Ar laser that may be due to the uniform incorporation of more Er ions into NWs with the exclusion of the formation of catalyst-induced deep levels in the band-gap. Pt would be used as a VLS catalyst for high performance optically active Er-SiNWs.

  16. Retention of Chs2p in the ER requires N-terminal CDK1-phosphorylation sites.

    PubMed

    Teh, Ee Mei; Chai, Chuan Chung; Yeong, Foong May

    2009-09-15

    In budding yeast, the secretory pathway is constitutively transporting cargoes such as invertase and alpha-factor throughout the cell division cycle. However, chitin synthase 2 (Chs2p), another cargo of the secretory pathway, is retained at the endoplasmic reticulum (ER) during mitosis when the mitotic kinase activity is high. Chs2p is exported from the ER to the mother-daughter neck only upon mitotic kinase destruction, indicating that the mitotic kinase activity is critical for the ER retention of Chs2p. However, a key question is whether the mitotic kinase acts directly upon Chs2p to prevent its ER export. We report here that mutation of Ser residues to Glu at 4 perfect CDK1-phosphorylation sites at the N-terminus of Chs2p leads to its retention in the ER when the mitotic kinase activity is absent. Conversely, Ser-to-Ala mutations result in the loss of Chs2p ER retention even when mitotic kinase activity is high. The mere overexpression of the non-destructible form of the mitotic cyclin in G(1) cells can confine the wild-type Chs2p but not the Ser-to-Ala mutant in the ER. Furthermore, overexpression of the Ser-to-Ala mutant kills cells. Time-lapsed imaging revealed that Chs2p is exported from the ER rapidly and synchronously to the Golgi upon metaphase release. Our data indicate that direct phosphorylation of Chs2p by the mitotic CDK1 helps restrain it in the ER during mitosis to prevent its rapid export in an untimely manner until after sister chromatid occurs and mitotic exit executed.

  17. TANGO1 assembles into rings around COPII coats at ER exit sites

    PubMed Central

    Pirozzi, Marinella; Zhang, Chong; Melville, David; Parashuraman, Seetharaman; Zimmermann, Timo

    2017-01-01

    TANGO1 (transport and Golgi organization 1) interacts with CTAGE5 and COPII components Sec23/Sec24 and recruits ERGIC-53 (endoplasmic reticulum [ER]–Golgi intermediate compartment 53)–containing membranes to generate a mega-transport carrier for export of collagens and apolipoproteins from the ER. We now show that TANGO1, at the ER, assembles in a ring that encircles COPII components. The C-terminal, proline-rich domains of TANGO1 molecules in the ring are initially tilted onto COPII coats but appear to be pushed apart as the carrier grows. These findings lend support to our suggestion that growth of transport carriers for exporting bulky cargoes requires addition of membranes and not simply COPII-mediated accretion of a larger surface of ER. TANGO1 remains at the neck of the newly forming transport carrier, which grows in size by addition of ERGIC-53–containing membranes to generate a transport intermediate for the export of bulky collagens. PMID:28280121

  18. Structural and photoluminescence properties of Ce, Dy, Er-doped ZnO nanoparticles

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

    Jayachandraiah, C.; Kumar, K. Siva; Krishnaiah, G., E-mail: ginnerik@gmail.com

    2015-06-24

    Undoped ZnO and rare earth elements (Ce, Dy and Er with 2 at. %) doped nanoparticles were synthesized by wet chemical co-precipitation method at 90°C with Polyvinylpyrrolidone (PVP) as capping agent. The structural, morphological, compositional and photoluminescence studies were performed with X-ray diffraction (XRD), Transmission electron microscopy (TEM), Energy dispersive spectroscopy (EDS), FTIR spectroscopy and Photoluminescence (PL) respectively. XRD results revealed hexagonal wurtzite structure with average particle size around 18 nm - 14 nm and are compatible with TEM results. EDS confirm the incorporation of Ce, Dy and Er elements into the host ZnO matrix and is validated by FTIR analysis. PLmore » studies showed a broad intensive emission peak at 558 nm in all the samples. The intensity for Er- doped ZnO found maximum with additional Er shoulder peaks at 516nm and 538 nm. No Ce, Dy emission centers were found in spectra.« less

  19. ER fluid applications to vibration control devices and an adaptive neural-net controller

    NASA Astrophysics Data System (ADS)

    Morishita, Shin; Ura, Tamaki

    1993-07-01

    Four applications of electrorheological (ER) fluid to vibration control actuators and an adaptive neural-net control system suitable for the controller of ER actuators are described: a shock absorber system for automobiles, a squeeze film damper bearing for rotational machines, a dynamic damper for multidegree-of-freedom structures, and a vibration isolator. An adaptive neural-net control system composed of a forward model network for structural identification and a controller network is introduced for the control system of these ER actuators. As an example study of intelligent vibration control systems, an experiment was performed in which the ER dynamic damper was attached to a beam structure and controlled by the present neural-net controller so that the vibration in several modes of the beam was reduced with a single dynamic damper.

  20. Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription.

    PubMed

    Marza, Esther; Taouji, Saïd; Barroso, Kim; Raymond, Anne-Aurélie; Guignard, Léo; Bonneu, Marc; Pallares-Lupon, Néstor; Dupuy, Jean-William; Fernandez-Zapico, Martin E; Rosenbaum, Jean; Palladino, Francesca; Dupuy, Denis; Chevet, Eric

    2015-03-01

    The accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPR(ER)) to restore ER homeostasis. The AAA(+) ATPase p97/CDC-48 plays key roles in ER stress by promoting both ER protein degradation and transcription of UPR(ER) genes. Although the mechanisms associated with protein degradation are now well established, the molecular events involved in the regulation of gene transcription by p97/CDC-48 remain unclear. Using a reporter-based genome-wide RNAi screen in combination with quantitative proteomic analysis in Caenorhabditis elegans, we have identified RUVB-2, a AAA(+) ATPase, as a novel repressor of a subset of UPR(ER) genes. We show that degradation of RUVB-2 by CDC-48 enhances expression of ER stress response genes through an XBP1-dependent mechanism. The functional interplay between CDC-48 and RUVB-2 in controlling transcription of select UPR(ER) genes appears conserved in human cells. Together, these results describe a novel role for p97/CDC-48, whereby its role in protein degradation is integrated with its role in regulating expression of ER stress response genes. © 2015 The Authors.

  1. Sensitizing properties of luminescence centers on the emission of Er3+ in Si-rich SiO2 film

    NASA Astrophysics Data System (ADS)

    Fu, Qianyu; Gao, Yuhan; Li, Dongsheng; Yang, Deren

    2016-05-01

    In this paper, we report on the luminescence-center (LC)-mediated excitation of Er3+ as a function of annealing temperature in Er-doped Si-rich SiO2 (SRO) films fabricated by electron beam evaporation. It is found that the annealing temperature has significant effects on the emission of Er3+ and the specific optical-active point-defects called LCs within Er-doped SRO films. Different luminescence centers generated by the evolution of microstructures during annealing process act as efficient sensitizers for Er3+ in the films when the annealing temperature is below 1100 °C. Moreover, the temperature dependence of the energy coupling between LCs and Er3+ demonstrates the effective phonon-mediated energy transfer process. In addition, when the annealing temperature reaches 1100 °C, the decreased density of activable erbium ions induced by the aggregation of Er will bring detrimental effects on the emission of Er3+. It is demonstrated that an appropriate annealing process can be designed to achieve efficiently enhanced emissions from Er3+ ions by optimizing the density of LCs and the coupling between Er3+ and LCs.

  2. Functional analysis of CYP6ER1, a P450 gene associated with imidacloprid resistance in Nilaparvata lugens.

    PubMed

    Pang, Rui; Chen, Meng; Liang, Zhikun; Yue, Xiangzhao; Ge, Hu; Zhang, Wenqing

    2016-10-10

    The cytochrome P450 CYP6ER1 has been reported to play an important role in imidacloprid resistance of the brown planthopper (BPH), Nilaparvata lugens, and is overexpressed in most resistant populations. In the present study, we confirmed that CYP6ER1 expression can be induced by certain levels of imidacloprid. Developmental expression analysis revealed that CYP6ER1 was expressed highly in the adult stage, and tissue distribution analysis showed that CYP6ER1 was expressed mainly in the fat body and midgut. RNA interference (RNAi) of CYP6ER1 and transgenic expression of CYP6ER1 in Drosophila melanogaster both suggested that the expression of CYP6ER1 is sufficient to confer imidacloprid resistance. Furthermore, we analyzed the interaction of imidacloprid and CYP6ER1 monooxygenase by using dynamic simulations and molecular docking. We found that Nitrogen atoms in the heterocycle of the imidacloprid molecule may bind to iron atoms in the center of the homology model of CYP6ER1 via 4,5-dihedro-1H-imidazole. This finding contributes to a better understanding of how CYP6ER1 takes part in the insecticide metabolism.

  3. Calibration of the ER-2 meteorological measurement system

    NASA Technical Reports Server (NTRS)

    Bowen, Stuart W.; Chan, K. Roland; Bui, T. Paul

    1991-01-01

    The Meteorological Measurement System (MMS) on the high altitude ER-2 aircraft was developed specifically for atmospheric research. The MMS provides accurate measurements of pressure, temperature, wind vector, position (longitude, latitude, altitude), pitch, roll, heading, angle of attack, angle of sideslip, true airspeed, aircraft eastward velocity, northward velocity, vertical acceleration, and time, at a sample rate of 5/s. MMS data products are presented in the form of either 5 or 1 Hz time series. The 1 Hz data stream, generally used by ER-2 investigators, is obtained from the 5 Hz data stream by filtering and desampling. The method of measurement of the meteorological parameters is given and the results of their analyses are discussed.

  4. WatER: The proposed Water Elevation Recovery satellite mission

    NASA Astrophysics Data System (ADS)

    Alsdorf, D.; Mognard, N.; Rodriguez, E.; Participants, W.

    2005-12-01

    Surface fresh water is essential for life, yet we have surprisingly poor knowledge of the spatial and temporal dynamics of surface water storage and discharge globally. The core mission objective is to describe and understand the continental water cycle and the hydrological processes (e.g., floodplain hydraulics) at work in a river basin. The key question that will be answered by WatER is: "Where is water stored on Earth's land surfaces, and how does this storage vary in space and time?" WatER will facilitate societal needs by (1) improving our understanding of flood hazards; (2) freely providing water volume information to countries who critically rely on rivers that cross political borders; and (3) mapping the variations in water bodies that contribute to disease vectors (e.g., malaria). Conventional altimeter profiles are, without question, incapable of supplying the measurements needed to address scientific and societal questions. WatER will repeatedly measure the spatially distributed water surface elevations (h) of wetlands, rivers, lakes, reservoirs, etc. Successive h measurements yield dh/dt, (t is time), hence a volumetric change in water stored or lost. Individual images of h yield dh/dx (x is distance), hence surface water slope, which is necessary for estimating streamflow. WatER's main instrument is a Ka-band radar interferometer (KaRIN) which is the only technology capable of supplying the required imaging capability of h. KaRIN has a rich heritage based on (1) the many highly successful ocean observing radar altimeters, (2) the Shuttle Radar Topography Mission (SRTM), and (3) the development effort of the Wide Swath Ocean Altimeter (WSOA). The interferometric altimeter is a near-nadir viewing, 120 km wideswath based instrument that uses interferometric SAR processing of the returned pulses to yield single-look 5m azimuth and 10m to 70m range resolution, with an elevation accuracy of approximately 50 cm. Polynomial based averaging of heights along the

  5. ER-stress and apoptosis: molecular mechanisms and potential relevance in infection.

    PubMed

    Häcker, Georg

    2014-10-01

    During ER-stress, one of the responses a cell can choose is apoptosis. Apoptosis generally is a cell's preferred response when other control mechanisms are overwhelmed. We now have a reasonably clear molecular picture what is happening once the apoptotic apparatus has been started. Unclear however are the majority of the upstream pathways that connect other signalling to apoptosis. During ER-stress, confirmed apoptosis-regulating targets are pro- and anti-apoptotic proteins of the Bcl-2-family, whose concerted action induces apoptosis. I will here discuss how mitochondrial apoptosis is triggered, how this is linked to the ER-stress response and in what way this may be relevant during microbial infections. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  6. [Preparation, characterization and upconversion fluorescence of NaYF4 : Yb, Er /graphene oxide nanocomposites].

    PubMed

    Ji, Tian-Hao; Qie, Nan; Wang, Ji-Mei; Hua, Yong-Yong; Ji, Zhi-Jiang

    2013-03-01

    NaYF4 : Yb, Er/rGO and SiO2-coated NaYF4 : Yb, Er/rGO nanocomposites can be prepared through "one-pot" and directly mixing preparation routes. Various measurement results show that the NaYF4 : Yb, Er in the nanocomposites exhibits a cubic a-type structure and nanoparticle-like morphology with a diameter range of 30-70 nm; the rGO layers are well-dispersed in the nanocomposites, and whereas the rGO obtained from "one-pot" preparation renders relatively better dispersion. Raman spectra demonstrate that there exists a surface coupling action between the two kinds of nanomaterials, and with the increase in the relative rGO content, such action becomes stronger. UC fluorescence measurement results reveal that the rGO has significantly quenching effect and optical-limiting performance on the UC fluorescence, particularly on the red-emission of the NaYFa : Yb, Er or SiO2-coated NaYF4 : Yb, Er nanoparticles. The red-emission intensity gradually decreases with an increase in the rGO content, but the green-emission shows less change. It should be stressed that, in comparison with NaYF4 : Yb, Er/rGO, with a similar rGO content, the red-emission intensity of SiO2-coated NaYF4 : Yb, Er/rGO decreases much obviously due to a stronger light-absorption caused by part rGO aggregation.

  7. The effects of energy transfer on the Er{sup 3+} 1.54 {mu}m luminescence in nanostructured Y{sub 2}O{sub 3} thin films with heterogeneously distributed Yb{sup 3+} and Er{sup 3+} codopants

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

    Hoang, J.; Chang, J. P.; Schwartz, Robert N.

    2012-09-15

    We report the effects of heterogeneous Yb{sup 3+} and Er{sup 3+} codoping in Y{sub 2}O{sub 3} thin films on the 1535 nm luminescence. Yb{sup 3+}:Er{sup 3+}:Y{sub 2}O{sub 3} thin films were deposited using sequential radical enhanced atomic layer deposition. The Yb{sup 3+} energy transfer was investigated for indirect and direct excitation of the Yb {sup 2}F{sub 7/2} state using 488 nm and 976 nm sources, respectively, and the trends were described in terms of Forster and Dexter's resonant energy transfer theory and a macroscopic rate equation formalism. The addition of 11 at. % Yb resulted in an increase in themore » effective Er{sup 3+} photoluminescence (PL) yield at 1535 nm by a factor of 14 and 42 under 488 nm and 976 nm excitations, respectively. As the Er{sub 2}O{sub 3} local thickness was increased to greater than 1.1 A, PL quenching occurred due to strong local Er{sup 3+}{r_reversible} Er{sup 3+} excitation migration leading to impurity quenching centers. In contrast, an increase in the local Yb{sub 2}O{sub 3} thickness generally resulted in an increase in the effective Er{sup 3+} PL yield, except when the Er{sub 2}O{sub 3} and Yb{sub 2}O{sub 3} layers were separated by more than 2.3 A or were adjacent, where weak Yb{sup 3+}{r_reversible} Er{sup 3+} coupling or strong Yb{sup 3+}{r_reversible} Yb{sup 3+} interlayer migration occurred, respectively. Finally, it is suggested that enhanced luminescence at steady state was observed under 488 nm excitation as a result of Er{sup 3+}{yields} Yb{sup 3+} energy back transfer coupled with strong Yb{sup 3+}{r_reversible} Yb{sup 3+} energy migration.« less

  8. The Role of ER Bodies in Brassicaceae Resistance under Clinorotation

    NASA Astrophysics Data System (ADS)

    Romanchuk, S. M.; Kordyum, E. L.

    2013-02-01

    Results of the electron-microscopic investigation of root apices of Arabidopsis thaliana 3- and 7-day old seedlings grown in the stationary conditions and under clinorotation are presented. It was shown the similarity in the root apex cell ultrastructure in control and under clinorotation. In the same time there were some differences in the ultrustructure of statocytes and the distal elongation zone under clinorotation. For the first time, the sensitivity of ER-bodies, which are derivative of granular endoplasmic reticulum and contain a β-glucosidase enzyme, to the influence of simulated microgravity that was demonstrated by increasing quantity and area of ER-bodies per cell section, as well as by higher variability of their shape under clinorotation. A degree of these changes correlated with the duration of clinorotation. On the basis of obtained data, a protective role of ER-bodies in adaptation of plants to microgravity is discussed.

  9. Precise satellite orbit determination with particular application to ERS-1

    NASA Astrophysics Data System (ADS)

    Fernandes, Maria Joana Afonso Pereira

    The motivation behind this study is twofold. First to assess the accuracy of ERS-1 long arc ephemerides using state of the art models. Second, to develop improved methods for determining precise ERS-1 orbits using either short or long arc techniques. The SATAN programs, for the computation of satellite orbits using laser data were used. Several facilities were added to the original programs: the processing of PRARE range and altimeter data, and a number of algorithms that allow more flexible solutions by adjusting a number of additional parameters. The first part of this study, before the launch of ERS-1, was done with SEAS AT data. The accuracy of SEASAT orbits computed with PRARE simulated data has been determined. The effect of temporal distribution of tracking data along the arc and the extent to which altimetry can replace range data have been investigated. The second part starts with the computation of ERS-1 long arc solutions using laser data. Some aspects of modelling the two main forces affecting ERS-l's orbit are investigated. With regard to the gravitational forces, the adjustment of a set of geopotential coefficients has been considered. With respect to atmospheric drag, extensive research has been carried out on determining the influence on orbit accuracy of the measurements of solar fluxes (P10.7 indices) and geomagnetic activity (Kp indices) used by the atmospheric model in the computation of atmospheric density at satellite height. Two new short arc methods have been developed: the Constrained and the Bayesian method. Both methods are dynamic and consist of solving for the 6 osculating elements. Using different techniques, both methods overcome the problem of normal matrix ill- conditioning by constraining the solution. The accuracy and applicability of these methods are discussed and compared with the traditional non-dynamic TAR method.

  10. High-fidelity Glucagon-CreER mouse line generated by CRISPR-Cas9 assisted gene targeting.

    PubMed

    Ackermann, Amanda M; Zhang, Jia; Heller, Aryel; Briker, Anna; Kaestner, Klaus H

    2017-03-01

    α-cells are the second most prominent cell type in pancreatic islets and are responsible for producing glucagon to increase plasma glucose levels in times of fasting. α-cell dysfunction and inappropriate glucagon secretion occur in both type 1 and type 2 diabetes. Thus, there is growing interest in studying both normal function and pathophysiology of α-cells. However, tools to target gene ablation or activation specifically of α-cells have been limited, compared to those available for β-cells. Previous Glucagon-Cre and Glucagon-CreER transgenic mouse lines have suffered from transgene silencing, and the only available Glucagon-CreER "knock-in" mouse line results in glucagon haploinsufficiency, which can confound the interpretation of gene deletion analyses. Therefore, we sought to develop a Glucagon-CreER T2 mouse line that would maintain normal glucagon expression and would be less susceptible to transgene silencing. We utilized CRISPR-Cas9 technology to insert an IRES-CreER T2 sequence into the 3' UTR of the Glucagon ( Gcg ) locus in mouse embryonic stem cells (ESCs). Targeted ESC clones were then injected into mouse blastocysts to obtain Gcg-CreER T2 mice. Recombination efficiency in GCG + pancreatic α-cells and glucagon-like peptide 1 positive (GLP1 + ) enteroendocrine L-cells was measured in Gcg-CreER T2 ; Rosa26-LSL-YFP mice injected with tamoxifen during fetal development and adulthood. Tamoxifen injection of Gcg-CreER T2 ; Rosa26-LSL-YFP mice induced high recombination efficiency of the Rosa26-LSL-YFP locus in perinatal and adult α-cells (88% and 95%, respectively), as well as in first-wave fetal α-cells (36%) and adult enteroendocrine L-cells (33%). Mice homozygous for the Gcg-CreER T2 allele were phenotypically normal. We successfully derived a Gcg-CreER T2 mouse line that expresses CreER T2 in pancreatic α-cells and enteroendocrine L-cells without disrupting preproglucagon gene expression. These mice will be a useful tool for performing

  11. Development of low-cost open source 3D gel printer "RepRap SWIM-ER"

    NASA Astrophysics Data System (ADS)

    Sato, Kei; Basher, Samiul; Ota, Takafumi; Tase, Taishi; Takamatsu, Kyuichiro; Saito, Azusa; Khosla, Ajit; Kawakami, Masaru; Furuawa, Hidemitsu

    2017-04-01

    Gels are soft and wet materials having low friction, good biocompatibility, and material permeability. It is expected that gel materials will be used as new kinds of industrial materials in the engineering and medical applications. But it cannot build a complicated shape. Soft & Wet Matter Engineering Laboratory developed a 3D gel Printer "SWIM-ER", has enabled modeling of complex shapes of the gel. However, this is expensive. Therefore not all of the gel researchers and the companies have such a device. To solve this problem, we manufacture a low-cost open-source 3D gel printer "RepRap SWIM-ER" from the RepRap. We made the components required to manufacture the "RepRap SWIM-ER" from the 3D printer and chose a light source. In addition, we produced the P-DN gel for RepRap SWIM-ER and conducted the molding test to confirm whether RepRap SWIM-ER can used it.

  12. Fabrication and Sintering Behavior of Er:SrF₂ Transparent Ceramics using Chemically Derived Powder.

    PubMed

    Liu, Jun; Liu, Peng; Wang, Jun; Xu, Xiaodong; Li, Dongzhen; Zhang, Jian; Nie, Xinming

    2018-03-22

    In this paper, we report the fabrication of high-quality 5 at. % Er 3+ ions doped SrF₂ transparent ceramics, the potential candidate materials for a mid-infrared laser-gain medium by hot-pressing at 700 °C for 40 h using a chemically-derived powder. The phase structure, densification, and microstructure evolution of the Er:SrF₂ ceramics were systematically investigated. In addition, the grain growth kinetic mechanism of Er:SrF₂ was clarified. The results showed lattice diffusion to be the grain growth mechanism in the Er:SrF₂ transparent ceramic of which highest in-line transmittance reached 92% at 2000 nm, i.e., very close to the theoretical transmittance value of SrF₂ single crystal. Furthermore, the emission spectra showed that the strongest emission band was located at 2735 nm. This means that it is possible to achieve a laser output of approximately 2.7 μm in the 5 at. % Er 3+ ions doped SrF₂ transparent ceramics.

  13. WWOX sensitises ovarian cancer cells to paclitaxel via modulation of the ER stress response.

    PubMed

    Janczar, Szymon; Nautiyal, Jaya; Xiao, Yi; Curry, Edward; Sun, Mingjun; Zanini, Elisa; Paige, Adam Jw; Gabra, Hani

    2017-07-27

    There are clear gaps in our understanding of genes and pathways through which cancer cells facilitate survival strategies as they become chemoresistant. Paclitaxel is used in the treatment of many cancers, but development of drug resistance is common. Along with being an antimitotic agent paclitaxel also activates endoplasmic reticulum (ER) stress. Here, we examine the role of WWOX (WW domain containing oxidoreductase), a gene frequently lost in several cancers, in mediating paclitaxel response. We examine the ER stress-mediated apoptotic response to paclitaxel in WWOX-transfected epithelial ovarian cancer (EOC) cells and following siRNA knockdown of WWOX. We show that WWOX-induced apoptosis following exposure of EOC cells to paclitaxel is related to ER stress and independent of the antimitotic action of taxanes. The apoptotic response to ER stress induced by WWOX re-expression could be reversed by WWOX siRNA in EOC cells. We report that paclitaxel treatment activates both the IRE-1 and PERK kinases and that the increase in paclitaxel-mediated cell death through WWOX is dependent on active ER stress pathway. Log-rank analysis of overall survival (OS) and progression-free survival (PFS) in two prominent EOC microarray data sets (Tothill and The Cancer Genome Atlas), encompassing ~800 patients in total, confirmed clinical relevance to our findings. High WWOX mRNA expression predicted longer OS and PFS in patients treated with paclitaxel, but not in patients who were treated with only cisplatin. The association of WWOX and survival was dependent on the expression level of glucose-related protein 78 (GRP78), a key ER stress marker in paclitaxel-treated patients. We conclude that WWOX sensitises EOC to paclitaxel via ER stress-induced apoptosis, and predicts clinical outcome in patients. Thus, ER stress response mechanisms could be targeted to overcome chemoresistance in cancer.

  14. Enhancement in magnetocaloric properties of ErCrO3 via A-site Gd substitution

    NASA Astrophysics Data System (ADS)

    Shi, Jianhang; Yin, Shiqi; Seehra, Mohindar S.; Jain, Menka

    2018-05-01

    Rare earth chromites (RCrO3) continue to be of considerable interest due to their intriguing physical properties such as spin-reorientation, multiferroicity, and magnetocaloric effect. In this paper, we compare the structural, magnetic, and magnetocaloric properties of bulk ErCrO3 with those of bulk Er0.33Gd0.67CrO3, the latter obtained by Gd substitution at the A-site (Er-site) and report substantial enhancement in the magnetocaloric response by Gd substitution. The samples prepared by the citrate route were structurally characterized at room temperature using x-ray diffraction (XRD), Raman spectroscopy, and scanning electron microscopy. The XRD measurements refined by Rietveld analysis indicate that both samples crystallized in the orthorhombically distorted perovskite structure with Pbnm space group. Magnetic measurements on both samples were carried out between 5 K and 300 K in magnetic fields up to 7 T and show that TNC r (where Cr3+ orders) for Er0.33Gd0.67CrO3 is enhanced to 155 K vs. 133 K for ErCrO3 with analogous changes in the other magnetic parameters. Isothermal magnetization M vs. H data at different temperatures were used to determine changes in the magnetic entropy ( -ΔS ) and relative cooling power (RCP) for the two samples showing considerable improvement with Gd substitution in bulk ErCrO3. The maximum value of -ΔS for Er0.33Gd0.67CrO3 is 27.6 J kg-1 K-1 at 5 K and 7 T with a RCP of 531.1 J kg-1, in comparison to maximum -ΔS = 10.7 J kg-1 K-1 at 15 K with an RCP of 416.4 J kg-1 for ErCrO3 at 7 T.

  15. Comparison of diode laser and Er:YAG lasers in the treatment of ankyloglossia.

    PubMed

    Aras, Mutan Hamdi; Göregen, Mustafa; Güngörmüş, Metin; Akgül, Hayati Murat

    2010-04-01

    The purpose of this study was to compare the tolerance of lingual frenectomy with regard to a local anesthesia requirement and comparison of postsurgical discomfort experienced by patients operated on with both diode and erbium:yttrium-aluminium-garnet (Er:YAG) lasers. Ankyloglossia, commonly known as tongue-tie, is a congenital oral anomaly characterized by a short lingual frenulum. A short lingual frenulum may contribute to feeding, speech, and mechanical tongue problems. Sixteen referred patients with tongue mobility complaints were included in this study. A GaAlAs laser device with a continuous wavelength of 808 nm was used in the diode group. Frenulums were incised by applying 2 W of laser power. The Er:YAG laser device with a continuous wavelength of 2940 nm was used in the Er:YAG group. Frenulums were incised by applying 1 W of laser power. The acceptability of the lingual frenectomy without local anesthesia and the degree of the postsurgical discomfort were evaluated. Although the majority of patients (six) could be operated on without local anesthesia in the Er:YAG group, all patients could not be operated on without local anesthetic agent in the diode group. There were no differences between the two groups with regard to pain, chewing, and speaking on the first or seventh day after surgery, whereas patients had more pain in the Er:YAG group than in the diode group the first 3 h after surgery. The results indicate that only the Er:YAG laser can be used for lingual frenectomy without local anesthesia, and there was no difference between the two groups regarding the degree of the postsurgical discomfort except in the first 3 h. In conclusion, these results indicate that the Er:YAG laser is more advantageous than the diode laser in minor soft-tissue surgery because it can be performed without local anesthesia and with only topical anesthesia.

  16. Particle-induced SIRT1 downregulation promotes osteoclastogenesis and osteolysis through ER stress regulation.

    PubMed

    Zhang, Liang; Bao, Dongmei; Li, Peng; Lu, Zhidong; Pang, Long; Chen, Zhirong; Guo, Haohui; Gao, Zhihui; Jin, Qunhua

    2018-08-01

    Sirtuin 1 (SIRT1) downregulation has been found to be induced by wear particles in aseptic prosthesis loosening (APL). Osteoclastogenesis and osteoclast activation are the main pathological factors associated with APL. However, whether SIRT1 downregulation contributes to the formation and activation of osteoclasts through the induction of endoplasmic reticulum (ER) stress is unclear. To address this, an osteolysis mouse model was used in which animals were treated with the SIRT1 activator, resveratrol (RES), or an ER stress inhibitor, 4-PBA, for two weeks. Osteolysis, osteoclastogenesis, and morphologic alteration of calvariae were observed by toluidine blue, TRAP, and H&E staining. SIRT1 expression and ER stress were evaluated by western blot analysis. In vitro, mouse macrophage RAW 264.7 cells were treated with polyethylene (PE) particles alone or combined with either RES or 4-PBA, and SIRT1 expression and ER stress were measured using western blot assays. Osteoclast differentiation was determined through TRAP staining. Osteoclast activation was evaluated by culturing osteoclast cells on bone slices followed by toluidine blue staining. Mechanistically, osteoclastogenesis-related MAPK activation, NFATc1 and c-Fos expression, and NF-κB translocation were determined. Both in vivo and in vitro experimental results indicated that PE particles induced SIRT1 downregulation and enhanced ER stress. SIRT1 activator RES and ER stress inhibitor 4-PBA significantly suppressed PE particle-induced osteoclast differentiation and osteolysis. In vitro experimental results showed that 4-PBA suppressed PE particle-induced ERK1/2, p38, and JNK activation, NFATc1 and c-Fos upregulation, as well as NF-κB p65 nucleus translocation. PE particle-induced downregulation of SIRT1 enhances ER stress and promotes osteoclast proliferation and bone resorption through regulation of c-Fos, NFATc1, and the MAPK and NF-κB signaling pathways. Copyright © 2018 Elsevier Masson SAS. All rights

  17. Theoretical modeling of diode-laser-pumped 3-μm Er3+ crystal lasers

    NASA Astrophysics Data System (ADS)

    Tikerpae, Mark; Jackson, Stuart D.; King, Terence A.

    1997-05-01

    We present results from a theoretical model that has been developed to simulate the 3-micrometer laser transition in Er3+ doped Y3Al5O12 (YAG), Y2Sc2Ga3O12 (YSGG), LiYF4 (YLF) and BaY2F8 (BaYF) host crystals. The rate equations for the lowest seven energy levels of Er3+ were solved numerically and laser action was simulated under cw, gain-switched (pulse pumped) and Q-switched operation with optical pumping at wavelengths of 975 nm and 795 nm. The relative performance of each laser crystal was compared under identical pumping and cavity conditions to establish the optimum crystal host, doping concentration and pump wavelength for each mode of operation. Some unexpected saturation effects were investigated that could limit the maximum practical pump fluence used for high energy Q-switched systems. We investigate possible additional multi-ion energy transfer processes that may cause the decrease in efficiency that is observed experimentally at high Er3+ ion concentrations. In addition, lower laser level deactivation by co-doping with Pr3+ in BaYF was simulated and compared with singly doped Er:BaYF for a range of Er3+ and Pr3+ concentrations. It was found that co-doping was not as effective as the cooperative upconversion process present in singly doped Er3+ crystals for efficient laser operation.

  18. Functional analysis of CYP6ER1, a P450 gene associated with imidacloprid resistance in Nilaparvata lugens

    PubMed Central

    Pang, Rui; Chen, Meng; Liang, Zhikun; Yue, Xiangzhao; Ge, Hu; Zhang, Wenqing

    2016-01-01

    The cytochrome P450 CYP6ER1 has been reported to play an important role in imidacloprid resistance of the brown planthopper (BPH), Nilaparvata lugens, and is overexpressed in most resistant populations. In the present study, we confirmed that CYP6ER1 expression can be induced by certain levels of imidacloprid. Developmental expression analysis revealed that CYP6ER1 was expressed highly in the adult stage, and tissue distribution analysis showed that CYP6ER1 was expressed mainly in the fat body and midgut. RNA interference (RNAi) of CYP6ER1 and transgenic expression of CYP6ER1 in Drosophila melanogaster both suggested that the expression of CYP6ER1 is sufficient to confer imidacloprid resistance. Furthermore, we analyzed the interaction of imidacloprid and CYP6ER1 monooxygenase by using dynamic simulations and molecular docking. We found that Nitrogen atoms in the heterocycle of the imidacloprid molecule may bind to iron atoms in the center of the homology model of CYP6ER1 via 4,5-dihedro-1H-imidazole. This finding contributes to a better understanding of how CYP6ER1 takes part in the insecticide metabolism. PMID:27721443

  19. Synaptotagmin SYTA forms ER-plasma membrane junctions that are recruited to plasmodesmata for plant virus movement.

    PubMed

    Levy, Amit; Zheng, Judy Y; Lazarowitz, Sondra G

    2015-08-03

    Metazoan synaptotagmins are Ca(2+) sensors that regulate exocytosis and endocytosis in various cell types, notably in nerve and neuroendocrine cells [1, 2]. Recently, the structurally related extended synaptotagmins were shown to tether the cortical ER to the plasma membrane in human and yeast cells to maintain ER morphology and stabilize ER-plasma membrane (ER-PM) contact sites for intracellular lipid and Ca(2+) signaling [3, 4]. The Arabidopsis synaptotagmin SYTA regulates endocytosis and the ability of plant virus movement proteins (MPs) to alter plasmodesmata to promote virus cell-to-cell transport [5, 6]. Yet how MPs modify plasmodesmata, the cellular functions of SYTA and how these aid MP activity, and the proteins essential to form plant cell ER-PM contact sites remain unknown. We addressed these questions using an Arabidopsis SYTA knockdown line syta-1 and a Tobamovirus movement protein MP(TVCV) [5, 7]. We report here that SYTA localized to ER-PM contact sites. These sites were depleted and the ER network collapsed in syta-1, and both reformed upon rescue with SYTA. MP(TVCV) accumulation in plasmodesmata, but not secretory trafficking, was also inhibited in syta-1. During infection, MP(TVCV) recruited SYTA to plasmodesmata, and SYTA and the cortical ER were subsequently remodeled to form viral replication sites adjacent to plasmodesmata in which MP(TVCV) and SYTA directly interacted caged within ER membrane. SYTA also accumulated in plasmodesmata active in MP(TVCV) transport. Our findings show that SYTA is essential to form ER-PM contact sites and suggest that MPs interact with SYTA to recruit these sites to alter plasmodesmata for virus cell-to-cell movement. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Highly spatially resolved structural and optical investigation of Bi nanoparticles in Y-Er disilicate thin films

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

    Scarangella, A.; Dipartimento di Fisica e Astronomia, Università di Catania, Via S. Sofia 64, 95123 Catania; Amiard, G.

    2016-08-08

    Er-containing silicon compatible materials have been widely used as infrared emitters for microphotonics application. In this field, the additional introduction of a proper sensitizer permits to increase the Er excitation cross sections, thus increasing its optical efficiency. This work aims to investigate the influence of a post-transition metal, bismuth, on the optical properties of erbium-yttrium disilicate thin films synthesized by magnetron co-sputtering. After thermal treatments at 1000 °C in O{sub 2} or N{sub 2} environment, the presence of small precipitates, about 6 nm in diameter, was evidenced by transmission electron microscopy analyses. The spatially resolved chemical nature of the nanoparticles was discernedmore » in the Si and O rich environments by means of scanning transmission electron microscopy–energy dispersive X-ray and scanning transmission electron microscopy–electron energy loss spectroscopy analyses performed with nanometric resolution. In particular, metallic Bi nanoparticles were stabilized in the N{sub 2} environment, being strongly detrimental for the Er emission. A different scenario was instead observed in O{sub 2}, where the formation of Bi silicate nanoparticles was demonstrated with the support of photoluminescence excitation spectroscopy. In particular, a broad band peaked at 255 nm, correlated to the excitation band of Bi silicate nanoparticles, was identified in Er excitation spectrum. Thus Bi silicate clusters act as sensitizer for Er ions, permitting to improve Er emission up to 250 times with respect to the resonant condition. Moreover, the Er decay time increases in the presence of the Bi silicate nanoparticles that act as cages for Er ions. These last results permit to further increase Er optical efficiency in the infrared range, suggesting (Bi + Er)-Y disilicate as a good candidate for applications in microphotonics.« less

  1. Er:YAG delamination of immersed biological membranes using sealed flexible hollow waveguides

    NASA Astrophysics Data System (ADS)

    Sagi-Dolev, A. M.; Dror, Jacob; Inberg, Alexandra; Ferencz, J. R.; Croitoru, Nathan I.

    1996-04-01

    The radiation of Er-YAG laser ((lambda) equals 2.94 micrometer) gives selective interaction with tissues. The extinction in soft tissues is only a few micrometers and in hard tissues is of the order of hundreds of micrometers. This makes this type of laser very suitable for treatments in dentistry, orthopedy, or ophthalmology. Because the usual silica fibers are not transmitting the radiation at lambda equals 2.94 micrometer of this laser, many applications cannot be presently performed. Fused silica hollow fibers for Er-YAG radiation were developed in our laboratory and several possible applications in dentistry, orthopedy and ophthalmology were indicated. Hole opening and implantation preparation of teeth were experimented, using Er-YAG laser and hollow plastic waveguide delivery systems. Hole drilling in cow bones was demonstrated for applications in orthopedy. A new procedure of delivering Er-YAG radiation on fibrotic membranes of inner eggshell as a model of the membranes in eyes was developed employing silica hollow waveguides of 0.5 and 0.7 mm ID or a plastic waveguide of 1.0 mm ID. For this purpose waveguides with sealed distal tip were employed to enable us to approach the delivery system through liquid media near to the membrane. This experiment demonstrates the possibility of surgical applications in vitectomy in ophthalmology using Er-YAG laser and silica hollow waveguides.

  2. [Study on the relationship between ER Rsa I gene polymorphism and children's dental fluorosis].

    PubMed

    Ba, Yue; Li, Hai-Xia; Yin, Gong-Ju; Wu, Wei-Hua; Yu, Bo; Cheng, Xue-Min; Cui, Liu-Xin

    2009-09-01

    To explore the distribution of ER Rsa I genotype in children who lived in the areas with or without high fluoride, and evaluate the relationship between ER Rsa I gene polymorphism and children's dental fluorosis. Children aged 8 to 12 years, born and raised in high fluoride areas and control areas in two counties of Henan Province were recruited. The Rsa I marker of ER gene was genotyped in 237 children composed of both dental fluorosis cases and controls by PCR-RFLP procedure. Urine fluoride was detected with fluoride ion selective electrode method. The frequency distribution of ER Rsa I genotype was rr 60.81% (45/74), Rr 27.02% (20/74), RR 12.16% (9/74) in children with fluorosis; rr 73.91% (51/69), Rr 20.29% (14/69), RR 5.80% (4/69) in children without fluorosis from high fluoride areas, and rr 63.83% (60/94), Rr 34.04% (32/94), RR 2.13% (2/94) in the children without fluorosis from control areas respectively. There were no significant differences in the three groups (P>0.05), but children carrying allele R of ER Rsa I had a significantly increased risk of dental fluorosis (OR=1.821, 95% CI: 1.013-3.274) compared to children carrying the allele r in endemic fluorosis areas. Although no significant difference was found in ER Rsa I genotype between cases and non-dental fluorosis in endemic fluorosis areas, children carrying R allele of ER Rsa I had a higher risk compared to children carrying r allele, and the further study is needed.

  3. A Hands-On Approach to Teaching Protein Translation & Translocation into the ER

    ERIC Educational Resources Information Center

    LaBonte, Michelle L.

    2013-01-01

    The process of protein translation and translocation into the endoplasmic reticulum (ER) can often be challenging for introductory college biology students to visualize. To help them understand how proteins become oriented in the ER membrane, I developed a hands-on activity in which students use Play-Doh to simulate the process of protein…

  4. NASA ER-2 Flies over Southern California Wildfires

    NASA Image and Video Library

    2017-12-11

    NASA pilot Tim Williams flies the ER-2 high altitude airborne science platform carrying Jet Propulsion Laboratory’s AVIRIS spectral instrument over the Southern California wildfires on December 7, 2017.

  5. Phosphorylation of ETS Transcription Factor ER81 in a Complex with Its Coactivators CREB-Binding Protein and p300

    PubMed Central

    Papoutsopoulou, Stamatia; Janknecht, Ralf

    2000-01-01

    The ETS protein ER81 is a DNA-binding factor capable of enhancing gene transcription and is implicated in cellular transformation, but presently the mechanisms of its actions are unclear. In this report, ER81 is shown to coimmunoprecipitate with the transcriptional coactivator CREB-binding protein (CBP) and the related p300 protein (together referred to as CBP/p300). Moreover, confocal laser microscopic studies demonstrated that ER81 and p300 colocalized to nuclear speckles. In vitro and in vivo interaction studies revealed that ER81 amino acids 249 to 429, which encompass the ETS DNA-binding domain, are responsible for binding to CBP/p300. However, mutation of a putative protein-protein interaction motif, LXXLL, in the ETS domain of ER81 did not affect interaction with CBP/p300, whereas DNA binding of ER81 was abolished. Furthermore, two regions within CBP, amino acids 451 to 721 and 1891 to 2175, are capable of binding to ER81. Consistent with the physical interaction between ER81 and the coactivators CBP and p300, ER81 transcriptional activity was potentiated by CBP/p300 overexpression. Moreover, an ER81-associated protein kinase activity was enhanced upon p300 overexpression. This protein kinase phosphorylates ER81 on serines 191 and 216, and mutation of these phosphorylation sites increased ER81 transcriptional activity in Mv1Lu cells but not in HeLa cells. Altogether, our data elucidate the mechanism of how ER81 regulates gene transcription, through interaction with the coactivators CBP and p300 and an associated kinase that may cell type specifically modulate the ability of ER81 to activate gene transcription. PMID:10982847

  6. Plant Endocytosis Requires the ER Membrane-Anchored Proteins VAP27-1 and VAP27-3.

    PubMed

    Stefano, Giovanni; Renna, Luciana; Wormsbaecher, Clarissa; Gamble, Jessie; Zienkiewicz, Krzysztof; Brandizzi, Federica

    2018-05-22

    Through yet-undefined mechanisms, the plant endoplasmic reticulum (ER) has a critical role in endocytosis. The plant ER establishes a close association with endosomes and contacts the plasma membrane (PM) at ER-PM contact sites (EPCSs) demarcated by the ER membrane-associated VAMP-associated-proteins (VAP). Here, we investigated two plant VAPs, VAP27-1 and VAP27-3, and found an interaction with clathrin and a requirement for the homeostasis of clathrin dynamics at endocytic membranes and endocytosis. We also demonstrated direct interaction of VAP27-proteins with phosphatidylinositol-phosphate lipids (PIPs) that populate endocytic membranes. These results support that, through interaction with PIPs, VAP27-proteins bridge the ER with endocytic membranes and maintain endocytic traffic, likely through their interaction with clathrin. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. A molecular ensemble in the rER for procollagen maturation.

    PubMed

    Ishikawa, Yoshihiro; Bächinger, Hans Peter

    2013-11-01

    Extracellular matrix (ECM) proteins create structural frameworks in tissues such as bone, skin, tendon and cartilage etc. These connective tissues play important roles in the development and homeostasis of organs. Collagen is the most abundant ECM protein and represents one third of all proteins in humans. The biosynthesis of ECM proteins occurs in the rough endoplasmic reticulum (rER). This review describes the current understanding of the biosynthesis and folding of procollagens, which are the precursor molecules of collagens, in the rER. Multiple folding enzymes and molecular chaperones are required for procollagen to establish specific posttranslational modifications, and facilitate folding and transport to the cell surface. Thus, this molecular ensemble in the rER contributes to ECM maturation and to the development and homeostasis of tissues. Mutations in this ensemble are likely candidates for connective tissue disorders. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Creating Smart-er Cities: An Overview

    ERIC Educational Resources Information Center

    Allwinkle, Sam; Cruickshank, Peter

    2011-01-01

    The following offers an overview of what it means for cities to be "smart." It draws the supporting definitions and critical insights into smart cities from a series of papers presented at the 2009 Trans-national Conference on Creating Smart(er) Cities. What the papers all have in common is their desire to overcome the all too often…

  9. Synthesis of Er-doped Lu2O3 nanoparticles and transparent ceramics

    NASA Astrophysics Data System (ADS)

    Serivalsatit, K.; Wasanapiarnpong, T.; Kucera, C.; Ballato, J.

    2013-05-01

    Transparent rare earth-doped Lu2O3 ceramics have received much attention for use in solid-state scintillator and laser applications. The fabrication of these ceramics, however, requires ultrafine and uniform powders as precursors. Presented here is the synthesis of Er-doped Lu2O3 nanopowders by a solution precipitation method using Er-doped lutetium sulfate solution and hexamethylenetetramine as a precipitant and the fabrication of Er-doped Lu2O3 transparent ceramics from these nanopowders. The precipitated precursors were calcined at 1100 °C for 4 h in order to convert the precursors into Lu2O3 nanoparticles with an average particle size of 60 nm. Thermal decomposition and phase evolution of the precursors were studied by simultaneous thermal analysis (STA), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Er-doped Lu2O3 transparent ceramics were fabricated from these nanopowders using vacuum sintering followed by hot isostatic pressing at 1700 °C for 8 h. The transparent ceramics exhibit an optical transmittance of 78% at a wavelength of 1.55 μm.

  10. ERS-1 - Our new window on the oceans for the 1990s

    NASA Astrophysics Data System (ADS)

    Llewellyn-Jones, D. T.

    1986-05-01

    ESA's First Remote Sensing Satellite (ERS-1) due for launch in 1989 will monitor a carefully selected set of geophysical parameters in an effort to describe the state of the sea-surface. The payload instruments of ERS-1, how they make their measurements, and how the data will be dealt with, are described and discussed. The payload consists of three microwave radars: (1) a wind and wave scatterometer, (2) a synthetic aperture radar, and (3) a radar altimeter. These instruments are complemented by an Along Track Scanning Radiometer and a Precise Range and Range-Rate Experiment. The concept of fast delivery data products is an essential element of the ERS-1 system, meaning that the processed ERS-1 data will be distributed to designated points of contact within three hours of being obtained by the spacecraft. It is concluded that these measurements will lead to a better scientific understanding of ocean-atmosphere interactions; moreover, they will pave the way to the application of such data products to a large range of commercial activities.

  11. Down- and up-conversion emissions in Er-doped transparent fluorotellurite glass-ceramics

    NASA Astrophysics Data System (ADS)

    Miguel, A.; Morea, R.; Gonzalo, J.; Fernandez, J.; Balda, R.

    2015-03-01

    In this work, we report the near infrared and upconversion emissions of Er3+-doped transparent fluorotellurite glassceramics obtained by heat treatment of the precursor Er-doped TeO2-ZnO-ZnF2 glass. Structural analysis shows that ErF3 nanocrystals nucleated in the glass-ceramic sample are homogeneously distributed in the glass matrix with a typical size of 45±10 nm. The comparison of the fluorescence properties of Er3+-doped precursor glass and glass-ceramic confirms the successful incorporation of the rare-earth into the nanocrystals. An enhancement of the red upconversion emission due to 4F9/2→4I15/2 transition together with weak emission bands due to transitions from 2H9/2, 4F3/2,5/2, and 4F7/2 levels to the ground state are observed under excitation at 801 nm in the glass-ceramic sample. The temporal evolution of the red emission together with the excitation upconversion spectrum suggest that energy transfer processes are responsible for the enhancement of the red emission.

  12. The EDOP radar system on the high-altitude NASA ER-2 aircraft

    USGS Publications Warehouse

    Heymsfield, G.M.; Bidwell, S.W.; Caylor, I.J.; Ameen, S.; Nicholson, S.; Boncyk, W.; Miller, L.; Vandemark, D.; Racette, P.E.; Dod, L.R.

    1996-01-01

    The NASA ER-2 high-altitude (20 km) aircraft that emulates a satellite view of precipitation systems carries a variety of passive and active (lidar) remote sensing instruments. A new Doppler weather radar system at X band (9.6 GHz) called the ER-2 Doppler radar (EDOP) has been developed and flown on the ER-2 aircraft. EDOP is a fully coherent Doppler weather radar with fixed nadir and forward pointing (33?? off nadir) beams that map out Doppler winds and reflectivities in the vertical plane along the aircraft motion vector. Doppler winds from the two beams can be used to derive vertical and along-track air motions. In addition, the forward beam provides linear depolarization measurements that are useful in discriminating microphysical characteristics of the precipitation. This paper deals with a general description of the EDOP instrument including the measurement concept, the system configuration and hardware, and recently obtained data examples from the instrument. The combined remote sensing package on the ER-2, along with EDOP, provides a unique platform for simulating spaceborne remote sensing of precipitation.

  13. Er:YAG laser-assisted hair transplantation in cicatricial alopecia.

    PubMed

    Podda, M; Spieth, K; Kaufmann, R

    2000-11-01

    Autologous hair transplantation and its combination with flap or reduction procedures is a common surgical approach to cover defects in cicatricial alopecias. Due to the poor recipient conditions present in scar tissue, it is crucial to minimize the trauma exerted on implantation holes in order to achieve good transplantation results. We sought to evaluate the "cold"-ablative properties of the Er:YAG laser for the generation of recipient holes in cicatricial alopecia. Patients with cicatricial alopecia of diverse etiology were treated with Er:YAG laser-assisted hair transplantation. Mini- or micrografts were inserted into recipient holes ablated with a pulse energy of 900-1200 mJ and a spot size of 1.0-1.6 mm. A fluence of 80-120 J/cm2 and 8-12 pulses gave an almost ideal combination of minimal thermal damage and tissue ablation down to the subcutis. With an apparent mini- and micrograft survival of 95% we achieved good cosmetic results after two to five transplant sessions in all patients. The Er:YAG laser is a novel effective tool to ablate recipient holes for autologous hair transplantation in cicatricial alopecia.

  14. Isotopic ratios in outbursting comet C/2015 ER61

    NASA Astrophysics Data System (ADS)

    Yang, Bin; Hutsemékers, Damien; Shinnaka, Yoshiharu; Opitom, Cyrielle; Manfroid, Jean; Jehin, Emmanuël; Meech, Karen J.; Hainaut, Olivier R.; Keane, Jacqueline V.; Gillon, Michaël

    2018-02-01

    Isotopic ratios in comets are critical to understanding the origin of cometary material and the physical and chemical conditions in the early solar nebula. Comet C/2015 ER61 (PANSTARRS) underwent an outburst with a total brightness increase of 2 magnitudes on the night of 2017 April 4. The sharp increase in brightness offered a rare opportunity to measure the isotopic ratios of the light elements in the coma of this comet. We obtained two high-resolution spectra of C/2015 ER61 with UVES/VLT on the nights of 2017 April 13 and 17. At the time of our observations, the comet was fading gradually following the outburst. We measured the nitrogen and carbon isotopic ratios from the CN violet (0, 0) band and found that 12C/13C = 100 ± 15, 14N/15N = 130 ± 15. In addition, we determined the 14N/15N ratio from four pairs of NH2 isotopolog lines and measured 14N/15N = 140 ± 28. The measured isotopic ratios of C/2015 ER61 do not deviate significantly from those of other comets.

  15. Measuring Trends in Salaries and Wages in Public Schools: ERS Composite Indicator of Changes. ERS Information Aid.

    ERIC Educational Resources Information Center

    Educational Research Service, Arlington, VA.

    The composite indicator, published annually by the Educational Research Service (ERS), was designed to reflect overall changes in average salaries and wages paid by public school systems. The purpose of this book is to describe the nature of the indicator, how it is compiled on a national and state basis, and how local school systems can compile…

  16. ZnO/Er2O3 core-shell nanorod arrays: Synthesis, properties and growth mechanism

    NASA Astrophysics Data System (ADS)

    Yang, Jun; Wang, Yongqian; Jiang, Tingting; Li, Yinchang; Yang, Xiande

    2015-01-01

    In this study, we demonstrated large-scale ZnO/Er2O3 core-shell nanorod arrays, which were successfully synthesized by a facile and simple electrodeposition method. The effect of varying the amount of Er2O3 in the range from 0.2 g to 1.0 g on morphology of ZnO nanorod arrays has been thoroughly investigated. The results indicate that the growth pattern of all the ZnO/Er2O3 shell-core nanorod arrays were along c-axis and perpendicular to the substrate as before, even more vertical. Photoluminescence measurement was carried out and the PL peaks at 382 nm, 438 nm and 462 nm were observed, which are considered to be due to free excitons and donor-bound excitons, respectively. The ZnO/Er2O3 core-shell nanorods exhibited improved optical property, which can be attributed to the enhanced donor density by the covered Er2O3. Finally, a possible growth mechanism of the ZnO nanostructures is discussed. The electrochemical deposition of ZnO/Er2O3 core-shell nanorod arrays including two stages, namely nucleation and growth process.

  17. Resonantly diode-pumped Er:YAG laser: 1470-nm versus 1530-nm CW pumping case

    NASA Astrophysics Data System (ADS)

    Kudryashov, Igor; Ter-Gabrielyan, Nikolai; Dubinskii, Mark

    2009-05-01

    Growing interest to high power lasers in the eye-safe spectral domain initiated a new wave of activity in developing solid-state lasers based on bulk Er3+-doped materials. The resonant pumping of SSL allows for shifting significant part of thermal load from gain medium itself to the pump diodes, thus greatly reducing gain medium thermal distortions deleterious to SSL power scaling with high beam quality. The two major resonant pumping bands in Er:YAG are centered around 1470 and 1532 nm. Pumping into each of these bands has its pros and contras. The best approach to resonant pumping of Er:YAG active media in terms of pump wavelength is yet to be determined. We report the investigation results of high power diode-pumped Er:YAG laser aimed at direct comparison of resonant pumping at 1470 and 1532 nm. Two sources used for pumping were: 1530-nm 10-diode bar stack (>300 W CW) and 1470-nm 10-diode bar stack (>650 W CW). Both pumps were spectrally narrowed by external volume Bragg gratings. The obtained spectral width of less than 1 nm allowed for 'in-line' pumping of Er3+ in either band. The obtained CW power of over 87 W is, to the best of our knowledge, the record high power reported for resonantly pumped Er:YAG DPSSL at room temperature.

  18. Effects of Er:YAG laser irradiation on human cartilage

    NASA Astrophysics Data System (ADS)

    Glinkowski, Wojciech; Brzozowska, Malgorzata; Ciszek, Bogdan; Rowinski, Jan; Strek, Wieslaw

    1996-03-01

    Irradiation of the hyaline or fibrous cartilage excised from the body of a human cadaver with Er:YAG laser beam, single pulse with a dose of 1 J, produces a crater with a depth of approximately 500 micrometers and a diameter varying from 5 to 300 micrometers. Histological examination has revealed that the laser-made craters were surrounded by a thin rim (2-10 micrometer) of charred and coagulated tissue. No damage was observed in the cartilage surrounding the rim. The presence of sharp demarcation between the tissue areas ablated by laser energy and the undamaged areas argues for the potential usefulness of the Er:YAG laser in surgery of cartilages.

  19. Calcium and ER stress mediate hepatic apoptosis after burn injury

    PubMed Central

    Gauglitz, Gerd G.; Song, Juquan; Kulp, Gabriela A.; Finnerty, Celeste C.; Cox, Robert A.; Barral, José M.; Herndon, David N.; Boehning, Darren

    2009-01-01

    Abstract A hallmark of the disease state following severe burn injury is decreased liver function, which results in gross metabolic derangements that compromise patient survival. The underlying mechanisms leading to hepatocyte dysfunction after burn are essentially unknown. The aim of the present study was to determine the underlying mechanisms leading to hepatocyte dysfunction and apoptosis after burn. Rats were randomized to either control (no burn) or burn (60% total body surface area burn) and sacrificed at various time‐points. Liver was either perfused to isolate primary rat hepatocytes, which were used for in vitro calcium imaging, or liver was harvested and processed for immunohistology, transmission electron microscopy, mitochondrial isolation, mass spectroscopy or Western blotting to determine the hepatic response to burn injury in vivo. We found that thermal injury leads to severely depleted endoplasmic reticulum (ER) calcium stores and consequent elevated cytosolic calcium concentrations in primary hepatocytes in vitro. Burn‐induced ER calcium depletion caused depressed hepatocyte responsiveness to signalling molecules that regulate hepatic homeostasis, such as vasopressin and the purinergic agonist ATP. In vivo, thermal injury resulted in activation of the ER stress response and major alterations in mitochondrial structure and function – effects which may be mediated by increased calcium release by inositol 1,4,5‐trisphosphate receptors. Our results reveal that thermal injury leads to dramatic hepatic disturbances in calcium homeostasis and resultant ER stress leading to mitochondrial abnormalities contributing to hepatic dysfunction and apoptosis after burn injury. PMID:20141609

  20. HDL-C Response Variability to Niacin ER in US Adults

    PubMed Central

    Christian, Jennifer B.; Olson, Eric J.; Allen, Jeffery K.; Lowe, Kimberly A.

    2013-01-01

    Background. Niacin is the most effective treatment currently available for raising HDL-C levels. Objective. To evaluate if gender and baseline lipid levels have an effect on the HDL-C response of niacin ER and to identify factors that predict response to niacin ER at the 500 mg dose. Material and Methods. The change in HDL-C effect between baseline and follow-up levels was quantified in absolute change as well as dichotomized into high versus low response (high response was defined as an HDL-C effect of >15% increase and low response was HDL-C <5%) in a sample of 834 individuals. Results. Both males and females with low HDL-C levels at baseline exhibited a response to treatment in the multivariate model (males, HDL-C <40 mg/dL: OR = 5.18, 95% CI: 2.36–11.39; females, HDL-C <50 mg/dL: OR = 5.40, 95% CI: 1.84–15.79). There was also a significant difference in the mean HDL-C effect between baseline and follow-up HDL-C levels in the 500 mg niacin ER dose group for both males (mean HDL-C effect = 0.08, P < 0.001) and females (mean HDL-C effect = 0.10, P = 0.019). Conclusion. Baseline HDL-C levels are the biggest predictor of response to niacin ER treatment for both males and females among the factors evaluated. PMID:23533734

  1. 76 FR 63818 - Special Conditions: Boeing Model 767-400ER Series Airplanes; Seats With Inflatable Lapbelts

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-14

    ... appropriate safety standards for the 767-400ER series airplanes because of a novel or unusual design feature...-1106; Special Conditions No. 25-448-SC] Special Conditions: Boeing Model 767-400ER Series Airplanes...- 400ER series airplane. These airplanes, as modified by Continental Airlines, will have a novel or...

  2. Isolation and characterization of a metastatic hybrid cell line generated by ER negative and ER positive breast cancer cells in mouse bone marrow.

    PubMed

    Mukhopadhyay, Keya De; Bandyopadhyay, Abhik; Chang, Ting-Tung A; Elkahloun, Abdel G; Cornell, John E; Yang, Junhua; Goins, Beth A; Yeh, I-Tien; Sun, Lu-Zhe

    2011-01-01

    The origin and the contribution of breast tumor heterogeneity to its progression are not clear. We investigated the effect of a growing orthotopic tumor formed by an aggressive estrogen receptor (ER)-negative breast cancer cell line on the metastatic potential of a less aggressive ER-positive breast cancer cell line for the elucidation of how the presence of heterogeneous cancer cells might affect each other's metastatic behavior. ER positive ZR-75-1/GFP/puro cells, resistant to puromycin and non-tumorigenic/non-metastatic without exogenous estrogen supplementation, were injected intracardiacally into mice bearing growing orthotopic tumors, formed by ER negative MDA-MB-231/GFP/Neo cells resistant to G418. A variant cell line B6, containing both estrogen-dependent and -independent cells, were isolated from GFP expressing cells in the bone marrow and re-inoculated in nude mice to generate an estrogen-independent cell line B6TC. The presence of ER negative orthotopic tumors resulted in bone metastasis of ZR-75-1 without estrogen supplementation. The newly established B6TC cell line was tumorigenic without estrogen supplementation and resistant to both puromycin and G418 suggesting its origin from the fusion of MDA-MB-231/GFP/Neo and ZR-75-1/GFP/puro in the mouse bone marrow. Compared to parental cells, B6TC cells were more metastatic to lung and bone after intracardiac inoculation. More significantly, B6TC mice also developed brain metastasis, which was not observed in the MDA-MB-231/GFP/Neo cell-inoculated mice. Low expression of ERα and CD24, and high expression of EMT-related markers such as Vimentin, CXCR4, and Integrin-β1 along with high CD44 and ALDH expression indicated stem cell-like characteristics of B6TC. Gene microarray analysis demonstrated a significantly different gene expression profile of B6TC in comparison to those of parental cell lines. Spontaneous generation of the novel hybrid cell line B6TC, in a metastatic site with stem cell-like properties

  3. Lipid disequilibrium disrupts ER proteostasis by impairing ERAD substrate glycan trimming and dislocation

    PubMed Central

    To, Milton; Peterson, Clark W. H.; Roberts, Melissa A.; Counihan, Jessica L.; Wu, Tiffany T.; Forster, Mercedes S.; Nomura, Daniel K.; Olzmann, James A.

    2017-01-01

    The endoplasmic reticulum (ER) mediates the folding, maturation, and deployment of the secretory proteome. Proteins that fail to achieve their native conformation are retained in the ER and targeted for clearance by ER-associated degradation (ERAD), a sophisticated process that mediates the ubiquitin-dependent delivery of substrates to the 26S proteasome for proteolysis. Recent findings indicate that inhibition of long-chain acyl-CoA synthetases with triacsin C, a fatty acid analogue, impairs lipid droplet (LD) biogenesis and ERAD, suggesting a role for LDs in ERAD. However, whether LDs are involved in the ERAD process remains an outstanding question. Using chemical and genetic approaches to disrupt diacylglycerol acyltransferase (DGAT)–dependent LD biogenesis, we provide evidence that LDs are dispensable for ERAD in mammalian cells. Instead, our results suggest that triacsin C causes global alterations in the cellular lipid landscape that disrupt ER proteostasis by interfering with the glycan trimming and dislocation steps of ERAD. Prolonged triacsin C treatment activates both the IRE1 and PERK branches of the unfolded protein response and ultimately leads to IRE1-dependent cell death. These findings identify an intimate relationship between fatty acid metabolism and ER proteostasis that influences cell viability. PMID:27881664

  4. Pharmacological reduction of ER stress protects against TDP-43 neuronal toxicity in vivo.

    PubMed

    Vaccaro, Alexandra; Patten, Shunmoogum A; Aggad, Dina; Julien, Carl; Maios, Claudia; Kabashi, Edor; Drapeau, Pierre; Parker, J Alex

    2013-07-01

    C. elegans and D. rerio expressing mutant TAR DNA Binding Protein 43 (TDP-43) are powerful in vivo animal models for the genetics and pharmacology of amyotrophic lateral sclerosis (ALS). Using these small-animal models of ALS, we previously identified methylene blue (MB) as a potent suppressor of TDP-43 toxicity. Consequently here we investigated how MB might exert its neuroprotective properties and found that it acts through reduction of the endoplasmic reticulum (ER) stress response. We tested other compounds known to be active in the ER unfolded protein response in worms and zebrafish expressing mutant human TDP-43 (mTDP-43). We identified three compounds: salubrinal, guanabenz and a new structurally related compound phenazine, which also reduced paralysis, neurodegeneration and oxidative stress in our mTDP-43 models. Using C. elegans genetics, we showed that all four compounds act as potent suppressors of mTDP-43 toxicity through reduction of the ER stress response. Interestingly, these compounds operate through different branches of the ER unfolded protein pathway to achieve a common neuroprotective action. Our results indicate that protein-folding homeostasis in the ER is an important target for therapeutic development in ALS and other TDP-43-related neurodegenerative diseases. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  5. Long non-coding RNA MIAT is estrogen-responsive and promotes estrogen-induced proliferation in ER-positive breast cancer cells.

    PubMed

    Li, Yuehua; Jiang, Baohong; Wu, Xiaoping; Huang, Qin; Chen, Wenqi; Zhu, Hongbo; Qu, Xiaofei; Xie, Liming; Ma, Xin; Huang, Guo

    2018-05-21

    Estrogen drives the development and progression of estrogen receptor (ER)-positive breast cancer. However, the detailed mechanism underlying ER-driven carcinogenesis remains unclear despite extensive studies. Previously reports indicated higher expression of long non-coding RNA (lncRNA) myocardial infarction associated transcript (MIAT) in ER-positive breast cancer tissues than in ER-negative tissues. However, the functional relevance of MIAT in ER-positive breast cancer tumorigenesis was poorly understood. Here, we investigated the role of lncRNA MIAT in ER-positive breast cancer cells. MIAT was over-expressed in ER-positive breast cancer tissues and ER-positive breast cancer cell line MCF-7. Activating estrogen signaling by diethylstilbestrol (DES) led to a dose- and time-dependent up-regulation of MIAT in MCF-7 cells that was dependent on ERα, as evidenced by ERα silencing and pharmacological inhibition using ER antagonist ICI 182780. Silencing MIAT decreased DES-induced MCF-7 cell proliferation while overexpressing MIAT increased MCF-7 cell proliferation. Further mechanistic study identified that MIAT was critical for G1 to S phase cell cycle transition. Taken together, these results suggest that lncRNA MIAT is an estrogen-inducible lncRNA and a key regulator in ER-positive breast cancer cell growth. MIAT could serve as a potential biomarker and promising therapeutic target for ER-positive breast cancer. Copyright © 2018. Published by Elsevier Inc.

  6. Restoration of Tamoxifen Sensitivity in Estrogen Receptor–Negative Breast Cancer Cells: Tamoxifen-Bound Reactivated ER Recruits Distinctive Corepressor Complexes

    PubMed Central

    Sharma, Dipali; Saxena, Neeraj K.; Davidson, Nancy E.; Vertino, Paula M.

    2010-01-01

    Breast tumors expressing estrogen receptor-α (ER) respond well to therapeutic strategies using selective ER modulators, such as tamoxifen. However, ~ 30% of invasive breast cancers are hormone independent because they lack ER expression due to hypermethylation of ER promoter. Treatment of ER-negative breast cancer cells with demethylating agents [5-aza-2′-deoxycytidine (5-aza-dC)] and histone deacetylase (HDAC) inhibitors (trichostatin A) leads to expression of ER mRNA and functional protein. Here, we examined whether epigenetically reactivated ER is a target for tamoxifen therapy. Following treatment with trichostatin A and 5-aza-dC, the formerly unresponsive ER-negative MDA-MB-231 breast cancer cells became responsive to tamoxifen. Tamoxifen-mediated inhibition of cell growth in these cells is mediated at least in part by the tamoxifen-bound ER. Tamoxifen-bound reactivated ER induces transcriptional repression at estrogen-responsive genes by ordered recruitment of multiple distinct chromatin-modifying complexes. Using chromatin immunoprecipitation, we show recruitment of two different corepressor complexes to ER-responsive promoters in a mutually exclusive and sequential manner: the nuclear receptor corepressor-HDAC3 complex followed by nucleosome remodeling and histone deacetylation complex. The mechanistic insight provided by this study might help in designing therapeutic strategies directed toward epigenetic mechanisms in the prevention or treatment of breast cancer. PMID:16778215

  7. Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology

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

    Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît

    Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. Wemore » have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. - Highlights: • NIH-3T3 cells lacking all three atlastin paralogs were generated using CRISPR/Cas9. • Cells lacking all atlastin GTPases exhibit far fewer 3-way ER tubule junctions. • ER morphology defects in atlastin knockout cells are rescued by distant plant and yeast orthologs. • Atlastin knock out cells

  8. Progesterone induces progesterone receptor gene (PGR) expression via rapid activation of protein kinase pathways required for cooperative estrogen receptor alpha (ER) and progesterone receptor (PR) genomic action at ER/PR target genes.

    PubMed

    Diep, Caroline H; Ahrendt, Hannah; Lange, Carol A

    2016-10-01

    Progesterone Receptors (PRs) are critical effectors of estrogen receptor (ER) signaling required for mammary gland development and reproductive proficiency. In breast and reproductive tract malignancies, PR expression is a clinical prognostic marker of ER action. While estrogens primarily regulate PR expression, other factors likely contribute to a dynamic range of receptor expression across diverse tissues. In this study, we identified estrogen-independent but progestin (R5020)-dependent regulation of ER target genes including PGR in ER+/PR+ cancer cell lines. R5020 (10nM-10μM range) induced dose-dependent PR mRNA and protein expression in the absence of estrogen but required both PR and ERα. Antagonists of either PR (RU486, onapristone) or ERα (ICI 182,780) attenuated R5020 induction of TFF1, CTSD, and PGR. Chromatin immunoprecipitation (ChIP) assays performed on ER+/PR+ cells demonstrated that both ERα and PR were recruited to the same ERE/Sp1 site-containing region of the PGR proximal promoter in response to high dose progestin (10μM). Recruitment of ERα and PR to chromatin and subsequent PR mRNA induction were dependent upon rapid activation of MAPK/ERK and AKT; inhibition of these kinase pathways via U0126 or LY294002 blocked these events. Overall, we have identified a novel mechanism of ERα activation initiated by rapid PR-dependent kinase pathway activation and associated with phosphorylation of ERα Ser118 for estrogen-independent but progestin-dependent ER/PR cross talk. These studies may provide insight into mechanisms of persistent ER-target gene expression during periods of hormone (i.e. estrogen) ablation and suggest caution following prolonged treatment with aromatase or CYP17 inhibitors (i.e. contexts when progesterone levels may be abnormally elevated). Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Combining autophagy-inducing peptides and brefeldin A delivered by perinuclear-localized mesoporous silica nanoparticles: a manipulation strategy for ER-phagy.

    PubMed

    Wang, Yimin; Zhao, Zhao; Wei, Fujing; Luo, Zewei; Duan, Yixiang

    2018-05-10

    Autophagic degradation of the endoplasmic reticulum (ER-phagy) has been found to play a critical role in human sensory neuropathy. So far, however, specific and efficient intervention means for ER-phagy remain unexplored. Herein, brefeldin A (BFA), a blocking agent on protein transport between the ER and Golgi, was screened from ER stress inducers. BFA was then delivered to the perinuclear area co-localized with the ER by a mesoporous silica nanoparticle-based drug-carrier functionalized with autophagy-inducing peptides of TAT-beclin 1 (MSNs-BFA), to evoke a perturbation of ER-phagy. The molecular mechanism of ER-phagy regulated by BFA was explored by biochemical evaluation including time-lapse live-cell fluorescence imaging. We found that MSNs-BFA treatment caused a lower mRNA/protein expression level of FAM134b even under a compensation of autophagic flux in U2OS cells, and resulted in ER-expansion. The fragmentation of the ER was blocked as a response to ER stress mediated by inactivation of the AKT/TSC/mTOR pathway. Our work developed an efficient external manipulation strategy to regulate ER-phagy and may contribute to the therapeutic application of autophagy-related major human diseases.

  10. Magnetic moment arrangement in amorphous Fe 0.66Er 0.19B 0.15

    NASA Astrophysics Data System (ADS)

    Szymański, K.; Kalska, B.; Satuła, D.; Dobrzyński, L.; Broddefalk, A.; Wäppling, R.; Nordblad, P.

    2002-11-01

    Magnetization measurements and Mössbauer spectroscopy with and without a monochromatic circularly polarized Mössbauer source (MCPMS) have been performed in order to determine the magnetic properties of the amorphous alloy Fe 0.66Er 0.19B 0.15. The system is found to order ferrimagnetically at TC=330 K and to show a compensation temperature ( Tcomp) at 120 K. A reorientation of the magnetic moments of iron and erbium during sample cooling through the compensation point in magnetic field is clearly displayed in the MCPMS data. The orientation of the net magnetic moment is due to the orientation of Fe moments above Tcomp and to Er moments at low temperatures. The results are compatible with a model of predominantly antiferromagnetic Fe-Er coupling accompanied by random local anisotropy acting on the Er moments.

  11. Upconversion properties of Er3+/Yb3+ co-doped TeO2-TiO2-K2O glasses.

    PubMed

    Su, Fangning; Deng, Zaide

    2006-01-01

    The Er3+/Yb3+ co-doped TeO2-TiO2-K2O glasses were prepared by conventional melting procedures, and their upconversion spectra were performed. The dependence of luminescence intensity on the ratio of Yb3+/Er3+ was studied, and the relationship between green upconversion luminescence intensity and Er3+ concentration is discussed in detail. The 546 nm green upconversion luminescence intensity is optimised in the studied glasses either when the Yb3+/Er3+ ratio is 25/1 and Er3+ concentration is 0.1 mol%, or when the Yb3+/Er3+ ratio is 10/1 and Er3+ concentration is 0.15 mol%. These glasses could be one of the potential candidates for LD pumping microchip solid-state lasers.

  12. Atmospheric Ionizing Radiation (AIR) ER-2 Preflight Analysis

    NASA Technical Reports Server (NTRS)

    Tai, Hsiang; Wilson, John W.; Maiden, D. L.

    1998-01-01

    Atmospheric ionizing radiation (AIR) produces chemically active radicals in biological tissues that alter the cell function or result in cell death. The AIR ER-2 flight measurements will enable scientists to study the radiation risk associated with the high-altitude operation of a commercial supersonic transport. The ER-2 radiation measurement flights will follow predetermined, carefully chosen courses to provide an appropriate database matrix which will enable the evaluation of predictive modeling techniques. Explicit scientific results such as dose rate, dose equivalent rate, magnetic cutoff, neutron flux, and air ionization rate associated with those flights are predicted by using the AIR model. Through these flight experiments, we will further increase our knowledge and understanding of the AIR environment and our ability to assess the risk from the associated hazard.

  13. Periodontal tissue healing following flap surgery using an Er:YAG laser in dogs.

    PubMed

    Mizutani, Koji; Aoki, Akira; Takasaki, Aristeo Atsushi; Kinoshita, Atsuhiro; Hayashi, Chie; Oda, Shigeru; Ishikawa, Isao

    2006-04-01

    The purpose of this study was to compare periodontal tissue healing following flap surgery using an Er:YAG laser with that of conventional surgery. Bilateral premolars with experimentally induced periodontitis in six dogs were treated by periodontal flap surgery. Degranulation and root debridement in the furcation were performed using an Er:YAG laser or curet. At 3 months postsurgery, animals were sacrificed and decalcified specimens were prepared for histological and histometric analysis. Degranulation and root debridement were effectively performed with an Er:YAG laser without major thermal damage and significantly faster than with a curet. Histologically, the amount of newly formed bone was significantly greater in the laser group than in the curet group, although both groups showed similar amounts of cementum formation and connective tissue attachment. The Er:YAG laser irradiation can be safely and effectively utilized in periodontal flap surgery, and has the potential to promote new bone formation. Copyright 2006 Wiley-Liss, Inc.

  14. The integrative epigenomic-transcriptomic landscape of ER positive breast cancer.

    PubMed

    Gao, Yang; Jones, Allison; Fasching, Peter A; Ruebner, Matthias; Beckmann, Matthias W; Widschwendter, Martin; Teschendorff, Andrew E

    2015-01-01

    While recent integrative analyses of copy number and gene expression data in breast cancer have revealed a complex molecular landscape with multiple subtypes and many oncogenic/tumour suppressor driver events, much less is known about the role of DNA methylation in shaping breast cancer taxonomy and defining driver events. Here, we applied a powerful integrative network algorithm to matched DNA methylation and RNA-Seq data for 724 estrogen receptor (ER)-positive (ER+) breast cancers and 111 normal adjacent tissue specimens from The Cancer Genome Atlas (TCGA) project, in order to identify putative epigenetic driver events and to explore the resulting molecular taxonomy. This revealed the existence of nine functionally deregulated epigenetic hotspots encompassing a total of 146 genes, which we were able to validate in independent data sets encompassing over 1000 ER+ breast cancers. Integrative clustering of the matched messenger RNA (mRNA) and DNA methylation data over these genes resulted in only two clusters, which correlated very strongly with the luminal-A and luminal B subtypes. Overall, luminal-A and luminal-B breast cancers shared the same epigenetically deregulated hotspots but with luminal-B cancers exhibiting increased aberrant DNA methylation patterns relative to normal tissue. We show that increased levels of DNA methylation and mRNA expression deviation from the normal state define a marker of poor prognosis. Our data further implicates epigenetic silencing of WNT signalling antagonists and bone morphogenetic proteins (BMP) as key events underlying both luminal subtypes but specially of luminal-B breast cancer. Finally, we show that DNA methylation changes within the identified epigenetic interactome hotspots do not exhibit mutually exclusive patterns within the same cancer sample, instead exhibiting coordinated changes within the sample. Our results indicate that the integrative DNA methylation and transcriptomic landscape of ER+ breast cancer is

  15. Optimal Er:YAG laser irradiation parameters for debridement of microstructured fixture surfaces of titanium dental implants.

    PubMed

    Taniguchi, Yoichi; Aoki, Akira; Mizutani, Koji; Takeuchi, Yasuo; Ichinose, Shizuko; Takasaki, Aristeo Atsushi; Schwarz, Frank; Izumi, Yuichi

    2013-07-01

    Er:YAG laser (ErL) irradiation has been reported to be effective for treating peri-implant disease. The present study seeks to evaluate morphological and elemental changes induced on microstructured surfaces of dental endosseous implants by high-pulse-repetition-rate ErL irradiation and to determine the optimal irradiation conditions for debriding contaminated microstructured surfaces. In experiment 1, dual acid-etched microstructured implants were irradiated by ErL (pulse energy, 30-50 mJ/pulse; repetition rate, 30 Hz) with and without water spray and for used and unused contact tips. Experiment 2 compared the ErL treatment with conventional mechanical treatments (metal/plastic curettes and ultrasonic scalers). In experiment 3, five commercially available microstructures were irradiated by ErL light (pulse energy, 30-50 mJ/pulse; pulse repetition rate, 30 Hz) while spraying water. In experiment 4, contaminated microstructured surfaces of three failed implants were debrided by ErL irradiation. After the experiments, all treated surfaces were assessed by stereomicroscopy, scanning electron microscopy (SEM), and/or energy-dispersive X-ray spectroscopy (EDS). The stereomicroscopy, SEM, and EDS results demonstrate that, unlike mechanical treatments, ErL irradiation at 30 mJ/pulse and 30 Hz with water spray induced no color or morphological changes to the microstructures except for the anodized implant surface, which was easily damaged. The optimized irradiation parameters effectively removed calcified deposits from contaminated titanium microstructures without causing substantial thermal damage. ErL irradiation at pulse energies below 30 mJ/pulse (10.6 J/cm(2)/pulse) and 30 Hz with water spray in near-contact mode seems to cause no damage and to be effective for debriding microstructured surfaces (except for anodized microstructures).

  16. Gain and noise figure enhancement of Er+3/Yb+3 co-doped fiber/Raman hybrid amplifier

    NASA Astrophysics Data System (ADS)

    Mahran, O.

    2016-02-01

    An Er/Yb co-doped fiber/Raman hybrid amplifier (HA) is proposed and studied theoretically and analytically to improve the gain and noise figure of optical amplifiers. The calculations are performed under a uniform dopant and steady-state conditions. The initial energy transfer efficiency for Er/Yb co-doped fiber amplifier (EYDFA) is introduced, while the amplified spontaneous emission (ASE) is neglected. The glass fiber used for both Er/Yb and Raman amplifiers is phosphate. Different pump powers are used for both EYDFA and RA with 1 μW input signal power, 1 m length of Er/Yb amplifier and 25 km length of Raman amplifier (RA). The proposed model is validated for Er/Yb co-doped amplifier and Raman amplifier separately by comparing the calculating results with the experimental data. A high gain and low noise figure at 200 mW Raman pump power and 500 mW Er/Yb pump power are obtained for the proposed HA as compared with the experimental results of EYDFA, Raman amplifier and the EDFA/Raman hybrid amplifier.

  17. Crystallographic and magnetic structure of the novel compound ErGe 1.83

    NASA Astrophysics Data System (ADS)

    Oleksyn, O.; Schobinger-Papamantellos, P.; Ritter, C.; de Groot, C. H.; Buschow, K. H. J.

    1997-02-01

    The crystal structure and the magnetic ordering of the novel orthorhombic compound ErGe 2-x has been studied by neutron powder diffraction and magnetic measurements. The crystal structure belongs to the DyGe 1.85-type (space group Cmc2 1)·ErGe 2-x ( x = 0.17 (2)) orders antiferromagnetically below TN = 6 K and displays a metamagnetic behaviour. The magnetic cell has the same size as the chemical unit cell ( q = 0 ). The magnetic space group is Cmc2 1 (Sh 36173). At T = 1.5 K the magnetic moments of the two erbium sites have the same ordered magnetic moment values of 7.63 (6) μB/Er and are antiferromagnetically coupled leading to an uniaxial structure along the a direction.

  18. 20 CFR 220.30 - Special period required for eligibility of widow(er)s.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... RAILROAD RETIREMENT ACT DETERMINING DISABILITY Disability Under the Railroad Retirement Act for Any Regular Employment § 220.30 Special period required for eligibility of widow(er)s. In order to be found disabled for any regular employment, a widow(er) must have a permanent physical or mental impairment which...

  19. Palmitate induces cisternal ER expansion via the activation of XBP-1/CCTα-mediated phospholipid accumulation in RAW 264.7 cells.

    PubMed

    Kim, Seong Keun; Oh, Eunhye; Yun, Mihee; Lee, Seong-Beom; Chae, Gue Tae

    2015-07-16

    Endoplasmic reticulum (ER) stress induces ER expansion. The expansion of the intracisternal space of the ER was found in macrophages associated with human atherosclerotic lesions. We also previously reported that palmitate induces cisternal ER expansion and necrosis in RAW 264.7 cells. In this study, we report on an investigation of the likely mechanism responsible for this palmitate-induced cisternal ER expansion in a mouse macrophage cell line, RAW 264.7 cells. RAW 264.7 cells were pre-treated with the designated inhibitor or siRNA, followed by treatment with palmitate. Changes in the ER structure were examined by transmission electron microscopy. The induction of ER stress was confirmed by an increase in the extent of phosphorylation of PERK, the expression of BiP and CHOP, and the splicing of XBP-1 mRNA. Phospholipid staining was performed with the LipidTOX Red phospholipidosis detection reagent. Related gene expressions were detected by quantitative real time-RT-PCR or RT-PCR. Palmitate was found to induce ER stress and cisternal ER expansion. In addition, palmitate-induced cisternal ER expansion was attenuated by ER stress inhibitors, such as 4-phenylbutyric acid (4-PBA) and tauroursodeoxycholic acid (TUDCA). The findings also show that palmitate induced-mRNA expression of CCTα, which increases phospholipid synthesis, was attenuated by the down-regulation of XBP-1, a part of ER stress. Furthermore, palmitate-induced phospholipid accumulation and cisternal ER expansion were attenuated by the down-regulation of XBP-1 or CCTα. The findings reported herein indicate that palmitate-induced cisternal ER expansion is dependent on the activation of XBP-1/CCTα-mediated phospholipid accumulation in RAW 264.7 cells.

  20. Homeostatic Regulation of the PI(4,5)P2-Ca2+ Signaling System at ER-PM Junctions

    PubMed Central

    Chang, Chi-Lun; Liou, Jen

    2016-01-01

    The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-Ca2+ signaling system is important for cell activation in response to various extracellular stimuli. This signaling system is initiated by receptor-induced hydrolysis of PI(4,5)P2 in the plasma membrane (PM) to generate the soluble second messenger inositol 1,4,5-trisphosphate (IP3). IP3 subsequently triggers the release of Ca2+ from the endoplasmic reticulum (ER) store to the cytosol to activate Ca2+-mediated responses, such as secretion and proliferation. The consumed PM PI(4,5)P2 and ER Ca2+ must be quickly restored to sustain signaling responses, and to maintain the homeostasis of PI(4,5)P2 and Ca2+. Since phosphatidylinositol (PI), the precursor lipid for PM PI(4,5)P2, is synthesized in the ER membrane, and a Ca2+ influx across the PM is required to refill the ER Ca2+ store, efficient communications between the ER and the PM are critical for the homeostatic regulation of the PI(4,5)P2-Ca2+ signaling system. This review describes the major findings that established the framework of the PI(4,5)P2-Ca2+ signaling system, and recent discoveries on feedback control mechanisms at ER-PM junctions that sustain the PI(4,5)P2-Ca2+ signaling system. Particular emphasis is placed on the characterization of ER-PM junctions where efficient communications between the ER and the PM occurs, and the activation mechanisms of proteins that dynamically localize to ER-PM junctions to provide the feedback control during PI(4,5)P2-Ca2+ signaling, including the ER Ca2+ sensor STIM1, the extended synaptotagmin E-Syt1, and the PI transfer protein Nir2. This review is part of a Special Issue entitled The Cellular Lipid Landscape. PMID:26924250

  1. Temperature rises during application of Er:YAG laser under different primary dentin thicknesses.

    PubMed

    Hubbezoglu, Ihsan; Unal, Murat; Zan, Recai; Hurmuzlu, Feridun

    2013-05-01

    The present study investigated the effects of the Er:YAG laser's different pulse repetition rates on temperature rise under various primary dentin thicknesses. The Er:YAG laser can be used for restorative approaches in clinics and is used to treat dental caries. There are some reports that explain the temperature rise effect of the Er:YAG laser. Recently, the Er:YAG laser has been found to play an important role in temperature rises during the application on dentin. Caries-free primary mandibular molars were prepared to obtain dentin discs with 0.5, 1, 1.5, and 2 mm thicknesses (n=10). These discs were placed between the Teflon mold cylinders of a temperature test apparatus. We preferred three pulse repetition rates of 10, 15, and 20 Hz with an energy density of 12.7 J/cm2 and a 230 μs pulse duration. All dentin discs were irradiated for 30 sec by the Er:YAG laser. Temperature rises were recorded using an L-type thermocouple and universal data loggers/scanners (E-680, Elimko Co., Turkey). Data were analyzed by two-way ANOVA and Tukey tests. Whereas the lowest temperature rise (0.44±0.09 °C) was measured from a 10 Hz pulse repetition rate at a dentin thickness of 2 mm, the highest temperature rise (3.86±0.43 °C) was measured from a 20 Hz pulse repetition rate at a 0.5 mm dentin thickness. Temperature rise did not reach critical value for pulpal injury in any primary dentin thicknesses irradiated by a high repetition rate of the Er:YAG laser.

  2. Treatment of actinic cheilitis with the Er:YAG laser.

    PubMed

    Armenores, Paul; James, Craig L; Walker, Patrick C; Huilgol, Shyamala C

    2010-10-01

    Actinic cheilitis is a common condition with the potential to develop into squamous cell carcinoma. Current treatments have varying cure rates and complications. The role of the erbium:yttrium-aluminum-garnet (Er:YAG) laser in the treatment of actinic cheilitis has not been widely published, despite offering theoretical advantages over current treatment modalities. To evaluate the outcome of a series of patients treated with the Er:YAG laser for actinic cheilitis. This was a retrospective, interventional, nonrandomized, sequential case series set in a tertiary referral, dermatologic surgery unit. Ninety-nine consecutive patients with actinic cheilitis treated with the Er:YAG laser between January 2001 and June 2008 underwent a case note review, of which 77 went on to a structured telephone interview. The main outcome measures were a subjective improvement in lip symptoms related to actinic cheilitis and objective improvement in the lips at routine follow-up. Mean time to interview follow-up was 65.7 months. Of those interviewed, 92.2% believed there had been an improvement in the cosmetic appearance of their lips; one hundred percent believed the function of their lips had improved or remained unchanged; and 84.8% remained completely disease free at the time of follow-up. The majority of patients (93.5%) were satisfied with the laser treatment. Scarring as a direct result of the laser occurred in 5.1% of patients. Retrospective nature of data collection; inability to interview all patients who underwent treatment. The Er:YAG laser is a successful modality for the treatment of actinic cheilitis with good functional and cosmetic results and only a small risk of long-term scarring. It should be considered as a first-line treatment for the disease. Copyright © 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  3. The NASA Earth Research-2 (ER-2) Aircraft: A Flying Laboratory for Earth Science Studies

    NASA Technical Reports Server (NTRS)

    Navarro, Robert

    2007-01-01

    The National Aeronautics and Space Administration Dryden Flight Research Center, Edwards, California, has two Lockheed Martin Corporation (Bethesda, Maryland) Earth Research-2 (ER2) aircraft that serve as high-altitude and long-range flying laboratories. The ER-2 aircraft has been successfully utilized to conduct scientific studies of stratospheric and tropospheric chemistry, land-use mapping, disaster assessment, preliminary testing and calibration and validation of satellite sensors. The research missions for the ER-2 aircraft are planned, implemented, and managed by the Dryden Flight Research Center Science Mission Directorate. Maintenance and instrument payload integration is conducted by Dryden personnel. The ER-2 aircraft provides experimenters with a wide array of payload accommodations areas with suitable environment control with required electrical and mechanical interfaces. Missions may be flown out of Dryden or from remote bases worldwide, according to research requirements. The NASA ER-2 aircraft is utilized by a variety of customers, including U.S. Government agencies, civilian organizations, universities, and state governments. The combination of the ER-2 aircraft s range, endurance, altitude, payload power, payload volume and payload weight capabilities complemented by a trained maintenance and operations team provides an excellent and unique platform system to the science community and other customers.

  4. Analysis of Shear Bond Strength and Morphology of Er:YAG Laser-Recycled Ceramic Orthodontic Brackets.

    PubMed

    Han, Ruo-qiao; Yang, Kai; Ji, Ling-fei; Ling, Chen

    2016-01-01

    The aim of this study was to compare the recycling of deboned ceramic brackets via an Er:YAG laser or via the traditional chairside processing methods of flaming and sandblasting; shear bond strength and morphological changes were evaluated in recycled brackets versus new brackets. 3M Clarity Self-Ligating Ceramic Brackets with a microcrystalline base were divided into groups subjected to flaming, sandblasting, or exposure to an Er:YAG laser. New ceramic brackets served as a control group. Shear bond strengths were determined with an Electroforce test machine and tested for statistical significance through analysis of variance. Morphological examinations of the recycled ceramic bracket bases were conducted with scanning electron microscopy and confocal laser scanning microscopy. Residue on the bracket base was analyzed with Raman spectroscopy. Faded, dark adhesive was left on recycled bracket bases processed via flaming. Adhesive was thoroughly removed by both sandblasting and exposure to an Er:YAG laser. Compared with new brackets, shear bond strength was lower after sandblasting (p < 0.05), but not after exposure to an Er:YAG laser. The Er:YAG laser caused no damage to the bracket. Er:YAG lasers effectively remove adhesive from the bases of ceramic brackets without damaging them; thus, this method may be preferred over other recycling methods.

  5. High-field magnetoelasticity of Tm2Co17 and comparison with Er2Co17

    NASA Astrophysics Data System (ADS)

    Andreev, A. V.; Zvyagin, A. A.; Skourski, Y.; Yasin, S.; Zherlitsyn, S.

    2017-11-01

    Acoustic properties (ultrasound velocity and attenuation) and magnetostriction were measured in pulsed fields up to 60 T applied along the c axis of Tm2Co17 single crystal. Similar to Er2Co17, the transition in Tm2Co17 is accompanied by clear anomalies in the sound velocity. The observed 0.3% jump of the sound velocity at the transition is negative in Tm2Co17, whereas it is positive in Er2Co17. The magnetostriction at the transition also differs very much from that in Er2Co17. In Tm2Co17, the transition is accompanied by a smooth minimum of 0.15 × 10-4 in longitudinal magnetostriction whereas in Er2Co17 by a very sharp expansion of much larger magnitude (1.2 × 10-4). In the transverse mode, the effect in Tm2Co17 looks as very broad minimum of low amplitude (<0.1 × 10-4) whereas in Er2Co17 as very sharp and large shrinkage (2.6 × 10-4). Thus, both the magnetoacoustics and magnetostriction are rather different in Tm2Co17 and Er2Co17. This supports different nature of the field-induced transitions in these compounds.

  6. Endothelial NOS activation induces the blood-brain barrier disruption via ER stress following status epilepticus.

    PubMed

    Ko, Ah-Reum; Kim, Ji Yang; Hyun, Hye-Won; Kim, Ji-Eun

    2015-10-05

    The blood-brain barrier (BBB) maintains the unique brain microenvironment, which is separated from the systemic circulating system. Since the endoplasmic reticulum (ER) is an important cell organelle that is responsible for protein synthesis, the correct folding and sorting of proteins contributing to cell survivals, ER stress is a potential cause of cell damage in various diseases. Therefore, it would be worthy to explore the the relationship between the ER stress and BBB disruption during vasogenic edema formation induced by epileptogenic insults. In the present study, we investigated the roles of ER stress in vasogenic edema and its related events in rat epilepsy models provoked by pilocarpine-induced status epilepticus (SE). SE-induced eNOS activation induces BBB breakdown via up-regulation of GRP78 expression and dysfunction of SMI-71 (an endothelial BBB marker) in the piriform cortex (PC). In addition, caveolin-1 peptide (an eNOS inhibitor) effectively attenuated GRP78 expression and down-regulation of SMI-71. Taken together, our findings suggest that eNOS-mediated ER stress may participate in SE-induced vasogenic edema formation. Therefore, the modulation of ER stress may be a considerable strategy for therapy in impairments of endothelial cell function. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. An ER-peroxisome tether exerts peroxisome population control in yeast

    PubMed Central

    Knoblach, Barbara; Sun, Xuejun; Coquelle, Nicolas; Fagarasanu, Andrei; Poirier, Richard L; Rachubinski, Richard A

    2013-01-01

    Eukaryotic cells compartmentalize biochemical reactions into membrane-enclosed organelles that must be faithfully propagated from one cell generation to the next. Transport and retention processes balance the partitioning of organelles between mother and daughter cells. Here we report the identification of an ER-peroxisome tether that links peroxisomes to the ER and ensures peroxisome population control in the yeast Saccharomyces cerevisiae. The tether consists of the peroxisome biogenic protein, Pex3p, and the peroxisome inheritance factor, Inp1p. Inp1p bridges the two compartments by acting as a molecular hinge between ER-bound Pex3p and peroxisomal Pex3p. Asymmetric peroxisome division leads to the formation of Inp1p-containing anchored peroxisomes and Inp1p-deficient mobile peroxisomes that segregate to the bud. While peroxisomes in mother cells are not released from tethering, de novo formation of tethers in the bud assists in the directionality of peroxisome transfer. Peroxisomes are thus stably maintained over generations of cells through their continued interaction with tethers. PMID:23900285

  8. Excessive ER stress and the resulting autophagic flux dysfunction contribute to fluoride-induced neurotoxicity.

    PubMed

    Niu, Qiang; Chen, Jingwen; Xia, Tao; Li, Pei; Zhou, Guoyu; Xu, Chunyan; Zhao, Qian; Dong, Lixin; Zhang, Shun; Wang, Aiguo

    2018-02-01

    Fluoride is capable of inducing neurotoxicity, but its mechanisms remain elusive. This study aimed to explore the roles of endoplasmic reticulum (ER) stress and autophagy in sodium fluoride (NaF)-induced neurotoxicity, focusing on the regulating role of ER stress in autophagy. The in vivo results demonstrated that NaF exposure impaired the learning and memory capabilities of rats, and resulted in histological and ultrastructural abnormalities in rat hippocampus. Moreover, NaF exposure induced excessive ER stress and associated apoptosis, as manifested by elevated IRE1α, GRP78, cleaved caspase-12 and cleaved-caspase-3, as well as defective autophagy, as shown by increased Beclin1, LC3-II and p62 expression in hippocampus. Consistently, the in vitro results further verified the findings of in vivo study that NaF induced excessive ER stress and defective autophagy in SH-SY5Y cells. Notably, inhibition of autophagy in NaF-treated SH-SY5Y cells with Wortmannin or Chloroquine decreased, while induction of autophagy by Rapamycin increased the cell viability. These results were correlated well with the immunofluorescence observations, thus confirming the pivotal role of autophagic flux dysfunction in NaF-induced cell death. Importantly, mitigation of ER stress by 4-phenylbutyrate in NaF-treated SH-SY5Y cells inhibited the expressions of autophagy markers, and decreased cell apoptosis. Taken together, these data suggest that neuronal death resulted from excessive ER stress and autophagic flux dysfunction contributes to fluoride-elicited neurotoxicity. Moreover, the autophagic flux dysfunction was mediated by excessive ER stress, which provided novel insight into a better understanding of fluoride-induced neurotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Sensitizing effect of Ho3+ on the Er3+: 2.7 μm-emission in fluoride glass

    NASA Astrophysics Data System (ADS)

    Huang, Feifei; Li, Xia; Liu, Xueqiang; Zhang, Junjie; Hu, Lili; Chen, Danping

    2014-03-01

    The fluorescence properties of 2.7 μm emission and energy transfer mechanism of Ho3+/Er3+ co-doped fluoride glass (ZBYA) have been investigated in the present paper. Ho3+ strengthens the Er3+: 2.7 μm emission in the ZBYA glasses due to the energy transfer from Er3+ to Ho3+, while the 1.5 μm emission decreases dramatically. The optimized concentration ratio of Er3+ to Ho3+ is found to be 1:1 in our glass system. The absorption and emission spectra are tested and the sample possesses large emission cross section (16.5 × 10-21 cm2) around 2.7 μm along with larger radiative transition probability (25.11 S-1) on the basis of Judd-Ofelt and Fuchtbauer-Ladenburg theories. Additionally, the energy transfer microparameters are calculated using Förster-Dexter theory and the result shows the energy transfer coefficient of Er3+:4I13/2 → Ho3+:5I7 is 24 times larger than that of Er3+:4I11/2 → Ho3+:5I6. Our results show that Er3+: 2.7 μm emission can be sensitized by Ho3+ efficiently, and this Er3+/Ho3+-codoped fluoride glasses might have potential application in mid-infrared lasers.

  10. Scanning capacitance microscopy of ErAs nanoparticles embedded in GaAs pn junctions

    NASA Astrophysics Data System (ADS)

    Park, K. W.; Nair, H. P.; Crook, A. M.; Bank, S. R.; Yu, E. T.

    2011-09-01

    Scanning capacitance microscopy is used to characterize the electronic properties of ErAs nanoparticles embedded in GaAs pn junctions grown by molecular beam epitaxy. Voltage-dependent capacitance images reveal localized variations in subsurface electronic structure near buried ErAs nanoparticles at lateral length scales of 20-30 nm. Numerical modeling indicates that these variations arise from inhomogeneities in charge modulation due to Fermi level pinning behavior associated with the embedded ErAs nanoparticles. Statistical analysis of image data yields an average particle radius of 6-8 nm—well below the direct resolution limit in scanning capacitance microscopy but discernible via analysis of patterns in nanoscale capacitance images.

  11. Increased intracellular proteolysis reduces disease severity in an ER stress-associated dwarfism.

    PubMed

    Mullan, Lorna A; Mularczyk, Ewa J; Kung, Louise H; Forouhan, Mitra; Wragg, Jordan Ma; Goodacre, Royston; Bateman, John F; Swanton, Eileithyia; Briggs, Michael D; Boot-Handford, Raymond P

    2017-10-02

    The short-limbed dwarfism metaphyseal chondrodysplasia type Schmid (MCDS) is linked to mutations in type X collagen, which increase ER stress by inducing misfolding of the mutant protein and subsequently disrupting hypertrophic chondrocyte differentiation. Here, we show that carbamazepine (CBZ), an autophagy-stimulating drug that is clinically approved for the treatment of seizures and bipolar disease, reduced the ER stress induced by 4 different MCDS-causing mutant forms of collagen X in human cell culture. Depending on the nature of the mutation, CBZ application stimulated proteolysis of misfolded collagen X by either autophagy or proteasomal degradation, thereby reducing intracellular accumulation of mutant collagen. In MCDS mice expressing the Col10a1.pN617K mutation, CBZ reduced the MCDS-associated expansion of the growth plate hypertrophic zone, attenuated enhanced expression of ER stress markers such as Bip and Atf4, increased bone growth, and reduced skeletal dysplasia. CBZ produced these beneficial effects by reducing the MCDS-associated abnormalities in hypertrophic chondrocyte differentiation. Stimulation of intracellular proteolysis using CBZ treatment may therefore be a clinically viable way of treating the ER stress-associated dwarfism MCDS.

  12. Cutting and coagulation during intraoral soft tissue surgery using Er: YAG laser.

    PubMed

    Onisor, I; Pecie, R; Chaskelis, I; Krejci, I

    2013-06-01

    To find the optimal techniques and parameters that enables Er:YAG laser to be used successfully for small intraoral soft tissue interventions, in respect to its cutting and coagulation abilities. In vitro pre-tests: 4 different Er:YAG laser units and one CO2 unit as the control were used for incision and coagulation on porcine lower jaws and optimal parameters were established for each type of intervention and each laser unit: energy, frequency, type, pulse duration and distance. 3 different types of intervention using Er:YAG units are presented: crown lengthening, gingivoplasty and maxillary labial frenectomy with parameters found in the in vitro pre-tests. The results showed a great decrease of the EMG activity of masseter and anterior temporalis muscles. Moreover, the height and width of the chewing cycles in the frontal plane increased after therapy. Er:YAG is able to provide good cutting and coagulation effects on soft tissues. Specific parameters have to be defined for each laser unit in order to obtain the desired effect. Reduced or absent water spray, defocused light beam, local anaesthesia and the most effective use of long pulses are methods to obtain optimal coagulation and bleeding control.

  13. Radiation hardening in sol-gel derived Er{sup 3+}-doped silica glasses

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

    Hari Babu, B., E-mail: hariphy2012@gmail.com, E-mail: matthieu.lancry@u-psud.fr; León Pichel, Mónica; Institut de Chimie Moléculaire et des Matériaux d'Orsay, UMR CNRS-UPSud 8182, Université Paris Sud, 91405 Orsay

    2015-09-28

    The aim of the present paper is to report the effect of radiation on the Er{sup 3+}-doped sol-gel silica glasses. A possible application of these sol-gel glasses could be their use in harsh radiation environments. The sol-gel glasses are fabricated by densification of erbium salt-soaked nanoporous silica xerogels through polymeric sol-gel technique. The radiation-induced attenuation of Er{sup 3+}-doped sol-gel silica is found to increase with erbium content. Electron paramagnetic resonance studies reveal the presence of E′{sub δ} point defects. This happens in the sol-gel aluminum-silica glass after an exposure to γ-rays (kGy) and in sol-gel silica glass after an exposuremore » to electrons (MGy). The concentration levels of these point defects are much lower in γ-ray irradiated sol-gel silica glasses. When the samples are co-doped with Al, the exposure to γ-ray radiation causes a possible reduction of the erbium valence from Er{sup 3+} to Er{sup 2+} ions. This process occurs in association with the formation of aluminum oxygen hole centers and different intrinsic point defects.« less

  14. Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network

    PubMed Central

    Park, Seong H.; Zhu, Peng-Peng; Parker, Rell L.; Blackstone, Craig

    2010-01-01

    Hereditary spastic paraplegias (HSPs; SPG1–45) are inherited neurological disorders characterized by lower extremity spastic weakness. More than half of HSP cases result from autosomal dominant mutations in atlastin-1 (also known as SPG3A), receptor expression enhancing protein 1 (REEP1; SPG31), or spastin (SPG4). The atlastin-1 GTPase interacts with spastin, a microtubule-severing ATPase, as well as with the DP1/Yop1p and reticulon families of ER-shaping proteins, and SPG3A caused by atlastin-1 mutations has been linked pathogenically to abnormal ER morphology. Here we investigated SPG31 by analyzing the distribution, interactions, and functions of REEP1. We determined that REEP1 is structurally related to the DP1/Yop1p family of ER-shaping proteins and localizes to the ER in cultured rat cerebral cortical neurons, where it colocalizes with spastin and atlastin-1. Upon overexpression in COS7 cells, REEP1 formed protein complexes with atlastin-1 and spastin within the tubular ER, and these interactions required hydrophobic hairpin domains in each of these proteins. REEP proteins were required for ER network formation in vitro, and REEP1 also bound microtubules and promoted ER alignment along the microtubule cytoskeleton in COS7 cells. A SPG31 mutant REEP1 lacking the C-terminal cytoplasmic region did not interact with microtubules and disrupted the ER network. These data indicate that the HSP proteins atlastin-1, spastin, and REEP1 interact within the tubular ER membrane in corticospinal neurons to coordinate ER shaping and microtubule dynamics. Thus, defects in tubular ER shaping and network interactions with the microtubule cytoskeleton seem to be the predominant pathogenic mechanism of HSP. PMID:20200447

  15. Resonantly diode-pumped continuous-wave and Q-switched Er:YAG laser at 1645 nm.

    PubMed

    Chang, N W H; Simakov, N; Hosken, D J; Munch, J; Ottaway, D J; Veitch, P J

    2010-06-21

    We describe an efficient Er:YAG laser that is resonantly pumped using continuous-wave (CW) laser diodes at 1470 nm. For CW lasing, it emits 6.1 W at 1645 nm with a slope efficiency of 36%, the highest efficiency reported for an Er:YAG laser that is pumped in this manner. In Q-switched operation, the laser produces diffraction-limited pulses with an average power of 2.5 W at 2 kHz PRF. To our knowledge this is the first Q-switched Er:YAG laser resonantly pumped by CW laser diodes.

  16. Artemisinin dimer anti-cancer activity correlates with heme-catalyzed ROS generation and ER stress induction

    PubMed Central

    Stockwin, Luke H.; Han, Bingnan; Yu, Sherry X.; Hollingshead, Melinda G.; ElSohly, Mahmoud A.; Gul, Waseem; Slade, Desmond; Galal, Ahmed M.; Newton, Dianne L.

    2009-01-01

    Analogs of the malaria therapeutic, artemisinin, possess in vitro and in vivo anti-cancer activity. In this study, two dimeric artemisinins (NSC724910 and 735847) were studied to determine their mechanism of action. Dimers were >1000 fold more active than monomer and treatment was associated with increased reactive oxygen species (ROS) and apoptosis induction. Dimer activity was inhibited by the anti-oxidant L-NAC, the iron chelator desferroxamine, and exogenous hemin. Similarly, induction of heme oxygenase (HMOX) with CoPPIX inhibited activity while inhibition of HMOX with SnPPIX enhanced it. These results emphasize the importance of iron, heme and ROS in activity. Microarray analysis of dimer treated cells identified DNA damage; iron/heme and cysteine/methionine metabolism, antioxidant response, and endoplasmic reticulum (ER) stress as affected pathways. Detection of an ER-stress response was relevant because in malaria, artemisinin inhibits pfATP6, the plasmodium orthologue of mammalian ER-resident SERCA Ca2+-ATPases. A comparative study of NSC735847 with thapsigargin, a specific SERCA inhibitor and ER-stress inducer showed similar behavior in terms of transcriptomic changes, induction of endogenous SERCA and ER calcium mobilization. However, thapsigargin had little effect on ROS production, modulated different ER-stress proteins and had greater potency against purified SERCA1. Furthermore, an inactive derivative of NSC735847 that lacked the endoperoxide had identical inhibitory activity against purified SERCA1, suggesting that direct inhibition of SERCA has little inference on overall cytotoxicity. In summary, these data implicate indirect ER-stress induction as a central mechanism of artemisinin dimer activity. PMID:19533749

  17. Intracellular zinc distribution in mitochondria, ER and the Golgi apparatus

    PubMed Central

    Lu, Qiping; Haragopal, Hariprakash; Slepchenko, Kira G; Stork, Christian; Li, Yang V

    2016-01-01

    Zinc (Zn2+) is required for numerous cellular functions. As such, the homeostasis and distribution of intracellular zinc can influence cellular metabolism and signaling. However, the exact distribution of free zinc within live cells remains elusive. Previously we showed the release of zinc from thapsigargin/IP3-sensitive endoplasmic reticulum (ER) storage in cortical neurons. In the present study, we investigated if other cellular organelles also contain free chelatable zinc and function as organelle storage for zinc. To identify free zinc within the organelles, live cells were co-stained with Zinpyr-1, a zinc fluorescent dye, and organelle-specific fluorescent dyes (MitoFluor Red 589: mitochondria; ER Tracker Red: endoplasmic reticulum; BODIPY TR ceramide: Golgi apparatus; Syto Red 64: nucleus). We examined organelles that represent potential storing sites for intracellular zinc. We showed that zinc fluorescence staining was co-localized with MitoFluor Red 589, ER Tracker Red, and BODIPY TR ceramide respectively, suggesting the presence of free zinc in mitochondria, endoplasmic reticulum, and the Golgi apparatus. On the other hand, cytosol and nucleus had nearly no detectable zinc fluorescence. It is known that nucleus contains high amount of zinc binding proteins that have high zinc binding affinity. The absence of zinc fluorescence suggests that there is little free zinc in these two regions. It also indicates that the zinc fluorescence detected in mitochondria, ER and Golgi apparatus represents free chelatable zinc. Taken together, our results support that these organelles are potential zinc storing organelles during cellular zinc homeostasis. PMID:27186321

  18. Endoplasmic reticulum calcium release potentiates the ER stress and cell death caused by an oxidative stress in MCF-7 cells.

    PubMed

    Dejeans, Nicolas; Tajeddine, Nicolas; Beck, Raphaël; Verrax, Julien; Taper, Henryk; Gailly, Philippe; Calderon, Pedro Buc

    2010-05-01

    Increase in cytosolic calcium concentration ([Ca2+](c)), release of endoplasmic reticulum (ER) calcium ([Ca2+](er)) and ER stress have been proposed to be involved in oxidative toxicity. Nevertheless, their relative involvements in the processes leading to cell death are not well defined. In this study, we investigated whether oxidative stress generated during ascorbate-driven menadione redox cycling (Asc/Men) could trigger these three events, and, if so, whether they contributed to Asc/Men cytoxicity in MCF-7 cells. Using microspectrofluorimetry, we demonstrated that Asc/Men-generated oxidative stress was associated with a slow and moderate increase in [Ca2+](c), largely preceding permeation of propidium iodide, and thus cell death. Asc/Men treatment was shown to partially deplete ER calcium stores after 90 min (decrease by 45% compared to control). This event was associated with ER stress activation, as shown by analysis of eIF2 phosphorylation and expression of the molecular chaperone GRP94. Thapsigargin (TG) was then used to study the effect of complete [Ca2+](er) emptying during the oxidative stress generated by Asc/Men. Surprisingly, the combination of TG and Asc/Men increased ER stress to a level considerably higher than that observed for either treatment alone, suggesting that [Ca2+](er) release alone is not sufficient to explain ER stress activation during oxidative stress. Finally, TG-mediated [Ca2+](er) release largely potentiated ER stress, DNA fragmentation and cell death caused by Asc/Men, supporting a role of ER stress in the process of Asc/Men cytotoxicity. Taken together, our results highlight the involvement of ER stress and [Ca2+](er) decrease in the process of oxidative stress-induced cell death in MCF-7 cells. 2009 Elsevier Inc. All rights reserved.

  19. Overcoming Endocrine Resistance by Targeting ER/FoxA1/IL 8 Axis

    DTIC Science & Technology

    2016-10-01

    INTRODUCTION Approximately 75% of breast cancers express the hormone estrogen receptor α (ER). As a critical determinant in estrogen response and oncogenic...factor of estrogen receptor α (ER)–chromatin binding and function, yet its aberration in endocrine-resistant (Endo-R) breast cancer is unknown. Here, we...positive tumors. FOXA1 | estrogen receptor | breast cancer | transcriptional reprogramming | endocrine resistance About 75% of breast cancers express

  20. Absence of exchange interaction between localized magnetic moments and conduction-electrons in diluted Er{sup 3+} gold-nanoparticles

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

    Lesseux, G. G., E-mail: lesseux@ifi.unicamp.br; Urbano, R. R.; Iwamoto, W.

    2014-05-07

    The Electron Spin Resonance (ESR) of diluted Er{sup 3+} magnetic ions in Au nanoparticles (NPs) is reported. The NPs were synthesized by reducing chloro triphenyl-phosphine gold(I) and erbium(III) trifluoroacetate. The Er{sup 3+} g-value along with the observed hyperfine splitting indicate that the Er{sup 3+} impurities are in a local cubic symmetry. Furthermore, the Er{sup 3+} ESR spectra show that the exchange interaction between the 4f and the conduction electrons (ce) is absent or negligible in Au{sub 1–x}Er{sub x} NPs, in contrast to the ESR results in bulk Au{sub 1–x}Er{sub x}. Therefore, the nature of this interaction needs to be reexaminedmore » at the nano scale range.« less

  1. ERMO3/MVP1/GOLD36 Is Involved in a Cell Type-Specific Mechanism for Maintaining ER Morphology in Arabidopsis thaliana

    PubMed Central

    Nakano, Ryohei Thomas; Matsushima, Ryo; Nagano, Atsushi J.; Fukao, Yoichiro; Fujiwara, Masayuki; Kondo, Maki; Nishimura, Mikio; Hara-Nishimura, Ikuko

    2012-01-01

    The endoplasmic reticulum (ER) has a unique, network-like morphology. The ER structures are composed of tubules, cisternae, and three-way junctions. This morphology is highly conserved among eukaryotes, but the molecular mechanism that maintains ER morphology has not yet been elucidated. In addition, certain Brassicaceae plants develop a unique ER-derived organelle called the ER body. This organelle accumulates large amounts of PYK10, a β-glucosidase, but its physiological functions are still obscure. We aimed to identify a novel factor required for maintaining the morphology of the ER, including ER bodies, and employed a forward-genetic approach using transgenic Arabidopsis thaliana (GFP-h) with fluorescently-labeled ER. We isolated and investigated a mutant (designated endoplasmic reticulum morphology3, ermo3) with huge aggregates and abnormal punctate structures of ER. ERMO3 encodes a GDSL-lipase/esterase family protein, also known as MVP1. Here, we showed that, although ERMO3/MVP1/GOLD36 was expressed ubiquitously, the morphological defects of ermo3 were specifically seen in a certain type of cells where ER bodies developed. Coimmunoprecipitation analysis combined with mass spectrometry revealed that ERMO3/MVP1/GOLD36 interacts with the PYK10 complex, a huge protein complex that is thought to be important for ER body-related defense systems. We also found that the depletion of transcription factor NAI1, a master regulator for ER body formation, suppressed the formation of ER-aggregates in ermo3 cells, suggesting that NAI1 expression plays an important role in the abnormal aggregation of ER. Our results suggest that ERMO3/MVP1/GOLD36 is required for preventing ER and other organelles from abnormal aggregation and for maintaining proper ER morphology in a coordinated manner with NAI1. PMID:23155454

  2. Water-assisted pulsed Er:YAG laser interaction with silicon

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

    Kim, Jaehun; Ki, Hyungson, E-mail: hski@unist.ac.kr

    2015-07-07

    Silicon is virtually transparent to the Er:YAG laser with a wavelength of 2.94 μm. In this study, we report that moderately doped silicon (1–10 Ω cm) can be processed by a pulsed Er:YAG laser with a pulse duration of 350 μs and a peak laser intensity of 1.7 × 10{sup 5} W/cm{sup 2} by applying a thin water layer on top of silicon as a light absorbing medium. In this way, water is heated first by strongly absorbing the laser energy and then heats up the silicon wafer indirectly. As the silicon temperature rises, the free carrier concentration and therefore the absorption coefficient of silicon willmore » increase significantly, which may enable the silicon to get directly processed by the Er:YAG laser when the water is vaporized completely. We also believe that the change in surface morphology after melting could contribute to the increase in the laser beam absorptance. It was observed that 525 nm-thick p-type wafer specimens were fully penetrated after 15 laser pulses were irradiated. Bright yellow flames were observed during the process, which indicates that the silicon surface reached the melting point.« less

  3. Temperature variation during apicectomy with Er:YAG laser.

    PubMed

    Bodrumlu, Emre; Keskiner, Ilker; Sumer, Mahmut; Sumer, A Pinar; Telcıoglu, N Tuba

    2012-08-01

    The purpose of this in vitro study was to evaluate the generated temperature of the Er:YAG laser, with three different pulse durations for apicectomy, compared with tungsten bur and surgical saw. Apicectomy is an endodontic surgery performed to remove the root apex and curette adjacent periapical tissue because of lesions of the apical area that are not healing properly. Sixty single-rooted extracted human teeth were resected by three cutting methods: tungsten bur, surgical saw, and Er:YAG laser irradiation with three different pulse durations; pulse duration 50 μs, pulse duration 100 μs, and pulse duration 300 μs. Teflon-insulated, type K thermocouples were used to measure temperature changes during the apicectomy process. Data were analyzed using the general linear models procedure of the SPSS statistical software program. Although there was no statistically significant difference for the mean values of temperature changes at 1 mm away to the cutting site of teeth, there was statistically significant difference among groups for the mean values of temperature changes at 3 mm away to the cutting site of teeth. Additionally, there was statistically significant difference among groups for the total time required for apicectomy. The laser irradiation with pulse duration 50 μs appears to have the lowest temperature rise and the shortest time required for apicectomy of the three pulse durations. However, Er:YAG laser for apicectomy in all pulse durations could be used safely for resection in endodontics in the presence of sufficient water.

  4. Ocean wind field measurement performance of the ERS-1 scatterometer

    NASA Technical Reports Server (NTRS)

    Hans, P.; Schuessler, H.

    1984-01-01

    The Active Microwave Instrumentation (AMI), which will be implemented on the ERS-1, is a 5.3 GHz multipurpose radar for land surface imaging, ocean wave spectrum measurement and wind observations over oceans. The imaging and wave measurements apply Synthetic Aperture Radar (SAR) techniques, while wind field detection is performed by the Scatterometer as part of the AMI. The Scatterometer system design was developed and optimized with the aid of a performance simulator. This paper, aimed at giving an overview, is presented about the: (1) ERS-1 Scatterometer system design; (2) Error budget; and the (3) Overall calibration concept.

  5. LOCAL TRANSLATION. Comment on "Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling".

    PubMed

    Reid, David W; Nicchitta, Christopher V

    2015-06-12

    Jan et al. (Research Articles, 7 November 2014, p. 716) propose that ribosomes translating secretome messenger RNAs (mRNAs) traffic from the cytosol to the endoplasmic reticulum (ER) upon emergence of the signal peptide and return to the cytosol after termination. An accounting of controls demonstrates that mRNAs initiate translation on ER-bound ribosomes and that ribosomes are retained on the ER through many cycles of translation. Copyright © 2015, American Association for the Advancement of Science.

  6. Fabrication and Sintering Behavior of Er:SrF2 Transparent Ceramics using Chemically Derived Powder

    PubMed Central

    Liu, Jun; Liu, Peng; Wang, Jun; Xu, Xiaodong; Li, Dongzhen; Zhang, Jian; Nie, Xinming

    2018-01-01

    In this paper, we report the fabrication of high-quality 5 at. % Er3+ ions doped SrF2 transparent ceramics, the potential candidate materials for a mid-infrared laser-gain medium by hot-pressing at 700 °C for 40 h using a chemically-derived powder. The phase structure, densification, and microstructure evolution of the Er:SrF2 ceramics were systematically investigated. In addition, the grain growth kinetic mechanism of Er:SrF2 was clarified. The results showed lattice diffusion to be the grain growth mechanism in the Er:SrF2 transparent ceramic of which highest in-line transmittance reached 92% at 2000 nm, i.e., very close to the theoretical transmittance value of SrF2 single crystal. Furthermore, the emission spectra showed that the strongest emission band was located at 2735 nm. This means that it is possible to achieve a laser output of approximately 2.7 μm in the 5 at. % Er3+ ions doped SrF2 transparent ceramics. PMID:29565322

  7. A class of dynamin-like GTPases involved in the generation of the tubular ER network

    PubMed Central

    Hu, Junjie; Shibata, Yoko; Zhu, Peng-Peng; Voss, Christiane; Rismanchi, Neggy; Prinz, William A.; Rapoport, Tom A.; Blackstone, Craig

    2009-01-01

    The endoplasmic reticulum (ER) consists of tubules that are shaped by the reticulons and DP1/Yop1p, but how the tubules form an interconnected network is unknown. Here, we show that mammalian atlastins, which are dynamin-like, integral membrane GTPases, interact with the tubule-shaping proteins. The atlastins localize to the tubular ER and are required for proper network formation in vivo and in vitro. Depletion of the atlastins or overexpression of dominant-negative forms inhibits tubule interconnections. The Sey1p GTPase in S. cerevisiae is likely a functional ortholog of the atlastins; it shares the same signature motifs and membrane topology and interacts genetically and physically with the tubule-shaping proteins. Cells simultaneously lacking Sey1p and a tubule-shaping protein have ER morphology defects. These results indicate that formation of the tubular ER network depends on conserved dynamin-like GTPases. Since atlastin-1 mutations cause a common form of hereditary spastic paraplegia, we suggest ER shaping defects as a novel neuropathogenic mechanism. PMID:19665976

  8. Arl6IP1 has the ability to shape the mammalian ER membrane in a reticulon-like fashion.

    PubMed

    Yamamoto, Yasunori; Yoshida, Asuka; Miyazaki, Naoyuki; Iwasaki, Kenji; Sakisaka, Toshiaki

    2014-02-15

    The ER (endoplasmic reticulum) consists of the nuclear envelope and a peripheral network of membrane sheets and tubules. Two classes of the evolutionarily conserved ER membrane proteins, reticulons and REEPs (receptor expression-enhancing proteins)/DP1 (deleted in polyposis locus 1)/Yop1 (YIP 1 partner), shape high-curvature ER tubules. In mammals, four members of the reticulon family and six members of the REEP family have been identified so far. In the present paper we report that Arl6IP1(ADP-ribosylation factor-like 6 interacting protein 1), an anti-apoptotic protein specific to multicellular organisms, is a potential player in shaping the ER tubules in mammalian cells. Arl6IP1, which does not share an overall primary sequence homology with reticulons, harbours reticulon-like short hairpin transmembrane domains and binds to atlastin, a GTPase that mediates the formation of the tubular ER network. Overexpression of Arl6IP1 induced extensive tubular structures of the ER and excluded a luminal protein. Furthermore, overexpression of Arl6IP1 stabilized the ER tubules, allowing the cells to maintain the ER tubules even in the absence of microtubules. Arl6IP1 constricted liposomes into tubules. The short hairpin structures of the transmembrane domains were required for the membrane-shaping activity of Arl6IP1. The results of the present study indicate that Arl6IP1 has the ability to shape high-curvature ER tubules in a reticulon-like fashion.

  9. Photoablation of the cornea with a Q-switched Er:YAG laser

    NASA Astrophysics Data System (ADS)

    Lubatschowski, Holger; Hetzel, U.; Kermani, Omid; Ziolek, Carsten; Drommer, Wolfgang; Ertmer, Wolfgang

    1997-12-01

    In this study the ablation characteristics and the wound healing process of rabbit cornea irradiated with a Q- switched Er:YAG laser was evaluated. The laser, emitting at 2.94 micrometers wavelength, has a pulse width of 100 ns. The spot size on the corneal surface was 1 mm in diameter at a fluence of 750 mJ/cm2. The laser beam was applied by a `flying spot' mode, performing refractive ablations of -7 to -8 dpt. As a biological model, the corneas of 9 rabbits were irradiated. The post-treatment follow-up was as long as 39 days. The treated corneas were investigated by light and electron microscopy. The wound healing on rabbit cornea of the Q-switched Er:YAG laser radiation in corneal tissue processing resembles to what is known from ArF- excimer laser application. To shorten the pulse width by means of Q-switching is one major key to the successful application of the Er:YAG laser for PRK.

  10. Resonantly diode laser pumped 1.6-μm Er:YAG laser

    NASA Astrophysics Data System (ADS)

    Garbuzov, Dmitri; Kudryashov, Igor; Dubinskii, Mark

    2005-06-01

    We report what is believed to be the first demonstration of direct resonant diode pumping of a 1.6-mm Er3+-doped bulk solid-state laser (DPSSL). The most of the results is obtained with pumping Er:YAG by the single mode diode laser packaged in fibered modules. The fibered modules, emitting at 1470 nm and 1530 nm wavelength with and without fiber grating (FBG) stabilization, have been used in pumping experiments. The very first results on high power DPSSL operation achieved with diode array pumping also will be presented. The highest absorbed photon conversion efficiency of 26% has been obtained for Er:YAG DPSSL using the 1470-nm single-mode module. Analysis of the DPSSL input-output characteristics suggests that the obtained slope efficiency can be increased at least up to 40% through the reduction of intracavity losses and pumping efficiency improvement. Diode pumped SSL (DPSSL) operates at a wavelength of 1617 nm and 1645 nm.

  11. A consensus prognostic gene expression classifier for ER positive breast cancer

    PubMed Central

    Teschendorff, Andrew E; Naderi, Ali; Barbosa-Morais, Nuno L; Pinder, Sarah E; Ellis, Ian O; Aparicio, Sam; Brenton, James D; Caldas, Carlos

    2006-01-01

    Background A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer. Results Here we perform a combined analysis of three major breast cancer microarray data sets to hone in on a universally valid prognostic molecular classifier in estrogen receptor (ER) positive tumors. Using a recently developed robust measure of prognostic separation, we further validate the prognostic classifier in three external independent cohorts, confirming the validity of our molecular classifier in a total of 877 ER positive samples. Furthermore, we find that molecular classifiers may not outperform classical prognostic indices but that they can be used in hybrid molecular-pathological classification schemes to improve prognostic separation. Conclusion The prognostic molecular classifier presented here is the first to be valid in over 877 ER positive breast cancer samples and across three different microarray platforms. Larger multi-institutional studies will be needed to fully determine the added prognostic value of molecular classifiers when combined with standard prognostic factors. PMID:17076897

  12. Effect of Er,Cr:YSGG laser on human dentin fluid flow.

    PubMed

    Al-Omari, Wael M; Palamara, Joseph E

    2013-11-01

    The aim of the current investigation was to assess the rate and magnitude of dentin fluid flow of dentinal surfaces irradiated with Er,Cr:YSGG laser. Twenty extracted third molars were sectioned, mounted, and irradiated with Er,Cr:YSGG laser at 3.5 and 4.5 W power settings. Specimens were connected to an automated fluid flow measurement apparatus (Flodec). The rate, magnitude, and direction of dentin fluid flow were recorded at baseline and after irradiation. Nonparametric Wilcoxon signed ranks repeated measure t test revealed a statistically significant reduction in fluid flow for all the power settings. The 4.5-W power output reduced the flow significantly more than the 3.5 W. The samples showed a baseline outward flow followed by inward flow due to irradiation then followed by decreased outward flow. It was concluded that Er,Cr:YSGG laser irradiation at 3.5 and 4.5 W significantly reduced dentinal fluid flow rate. The reduction was directly proportional to power output.

  13. Highly efficient dual-wavelength mid-infrared CW Laser in diode end-pumped Er:SrF2 single crystals

    PubMed Central

    Ma, Weiwei; Qian, Xiaobo; Wang, Jingya; Liu, Jingjing; Fan, Xiuwei; Liu, Jie; Su, Liangbi; Xu, Jun

    2016-01-01

    The spectral properties and laser performance of Er:SrF2 single crystals were investigated and compared with Er:CaF2. Er:SrF2 crystals have larger absorption cross-sections at the pumping wavelength, larger mid-infrared stimulated emission cross-sections and much longer fluorescence lifetimes of the upper laser level (Er3+:4I11/2 level) than those of Er:CaF2 crystals. Dual-wavelength continuous-wave (CW) lasers around 2.8 μm were demonstrated in both 4at.% and 10at.% Er:SrF2 single crystals under 972 nm laser diode (LD) end pumping. The laser wavelengths are 2789.3 nm and 2791.8 nm in the former, and 2786.4 nm and 2790.7 nm in the latter, respectively. The best laser performance has been demonstrated in lightly doped 4at.% Er:SrF2 with a low threshold of 0.100 W, a high slope efficiency of 22.0%, an maximum output power of 0.483 W. PMID:27811994

  14. Highly efficient dual-wavelength mid-infrared CW Laser in diode end-pumped Er:SrF2 single crystals.

    PubMed

    Ma, Weiwei; Qian, Xiaobo; Wang, Jingya; Liu, Jingjing; Fan, Xiuwei; Liu, Jie; Su, Liangbi; Xu, Jun

    2016-11-04

    The spectral properties and laser performance of Er:SrF 2 single crystals were investigated and compared with Er:CaF 2 . Er:SrF 2 crystals have larger absorption cross-sections at the pumping wavelength, larger mid-infrared stimulated emission cross-sections and much longer fluorescence lifetimes of the upper laser level (Er 3+ : 4 I 11/2 level) than those of Er:CaF 2 crystals. Dual-wavelength continuous-wave (CW) lasers around 2.8 μm were demonstrated in both 4at.% and 10at.% Er:SrF 2 single crystals under 972 nm laser diode (LD) end pumping. The laser wavelengths are 2789.3 nm and 2791.8 nm in the former, and 2786.4 nm and 2790.7 nm in the latter, respectively. The best laser performance has been demonstrated in lightly doped 4at.% Er:SrF 2 with a low threshold of 0.100 W, a high slope efficiency of 22.0%, an maximum output power of 0.483 W.

  15. Highly efficient dual-wavelength mid-infrared CW Laser in diode end-pumped Er:SrF2 single crystals

    NASA Astrophysics Data System (ADS)

    Ma, Weiwei; Qian, Xiaobo; Wang, Jingya; Liu, Jingjing; Fan, Xiuwei; Liu, Jie; Su, Liangbi; Xu, Jun

    2016-11-01

    The spectral properties and laser performance of Er:SrF2 single crystals were investigated and compared with Er:CaF2. Er:SrF2 crystals have larger absorption cross-sections at the pumping wavelength, larger mid-infrared stimulated emission cross-sections and much longer fluorescence lifetimes of the upper laser level (Er3+:4I11/2 level) than those of Er:CaF2 crystals. Dual-wavelength continuous-wave (CW) lasers around 2.8 μm were demonstrated in both 4at.% and 10at.% Er:SrF2 single crystals under 972 nm laser diode (LD) end pumping. The laser wavelengths are 2789.3 nm and 2791.8 nm in the former, and 2786.4 nm and 2790.7 nm in the latter, respectively. The best laser performance has been demonstrated in lightly doped 4at.% Er:SrF2 with a low threshold of 0.100 W, a high slope efficiency of 22.0%, an maximum output power of 0.483 W.

  16. Analysis of Shear Bond Strength and Morphology of Er:YAG Laser-Recycled Ceramic Orthodontic Brackets

    PubMed Central

    Han, Ruo-qiao; Ji, Ling-fei; Ling, Chen

    2016-01-01

    Objective. The aim of this study was to compare the recycling of deboned ceramic brackets via an Er:YAG laser or via the traditional chairside processing methods of flaming and sandblasting; shear bond strength and morphological changes were evaluated in recycled brackets versus new brackets. Materials and Methods. 3M Clarity Self-Ligating Ceramic Brackets with a microcrystalline base were divided into groups subjected to flaming, sandblasting, or exposure to an Er:YAG laser. New ceramic brackets served as a control group. Shear bond strengths were determined with an Electroforce test machine and tested for statistical significance through analysis of variance. Morphological examinations of the recycled ceramic bracket bases were conducted with scanning electron microscopy and confocal laser scanning microscopy. Residue on the bracket base was analyzed with Raman spectroscopy. Results. Faded, dark adhesive was left on recycled bracket bases processed via flaming. Adhesive was thoroughly removed by both sandblasting and exposure to an Er:YAG laser. Compared with new brackets, shear bond strength was lower after sandblasting (p < 0.05), but not after exposure to an Er:YAG laser. The Er:YAG laser caused no damage to the bracket. Conclusion. Er:YAG lasers effectively remove adhesive from the bases of ceramic brackets without damaging them; thus, this method may be preferred over other recycling methods. PMID:27047964

  17. Scanning electron microscopic study of the effects of Er:YAG laser on root cementum.

    PubMed

    Fujii, T; Baehni, P C; Kawai, O; Kawakami, T; Matsuda, K; Kowashi, Y

    1998-11-01

    Use of Er:YAG laser has been proposed for the removal of microbial deposits and calculus present on teeth affected by periodontal disease. However, the influence of Er:YAG laser irradiation on root surfaces has not yet been fully investigated. The aim of the present study was to evaluate the effects of Er:YAG laser irradiation on root cementum by scanning electron microscopy (SEM). Specimens were obtained from extracted human periodontally-diseased teeth using a water-cooled high-speed bur. An Er:YAG laser beam was then applied at various powers ranging from 25 to 100 mJ/ pulse/sec. The laser irradiation was performed under water irrigation, with the tip held perpendicular to the root surface in the contact mode. Following laser exposure, specimens were fixed, dehydrated, and dried at critical-point in liquid CO2. After mounting on SEM plates and sputter-coating with gold, the cementum surface was examined by SEM. Observations of the root surface showed a relatively flat surface in control specimens. In Er:YAG exposed specimens, the laser beam created a circular, notched-edge, crater-like defect on the root. The bottom of the lesion showed an irregular and sharp-pointed surface. Subsequently, the specimens were fractured with a sharp scalpel perpendicularly to the surface. SEM observations of these specimens showed a 15 microm layer of damaged tissue within the laser-irradiated cementum. The tissue presented an amorphous appearance and the Sharpey's and matrix fiber bundles were not clearly distinguishable. These observations indicate that cementum tissue could be damaged by Er:YAG laser irradiation.

  18. Sensitizing properties of luminescence centers on the emission of Er{sup 3+} in Si-rich SiO{sub 2} film

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

    Fu, Qianyu; Gao, Yuhan; Li, Dongsheng, E-mail: mselds@zju.edu.cn

    2016-05-28

    In this paper, we report on the luminescence-center (LC)-mediated excitation of Er{sup 3+} as a function of annealing temperature in Er-doped Si-rich SiO{sub 2} (SRO) films fabricated by electron beam evaporation. It is found that the annealing temperature has significant effects on the emission of Er{sup 3+} and the specific optical-active point-defects called LCs within Er-doped SRO films. Different luminescence centers generated by the evolution of microstructures during annealing process act as efficient sensitizers for Er{sup 3+} in the films when the annealing temperature is below 1100 °C. Moreover, the temperature dependence of the energy coupling between LCs and Er{sup 3+}more » demonstrates the effective phonon-mediated energy transfer process. In addition, when the annealing temperature reaches 1100 °C, the decreased density of activable erbium ions induced by the aggregation of Er will bring detrimental effects on the emission of Er{sup 3+}. It is demonstrated that an appropriate annealing process can be designed to achieve efficiently enhanced emissions from Er{sup 3+} ions by optimizing the density of LCs and the coupling between Er{sup 3+} and LCs.« less

  19. ER-associated SNAREs and Sey1p mediate nuclear fusion at two distinct steps during yeast mating.

    PubMed

    Rogers, Jason V; Arlow, Tim; Inkellis, Elizabeth R; Koo, Timothy S; Rose, Mark D

    2013-12-01

    During yeast mating, two haploid nuclei fuse membranes to form a single diploid nucleus. However, the known proteins required for nuclear fusion are unlikely to function as direct fusogens (i.e., they are unlikely to directly catalyze lipid bilayer fusion) based on their predicted structure and localization. Therefore we screened known fusogens from vesicle trafficking (soluble N-ethylmaleimide-sensitive factor attachment protein receptors [SNAREs]) and homotypic endoplasmic reticulum (ER) fusion (Sey1p) for additional roles in nuclear fusion. Here we demonstrate that the ER-localized SNAREs Sec20p, Ufe1p, Use1p, and Bos1p are required for efficient nuclear fusion. In contrast, Sey1p is required indirectly for nuclear fusion; sey1Δ zygotes accumulate ER at the zone of cell fusion, causing a block in nuclear congression. However, double mutants of Sey1p and Sec20p, Ufe1p, or Use1p, but not Bos1p, display extreme ER morphology defects, worse than either single mutant, suggesting that retrograde SNAREs fuse ER in the absence of Sey1p. Together these data demonstrate that SNAREs mediate nuclear fusion, ER fusion after cell fusion is necessary to complete nuclear congression, and there exists a SNARE-mediated, Sey1p-independent ER fusion pathway.

  20. Insights on the involvement of (-)-epigallocatechin gallate in ER stress-mediated apoptosis in age-related macular degeneration.

    PubMed

    Karthikeyan, Bose; Harini, Lakshminarasimhan; Krishnakumar, Vaithilingam; Kannan, Velu Rajesh; Sundar, Krishnan; Kathiresan, Thandavarayan

    2017-01-01

    Endoplasmic reticulum (ER) stress-mediated apoptosis is a well-known factor in the pathogenesis of age-related macular degeneration (AMD). ER stress leads to accumulation of misfolded proteins, which in turn activates unfolded protein response (UPR) of the cell for its survival. The prolonged UPR of ER stress promotes cell death; however, the transition between adaptation and ER stress-induced apoptosis has not been clearly understood. Hence, the present study investigates the regulatory effect of (-)-epigallocatechin gallate (EGCG) on ER stress-induced by hydrogen peroxide (H 2 O 2 ) and disturbance of calcium homeostasis by thapsigargin (TG) in mouse retinal pigment epithelial (MRPE) cells. The oxidant molecules influenced MRPE cells showed an increased level of intracellular calcium [Ca 2+ ] i in ER and transferred to mitochondria through ER-mitochondrial tether site then increased ROS production. EGCG restores [Ca 2+ ] i homeostasis by decreasing ROS production through inhibition of prohibitin1 which regulate ER-mitochondrial tether site and inhibit apoptosis. Effect of EGCG on ER stress-mediated apoptosis was elucidated by exploring the UPR signalling pathways. EGCG downregulated GRP78, CHOP, PERK, ERO1α, IRE1α, cleaved PARP, cleaved caspase 3, caspase 12 and upregulated expression of calnexinin MRPE cells. In addition to this, inhibition of apoptosis by EGCG was also confirmed with expression of proteins Akt, PTEN and GSK3β. MRPE cells with EGCG upregulates phosphorylation of Akt at ser473 and phospho ser380 of PTEN, but phosphorylation at ser9 of GSK3β was inhibited. Further, constitutively active (myristoylated) CA-Akt transfected in MRPE cells had an increased Akt activity in EGCG influenced cells. These findings strongly suggest that antioxidant molecules inhibit cell death through the proper balancing of [Ca 2+ ] i and ROS production in order to maintain UPR of ER in MRPE cells. Thus, modulation of UPR signalling may provide a potential target for

  1. An exploration of factors associated with post-traumatic stress in ER nurses.

    PubMed

    Lavoie, Stéphane; Talbot, Lise R; Mathieu, Luc; Dallaire, Clémence; Dubois, Marie-France; Courcy, François

    2016-03-01

    Emergency room (ER) nurses are frequently exposed to traumatic events (TE) at work. These events can lead to symptoms of post-traumatic stress disorder (PTSD). The goal of the present study was to describe the factors associated with PTSD symptoms. A cross-sectional descriptive correlational design was used. The sample consisted of 35 nurses from an ER in Québec (Canada). Data were collected through self-administered questionnaires. TEs presenting a grief component (e.g. intentional injury to a child and patient suicide) are positively associated with peritraumatic distress (PD) in the days after the event. PD is positively associated with PTSD symptoms. Two personality traits (neuroticism and extraversion) should also be considered. Neuroticism is positively associated with PD whereas extraversion is negatively associated with PD and PTSD symptoms. The results are consistent with the literature, but some of these results are new to nurses. They suggest that in this population, TEs in the ER represent 'red flags'. Their occurrence should mobilise support structures. PD and its personality traits are also key factors to consider. To provide adequate support for nurses, ER managers should be on the alert for these conditions. Interventions should be adapted to these findings. © 2015 John Wiley & Sons Ltd.

  2. ER-associated degradation is required for vasopressin prohormone processing and systemic water homeostasis

    PubMed Central

    Somlo, Diane R.M.; Kim, Geun Hyang; Prescianotto-Baschong, Cristina; Sun, Shengyi; Beuret, Nicole; Long, Qiaoming; Rutishauser, Jonas

    2017-01-01

    Peptide hormones are crucial regulators of many aspects of human physiology. Mutations that alter these signaling peptides are associated with physiological imbalances that underlie diseases. However, the conformational maturation of peptide hormone precursors (prohormones) in the ER remains largely unexplored. Here, we report that conformational maturation of proAVP, the precursor for the antidiuretic hormone arginine-vasopressin, within the ER requires the ER-associated degradation (ERAD) activity of the Sel1L-Hrd1 protein complex. Serum hyperosmolality induces expression of both ERAD components and proAVP in AVP-producing neurons. Mice with global or AVP neuron–specific ablation of Se1L-Hrd1 ERAD progressively developed polyuria and polydipsia, characteristics of diabetes insipidus. Mechanistically, we found that ERAD deficiency causes marked ER retention and aggregation of a large proportion of all proAVP protein. Further, we show that proAVP is an endogenous substrate of Sel1L-Hrd1 ERAD. The inability to clear misfolded proAVP with highly reactive cysteine thiols in the absence of Sel1L-Hrd1 ERAD causes proAVP to accumulate and participate in inappropriate intermolecular disulfide–bonded aggregates, promoted by the enzymatic activity of protein disulfide isomerase (PDI). This study highlights a pathway linking ERAD to prohormone conformational maturation in neuroendocrine cells, expanding the role of ERAD in providing a conducive ER environment for nascent proteins to reach proper conformation. PMID:28920920

  3. Experimental study using ER-YAG laser in discs: changes in glycosaminoglycan content and synthesis in discs

    NASA Astrophysics Data System (ADS)

    Maehara, Kazuyuki; Nakai, Sadaaki; Naga, Kumi; Nishimoto, Seiji

    2004-09-01

    Changes in discs after Er-Yag laser irradiation are scarcely reported. We made an experimental study using white rabbits and Er-Yag laser. Under general anesthesia, Er-Yag laser was irradiated into lumbar discs. Three or 8 weeks after irradiation, rabbits were sacrificed, and these discs were extracted. The quantitative analysis of the glycosaminoglycan content in the annulus fibrosus, and the incorporation of 35S-sulfate in chondroitin 4 sulfate were measured. The results showed, the increased incorporation of 35S-sulfate in chondroitin 4 sulfate and chondroitin 6 sulfates in groups of laser irradiation may indicate Er-Yag laser irradiation in nucleus pulposus, accelerated glycosaminoglycan production, in the annulus fibrosus. But no difference of unsaturated isomers of chondroitin 4 sulfate, and chondroitin 6 sulfate, and no difference of saturated isomer of keratan sulfate indicate, the influence of Er-Yag laser irradiation was not so high, as to bring the quantitative changes of matrix of annulus fibrosus in term of 8 weeks.

  4. Spatial and Functional Aspects of ER-Golgi Rabs and Tethers

    PubMed Central

    Saraste, Jaakko

    2016-01-01

    Two conserved Rab GTPases, Rab1 and Rab2, play important roles in biosynthetic-secretory trafficking between the endoplasmic reticulum (ER) and the Golgi apparatus in mammalian cells. Both are expressed as two isoforms that regulate anterograde transport via the intermediate compartment (IC) to the Golgi, but are also required for transport in the retrograde direction. Moreover, Rab1 has been implicated in the formation of autophagosomes. Rab1 and Rab2 have numerous effectors or partners that function in membrane tethering, but also have other roles. These include the coiled-coil proteins p115, GM130, giantin, golgin-84, and GMAP-210, as well as the multisubunit COG (conserved oligomeric Golgi) and TRAPP (transport protein particle) tethering complexes. TRAPP also acts as the GTP exchange factor (GEF) in the activation of Rab1. According to the traditional view of the IC elements as motile, transient structures, the functions of the Rabs could take place at the two ends of the ER-Golgi itinerary, i.e., at ER exit sites (ERES) and/or cis-Golgi. However, there is considerable evidence for their specific association with the IC, including its recently identified pericentrosomal domain (pcIC), where many of the effectors turn out to be present, thus being able to exert their functions at the pre-Golgi level. The IC localization of these proteins is of particular interest based on the imaging of Rab1 dynamics, indicating that the IC is a stable organelle that bidirectionally communicates with the ER and Golgi, and is functionally linked to the endosomal system via the pcIC. PMID:27148530

  5. Magnetic properties and large reversible magnetocaloric effect in Er3Pd2

    NASA Astrophysics Data System (ADS)

    Maji, Bibekananda; Ray, Mayukh K.; Modak, M.; Mondal, S.; Suresh, K. G.; Banerjee, S.

    2018-06-01

    The magnetic properties and magnetocaloric effect (MCE) of binary intermetallic compound Er3Pd2 were studied. It exhibits a paramagnetic (PM) to antiferromagnetic (AFM) transition at Néel temperature (TN) = 10 K. A large reversible MCE was observed which is related to a second order magnetic transition from PM to AFM state. The values of maximum magnetic entropy change (- Δ SMmax) and adiabatic temperature change (Δ Tadmax) reach 8.9 J/kg-K and 2.9 K respectively for the field change of 50 kOe with no obvious hysteresis loss. The effective magnetic moment was determined to be 10.16 μB/Er3+, which is notably higher than that of free ion value of Er3+ (9.59 μB), suggests that Pd ions also have considerable amount of magnetic moments in this compound.

  6. Er3+ -doped anatase TiO2 nanocrystals: crystal-field levels, excited-state dynamics, upconversion, and defect luminescence.

    PubMed

    Luo, Wenqin; Fu, Chengyu; Li, Renfu; Liu, Yongsheng; Zhu, Haomiao; Chen, Xueyuan

    2011-11-04

    A comprehensive survey of electronic structure and optical properties of rare-earth ions embedded in semiconductor nanocrystals (NCs) is of vital importance for their potential applications in areas as diverse as luminescent bioprobes, lighting, and displays. Er3+ -doped anatase TiO2 NCs, synthesized via a facile sol-gel solvothermal method, exhibit intense and well-resolved intra-4f emissions of Er3+ . Crystal-field (CF) spectra of Er3+ in TiO2 NCs are systematically studied by means of high-resolution emission and excitation spectra at 10-300 K. The CF analysis of Er3+ assuming a site symmetry of C(2v) yields a small root-mean-square deviation of 25.1 cm(-1) and reveals the relatively large CF strength (549 cm(-1) ) of Er3+, thus verifying the rationality of the C(2v) symmetry assignment of Er3+ in anatase TiO2 NCs. Based on a simplified thermalization model for the temperature-dependent photoluminescence (PL) dynamics from (4) S(3/2) , the intrinsic radiative luminescence lifetimes of (4) S(3/2) and (2) H(11/2) are experimentally determined to be 3.70 and 1.73 μs, respectively. Green and red upconversion (UC) luminescence of Er3+ can be achieved upon laser excitation at 974.5 nm. The UC intensity of Er3+ in Yb/Er-codoped NCs is found to be about five times higher than that of Er-singly-doped counterparts as a result of efficient Yb3+ sensitization and energy transfer upconversion (ETU) evidenced by its distinct UC luminescence dynamics. Furthermore, the origin of defect luminescence is revealed based on the temperature-dependent PL spectra upon excitation above the TiO2 bandgap at 325 nm. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. AAV delivery of GRP78/BiP promotes adaptation of human RPE cell to ER stress.

    PubMed

    Ghaderi, Shima; Ahmadian, Shahin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Samiei, Shahram; Kheitan, Samira; Pirmardan, Ehsan R

    2018-02-01

    Adeno associated virus (AAV)-mediated gene delivery of GRP78 (78 kDa glucose-regulated protein) attenuates the condition of endoplasmic reticulum (ER) stress and prevents apoptotic loss of photoreceptors in Retinitis pigmentosa (RP) rats. In the current study we overexpressed Grp78 with the help of AAV-2 in primary human retinal pigmented epithelium (hRPE) cell cultures and examined its effect on cell response to ER stress. The purpose of this work was studying potential stimulating effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress, as an in vitro model for RPE degeneration. To investigate the effect of Grp78 overexpression on unfolded protein response (UPR) markers under ER stress, hRPE primary cultures were transduced by recombinant virus rAAV/Grp78, and treated with ER stressor drug, tunicamycin. Expression changes of four UPR markers including GRP78, PERK, ATF6α, and GADD153/CHOP, were assessed by real-time PCR and western blotting. We found that GRP78 has a great contribution in modulation of UPR markers to favor adaptive response in ER-stressed hRPE cells. In fact, GRP78 overexpression affected adaptation and apoptotic phases of early UPR, through enhancement of two master regulators/ER stress sensors (PERK and ATF6α) and down-regulation of a key pro-apoptotic cascade activator (GADD153/CHOP). Together these findings demonstrate the promoting effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress. This protein with anti-apoptotic actions in the early UPR and important role in cell fate regulation, can be recruited as a useful candidate for future investigations of RPE degenerative diseases. © 2017 Wiley Periodicals, Inc.

  8. New insights on the functional role of URG7 in the cellular response to ER stress.

    PubMed

    Armentano, Maria Francesca; Caterino, Marianna; Miglionico, Rocchina; Ostuni, Angela; Pace, Maria Carmela; Cozzolino, Flora; Monti, Maria; Milella, Luigi; Carmosino, Monica; Pucci, Piero; Bisaccia, Faustino

    2018-04-28

    Up-regulated Gene clone 7 (URG7) is an ER resident protein, whose expression is up-regulated in the presence of hepatitis B virus X antigen (HBxAg) during HBV infection. In virus-infected hepatocytes, URG7 shows an anti-apoptotic activity due to the PI3K/AKT signalling activation, does not seem to have tumorigenic properties, but it appears to promote the development and progression of fibrosis. However, the molecular mechanisms underlying URG7 activity remain largely unknown. To shed light on URG7 activity, we first analysed its interactome in HepG2 transfected cells: this analysis suggests that URG7 could have a role in affecting protein synthesis, folding and promoting proteins degradation. Moreover, keeping into account its subcellular localisation in the ER and that several viral infections give rise to ER stress, a panel of experiments was performed to evaluate a putative role of URG7 in ER stress. Our main results demonstrate that in ER-stressed cells URG7 is able to modulate the expression of Unfolded Protein Response (UPR) markers towards survival outcomes, up-regulating GRP78 protein and down-regulating the pro-apoptotic protein CHOP. Furthermore, URG7 reduces the ER stress by decreasing the amount of unfolded proteins, by increasing both the total protein ubiquitination and the AKT activation and reducing Caspase 3 activation. All together these data suggest that URG7 plays a pivotal role as a reliever of ER stress-induced apoptosis. This is the first characterisation of URG7 activity under ER stress conditions. The results presented here will help to hypothesise new strategies to counteract the antiapoptotic activity of URG7 in the context of the viral infection. © 2018 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  9. Retention mechanisms for ER and Golgi membrane proteins.

    PubMed

    Gao, Caiji; Cai, Yi; Wang, Yejun; Kang, Byung-Ho; Aniento, Fernando; Robinson, David G; Jiang, Liwen

    2014-08-01

    Unless there are mechanisms to selectively retain membrane proteins in the endoplasmic reticulum (ER) or in the Golgi apparatus, they automatically proceed downstream to the plasma or vacuole membranes. Two types of coat protein complex I (COPI)-interacting motifs in the cytosolic tails of membrane proteins seem to facilitate membrane retention in the early secretory pathway of plants: a dilysine (KKXX) motif (which is typical of p24 proteins) for the ER and a KXE/D motif (which occurs in the Arabidopsis endomembrane protein EMP12) for the Golgi apparatus. The KXE/D motif is highly conserved in all eukaryotic EMPs and is additionally present in hundreds of other proteins of unknown subcellular localization and function. This novel signal may represent a new general mechanism for Golgi targeting and the retention of polytopic integral membrane proteins. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Er3+ phosphate glass optical waveguide amplifiers at 1.5 μm on silicon

    NASA Astrophysics Data System (ADS)

    Yan, Yingchao; Faber, Anne J.; de Waal, Henk

    1996-01-01

    RF-sputtering techniques were employed to produce Er-doped phosphate glass films on thermally oxidized silicon wafers. Film compositions were characterized by X-ray photoelectron spectroscopy. As-deposited films showed very low Er luminescence lifetimes. By postannealing of deposited films in pure oxygen, Er photoluminescence emission lifetime of the 4I13/2 - 4I15/2 transition could be increased from 1 - 2 ms to 8 - 9 ms. The long Er lifetime of the deposited films is very promising for achieving an optical gain. A dependence of measured lifetimes on pump power was observed which are related to a up-conversion quenching process. After postannealing, the sputtered waveguides showed relatively low attenuation loss at the potential pumping and signaling wavelengths. The loss spectrum from 700 nm to 1600 nm was measured by two-prism coupling. The films were easy to be patterned by lithography and ridge channel waveguides were developed by argon plasma etching.

  11. An N-Terminal ER Export Signal Facilitates the Plasma Membrane Targeting of HCN1 Channels in Photoreceptors.

    PubMed

    Pan, Yuan; Laird, Joseph G; Yamaguchi, David M; Baker, Sheila A

    2015-06-01

    Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels are widely expressed in the retina. In photoreceptors, the hyperpolarization-activated current (Ih) carried by HCN1 is important for shaping the light response. It has been shown in multiple systems that trafficking HCN1 channels to specific compartments is key to their function. The localization of HCN1 in photoreceptors is concentrated in the plasma membrane of the inner segment (IS). The mechanisms controlling this localization are not understood. We previously identified a di-arginine endoplasmic reticulum (ER) retention motif that negatively regulates the surface targeting of HCN1. In this study, we sought to identify a forward trafficking signal that could counter the function of the ER retention signal. We studied trafficking of HCN1 and several mutants by imaging their subcellular localization in transgenic X. laevis photoreceptors. Velocity sedimentation was used to assay the assembly state of HCN1 channels. We found the HCN1 N-terminus can redirect a membrane reporter from outer segments (OS) to the plasma membrane of the IS. The sequence necessary for this behavior was mapped to a 20 amino acid region containing a leucine-based ER export motif. The ER export signal is necessary for forward trafficking but not channel oligomerization. Moreover, this ER export signal alone counteracted the di-arginine ER retention signal. We identified an ER export signal in HCN1 that functions with the ER retention signal to maintain equilibrium of HCN1 between the endomembrane system and the plasma membrane.

  12. An N-Terminal ER Export Signal Facilitates the Plasma Membrane Targeting of HCN1 Channels in Photoreceptors

    PubMed Central

    Pan, Yuan; Laird, Joseph G.; Yamaguchi, David M.; Baker, Sheila A.

    2015-01-01

    Purpose. Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels are widely expressed in the retina. In photoreceptors, the hyperpolarization-activated current (Ih) carried by HCN1 is important for shaping the light response. It has been shown in multiple systems that trafficking HCN1 channels to specific compartments is key to their function. The localization of HCN1 in photoreceptors is concentrated in the plasma membrane of the inner segment (IS). The mechanisms controlling this localization are not understood. We previously identified a di-arginine endoplasmic reticulum (ER) retention motif that negatively regulates the surface targeting of HCN1. In this study, we sought to identify a forward trafficking signal that could counter the function of the ER retention signal. Methods. We studied trafficking of HCN1 and several mutants by imaging their subcellular localization in transgenic X. laevis photoreceptors. Velocity sedimentation was used to assay the assembly state of HCN1 channels. Results. We found the HCN1 N-terminus can redirect a membrane reporter from outer segments (OS) to the plasma membrane of the IS. The sequence necessary for this behavior was mapped to a 20 amino acid region containing a leucine-based ER export motif. The ER export signal is necessary for forward trafficking but not channel oligomerization. Moreover, this ER export signal alone counteracted the di-arginine ER retention signal. Conclusions. We identified an ER export signal in HCN1 that functions with the ER retention signal to maintain equilibrium of HCN1 between the endomembrane system and the plasma membrane. PMID:26030105

  13. Synthesis, Structural Characterization and Up-Conversion Luminescence Properties of NaYF4:Er3+,Yb3+@MOFs Nanocomposites

    NASA Astrophysics Data System (ADS)

    Giang, Lam Thi Kieu; Marciniak, Lukasz; Huy, Tran Quang; Vu, Nguyen; Le, Ngo Thi Hong; Binh, Nguyen Thanh; Lam, Tran Dai; Minh, Le Quoc

    2017-10-01

    This paper describes a facile synthesis of NaYF4:Er3+,Yb3+ nanoparticles embraced in metal-organic frameworks (MOFs), known as NaYF4:Er3+, Yb3+@MOFs core/shell nanostructures, by using iron(III) carboxylate (MIL-100) and zeolitic imidazolate frameworks (ZIF-8). Morphological, structural and optical characterization of these nanostructures were investigated by field emission-scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, and up-conversion luminescence measurements. Results showed that spherical-shaped NaYF4:Er3+,Yb3+@MIL-100 nanocomposites with diameters of 150-250 nm, and rod-shaped NaYF4:Er3+,Yb3+@ZIF-8 nanocomposites with lengths of 300-550 nm, were successfully synthesized. Under a 980-nm laser excitation at room temperature, the NaYF4:Er3+,Yb3+@MOFs nanocomposites exhibited strong up-conversion luminescence with two emission bands in the green part of spectrum at 520 nm and 540 nm corresponding to the 2H11/2 → 4I15/2 and 4S3/2 → 4I15/2 transitions of Er3+ ions, respectively, and a red emission band at 655 nm corresponding to the 4F9/2 → 4I15/2 transition of Er3+ ions. The above properties of NaYF4:Er3+,Yb3+@MOFs make them promising candidates for applications in biotechnology.

  14. 20 CFR 222.24 - Relationship as remarried widow(er).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FAMILY RELATIONSHIPS Relationship as Divorced Spouse, Surviving Divorced Spouse, or Remarried Widow(er... the employee in care and remarries, but this marriage is to a person who is entitled to a retirement...

  15. 20 CFR 222.24 - Relationship as remarried widow(er).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... FAMILY RELATIONSHIPS Relationship as Divorced Spouse, Surviving Divorced Spouse, or Remarried Widow(er... the employee in care and remarries, but this marriage is to a person who is entitled to a retirement...

  16. 20 CFR 222.24 - Relationship as remarried widow(er).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... FAMILY RELATIONSHIPS Relationship as Divorced Spouse, Surviving Divorced Spouse, or Remarried Widow(er... the employee in care and remarries, but this marriage is to a person who is entitled to a retirement...

  17. 20 CFR 222.24 - Relationship as remarried widow(er).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... FAMILY RELATIONSHIPS Relationship as Divorced Spouse, Surviving Divorced Spouse, or Remarried Widow(er... the employee in care and remarries, but this marriage is to a person who is entitled to a retirement...

  18. Post examination of copper ER sensors exposed to bentonite

    NASA Astrophysics Data System (ADS)

    Kosec, Tadeja; Kranjc, Andrej; Rosborg, Bo; Legat, Andraž

    2015-04-01

    Copper corrosion in saline solutions under oxic conditions is one of concerns for the early periods of disposal of spent nuclear fuel in deep geological repositories. The main aim of the study was to investigate the corrosion behaviour of copper during this oxic period. The corrosion rate of pure copper was measured by means of thin electrical resistance (ER) sensors that were placed in a test package containing an oxic bentonite/saline groundwater environment at room temperature for a period of four years. Additionally, the corrosion rate was monitored by electrochemical impedance spectroscopy (EIS) measurements that were performed on the same ER sensors. By the end of the exposure period the corrosion rate, as estimated by both methods, had dropped to approximately 1.0 μm/year. The corrosion rate was also estimated by the examination of metallographic cross sections. The post examination tests which were used to determine the type and extent of corrosion products included different spectroscopic techniques (XRD and Raman analysis). It was confirmed that the corrosion rate obtained by means of physical (ER) and electrochemical techniques (EIS) was consistent with that estimated from the metallographic cross section analysis. The corrosion products consisted of cuprous oxide and paratacamite, which was very abundant. From the types of attack it can be concluded that the investigated samples of copper in bentonite underwent uneven general corrosion.

  19. ER stress upregulated PGE2/IFNγ-induced IL-6 expression and down-regulated iNOS expression in glial cells

    NASA Astrophysics Data System (ADS)

    Hosoi, Toru; Honda, Miya; Oba, Tatsuya; Ozawa, Koichiro

    2013-12-01

    The disruption of endoplasmic reticulum (ER) function can lead to neurodegenerative disorders, in which inflammation has also been implicated. We investigated the possible correlation between ER stress and immune function using glial cells. We demonstrated that ER stress synergistically enhanced prostaglandin (PG) E2 + interferon (IFN) γ-induced interleukin (IL)-6 production. This effect was mediated through cAMP. Immune-activated glial cells produced inducible nitric oxide synthase (iNOS). Interestingly, ER stress inhibited PGE2 + IFNγ-induced iNOS expression. Similar results were obtained when cells were treated with dbcAMP + IFNγ. Thus, cAMP has a dual effect on immune reactions; cAMP up-regulated IL-6 expression, but down-regulated iNOS expression under ER stress. Therefore, our results suggest a link between ER stress and immune reactions in neurodegenerative diseases.

  20. Suppression of planar defects in the molecular beam epitaxy of GaAs/ErAs/GaAs heterostructures

    NASA Astrophysics Data System (ADS)

    Crook, Adam M.; Nair, Hari P.; Ferrer, Domingo A.; Bank, Seth R.

    2011-08-01

    We present a growth method that overcomes the mismatch in rotational symmetry of ErAs and conventional III-V semiconductors, allowing for epitaxially integrated semimetal/semiconductor heterostructures. Transmission electron microscopy and reflection high-energy electron diffraction reveal defect-free overgrowth of ErAs layers, consisting of >2× the total amount of ErAs that can be embedded with conventional layer-by-layer growth methods. We utilize epitaxial ErAs nanoparticles, overgrown with GaAs, as a seed to grow full films of ErAs. Growth proceeds by diffusion of erbium atoms through the GaAs spacer, which remains registered to the underlying substrate, preventing planar defect formation during subsequent GaAs growth. This growth method is promising for metal/semiconductor heterostructures that serve as embedded Ohmic contacts to epitaxial layers and epitaxially integrated active plasmonic devices.

  1. Potential emerging treatment in vitiligo using Er:YAG in combination with 5FU and clobetasol.

    PubMed

    Mokhtari, Fatemeh; Bostakian, Anis; Shahmoradi, Zabihollah; Jafari-Koshki, Tohid; Iraji, Fariba; Faghihi, Gita; Hosseini, Sayed Mohsen; Bafandeh, Behzad

    2018-04-01

    Vitiligo is a pigmentary disorder of skin affecting at least 1% of the world population of all races in both sexes. Its importance is mainly due to subsequent social and psychological problems rather than clinical complications. Various treatment choices are available for vitiligo; however, laser-based courses have shown to give more acceptable results. The aim of this trial was to evaluate the efficacy of Er:YAG laser as a supplementary medicine to topical 5FU and clobetasol in vitiligo patients. Two comparable vitiligo patches from 38 eligible patients were randomized to receive topical 5FU and clobetasol in control group and additional Er:YAG laser in intervention group. Major outcomes of interest were the size of patch and pigmentation score at randomization and 2 and 4 months after therapy. Final sample included 18 (47%) male patients and age of 35.66±8.04. The performance Er:YAG group was superior in all sites. Reduction in the size of patches was greater in Er:YAG group (p-value=.004). Also, this group showed a higher pigmentation scores in the trial period than control group (p-value<.001). Greater reduction in the size and increase in pigmentation score was seen in Er:YAG group especially for short periods after therapy and repeating laser sessions may help improving final outcomes. Er:AYG could help in reducing complications of long-term topical treatments, achieving faster response, and improving patient adherence. © 2017 Wiley Periodicals, Inc.

  2. Microstructures and properties of superconducting Y-ErBaCuO thin films obtained from disordered Y-ErBaF2Cu films

    NASA Technical Reports Server (NTRS)

    Cikmach, P.; Diociaiuti, M.; Fontana, A.; Giovannella, C.; Iannuzzi, M.; Lucchini, C.; Merlo, V.; Messi, R.; Paoluzi, L.; Scopa, L.

    1991-01-01

    The preparation procedure used to obtain superconducting thin films by radio frequency magnetron sputtering of a single mosaic target is described in detail. The single mosaic target is composed of (Y-Er), BaF2, and Cu.

  3. Resveratrol Enhances Palmitate-Induced ER Stress and Apoptosis in Cancer Cells

    PubMed Central

    Rojas, Cristina; Pan-Castillo, Belén; Valls, Cristina; Pujadas, Gerard; Garcia-Vallve, Santi; Arola, Lluis; Mulero, Miquel

    2014-01-01

    Background Palmitate, a saturated fatty acid (FA), is known to induce toxicity and cell death in various types of cells. Resveratrol (RSV) is able to prevent pathogenesis and/or decelerate the progression of a variety of diseases. Several in vitro and in vivo studies have also shown a protective effect of RSV on fat accumulation induced by FAs. Additionally, endoplasmic reticulum (ER) stress has recently been linked to cellular adipogenic responses. To address the hypothesis that the RSV effect on excessive fat accumulation promoted by elevated saturated FAs could be partially mediated by a reduction of ER stress, we studied the RSV action on experimentally induced ER stress using palmitate in several cancer cell lines. Principal Findings We show that, unexpectedly, RSV promotes an amplification of palmitate toxicity and cell death and that this mechanism is likely due to a perturbation of palmitate accumulation in the triglyceride form and to a less important membrane fluidity variation. Additionally, RSV decreases radical oxygen species (ROS) generation in palmitate-treated cells but leads to enhanced X-box binding protein-1 (XBP1) splicing and C/EBP homologous protein (CHOP) expression. These molecular effects are induced simultaneously to caspase-3 cleavage, suggesting that RSV promotes palmitate lipoapoptosis primarily through an ER stress-dependent mechanism. Moreover, the lipotoxicity reversion induced by eicosapentaenoic acid (EPA) or by a liver X receptor (LXR) agonist reinforces the hypothesis that RSV-mediated inhibition of palmitate channeling into triglyceride pools could be a key factor in the aggravation of palmitate-induced cytotoxicity. Conclusions Our results suggest that RSV exerts its cytotoxic role in cancer cells exposed to a saturated FA context primarily by triglyceride accumulation inhibition, probably leading to an intracellular palmitate accumulation that triggers a lipid-mediated cell death. Additionally, this cell death is promoted by

  4. ER-associated SNAREs and Sey1p mediate nuclear fusion at two distinct steps during yeast mating

    PubMed Central

    Rogers, Jason V.; Arlow, Tim; Inkellis, Elizabeth R.; Koo, Timothy S.; Rose, Mark D.

    2013-01-01

    During yeast mating, two haploid nuclei fuse membranes to form a single diploid nucleus. However, the known proteins required for nuclear fusion are unlikely to function as direct fusogens (i.e., they are unlikely to directly catalyze lipid bilayer fusion) based on their predicted structure and localization. Therefore we screened known fusogens from vesicle trafficking (soluble N-ethylmaleimide–sensitive factor attachment protein receptors [SNAREs]) and homotypic endoplasmic reticulum (ER) fusion (Sey1p) for additional roles in nuclear fusion. Here we demonstrate that the ER-localized SNAREs Sec20p, Ufe1p, Use1p, and Bos1p are required for efficient nuclear fusion. In contrast, Sey1p is required indirectly for nuclear fusion; sey1Δ zygotes accumulate ER at the zone of cell fusion, causing a block in nuclear congression. However, double mutants of Sey1p and Sec20p, Ufe1p, or Use1p, but not Bos1p, display extreme ER morphology defects, worse than either single mutant, suggesting that retrograde SNAREs fuse ER in the absence of Sey1p. Together these data demonstrate that SNAREs mediate nuclear fusion, ER fusion after cell fusion is necessary to complete nuclear congression, and there exists a SNARE-mediated, Sey1p-independent ER fusion pathway. PMID:24152736

  5. Co-operative energy transfer in Yb3+-Er3+ co-doped SrGdxOy upconverting phosphor

    NASA Astrophysics Data System (ADS)

    Kumar, Ashwini; Pathak, Trilok K.; Dhoble, S. J.; . Terblans, J. J.; Swart, H. C.

    2018-04-01

    Upconversion nanoparticles (UCNPs) have shown considerable interest in many fields; however, low upconversion efficiency of UCNPs is still the most severe limitation of their applications. Yb3+ and Er3+ co-doped SrGd4O7/Gd2O3(SGO) upconversion (UC) phosphors were synthesized by a modified co-precipitation process. The UC properties were investigated by direct excitation with a 980 nm laser. It was observed that the as prepared materials showed relatively strong green emission, while upon the incorporation of the Er3+ ion, there was an increase in the upconversion luminescence intensity for the red component. The effect of different doping concentration of Er3+on the emission spectra and X-ray diffraction patterns of the UC materials have also been studied. The luminescence lifetimes and Commission Internationale de L'Eclairage coordinates for these as prepared samples were determined to understand the energy transfer (ET) mechanisms occurring between Yb3+ and Er3+ in the SGO host matrix. The UC luminescence intensity as a function of laser pump power was monitored and it was confirmed that the UC process in SGO:Yb3+/Er3+is a two-photon absorption process. The findings reported here are expected to provide a better approach for understanding of the ET mechanisms in the oxide based Yb3+/Er3+ co-doped UC phosphors. This study might be helpful in precisely defined applications where optical transitions are essential criterion and this can be easily achieved by smart tuning of the emission properties of Yb3+/Er3+ co-doped UC phosphors.

  6. Detection of the supercycle in V4140 Sagittarii: First eclipsing ER Ursae Majoris-like object

    NASA Astrophysics Data System (ADS)

    Kato, Taichi; Hambsch, Franz-Josef; Cook, Lewis M.

    2018-05-01

    We observed the deeply eclipsing SU UMa-type dwarf nova V4140 Sgr and established the very short supercycle of 69.7(3) d. There were several short outbursts between superoutbursts. These values, together with the short orbital period (0.06143 d), were similar to, but not as extreme as, those of ER UMa-type dwarf novae. The object is thus the first, long sought, eclipsing ER UMa-like object. This ER UMa-like nature can naturally explain the high (apparent) quiescent viscosity and unusual temperature profile in quiescence, which were claimed observational features against the thermal-tidal instability model. The apparently unusual outburst behavior can be reasonably explained by a combination of this ER UMa-like nature and the high orbital inclination, and there is no need to introduce mass transfer bursts from its donor star.

  7. Microwave hydrothermal synthesis and upconversion properties of Yb3+/Er3+ doped YVO4 nanoparticles

    NASA Astrophysics Data System (ADS)

    Kshetri, Yuwaraj K.; Regmi, Chhabilal; Kim, Hak-Soo; Wohn Lee, Soo; Kim, Tae-Ho

    2018-05-01

    Yb3+ and Er3+ doped YVO4 (Yb3+/Er3+:YVO4) nanoparticles with highly efficient near-infrared to visible upconversion properties have been synthesized by microwave hydrothermal process. Uniform-sized Yb3+/Er3+:YVO4 nanoparticles were synthesized within 1 h at 140 °C which is relatively faster than the conventional hydrothermal process. Under 980 nm laser excitation, strong green and less strong red emissions are observed which are attributed to 2H11/2, 4S3/2 to 4I15/2 and 4F9/2 to 4I15/2 transitions of Er3+ respectively. The emission intensity is found to depend strongly on the concentration of Yb3+. The quadratic dependence of upconversion intensity on the excitation power indicates that the upconversion process is governed by two-photon absorption process.

  8. Detection of the supercycle in V4140 Sagittarii: First eclipsing ER Ursae Majoris-like object

    NASA Astrophysics Data System (ADS)

    Kato, Taichi; Hambsch, Franz-Josef; Cook, Lewis M.

    2018-06-01

    We observed the deeply eclipsing SU UMa-type dwarf nova V4140 Sgr and established the very short supercycle of 69.7(3) d. There were several short outbursts between superoutbursts. These values, together with the short orbital period (0.06143 d), were similar to, but not as extreme as, those of ER UMa-type dwarf novae. The object is thus the first, long sought, eclipsing ER UMa-like object. This ER UMa-like nature can naturally explain the high (apparent) quiescent viscosity and unusual temperature profile in quiescence, which were claimed observational features against the thermal-tidal instability model. The apparently unusual outburst behavior can be reasonably explained by a combination of this ER UMa-like nature and the high orbital inclination, and there is no need to introduce mass transfer bursts from its donor star.

  9. Microwave hydrothermal synthesis and upconversion properties of Yb3+/Er3+ doped YVO4 nanoparticles.

    PubMed

    Kshetri, Yuwaraj K; Regmi, Chhabilal; Kim, Hak-Soo; Lee, Soo Wohn; Kim, Tae-Ho

    2018-05-18

    Yb 3+ and Er 3+ doped YVO 4 (Yb 3+ /Er 3+ :YVO 4 ) nanoparticles with highly efficient near-infrared to visible upconversion properties have been synthesized by microwave hydrothermal process. Uniform-sized Yb 3+ /Er 3+ :YVO 4 nanoparticles were synthesized within 1 h at 140 °C which is relatively faster than the conventional hydrothermal process. Under 980 nm laser excitation, strong green and less strong red emissions are observed which are attributed to 2 H 11/2 , 4 S 3/2 to 4 I 15/2 and 4 F 9/2 to 4 I 15/2 transitions of Er 3+ respectively. The emission intensity is found to depend strongly on the concentration of Yb 3+ . The quadratic dependence of upconversion intensity on the excitation power indicates that the upconversion process is governed by two-photon absorption process.

  10. Excitation and De-Excitation Mechanisms of Er-Doped GaAs and A1GaAs.

    DTIC Science & Technology

    1992-12-01

    AD-A258 814 EXCITATION AND DE -EXCITATION MECHANISMS OF Er-DOPED GaAs AND A1GaAs DISSERTATION David W. Elsaesser, Captain, USAF DTICY. ft £ICTE’’ )AN...0 8 1993U -o Wo- .%Approved for public release; Distribution unlimited 93 1 04 022 AFIT/DS/ENP/92-5 EXCITATION AND DE -EXCITATION MECHANISMS OF Er...public release; Distribution unlimited AFIT/DS/ENP/92D-005 EXCITATION AND DE -EXCITATION MECHANISMS OF Er-DOPED GaAs AND A1GaAs 4 toFlor -- David W

  11. Er:YAG laser for the surgical treatment of the carpal tunnel syndrome

    NASA Astrophysics Data System (ADS)

    Russ, Detlef; Ebinger, Thomas; Illich, Wolfgang; Steiner, Rudolf W.

    2003-10-01

    We developed a new surgical procedure to improve the recurrence rate using an Er:YAG laser as dissection tool for the carpal ligament with the objective to ablate a small amount of the carpal ligament and to denaturate its ends. The Er:YAG Laser was transmitted to the applicator via a GeO fiber. With this system we proceeded 10 carpal ligament dissections without any complications in the follow-up period. All patients were free of pain and recurrence.

  12. Neuroprotective Effects of Protein Tyrosine Phosphatase 1B Inhibition against ER Stress-Induced Toxicity

    PubMed Central

    Jeon, Yu-Mi; Lee, Shinrye; Kim, Seyeon; Kwon, Younghwi; Kim, Kiyoung; Chung, Chang Geon; Lee, Seongsoo; Lee, Sung Bae; Kim, Hyung-Jun

    2017-01-01

    Several lines of evidence suggest that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Protein tyrosine phosphatase 1B (PTP1B) is known to regulate the ER stress signaling pathway, but its role in neuronal systems in terms of ER stress remains largely unknown. Here, we showed that rotenone-induced toxicity in human neuroblastoma cell lines and mouse primary cortical neurons was ameliorated by PTP1B inhibition. Moreover, the increase in the level of ER stress markers (eIF2α phosphorylation and PERK phosphorylation) induced by rotenone treatment was obviously suppressed by concomitant PTP1B inhibition. However, the rotenone-induced production of reactive oxygen species (ROS) was not affected by PTP1B inhibition, suggesting that the neuroprotective effect of the PTP1B inhibitor is not associated with ROS production. Moreover, we found that MG132-induced toxicity involving proteasome inhibition was also ameliorated by PTP1B inhibition in a human neuroblastoma cell line and mouse primary cortical neurons. Consistently, downregulation of the PTP1B homologue gene in Drosophila mitigated rotenone- and MG132-induced toxicity. Taken together, these findings indicate that PTP1B inhibition may represent a novel therapeutic approach for ER stress-mediated neurodegenerative diseases. PMID:28359145

  13. Resonantly diode-pumped eye-safe Er:YAG laser with fiber-shaped crystal

    NASA Astrophysics Data System (ADS)

    Němec, Michal; Šulc, Jan; Hlinomaz, Kryštof; Jelínková, Helena; Nejezchleb, Karel; Čech, Miroslav

    2018-02-01

    Solid-state eye-safe lasers are interesting sources for various applications, such as lidar, remote sensing, and ranging. A resonantly diode-pumped Er:YAG laser could be one of them allowing to reach a tunable laser emission in 1.6 μm spectral region. To overcome low pump absorption and poor pumping beam quality generated by commercially available laser diode, an active medium could be formed to long and thin laser rod guiding pumping radiation. Such an effective cooling during a high power pumping, which is a "crystal-fiber" benefit, may be useful for "standard" crystal active medium. The main goal of this work was to investigate the laser characteristics of new developed Er:YAG crystal with a special shape for diode-pumping. Er:YAG fiber-shape crystal with square cross-section (1x1mm) and 40mm in length was doped by 0.1% Er3+ ions. All sides of this crystal were polished and in addition the end-faces of it were antireflection coatings for the wavelength 1470 and 1645 nm. As a pump system, a fiber coupled laser diode (f = 10 Hz, t = 10 ms) emitting radiation at 1465 nm wavelength was used. Er:YAG fiber-shape crystal was placed onto a copper holder in the 85 mm long plan-concave resonator consisting of a pump flat mirror and output curved (r = 150 mm) coupler with a reflectivity of 96 % @ 1645 nm. The dependence of the output peak power on absorbed pump power was investigated and the maximum 0.8 W was obtained. The corresponding slope efficiency was 14.5 %. The emitting wavelength was equaled to 1645 nm (4 nm linewidth, FWHM). The spatial beam structure was close to the Gaussian mode.

  14. Molecular mechanism of ER stress-induced pre-emptive quality control involving association of the translocon, Derlin-1, and HRD1.

    PubMed

    Kadowaki, Hisae; Satrimafitrah, Pasjan; Takami, Yasunari; Nishitoh, Hideki

    2018-05-09

    The maintenance of endoplasmic reticulum (ER) homeostasis is essential for cell function. ER stress-induced pre-emptive quality control (ERpQC) helps alleviate the burden to a stressed ER by limiting further protein loading. We have previously reported the mechanisms of ERpQC, which includes a rerouting step and a degradation step. Under ER stress conditions, Derlin family proteins (Derlins), which are components of ER-associated degradation, reroute specific ER-targeting proteins to the cytosol. Newly synthesized rerouted polypeptides are degraded via the cytosolic chaperone Bag6 and the AAA-ATPase p97 in the ubiquitin-proteasome system. However, the mechanisms by which ER-targeting proteins are rerouted from the ER translocation pathway to the cytosolic degradation pathway and how the E3 ligase ubiquitinates ERpQC substrates remain unclear. Here, we show that ERpQC substrates are captured by the carboxyl-terminus region of Derlin-1 and ubiquitinated by the HRD1 E3 ubiquitin ligase prior to degradation. Moreover, HRD1 forms a large ERpQC-related complex composed of Sec61α and Derlin-1 during ER stress. These findings indicate that the association of the degradation factor HRD1 with the translocon and the rerouting factor Derlin-1 may be necessary for the smooth and effective clearance of ERpQC substrates.

  15. Morbillivirus Glycoprotein Expression Induces ER Stress, Alters Ca2+ Homeostasis and Results in the Release of Vasostatin

    PubMed Central

    Doucey, Marie-Agnès; Rosso, Lia; Curie, Thomas; Montagner, Alexandra; Wittek, Riccardo; Vandelvelde, Marc; Zurbriggen, Andreas; Hirling, Harald; Desvergne, Béatrice

    2012-01-01

    Although the pathology of Morbillivirus in the central nervous system (CNS) is well described, the molecular basis of neurodegenerative events still remains poorly understood. As a model to explore Morbillivirus-mediated CNS dysfunctions, we used canine distemper virus (CDV) that we inoculated into two different cell systems: a monkey cell line (Vero) and rat primary hippocampal neurons. Importantly, the recombinant CDV used in these studies not only efficiently infects both cell types but recapitulates the uncommon, non-cytolytic cell-to-cell spread mediated by virulent CDVs in brain of dogs. Here, we demonstrated that both CDV surface glycoproteins (F and H) markedly accumulated in the endoplasmic reticulum (ER). This accumulation triggered an ER stress, characterized by increased expression of the ER resident chaperon calnexin and the proapoptotic transcription factor CHOP/GADD 153. The expression of calreticulin (CRT), another ER resident chaperon critically involved in the response to misfolded proteins and in Ca2+ homeostasis, was also upregulated. Transient expression of recombinant CDV F and H surface glycoproteins in Vero cells and primary hippocampal neurons further confirmed a correlation between their accumulation in the ER, CRT upregulation, ER stress and disruption of ER Ca2+ homeostasis. Furthermore, CDV infection induced CRT fragmentation with re-localisation of a CRT amino-terminal fragment, also known as vasostatin, on the surface of infected and neighbouring non-infected cells. Altogether, these results suggest that ER stress, CRT fragmentation and re-localization on the cell surface may contribute to cytotoxic effects and ensuing cell dysfunctions triggered by Morbillivirus, a mechanism that might potentially be relevant for other neurotropic viruses. PMID:22403712

  16. Differentially expressed proteins in ER+ MCF7 and ER- MDA- MB-231 human breast cancer cells by RhoGDI-α silencing and overexpression.

    PubMed

    Hooshmand, Somayeh; Ghaderi, Abbas; Yusoff, Khatijah; Thilakavathy, Karuppiah; Rosli, Rozita; Mojtahedi, Zahra

    2014-01-01

    The consequence of Rho GDP dissociation inhibitor alpha (RhoGDIα) activity on migration and invasion of estrogen receptor positive (ER+) and negative (ER-) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDIα and other proteins interacting directly or indirectly with RhoGDIα in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest. ER+ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time- of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDIα using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDIα. The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDIα in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDIα in MCF7, while only one protein was identified in the upregulation of RhoGDIα in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-α activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells. Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDIα with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.

  17. Synthesis, Structural Property, Photophysical Property, Photocatalytic Property of Novel ZnBiErO4 under Visible Light Irradiation

    PubMed Central

    Zhuang, Yan

    2018-01-01

    A novel photocatalyst ZnBiErO4 was firstly synthesized by solid-state reaction method and its structural and photocatalytic properties were analyzed by scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and UV-Vis diffuse reflectance. The results demonstrated that ZnBiErO4 crystallized with tetragonal crystal structure with space group I41/A. The lattice parameters for ZnBiErO4 were proved to be a = b = 10.255738 Å and c = 9.938888 Å. The band gap of ZnBiErO4 was estimated to be about 1.69 eV. Compared with nitrogen doped TiO2, ZnBiErO4 showed excellent photocatalytic activities for degrading methyl blue during visible light irradiation. The photocatalytic degradation of methyl blue with ZnBiErO4 or N-doped TiO2 as catalyst followed the first-order reaction kinetics. Moreover, the apparent first-order rate constant of ZnBiErO4 or N-doped TiO2 was 0.01607 min−1 or 0.00435 min−1. The reduction of total organic carbon, formation of inorganic products, such as SO42− and NO3− and the evolution of CO2 revealed the continuous mineralization of methyl blue during the photocatalytic process. ZnBiErO4 photocatalyst had great potential to purify textile industry wastewater. PMID:29463016

  18. A Role for MEK-Interacting Protein 1 in Hormone Responsiveness of ER Positive Breast Cancer Cells

    DTIC Science & Technology

    2010-07-01

    positive, but not ER-negative, breast cancer cell lines. 2) The cell death observed in ER- positiv e cell lin es was associated with an a pproximate...and stained after 24 h, then counted. Top panel: photographs of stained cells. Bottom panel: Quantitation of migrated cells, normalized to control...function and breast cancer biology. W e therefore hypothesized that MP1 m ight play an im portant role in ER positiv e breast cancer cells. To test this

  19. Amazon Rain Forest Classification Using J-ERS-1 SAR Data

    NASA Technical Reports Server (NTRS)

    Freeman, A.; Kramer, C.; Alves, M.; Chapman, B.

    1994-01-01

    The Amazon rain forest is a region of the earth that is undergoing rapid change. Man-made disturbance, such as clear cutting for agriculture or mining, is altering the rain forest ecosystem. For many parts of the rain forest, seasonal changes from the wet to the dry season are also significant. Changes in the seasonal cycle of flooding and draining can cause significant alterations in the forest ecosystem.Because much of the Amazon basin is regularly covered by thick clouds, optical and infrared coverage from the LANDSAT and SPOT satellites is sporadic. Imaging radar offers a much better potential for regular monitoring of changes in this region. In particular, the J-ERS-1 satellite carries an L-band HH SAR system, which via an on-board tape recorder, can collect data from almost anywhere on the globe at any time of year.In this paper, we show how J-ERS-1 radar images can be used to accurately classify different forest types (i.e., forest, hill forest, flooded forest), disturbed areas such as clear cuts and urban areas, and river courses in the Amazon basin. J-ERS-1 data has also shown significant differences between the dry and wet season, indicating a strong potential for monitoring seasonal change. The algorithm used to classify J-ERS-1 data is a standard maximum-likelihood classifier, using the radar image local mean and standard deviation of texture as input. Rivers and clear cuts are detected using edge detection and region-growing algorithms. Since this classifier is intended to operate successfully on data taken over the entire Amazon, several options are available to enable the user to modify the algorithm to suit a particular image.

  20. High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size.

    PubMed

    Bourdier, Guillaume; Flore, Patrice; Sanchez, Hervé; Pepin, Jean-Louis; Belaidi, Elise; Arnaud, Claire

    2016-01-15

    Chronic intermittent hypoxia (IH) is described as the major detrimental factor leading to cardiovascular morbimortality in obstructive sleep apnea (OSA) patients. OSA patients exhibit increased infarct size after a myocardial event, and previous animal studies have shown that chronic IH could be the main mechanism. Endoplasmic reticulum (ER) stress plays a major role in the pathophysiology of cardiovascular disease. High-intensity training (HIT) exerts beneficial effects on the cardiovascular system. Thus, we hypothesized that HIT could prevent IH-induced ER stress and the increase in infarct size. Male Wistar rats were exposed to 21 days of IH (21-5% fraction of inspired O2, 60-s cycle, 8 h/day) or normoxia. After 1 wk of IH alone, rats were submitted daily to both IH and HIT (2 × 24 min, 15-30m/min). Rat hearts were either rapidly frozen to evaluate ER stress by Western blot analysis or submitted to an ischemia-reperfusion protocol ex vivo (30 min of global ischemia/120 min of reperfusion). IH induced cardiac proapoptotic ER stress, characterized by increased expression of glucose-regulated protein kinase 78, phosphorylated protein kinase-like ER kinase, activating transcription factor 4, and C/EBP homologous protein. IH-induced myocardial apoptosis was confirmed by increased expression of cleaved caspase-3. These IH-associated proapoptotic alterations were associated with a significant increase in infarct size (35.4 ± 3.2% vs. 22.7 ± 1.7% of ventricles in IH + sedenary and normoxia + sedentary groups, respectively, P < 0.05). HIT prevented both the IH-induced proapoptotic ER stress and increased myocardial infarct size (28.8 ± 3.9% and 21.0 ± 5.1% in IH + HIT and normoxia + HIT groups, respectively, P = 0.28). In conclusion, these findings suggest that HIT could represent a preventive strategy to limit IH-induced myocardial ischemia-reperfusion damages in OSA patients. Copyright © 2016 the American Physiological Society.

  1. Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity.

    PubMed

    Chen, Yaqin; Wu, Zhihong; Zhao, Shuiping; Xiang, Rong

    2016-06-08

    Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese.

  2. Structure-activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro.

    PubMed

    Hammad, Ayat S; Ravindran, Sreenithya; Khalil, Ashraf; Munusamy, Shankar

    2017-05-01

    Endoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD. Piperine and its analogs have been reported to exhibit multiple pharmacological activities; however, their efficacy against ER stress in kidney cells has not been studied yet. Hence, the goal of this study was to synthesize amide-substituted piperine analogs and screen them for pharmacological activity to relieve ER stress using an in vitro model of tunicamycin-induced ER stress using normal rat kidney (NRK-52E) cells. Five amide-substituted piperine analogs were synthesized and their chemical structures were elucidated by pertinent spectroscopic techniques. An in vitro model of ER stress was developed using tunicamycin, and the compounds of interest were screened for their effect on cell viability, and the expression of ER chaperone GRP78, the pro-apoptotic ER stress marker CHOP, and apoptotic caspases 3 and 12 (via western blotting). Our findings indicate that exposure to tunicamycin (0.5 μg/mL) for 2 h induces the expression of GRP78 and CHOP, and apoptotic markers (caspase-3 and caspase-12) and causes a significant reduction in renal cell viability. Pre-treatment of cells with piperine and its cyclohexylamino analog decreased the tunicamycin-induced upregulation of GRP78 and CHOP and cell death. Taken together, our findings demonstrate that piperine and its analogs differentially regulate ER stress, and thus represent potential therapeutic agents to treat ER stress-related renal disorders. Graphical Abstract Piperine (PIP) reduces the expression of ER stress markers (GRP78 and CHOP) induced by pathologic stimuli and consequently decreases the activation of apoptotic caspase-12 and caspase-3; all of which contributes to its chemical chaperone and cytoprotective properties to protect

  3. Upconversion luminescence from Er-N codoped of ZnO nanowires prepared by ion implantation method

    NASA Astrophysics Data System (ADS)

    Zhong, Kun; Xu, Jie; Su, Jing; Chen, Yu lin

    2011-02-01

    Nitrogen and erbium co-doped of ZnO nanowires (NWs) are fabricated by ion implantation and subsequent annealing in air. The incorporation of Er3+ and N+ ions is verified by energy dispersive X-ray spectroscopy (EDS) and Raman spectra. The samples exhibit upconversion photoluminescence around ∼550 nm and ∼660 nm under an excitation at 980 nm. It is discovered that the N-doped can drastically increase the upconversion photoluminescence intensity by modifying the local structure around Er3+ in ZnO matrix. The enhancement of the PL intensity by the N-doped is caused by the formation of ErO6-xNx octahedron complexes. With the increase of the annealing temperature (Ta), the Er3+ ions diffuse towards the surface of the NWs, which benefits the red emission and evokes the variation of intensity ratio owing to the existence of some organic groups.

  4. Implication of altered ubiquitin-proteasome system and ER stress in the muscle atrophy of diabetic rats.

    PubMed

    Reddy, S Sreenivasa; Shruthi, Karnam; Prabhakar, Y Konda; Sailaja, Gummadi; Reddy, G Bhanuprakash

    2018-02-01

    Skeletal muscle is adversely affected in type-1 diabetes, and excessively stimulated ubiquitin-proteasome system (UPS) was found to be a leading cause of muscle wasting or atrophy. The role of endoplasmic reticulum (ER) stress in muscle atrophy of type-1 diabetes is not known. Hence, we investigated the role of UPS and ER stress in the muscle atrophy of chronic diabetes rat model. Diabetes was induced with streptozotocin (STZ) in male Sprague-Dawley rats and were sacrificed 2- and 4-months thereafter to collect gastrocnemius muscle. In another experiment, 2-months post-STZ-injection diabetic rats were treated with MG132, a proteasome inhibitor, for the next 2-months and gastrocnemius muscle was collected. The muscle fiber cross-sectional area was diminished in diabetic rats. The expression of UPS components: E1, MURF1, TRIM72, UCHL1, UCHL5, ubiquitinated proteins, and proteasome activity were elevated in the diabetic rats indicating activated UPS. Altered expression of ER-associated degradation (ERAD) components and increased ER stress markers were detected in 4-months diabetic rats. Proteasome inhibition by MG132 alleviated alterations in the UPS and ER stress in diabetic rat muscle. Increased UPS activity and ER stress were implicated in the muscle atrophy of diabetic rats and proteasome inhibition exhibited beneficiary outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A RET-ER81-NRG1 Signaling Pathway Drives the Development of Pacinian Corpuscles.

    PubMed

    Fleming, Michael S; Li, Jian J; Ramos, Daniel; Li, Tong; Talmage, David A; Abe, Shin-Ichi; Arber, Silvia; Luo, Wenqin

    2016-10-05

    Axon-Schwann cell interactions are crucial for the development, function, and repair of the peripheral nervous system, but mechanisms underlying communication between axons and nonmyelinating Schwann cells are unclear. Here, we show that ER81 is functionally required in a subset of mouse RET + mechanosensory neurons for formation of Pacinian corpuscles, which are composed of a single myelinated axon and multiple layers of nonmyelinating Schwann cells, and Ret is required for the maintenance of Er81 expression. Interestingly, Er81 mutants have normal myelination but exhibit deficient interactions between axons and corpuscle-forming nonmyelinating Schwann cells. Finally, ablating Neuregulin-1 (Nrg1) in mechanosensory neurons results in no Pacinian corpuscles, and an Nrg1 isoform not required for communication with myelinating Schwann cells is specifically decreased in Er81-null somatosensory neurons. Collectively, our results suggest that a RET-ER81-NRG1 signaling pathway promotes axon communication with nonmyelinating Schwann cells, and that neurons use distinct mechanisms to interact with different types of Schwann cells. Communication between neurons and Schwann cells is critical for development, normal function, and regeneration of the peripheral nervous system. Despite many studies about axonal communication with myelinating Schwann cells, mostly via a specific isoform of Neuregulin1, the molecular nature of axonal communication with nonmyelinating Schwann cells is poorly understood. Here, we described a RET-ER81-Neuregulin1 signaling pathway in neurons innervating Pacinian corpuscle somatosensory end organs, which is essential for communication between the innervating axon and the end organ nonmyelinating Schwann cells. We also showed that this signaling pathway uses isoforms of Neuregulin1 that are not involved in myelination, providing evidence that neurons use different isoforms of Neuregulin1 to interact with different types of Schwann cells. Copyright

  6. Buckling reversal of the Si(111) bilayer termination of 2-dimensional ErSi2 upon H dosing

    NASA Astrophysics Data System (ADS)

    Wetzel, P.; Pirri, C.; Gewinner, G.

    1997-05-01

    Hydrogen-induced reconstruction of 2-dimensional (2D) ErSi2 epitaxially grown on Si(111) is studied by Auger-electron diffraction (AED) and low-energy electron diffraction (LEED). The intensity of the Er MNN Auger line is measured vs. polar angle along the [1 - 2 1] and [- 1 2 - 1] azimuths for clean and H-saturated (1 × 1) ErSi2 silicides. The atomic structure of clean 2D silicide, previously established by AED as well as other techniques, consists of a hexagonal monolayer of Er located underneath a buckled Si layer comparable to the Si(111) substrate double layers. Moreover, for clean 2D ErSi2 only the B-type orientation is observed, i.e. the buckled Si top layer is always rotated by 180° around the surface normal relative to the relevant double layers of the substrate. After atomic H saturation, AED reveals drastic changes in the silicide structure involving a major most remarkable reconstruction of the Si bilayer termination. The latter is found to switch from B-type to A-type orientation upon H dosing, i.e. H-saturated 2D ErSi2 exhibits a buckled Si top layer oriented in the same way as the substrate double layers. A comparison with single scattering cluster simulations demonstrates that the latter phenomenon is accompanied by a large expansion of the Er-Si interlayer spacing close to 0.3 Å.

  7. Phase Competition in the Palmer-Chalker X Y Pyrochlore Er2Pt2O7

    NASA Astrophysics Data System (ADS)

    Hallas, A. M.; Gaudet, J.; Butch, N. P.; Xu, Guangyong; Tachibana, M.; Wiebe, C. R.; Luke, G. M.; Gaulin, B. D.

    2017-11-01

    We report neutron scattering measurements on Er2Pt2O7 , a new addition to the X Y family of frustrated pyrochlore magnets. Symmetry analysis of our elastic scattering data shows that Er2Pt2O7 orders into the k =0 , Γ7 magnetic structure (the Palmer-Chalker state), at TN=0.38 K . This contrasts with its sister X Y pyrochlore antiferromagnets Er2Ti2O7 and Er2Ge2O7 , both of which order into Γ5 magnetic structures at much higher temperatures, TN=1.2 and 1.4 K, respectively. In this temperature range, the magnetic heat capacity of Er2Pt2O7 contains a broad anomaly centered at T*=1.5 K . Our inelastic neutron scattering measurements reveal that this broad heat capacity anomaly sets the temperature scale for strong short-range spin fluctuations. Below TN=0.38 K , Er2Pt2O7 displays a gapped spin-wave spectrum with an intense, flat band of excitations at lower energy and a weak, diffusive band of excitations at higher energy. The flat band is well described by classical spin-wave calculations, but these calculations also predict sharp dispersive branches at higher energy, a striking discrepancy with the experimental data. This, in concert with the strong suppression of TN, is attributable to enhanced quantum fluctuations due to phase competition between the Γ7 and Γ5 states that border each other within a classically predicted phase diagram.

  8. Upconversion emission study of Er{sup 3+} doped CaMoO{sub 4} phosphor

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

    Sinha, Shriya, E-mail: Shriya.sinha6@gmail.com; Mahata, Manoj Kumar; Kumar, Kaushal

    2016-05-06

    The infrared to visible upconversion emission in Er{sup 3+} doped CaMoO{sub 4} phosphor has been investigated upon 980 nm diode laser excitation. The X-ray diffraction analysis reveals well crystalline nature and tetragonal phase structure of the prepared phosphor annealed at 800 °C. The Er{sup 3+} doped CaMoO{sub 4} phosphor has shown intense green upconversion emission upon 980 nm didode laser excitation. The green emission bands at 530 nm and 552 nm corresponds to the {sup 2}H{sub 11/2}→{sup 4}I{sub 15/2} and {sup 4}S{sub 3/2}→{sup 4}I{sub 15/2} electronic transitions, respectively of Er{sup 3+} ion. The very weak red emission band around 656more » nm is assigned to the {sup 4}F{sub 9/2}→{sup 4}I{sub 15/2} transition of Er{sup 3+} ion. The CIE color coordinate exhibits the emission color in intense green region, indicating the use of present phosphor in display device applications.« less

  9. Effects of Different Combinations of Er:YAG Laser-Adhesives on Enamel Demineralization and Bracket Bond Strength.

    PubMed

    Çokakoğlu, Serpil; Nalçacı, Ruhi; Üşümez, Serdar; Malkoç, Sıddık

    2016-04-01

    The purpose of this study was to investigate the demineralization around brackets and shear bond strength (SBS) of brackets bonded to Er:YAG laser-irradiated enamel at different power settings with various adhesive systems combinations. A total of 108 premolar teeth were used in this study. Teeth were assigned into three groups according to the etching procedure, then each group divided into three subgroups based on the application of different adhesive systems. There were a total of nine groups as follows. Group 1: Acid + Transbond XT Primer; group 2: Er:YAG (100 mJ, 10 Hz) etching + Transbond XT Primer; group 3: Er:YAG (200 mJ, 10 Hz) etching + Transbond XT Primer; group 4: Transbond Plus self-etching primer (SEP); group 5: Er:YAG (100 mJ, 10 Hz) etching + Transbond Plus SEP; group 6: Er:YAG (200 mJ, 10 Hz) etching + Transbond Plus SEP; group 7: Clearfil Protect Bond; group 8: Er:YAG (100 mJ, 10 Hz) etching + Clearfil Protect Bond; group 9: Er:YAG (200 mJ, 10 Hz) etching + Clearfil Protect Bond. Brackets were bonded with Transbond XT Adhesive Paste in all groups. Teeth to be evaluated for demineralization and SBS were exposed to pH and thermal cyclings, respectively. Then, demineralization samples were scanned with micro-CT to determine lesion depth values. For SBS test, a universal testing machine was used and adhesive remnant was index scored after debonding. Data were analyzed statistically. No significant differences were found among the lesion depth values of the various groups, except for G7 and G8, in which the lowest values were recorded. The lowest SBS values were in G7, whereas the highest were in G9. The differences between the other groups were not significant. Er:YAG laser did not have a positive effect on prevention of enamel demineralization. When two step self-etch adhesive is preferred for bonding brackets, laser etching at 1 W (100 mJ, 10 Hz) is suggested to improve SBS of brackets.

  10. Lifetime moderate-to-vigorous physical activity and ER/PR/HER-defined post-menopausal breast cancer risk.

    PubMed

    Shi, Joy; Kobayashi, Lindsay C; Grundy, Anne; Richardson, Harriet; SenGupta, Sandip K; Lohrisch, Caroline A; Spinelli, John J; Aronson, Kristan J

    2017-08-01

    To assess the relationship of moderate-to-vigorous physical activity (MVPA) in leisure-time, household, and occupational domains across the total lifetime and in four age periods with breast cancer risk, as defined by estrogen receptor (ER)/progesterone receptor (PR) status and ER/PR/human epidermal growth factor-2 (HER2) status, among post-menopausal women. Data were from 692 women with incident breast cancer and 644 controls in the Canadian Breast Cancer Study, a case-control study of women aged 40-80 years in British Columbia and Ontario. Mean metabolic equivalent (MET)-hours/week for questionnaire-assessed leisure-time, household, and occupational MVPA were calculated for the total lifetime and four age periods (12-17, 18-34, 45-49, and ≥50 years). Odds ratios (ORs) for the relationships between domain-specific MVPA at each lifetime period and risks of ER/PR-defined and ER/PR/HER2-defined breast cancers were estimated using polytomous logistic regression. Trend tests for dose-response relationships were calculated for the ORs across increasing tertiles of mean MET-hours/week of MVPA. Total lifetime leisure-time MVPA was associated with reduced risk of ER-/PR- breast cancer in a dose-response fashion (p trend  = 0.014). In contrast, total lifetime household MVPA was associated with reduced risk of ER+ and/or PR+ breast cancer (p trend  < 0.001). When further stratified by HER2 status, the effect of leisure-time MVPA appeared confined to HER2- breast cancers, and the effect of household MVPA did not differ according to HER2 status. Similar trends were observed when stratified by age period. Lifetime leisure-time MVPA appeared to be associated with reduced risk of ER-/PR-/HER2- breast cancers and lifetime household MVPA was associated with reduced risk of ER+ and/or PR+ breast cancer, regardless of HER2 status.

  11. 78 FR 4857 - Agency Information Collection Activities: Petition for Amerasian, Widow(er), or Special Immigrant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-23

    ... DEPARTMENT OF HOMELAND SECURITY U.S. Citizenship and Immigration Services [OMB Control Number 1615-0020] Agency Information Collection Activities: Petition for Amerasian, Widow(er), or Special Immigrant...(er), or Special Immigrant (3) Agency form number, if any, and the applicable component of the DHS...

  12. 77 FR 65704 - Agency Information Collection Activities: Petition for Amerasian, Widow(er), or Special Immigrant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-30

    ... DEPARTMENT OF HOMELAND SECURITY U.S. Citizenship and Immigration Services [OMB Control Number 1615-0020] Agency Information Collection Activities: Petition for Amerasian, Widow(er), or Special Immigrant.../Collection: Petition for Amerasian, Widow(er), or Special Immigrant. (3) Agency form number, if any, and the...

  13. Effect of Er3+ concentration on the luminescence properties of Al2O3-ZrO2 powder

    NASA Astrophysics Data System (ADS)

    Clabel H., J. L.; Rivera, V. A. G.; Nogueira, I. C.; Leite, E. R.; Siu Li, M.; Marega, E.

    2016-12-01

    This manuscript reports on the effects of the luminescence properties of Er3+ on Al2O3-ZrO2 powder synthesized by the conventional solid-state method. The best conditions found for the calcinations were 1500 °C and 4 h. The structural dependence of the luminescence on Er3+:Al2O3-ZrO2 is associated with phase transformations of the Al2O3-ZrO2 host and presence of the OH group. Green and red emissions at room temperature from the 2H11/2, 4S3/2 → 4I15/2 and 4F9/2 → 4I15/2 levels of Er3+ ions were observed under 482 nm pumping. The green-to-red emission intensity ratios and CIE chromaticity coordinates were determined from emission spectra for the evaluation of light emitted as a function of the Er3+ concentration. The Er3+ luminescence quenching due to group OH and variation in the Er3+ concentration plays an important role in the definition of the luminescent response.

  14. Cross-sectional scanning thermal microscopy of ErAs/GaAs superlattices grown by molecular beam epitaxy

    NASA Astrophysics Data System (ADS)

    Park, K. W.; Krivoy, E. M.; Nair, H. P.; Bank, S. R.; Yu, E. T.

    2015-07-01

    Scanning thermal microscopy has been implemented in a cross-sectional geometry, and its application for quantitative, nanoscale analysis of thermal conductivity is demonstrated in studies of an ErAs/GaAs nanocomposite superlattice. Spurious measurement effects, attributable to local thermal transport through air, were observed near large step edges, but could be eliminated by thermocompression bonding to an additional structure. Using this approach, bonding of an ErAs/GaAs superlattice grown on GaAs to a silicon-on-insulator wafer enabled thermal signals to be obtained simultaneously from Si, SiO2, GaAs, and ErAs/GaAs superlattice. When combined with numerical modeling, the thermal conductivity of the ErAs/GaAs superlattice measured using this approach was 11 ± 4 W m-1 K-1.

  15. Cross-sectional scanning thermal microscopy of ErAs/GaAs superlattices grown by molecular beam epitaxy.

    PubMed

    Park, K W; Krivoy, E M; Nair, H P; Bank, S R; Yu, E T

    2015-07-03

    Scanning thermal microscopy has been implemented in a cross-sectional geometry, and its application for quantitative, nanoscale analysis of thermal conductivity is demonstrated in studies of an ErAs/GaAs nanocomposite superlattice. Spurious measurement effects, attributable to local thermal transport through air, were observed near large step edges, but could be eliminated by thermocompression bonding to an additional structure. Using this approach, bonding of an ErAs/GaAs superlattice grown on GaAs to a silicon-on-insulator wafer enabled thermal signals to be obtained simultaneously from Si, SiO2, GaAs, and ErAs/GaAs superlattice. When combined with numerical modeling, the thermal conductivity of the ErAs/GaAs superlattice measured using this approach was 11 ± 4 W m(-1) K(-1).

  16. Validation of ERS-1 environmental data products

    NASA Technical Reports Server (NTRS)

    Goodberlet, Mark A.; Swift, Calvin T.; Wilkerson, John C.

    1994-01-01

    Evaluation of the launch-version algorithms used by the European Space Agency (ESA) to derive wind field and ocean wave estimates from measurements of sensors aboard the European Remote Sensing satellite, ERS-1, has been accomplished through comparison of the derived parameters with coincident measurements made by 24 open ocean buoys maintained by the National Oceanic and Atmospheric Administration). During the period from November 1, 1991 through February 28, 1992, data bases with 577 and 485 pairs of coincident sensor/buoy wind and wave measurements were collected for the Active Microwave Instrument (AMI) and Radar Altimeter (RA) respectively. Based on these data, algorithm retrieval accuracy is estimated to be plus or minus 4 m/s for AMI wind speed, plus or minus 3 m/s for RA wind speed and plus or minus 0.6 m for RA wave height. After removing 180 degree ambiguity errors, the AMI wind direction retrieval accuracy was estimated at plus or minus 28 degrees. All of the ERS-1 wind and wave retrievals are relatively unbiased. These results should be viewed as interim since improved algorithms are under development. As final versions are implemented, additional assessments should be conducted to complete the validation.

  17. Compact pulsed high-energy Er:glass laser

    NASA Astrophysics Data System (ADS)

    Wan, Peng; Liu, Jian

    2012-03-01

    Bulk Erbium-doped lasers are widely used for long-distance telemetry and ranging. In some applications such as coherent Doppler radars, laser outputs with a relatively long pulse width, good beam profile and pulse shape are required. High energy Q-switched Er:glass lasers were demonstrated by use of electro-optic (E/O) Q-switching or frustrated total internal reflection (FTIR) Q-switching. However, the output pulse durations in these lasers were fixed to relatively small values and extremely hard to tune. We report here on developing a novel and compact Q-switched Er:Yb co-doped phosphate glass laser at an eye-safe wavelength of 1.5 μm. A rotating mirror was used as a Q-switch. Co-linear pump scheme was used to maintain a good output beam profile. Near-perfect Gaussian temporal shape was obtained in our experiment. By changing motor rotation speed, pulse duration was tunable and up to 240 ns was achieved. In our preliminary experiment, output pulse energies of 44 mJ and 4.5 mJ were obtained in free-running and Q-switched operation modes respectively.

  18. ER stress and genomic instability induced by gamma radiation in mice primary cultured glial cells.

    PubMed

    Chatterjee, Jit; Nairy, Rajesha K; Langhnoja, Jaldeep; Tripathi, Ashutosh; Patil, Rajashekhar K; Pillai, Prakash P; Mustak, Mohammed S

    2018-06-01

    Ionizing radiation induces various pathophysiological conditions by altering central nervous system (CNS) homeostasis, leading to neurodegenerative diseases. However, the potential effect of ionizing radiation response on cellular physiology in glial cells is unclear. In the present study, micronucleus test, comet assay, and RT-PCR were performed to investigate the potential effect of gamma radiation in cultured oligodendrocytes and astrocytes with respect to genomic instability, Endoplasmic Reticulum (ER) stress, and inflammation. Further, we studied the effect of alteration in ER stress specific gene expression in cortex post whole body radiation in mice. Results showed that exposure of gamma radiation of 2Gy in-vitro cultured astrocytes and oligodendrocytes and 7Gy in-vivo induced ER stress and Inflammation along with profuse DNA damage and Chromosomal abnormality. Additionally, we observed downregulation of myelin basic protein levels in cultured oligodendrocytes exposed to radiation. The present data suggests that ER stress and pro inflammatory cytokines serve as the major players in inducing glial cell dysfunction post gamma irradiation along with induction of genomic instability. Taken together, these results indicate that ER stress, DNA damage, and inflammatory pathways may be critical events leading to glial cell dysfunction and subsequent cell death following exposure to ionizing radiation.

  19. Enhanced light emission near 2.7 μm from Er-Nd co-doped germanate glass

    NASA Astrophysics Data System (ADS)

    Bai, Gongxun; Tao, Lili; Li, Kefeng; Hu, Lili; Tsang, Yuen Hong

    2013-04-01

    Laser glass gain medium that can convert low cost 808 nm diode laser into 2.7 μm has attracted considerable interest due to its potential application for medical surgery fiber laser system. In this study, enhanced 2.7 μm emission has been achieved in Er3+:germanate glass by co-doping with Nd3+ ions under the excitation of an 808 nm diode laser. In the co-doped sample, the experimental results show that the harmful visible emissions via up-conversion were effectively restricted. The reduction of 1.5 μm emission was also detected in the co-doped sample, which indicates significant de-excitation of 4I13/2 Er3+ ion through energy transfer and non-radiative decay in Nd3+ ions. In conclusion, the 2.7 μm emission enhancement achieved was due to the increased optical absorption of 808 nm, efficient energy transfer (ET) with efficiency of 81.73% between Er3+ and Nd3+ ions, and shortening the lifetime of the lower lasing level 4I13/2 Er3+ in the co-doped sample. Therefore, Er3+/Nd3+ co-doped germanate glass could be used to fabricate fiber optical gain media for 2.7 μm laser generation.

  20. Comparisons of the NASA ER-2 meteorological measurement system with radar tracking and radiosonde data

    NASA Technical Reports Server (NTRS)

    Gaines, Steven E.; Bowen, Stuart W.; Hipskind, R. S.; Bui, T. P.; Chan, K. R.

    1992-01-01

    Measurements of aircraft longitude, latitude, and velocity, and measurements of atmospheric pressure, temperature, and horizontal wind from the meteorological measurement system (MMS) on board the NASA ER-2 aircraft were compared with independent measurements of these quantities from radiosondes and radar tracking of both the ER-2 and radiosonde balloons. In general, the comparisons were good and within the expected measurement accuracy and natural variability of the meteorological parameters. Radar tracking of the ER-2 resolved the velocity and position drift of the inertial navigation system (INS). The rms errors in the horizontal velocity components of the ER-2, due to INS errors, were found to be 0.5 m/s. The magnitude of the drift in longitude and latitude depends on the sign and magnitude of the corresponding component velocity drift and can be a few hundredths of a degree. The radar altitudes of the ER-2 and radiosondes were used as the basis for comparing measurements of atmospheric pressure, temperature, and horizontal wind from these two platforms. The uncertainty in the MMS horizontal wind measurement is estimated to be +/- 2.5 m/s. The accuracy of the MMS pressure and temperature measurements were inferred to be +/- 0.3 hPa and +/- 0.3 K.

  1. ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells.

    PubMed

    Bassoy, Esen Yonca; Kasahara, Atsuko; Chiusolo, Valentina; Jacquemin, Guillaume; Boydell, Emma; Zamorano, Sebastian; Riccadonna, Cristina; Pellegatta, Serena; Hulo, Nicolas; Dutoit, Valérie; Derouazi, Madiha; Dietrich, Pierre Yves; Walker, Paul R; Martinvalet, Denis

    2017-06-01

    Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem-like cells (GSC) being more sensitive to cytotoxic lymphocyte-mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER-mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER-mitochondria contacts compared to GDCs. Forced ER-mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER-mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma. © 2017 The Authors.

  2. Conductivity and structure of ErAs nanoparticles embedded in GaAs pn junctions analyzed via conductive atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Park, K. W.; Dasika, V. D.; Nair, H. P.; Crook, A. M.; Bank, S. R.; Yu, E. T.

    2012-06-01

    We have used conductive atomic force microscopy to investigate the influence of growth temperature on local current flow in GaAs pn junctions with embedded ErAs nanoparticles grown by molecular beam epitaxy. Three sets of samples, one with 1 ML ErAs deposited at different growth temperatures and two grown at 530 °C and 575 °C with varying ErAs depositions, were characterized. Statistical analysis of local current images suggests that the structures grown at 575 °C have about 3 times thicker ErAs nanoparticles than structures grown at 530 °C, resulting in degradation of conductivity due to reduced ErAs coverage. These findings explain previous studies of macroscopic tunnel junctions.

  3. Lack of adjunctive benefit of Er:YAG laser in non-surgical periodontal treatment: a randomized split-mouth clinical trial.

    PubMed

    Rotundo, Roberto; Nieri, Michele; Cairo, Francesco; Franceschi, Debora; Mervelt, Jana; Bonaccini, Daniele; Esposito, Marco; Pini-Prato, Giovanpaolo

    2010-06-01

    This split-mouth, randomized, clinical trial aimed to evaluate the efficacy of erbium-doped:yttrium-aluminium-garnet (Er:YAG) laser application in non-surgical periodontal treatment. A total of 27 patients underwent four modalities of non-surgical therapy: supragingival debridement; scaling and root planing (SRP)+Er:YAG laser; Er:YAG laser; and SRP. Each strategy was randomly assigned and performed in one of the four quadrants. Clinical outcomes were evaluated at 3 and 6 months. Subjective benefits of patients have been evaluated by means of questionnaires. Six months after therapy, Er:YAG laser showed no statistical difference in clinical attachment gain with respect to supragingival scaling [0.15 mm (95% CI -0.16; 0.46)], while SRP showed a greater attachment gain than the supragingival scaling [0.37 mm (95% CI 0.05; 0.68)]. No difference resulted between Er:YAG laser+SRP and SRP alone [0.05 mm (95% CI -0.25; 0.36)]. The adjunctive use of Er:YAG laser to conventional SRP did not reveal a more effective result than SRP alone. Furthermore, the sites treated with Er:YAG laser showed similar results of the sites treated with supragingival scaling.

  4. Task-dependent activation of distinct fast and slow(er) motor pathways during motor imagery.

    PubMed

    Keller, Martin; Taube, Wolfgang; Lauber, Benedikt

    2018-02-22

    Motor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions. The aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions. H-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest. In contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions. This study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Arctic geodynamics: Continental shelf and deep ocean geophysics. ERS-1 satellite altimetry: A first look

    NASA Technical Reports Server (NTRS)

    Anderson, Allen Joel; Sandwell, David T.; Marquart, Gabriele; Scherneck, Hans-Georg

    1993-01-01

    An overall review of the Arctic Geodynamics project is presented. A composite gravity field model of the region based upon altimetry data from ERS-1, Geosat, and Seasat is made. ERS-1 altimetry covers unique Arctic and Antarctic latitudes above 72 deg. Both areas contain large continental shelf areas, passive margins, as well as recently formed deep ocean areas. Until ERS-1 it was not possible to study these areas with satellite altimetry. Gravity field solutions for the Barents sea, portions of the Arctic ocean, and the Norwegian sea north of Iceland are shown. The gravity anomalies around Svalbard (Spitsbergen) and Bear island are particularly large, indicating large isostatic anomalies which remain from the recent breakup of Greenland from Scandinavian. Recently released gravity data from the Armed Forces Topographic Service of Russia cover a portion of the Barents and Kara seas. A comparison of this data with the ERS-1 produced gravity field is shown.

  6. (abstract) Monitoring the Freeze/Thaw Transitions in Taiga Forests Using ERS-1 SAR

    NASA Technical Reports Server (NTRS)

    Rignot, E.; Williams, C.; Donald, K. Mc; Way, J. B.; Zimmerman, R.; Viereck, L.

    1994-01-01

    Automated recording stations have been installed at the Bonanza Creek Experimental Forest, a Long Term Ecological Research (LTER) site located near Fairbanks, Alaska, in a forest stand of the Tanana River floodplain underlain by discontinuous permafrost. These stations provide a continuous record of dielectric constant and temperature of tree trunks, and soil moisture and temperature profiles down to the root zone. Along with the weather stations deployed at the same location, these measurements provide a continuous record of the environmental and phenologic conditions of the forest during a complete seasonal cycle. At the same time, ERS-1 SAR imaged the study site repeatedly from space to provide radar backscatter measurements of the forest approximately three times a month. Here, we examine the temporal dynamic of ERS-1 SAR measurements in relation with the changing environmental and phenologic state of the forest canopy and of the forest ground layers during the winter/spring and fall/winter transitions of 1992 and 1993. During these transitions, we examine whether changes in radar backscatter observed by ERS-1 may be related to freezing or thawing of the soil and vegetation in order to determine the start and end of the growing season for the forest. The results of this analysis are used in turn to determine whether similar changes are observed over larger regions. Mosaics of SAR data generated along three different North-South Alaskan ERS-1 transects that intercept with our study site are used in combination with hourly air temperature and daily precipitation rates gathered at airport weather stations by the National Weather Service. Results obtained using ERS-1 data collected from January 1992 to mid-1993 will be discussed.

  7. ER residency of the ceramide phosphoethanolamine synthase SMSr relies on homotypic oligomerization mediated by its SAM domain.

    PubMed

    Cabukusta, Birol; Kol, Matthijs; Kneller, Laura; Hilderink, Angelika; Bickert, Andreas; Mina, John G M; Korneev, Sergei; Holthuis, Joost C M

    2017-01-25

    SMSr/SAMD8 is an ER-resident ceramide phosphoethanolamine synthase with a critical role in controlling ER ceramides and suppressing ceramide-induced apoptosis in cultured cells. SMSr-mediated ceramide homeostasis relies on the enzyme's catalytic activity as well as on its N-terminal sterile α-motif or SAM domain. Here we report that SMSr-SAM is structurally and functionally related to the SAM domain of diacylglycerol kinase DGKδ, a central regulator of lipid signaling at the plasma membrane. Native gel electrophoresis indicates that both SAM domains form homotypic oligomers. Chemical crosslinking studies show that SMSr self-associates into ER-resident trimers and hexamers that resemble the helical oligomers formed by DGKδ-SAM. Residues critical for DGKδ-SAM oligomerization are conserved in SMSr-SAM and their substitution causes a dissociation of SMSr oligomers as well as a partial redistribution of the enzyme to the Golgi. Conversely, treatment of cells with curcumin, a drug disrupting ceramide and Ca 2+ homeostasis in the ER, stabilizes SMSr oligomers and promotes retention of the enzyme in the ER. Our data provide first demonstration of a multi-pass membrane protein that undergoes homotypic oligomerization via its SAM domain and indicate that SAM-mediated self-assembly of SMSr is required for efficient retention of the enzyme in the ER.

  8. ER residency of the ceramide phosphoethanolamine synthase SMSr relies on homotypic oligomerization mediated by its SAM domain

    PubMed Central

    Cabukusta, Birol; Kol, Matthijs; Kneller, Laura; Hilderink, Angelika; Bickert, Andreas; Mina, John G. M.; Korneev, Sergei; Holthuis, Joost C. M.

    2017-01-01

    SMSr/SAMD8 is an ER-resident ceramide phosphoethanolamine synthase with a critical role in controlling ER ceramides and suppressing ceramide-induced apoptosis in cultured cells. SMSr-mediated ceramide homeostasis relies on the enzyme’s catalytic activity as well as on its N-terminal sterile α-motif or SAM domain. Here we report that SMSr-SAM is structurally and functionally related to the SAM domain of diacylglycerol kinase DGKδ, a central regulator of lipid signaling at the plasma membrane. Native gel electrophoresis indicates that both SAM domains form homotypic oligomers. Chemical crosslinking studies show that SMSr self-associates into ER-resident trimers and hexamers that resemble the helical oligomers formed by DGKδ-SAM. Residues critical for DGKδ-SAM oligomerization are conserved in SMSr-SAM and their substitution causes a dissociation of SMSr oligomers as well as a partial redistribution of the enzyme to the Golgi. Conversely, treatment of cells with curcumin, a drug disrupting ceramide and Ca2+ homeostasis in the ER, stabilizes SMSr oligomers and promotes retention of the enzyme in the ER. Our data provide first demonstration of a multi-pass membrane protein that undergoes homotypic oligomerization via its SAM domain and indicate that SAM-mediated self-assembly of SMSr is required for efficient retention of the enzyme in the ER. PMID:28120887

  9. Role of Er3+ concentration in high-resolution spectra of BaY2 F8 single crystals

    NASA Astrophysics Data System (ADS)

    Baraldi, A.; Capelletti, R.; Mazzera, M.; Ponzoni, A.; Amoretti, G.; Magnani, N.; Toncelli, A.; Tonelli, M.

    2005-08-01

    Fourier transform absorption spectroscopy with a resolution as fine as 0.02cm-1 was applied to Er3+ -doped monoclinic BaY2F8 laser crystals in a wide wave number range (500-24000cm-1) and in the temperature range 9-300 K. The careful analysis of the complex narrow line spectra induced by Er3+ allowed us to determine with high accuracy the crystal field splitting of the fundamental I15/24 and of the excited I13/24 , I11/24 , I9/24 , F9/24 , S3/24 , H11/22 , F7/24 , F5/24 , and F3/24 manifolds. On the basis of the experimental data, the crystal-field parameters were determined and Newman’s superposition model was applied: in this way a slight displacement of Er3+ with respect to the Y3+ position was foreseen. The Judd-Ofelt parameters were evaluated: the lifetime values deduced from them were compared to the experimental ones and discussed. The effects caused by increasing Er3+ concentrations (0.5%, 2%, 12%, and 20% atomic fraction) were studied in detail. The new lines, the line broadening, and the line-shape changes were explained in terms of Er3+-Er3+ interaction.

  10. Spastin, atlastin, and ER relocalization are involved in axon but not dendrite regeneration

    PubMed Central

    Rao, Kavitha; Stone, Michelle C.; Weiner, Alexis T.; Gheres, Kyle W.; Zhou, Chaoming; Deitcher, David L.; Levitan, Edwin S.; Rolls, Melissa M.

    2016-01-01

    Mutations in >50 genes, including spastin and atlastin, lead to hereditary spastic paraplegia (HSP). We previously demonstrated that reduction of spastin leads to a deficit in axon regeneration in a Drosophila model. Axon regeneration was similarly impaired in neurons when HSP proteins atlastin, seipin, and spichthyin were reduced. Impaired regeneration was dependent on genetic background and was observed when partial reduction of HSP proteins was combined with expression of dominant-negative microtubule regulators, suggesting that HSP proteins work with microtubules to promote regeneration. Microtubule rearrangements triggered by axon injury were, however, normal in all genotypes. We examined other markers to identify additional changes associated with regeneration. Whereas mitochondria, endosomes, and ribosomes did not exhibit dramatic repatterning during regeneration, the endoplasmic reticulum (ER) was frequently concentrated near the tip of the growing axon. In atlastin RNAi and spastin mutant animals, ER accumulation near single growing axon tips was impaired. ER tip concentration was observed only during axon regeneration and not during dendrite regeneration. In addition, dendrite regeneration was unaffected by reduction of spastin or atlastin. We propose that the HSP proteins spastin and atlastin promote axon regeneration by coordinating concentration of the ER and microtubules at the growing axon tip. PMID:27605706

  11. Tm3+-doped lead silicate glass sensitized by Er3+ for efficient 2 μm mid-infrared laser material

    NASA Astrophysics Data System (ADS)

    Zhang, Junjie; Wang, Ning; Guo, Yanyan; Cai, Muzhi; Tian, Ying; Huang, Feifei; Xu, Shiqing

    2018-06-01

    Er3+/Tm3+ co-doped lead silicate glasses with low phonon (953 cm-1) and good thermal stability were synthesized. The 2 μm mid-infrared emission resulting from the 3F4 → 3H6 transition of Tm3+ sensitized by Er3+ has been observed by 808 nm LD pumping. The optimal luminescence intensity was obtained in the sample with 1Tm2O3/2.5Er2O3 co-doped. Moreover, the energy transfer mechanism from Er3+ to Tm3+ ion was analyzed. Absorption and emission cross section have been calculated. The calculated maximum emission cross section of Tm3+ is 2.689 × 10-21 cm2 at 1863 nm. Microparameters of energy transfer between Er3+ and Tm3+ ions have also been analyzed. These results ensure that the prepared Er3+/Tm3+ co-doped lead silicate glasses have excellent spectroscopic properties in mid-infrared region and provide a beneficial guide for mid-infrared laser material.

  12. Structural Loading on the QCM/SAW Instrument Aboard the ER-2 Used for Atmospheric Testing

    NASA Technical Reports Server (NTRS)

    Bainum, Peter M.; Jones, Phyllis D.; Irish, Sandra M.; Xing, Guang-Qian

    1998-01-01

    Several experiments have been proposed to capture and evaluate samples of the atmosphere where SST's travel. One means to achieve this is to utilize the quartz crystal microbalance (QCM) / surface acoustical wave (SAW) instrument installed aboard the ER-2, formerly the U-2 reconnaissance aircraft. The QCM is a cascade impactor designed to perform in-situ, real-time measurements of aerosols and chemical vapors at an altitude of 60,000-70,000 feet. The primary use of the ER-2 is by NASA for Earth resources to test new sensor systems before being placed aboard satellites. One of the main reasons the ER-2 is used for this flight experiment is its capability to fly approximately twelve miles above the sea level (can reach an altitude of 78,000 feet). Because the ER-2 operates at such a high altitude, it is of special interest to scientists interested in space exploration or supersonic aircraft. The purpose of some of the experiments is to extinct data from the atmosphere around the ER-2. For the current CSTEA flight experiment, the housing of the QCM is in a frame that connects to an outer pod that attaches to the fuselage of the ER-2. Due to the location of the QCM within the housing frame and the location of the pod on the ER-2, the pod and its contents are subject to structural loads. In addition to structural loads, structural vibrations are also of importance because the QCM output data is based on the determination of beat frequencies between a pair of oscillators (one coated, the second uncoated, according to the chemical reaction being monitored). A structural analysis of this system can indicate whether potential resonances may exist between the (higher) structural modal frequencies and the beat frequencies. In addition undesirable deformations may result due to maximum expected static or dynamic loads during typical flight conditions. If the deformations are excessive they may adversely affect the accuracy the instrumentation output.

  13. Alterations in Ca2+ Signalling via ER-Mitochondria Contact Site Remodelling in Cancer.

    PubMed

    Kerkhofs, Martijn; Giorgi, Carlotta; Marchi, Saverio; Seitaj, Bruno; Parys, Jan B; Pinton, Paolo; Bultynck, Geert; Bittremieux, Mart

    2017-01-01

    Inter-organellar contact sites establish microdomains for localised Ca 2+ -signalling events. One of these microdomains is established between the ER and the mitochondria. Importantly, the so-called mitochondria-associated ER membranes (MAMs) contain, besides structural proteins and proteins involved in lipid exchange, several Ca 2+ -transport systems, mediating efficient Ca 2+ transfer from the ER to the mitochondria. These Ca 2+ signals critically control several mitochondrial functions, thereby impacting cell metabolism, cell death and survival, proliferation and migration. Hence, the MAMs have emerged as critical signalling hubs in physiology, while their dysregulation is an important factor that drives or at least contributes to oncogenesis and tumour progression. In this book chapter, we will provide an overview of the role of the MAMs in cell function and how alterations in the MAM composition contribute to oncogenic features and behaviours.

  14. Inhibition of ER stress and unfolding protein response pathways causes skeletal muscle wasting during cancer cachexia.

    PubMed

    Bohnert, Kyle R; Gallot, Yann S; Sato, Shuichi; Xiong, Guangyan; Hindi, Sajedah M; Kumar, Ashok

    2016-09-01

    Cachexia is a devastating syndrome that causes morbidity and mortality in a large number of patients with cancer. However, the mechanisms of cancer cachexia remain poorly understood. Accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes stress. The ER responds to this stress through activating certain pathways commonly known as the unfolding protein response (UPR). The main function of UPR is to restore homeostasis, but excessive or prolonged activation of UPR can lead to pathologic conditions. In this study, we examined the role of ER stress and UPR in regulation of skeletal muscle mass in naïve conditions and during cancer cachexia. Our results demonstrate that multiple markers of ER stress are highly activated in skeletal muscle of Lewis lung carcinoma (LLC) and Apc(Min/+) mouse models of cancer cachexia. Treatment of mice with 4-phenylbutyrate (4-PBA), a chemical chaperon and a potent inhibitor of ER stress, significantly reduced skeletal muscle strength and mass in both control and LLC-bearing mice. Blocking the UPR also increased the proportion of fast-type fibers in soleus muscle of both control and LLC-bearing mice. Inhibition of UPR reduced the activity of Akt/mTOR pathway and increased the expression of the components of the ubiquitin-proteasome system and autophagy in LLC-bearing mice. Moreover, we found that the inhibition of UPR causes severe atrophy in cultured myotubes. Our study provides initial evidence that ER stress and UPR pathways are essential for maintaining skeletal muscle mass and strength and for protection against cancer cachexia.-Bohnert, K. R., Gallot, Y. S., Sato, S., Xiong, G., Hindi, S. M., Kumar, A. Inhibition of ER stress and unfolding protein response pathways causes skeletal muscle wasting during cancer cachexia. © FASEB.

  15. 20 CFR 216.63 - Who is eligible for an annuity as a remarried widow(er).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... retirement, disability, widow(er)'s, mother's, father's, parent's, or disabled child's benefit under the... RAILROAD RETIREMENT ACT ELIGIBILITY FOR AN ANNUITY Widow(er), Surviving Divorced Spouse, and Remarried... reduced annuity); (5) Has not attained retirement age but has in his or her care a child who either is...

  16. Structural basis for a hand-like site in the calcium sensor CatchER with fast kinetics

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

    Zhang, Ying; Reddish, Florence; Tang, Shen

    2013-12-01

    High-resolution crystal structures of the designed calcium sensor CatchER revealed snapshots of calcium and gadolinium ions binding within the designed site in agreement with its fast kinetics. Calcium ions, which are important signaling molecules, can be detected in the endoplasmic reticulum by an engineered mutant of green fluorescent protein (GFP) designated CatchER with a fast off-rate. High resolution (1.78–1.20 Å) crystal structures were analyzed for CatchER in the apo form and in complexes with calcium or gadolinium to probe the binding site for metal ions. While CatchER exhibits a 1:1 binding stoichiometry in solution, two positions were observed for eachmore » of the metal ions bound within the hand-like site formed by the carboxylate side chains of the mutated residues S147E, S202D, Q204E, F223E and T225E that may be responsible for its fast kinetic properties. Comparison of the structures of CatchER, wild-type GFP and enhanced GFP confirmed that different conformations of Thr203 and Glu222 are associated with the two forms of Tyr66 of the chromophore which are responsible for the absorbance wavelengths of the different proteins. Calcium binding to CatchER may shift the equilibrium for conformational population of the Glu222 side chain and lead to further changes in its optical properties.« less

  17. Human MI-ER1 Alpha and Beta Function as Transcriptional Repressors by Recruitment of Histone Deacetylase 1 to Their Conserved ELM2 Domain

    PubMed Central

    Ding, Zhihu; Gillespie, Laura L.; Paterno, Gary D.

    2003-01-01

    mi-er1 (previously called er1) was first isolated from Xenopus laevis embryonic cells as a novel fibroblast growth factor-regulated immediate-early gene. Xmi-er1 was shown to encode a nuclear protein with an N-terminal acidic transcription activation domain. The human orthologue of mi-er1 (hmi-er1) displays 91% similarity to the Xenopus sequence at the amino acid level and was shown to be upregulated in breast carcinoma cell lines and tumors. Alternative splicing at the 3′ end of hmi-er1 produces two major isoforms, hMI-ER1α and hMI-ER1β, which contain distinct C-terminal domains. In this study, we investigated the role of hMI-ER1α and hMI-ER1β in the regulation of transcription. Using fusion proteins of hMI-ER1α or hMI-ER1β tethered to the GAL4 DNA binding domain, we show that both isoforms, when recruited to the G5tkCAT minimal promoter, function to repress transcription. We demonstrate that this repressor activity is due to interaction and recruitment of a trichostatin A-sensitive histone deacetylase 1 (HDAC1). Furthermore, deletion analysis revealed that recruitment of HDAC1 to hMI-ER1α and hMI-ER1β occurs through their common ELM2 domain. The ELM2 domain was first described in the Caenorhabditis elegans Egl-27 protein and is present in a number of SANT domain-containing transcription factors. This is the first report of a function for the ELM2 domain, highlighting its role in the regulation of transcription. PMID:12482978

  18. Human MI-ER1 alpha and beta function as transcriptional repressors by recruitment of histone deacetylase 1 to their conserved ELM2 domain.

    PubMed

    Ding, Zhihu; Gillespie, Laura L; Paterno, Gary D

    2003-01-01

    mi-er1 (previously called er1) was first isolated from Xenopus laevis embryonic cells as a novel fibroblast growth factor-regulated immediate-early gene. Xmi-er1 was shown to encode a nuclear protein with an N-terminal acidic transcription activation domain. The human orthologue of mi-er1 (hmi-er1) displays 91% similarity to the Xenopus sequence at the amino acid level and was shown to be upregulated in breast carcinoma cell lines and tumors. Alternative splicing at the 3' end of hmi-er1 produces two major isoforms, hMI-ER1alpha and hMI-ER1beta, which contain distinct C-terminal domains. In this study, we investigated the role of hMI-ER1alpha and hMI-ER1beta in the regulation of transcription. Using fusion proteins of hMI-ER1alpha or hMI-ER1beta tethered to the GAL4 DNA binding domain, we show that both isoforms, when recruited to the G5tkCAT minimal promoter, function to repress transcription. We demonstrate that this repressor activity is due to interaction and recruitment of a trichostatin A-sensitive histone deacetylase 1 (HDAC1). Furthermore, deletion analysis revealed that recruitment of HDAC1 to hMI-ER1alpha and hMI-ER1beta occurs through their common ELM2 domain. The ELM2 domain was first described in the Caenorhabditis elegans Egl-27 protein and is present in a number of SANT domain-containing transcription factors. This is the first report of a function for the ELM2 domain, highlighting its role in the regulation of transcription.

  19. ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish

    PubMed Central

    Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L.; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi

    2013-01-01

    ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra. PMID:23447699

  20. ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish.

    PubMed

    Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi

    2013-05-01

    ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra.

  1. Temperature influence on spectroscopic properties and 2.7-μm lasing of Er:YAP crystal

    NASA Astrophysics Data System (ADS)

    Švejkar, Richard; Šulc, Jan; Němec, Michal; Jelínková, Helena; Nejezchleb, Karel; Čech, Miroslav

    2018-02-01

    The spectroscopic and laser properties of Er:YAP crystal, that is appropriate for generation at 2.7 μm, in temperature range 78 - 400 K are presented. The sample of Er:YAP (1 at. % of Er3+) had face-polished plan-parallel faces without anti-reflection coatings (thickness 4.47 mm). During experiments the Er:YAP was attached to temperature controlled copper holder and it was placed in vacuum chamber. The transmission and emission spectra together with the fluorescence decay time were measured depending on temperature. The Er:YAP crystal was longitudinally pumped by radiation from laser diode that works in pulse regime (repetition rate 66.6 Hz, pulse duration 1.5 ms, pump wavelength 972.5 nm) or in CW regime. Laser resonator was hemispherical, 145 mm in length with flat pumping mirror (HR @ 2.7 μm) and spherical output coupler (r = 150 mm, R = 95 % @ 2.5 - 2.8 μm). The fluorescence decay time of manifold 4I11/2 (upper laser level) became shorter and intensity of up-conversion radiation was increasing with decreasing temperature. In pulsed regime, the highest slope efficiency with respect to absorbed mean power was 1.27 % at 78 K. The maximum output of mean power was 3.5 mW at 78 K, i.e. 8.7 times higher than measured this value at 300 K. The maximal output power 27 mW with slope efficiency up to 3.5 % was achieved in CW. The radiation generated by Er:YAP laser (2.73 μm) is close to absorption peak of water (3 μm) thus this wavelength can be use in medicine and spectroscopy.

  2. CO2 and Er:YAG laser interaction with grass tissues

    NASA Astrophysics Data System (ADS)

    Kim, Jaehun; Ki, Hyungson

    2013-01-01

    Plant leaves are multi-component optical materials consisting of water, pigments, and dry matter, among which water is the predominant constituent. In this article, we investigate laser interaction with grass using CO2 and Er:YAG lasers theoretically and experimentally, especially targeting water in grass tissues. We have first studied the optical properties of light absorbing constituents of grass theoretically, and then have identified interaction regimes and constructed interaction maps through a systematic experiment. Using the interaction maps, we have studied how interaction regimes change as process parameters are varied. This study reveals some interesting findings concerning carbonization and ablation mechanisms, the effect of laser beam diameter, and the ablation efficiency and quality of CO2 and Er:YAG lasers.

  3. Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy

    PubMed Central

    McLelland, Gian-Luca; Goiran, Thomas; Yi, Wei; Dorval, Geneviève; Chen, Carol X; Lauinger, Nadine D; Krahn, Andrea I; Valimehr, Sepideh; Rakovic, Aleksandar; Rouiller, Isabelle; Durcan, Thomas M; Trempe, Jean-François

    2018-01-01

    Despite their importance as signaling hubs, the function of mitochondria-ER contact sites in mitochondrial quality control pathways remains unexplored. Here we describe a mechanism by which Mfn2, a mitochondria-ER tether, gates the autophagic turnover of mitochondria by PINK1 and parkin. Mitochondria-ER appositions are destroyed during mitophagy, and reducing mitochondria-ER contacts increases the rate of mitochondrial degradation. Mechanistically, parkin/PINK1 catalyze a rapid burst of Mfn2 phosphoubiquitination to trigger p97-dependent disassembly of Mfn2 complexes from the outer mitochondrial membrane, dissociating mitochondria from the ER. We additionally demonstrate that a major portion of the facilitatory effect of p97 on mitophagy is epistatic to Mfn2 and promotes the availability of other parkin substrates such as VDAC1. Finally, we reconstitute the action of these factors on Mfn2 and VDAC1 ubiquitination in a cell-free assay. We show that mitochondria-ER tethering suppresses mitophagy and describe a parkin-/PINK1-dependent mechanism that regulates the destruction of mitochondria-ER contact sites. PMID:29676259

  4. Optimized design of Yb3+/Er3+-codoped cross-coupled integrated microring resonator arrays

    NASA Astrophysics Data System (ADS)

    Gǎlǎtus, Ramona; Vallés, Juan A.

    2014-09-01

    In this work the analytical model of the scattering response of a highly Yb3+/Er3+-codoped phosphate glass microring resonator array is developed. The microscopic statistical formalism is used to simulate its performance as a wavelengthselective amplifier. The performance of the integrated add-drop filter was investigated based on the signal transfer functions for Through and Drop ports, correlated the with gain coefficient and its dependence on pump power, signal power and Yb3+/Er3+- dopants concentration. In consequence, microring arrays with gain operating in the near infrared spectral range and, in particular, in the 1.5-mm wavelength band (emission band of Er-doped fiber amplifiers and lasers, already used in several bio/chemical sensing tasks) are highly attractive.

  5. Study of broadband near-infrared emission in Tm3+-Er3+ codoped TeO2-WO3-PbO glasses.

    PubMed

    Balda, R; Fernández, J; Fernández-Navarro, J M

    2009-05-25

    In this work, we report the near-infrared emission properties of Tm(3+)-Er(3+) codoped tellurite TeO(2)-WO(3)-PbO glasses under 794 nm excitation. A broad emission from 1350 to 1750 nm corresponding to the Tm(3+) and Er(3+) emissions is observed. The full width at half-maximum of this broadband increases with increasing [Tm]/[Er] concentration ratio up to a value of ~ 160 nm. The energy transfer between Tm(3+) and Er(3+) ions is evidenced by both the temporal behavior of the near-infrared luminescence and the effect of Tm3+ codoping on the visible upconversion of Er(3+) ions.

  6. Oligoethylene Glycol-substituted Aza-BODIPY Dyes As Red Emitting ER-Probes

    PubMed Central

    Kamkaew, Anyanee; Thavornpradit, Sopida; Puangsamlee, Thamon; Xin, Dongyue; Wanichacheva, Nantanit; Burgess, Kevin

    2015-01-01

    This study features aza-BODIPY (BF2-chelated azadipyrromethene) dyes with two aromatic substituents linked by oligoethylene glycol fragments to increase hydrophilicity of aza-BODIPY for applications in intracellular imaging. To prepare these, two chalcones were attached α,ω onto oligoethylene glycol fragments, then reacted with nitromethane anion. Conjugate addition products from this reaction were then subjected to typical conditions for synthesis of aza-BODIPY dyes (NH4OAc, nBuOH, 120 °C); formation of boracycles in this reaction was concomitant with creation of macrocycles containing the oligoethylene glycol fragments. Similar dyes with acyclic oligoelythene glycol substituents in the same position were used to compare the efficiencies of the intra- and inter-molecular aza-BODIPY forming reactions, and the characteristics of the products. All the fluors with oligoethylene glycol fragments, ie cyclic or acyclic, localized in the endoplasmic reticulum of a fibroblast cell line (WEHI-13VAR), the human pancreatic cancer cell line (PANC-1, rough ER predominates) and human liver cancer cell line (HepG2, smooth ER prevalent). These fluors are potentially useful for near IR (λmax emis at 730 nm) ER staining probes. PMID:26138325

  7. A spastic paraplegia mouse model reveals REEP1-dependent ER shaping.

    PubMed

    Beetz, Christian; Koch, Nicole; Khundadze, Mukhran; Zimmer, Geraldine; Nietzsche, Sandor; Hertel, Nicole; Huebner, Antje-Kathrin; Mumtaz, Rizwan; Schweizer, Michaela; Dirren, Elisabeth; Karle, Kathrin N; Irintchev, Andrey; Alvarez, Victoria; Redies, Christoph; Westermann, Martin; Kurth, Ingo; Deufel, Thomas; Kessels, Michael M; Qualmann, Britta; Hübner, Christian A

    2013-10-01

    Axonopathies are a group of clinically diverse disorders characterized by the progressive degeneration of the axons of specific neurons. In hereditary spastic paraplegia (HSP), the axons of cortical motor neurons degenerate and cause a spastic movement disorder. HSP is linked to mutations in several loci known collectively as the spastic paraplegia genes (SPGs). We identified a heterozygous receptor accessory protein 1 (REEP1) exon 2 deletion in a patient suffering from the autosomal dominantly inherited HSP variant SPG31. We generated the corresponding mouse model to study the underlying cellular pathology. Mice with heterozygous deletion of exon 2 in Reep1 displayed a gait disorder closely resembling SPG31 in humans. Homozygous exon 2 deletion resulted in the complete loss of REEP1 and a more severe phenotype with earlier onset. At the molecular level, we demonstrated that REEP1 is a neuron-specific, membrane-binding, and membrane curvature-inducing protein that resides in the ER. We further show that Reep1 expression was prominent in cortical motor neurons. In REEP1-deficient mice, these neurons showed reduced complexity of the peripheral ER upon ultrastructural analysis. Our study connects proper neuronal ER architecture to long-term axon survival.

  8. 75 FR 26643 - Special Conditions: Rockwell Collins, Inc., Boeing Model 737-700/-700C/-800/-900 and -900ER...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... -900 ER series airplanes because of a novel or unusual design feature, special conditions are... and -900ER Series Airplanes Equipped With Rockwell HGS- 4000 Head-Up Guidance System With Enhanced.../-700C/-800/-900 and -900ER series airplanes equipped with the Rockwell HGS-4000 Head-Up Guidance System...

  9. ER stress and subsequent activated calpain play a pivotal role in skeletal muscle wasting after severe burn injury

    PubMed Central

    Shen, Chuanan; Li, Dawei; Wang, Xiaoteng

    2017-01-01

    Severe burns are typically followed by hypermetabolism characterized by significant muscle wasting, which causes considerable morbidity and mortality. The aim of the present study was to explore the underlying mechanisms of skeletal muscle damage/wasting post-burn. Rats were randomized to the sham, sham+4-phenylbutyrate (4-PBA, a pharmacological chaperone promoting endoplasmic reticulum (ER) folding/trafficking, commonly considered as an inhibitor of ER), burn (30% total body surface area), and burn+4-PBA groups; and sacrificed at 1, 4, 7, 14 days after the burn injury. Tibial anterior muscle was harvested for transmission electron microscopy, calcium imaging, gene expression and protein analysis of ER stress / ubiquitin-proteasome system / autophagy, and calpain activity measurement. The results showed that ER stress markers were increased in the burn group compared with the sham group, especially at post-burn days 4 and 7, which might consequently elevate cytoplasmic calcium concentration, promote calpain production as well as activation, and cause skeletal muscle damage/wasting of TA muscle after severe burn injury. Interestingly, treatment with 4-PBA prevented burn-induced ER swelling and altered protein expression of ER stress markers and calcium release, attenuating calpain activation and skeletal muscle damage/wasting after severe burn injury. Atrogin-1 and LC3-II/LC3-I ratio were also increased in the burn group compared with the sham group, while MuRF-1 remained unchanged; 4-PBA decreased atrogin-1 in the burn group. Taken together, these findings suggested that severe burn injury induces ER stress, which in turns causes calpain activation. ER stress and subsequent activated calpain play a critical role in skeletal muscle damage/wasting in burned rats. PMID:29028830

  10. Mammary Ductal Environment Is Necessary for Faithful Maintenance of Estrogen Signaling in ER+ Breast Cancer

    PubMed Central

    Haricharan, Svasti; Lei, Jonathan; Ellis, Matthew

    2016-01-01

    In this issue of Cancer Cell, Sflomos et al. (2016) describe a robust preclinical animal model of ER+ breast cancer. The authors identify the critical role of the breast microenvironment in determining hormone response of ER+ breast cancer cells and in driving the luminal phenotype of breast cancer. PMID:26977876

  11. Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription

    PubMed Central

    Marza, Esther; Taouji, Saïd; Barroso, Kim; Raymond, Anne-Aurélie; Guignard, Léo; Bonneu, Marc; Pallares-Lupon, Néstor; Dupuy, Jean-William; Fernandez-Zapico, Martin E; Rosenbaum, Jean; Palladino, Francesca; Dupuy, Denis; Chevet, Eric

    2015-01-01

    The accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPRER) to restore ER homeostasis. The AAA+ ATPase p97/CDC-48 plays key roles in ER stress by promoting both ER protein degradation and transcription of UPRER genes. Although the mechanisms associated with protein degradation are now well established, the molecular events involved in the regulation of gene transcription by p97/CDC-48 remain unclear. Using a reporter-based genome-wide RNAi screen in combination with quantitative proteomic analysis in Caenorhabditis elegans, we have identified RUVB-2, a AAA+ ATPase, as a novel repressor of a subset of UPRER genes. We show that degradation of RUVB-2 by CDC-48 enhances expression of ER stress response genes through an XBP1-dependent mechanism. The functional interplay between CDC-48 and RUVB-2 in controlling transcription of select UPRER genes appears conserved in human cells. Together, these results describe a novel role for p97/CDC-48, whereby its role in protein degradation is integrated with its role in regulating expression of ER stress response genes. PMID:25652260

  12. Preparation and spectroscopic characterization of two HoCl 3-galactitol complexes and one ErCl 3-galactitol complex

    NASA Astrophysics Data System (ADS)

    Hua, Xiaohui; Pan, Qinghua; Yu, Lei; Xue, Junhui; Yang, Limin; Xu, Yizhuang; Zhao, Guozhong; Li, Weihong; Wang, Zheming; Wu, Jinguang; Liu, Kexin; Chen, Jia'er

    2011-07-01

    The interactions between metal ions and hydroxyl groups of carbohydrates are important for their possible biological activities. Here two HoCl 3-galactitol complexes ([Ho(galac)(H 2O) 3)]Cl 3·0.5galac) (HoG(I)) and ([Ho 2(galac)(H 2O) 12)]Cl 6·2H 2O) (HoG(II))) and one ErCl 3-galactitol complex ([Er(galac)(H 2O) 3)]Cl 3·0.5galac)(ErG)) were prepared and characterized. The possible structures of HoG(I) and ErG were deduced from FTIR, elemental analysis, ESI-MS, FIR, THz and TGA results. It is suggested that Ho 3+ or Er 3+ is 9-coordinated with six hydroxyl groups from two galactitol molecules and three water molecules, and another galactitol molecule is hydrogen-bonded in HoG(I) and ErG and the ratio of metal to ligand is 1:1.5. The structure of HoG(II) was determined by FTIR and X-ray diffraction analyses. The results demonstrate that lanthanide ions with galactitol may form two compounds in a system and different topological structures can be obtained.

  13. Identification of ER proteins involved in the functional organisation of the early secretory pathway in Drosophila cells by a targeted RNAi screen.

    PubMed

    Kondylis, Vangelis; Tang, Yang; Fuchs, Florian; Boutros, Michael; Rabouille, Catherine

    2011-02-23

    In Drosophila, the early secretory apparatus comprises discrete paired Golgi stacks in close proximity to exit sites from the endoplasmic reticulum (tER sites), thus forming tER-Golgi units. Although many components involved in secretion have been identified, the structural components sustaining its organisation are less known. Here we set out to identify novel ER resident proteins involved in the of tER-Golgi unit organisation. To do so, we designed a novel screening strategy combining a bioinformatics pre-selection with an RNAi screen. We first selected 156 proteins exhibiting known or related ER retention/retrieval signals from a list of proteins predicted to have a signal sequence. We then performed a microscopy-based primary and confirmation RNAi screen in Drosophila S2 cells directly scoring the organisation of the tER-Golgi units. We identified 49 hits, most of which leading to an increased number of smaller tER-Golgi units (MG for "more and smaller Golgi") upon depletion. 16 of them were validated and characterised, showing that this phenotype was not due to an inhibition in secretion, a block in G2, or ER stress. Interestingly, the MG phenotype was often accompanied by an increase in the cell volume. Out of 6 proteins, 4 were localised to the ER. This work has identified novel proteins involved in the organisation of the Drosophila early secretory pathway. It contributes to the effort of assigning protein functions to gene annotation in the secretory pathway, and analysis of the MG hits revealed an enrichment of ER proteins. These results suggest a link between ER localisation, aspects of cell metabolism and tER-Golgi structural organisation.

  14. Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity.

    PubMed

    Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

    2016-05-23

    The uroguanylin-GUCY2C gut-brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ER(T2)-Rosa-STOP(loxP/loxP)-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms

  15. Discovery of a Novel er1 Allele Conferring Powdery Mildew Resistance in Chinese Pea (Pisum sativum L.) Landraces

    PubMed Central

    Sun, Suli; Fu, Haining; Wang, Zhongyi; Duan, Canxing; Zong, Xuxiao; Zhu, Zhendong

    2016-01-01

    Pea powdery mildew, caused by Erysiphe pisi D.C., is an important disease worldwide. Deployment of resistant varieties is the main way to control this disease. This study aimed to screen Chinese pea (Pisum sativum L.) landraces resistant to E. pisi, and to characterize the resistance gene(s) at the er1 locus in the resistant landraces, and to develop functional marker(s) specific to the novel er1 allele. The 322 landraces showed different resistance levels. Among them, 12 (3.73%), 4 (1.24%) and 17 (5.28%) landraces showed immunity, high resistance and resistance to E. pisi, respectively. The other landraces appeared susceptible or highly susceptible to E. pisi. Most of the immune and highly resistant landraces were collected from Yunnan province. To characterize the resistance gene at the er1 locus, cDNA sequences of PsMLO1 gene were determined in 12 immune and four highly resistant accessions. The cDNAs of PsMLO1 from the immune landrace G0005576 produced three distinct transcripts, characterized by a 129-bp deletion, and 155-bp and 220-bp insertions, which were consistent with those of er1-2 allele. The PsMLO1 cDNAs in the other 15 resistant landraces produced identical transcripts, which had a new point mutation (T→C) at position 1121 of PsMLO1, indicating a novel er1 allele, designated as er1-6. This mutation caused a leucine to proline change in the amino acid sequence. Subsequently, the resistance allele er1-6 in landrace G0001778 was confirmed by resistance inheritance analysis and genetic mapping on the region of the er1 locus using populations derived from G0001778 × Bawan 6. Finally, a functional marker specific to er1-6, SNP1121, was developed using the high-resolution melting technique, which could be used in pea breeding via marker-assisted selection. The results described here provide valuable genetic information for Chinese pea landraces and a powerful tool for pea breeders. PMID:26809053

  16. Polarity of the ascidian egg cortex and relocalization of cER and mRNAs in the early embryo.

    PubMed

    Prodon, François; Dru, Philippe; Roegiers, Fabrice; Sardet, Christian

    2005-06-01

    The mature ascidian oocyte is a large cell containing cytoplasmic and cortical domains polarized along a primary animal-vegetal (a-v) axis. The oocyte cortex is characterized by a gradient distribution of a submembrane monolayer of cortical rough endoplasmic reticulum (cER) and associated maternal postplasmic/PEM mRNAs (cER-mRNA domain). Between fertilization and first cleavage, this cER-mRNA domain is first concentrated vegetally and then relocated towards the posterior pole via microfilament-driven cortical contractions and spermaster-microtubule-driven translocations. The cER-mRNA domain further concentrates in a macroscopic cortical structure called the centrosome attracting body (CAB), which mediates a series of asymmetric divisions starting at the eight-cell stage. This results in the segregation of determinant mRNAs and their products in posterior cells of the embryo precursors of the muscle and germ line. Using two species of ascidians (Ciona intestinalis and Phallusia mammillata), we have pursued and amplified the work initiated in Halocynthia roretzi. We have analysed the cortical reorganizations in whole cells and in cortical fragments isolated from oocytes and from synchronously developing zygotes and embryos. After fertilization, we observe that a cortical patch rich in microfilaments encircles the cER-mRNA domain, concentrated into a cortical cap at the vegetal/contraction pole (indicating the future dorsal pole). Isolated cortices also retain microtubule asters rich in cER (indicating the future posterior pole). Before mitosis, parts of the cER-mRNA domain are detected, together with short microtubules, in isolated posterior (but not anterior) cortices. At the eight-cell stage, the posteriorly located cER-mRNA domain undergoes a cell-cycle-dependant compaction into the CAB. The CAB with embedded centrosomal microtubules can be isolated with cortical fragments from eight-cell-stage embryos. These and previous observations indicate that cytoskeleton

  17. Simulation of medical Q-switch flash-pumped Er:YAG laser

    NASA Astrophysics Data System (ADS)

    -Yan-lin, Wang; Huang-Chuyun; Yao-Yucheng; Xiaolin, Zou

    2011-01-01

    Er: YAG laser, the wavelength is 2940nm, can be absorbed strongly by water. The absorption coefficient is as high as 13000 cm-1. As the water strong absorption, Erbium laser can bring shallow penetration depth and smaller surrounding tissue injury in most soft tissue and hard tissue. At the same time, the interaction between 2940nm radiation and biological tissue saturated with water is equivalent to instantaneous heating within limited volume, thus resulting in the phenomenon of micro-explosion to removal organization. Different parameters can be set up to cut enamel, dentin, caries and soft tissue. For the development and optimization of laser system, it is a practical choice to use laser modeling to predict the influence of various parameters for laser performance. Aim at the status of low Erbium laser output power, flash-pumped Er: YAG laser performance was simulated to obtain optical output in theory. the rate equation model was obtained and used to predict the change of population densities in various manifolds and use the technology of Q-switch the simulate laser output for different design parameters and results showed that Er: YAG laser output energy can achieve the maximum average output power of 9.8W under the given parameters. The model can be used to find the potential laser systems that meet application requirements.

  18. Effects of Different Combinations of Er:YAG Laser-Adhesives on Enamel Demineralization and Bracket Bond Strength

    PubMed Central

    Nalçacı, Ruhi; Üşümez, Serdar; Malkoç, Sıddık

    2016-01-01

    Abstract Objective: The purpose of this study was to investigate the demineralization around brackets and shear bond strength (SBS) of brackets bonded to Er:YAG laser-irradiated enamel at different power settings with various adhesive systems combinations. Methods: A total of 108 premolar teeth were used in this study. Teeth were assigned into three groups according to the etching procedure, then each group divided into three subgroups based on the application of different adhesive systems. There were a total of nine groups as follows. Group 1: Acid + Transbond XT Primer; group 2: Er:YAG (100 mJ, 10 Hz) etching + Transbond XT Primer; group 3: Er:YAG (200 mJ, 10 Hz) etching + Transbond XT Primer; group 4: Transbond Plus self-etching primer (SEP); group 5: Er:YAG (100 mJ, 10 Hz) etching + Transbond Plus SEP; group 6: Er:YAG (200 mJ, 10 Hz) etching + Transbond Plus SEP; group 7: Clearfil Protect Bond; group 8: Er:YAG (100 mJ, 10 Hz) etching + Clearfil Protect Bond; group 9: Er:YAG (200 mJ, 10 Hz) etching + Clearfil Protect Bond. Brackets were bonded with Transbond XT Adhesive Paste in all groups. Teeth to be evaluated for demineralization and SBS were exposed to pH and thermal cyclings, respectively. Then, demineralization samples were scanned with micro-CT to determine lesion depth values. For SBS test, a universal testing machine was used and adhesive remnant was index scored after debonding. Data were analyzed statistically. Results: No significant differences were found among the lesion depth values of the various groups, except for G7 and G8, in which the lowest values were recorded. The lowest SBS values were in G7, whereas the highest were in G9. The differences between the other groups were not significant. Conclusions: Er:YAG laser did not have a positive effect on prevention of enamel demineralization. When two step self-etch adhesive is preferred for bonding brackets, laser etching at 1 W (100 mJ, 10 Hz) is

  19. ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells.

    PubMed

    Lewis, Samantha C; Uchiyama, Lauren F; Nunnari, Jodi

    2016-07-15

    Mitochondrial DNA (mtDNA) encodes RNAs and proteins critical for cell function. In human cells, hundreds to thousands of mtDNA copies are replicated asynchronously, packaged into protein-DNA nucleoids, and distributed within a dynamic mitochondrial network. The mechanisms that govern how nucleoids are chosen for replication and distribution are not understood. Mitochondrial distribution depends on division, which occurs at endoplasmic reticulum (ER)-mitochondria contact sites. These sites were spatially linked to a subset of nucleoids selectively marked by mtDNA polymerase and engaged in mtDNA synthesis--events that occurred upstream of mitochondrial constriction and division machine assembly. Our data suggest that ER tubules proximal to nucleoids are necessary but not sufficient for mtDNA synthesis. Thus, ER-mitochondria contacts coordinate licensing of mtDNA synthesis with division to distribute newly replicated nucleoids to daughter mitochondria. Copyright © 2016, American Association for the Advancement of Science.

  20. Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology.

    PubMed

    Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît; Maldonado-Báez, Lymarie; Park, Seong Hee; Blackstone, Craig

    2016-11-15

    Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. Published by Elsevier Inc.