EXPRESSION PATTERNS OF ESTROGEN RECEPTORS IN THE CENTRAL AUDITORY SYSTEM CHANGE IN PREPUBERTAL AND AGED MICE

PubMed Central

Charitidi, K.; Frisina, R. D.; Vasilyeva, O. N.; Zhu, X.; Canlon, B.

2011-01-01

Estrogens are important in the development, maintenance and physiology of the CNS. Several studies have shown their effects on the processing of hearing in both males and females, and these effects, in part, are thought to result from regulation of the transcription of genes via their classical estrogen receptor (ER) pathway. In order to understand the spatiotemporal changes that occur with age, we have studied the expression of ERs in the central auditory pathway in prepubertal and aged CBA mice with immunohistochemistry. In prepubertal mice a clear dichotomy was noted between the expression of ERα and ERβ. ERβ-positive neurons were found in the metencephalon whereas the majority of ERα was found in mesencephalon, diencephalon or the telencephalon. In the aged animals a different pattern of ER expression was found in terms of location and overall intensity. These age-induced changes in the expression pattern were generally not uniform, suggesting that region-specific mechanisms regulate the ERs’ age-related expression. Neither the prepubertal nor the aged animals showed sex differences in any auditory structure. Our results demonstrate different age-dependent spatial and temporal changes in the pattern of expression of ERα and ERβ, suggesting that each ER type may be involved in distinct roles across the central auditory pathway in different periods of maturation. PMID:20736049

The neoclassical ``Electron Root'' feature in the Wendelstein-7-AS stellarator

NASA Astrophysics Data System (ADS)

Maaßberg, H.; Beidler, C. D.; Gasparino, U.; Romé, M.; Dyabilin, K. S.; Marushchenko, N. B.; Murakami, S.

2000-01-01

The neoclassical prediction of the "electron root," i.e., a strongly positive radial electric field, Er (being the solution of the ambipolarity condition of the particle fluxes), is analyzed for low-density discharges in Wendelstein-7-AS [G. Grieger, W. Lotz, P. Merkel, et al., Phys. Fluids B 4, 2081 (1992)]. In these electron cyclotron resonance heated (ECRH) discharges with highly localized central power deposition, peaked Te profiles [with Te(0) up to 6 keV and with Ti≪Te] and strongly positive Er in the central region are measured. It is shown that this "electron root" feature at W7-AS is driven by ripple-trapped suprathermal electrons generated by the ECRH. The fraction of ripple-trapped particles in the ECRH launching plane, which can be varied at W7-AS, is found to be the most important. After switching off the heating the "electron root" feature disappears nearly immediately, i.e., two different time scales for the electron temperature decay in the central region are observed. Monte Carlo simulations in five-dimensional phase space are presented, clearly indicating that the additional "convective" electron fluxes driven by the ECRH are of the same order as the ambipolar neoclassical prediction for the "ion root" at much lower Er. For the predicted "electron root," the ion fluxes calculated based on the traditional neoclassical ordering are much too small; shortcomings of the usual approach are indentified and a new ordering scheme is proposed.

Comparison of estrogen receptor results from pathology reports with results from central laboratory testing.

PubMed

Collins, Laura C; Marotti, Jonathan D; Baer, Heather J; Tamimi, Rulla M

2008-02-06

We compared estrogen receptor (ER) assay results abstracted from pathology reports with ER results determined on the same specimens by a central laboratory with an immunohistochemical assay. Paraffin sections were cut from tissue microarrays containing 3093 breast cancer specimens from women enrolled in the Nurses' Health Study, 1851 of which had both pathology reports and tissue available for central laboratory testing. All sections were immunostained for ER at the same time. The original assays were biochemical for 1512 (81.7%) of the 1851 specimens, immunohistochemical for 336 (18.2%), and immunofluorescent for three (0.2%). ER results from pathology reports and repeat central laboratory testing were in agreement for 87.3% of specimens (1615 of the 1851 specimens; kappa statistic = 0.64, P < .001). When the comparison was restricted to the specimens for which the ER assays were originally performed by immunohistochemistry, the agreement rate increased to 92.3% of specimens (310 of the 336 specimens; kappa statistic = 0.78, P < .001). Thus, ER assay results from pathology reports appear to be a reasonable alternative to central laboratory ER testing for large, population-based studies of patients with breast cancer.

Comparison of Estrogen Receptor Assay Results from Pathology Reports with Results from Central Laboratory Testing: Implications for Population-Based Studies of Breast Cancer

PubMed Central

Collins, LC; Marotti, J; Baer, HJ; Deitz, AC; Colditz, GA; Tamimi, RM

2014-01-01

Population-based studies of women with breast cancer commonly utilize information culled from pathology reports rather than central pathology review. The reliability of this information, particularly with regard to tumor biomarker results, is of concern. To address this, we evaluated the concordance between estrogen receptor (ER) results as determined from the original pathology reports and ER results obtained on the same specimens following testing in a single laboratory. Tissue microarrays (TMAs) were constructed from paraffin blocks of 3,167 breast cancers that developed in women enrolled in the Nurses’ Health Study. ER immunostains were performed on all TMA sections in single run. Results of ER immunostains performed on the TMA sections were compared with ER assay results abstracted from pathology reports. Among 1,851 cases of invasive breast cancer in which both ER results from pathology reports and central ER test results were available, the reported ER status and the ER status as determined from immunostains on TMAs were in agreement in 1,651 cases (87.3 %; kappa value 0.64, p<0.0001). When the comparison was restricted to ER assays originally performed by immunohistochemistry, the agreement rate increased to 92.3% (kappa value 0.78, p<0.0001). These results provide a framework for the accuracy of ER results abstracted from clinical records. Further, they suggest that utilizing ER assay results from pathology reports is a reasonable, albeit imperfect, alternative to central laboratory ER testing for large, population-based studies of patients with breast cancer. PMID:18230800

77 FR 5503 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-03

... Contract Funding, L.L.C., Central Power & Lime LLC, Cedar Brakes II, L.L.C., J.P. Morgan Commodities Canada..., L.L.C., et al.--Supplement to Updated Market Power Analysis for the Northeast Region. Filed Date: 1... that the Commission received the following electric rate filings: Docket Numbers: ER08-1056-005...

Coexistence of immune-neuro-endocrine substances in the rat central neurons.

PubMed

Zhu, C; Liu, Q; Wei, Y; Ma, C; Hao, J; Yan, P

1999-01-01

To investigate the expression of interleukin-2 (IL-2), metabotropic glutamate receptor subunit 1 (mGluR1) and estrogen receptor (ER) in neurons of the rat central nervous system (CNS) and identify the coexistence possibility of these immune-neuro-endocrine substances in the central neurons, the tri-labeling immunocytochemical technique with different species-specific primary antibodies (goat anti-IL-2 antibody, rabbit anti-mGluR1 antibody and mouse anti-ER antibody) were used to incubate two serial neighbor sections (one for demonstrating IL-2, another for mGluR1 and ER) of the cerebral cortex, medulla oblongata and spinal cord. There were IL-2-, mGluR1- and ER-immunoreactivity (IR)-positive labeled neurons in the above-mentioned central areas. The IL-2-IR production showed brown color, located in the cytoplasm; In the neighbor serial section, the mGluR1-IR, production showed blue-black color, located on the cell membrane; the ER-IR production also showed brown color, located in the cytoplasm and nuclei. There were mGluR1/ER double-labeled cells in the same section, which accounted for about 50%-60% of the total single and double labeled neurons. It was identified by projection check of serial neighbor sections that had mGluR1/ER/IL-2 tri-labeled cells, which accounted for about 30% of total mGluR1/ER double-labeled neurons. The results indicate that mGluR1, ER and Il-2 can coexist in the same rat central neurons, therefore, providing morphological basis for the theory about immune-neuro-endocrine network at the cellular level for the first time.

Hysteresis in the Central African Rainforest

NASA Astrophysics Data System (ADS)

Pietsch, Stephan Alexander; Elias Bednar, Johannes; Gautam, Sishir; Petritsch, Richard; Schier, Franziska; Stanzl, Patrick

2014-05-01

Past climate change caused severe disturbances of the Central African rainforest belt, with forest fragmentation and re-expansion due to drier and wetter climate conditions. Besides climate, human induced forest degradation affected biodiversity, structure and carbon storage of Congo basin rainforests. Information on climatically stable, mature rainforest, unaffected by human induced disturbances, provides means of assessing the impact of forest degradation and may serve as benchmarks of carbon carrying capacity over regions with similar site and climate conditions. BioGeoChemical (BGC) ecosystem models explicitly consider the impacts of site and climate conditions and may assess benchmark levels over regions devoid of undisturbed conditions. We will present a BGC-model validation for the Western Congolian Lowland Rainforest (WCLRF) using field data from a recently confirmed forest refuge, show model - data comparisons for disturbed und undisturbed forests under different site and climate conditions as well as for sites with repeated assessment of biodiversity and standing biomass during recovery from intensive exploitation. We will present climatic thresholds for WCLRF stability, analyse the relationship between resilience, standing C-stocks and change in climate and finally provide evidence of hysteresis.

Along-strike variation in deformation style inferred from kinematic reconstruction and strain rate analysis: A case study of the Ethiopian Rift

NASA Astrophysics Data System (ADS)

Muluneh, Ameha A.; Cuffaro, Marco; Kidane, Tesfaye

2017-09-01

In this paper we combine kinematic reconstruction and seismic strain rate analysis to understand the along-strike variation in strain accommodation in the Ethiopian Rift (ER) evolution. The reconstruction poles close the southern and central ER at 19 and 15 Myr, respectively whereas there is 34 ± 14 km overlap in the northern ER at 11 Myr. Using Kostrov summation, seismic strain rates of 6.81 ×10-9 yr-1 and 0.06 × 10-9 yr-1 are obtained for the south-central and northern ER, respectively. Comparison of the seismic and geodetic strain rates shows that seismic deformation dominates the south and central ER contrary to the northern ER that deforms aseismically. The results obtained indicate that Nubia/Somalia plate reconstructions together with information on the onset of rifting overestimate the kinematics of the northern ER. We argue that magmatic processes play significant role in accommodating the ∼ 2 Myr opening of the rift. Our findings agree well with previous geophysical and geological studies in the Ethiopian Rift.

Different redox sensitivity of endoplasmic reticulum associated degradation clients suggests a novel role for disulphide bonds in secretory proteins.

PubMed

Medraño-Fernandez, Iria; Fagioli, Claudio; Mezghrani, Alexandre; Otsu, Mieko; Sitia, Roberto

2014-04-01

To maintain proteostasis in the endoplasmic reticulum (ER), terminally misfolded secretory proteins must be recognized, partially unfolded, and dislocated to the cytosol for proteasomal destruction, in a complex process called ER-associated degradation (ERAD). Dislocation implies reduction of inter-chain disulphide bonds. When in its reduced form, protein disulphide isomerase (PDI) can act not only as a reductase but also as an unfoldase, preparing substrates for dislocation. PDI oxidation by Ero1 favours substrate release and transport across the ER membrane. Here we addressed the redox dependency of ERAD and found that DTT stimulates the dislocation of proteins with DTT-resistant disulphide bonds (i.e., orphan Ig-μ chains) but stabilizes a ribophorin mutant (Ri332) devoid of them. DTT promotes the association of Ri332, but not of Ig-µ, with PDI. This discrepancy may suggest that disulphide bonds in cargo proteins can be utilized to oxidize PDI, hence facilitating substrate detachment and degradation also in the absence of Ero1. Accordingly, Ero1 silencing retards Ri332 degradation, but has little if any effect on Ig-µ. Thus, some disulphides can increase the stability and simultaneously favour quality control of secretory proteins.

Dust discs around low-mass main-sequence stars

NASA Technical Reports Server (NTRS)

Wolstencroft, R. D.; Walker, Helen J.

1988-01-01

The current understanding of the formation of circumstellar disks as a natural accompaniment to the process of low-mass star formation is examined. Models of the thermal emission from the dust disks around the prototype stars Alpha Lyr, Alpha PsA, Beta Pic, and Epsilon Eri are discussed, which indicate that the central regions of three of these disks are almost devoid of dust within radii ranging between 17 and 26 AU, with the temperature of the hottest zone lying between about 115 and 210 K. One possible explanation of the dust-free zones is the presence of a planet at the inner boundary of each cloud which sweeps up grains crossing its orbit.

Characteristics of X-Ray Emission from the PFRC-2 Capacitively Coupled Plasma

NASA Astrophysics Data System (ADS)

Oliver, Richard; Pearcy, Jacob; Jandovitz, Peter; Swanson, Charles; Matteucci, Jackson; Cohen, Samuel; PFRC Team

2015-11-01

It is uncertain what causes keV X-rays emitted from the central-cell region of a cool (bulk Te ~ 4 eV), tenuous (ne ~1010 cm-3), 5 cm diameter, weakly ionized hydrogen plasma column generated in a tandem high-mirror-ratio mirror machine (PFRC-2 device) by a low-power, external, capacitively-coupled RF (27 MHz) antenna. We explored whether the energetic electrons responsible for the X-rays exist only in the central cell (ER) or also in the asymmetric mirror regions at opposite ends of the machine, as well as how the spectra compare if they do exist in both regions. To address this, we have designed, built, calibrated, installed and operated an X-ray detector system to view the PFRC-2 region near the RF antenna in one end cell (MC). We observe somewhat different X-ray spectra emanating from the two regions. The system comprises two Amptek XR-100CR detectors with moveable slits that scan across the plasma column. Further control of radial resolution (to 0.4 cm) is afforded by changing the detector-to-slit distance. Calibrations were performed with an 55Fe source. These data are being used to understand the source of the fast electrons that create the X-rays in the MC and in the ER. This work is supported by the US DOE Contract No. DE-AC02-09CH11466 and the Princeton Environmental Institute.

Self-focused cognitive emotion regulation style as associated with widespread diminished EEG fractal dimension.

PubMed

Bornas, Xavier; Tortella-Feliu, Miquel; Balle, Maria; Llabrés, Jordi

2013-01-01

The cognitive regulation of emotions is important for human adaptation. Self-focused emotion regulation (ER) strategies have been linked to the development and persistence of anxiety and depression. A vast array of research has provided valuable knowledge about the neural correlates of the use of specific self-focused ER strategies; however, the resting neural correlates of cognitive ER styles, which reflect an individual's disposition to engage in different forms of ER in order to manage distress, are largely unknown. In this study, associations between theoretically negative ER style (self-focused or not) and the complexity (fractal dimension, FD) of the resting EEG at frontal, central, parietal, and occipital regions were investigated in 58 healthy volunteers. The Cognitive Emotion Regulation Questionnaire was used as the self-report measure of ER style. Results showed that a diminished FD over the scalp significantly correlated with self-focused ER style scores, even after controlling for negative affect, which has been also considered to influence the use of ER strategies. The lower the EEG FD, the higher were the self-focused ER style scores. Correlational analyses of specific self-focused ER strategies showed that self-blaming and rumination were negatively associated with diminished FD of the EEG, but catastrophizing and blaming others were not. No significant correlations were found for ER strategies more focused on situation or others. Results are discussed within the self-organized criticality theory of brain dynamics: The diminished FD of the EEG may reflect a disposition to engage in self-focused ER strategies as people prone to ruminate and self-blame show a less complex resting EEG activity, which may make it more difficult for them to exit their negative emotional state.

Chemical control of brush in ponderosa pine forests of central Oregon.

Treesearch

Walter G. Dahms

1961-01-01

The many acres of forest land that are occupied by brush in central Oregon represent a large-scale waste of timber-growing capacity and a major economic loss to the area. Although large brushfields devoid of tree growth present the most spectacular examples of loss, less obvious but equally important brush problems are common in established timber stands. Brush...

[Central interdisciplinary emergency department. Organization of emergency medicine from the perspective of hospital management].

PubMed

Mayer, U; Debatin, J F

2011-04-01

The treatment of emergencies in a hospital should be organized in a central interdisciplinary emergency department (ER). It is the main entrance for all patients with acute illness or injuries. There are multiple advantages of such a central unit. Quality of treatment and economic efficiency is improved. The interdisciplinary diagnostics and treatment at one place prevents time-consuming and unnecessary transport. The fact that more complex diseases and injuries need specialized doctors in specific disciplines should be considered in personnel planning of the ER. To reinsure that the entire medical staff of the hospital is familiar with the daily routine and clinical pathways of the ER, doctors from other departments of the hospital should always be part of the ER team.

Deficiency in the mitochondrial apoptotic pathway reveals the toxic potential of autophagy under ER stress conditions.

PubMed

Deegan, Shane; Saveljeva, Svetlana; Logue, Susan E; Pakos-Zebrucka, Karolina; Gupta, Sanjeev; Vandenabeele, Peter; Bertrand, Mathieu J M; Samali, Afshin

2014-01-01

Endoplasmic reticulum (ER) stress-induced cell death is normally associated with activation of the mitochondrial apoptotic pathway, which is characterized by CYCS (cytochrome c, somatic) release, apoptosome formation, and caspase activation, resulting in cell death. In this study, we demonstrate that under conditions of ER stress cells devoid of CASP9/caspase-9 or BAX and BAK1, and therefore defective in the mitochondrial apoptotic pathway, still undergo a delayed form of cell death associated with the activation of caspases, therefore revealing the existence of an alternative stress-induced caspase activation pathway. We identified CASP8/caspase-8 as the apical protease in this caspase cascade, and found that knockdown of either of the key autophagic genes, ATG5 or ATG7, impacted on CASP8 activation and cell death induction, highlighting the crucial role of autophagy in the activation of this novel ER stress-induced death pathway. In line with this, we identified a protein complex composed of ATG5, FADD, and pro-CASP8 whose assembly coincides with caspase activation and cell death induction. Together, our results reveal the toxic potential of autophagy in cells undergoing ER stress that are defective in the mitochondrial apoptotic pathway, and suggest a model in which the autophagosome functions as a platform facilitating pro-CASP8 activation. Chemoresistance, a common problem in the treatment of cancer, is frequently caused by the downregulation of key mitochondrial death effector proteins. Alternate stress-induced apoptotic pathways, such as the one described here, may become of particular relevance for tackling the problem of chemoresistance in cancer cells.

Polymorphic organization of the endoplasmic reticulum of the Malpighian tubule. Evidence for a transcellular route.

PubMed

Berthelet, F; Beaudry-Lonergan, M; Linares, H; Whittembury, G; Bergeron, M

1987-01-01

Isosmotic fluid absorption carried out by many mammalian epithelia appears to be similar to the isosmotic secretion of insect epithelia such as the Malpighian tubules, which are responsible for urine formation and osmoregulation. We have studied by electron microscopy (80 kV) the three-dimensional characteristics of organelles in the Malpighian tubules of Rhodnius prolixus using thick sections (0.3-0.5 microns) and uranyl and lead impregnation. The ER presents a different organization in the upper (distal) and lower (proximal) segments of the Malpighian tubule. In distal secretory segment, the ER forms a network made of chains of vesicles having irregular shapes (ca. 0.06 micron in diameter) connected to each other by canaliculi while in the lower absorptive segment, the ER is made of parallel saccules arranged in stacks or whorls in the central region of the cytoplasm. In both segments, the ER network extends throughout the cytoplasm from the basolateral infoldings to the apex between the many mitochondria present in these two areas. A unique feature of these cells, revealed by thick sections, is the presence in each microvillus of either a mitochondrion or an ER canaliculus in continuity with the ER network. The ER does not seem to have any specific association with mitochondria or other organelles. As in the mammalian nephron, this ER organization is most likely related to specific segmental functions and adds support to its potential role as a transcellular epithelial route.

Kids SIP smartER: A Feasibility Study to Reduce Sugar-Sweetened Beverage Consumption Among Middle School Youth in Central Appalachia.

PubMed

Lane, Hannah; Porter, Kathleen J; Hecht, Erin; Harris, Priscilla; Kraak, Vivica; Zoellner, Jamie

2017-01-01

To test the feasibility of Kids SIP smartER, a school-based intervention to reduce consumption of sugar-sweetened beverages (SSBs). Matched-contact randomized crossover study with mixed-methods analysis. One middle school in rural, Appalachian Virginia. Seventy-four sixth and seventh graders (5 classrooms) received Kids SIP smartER in random order over 2 intervention periods. Feasibility outcomes were assessed among 2 teachers. Kids SIP smartER consisted of 6 lessons grounded in the Theory of Planned Behavior, media literacy, and public health literacy and aimed to improve individual SSB behaviors and understanding of media literacy and prevalent regional disparities. The matched-contact intervention promoted physical activity. Beverage Intake Questionnaire-15 (SSB consumption), validated theory questionnaires, feasibility questionnaires (student and teacher), student focus groups, teacher interviews, and process data (eg, attendance). Repeated measures analysis of variances across 3 time points, descriptive statistics, and deductive analysis of qualitative data. During the first intervention period, students receiving Kids SIP smartER (n = 43) significantly reduced SSBs by 11 ounces/day ( P = .01) and improved media ( P < .001) and public health literacy ( P < .01) understanding; however, only media literacy showed between-group differences ( P < .01). Students and teachers found Kids SIP smartER acceptable, in-demand, practical, and implementable within existing resources. Kids SIP smartER is feasible in an underresourced, rural school setting. Results will inform further development and large-scale testing of Kids SIP smartER to reduce SSBs among rural adolescents.

C/EBPβ LIP augments cell death by inducing osteoglycin.

PubMed

Wassermann-Dozorets, Rina; Rubinstein, Menachem

2017-04-06

Many types of tumor cell are devoid of the extracellular matrix proteoglycan osteoglycin (Ogn), but its role in tumor biology is poorly studied. Here we show that RNAi of Ogn attenuates stress-triggered cell death, whereas its overexpression increases cell death. We found that the transcription factor C/EBPβ regulates the expression of Ogn. C/EBPβ is expressed as a full-length, active form (LAP) and as a truncated, dominant-negative form (LIP), and the LIP/LAP ratio is positively correlated with the extent of cell death under stress. For example, we reported that drug-resistant tumor cells lack LIP altogether, and its supplementation abolished their resistance to chemotherapy and to endoplasmic reticulum (ER) stress. Here we further show that elevated LIP/LAP ratio robustly increased Ogn expression and cell death under stress by modulating the mitogen-activated protein kinase/activator protein 1 pathway (MAPK/AP-1). Our findings suggest that LIP deficiency renders tumor cell resistant to ER stress by preventing the induction of Ogn.

Variables that influence energy partition in asymmetric reconnection

NASA Astrophysics Data System (ADS)

Wang, S.; Chen, L. J.; Bessho, N.; Hesse, M.; Yamada, M.; Yoo, J.

2017-12-01

The energy conversion in the diffusion region during asymmetric reconnection is studied using particle-in-cell (PIC) simulations and measurements from the Magnetospheric Multiscale (MMS) spacecraft. The simulation analysis shows that the energy partition is highly region-dependent and varies with the guide field strength. Without a guide field, within the central electron diffusion region, the input magnetic energy is mostly converted to the electron thermal energies; half of the magnetic energy input to the region extending from the X-line to a few ion inertial lengths downstream where the ion outflow peaks is converted to the plasma energy gain, with approximately equal partition between ions and electrons, similar to the laboratory results from the Magnetic Reconnection Experiment (MRX); over the entire ion diffusion region, about half of the energy goes to ions, and 20% goes to electrons. Electrons obtain energies mainly from the reconnection electric field (Er). For the ion total energy gain in the diffusion region, about 2/3 comes from the in-plane electrostatic field Ein and 1/3 comes from Er. Adding a guide field tends to reduce the plasma energy gain through reducing the contribution from Ein, even though the reconnection rates are similar. The energy partition in the diffusion region observed by MMS is estimated and compared with the results from PIC simulations and MRX experiments.

Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis.

PubMed

Valberg, S J; McKenzie, E C; Eyrich, L V; Shivers, J; Barnes, N E; Finno, C J

2016-09-01

Although exertional rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with exertional myopathies (retro-ER). Prospective and retrospective histopathological description. Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent exertional rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann-Whitney U and Fisher's exact tests. Centrally located myonuclei in mature myofibres were found in significantly more (P<0.05) pro-ER (12/13) and retro-ER (21/25) horses than controls (4/14). Degenerating myofibres were not evident in any biopsies. Retro-ER horses had amylase-resistant polysaccharide (6/25, P<0.05) and higher scores for cytoplasmic glycogen, rimmed vacuoles and rod-like bodies. A few control horses (3/14) and significantly (P<0.05) more pro-ER (12/13) and retro-ER (18/25) horses had disrupted myofibrillar alignment and large desmin and αβ-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of β-glycogen particles were identified on electron microscopy of the 2 pro-ER samples. In a subset of Arabian horses with intermittent episodes of exertional rhabdomyolysis, ectopic accumulation of cytoskeletal proteins and Z-disc degeneration bear a strong resemblance to a myofibrillar myopathy. While many of these horses were previously diagnosed with type 2 polysaccharide storage myopathy, pools of glycogen forming within disrupted myofibrils appeared to give the false appearance of a glycogen storage disorder. © 2015 EVJ Ltd.

Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis

PubMed Central

VALBERG, S. J.; McKENZIE, E. C.; EYRICH, L. V.; SHIVERS, J.; BARNES, N. E.; FINNO, C. J.

2016-01-01

Summary Reasons for performing study Although exertional rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. Objectives To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with exertional myopathies (retro-ER). Study design Prospective and retrospective histopathological description. Methods Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent exertional rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann–Whitney U and Fisher's exact tests. Results Centrally located myonuclei in mature myofibres were found in significantly more (P<0.05) pro-ER (12/13) and retro-ER (21/25) horses than controls (4/14). Degenerating myofibres were not evident in any biopsies. Retro-ER horses had amylase-resistant polysaccharide (6/25, P<0.05) and higher scores for cytoplasmic glycogen, rimmed vacuoles and rod-like bodies. A few control horses (3/14) and significantly (P<0.05) more pro-ER (12/13) and retro-ER (18/25) horses had disrupted myofibrillar alignment and large desmin and αβ-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of β-glycogen particles were identified on electron microscopy of the 2 pro-ER samples. Conclusions In a subset of Arabian horses with intermittent episodes of exertional rhabdomyolysis, ectopic accumulation of cytoskeletal proteins and Z-disc degeneration bear a strong resemblance to a myofibrillar myopathy. While many of these horses were previously diagnosed with type 2 polysaccharide storage myopathy, pools of glycogen forming within disrupted myofibrils appeared to give the false appearance of a glycogen storage disorder. PMID:26234161

Early Upper Paleolithic colonization across Europe: Time and mode of the Gravettian diffusion

PubMed Central

Cascalheira, João; Gonçalves, Célia

2017-01-01

This study presents new models on the origin, speed and mode of the wave-of-advance leading to the definitive occupation of Europe’s outskirts by Anatomically Modern Humans, during the Gravettian, between c. 37 and 30 ka ago. These models provide the estimation for possible demic dispersal routes for AMH at a stable spread rate of c. 0.7 km/year, with the likely origin in Central Europe at the site of Geissenklosterle in Germany and reaching all areas of the European landscape. The results imply that: 1. The arrival of the Gravettian populations into the far eastern European plains and to southern Iberia found regions with very low human occupation or even devoid of hominins; 2. Human demography was likely lower than previous estimates for the Upper Paleolithic; 3. The likely early AMH paths across Europe followed the European central plains and the Mediterranean coast to reach to the ends of the Italian and Iberian peninsulas. PMID:28542642

The C-terminal domain of TRPV4 is essential for plasma membrane localization.

PubMed

Becker, Daniel; Müller, Margarethe; Leuner, Kristina; Jendrach, Marina

2008-02-01

Many members of the TRP superfamily oligomerize in the ER before trafficking to the plasma membrane. For membrane localization of the non-selective cation channel TRPV4 specific domains in the N-terminus are required, but the role of the C-terminus in the oligomerization and trafficking process has been not determined until now. Therefore, the localization of recombinant TRPV4 in two cell models was analyzed: HaCaT keratinocytes that express TRPV4 endogenously were compared to CHO cells that are devoid of endogenous TRPV4. When deletions were introduced in the C-terminal domain three states of TRPV4 localization were defined: a truncated TRPV4 protein of 855 amino acids was exported to the plasma membrane like the full-length channel (871 aa) and was also functional. Mutants with a length of 828 to 844 amino acids remained in the ER of CHO cells, but in HaCaT cells plasma membrane localization was partially rescued by oligomerization with endogenous TRPV4. This was confirmed by coexpression of recombinant full-length TRPV4 together with these deletion mutants, which resulted in an almost complete plasma membrane localization of both proteins and significant FRET in the plasma membrane and the ER. All deletions upstream of amino acid 828 resulted in total ER retention that could not rescued by coexpression with the full-length protein. However, these deletion mutants did not impair export of full-length TRPV4, implying that no oligomerization took place. These data indicate that the C-terminus of TRPV4 is required for oligomerization, which takes place in the ER and precedes plasma membrane trafficking.

[Multiply upconversion emission in oxyfluoride ceramics].

PubMed

Xiao, Si-guo; Yang, Xiao-liang; Liu, Zhen-wei

2003-02-01

Oxyfluoride ceramics with the host composition of SiO2 and PbF2 have been prepared. X-ray diffraction analysis of the ceramics revealed that fluoride type beta-PbF2 solid solution regions are precipitated in the glass matrix. Rare earth ions in the beta-PbF2 solid solution show highly efficient upconversion performance due to the very small multi-phonon relaxation rates. Eight upconversion emission bands whose central wavelength are 846, 803, 665, 549, 523, 487, 456 and 411 nm have been observed when the sample was excited with 930 nm diode light. Four possible energy transfer processes between Er3+ and Yb3+ cause the electronic population of high energy level of Er3+ and realize the abound upconversion luminescence bands.

Mice deficient for ERAD machinery component Sel1L develop central diabetes insipidus.

PubMed

Bichet, Daniel G; Lussier, Yoann

2017-10-02

Deficiency of the antidiuretic hormone arginine vasopressin (AVP) underlies diabetes insipidus, which is characterized by the excretion of abnormally large volumes of dilute urine and persistent thirst. In this issue of the JCI, Shi et al. report that Sel1L-Hrd1 ER-associated degradation (ERAD) is responsible for the clearance of misfolded pro-arginine vasopressin (proAVP) in the ER. Additionally, mice with Sel1L deficiency, either globally or specifically within AVP-expressing neurons, developed central diabetes insipidus. The results of this study demonstrate a role for ERAD in neuroendocrine cells and serve as a clinical example of the effect of misfolded ER proteins retrotranslocated through the membrane into the cytosol, where they are polyubiquitinated, extracted from the ER membrane, and degraded by the proteasome. Moreover, proAVP misfolding in hereditary central diabetes insipidus likely shares common physiopathological mechanisms with proinsulin misfolding in hereditary diabetes mellitus of youth.

Plateaus Up Close

NASA Image and Video Library

2017-04-10

Saturn's C ring isn't uniformly bright. Instead, about a dozen regions of the ring stand out as noticeably brighter than the rest of the ring, while about half a dozen regions are devoid of ring material. Scientists call the bright regions "plateaus" and the devoid regions "gaps." Scientists have determined that the plateaus are relatively bright because they have higher particle density and reflect more light, but researchers haven't solved the trickier puzzle of how the plateaus are created and maintained. This view looks toward the sunlit side of the rings from about 62 degrees above the ring plane. The image was taken Jan. 9, 2017 in green light with the Cassini spacecraft's narrow-angle camera. Cassini obtained the image while approximately 194,000 miles (312,000 kilometers) from Saturn and at a Sun-Saturn-spacecraft, or phase, angle of 67 degrees. Image scale is 1.2 miles (2 kilometers) per pixel. https://photojournal.jpl.nasa.gov/catalog/PIA20529

Nectar production in oilseeds: Food for pollinators in an agricultural landscape

USDA-ARS?s Scientific Manuscript database

Pollinating insects are in decline throughout the world, driven by a combination of factors including the loss of forage resources. The corn- and soybean-dominated agriculture of the Central and Midwestern US produces a landscape relatively devoid of nectar and pollen resources. Introducing specialt...

Comparison of vesicular-arbuscular mycorrhizae in plants from disturbed and adjacent undisturbed regions of a coastal salt marsh in Clinton, Connecticut, USA

NASA Astrophysics Data System (ADS)

Cooke, John C.; Lefor, Michael W.

1990-01-01

Roots of salt marsh plant species Spartina alterniflora, S. patens, Distichlis spicata, and others were examined for the presence of vesicular-arbuscular mycorrhizal (VAM) fungi. Samples were taken from introduced planted material in a salt marsh restoration project and from native material in adjacent marsh areas along the Indian River, Clinton, Connecticut, USA. After ten years the replanted area still has sites devoid of vegetation. The salt marsh plants introduced there were devoid of VAM fungi, while high marsh species from the adjacent undisturbed region showed consistent infection, leading the authors to suggest that VAM fungal infection of planting stocks may be a factor in the success of marsh restoration.

Statolith sedimentation kinetics and force transduction to the cortical endoplasmic reticulum in gravity-sensing Arabidopsis columella cells.

PubMed

Leitz, Guenther; Kang, Byung-Ho; Schoenwaelder, Monica E A; Staehelin, L Andrew

2009-03-01

The starch statolith hypothesis of gravity sensing in plants postulates that the sedimentation of statoliths in specialized statocytes (columella cells) provides the means for converting the gravitational potential energy into a biochemical signal. We have analyzed the sedimentation kinetics of statoliths in the central S2 columella cells of Arabidopsis thaliana. The statoliths can form compact aggregates with gap sizes between statoliths approaching <30 nm. Significant intra-aggregate sliding motions of individual statoliths suggest a contribution of hydrodynamic forces to the motion of statoliths. The reorientation of the columella cells accelerates the statoliths toward the central cytoplasm within <1 s of reorientation. During the subsequent sedimentation phase, the statoliths tend to move at a distance to the cortical endoplasmic reticulum (ER) boundary and interact only transiently with the ER. Statoliths moved by laser tweezers against the ER boundary experience an elastic lift force upon release from the optical trap. High-resolution electron tomography analysis of statolith-to-ER contact sites indicate that the weight of statoliths is sufficient to locally deform the ER membranes that can potentially activate mechanosensitive ion channels. We suggest that in root columella cells, the transduction of the kinetic energy of sedimenting statoliths into a biochemical signal involves a combination of statolith-driven motion of the cytosol, statolith-induced deformation of the ER membranes, and a rapid release of kinetic energy from the ER during reorientation to activate mechanosensitive sites within the central columella cells.

Statolith Sedimentation Kinetics and Force Transduction to the Cortical Endoplasmic Reticulum in Gravity-Sensing Arabidopsis Columella Cells[W][OA

PubMed Central

Leitz, Guenther; Kang, Byung-Ho; Schoenwaelder, Monica E.A.; Staehelin, L. Andrew

2009-01-01

The starch statolith hypothesis of gravity sensing in plants postulates that the sedimentation of statoliths in specialized statocytes (columella cells) provides the means for converting the gravitational potential energy into a biochemical signal. We have analyzed the sedimentation kinetics of statoliths in the central S2 columella cells of Arabidopsis thaliana. The statoliths can form compact aggregates with gap sizes between statoliths approaching <30 nm. Significant intra-aggregate sliding motions of individual statoliths suggest a contribution of hydrodynamic forces to the motion of statoliths. The reorientation of the columella cells accelerates the statoliths toward the central cytoplasm within <1 s of reorientation. During the subsequent sedimentation phase, the statoliths tend to move at a distance to the cortical endoplasmic reticulum (ER) boundary and interact only transiently with the ER. Statoliths moved by laser tweezers against the ER boundary experience an elastic lift force upon release from the optical trap. High-resolution electron tomography analysis of statolith-to-ER contact sites indicate that the weight of statoliths is sufficient to locally deform the ER membranes that can potentially activate mechanosensitive ion channels. We suggest that in root columella cells, the transduction of the kinetic energy of sedimenting statoliths into a biochemical signal involves a combination of statolith-driven motion of the cytosol, statolith-induced deformation of the ER membranes, and a rapid release of kinetic energy from the ER during reorientation to activate mechanosensitive sites within the central columella cells. PMID:19276442

Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline

PubMed Central

Gaspar, Maria L.; Chang, Yu-Fang; Jesch, Stephen A.; Aregullin, Manuel; Henry, Susan A.

2017-01-01

In the yeast Saccharomyces cerevisiae, the Opi1p repressor controls the expression of INO1 via the Opi1p/Ino2p–Ino4p regulatory circuit. Inositol depletion favors Opi1p interaction with both Scs2p and phosphatidic acid at the endoplasmic reticulum (ER) membrane. Inositol supplementation, however, favors the translocation of Opi1p from the ER into the nucleus, where it interacts with the Ino2p–Ino4p complex, attenuating transcription of INO1. A strain devoid of Scs2p (scs2Δ) and a mutant, OPI1FFAT, lacking the ability to interact with Scs2p were utilized to examine the specific role(s) of the Opi1p–Scs2p interaction in the regulation of INO1 expression and overall lipid metabolism. Loss of the Opi1p–Scs2p interaction reduced INO1 expression and conferred inositol auxotrophy. Moreover, inositol depletion in strains lacking this interaction resulted in Opi1p being localized to sites of lipid droplet formation, coincident with increased synthesis of triacylglycerol. Supplementation of choline to inositol-depleted growth medium led to decreased TAG synthesis in all three strains. However, in strains lacking the Opi1p–Scs2p interaction, Opi1p remained in the nucleus, preventing expression of INO1. These data support the conclusion that a specific pool of phosphatidic acid, associated with lipid droplet formation in the perinuclear ER, is responsible for the initial rapid exit of Opi1p from the nucleus to the ER and is required for INO1 expression in the presence of choline. Moreover, the mitochondria-specific phospholipid, cardiolipin, was significantly reduced in both strains compromised for Opi1p–Scs2p interaction, indicating that this interaction is required for the transfer of phosphatidic acid from the ER to the mitochondria for cardiolipin synthesis. PMID:28924045

Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline.

PubMed

Gaspar, Maria L; Chang, Yu-Fang; Jesch, Stephen A; Aregullin, Manuel; Henry, Susan A

2017-11-10

In the yeast Saccharomyces cerevisiae , the Opi1p repressor controls the expression of INO1 via the Opi1p/Ino2p-Ino4p regulatory circuit. Inositol depletion favors Opi1p interaction with both Scs2p and phosphatidic acid at the endoplasmic reticulum (ER) membrane. Inositol supplementation, however, favors the translocation of Opi1p from the ER into the nucleus, where it interacts with the Ino2p-Ino4p complex, attenuating transcription of INO1 A strain devoid of Scs2p ( scs2 Δ) and a mutant, OPI1FFAT , lacking the ability to interact with Scs2p were utilized to examine the specific role(s) of the Opi1p-Scs2p interaction in the regulation of INO1 expression and overall lipid metabolism. Loss of the Opi1p-Scs2p interaction reduced INO1 expression and conferred inositol auxotrophy. Moreover, inositol depletion in strains lacking this interaction resulted in Opi1p being localized to sites of lipid droplet formation, coincident with increased synthesis of triacylglycerol. Supplementation of choline to inositol-depleted growth medium led to decreased TAG synthesis in all three strains. However, in strains lacking the Opi1p-Scs2p interaction, Opi1p remained in the nucleus, preventing expression of INO1 These data support the conclusion that a specific pool of phosphatidic acid, associated with lipid droplet formation in the perinuclear ER, is responsible for the initial rapid exit of Opi1p from the nucleus to the ER and is required for INO1 expression in the presence of choline. Moreover, the mitochondria-specific phospholipid, cardiolipin, was significantly reduced in both strains compromised for Opi1p-Scs2p interaction, indicating that this interaction is required for the transfer of phosphatidic acid from the ER to the mitochondria for cardiolipin synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

77 FR 58375 - Notice of FERC Staff Attendance at the Entergy Regional State Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-20

... No. ER11-2131, Entergy Arkansas, Inc. Docket No. ER11-2132, Entergy Gulf States, Louisiana, LLC Docket No. ER11-2133, Entergy Gulf States, Louisiana, LLC Docket No. ER11-2134, Entergy Mississippi, Inc... Entergy Regional State Committee Meeting The Federal Energy Regulatory Commission (Commission) hereby...

Will Elephants Soon Disappear from West African Savannahs?

PubMed Central

Bouché, Philippe; Douglas-Hamilton, Iain; Wittemyer, George; Nianogo, Aimé J.; Doucet, Jean-Louis; Lejeune, Philippe; Vermeulen, Cédric

2011-01-01

Precipitous declines in Africa's native fauna and flora are recognized, but few comprehensive records of these changes have been compiled. Here, we present population trends for African elephants in the 6,213,000 km2 Sudano-Sahelian range of West and Central Africa assessed through the analysis of aerial and ground surveys conducted over the past 4 decades. These surveys are focused on the best protected areas in the region, and therefore represent the best case scenario for the northern savanna elephants. A minimum of 7,745 elephants currently inhabit the entire region, representing a minimum decline of 50% from estimates four decades ago for these protected areas. Most of the historic range is now devoid of elephants and, therefore, was not surveyed. Of the 23 surveyed elephant populations, half are estimated to number less than 200 individuals. Historically, most populations numbering less than 200 individuals in the region were extirpated within a few decades. Declines differed by region, with Central African populations experiencing much higher declines (−76%) than those in West Africa (−33%). As a result, elephants in West Africa now account for 86% of the total surveyed. Range wide, two refuge zones retain elephants, one in West and the other in Central Africa. These zones are separated by a large distance (∼900 km) of high density human land use, suggesting connectivity between the regions is permanently cut. Within each zone, however, sporadic contacts between populations remain. Retaining such connectivity should be a high priority for conservation of elephants in this region. Specific corridors designed to reduce the isolation of the surveyed populations are proposed. The strong commitment of governments, effective law enforcement to control the illegal ivory trade and the involvement of local communities and private partners are all critical to securing the future of elephants inhabiting Africa's northern savannas. PMID:21731620

Convective Distribution of Tropospheric Ozone and Tracers in the Central American ITCZ Region: Evidence from Observations During TC4

NASA Technical Reports Server (NTRS)

Avery, Melody; Twohy, Cynthia; MCabe, David; Joiner, Joanna; Severance, Kurt; Atlas, Eliot; Blake, Donald; Bui, T. P.; Crounse, John; Dibb, Jack;

Discordance in pathology report after central pathology review: Implications for breast cancer adjuvant treatment.

PubMed

Orlando, Laura; Viale, Giuseppe; Bria, Emilio; Lutrino, Eufemia Stefania; Sperduti, Isabella; Carbognin, Luisa; Schiavone, Paola; Quaranta, Annamaria; Fedele, Palma; Caliolo, Chiara; Calvani, Nicola; Criscuolo, Mario; Cinieri, Saverio

2016-12-01

Pathological predictive factors are the most important markers when selecting early breast cancer adjuvant therapy. In randomized clinical trials the variability in pathology report after central pathology review is noteworthy. We evaluated the discordance rate (DR) and inter-rater agreement between local and central histopathological report and the clinical implication on treatment decision. A retrospective analysis was conducted in a series of consecutive early breast cancer tumors diagnosed by local pathologists and subsequently reviewed at the Pathology Division of European Institute of Oncology. The inter-rater agreement (k) between local and central pathology was calculated for Ki-67, grading, hormone receptors (ER/PgR) and HER2/neu. The Bland-Altman plots were derived to determine discrepancies in Ki-67, ER and PgR. DR was calculated for ER/PgR and HER2. From 2007 to 2013, 187 pathology specimens from 10 Cancer Centers were reviewed. Substantial agreement was observed for ER (k0.612; 95% CI, 0538-0.686), PgR (k0.659; 95% CI, 0580-0.737), Ki-67 (k0.609; 95% CI, 0.534-0.684) and grading (k0.669; 95% CI, 0.569-0.769). Moderate agreement was found for HER2 (k0.546; 95% CI, 0444-0.649). DR was 9.5% (negativity to positivity) and 31.7% (positivity to negativity) for HER2 and 26.2% (negativity to positivity) and 12.5% (positivity to negativity) for ER/PgR. According to changes in Her2 and ER/PgR status, 23 (12.2%) and 33 (17.6%) systemic prescription were respectively modified. In our retrospective analysis, central pathological review has a significant impact in the decision-making process in early breast cancer, as shown in clinical trials. Further studies are warranted to confirm these provocative results. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Census 2004 of the Italian Renal and Dialysis Units. Emilia-Romagna, Toscana].

PubMed

Lusenti, T; Santoro, A; Cappelli, G; Cagnoli, L; Moriconi, L; Rindi, P; Lippi, A; Alloatti, S

2006-01-01

The 2004 SIN census of the Italian nephrology and dialysis centres showed many interesting data about the epidemiology and the organization in the Regions of Emilia-Romagna (ER) and Tuscany (T). A) Epidemiology: incidence of dialysis patients 169 pmp (patients per million population) in ER, 147 ppm in T; prevalence of dialysis patients 639 pmp and 665 pmp, respectively; prevalence of transplanted patients 325 ppm in ER and 233 pmp in T; gross mortality of dialysis patients 16.3% and 13.4%, respectively; B) Type of vascular access in prevalently dialysis patients: arteriovenous fistula 83% and 78%; central venous catheter 13% and 12%; vascular graft 5% and 9%. C) Structural resources: nephrology beds 44 mp (per million population) and 50 mp; dialysis places 157 and 146 mp. D) Personnel resources : renal physicians 29 and 41 mp; renal nurses 171 and 202 mp ; each renal physician cares for 22 and 16 dialysis patients, and each renal nurse takes care of 3.7 and 3.3 dialysis patients. E) Activity: hospital admissions 1572, 1769 pmp; renal biopsies 115 and 166 pmp.

Aqueous Angiography–Mediated Guidance of Trabecular Bypass Improves Angiographic Outflow in Human Enucleated Eyes

PubMed Central

Huang, Alex S.; Saraswathy, Sindhu; Dastiridou, Anna; Begian, Alan; Mohindroo, Chirayu; Tan, James C. H.; Francis, Brian A.; Hinton, David R.; Weinreb, Robert N.

2016-01-01

Purpose To assess the ability of trabecular micro-bypass stents to improve aqueous humor outflow (AHO) in regions initially devoid of AHO as assessed by aqueous angiography. Methods Enucleated human eyes (14 total from 7 males and 3 females [ages 52–84]) were obtained from an eye bank within 48 hours of death. Eyes were oriented by inferior oblique insertion, and aqueous angiography was performed with indocyanine green (ICG; 0.4%) or fluorescein (2.5%) at 10 mm Hg. With an angiographer, infrared and fluorescent images were acquired. Concurrent anterior segment optical coherence tomography (OCT) was performed, and fixable fluorescent dextrans were introduced into the eye for histologic analysis of angiographically positive and negative areas. Experimentally, some eyes (n = 11) first received ICG aqueous angiography to determine angiographic patterns. These eyes then underwent trabecular micro-bypass sham or stent placement in regions initially devoid of angiographic signal. This was followed by fluorescein aqueous angiography to query the effects. Results Aqueous angiography in human eyes yielded high-quality images with segmental patterns. Distally, angiographically positive but not negative areas demonstrated intrascleral lumens on OCT images. Aqueous angiography with fluorescent dextrans led to their trapping in AHO pathways. Trabecular bypass but not sham in regions initially devoid of ICG aqueous angiography led to increased aqueous angiography as assessed by fluorescein (P = 0.043). Conclusions Using sequential aqueous angiography in an enucleated human eye model system, regions initially without angiographic flow or signal could be recruited for AHO using a trabecular bypass stent. PMID:27588614

Hayward Fault, California Interferogram

NASA Image and Video Library

2000-08-17

This image of California Hayward fault is an interferogram created using a pair of images taken by ESA ERS-1 and ERS-2 in June 1992 and September 1997 over the central San Francisco Bay in California.

Active Microwave Remote Sensing Observations of Weddell Sea Ice

NASA Technical Reports Server (NTRS)

Drinkwater, Mark R.

1997-01-01

Since July 1991, the European Space Agency's ERS-1 and ERS-2 satellites have acquired radar data of the Weddell Sea, Antarctica. The Active Microwave Instrument on board ERS has two modes; SAR and Scatterometer. Two receiving stations enable direct downlink and recording of high bit-rate, high resolution SAR image data of this region. When not in an imaging mode, when direct SAR downlink is not possible, or when a receiving station is inoperable, the latter mode allows normalized radar cross-section data to be acquired. These low bit-rate ERS scatterometer data are tape recorded, downlinked and processed off-line. Recent advances in image generation from Scatterometer backscatter measurements enable complementary medium-scale resolution images to be made during periods when SAR images cannot be acquired. Together, these combined C-band microwave image data have for the first time enabled uninterrupted night and day coverage of the Weddell Sea region at both high (25 m) and medium-scale (-20 km) resolutions. C-band ERS-1 radar data are analyzed in conjunction with field data from two simultaneous field experiments in 1992. Satellite radar signature data are compared with shipborne radar data to extract a regional and seasonal signature database for recognition of ice types in the images. Performance of automated sea-ice tracking algorithms is tested on Antarctic data to evaluate their success. Examples demonstrate that both winter and summer ice can be effectively tracked. The kinematics of the main ice zones within the Weddell Sea are illustrated, together with the complementary time-dependencies in their radar signatures. Time-series of satellite images are used to illustrate the development of the Weddell Sea ice cover from its austral summer minimum (February) to its winter maximum (September). The combination of time-dependent microwave signatures and ice dynamics tracking enable various drift regimes to be defined which relate closely to the circulation of the sea ice in response to current and wind forcing and iceberg barriers. These are closely related to continental-shelf or central basin regimes, in which tidal forcing or barotropic circulation patterns appear to influence the sea-ice motion, respectively. These regimes provide valuable information about the regions of most prolific ice growth and influence of ice conditions upon air-sea-ice exchange processes in the Weddell Sea.

Impacts of droughts on carbon sequestration by China's terrestrial ecosystems from 2000 to 2011

NASA Astrophysics Data System (ADS)

Liu, Y.; Zhou, Y.; Ju, W.; Wang, S.; Wu, X.; He, M.; Zhu, G.

2014-05-01

In recent years, China's terrestrial ecosystems have experienced frequent droughts. How these droughts have affected carbon sequestration by the terrestrial ecosystems is still unclear. In this study, the process-based Boreal Ecosystem Productivity Simulator (BEPS) model, driven by remotely sensed vegetation parameters, was employed to assess the effects of droughts on net ecosystem productivity (NEP) of terrestrial ecosystems in China from 2000 to 2011. Droughts of differing severity, as indicated by a standard precipitation index (SPI), hit terrestrial ecosystems in China extensively in 2001, 2006, 2009, and 2011. The national total annual NEP exhibited the slight decline of -11.3 Tg C yr-2 during the aforementioned years of extensive droughts. The NEP reduction ranged from 61.1 Tg C yr-1 to 168.8 Tg C yr-1. National and regional total NEP anomalies were correlated with the annual mean SPI, especially in Northwest China, North China, Central China, and Southwest China. The reductions in annual NEP in 2001 and 2011 might have been caused by a larger decrease in annual gross primary productivity (GPP) than in annual ecosystem respiration (ER). The reductions experienced in 2009 might be due to a decrease in annual GPP and an increase in annual ER, while reductions in 2006 could stem from a larger increase in ER than in GPP. The effects of droughts on NEP lagged up to 3-6 months, due to different responses of GPP and ER. In eastern China, where is humid and warm, droughts have predominant and short-term lagged influences on NEP. In western regions, cold and arid, the drought effects on NEP were relatively weaker but prone to lasting longer.

Weekly cycles of formaldehyde and nitrogen dioxide in the atmosphere over Northern Eurasia: anthropogenic or natural?

NASA Astrophysics Data System (ADS)

Sitnov, S. I.; Mokhov, I. I.

2017-11-01

Using data from the OMI (Aura) satellite instrument, the weekly cycles in the regional atmospheric contents of formaldehyde (CH2O) and nitrogen dioxide (NO2) over European Russia (ER) and Western Siberia (WS) are investigated. The weekly signals in the regional CH2O content are found to be in the opposite phase over ER and WS, but in phase with the weekly signals in the regional surface temperatures in the corresponding regions. Contrary with CH2O, the weekly signals in the regional NO2 content over ER and WS are in phase, manifesting themselves as the "weekend effects" with minima on Sunday and maxima on weekdays. The antiphase weekly signals in the regional CH2O contents over ER and WS can be associated with the dependence of biogenic isoprene emission on the regional surface temperature, influenced by the long Rossby-type waves.

Habitat manipulation of Exposed Riverine Sediments (ERS) how does microhabitat, microclimate and food availability influence beetle distributions?

NASA Astrophysics Data System (ADS)

Henshall, S. E.; Sadler, J. P.; Hannah, D. M.

2009-04-01

Exposed riverine sediments (ERS) are frequently inundated areas of relatively un-vegetated, fluvially deposited sediment (sand, silt, gravel and pebble). These habitats provide an important interface allowing the interaction of aquatic and terrestrial habitats and species. ERS are highly valuable for many rare and specialist invertebrates particularly beetles. Within an area of ERS, beetle species richness tends to be highest along the water's edge. This higher species richness may be linked to: (1) the availability of food items in the form of emerging and stranded aquatic invertebrates and (2) favourable physical microhabitat conditions in terms of temperature and moisture. This paper explores the role of microclimate and food availability by creating areas of ‘water's edge' habitat in the centre of a gravel bar. Typically these areas are drier, reach higher temperatures and devoid of emerging aquatic invertebrate prey. Four 2m x 2m experimental plots were created: one wet plot, one wet- fed plot, one dry-fed plot and one dry plot (control). These plots were each replicated on three separate areas of ERS. Sixty colour marked ERS specialist ground beetles (Bembidion atrocaeruleum) were released into each plot to monitor beetle persistence and movement on and between plots. The plots were maintained wet using a capillary pump system, and fed with dried blood worms for 30 days. Sediment temperature (0.05 m depth) was measured at 15 minute intervals and spot measurements of surface temperature were taken daily. A hand search was carried out on 25% of each plot after 7, 14, 21 and 30 days. Significant temperature differences were observed between the wet and dry sediment and air temperature. The wet plots on average were 1.8oC cooler than the dry plots and had a reduced temperature range. Both wet and dry sediments remained significantly warmer than air temperature. The wet and wet-fed plots yielded significantly greater numbers of beetles and marked beetles than the dry and dry-fed plots; however, no significant difference was found between the wet and wet-fed plots. These results indicate that microhabitat in terms of increased moisture and lower temperature is the driving factor influencing beetle distribution and movement. Food alone is not as influential. ERS carabid beetles may be using lower temperatures and increased moisture as a cue for aquatic food availability.

Investigation of the effect of erythrosine B on amyloid beta peptide using molecular modeling.

PubMed

Lee, Juho; Kwon, Inchan; Jang, Seung Soon; Cho, Art E

2016-04-01

Neurotoxic plaques composed of 39 to 42 residue-long amyloid beta peptides (Aβs) are copiously present in the brains of patients with Alzheimer's disease (AD). Erythrosine B (ER), a xanthene food dye, inhibits the formation of Aβ fibrils and Aβ-associated cytotoxicity in vitro. Here, in an attempt to elucidate the inhibition mechanism, we performed molecular dynamics (MD) simulations to demonstrate the conformational change of Aβ40 induced by ER molecules in atomistic detail. During the simulation, the ER bound to the surfaces of both N-terminus and C-terminus regions of Aβ40. Our result shows that ER interacts with the aromatic side chains at the N-terminus region resulting in destabilization of the inter-chain stacking of Aβ40. Moreover, the stablility of the helical structures at the residues from 13 to 16 suggests that ER disturbs conformational transition of Aβ40. At the C-terminus region, the bound ER blocks water molecules and stabilizes the α-helical structure. Regardless of the number of ER molecules used, the interruption of the formation of the salt-bridge between aspartic acid 23 and lysine 28 occurred. To further validate our analysis, binding free energies of ER at each binding site were evaluated. The finding of stronger binding energy at the N-terminus region supports an inhibition mechanism induced by stacking interaction between ER and phenylalanine. These findings could aid present and future treatment studies for AD by clarifying the inhibition mechanism of ER on the conformational transition of Aβ40 at the molecular level.

Boulder Strewn Plain in Northern Utopia Planitia

NASA Image and Video Library

2010-03-31

This image taken by NASA Mars Reconnaissance Orbiter in the Cydnus Rupes region, shows that the northern plains of Mars are rock and boulder strewn landscapes otherwise devoid of major features except a few impact craters.

Extended Empirical Roadside Shadowing model from ACTS mobile measurements

NASA Technical Reports Server (NTRS)

Goldhirsh, Julius; Vogel, Wolfhard

1995-01-01

Employing multiple data bases derived from land-mobile satellite measurements using the Advanced Communications Technology Satellite (ACTS) at 20 GHz, MARECS B-2 at 1.5 GHz, and helicopter measurements at 870 MHz and 1.5 GHz, the Empirical Road Side Shadowing Model (ERS) has been extended. The new model (Extended Empirical Roadside Shadowing Model, EERS) may now be employed at frequencies from UHF to 20 GHz, at elevation angles from 7 to 60 deg and at percentages from 1 to 80 percent (0 dB fade). The EERS distributions are validated against measured ones and fade deviations associated with the model are assessed. A model is also presented for estimating the effects of foliage (or non-foliage) on 20 GHz distributions, given distributions from deciduous trees devoid of leaves (or in full foliage).

[Naïve Bayes classification for classifying injury-cause groups from Emergency Room data in the Friuli Venezia Giulia region (Northern Italy)].

PubMed

Valent, Francesca; Clagnan, Elena; Zanier, Loris

2014-01-01

to assess whether Naïve Bayes Classification could be used to classify injury causes from the Emergency Room (ER) database, because in the Friuli Venezia Giulia Region (Northern Italy) the electronic ER data have never been used to study the epidemiology of injuries, because the proportion of generic "accidental" causes is much higher than that of injuries with a specific cause. application of the Naïve Bayes Classification method to the regional ER database. sensitivity, specificity, positive and negative predictive values, agreement, and the kappa statistic were calculated for the train dataset and the distribution of causes of injury for the test dataset. on 22.248 records with known cause, the classifications assigned by the model agreed moderately (kappa =0.53) with those assigned by ER personnel. The model was then used on 76.660 unclassified cases. Although sensitivity and positive predictive value of the method were generally poor, mainly due to limitations in the ER data, it allowed to estimate for the first time the frequency of specific injury causes in the Region. the model was useful to provide the "big picture" of non-fatal injuries in the Region. To improve the collection of injury data at the ER, the options available for injury classification in the ER software are being revised to make categories exhaustive and mutually exclusive.

77 FR 12283 - Notice of FERC Staff Attendance at the Entergy Regional State Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

...-2131 Entergy Arkansas, Inc. Docket No. ER11-2132 Entergy Gulf States, Louisiana, LLC. Docket No. ER11-2133 Entergy Gulf States, Louisiana, LLC. Docket No. ER11-2134 Entergy Mississippi, Inc. Docket No... Entergy Regional State Committee Meeting The Federal Energy Regulatory Commission hereby gives notice that...

Resilience landscapes for Congo basin rainforests vs. climate and management impacts

NASA Astrophysics Data System (ADS)

Pietsch, Stephan Alexander; Gautam, Sishir; Elias Bednar, Johannes; Stanzl, Patrick; Mosnier, Aline; Obersteiner, Michael

2015-04-01

Past climate change caused severe disturbances of the Central African rainforest belt, with forest fragmentation and re-expansion due to drier and wetter climate conditions. Besides climate, human induced forest degradation affected biodiversity, structure and carbon storage of Congo basin rainforests. Information on climatically stable, mature rainforest, unaffected by human induced disturbances, provides means of assessing the impact of forest degradation and may serve as benchmarks of carbon carrying capacity over regions with similar site and climate conditions. BioGeoChemical (BGC) ecosystem models explicitly consider the impacts of site and climate conditions and may assess benchmark levels over regions devoid of undisturbed conditions. We will present a BGC-model validation for the Western Congolian Lowland Rainforest (WCLRF) using field data from a recently confirmed forest refuge, show model - data comparisons for disturbed und undisturbed forests under different site and climate conditions as well as for sites with repeated assessment of biodiversity and standing biomass during recovery from intensive exploitation. We will present climatic thresholds for WCLRF stability, and construct resilience landscapes for current day conditions vs. climate and management impacts.

Distribution of desert varnish in Arizona

NASA Technical Reports Server (NTRS)

Elvidge, Christopher D.

1989-01-01

Desert varnish is the dark coat of clay and ferromanganese oxides developed on exposed rock surfaces in arid regions. It forms from the accretion of material from windblown dust. The distribution of desert varnish was mapped in Arizona. It was discovered that desert varnish could be mapped on a regional scale. Well developed desert varnish is common on stable rock surfaces in areas having alkaline soils and less than about 25 cm of annual precipitation. Rock surfaces in areas having more than 40 cm of annual precipitation are generally devoid of desert varnish. An experiment was conducted with varnished desert pavement stone. The stones were broken in half and half was set on a roof in central Illinois from April until October. Removed from the alkaline desert environment, it only took seven months for the varnish to develop an eroded appearance. This experiment graphically illustrates the dependency of desert varnish on alkalinity. In this context, the zones of eroded desert varnish in Arizona indicate that the area of active desert varnish formation has fluctuated, expanding in drier times and contracting/eroding in wetter times.

Homo-trimerization is essential for the transcription factor function of Myrf for oligodendrocyte differentiation.

PubMed

Kim, Dongkyeong; Choi, Jin-Ok; Fan, Chuandong; Shearer, Randall S; Sharif, Mohamed; Busch, Patrick; Park, Yungki

2017-05-19

Myrf is a key transcription factor for oligodendrocyte differentiation and central nervous system myelination. We and others have previously shown that Myrf is generated as a membrane protein in the endoplasmic reticulum (ER), and that it undergoes auto-processing to release its N-terminal fragment from the ER, which enters the nucleus to work as a transcription factor. These previous studies allow a glimpse into the unusual complexity behind the biogenesis and function of the transcription factor domain of Myrf. Here, we report that Myrf N-terminal fragments assemble into stable homo-trimers before ER release. Consequently, Myrf N-terminal fragments are released from the ER only as homo-trimers. Our re-analysis of a previous genetic screening result in Caenorhabditis elegans shows that homo-trimerization is essential for the biological functions of Myrf N-terminal fragment, and that the region adjacent to the DNA-binding domain is pivotal to its homo-trimerization. Further, our computational analysis uncovered a novel homo-trimeric DNA motif that mediates the homo-trimeric DNA binding of Myrf N-terminal fragments. Importantly, we found that homo-trimerization defines the DNA binding specificity of Myrf N-terminal fragments. In sum, our study elucidates the molecular mechanism governing the biogenesis and function of Myrf N-terminal fragments and its physiological significance. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cellular stress and apoptosis contribute to the pathogenesis of autism spectrum disorder.

PubMed

Dong, Daoyin; Zielke, Horst Ronald; Yeh, David; Yang, Peixin

2018-05-15

The molecular pathogenesis of autism spectrum disorder, a neurodevelopmental disorder, is still elusive. In this study, we investigated the possible roles of endoplasmic reticulum (ER) stress, oxidative stress, and apoptosis as molecular mechanisms underlying autism. This study compared the activation of ER stress signals (protein kinase R-like endoplasmic reticulum kinase [PERK], activating transcription factor 6 [ATF6], inositol-requiring enzyme 1 alpha [IRE1α]) in different brain regions (prefrontal cortex, hippocampus, cerebellum) in subjects with autism and in age-matched controls. Our data showed that the activation of three signals of ER stress varies in different regions of the autistic brain. IRE1α was activated in cerebellum and prefrontal cortex but ATF6 was activated in hippocampus. PERK was not activated in the three regions. Furthermore, the activation of ER stress was confirmed because the expression of C/EBP-homologous protein (CHOP), which is the common downstream indicators of ER stress signals, and most of ER chaperones were upregulated in the three regions. Consistent with the induction of ER stress, apoptosis was found in the three regions by detecting the cleavage of caspase 8 and poly(ADP-ribose) polymerase as well as using the transferase dUTP nick end labeling assay. Moreover, our data showed that oxidative stress was responsible for ER stress and apoptosis because the levels of 4-Hydroxynonenal and nitrotyrosine-modified proteins were significantly increased in the three regions. In conclusion, these data indicate that cellular stress and apoptosis may play important roles in the pathogenesis of autism. Autism Res 2018. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Autism results in significant morbidity and mortality in children. The functional and molecular changes in the autistic brains are unclear. The present study utilized autistic brain tissues from the National Institute of Child Health and Human Development's Brain Tissue Bank for the analysis of cellular and molecular changes in autistic brains. Three key brain regions, the hippocampus, the cerebellum, and the frontal cortex, in six cases of autistic brains and six cases of non-autistic brains from 6 to 16 years old deceased children, were analyzed. The current study investigated the possible roles of endoplasmic reticulum (ER) stress, oxidative stress, and apoptosis as molecular mechanisms underlying autism. The activation of three signals of ER stress (protein kinase R-like endoplasmic reticulum kinase, activating transcription factor 6, inositol-requiring enzyme 1 alpha) varies in different regions. The occurrence of ER stress leads to apoptosis in autistic brains. ER stress may result from oxidative stress because of elevated levels of the oxidative stress markers: 4-Hydroxynonenal and nitrotyrosine-modified proteins in autistic brains. These findings suggest that cellular stress and apoptosis may contribute to the autistic phenotype. Pharmaceuticals and/or dietary supplements, which can alleviate ER stress, oxidative stress and apoptosis, may be effective in ameliorating adverse phenotypes associated with autism. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing

PubMed Central

Stalder, Lukas; Heusermann, Wolf; Sokol, Lena; Trojer, Dominic; Wirz, Joel; Hean, Justin; Fritzsche, Anja; Aeschimann, Florian; Pfanzagl, Vera; Basselet, Pascal; Weiler, Jan; Hintersteiner, Martin; Morrissey, David V; Meisner-Kober, Nicole C

2013-01-01

Despite progress in mechanistic understanding of the RNA interference (RNAi) pathways, the subcellular sites of RNA silencing remain under debate. Here we show that loading of lipid-transfected siRNAs and endogenous microRNAs (miRNA) into RISC (RNA-induced silencing complexes), encounter of the target mRNA, and Ago2-mediated mRNA slicing in mammalian cells are nucleated at the rough endoplasmic reticulum (rER). Although the major RNAi pathway proteins are found in most subcellular compartments, the miRNA- and siRNA-loaded Ago2 populations co-sediment almost exclusively with the rER membranes, together with the RISC loading complex (RLC) factors Dicer, TAR RNA binding protein (TRBP) and protein activator of the interferon-induced protein kinase (PACT). Fractionation and membrane co-immune precipitations further confirm that siRNA-loaded Ago2 physically associates with the cytosolic side of the rER membrane. Additionally, RLC-associated double-stranded siRNA, diagnostic of RISC loading, and RISC-mediated mRNA cleavage products exclusively co-sediment with rER. Finally, we identify TRBP and PACT as key factors anchoring RISC to ER membranes in an RNA-independent manner. Together, our findings demonstrate that the outer rER membrane is a central nucleation site of siRNA-mediated RNA silencing. PMID:23511973

Genealogical approaches to the temporal origins of the Central American Gap: speciation and divergence in pacific Chthamalus (Sessilia: Chthamalidae).

PubMed

Meyers, Meredith K; Pankey, M Sabrina; Wares, John P

2013-03-01

A large section of the tropical Eastern Pacific coastline is nearly devoid of reef or consolidated habitat, and is known as the Central American Gap as it is associated with a biogeographic transition in fish and invertebrate species. We analyze phylogeographic data for intertidal barnacles (Chthamalus) to identify relevant temporal patterns that describe the origins of this biogeographic transition (the Mexican-Panamic Transition Zone). These contrasts of populations on either side of the transition zone include two pairs of closely related species (C. panamensis and C. hedgecocki; C. southwardorum and a Southern form of C. southwardorum), as well as gene flow data within one species (C. panamensis) that currently is found on both sides of the boundary between provinces. Using sequence data from a prior phylogenetic study, we used traditional (net nucleotide divergence) measures as well as coalescent analyses that incorporate the isolation-migration model to identify the likely time of separation between Northern and Southern taxa in two species pairs. A total of 67 individuals were sequenced at two mitochondrial (cytochrome c oxidase I, 16S) and one nuclear (elongation factor 1-alpha) gene regions. Our analyses indicate that the regional isolation of these intertidal barnacles occurred approximately 315-400kya, with subsequent expansion of C. panamensis from the Southern region into the North much more recently. There are insufficient survey data to conclusively document the absence of species from this group within the Central American Gap region near the Gulf of Tehuantepec. However, appropriate habitat is quite sparse in this region and other environmental factors, including upwelling and water temperature, are likely to be associated with isolation of many species in the Mexican and Panamic provinces sensu stricto. Some taxa may maintain gene flow across this region, but very few genetic studies have been completed on such taxa. Until further work is done, distinguishing between prior hypotheses of a faunal gap, or a faunal transition zone, is somewhat speculative. Additional taxonomic revision will be necessary in Chthamalus but is beyond the scope of this paper.

The Role of Sigma-1 Receptor, an Intracellular Chaperone in Neurodegenerative Diseases.

PubMed

Penke, Botond; Fulop, Livia; Szucs, Maria; Frecska, Ede

2018-01-01

Widespread protein aggregation occurs in the living system under stress or during aging, owing to disturbance of endoplasmic reticulum (ER) proteostasis. Many neurodegenerative diseases may have a common mechanism: the failure of protein homeostasis. Perturbation of ER results in unfolded protein response (UPR). Prolonged chronical UPR may activate apoptotic pathways and cause cell death. Research articles on Sigma-1 receptor were reviewed. ER is associated to mitochondria by the mitochondria-associated ER-membrane, MAM. The sigma-1 receptor (Sig-1R), a well-known ER-chaperone localizes in the MAM. It serves for Ca2+-signaling between the ER and mitochondria, involved in ion channel activities and especially important during neuronal differentiation. Sig-1R acts as central modulator in inter-organelle signaling. Sig-1R helps cell survival by attenuating ER-stress. According to sequence based predictions Sig-1R is a 223 amino acid protein with two transmembrane (2TM) domains. The X-ray structure of the Sig-1R [1] showed a membrane-bound trimeric assembly with one transmembrane (1TM) region. Despite the in vitro determined assembly, the results of in vivo studies are rather consistent with the 2TM structure. The receptor has unique and versatile pharmacological profile. Dimethyl tryptamine (DMT) and neuroactive steroids are endogenous ligands that activate Sig-1R. The receptor has a plethora of interacting client proteins. Sig-1R exists in oligomeric structures (dimer-trimer-octamer-multimer) and this fact may explain interaction with diverse proteins. Sig-1R agonists have been used in the treatment of different neurodegenerative diseases, e.g. Alzheimer's and Parkinson's diseases (AD and PD) and amyotrophic lateral sclerosis. Utilization of Sig-1R agents early in AD and similar other diseases has remained an overlooked therapeutic opportunity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Characteristics of nighttime E-region over Arecibo: Dependence on solar flux and geomagnetic variations

NASA Astrophysics Data System (ADS)

Raizada, Shikha; Brum, Christiano G. M.; Mathews, John D.; Gonzalez, Cristina; Franco, Efmi

2018-04-01

Electron concentration (Ne) inferred from Incoherent Scatter Radar (ISR) measurements has been used to determine the influence of solar flux and geomagnetic activity in the ionospheric E-region over Arecibo Observatory (AO). The approach is based on the determination of column integrated Ne, referred to as E-region total electron content (ErTEC) between 80 and 150 km altitude regions. The results discussed in this work are for the AO nighttime period. The study reveals higher ErTEC values during the low solar flux periods for all the seasons except for summer period. It is found that the E-region column abundance is higher in equinox periods than in the winter for low solar activity conditions. The column integrated Ne during the post-sunset/pre-sunrise periods always exceeds the midnight minima, independent of season or solar activity. This behavior has been attributed to the variations in the coupling processes from the F-region. The response of ErTEC to the geomagnetic variability is also examined for different solar flux conditions and seasons. During high solar flux periods, changes in Kp cause an ErTEC increase in summer and equinox, while producing a negative storm-like effect during the winter. Variations in ErTEC due to geomagnetic activity during low solar flux periods produce maximum variability in the E-region during equinox periods, while resulting in an increase/decrease in ErTEC before local midnight during the winter/summer periods, respectively.

78 FR 69661 - Notice of FERC Staff Attendance at the Entergy Regional State Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

.... ER12-1384 Entergy Gulf States Docket No. ER12-1385 Louisiana, L.L.C. Entergy Louisiana, LLC... Arkansas, Inc........ Docket No. ER13-1508 Entergy Gulf States Docket No. ER13-1509 Louisiana, L.L.C... Arkansas, Inc........ Docket No. ER14-75 Entergy Gulf States Docket No. ER14-76 Louisiana, L.L.C. Entergy...

Alpha-Synuclein Expression Restricts RNA Viral Infections in the Brain.

PubMed

Beatman, Erica L; Massey, Aaron; Shives, Katherine D; Burrack, Kristina S; Chamanian, Mastooreh; Morrison, Thomas E; Beckham, J David

2015-12-30

We have discovered that native, neuronal expression of alpha-synuclein (Asyn) inhibits viral infection, injury, and disease in the central nervous system (CNS). Enveloped RNA viruses, such as West Nile virus (WNV), invade the CNS and cause encephalitis, yet little is known about the innate neuron-specific inhibitors of viral infections in the CNS. Following WNV infection of primary neurons, we found that Asyn protein expression is increased. The infectious titer of WNV and Venezuelan equine encephalitis virus (VEEV) TC83 in the brains of Asyn-knockout mice exhibited a mean increase of 10(4.5) infectious viral particles compared to the titers in wild-type and heterozygote littermates. Asyn-knockout mice also exhibited significantly increased virus-induced mortality compared to Asyn heterozygote or homozygote control mice. Virus-induced Asyn localized to perinuclear, neuronal regions expressing viral envelope protein and the endoplasmic reticulum (ER)-associated trafficking protein Rab1. In Asyn-knockout primary neuronal cultures, the levels of expression of ER signaling pathways, known to support WNV replication, were significantly elevated before and during viral infection compared to those in Asyn-expressing primary neuronal cultures. We propose a model in which virus-induced Asyn localizes to ER-derived membranes, modulates virus-induced ER stress signaling, and inhibits viral replication, growth, and injury in the CNS. These data provide a novel and important functional role for the expression of native alpha-synuclein, a protein that is closely associated with the development of Parkinson's disease. Neuroinvasive viruses such as West Nile virus are able to infect neurons and cause severe disease, such as encephalitis, or infection of brain tissue. Following viral infection in the central nervous system, only select neurons are infected, implying that neurons exhibit innate resistance to viral infections. We discovered that native neuronal expression of alpha-synuclein inhibited viral infection in the central nervous system. When the gene for alpha-synuclein was deleted, mice exhibited significantly decreased survival, markedly increased viral growth in the brain, and evidence of increased neuron injury. Virus-induced alpha-synuclein localized to intracellular neuron membranes, and in the absence of alpha-synuclein expression, specific endoplasmic reticulum stress signaling events were significantly increased. We describe a new neuron-specific inhibitor of viral infections in the central nervous system. Given the importance of alpha-synuclein as a cause of Parkinson's disease, these data also ascribe a novel functional role for the native expression of alpha-synuclein in the CNS. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

[Estrogen receptor alpha in obesity and diabetes].

PubMed

Cahua-Pablo, José Ángel; Flores-Alfaro, Eugenia; Cruz, Miguel

2016-01-01

Estradiol (E2) is an important hormone in reproductive physiology, cardiovascular, skeletal and in the central nervous system (CNS). In human and rodents, E2 and its receptors are involved in the control of energy and glucose metabolism in health and metabolic diseases. The estrogen receptor (ER) belongs to the superfamily of nuclear receptors (NR), which are transcription factors that regulate gene expression. Three ER, ER-alpha, ER-beta and the G protein-coupled ER (GPER; also called GPR30) in tissues are involved in glucose and lipid homeostasis. Also, it may have important implications for risk factors associated with metabolic syndrome (MS), insulin resistance (IR), obesity and type 2 diabetes (T2D).

Targeted discovery of single-nucleotide polymorphisms in an unmarked wheat chromosomal region containing the Hessian fly resistance gene H33

USDA-ARS?s Scientific Manuscript database

The highly effective Hessian fly-resistance gene, H33, was introgressed from durum wheat into common wheat and genetically mapped to chromosome 3AS, in previous research. However, H33 located to a region that is well-known to be devoid of molecular markers, with the closest flanking simple sequence ...

The impact of the unfolded protein response on human disease

PubMed Central

Wang, Shiyu

2012-01-01

A central function of the endoplasmic reticulum (ER) is to coordinate protein biosynthetic and secretory activities in the cell. Alterations in ER homeostasis cause accumulation of misfolded/unfolded proteins in the ER. To maintain ER homeostasis, eukaryotic cells have evolved the unfolded protein response (UPR), an essential adaptive intracellular signaling pathway that responds to metabolic, oxidative stress, and inflammatory response pathways. The UPR has been implicated in a variety of diseases including metabolic disease, neurodegenerative disease, inflammatory disease, and cancer. Signaling components of the UPR are emerging as potential targets for intervention and treatment of human disease. PMID:22733998

75 FR 19964 - Notice of Staff Attendance at Southwest Power Pool Regional State Committee Meeting and Southwest...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

... Power Pool, Inc. Docket No. ER10-696, Southwest Power Pool, Inc. Docket No. ER10-697, Southwest Power Pool, Inc. Docket No. ER10-698, Southwest Power Pool, Inc. Docket No. ER10-700, Southwest Power Pool...

Androgen deprivation by adrenal suppression using low-dose hydrocortisone for the treatment of breast carcinoma with apocrine features: a case report illustrating this new paradigm.

PubMed

Jongen, Lynn; Paridaens, Robert; Floris, Giuseppe; Wildiers, Hans; Neven, Patrick

2016-02-01

We report on a postmenopausal patient with a secondary metastatic apocrine breast cancer successfully treated with low-dose hydrocortisone only following several lines of chemotherapy. The tumor cells in the primary and metastatic lesion exhibited a 'triple-negative' status (estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-negative); the androgen receptor (AR) was strongly expressed. Twenty milligrams of hydrocortisone, a low substitution dose known to suppress adrenal steroid production, twice daily led to a clinical benefit lasting for one year, with symptom control, radiologically stable disease, and steady decrease in CA15.3. Our observation demonstrates that an AR-expressing apocrine breast cancer may respond to androgen deprivation, as an ER-positive breast cancer may benefit from estrogen deprivation. It highlights the importance of further research targeting the AR pathway in apocrine carcinoma, for which androgens represent the sole (known) steroid hormone stimulating tumor growth. Future clinical trials should not only focus on AR inhibitors like enzalutamide, but also on ablative modalities like low-dose hydrocortisone aiming at medical adrenalectomy. This method of androgen deprivation is largely available, cheap, and nearly devoid of toxicity.

Complete Genome Sequence of ER2796, a DNA Methyltransferase-Deficient Strain of Escherichia coli K-12.

PubMed

Anton, Brian P; Mongodin, Emmanuel F; Agrawal, Sonia; Fomenkov, Alexey; Byrd, Devon R; Roberts, Richard J; Raleigh, Elisabeth A

2015-01-01

We report the complete sequence of ER2796, a laboratory strain of Escherichia coli K-12 that is completely defective in DNA methylation. Because of its lack of any native methylation, it is extremely useful as a host into which heterologous DNA methyltransferase genes can be cloned and the recognition sequences of their products deduced by Pacific Biosciences Single-Molecule Real Time (SMRT) sequencing. The genome was itself sequenced from a long-insert library using the SMRT platform, resulting in a single closed contig devoid of methylated bases. Comparison with K-12 MG1655, the first E. coli K-12 strain to be sequenced, shows an essentially co-linear relationship with no major rearrangements despite many generations of laboratory manipulation. The comparison revealed a total of 41 insertions and deletions, and 228 single base pair substitutions. In addition, the long-read approach facilitated the surprising discovery of four gene conversion events, three involving rRNA operons and one between two cryptic prophages. Such events thus contribute both to genomic homogenization and to bacteriophage diversification. As one of relatively few laboratory strains of E. coli to be sequenced, the genome also reveals the sequence changes underlying a number of classical mutant alleles including those affecting the various native DNA methylation systems.

Complete Genome Sequence of ER2796, a DNA Methyltransferase-Deficient Strain of Escherichia coli K-12

PubMed Central

Anton, Brian P.; Mongodin, Emmanuel F.; Agrawal, Sonia; Fomenkov, Alexey; Byrd, Devon R.; Roberts, Richard J.; Raleigh, Elisabeth A.

2015-01-01

We report the complete sequence of ER2796, a laboratory strain of Escherichia coli K-12 that is completely defective in DNA methylation. Because of its lack of any native methylation, it is extremely useful as a host into which heterologous DNA methyltransferase genes can be cloned and the recognition sequences of their products deduced by Pacific Biosciences Single-Molecule Real Time (SMRT) sequencing. The genome was itself sequenced from a long-insert library using the SMRT platform, resulting in a single closed contig devoid of methylated bases. Comparison with K-12 MG1655, the first E. coli K-12 strain to be sequenced, shows an essentially co-linear relationship with no major rearrangements despite many generations of laboratory manipulation. The comparison revealed a total of 41 insertions and deletions, and 228 single base pair substitutions. In addition, the long-read approach facilitated the surprising discovery of four gene conversion events, three involving rRNA operons and one between two cryptic prophages. Such events thus contribute both to genomic homogenization and to bacteriophage diversification. As one of relatively few laboratory strains of E. coli to be sequenced, the genome also reveals the sequence changes underlying a number of classical mutant alleles including those affecting the various native DNA methylation systems. PMID:26010885

Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms

PubMed Central

Wang, Ying; Lei, Jianxun; Gupta, Mihir; Peng, Fei; Lam, Sarah; Jha, Ritu; Raduenz, Ellis; Beitz, Al J.; Gupta, Kalpna

2016-01-01

Integrative approaches such as electroacupuncture, devoid of drug effects are gaining prominence for treating pain. Understanding the mechanisms of electroacupuncture induced analgesia would benefit chronic pain conditions such as sickle cell disease (SCD), for which patients may require opioid analgesics throughout life. Mouse models are instructive in developing a mechanistic understanding of pain, but the anesthesia/restraint required to administer electroacupuncture may alter the underlying mechanisms. To overcome these limitations, we developed a method to perform electroacupuncture in conscious, freely moving, unrestrained mice. Using this technique we demonstrate a significant analgesic effect in transgenic mouse models of SCD and cancer as well as complete Freund’s adjuvant-induced pain. We demonstrate a comprehensive antinociceptive effect on mechanical, cold and deep tissue hyperalagesia in both genders. Interestingly, individual mice showed a variable response to electroacupuncture, categorized into high-, moderate-, and non-responders. Mechanistically, electroacupuncture significantly ameliorated inflammatory and nociceptive mediators both peripherally and centrally in sickle mice correlative to the antinociceptive response. Application of sub-optimal doses of morphine in electroacupuncture-treated moderate-responders produced equivalent antinociception as obtained in high-responders. Electroacupuncture in conscious freely moving mice offers an effective approach to develop a mechanism-based understanding of analgesia devoid of the influence of anesthetics or restraints. PMID:27687125

Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms.

PubMed

Wang, Ying; Lei, Jianxun; Gupta, Mihir; Peng, Fei; Lam, Sarah; Jha, Ritu; Raduenz, Ellis; Beitz, Al J; Gupta, Kalpna

2016-09-30

Integrative approaches such as electroacupuncture, devoid of drug effects are gaining prominence for treating pain. Understanding the mechanisms of electroacupuncture induced analgesia would benefit chronic pain conditions such as sickle cell disease (SCD), for which patients may require opioid analgesics throughout life. Mouse models are instructive in developing a mechanistic understanding of pain, but the anesthesia/restraint required to administer electroacupuncture may alter the underlying mechanisms. To overcome these limitations, we developed a method to perform electroacupuncture in conscious, freely moving, unrestrained mice. Using this technique we demonstrate a significant analgesic effect in transgenic mouse models of SCD and cancer as well as complete Freund's adjuvant-induced pain. We demonstrate a comprehensive antinociceptive effect on mechanical, cold and deep tissue hyperalagesia in both genders. Interestingly, individual mice showed a variable response to electroacupuncture, categorized into high-, moderate-, and non-responders. Mechanistically, electroacupuncture significantly ameliorated inflammatory and nociceptive mediators both peripherally and centrally in sickle mice correlative to the antinociceptive response. Application of sub-optimal doses of morphine in electroacupuncture-treated moderate-responders produced equivalent antinociception as obtained in high-responders. Electroacupuncture in conscious freely moving mice offers an effective approach to develop a mechanism-based understanding of analgesia devoid of the influence of anesthetics or restraints.

Emission intensity of the λ = 1.54 μm line in ZnO films grown by magnetron sputtering, diffusion doped with Ce, Yb, Er

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

Mezdrogina, M. M., E-mail: margeret.m@mail.ioffe.ru; Eremenko, M. V.; Smirnov, A. N.

2015-08-15

The effect of the Er{sup 3+}-ion excitation type on the photoluminescence spectra of crystalline ZnO(ZnO〈Ce, Yb, Er〉) films is determined in the cases of resonant (λ = 532 nm, Er{sup 3+}-ion transition from {sup 4}S{sub 3/2}, {sup 2}H{sub 11/2} levels to {sup 4}I{sub 15/2}) and non-resonant (λ = 325 nm, in the region near the ZnO band-edge emission) excitation. It is shown that resonant excitation gives rise to lines with various emission intensities, characteristic of the Er{sup 3+}-ion intracenter 4f transition with λ = 1535 nm when doping crystalline ZnO films with three rare-earth ions (REIs, Ce, Yb, Er) ormore » with two impurities (Ce, Er) or (Er, Yb), independently of the measurement temperature (T = 83 and 300 K). The doping of crystalline ZnO films with rare-earth impurities (Ce, Yb, Er) leads to the efficient transfer of energy to REIs, a consequence of which is the intense emission of an Er{sup 3+} ion in the IR spectral region at λ{sub max} = 1535 nm. The kick-out diffusion mechanism is used upon the sequential introduction of impurities into semiconductor matrices and during the postgrowth annealing of the ZnO films under study. The crystalline ZnO films doped with Ce, Yb, Er also exhibit intense emission in the visible spectral region at room temperature, which makes them promising materials for optoelectronics.« less

78 FR 4142 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-18

... I, L.L.C., Cedar Brakes II, L.L.C., Central Power & Lime LLC, Utility Contract Funding, L.L.C... Energy Services, LLC, Champion Energy, LLC. Description: Updated Market Power Analysis for the Southwest... that the Commission received the following electric rate filings: Docket Numbers: ER10-2331-014; ER10...

78 FR 25072 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-29

...., Central Power & Lime LLC, Triton Power Michigan LLC, Utility Contract Funding, L.L.C. Description...: ER13-1097-001. Applicants: Central Power & Lime LLC. Description: Amendment to revisions to market...

77 FR 33212 - Notice of FERC Staff Attendance at the Entergy Regional State Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-05

... Gulf States, Louisiana, LLC Docket No. ER11-2133 Entergy Gulf States, Louisiana, LLC Docket No. ER11... Entergy Regional State Committee Meeting The Federal Energy Regulatory Commission (Commission) hereby... the Commission's ongoing outreach efforts. Entergy Regional State Committee Meeting June 6, 2012-June...

Intense green and red upconversion emission of Er3+,Yb3+ co-doped CaZrO3 obtained by a solution combustion reaction

NASA Astrophysics Data System (ADS)

Singh, Vijay; Kumar Rai, Vineet; Haase, Markus

2012-09-01

CaZrO3 phosphors co-doped with Er3+ and Yb3+ ions have been prepared by the urea combustion route. The formation of the orthorhombic phase of CaZrO3 was confirmed by powder x-ray diffraction. The absorption in the 280-1800 nm region and excitation spectrum corresponding to the emission at 545 nm for CaZrO3:Er3+/CaZrO3:Er3+,Yb3+ phosphors have been recorded. Upon excitation at 978 nm, the material displays strong energy transfer upconversion emission in the green and red spectral regions. The upconversion emission of the CaZrO3:Er3+,Yb3+ co-doped material shows an increased red-to-green ratio, indicating cross relaxation between Er3+ ions.

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 within the transmembrane region undergo an ER-stress mediated cell apoptosis. PMID:21298055

Unshielded asymmetric transmit-only and endorectal receive-only radiofrequency coil for (23) Na MRI of the prostate at 3 tesla.

PubMed

Farag, Adam; Peterson, Justin Charles; Szekeres, Trevor; Bauman, Glenn; Chin, Joseph; Romagnoli, Cesare; Bartha, Robert; Scholl, Timothy J

2015-08-01

To develop and optimize radiofrequency (RF) hardware for the detection of endogenous sodium ((23) Na) by 3.0 Tesla (T) MRI in the human prostate. A transmit-only receive-only (TORO) RF system of resonators consisting of an unshielded, asymmetric, quadrature birdcage (transmit), and an endorectal (ER), linear, surface (receive) coil were developed and tested on a 3T MRI scanner. Two different ER receivers were constructed; a single-tuned ((23) Na) and a dual-tuned ((1) H/(23) Na). Both receivers were evaluated by the measurements of signal-to-noise ratio (SNR) and B1 homogeneity. For tissue sodium concentration (TSC) quantification, vials containing known sodium concentrations were incorporated into the ER. The system was used to measure the prostate TSC of three men (age 55 ± 5 years) with biopsy-proven prostate cancer. B1 field inhomogeneity of the asymmetric transmitter was estimated to be less than 5%. The mean SNR measured in a region of interest within the prostate using the single-tuned ER coil was 54.0 ± 4.6. The mean TSC in the central gland was 60.2 ± 5.7 mmol/L and in the peripheral gland was 70.5 ± 9.0 mmol/L. A TORO system was developed and optimized for (23) Na MRI of the human prostate which showed good sensitivity throughout the prostate for quantitative measurement of TSC. © 2014 Wiley Periodicals, Inc.

Coordination of golgin tethering and SNARE assembly: GM130 binds syntaxin 5 in a p115-regulated manner.

PubMed

Diao, Aipo; Frost, Laura; Morohashi, Yuichi; Lowe, Martin

2008-03-14

During membrane traffic, transport carriers are first tethered to the target membrane prior to undergoing fusion. Mechanisms exist to connect tethering with fusion, but in most cases, the details remain poorly understood. GM130 is a member of the golgin family of coiled-coil proteins tat is involved in membrane tethering at the endoplasmic reticulum (ER) to Golgi intermediate compartment and cis-Golgi. Here, we demonstrate that GM130 interacts with syntaxin 5, a t-SNARE also localized to the early secretory pathway. Binding to syntaxin 5 is specific, direct, and mediated by the membrane-proximal region of GM130. Interestingly, interaction with syntaxin 5 is inhibited by the binding of the vesicle docking protein p115 to a distal binding site in GM130. The interaction between GM130 and the small GTPase Rab1 is also inhibited by p115 binding. Our findings suggest a mechanism for coupling membrane tethering and fusion at the ER to Golgi intermediate compartment and cis-Golgi, with GM130 playing a central role in linking these processes. Consistent with this hypothesis, we find that depletion of GM130 by RNA interference slows the rate of ER to Golgi trafficking in vivo. The interactions of GM130 with syntaxin 5 and Rab1 are also regulated by mitotic phosphorylation, which is likely to contribute to the inhibition of ER to Golgi trafficking that occurs when mammalian cells enter mitosis.

Neural Global Pattern Similarity Underlies True and False Memories.

PubMed

Ye, Zhifang; Zhu, Bi; Zhuang, Liping; Lu, Zhonglin; Chen, Chuansheng; Xue, Gui

2016-06-22

The neural processes giving rise to human memory strength signals remain poorly understood. Inspired by formal computational models that posit a central role of global matching in memory strength, we tested a novel hypothesis that the strengths of both true and false memories arise from the global similarity of an item's neural activation pattern during retrieval to that of all the studied items during encoding (i.e., the encoding-retrieval neural global pattern similarity [ER-nGPS]). We revealed multiple ER-nGPS signals that carried distinct information and contributed differentially to true and false memories: Whereas the ER-nGPS in the parietal regions reflected semantic similarity and was scaled with the recognition strengths of both true and false memories, ER-nGPS in the visual cortex contributed solely to true memory. Moreover, ER-nGPS differences between the parietal and visual cortices were correlated with frontal monitoring processes. By combining computational and neuroimaging approaches, our results advance a mechanistic understanding of memory strength in recognition. What neural processes give rise to memory strength signals, and lead to our conscious feelings of familiarity? Using fMRI, we found that the memory strength of a given item depends not only on how it was encoded during learning, but also on the similarity of its neural representation with other studied items. The global neural matching signal, mainly in the parietal lobule, could account for the memory strengths of both studied and unstudied items. Interestingly, a different global matching signal, originated from the visual cortex, could distinguish true from false memories. The findings reveal multiple neural mechanisms underlying the memory strengths of events registered in the brain. Copyright © 2016 the authors 0270-6474/16/366792-11$15.00/0.

75 FR 76714 - Combined Notice of Filings No. 2

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-09

... Wednesday, December 22, 2010. Docket Numbers: ER11-2267-000. Applicants: Central Power & Lime LLC. Description: Central Power & Lime LLC submits tariff filing per 35: Order 697 Compliance Filing to be...

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.

Ultrastructural Aspects of the Prenatal Bovine Ovary Differentiation with a Special Focus on the Interstitial Cells.

PubMed

Kenngott, R A-M; Scholz, W; Sinowatz, F

2016-10-01

The aim of this investigation was to study the ultrastructural features during the development of fetal bovine ovaries (crown rump length ranging from 11.4 to 94.0 cm). An interesting observation was the occurrence of big elongated cells containing a variety of electron dense granules and light homogenous vacuoles/bodies. They were located between the stroma cells surrounding the germ cell cord ends, adjacent to the first formed primordial follicles, typically situated near blood vessels. ER alpha and ER beta receptor positive cells could be detected in the same regions by means of immunohistochemistry. Intercellular bridges linked the germ cells nests oogonia. Germ cell cords consisted of centrally located, large, pale oogonia, surrounded by elongated somatic cells with very long cytoplasm extensions. Primordial follicles with flat pale follicular cells could be observed on the inner end of the cords. Extrusions of the outer nuclear membrane could often been recognised in voluminous oocytes. © 2016 Blackwell Verlag GmbH.

Lipid droplets form from distinct regions of the cell in the fission yeast Schizosaccharomyces pombe

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

Meyers, Alex; del Rio, Zuania P.; Beaver, Rachael A.

Eukaryotic cells store cholesterol/sterol esters (SEs) and triacylglycerols (TAGs) in lipid droplets, which form from the contiguous endoplasmic reticulum (ER) network. However, it is not known if droplets preferentially form from certain regions of the ER over others. Here, we used fission yeast Schizosaccharomyces pombe cells where the nuclear and cortical/peripheral ER domains are distinguishable by light microscopy to show that SE-enriched lipid droplets form away from the nucleus at the cell tips, whereas TAG-enriched lipid droplets form around the nucleus. Sterols localize to the regions of the cells where droplets enriched in SEs are observed. TAG droplet formation aroundmore » the nucleus appears to be a strong function of diacylglycerol (DAG) homeostasis with Cpt1p, which coverts DAG into phosphatidylcholine and phosphatidylethanolamine localized exclusively to the nuclear ER. Also, Dgk1p, which converts DAG into phosphatidic acid localized strongly to the nuclear ER over the cortical/peripheral ER. We also show that TAG more readily translocates from the ER to lipid droplets than do SEs. Lastly, the results augment the standard lipid droplet formation model, which has SEs and TAGs flowing into the same nascent lipid droplet regardless of its biogenesis point in the cell.« less

Lipid droplets form from distinct regions of the cell in the fission yeast Schizosaccharomyces pombe

DOE PAGES

Meyers, Alex; del Rio, Zuania P.; Beaver, Rachael A.; ...

2016-04-29

Eukaryotic cells store cholesterol/sterol esters (SEs) and triacylglycerols (TAGs) in lipid droplets, which form from the contiguous endoplasmic reticulum (ER) network. However, it is not known if droplets preferentially form from certain regions of the ER over others. Here, we used fission yeast Schizosaccharomyces pombe cells where the nuclear and cortical/peripheral ER domains are distinguishable by light microscopy to show that SE-enriched lipid droplets form away from the nucleus at the cell tips, whereas TAG-enriched lipid droplets form around the nucleus. Sterols localize to the regions of the cells where droplets enriched in SEs are observed. TAG droplet formation aroundmore » the nucleus appears to be a strong function of diacylglycerol (DAG) homeostasis with Cpt1p, which coverts DAG into phosphatidylcholine and phosphatidylethanolamine localized exclusively to the nuclear ER. Also, Dgk1p, which converts DAG into phosphatidic acid localized strongly to the nuclear ER over the cortical/peripheral ER. We also show that TAG more readily translocates from the ER to lipid droplets than do SEs. Lastly, the results augment the standard lipid droplet formation model, which has SEs and TAGs flowing into the same nascent lipid droplet regardless of its biogenesis point in the cell.« less

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.

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.

Cytoskeleton in gravisensing and signal transductionof lower plants

NASA Astrophysics Data System (ADS)

Braun, M.

Characean rhizoids and protonemata are favourable cell types for studying tip growth and gravisensing. Both processes are highly dependent on the actin cytoskeleton. The multiple functions and different arrangements of actin in both cell types are regulated by the concerted action of actin-binding proteins. Monomer- binding profilin is distributed evenly throughout the cytoplasm and is likely to be involved in the regulation of the polymerization state of actin. Actin-severing ADF, spectrin- and actinin-like epitopes concentrate in a central prominent spot in the apex of both cell types, where they colocalize with a dense, spherical actin array and a unique aggregation of endoplasmic reticulum (ER), the structural center of the tip - growth organizing Spitzenkörper. The ER aggregate disintegrates and immuno- localization of the actin-binding proteins fails when tip growth is arrested; the epitopes reappear when tip growth resumes. Actin filaments form a meshwork of axially oriented filaments in the subapical zone and focus in this central apical area which seems to represent their apical polymerization site. The rapid turn-over and rearrangement of actin might be under control of ADF and profilin. Spectrin- and actinin-like proteins are candidates for establishing the actin-mediated anchoring and maintaining of the ER aggregate. They could also provide a mechanism for recruiting specific membrane proteins that create the particular physiological environment for gravity-oriented tip growth. The positioning and sedimentation of statoliths in the subapical region (crucial for gravisensing) is highly coordinated by actomyosin. Non-invasive infrared laser micromanipulation techniques, centri- fugation and experiments in microgravity revealed that reorientation of the growth direction was initiated when at least 2-3 statoliths were directed to specific areas of the plasma membrane by actomyosin and gravitational forces. The statolith-sensitive area is confined to the statolith region (10-35 μm) in positively gravitropic rhizoids, whereas in negatively gravitropic protonemata, it is limited to the apical plasma membrane (0-10 μm). The statolith-sensitive plasma-membrane areas represent the primary sites for graviperception, where the information derived from statolith sedimentation is transformed into physiological signals which trigger the molecular mechanisms of the opposite graviresponses in characean rhizoids and protonemata

77 FR 3471 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-24

...: J.P. Morgan Ventures Energy Corporation, Triton Power Michigan LLC, BE Allegheny LLC, BE CA LLC, BE Ironwood LLC, BE KJ LLC, BE Rayle LLC, BE Alabama LLC, BE Louisiana LLC, Cedar Brakes I LLC, Central Power... that the Commission received the following electric rate filings: Docket Numbers: ER10-2319-002; ER10...

A full-spectrum photocatalyst with strong near-infrared photoactivity derived from synergy of nano-heterostructured Er3+-doped multi-phase oxides.

PubMed

Chen, Huabin; Liu, Wenxia; Hu, Bin; Qin, Zhuozhuo; Liu, Hong

2017-12-07

The development of full-spectrum photocatalysts active in the near-infrared (NIR) region has gained increasing attention in the photodegradation of organic pollutants. Herein, we designed a full-spectrum photocatalyst with strong NIR photoactivity based on the synergy of Er 3+ -doped ZnO-CuO-ZnAl 2 O 4 multi-phase oxides (Er 3+ -doped Zn/Cu/Al-MPO) via the formation of n-p-n double heterojunctions. The photocatalyst was prepared by synthesizing nanosheets of a Zn/Cu/Al/Er hydrotalcite-like compound (Zn/Cu/Al/Er-HLC) with a co-precipitation method followed by calcination of the nanosheets at 800 °C. The as-prepared Er 3+ -doped Zn/Cu/Al-MPO inherits the nanosheet morphology of Zn/Cu/Al/Er-HLC, and displays over-doubled photoactivity in the entire ultraviolet (UV), visible and NIR regions compared to undoped Zn/Cu/Al-MPO. The excellent photocatalytic activity of Er 3+ -doped Zn/Cu/Al-MPO, especially its strong NIR photoactivity, is ascribed to its Er 3+ -doped CuO-involved multi-crystalline phase heterostructure, i.e., n-p-n double heterojunctions, which does not only offer an enhanced NIR absorption but also promotes the separation of photogenerated charge carriers. Importantly, the synergy of all the parts of the n-p-n double heterojuctions plays an important role in interface band structure regulation for the enhancement of the photocatalytic properties of Er 3+ -doped Zn/Cu/Al-MPO. This work has demonstrated the feasibility of utilizing hydrotalcite-like precursors in the design of full-spectrum photocatalysts active in the NIR region.

Improving health promotion through central rating of interventions: the need for Responsive Guidance.

PubMed

Kok, Maarten Olivier; Bal, Roland; Roelofs, Caspar David; Schuit, Albertine Jantine

2017-11-23

In several countries, attempts are made to improve health promotion by centrally rating the effectiveness of health promotion interventions. The Dutch Effectiveness Rating System (ERS) for health promotion interventions is an improvement-oriented approach in which multi-disciplinary expert committees rate available health promotion interventions as 'theoretically sound', 'probably effective' or 'proven effective'. The aim of this study is to explore the functioning of the ERS and the perspective of researchers, policy-makers and practitioners regarding its contribution to improvement. We interviewed 53 selected key informants from research, policy and practice in the Netherlands and observed the assessment of 12 interventions. Between 2008 and 2012, a total of 94 interventions were submitted to the ERS, of which 23 were rejected, 58 were rated as 'theoretically sound', 10 were rated as 'probably effective' and 3 were rated as 'proven effective'. According to participants, the ERS was intended to facilitate both the improvement of available interventions and the improvement of health promotion in practice. While participants expected that describing and rating interventions promoted learning and enhanced the transferability of interventions, they were concerned that the ERS approach was not suitable for guiding intervention development and improving health promotion in practice. The expert committees that assessed the interventions struggled with a lack of norms for the relevance of effects and questions about how effects should be studied and rated. Health promotion practitioners were concerned that the ERS neglected the local adaptation of interventions and did not encourage the improvement of aspects like applicability and costs. Policy-makers and practitioners were worried that the lack of proven effectiveness legitimised cutbacks rather than learning and advancing health promotion. While measuring and centrally rating the effectiveness of interventions can be beneficial, the evidence based-inspired ERS approach is too limited to guide both intervention development and the improvement of health promotion in practice. To better contribute to improving health promotion, a more reflexive and responsive guidance approach is required, namely one which stimulates the improvement of different intervention aspects, provides targeted recommendations to practitioners and provides feedback to those who develop and rate interventions.

Regional and long-range transport scenarios for photo-oxidants on the Mediterranean basin in summer

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

Millan, M.; Mantilla, E.; Salvador, R.

1996-12-31

Atmospheric research, begun in 1988, has shown that the dynamics of air pollutants in the Mediterranean basin in summer are governed by processes ranging from local to large meso-scale with diurnal cycles. Large scale convection over some regions, and up-slope winds in others, can inject aged pollutants into the Mid-troposphere, where they can participate in long-range processes within Southern and Central Europe. Two scenarios have been identified for the regional and long-range transport of photo-oxidants and other pollutants within, and out of, the Western Mediterranean basin. The first scenario involves the pollutants injected over the Spanish Central Plateau directly intomore » the mid-troposphere, and the second, the reservoir layers created along the Mediterranean coast. In the second scenario the key components are: the semi-permanent high(er) pressure area over the colder waters in the Gulf of Lion-Western Mediterranean basin, the mountain ranges which surround it, and the coastal processes. During the day the coastal circulations renovate the upper reservoir layers while the lower ones are drawn inland with the sea-breeze, and effective flow is mostly perpendicular to the coast.« less

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

The Role of B Vitamins in Marine Biogeochemistry

NASA Astrophysics Data System (ADS)

Sañudo-Wilhelmy, Sergio A.; Gómez-Consarnau, Laura; Suffridge, Christopher; Webb, Eric A.

2014-01-01

The soluble B vitamins (B1, B7, and B12) have long been recognized as playing a central metabolic role in marine phytoplankton and bacteria; however, the importance of these organic external metabolites in marine ecology has been largely disregarded, as most research has focused on inorganic nutrients and trace metals. Using recently available genomic data combined with culture-based surveys of vitamin auxotrophy (i.e., vitamin requirements), we show that this auxotrophy is widespread in the marine environment and occurs in both autotrophs and heterotrophs residing in oligotrophic and eutrophic environments. Our analysis shows that vitamins originate from the activities of some bacteria and algae and that taxonomic changes observed in marine phytoplankton communities could be the result of their specific vitamin requirements and/or vitamin availability. Dissolved vitamin concentration measurements show that large areas of the world ocean are devoid of B vitamins, suggesting that vitamin limitation could be important for the efficiency of carbon and nitrogen fixation in those regions.

Endoplasmic reticulum stress in obesity and obesity-related disorders: An expanded view.

PubMed

Pagliassotti, Michael J; Kim, Paul Y; Estrada, Andrea L; Stewart, Claire M; Gentile, Christopher L

2016-09-01

The endoplasmic reticulum (ER) is most notable for its central roles in calcium ion storage, lipid biosynthesis, and protein sorting and processing. By virtue of its extensive membrane contact sites that connect the ER to most other organelles and to the plasma membrane, the ER can also regulate diverse cellular processes including inflammatory and insulin signaling, nutrient metabolism, and cell proliferation and death via a signaling pathway called the unfolded protein response (UPR). Chronic UPR activation has been observed in liver and/or adipose tissue of dietary and genetic murine models of obesity, and in human obesity and non-alcoholic fatty liver disease (NAFLD). Activation of the UPR in obesity and obesity-related disorders likely has two origins. One linked to classic ER stress involving the ER lumen and one linked to alterations to the ER membrane environment. This review discusses both of these origins and also considers the role of post-translational protein modifications, such as acetylation and palmitoylation, and ER-mitochondrial interactions to obesity-mediated impairments in the ER and activation of the UPR. Copyright © 2016 Elsevier Inc. All rights reserved.

Endoplasmic Reticulum Stress in Obesity and Obesity-Related Disorders: An Expanded View

PubMed Central

Pagliassotti, M.J.; Kim, P. Y.; Estrada, A.L.; Stewart, C.M.; Gentile, C.L.

2016-01-01

The Endoplasmic Reticulum (ER) is most notable for its central roles in calcium ion storage, lipid biosynthesis, and protein sorting and processing. By virtue of its extensive membrane contact sites that connect the ER to most other organelles and to the plasma membrane, the ER can also regulate diverse cellular processes including inflammatory and insulin signaling, nutrient metabolism, and cell proliferation and death via a signaling pathway called the unfolded protein response (UPR). Chronic UPR activation has been observed in liver and/or adipose tissue of dietary and genetic murine models of obesity, and in human obesity and non-alcoholic fatty liver disease (NAFLD). Activation of the UPR in obesity and obesity-related disorders likely has two origins. One linked to classic ER stress involving the ER lumen and one linked to alterations to the ER membrane environment. This review discusses both of these origins and also considers the role of post-translational protein modifications, such as acetylation and palmitoylation, and ER-mitochondrial interactions to obesity-mediated impairments in the ER and activation of the UPR. PMID:27506731

Magnetic field and radiative transfer modelling of a quiescent prominence

NASA Astrophysics Data System (ADS)

Gunár, S.; Schwartz, P.; Dudík, J.; Schmieder, B.; Heinzel, P.; Jurčák, J.

2014-07-01

Aims: The aim of this work is to analyse the multi-instrument observations of the June 22, 2010 prominence to study its structure in detail, including the prominence-corona transition region and the dark bubble located below the prominence body. Methods: We combined results of the 3D magnetic field modelling with 2D prominence fine structure radiative transfer models to fully exploit the available observations. Results: The 3D linear force-free field model with the unsheared bipole reproduces the morphology of the analysed prominence reasonably well, thus providing useful information about its magnetic field configuration and the location of the magnetic dips. The 2D models of the prominence fine structures provide a good representation of the local plasma configuration in the region dominated by the quasi-vertical threads. However, the low observed Lyman-α central intensities and the morphology of the analysed prominence suggest that its upper central part is not directly illuminated from the solar surface. Conclusions: This multi-disciplinary prominence study allows us to argue that a large part of the prominence-corona transition region plasma can be located inside the magnetic dips in small-scale features that surround the cool prominence material located in the dip centre. We also argue that the dark prominence bubbles can be formed because of perturbations of the prominence magnetic field by parasitic bipoles, causing them to be devoid of the magnetic dips. Magnetic dips, however, form thin layers that surround these bubbles, which might explain the occurrence of the cool prominence material in the lines of sight intersecting the prominence bubbles. Movie and Appendix A are available in electronic form at http://www.aanda.org

Point mutations in the post-M2 region of human alpha-ENaC regulate cation selectivity.

PubMed

Ji, H L; Parker, S; Langloh, A L; Fuller, C M; Benos, D J

2001-07-01

We tested the hypothesis that an arginine-rich region immediately following the second transmembrane domain may constitute part of the inner mouth of the epithelial Na+ channel (ENaC) pore and, hence, influence conduction and/or selectivity properties of the channel by expressing double point mutants in Xenopus oocytes. Double point mutations of arginines in this post-M2 region of the human alpha-ENaC (alpha-hENaC) led to a decrease and increase in the macroscopic conductance of alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, respectively, but had no effect on the single-channel conductance of either double point mutant. However, the apparent equilibrium dissociation constant for Na+ was decreased for both alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, and the maximum amiloride-sensitive Na+ current was decreased for alphaR586E,R587Ebetagamma-hENaC and increased for alphaR589E,R591Ebetagamma-hENaC. The relative permeabilities of Li+ and K+ vs. Na+ were increased 11.25- to 27.57-fold for alphaR586E,R587Ebetagamma-hENaC compared with wild type. The relative ion permeability of these double mutants and wild-type ENaC was inversely related to the crystal diameter of the permeant ions. Thus the region of positive charge is important for the ion permeation properties of the channel and may form part of the pore itself.

Non-neurogenic SVZ-like niche in dolphins, mammals devoid of olfaction.

PubMed

Parolisi, Roberta; Cozzi, Bruno; Bonfanti, Luca

2017-08-01

Adult neurogenesis has been implicated in brain plasticity and brain repair. In mammals, it is mostly restricted to specific brain regions and specific physiological functions. The function and evolutionary history of mammalian adult neurogenesis has been elusive so far. The largest neurogenic site in mammals (subventricular zone, SVZ) generates neurons destined to populate the olfactory bulb. The SVZ neurogenic activity appears to be related to the dependence of the species on olfaction since it occurs at high rates throughout life in animals strongly dependent on this function for their survival. Indeed, it dramatically decreases in humans, who do not depend so much on it. This study investigates whether the SVZ neurogenic site exists in mammals devoid of olfaction and olfactory brain structures, such as dolphins. Our results demonstate that a small SVZ-like region persists in these aquatic mammals. However, this region seems to have lost its neurogenic capabilities since neonatal stages. In addition, instead of the typical newly generated neuroblasts, some mature neurons were observed in the dolphin SVZ. Since cetaceans evolved from terrestrial ancestors, non-neurogenic SVZ may indicate extinction of adult neurogenesis in the absence of olfactory function, with the retention of an SVZ-like anatomical region either vestigial or of still unknown role.

Admixture Mapping of African-American Women in the AMBER Consortium Identifies New Loci for Breast Cancer and Estrogen-Receptor Subtypes.

PubMed

Ruiz-Narváez, Edward A; Sucheston-Campbell, Lara; Bensen, Jeannette T; Yao, Song; Haddad, Stephen; Haiman, Christopher A; Bandera, Elisa V; John, Esther M; Bernstein, Leslie; Hu, Jennifer J; Ziegler, Regina G; Deming, Sandra L; Olshan, Andrew F; Ambrosone, Christine B; Palmer, Julie R; Lunetta, Kathryn L

2016-01-01

Recent genetic admixture coupled with striking differences in incidence of estrogen receptor (ER) breast cancer subtypes, as well as severity, between women of African and European ancestry, provides an excellent rationale for performing admixture mapping in African American women with breast cancer risk. We performed the largest breast cancer admixture mapping study with in African American women to identify novel genomic regions associated with the disease. We conducted a genome-wide admixture scan using 2,624 autosomal ancestry informative markers (AIMs) in 3,629 breast cancer cases (including 1,968 ER-positive, 1093 ER-negative, and 601 triple-negative) and 4,658 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, a collaborative study of four large geographically different epidemiological studies of breast cancer in African American women. We used an independent case-control study to test for SNP association in regions with genome-wide significant admixture signals. We found two novel genome-wide significant regions of excess African ancestry, 4p16.1 and 17q25.1, associated with ER-positive breast cancer. Two regions known to harbor breast cancer variants, 10q26 and 11q13, were also identified with excess of African ancestry. Fine-mapping of the identified genome-wide significant regions suggests the presence of significant genetic associations with ER-positive breast cancer in 4p16.1 and 11q13. In summary, we identified three novel genomic regions associated with breast cancer risk by ER status, suggesting that additional previously unidentified variants may contribute to the racial differences in breast cancer risk in the African American population.

78 FR 7425 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-01

... Allegheny LLC, BE CA LLC, BE Ironwood LLC, BE KJ LLC, BE Louisiana LLC, BE Rayle LLC, Cedar Brakes I, L.L.C., Cedar Brakes II, L.L.C., Central Power & Lime LLC, Triton Power Michigan LLC, Utility Contract Funding... that the Commission received the following electric rate filings: Docket Numbers: ER10-1707-002; ER11...

SELF-CANCELLATION OF EPHEMERAL REGIONS IN THE QUIET SUN

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

Yang, Shuhong; Zhang, Jun; Li, Ting

2012-06-20

With the observations from the Helioseismic and Magnetic Imager aboard the Solar Dynamics Observatory, we statistically investigate the ephemeral regions (ERs) in the quiet Sun. We find that there are two types of ERs: normal ERs (NERs) and self-canceled ERs (SERs). Each NER emerges and grows with separation of its opposite polarity patches which will cancel or coalesce with other surrounding magnetic flux. Each SER also emerges and grows and its dipolar patches separate at first, but a part of the magnetic flux of the SER will move together and cancel gradually, which is described with the term 'self-cancellation' bymore » us. We identify 2988 ERs, among which there are 190 SERs, about 6.4% of the ERs. The mean value of self-cancellation fraction of SERs is 62.5%, and the total self-canceled flux of SERs is 9.8% of the total ER flux. Our results also reveal that the higher the ER magnetic flux is, (1) the easier the performance of ER self-cancellation is, (2) the smaller the self-cancellation fraction is, and (3) the more the self-canceled flux is. We think that the self-cancellation of SERs is caused by the submergence of magnetic loops connecting the dipolar patches, without magnetic energy release.« less

Entry and Exit Mechanisms at the cis-Face of the Golgi Complex

PubMed Central

Lorente-Rodríguez, Andrés; Barlowe, Charles

2011-01-01

Vesicular transport of protein and lipid cargo from the endoplasmic reticulum (ER) to cis-Golgi compartments depends on coat protein complexes, Rab GTPases, tethering factors, and membrane fusion catalysts. ER-derived vesicles deliver cargo to an ER-Golgi intermediate compartment (ERGIC) that then fuses with and/or matures into cis-Golgi compartments. The forward transport pathway to cis-Golgi compartments is balanced by a retrograde directed pathway that recycles transport machinery back to the ER. How trafficking through the ERGIC and cis-Golgi is coordinated to maintain organelle structure and function is poorly understood and highlights central questions regarding trafficking routes and organization of the early secretory pathway. PMID:21482742

Rootcap structure in wild type and in a starchless mutant of Arabidopsis

NASA Technical Reports Server (NTRS)

Sack, F. D.; Kiss, J. Z.

1989-01-01

Rootcaps of the wild type (WT) and of a starchless, gravitropic mutant (TC7) of Arabidopsis thaliana L. were examined by electron microscopy to identify cellular polarities with respect to gravity. In columella cells, nuclei are located proximally, and the nuclear envelope is continuous with endoplasmic reticulum (ER) that is in turn connected to nearby plasmodesmata. Impregnation of ER with osmium ferricyanide revealed numerous contacts between columella plastids and ER in both genotypes. ER is present mostly in the outer regions of the columella protoplast except in older columella cells that are developing into peripheral cells. In vertical roots, only columella cells that are intermediate in development (story 2 cells) have a higher surface density (S) of ER in the distal compared to proximal regions of the cell. The distal but not the proximal S of the ER is constant throughout columella development. Plastids are less sedimented in TC7 columella cells compared to those of the WT. It is hypothesized that plastid contact with the ER plays a role in gravity perception in both genotypes.

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.

PubMed

Martínez-Sánchez, Noelia; Seoane-Collazo, Patricia; Contreras, Cristina; Varela, Luis; Villarroya, Joan; Rial-Pensado, Eva; Buqué, Xabier; Aurrekoetxea, Igor; Delgado, Teresa C; Vázquez-Martínez, Rafael; González-García, Ismael; Roa, Juan; Whittle, Andrew J; Gomez-Santos, Beatriz; Velagapudi, Vidya; Tung, Y C Loraine; Morgan, Donald A; Voshol, Peter J; Martínez de Morentin, Pablo B; López-González, Tania; Liñares-Pose, Laura; Gonzalez, Francisco; Chatterjee, Krishna; Sobrino, Tomás; Medina-Gómez, Gema; Davis, Roger J; Casals, Núria; Orešič, Matej; Coll, Anthony P; Vidal-Puig, Antonio; Mittag, Jens; Tena-Sempere, Manuel; Malagón, María M; Diéguez, Carlos; Martínez-Chantar, María Luz; Aspichueta, Patricia; Rahmouni, Kamal; Nogueiras, Rubén; Sabio, Guadalupe; Villarroya, Francesc; López, Miguel

2017-07-05

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Plasma membrane domains enriched in cortical endoplasmic reticulum function as membrane protein trafficking hubs.

PubMed

Fox, Philip D; Haberkorn, Christopher J; Weigel, Aubrey V; Higgins, Jenny L; Akin, Elizabeth J; Kennedy, Matthew J; Krapf, Diego; Tamkun, Michael M

2013-09-01

In mammalian cells, the cortical endoplasmic reticulum (cER) is a network of tubules and cisterns that lie in close apposition to the plasma membrane (PM). We provide evidence that PM domains enriched in underlying cER function as trafficking hubs for insertion and removal of PM proteins in HEK 293 cells. By simultaneously visualizing cER and various transmembrane protein cargoes with total internal reflectance fluorescence microscopy, we demonstrate that the majority of exocytotic delivery events for a recycled membrane protein or for a membrane protein being delivered to the PM for the first time occur at regions enriched in cER. Likewise, we observed recurring clathrin clusters and functional endocytosis of PM proteins preferentially at the cER-enriched regions. Thus the cER network serves to organize the molecular machinery for both insertion and removal of cell surface proteins, highlighting a novel role for these unique cellular microdomains in membrane trafficking.

Plasma membrane domains enriched in cortical endoplasmic reticulum function as membrane protein trafficking hubs

PubMed Central

Fox, Philip D.; Haberkorn, Christopher J.; Weigel, Aubrey V.; Higgins, Jenny L.; Akin, Elizabeth J.; Kennedy, Matthew J.; Krapf, Diego; Tamkun, Michael M.

2013-01-01

In mammalian cells, the cortical endoplasmic reticulum (cER) is a network of tubules and cisterns that lie in close apposition to the plasma membrane (PM). We provide evidence that PM domains enriched in underlying cER function as trafficking hubs for insertion and removal of PM proteins in HEK 293 cells. By simultaneously visualizing cER and various transmembrane protein cargoes with total internal reflectance fluorescence microscopy, we demonstrate that the majority of exocytotic delivery events for a recycled membrane protein or for a membrane protein being delivered to the PM for the first time occur at regions enriched in cER. Likewise, we observed recurring clathrin clusters and functional endocytosis of PM proteins preferentially at the cER-enriched regions. Thus the cER network serves to organize the molecular machinery for both insertion and removal of cell surface proteins, highlighting a novel role for these unique cellular microdomains in membrane trafficking. PMID:23864710

Myosin XI-dependent formation of tubular structures from endoplasmic reticulum isolated from tobacco cultured BY-2 cells.

PubMed

Yokota, Etsuo; Ueda, Haruko; Hashimoto, Kohsuke; Orii, Hidefumi; Shimada, Tomoo; Hara-Nishimura, Ikuko; Shimmen, Teruo

2011-05-01

The reticular network of the endoplasmic reticulum (ER) consists of tubular and lamellar elements and is arranged in the cortical region of plant cells. This network constantly shows shape change and remodeling motion. Tubular ER structures were formed when GTP was added to the ER vesicles isolated from tobacco (Nicotiana tabacum) cultured BY-2 cells expressing ER-localized green fluorescent protein. The hydrolysis of GTP during ER tubule formation was higher than that under conditions in which ER tubule formation was not induced. Furthermore, a shearing force, such as the flow of liquid, was needed for the elongation/extension of the ER tubule. The shearing force was assumed to correspond to the force generated by the actomyosin system in vivo. To confirm this hypothesis, the S12 fraction was prepared, which contained both cytosol and microsome fractions, including two classes of myosins, XI (175-kD myosin) and VIII (BY-2 myosin VIII-1), and ER-localized green fluorescent protein vesicles. The ER tubules and their mesh-like structures were arranged in the S12 fraction efficiently by the addition of ATP, GTP, and exogenous filamentous actin. The tubule formation was significantly inhibited by the depletion of 175-kD myosin from the S12 fraction but not BY-2 myosin VIII-1. Furthermore, a recombinant carboxyl-terminal tail region of 175-kD myosin also suppressed ER tubule formation. The tips of tubules moved along filamentous actin during tubule elongation. These results indicated that the motive force generated by the actomyosin system contributes to the formation of ER tubules, suggesting that myosin XI is responsible not only for the transport of ER in cytoplasm but also for the reticular organization of cortical ER.

Myosin XI-Dependent Formation of Tubular Structures from Endoplasmic Reticulum Isolated from Tobacco Cultured BY-2 Cells1[W][OA

PubMed Central

Yokota, Etsuo; Ueda, Haruko; Hashimoto, Kohsuke; Orii, Hidefumi; Shimada, Tomoo; Hara-Nishimura, Ikuko; Shimmen, Teruo

2011-01-01

The reticular network of the endoplasmic reticulum (ER) consists of tubular and lamellar elements and is arranged in the cortical region of plant cells. This network constantly shows shape change and remodeling motion. Tubular ER structures were formed when GTP was added to the ER vesicles isolated from tobacco (Nicotiana tabacum) cultured BY-2 cells expressing ER-localized green fluorescent protein. The hydrolysis of GTP during ER tubule formation was higher than that under conditions in which ER tubule formation was not induced. Furthermore, a shearing force, such as the flow of liquid, was needed for the elongation/extension of the ER tubule. The shearing force was assumed to correspond to the force generated by the actomyosin system in vivo. To confirm this hypothesis, the S12 fraction was prepared, which contained both cytosol and microsome fractions, including two classes of myosins, XI (175-kD myosin) and VIII (BY-2 myosin VIII-1), and ER-localized green fluorescent protein vesicles. The ER tubules and their mesh-like structures were arranged in the S12 fraction efficiently by the addition of ATP, GTP, and exogenous filamentous actin. The tubule formation was significantly inhibited by the depletion of 175-kD myosin from the S12 fraction but not BY-2 myosin VIII-1. Furthermore, a recombinant carboxyl-terminal tail region of 175-kD myosin also suppressed ER tubule formation. The tips of tubules moved along filamentous actin during tubule elongation. These results indicated that the motive force generated by the actomyosin system contributes to the formation of ER tubules, suggesting that myosin XI is responsible not only for the transport of ER in cytoplasm but also for the reticular organization of cortical ER. PMID:21427277

Early postcaldera rhyolite and structural resurgence at Long Valley Caldera, California

NASA Astrophysics Data System (ADS)

Hildreth, Wes; Fierstein, Judy; Calvert, Andrew

2017-04-01

After the 767-ka caldera-forming eruption of 650 km3 of rhyolite magma as the Bishop Tuff, 90-100 km3 of similar rhyolite erupted in the west-central part of Long Valley caldera in as many as 40 batches spread over the 110,000-year interval from 750 ka to 640 ka. Centrally, this Early Rhyolite (ER) is as thick as 622 m, but it spread radially to cover much of the caldera floor, where half its area is now concealed by post-ER sediments and lavas. At least 75% of the ER is aphyric rhyolite tuff. Drillholes encountered 22 (altered) ER lava flows intercalated in the pyroclastic pile, and another 11 units of (largely fresh) ER lava are exposed on the caldera's resurgent dome and at Lookout Mountain. Exposed units have been distinguished, mapped, studied petrographically and chemically, and radioisotopically dated; each is described in detail. Their phenocryst contents range from 0 to 2.5 wt%. All the phyric units have plagioclase, orthopyroxene, and ilmenite; most have biotite and rare tiny magnetite, and a few contain rare zircon. The compositional range of fresh obsidians is narrow-74.3-75.0% SiO2, 1.21-1.37% FeO*, and 5.12-5.26% K2O, but wider variations in Ti, Ba, Sr, and Zr permit distinction of individual units and eruptive groups. The limited chemical and petrographic variability shown by so many ER batches released episodically for 110,000 years suggests a thermally buffered and well-stirred reservoir. The ER central area, where ER eruptions had taken place, was uplifted 400 m to form a structural dome 10 km in diameter. Most of the inflation is attributable to 10 sills of ER that intrude the Bishop Tuff beneath the uplift, but other processes potentially contributing to resurgence are also considered. As shown by erratics of Mesozoic rocks ice-rafted from the Sierra Nevada and dropped on ER lavas, much of the ER had erupted early enough and at low enough elevation to be inundated by the intracaldera lake and was only later lifted by the resurgence that also raised clusters of the erratics hundreds of meters higher than any shoreline. Most of the uplift was over by 570 ka, but dome-crossing faults that exhibit normal throw of 10-30 m cut lavas as young as 175-125 ka. For most elements, chemical ranges of the ER lie within those of the zoned Bishop Tuff, which had erupted earlier from the same place. Only Ba, Zr, Hf, and Eu/Eu* extend to ranges outside those of the Bishop Tuff, nominally to less evolved compositions. Initial 87Sr/86Sr values of ER are likewise within the range of the Bishop Tuff, but ER ratios of 143Nd/144Nd and 206Pb/204Pb extend beyond those of the Bishop Tuff to values slightly more influenced by upper-crustal contributions. FeTi-oxide geothermometry yields 752°-844 °C for ER, compared to 700°-820 °C for the Bishop Tuff. ER fO2 values are 0.5-1.0 log units more reduced than those of the T-fO2 array of the Bishop Tuff. The postcaldera reduction may reflect reaction with graphite from the black lithics of Paleozoic graphitic metapelite so abundant in the Bishop Tuff. Much of the pumice emplaced during the later half of the Bishop Tuff eruption has 10-25 wt% phenocrysts, dominantly quartz and sanidine, but the 100 km3 of ER has only 0-2.5 wt% and completely lacks quartz and sanidine. Postcaldera processes, including mixing, volatile ascent, and crystal resorption, as well as potential contaminants and magmatic inputs, are all considered.

A 22,000-year record of monsoonal precipitation from northern Chile's Atacama Desert

USGS Publications Warehouse

Betancourt, J.L.; Latorre, C.; Rech, J.A.; Quade, Jay; Rylander, K.A.

2000-01-01

Fossil rodent middens and wetland deposits from the central Atacama Desert (22° to 24°S) indicate increasing summer precipitation, grass cover, and groundwater levels from 16.2 to 10.5 calendar kiloyears before present (ky B.P.). Higher elevation shrubs and summer-flowering grasses expanded downslope across what is now the edge of Absolute Desert, a broad expanse now largely devoid of rainfall and vegetation. Paradoxically, this pluvial period coincided with the summer insolation minimum and reduced adiabatic heating over the central Andes. Summer precipitation over the central Andes and central Atacama may depend on remote teleconnections between seasonal insolation forcing in both hemispheres, the Asian monsoon, and Pacific sea surface temperature gradients. A less pronounced episode of higher groundwater levels in the central Atacama from 8 to 3 ky B.P. conflicts with an extreme lowstand of Lake Titicaca, indicating either different climatic forcing or different response times and sensitivities to climatic change.

A 22,000-Year Record of Monsoonal Precipitation from Northern Chile's Atacama Desert.

PubMed

Betancourt; Latorre; Rech; Quade; Rylander

2000-09-01

Fossil rodent middens and wetland deposits from the central Atacama Desert (22 degrees to 24 degrees S) indicate increasing summer precipitation, grass cover, and groundwater levels from 16.2 to 10.5 calendar kiloyears before present (ky B.P.). Higher elevation shrubs and summer-flowering grasses expanded downslope across what is now the edge of Absolute Desert, a broad expanse now largely devoid of rainfall and vegetation. Paradoxically, this pluvial period coincided with the summer insolation minimum and reduced adiabatic heating over the central Andes. Summer precipitation over the central Andes and central Atacama may depend on remote teleconnections between seasonal insolation forcing in both hemispheres, the Asian monsoon, and Pacific sea surface temperature gradients. A less pronounced episode of higher groundwater levels in the central Atacama from 8 to 3 ky B.P. conflicts with an extreme lowstand of Lake Titicaca, indicating either different climatic forcing or different response times and sensitivities to climatic change.

Estrogen Receptor (ER) Subtype Selectivity Identifies 8-Prenylapigenin as an ERβ Agonist from Glycyrrhiza inflata and Highlights the Importance of Chemical and Biological Authentication.

PubMed

Hajirahimkhan, Atieh; Mbachu, Obinna; Simmler, Charlotte; Ellis, Sarah G; Dong, Huali; Nikolic, Dejan; Lankin, David C; van Breemen, Richard B; Chen, Shao-Nong; Pauli, Guido F; Dietz, Birgit M; Bolton, Judy L

2018-04-27

Postmenopausal women are increasingly using botanicals for menopausal symptom relief due to the increased breast cancer risk associated with traditional estrogen therapy. The deleterious effects of estrogens are associated with estrogen receptor (ER)α-dependent proliferation, while ERβ activation could enhance safety by opposing ERα effects. Three medicinal licorice species, Glycyrrhiza glabra ( G. glabra), G. uralensis, and G. inflata, were studied for their differential estrogenic efficacy. The data showed higher estrogenic potency for G. inflata in an alkaline phosphatase induction assay in Ishikawa cells (ERα) and an estrogen responsive element (ERE)-luciferase assay in MDA-MB-231/β41 breast cancer cells (ERβ). Bioassay-guided fractionation of G. inflata led to the isolation of 8-prenylapigenin (3). Surprisingly, a commercial batch of 3 was devoid of estrogenic activity. Quality control by MS and qNMR revealed an incorrect compound, 4'- O-methylbroussochalcone B (10), illustrating the importance of both structural and purity verification prior to any biological investigations. Authentic and pure 3 displayed 14-fold preferential ERβ agonist activity. Quantitative analyses revealed that 3 was 33 times more concentrated in G. inflata compared to the other medicinal licorice extracts. These data suggest that standardization of G. inflata to 3 might enhance the safety and efficacy of G. inflata supplements used for postmenopausal women's health.

Characterization of the distribution of rotational torque on electrorotation chips with 3D electrodes.

PubMed

Bahrieh, Garsha; Özgür, Ebru; Koyuncuoğlu, Aziz; Erdem, Murat; Gündüz, Ufuk; Külah, Haluk

2015-08-01

This is a study of in-plane and out-of-plane distribution of rotational torque (ROT-T) and effective electric field (EEF) on electrorotation (ER) devices with 3D electrodes using finite element modeling (FEM) and experimental method. The objective of this study is to investigate electrical characteristics of the ER devices with five different electrode geometries and obtain an optimum structure for ER experiments. Further, it provides a comparison between characteristics of the 3D electrodes and traditionally used 2D electrodes. 3D distributions of EEF were studied by the time-variant FEM. FEM results were verified experimentally by studying the rotation of biological cells. The results show that the variations of ROT-T and EEF over the measurement area of the devices are considerably large. This can potentially lead to misinterpretation of recorded data. Therefore, it is essential to specify the boundaries of the measurement area with minimum deviation from the central EEF. For this purpose, FE analyses were utilized to specify the optimal region. Thereby, with confining the measurements to these regions, the dependency of ROT-T on the spatial position of the particles can be eliminated. Comparisons have been made on the sustainability of the EEF and ROT-T distributions for each device, to find an optimum design. Analyses of the devices prove that utilization of the 3D electrodes eliminate irregularities of EEF and ROT-T along the z-axis. The Results show that triangular electrodes provide the highest sustainability for the in-plane ROT-T and EEF distribution, while the oblate elliptical and circular electrodes have the lowest variances along the z-axis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The climate changes in the sub-basin of the Oum Er rbia central and the impact on the surface waters.

NASA Astrophysics Data System (ADS)

Echakraoui, Zhour; Boukdir, Ahmed.; Aderoju, Olaide.; Hassan Ben-Saïd, El; Zitouni, Abdelhamid.; El maslouhi, Rachid; Guerner Dias, António

2018-05-01

Observations and model results indicate that climate trends in North Africa show both drying and warming over the past few decades, according to the latest Intergovernmental Panel on Climate Change (IPCC) assessment. During the last decades, due to changes in climatic and environmental conditions, water resources available in Morocco are decreasing. They are, moreover, subject to extreme cyclical variations and to soaring water demands because of rapid population growth, improvement of living standards, industrial development and expansion of irrigated agriculture. The pressure on these water resources is accompanied by a growing and increasingly serious degradation of their quality. This is found at the level of average of air temperatures that are continuously growing and at the level of precipitation with an average potential of water in the area with a significant decrease in the last forty years. The purpose of this work is to make a study on the impact of climate change on water resources that exist in the basin of the Oum Er Rbia Central, and to give justifiable results regarding the evolution of climate change over time. From the created database, we brought out diagrams, curves and maps of the evolution of climate change that show the results below: The study of the evolution of rainfall recorded since 1934 and the breaks in time series highlighted two methodologically distinct periods: a wet period with high rainfall (1986 - 1971), a dry season and low rainfall (1970/71 to 2007). Observed climatic trends, calculated over the period of 1935-2007 and reported in the study, indicate the following: On an annual basis, changes in precipitation were not significant and varied from one region to another. On the other hand, spring rainfall declined significantly in the northern part of Morocco at a rate of 0.5 mm / day per decade; That the area experienced an average annual rainfall reduction of 70 mm (20%) over this period compared to 1940-1980. The area is a hydraulic region that is already experiencing a water deficit. The sharp decline in water supplies since 1980-2007 (by 40% compared with 1940- 1980) and the increase in demand and water degradation by different causes; The annual average flows measured at the the central Oum Er Rbia stations were reduced by considerable hydrological deficits ranging between 40.8 and 49.5%. Global warming and rainfall regression are added to the intrinsic conditions of sub basins of the Oum Er Rbia Central (especially waterproofing of land and the lack of groundwater reservoir) to increase its vulnerability to water scarcity. This critical situation requires adapting good management methods of meteorological water as the only source of water in this basin.You should leave 8 mm of space above the abstract and 10 mm after the abstract. The heading Abstract should be typed in bold 9- point Arial. The body of the abstract should be typed in normal 9-point Times in a single paragraph, immediately following the heading. The text should be set to 1 line spacing. The abstract should be centred across the page, indented 17 mm from the left and right page margins and justified. It should not normally exceed 200 words.

Parameters in fractional laser assisted delivery of topical anesthetics: Role of laser type and laser settings.

PubMed

Meesters, Arne A; Nieboer, Marilin J; Kezic, Sanja; de Rie, Menno A; Wolkerstorfer, Albert

2018-05-07

Efficacy of topical anesthetics can be enhanced by pretreatment of the skin with ablative fractional lasers. However, little is known about the role of parameters such as laser modality and laser density settings in this technique. Aims of this study were to compare the efficacy of pretreatment with two different ablative fractional laser modalities, a CO 2 laser and an Er:YAG laser, and to assess the role of laser density in ablative fractional laser assisted topical anesthesia. In each of 15 healthy subjects, four 10 × 10 mm test regions on the back were randomized to pretreatment (70-75 μm ablation depth) with CO 2 laser at 5% density, CO 2 laser at 15% density, Er:YAG laser at 5% density or Er:YAG laser at 15% density. Articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml solution was applied under occlusion to all four test regions. After 15 minutes, a pass with the CO 2 laser (1,500 μm ablation depth) was administered as pain stimulus to each test region. A reference pain stimulus was given on unanesthetized skin. The main outcome parameter, pain, was scored on a 0-10 visual analogue scale (VAS) after each pain stimulus. Median VAS scores were 1.50 [CO 2 5%], 0.50 [CO 2 15%], 1.50 [Er:YAG 5%], 0.43 [Er:YAG 15%], and 4.50 [unanesthetized reference]. VAS scores for all pretreated test regions were significantly lower compared to the untreated reference region (P < 0.01). We found no significant difference in VAS scores between the CO 2 and the Er:YAG laser pretreated regions. However, VAS scores were significantly lower at 15% density compared to 5% density for both for the CO 2 laser (P < 0.05) and the Er:YAG laser (P < 0.01). Pretreatment with the CO 2 laser was considered slightly more painful than pretreatment with Er:YAG laser by the subjects. Fractional laser assisted topical anesthesia is effective even with very low energy settings and an occlusion time of only 15 minutes. Both the CO 2 laser and the Er:YAG laser can be used to assist topical anesthesia although the CO 2 laser pretreatment is experienced as more painful. In our study settings, using articaine/epinephrine solution and an occlusion time of 15 minutes, a density of 15% was more effective than 5%. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Evaluation of Central Services Professional Learning Teams as of Spring 2010. Eye on Evaluation. E&R Report No. 10.06

ERIC Educational Resources Information Center

Baenen, Nancy; Jackl, Andrew

2010-01-01

The Wake County Public School System (WCPSS) board policy states that central services staff are to support school implementation of Professional Learning Teams (PLTs) and to participate in PLTs at the central level. Central staff support school efforts in a variety of ways, and over 85% of principals at each level reported this support was…

Structural and optical studies of Er3+-doped alkali/alkaline oxide containing zinc boro-aluminosilicate glasses for 1.5 μm optical amplifier applications

NASA Astrophysics Data System (ADS)

Kaky, Kawa M.; Lakshminarayana, G.; Baki, S. O.; Lira, A.; Caldiño, U.; Meza-Rocha, A. N.; Falcony, C.; Kityk, I. V.; Taufiq-Yap, Y. H.; Halimah, M. K.; Mahdi, M. A.

2017-07-01

In the present work, we report on the optical spectral properties of Er3+-doped zinc boro-aluminosilicate glasses with an addition of 10 mol % alkali/alkaline modifier regarding the fabrication of new optical materials for optical amplifiers. A total of 10 glasses were prepared using melt-quenching technique with the compositions (40-x)B2O3 - 10SiO2 - 10Al2O3 - 30ZnO - 10Li2O - xEr2O3 and (40-x)B2O3 - 10SiO2 - 10Al2O3 - 30ZnO - 10MgO - xEr2O3 (x = 0.1, 0.25, 0.5, 1.0, and 2.0 mol %). We confirm the amorphous-like structure for all the prepared glasses using X-ray diffraction (XRD). To study the functional groups of the glass composition after the melt-quenching process, Raman spectroscopy was used, and various structural units such as triangular and tetrahedral-borates (BO3 and BO4) have been identified. All the samples were characterized using optical absorption for UV, visible and NIR regions. Judd-Ofelt (JO) intensity parameters (Ωλ, λ = 2, 4 and 6) were calculated from the optical absorption spectra of two glasses LiEr 2.0 and MgEr 2.0 (doped with 2 mol % of Er3+). JO parameters for LiEr 2.0 and MgEr 2.0 glasses follow the trend as Ω6>Ω2>Ω4. Using Judd-Ofelt intensity parameters, we obtained radiative probability A (S-1), branching ratios (β), radiative decay lifetimes τrad (μs) of emissions from excited Er+3 ions in LiEr 2.0 and MgEr 2.0 to all lower levels. Quantum efficiency (η) of 4I13/2 and 4S3/2 levels for LiEr 2.0 and MgEr 2.0 with and without 4D7/2 level was calculated using the radiative decay lifetimes τrad. (μs) and measured lifetimes τexp. (μs). We measured the visible photoluminescence under 377 nm excitation for both LiEr and MgEr glass series within the region 390-580 nm. Three bands were observed in the visible region at 407 nm, 530 nm, and 554 nm, as a result of 2H9/2 → 4I15/2, 2H11/2 → 4I15/2 and 4S3/2 → 4I15/2 transitions, respectively. Decay lifetimes for emissions at 407 nm, 530 nm, and 554 nm were measured and they show single exponential behavior for all the LiEr and MgEr glass series. From the photoluminescence and radiative decay lifetimes (τrad), we calculated the full-width at half-maximum (FWHM), emission cross-section (σPE) and bandwidth gain (FWHM × σPE) parameters. Near-infrared photoluminescence under 980 nm excitation was measured for all the LiEr and MgEr glass series in the region 1420-1620 nm. NIR emissions show a broadband centered at ∼1530 nm due to the transition of Er3+: 4I13/2 → 4I15/2. Decay lifetimes for NIR emission at ∼1530 nm were measured and they show a quite exponential nature for all the LiEr and MgEr glass series. From the NIR emission spectra and decay lifetimes, we calculated the full-width at half-maximum (FWHM), the emission cross-section (σPE) and the bandwidth gain (FWHM × σPE) for the NIR emission and it shows FWHM of 50-70 nm for prepared glasses, emission cross-section of (∼3.5) × 10-20 cm2, while bandwidth gain was (∼25) × 10-26 cm3.

Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress

PubMed Central

Wang, Jie; Pareja, Kristeen A; Kaiser, Chris A; Sevier, Carolyn S

2014-01-01

Oxidative protein folding in the endoplasmic reticulum (ER) has emerged as a potentially significant source of cellular reactive oxygen species (ROS). Recent studies suggest that levels of ROS generated as a byproduct of oxidative folding rival those produced by mitochondrial respiration. Mechanisms that protect cells against oxidant accumulation within the ER have begun to be elucidated yet many questions still remain regarding how cells prevent oxidant-induced damage from ER folding events. Here we report a new role for a central well-characterized player in ER homeostasis as a direct sensor of ER redox imbalance. Specifically we show that a conserved cysteine in the lumenal chaperone BiP is susceptible to oxidation by peroxide, and we demonstrate that oxidation of this conserved cysteine disrupts BiP's ATPase cycle. We propose that alteration of BiP activity upon oxidation helps cells cope with disruption to oxidative folding within the ER during oxidative stress. DOI: http://dx.doi.org/10.7554/eLife.03496.001 PMID:25053742

Fluorescence anisotropy microplate assay to investigate the interaction of full-length steroid receptor coactivator-1a with steroid receptors

PubMed Central

Zhang, Chen; Nordeen, Steven K.; Shapiro, David J.

2013-01-01

Estrogens, acting via estrogen receptor (ER) play key roles in growth, differentiation and gene regulation in the reproductive, central nervous and skeletal systems. ER-mediated gene transcription contributes to the development and spread of breast, uterine, and liver cancer. Steroid receptor coactivator-1a (SRC1a) belongs to the P160 family of coactivators, which is the best known of the many coactivators implicated in ER-mediated transactivation. Binding of full-length P160 coactivators to steroid receptors has been difficult to investigate in vitro. This chapter details how to investigate the interaction of SRC1a with ER using the fluorescence anisotropy/polarization microplate assay (FAMA). PMID:23436375

Kinetic analysis of central ( sup 11 C)raclopride binding to D2-dopamine receptors studied by PET--a comparison to the equilibrium analysis

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

Farde, L.; Eriksson, L.; Blomquist, G.

1989-10-01

(11C)Raclopride binding to central D2-dopamine receptors in humans has previously been examined by positron emission tomography (PET). Based on the rapid occurrence of binding equilibrium, a saturation analysis has been developed for the determination of receptor density (Bmax) and affinity (Kd). For analysis of PET measurements obtained with other ligands, a kinetic three-compartment model has been used. In the present study, the brain uptake of (11C)raclopride was analyzed further by applying both a kinetic and an equilibrium analysis to data obtained from four PET experiments in each of three healthy subjects. First regional CBV was determined. In the second andmore » third experiment, (11C)-raclopride with high and low specific activity was used. In a fourth experiment, the (11C)raclopride enantiomer (11C)FLB472 was used to examine the concentration of free radioligand and nonspecific binding in brain. Radio-activity in arterial blood was measured using an automated blood sampling system. Bmax and Kd values for (11C)raclopride binding could be determined also with the kinetic analysis. As expected theoretically, those values were similar to those obtained with the equilibrium analysis. In addition, the kinetic analysis allowed separate determination of the association and dissociation rate constants, kon and koff, respectively. Examination of (11C)raclopride and (11C)FLB472 uptake in brain regions devoid of specific D2-dopamine receptor binding indicated a fourth compartment in which uptake was reversible, nonstereoselective, and nonsaturable in the dose range studied.« less

Changes in Central Walker Lane Strain Accommodation near Bridgeport, California; as told by the Stanislaus Group

NASA Astrophysics Data System (ADS)

Carlson, C. W.; Pluhar, C. J.; Glen, J. M.; Farner, M. J.

2012-12-01

Accommodating ~20-25% of the dextral-motion between the Pacific and North American plates the Walker Lane is represented as an elongate, NW oriented, region of active tectonics positioned between the northwesterly-translating Sierra Nevada microplate and the east-west extension of the Basin and Range. This region of transtension is being variably accommodated on regional-scale systems of predominantly strike-slip faulting. At the western edge of the central Walker Lane (ca. 38°-39°N latitude) is a region of crustal-scale blocks bounded by wedge-shaped depositional-basins and normal-fault systems, here defined as the west-central Walker Lane (WCWL). Devoid of obvious strike-slip faulting, the presence of tectonic-block vertical-axis rotations in the WCWL represents unrecognized components of dextral-shearing and/or changes of strain-accommodation over time. We use paleomagnetic reference directions for Eureka Valley Tuff (EVT) members of the late Miocene Stanislaus Group as spatial and temporal markers for documentation of tectonic-block vertical-axis rotations near Bridgeport, CA. Study-site rotations revealed discrete rotational domains of mean vertical-axis rotation ranging from ~10°-30° with heterogeneous regional distribution. Additionally, the highest measured magnitudes of vertical-axis rotation (~50°-60° CW) define a 'Region of High Strain' that includes the wedge-shaped Bridgeport Valley (Basin). This study revealed previously-unrecognized tectonic rotation of reference direction sites from prior studies for two (By-Day and Upper) of the three members of the EVT, resulting in under-estimates of regional strain accommodation by these studies. Mean remanent directions and virtual geomagnetic poles utilized in our study yielded a recalculated reference direction for the By-Day member of: Dec.=353.2°; Inc.= 43.7°; α95=10.1, in agreement with new measurements in the stable Sierra Nevada. This recalculated direction confirmed the presence of previously unrecognized reference site rotations, and provided an additional reference direction for determining vertical-axis rotation magnitudes. We present a kinematic model based on mean rotation magnitudes of ~30° CW for the Sweetwater Mountains and Bodie Hills that accounts for rotational-strain accommodation of dextral shear in the WCWL since the late Miocene. This model considers rotational magnitudes, paleostrain indicators, edge-effects, and strain-accommodating structures of rotating crustal blocks to represent changes in regional strain accommodation over time. The results and models presented here elucidate the complicated and evolving nature of the WCWL, and further understanding of variations in strain accommodation for the Walker Lane.

Contribution of a membrane estrogen receptor to the estrogenic regulation of body temperature and energy homeostasis.

PubMed

Roepke, Troy A; Bosch, Martha A; Rick, Elizabeth A; Lee, Benjamin; Wagner, Edward J; Seidlova-Wuttke, Dana; Wuttke, Wolfgang; Scanlan, Thomas S; Rønnekleiv, Oline K; Kelly, Martin J

2010-10-01

The hypothalamus is a key region of the central nervous system involved in the control of homeostasis, including energy and core body temperature (Tc). 17β-Estradiol (E2) regulates Tc, in part, via actions in the basal hypothalamus and preoptic area. E2 primarily controls hypothalamic functions via the nuclear steroid receptors, estrogen receptor α/β. However, we have previously described an E2-responsive, Gq-coupled membrane receptor that reduces the postsynaptic inhibitory γ-aminobutyric acid-ergic tone and attenuates postovariectomy body weight gain in female guinea pigs through the administration of a selective Gq-mER ligand, STX. To determine the role of Gq-mER in regulating Tc, energy and bone homeostasis, ovariectomized female guinea pigs, implanted ip with temperature probes, were treated with STX or E2 for 7-8 wk. Tc was recorded for 4 wk, whereas food intake and body weight were monitored daily. Bone density and fat accumulation were determined postmortem. Both E2 and STX significantly reduced Tc in the females compared with controls. STX, similar to E2, reduced food intake and fat accumulation and increased tibial bone density. Therefore, a Gq-mER-coupled signaling pathway appears to be involved in maintaining homeostatic functions and may constitute a novel therapeutic target for treatment of hypoestrogenic symptoms.

A molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress.

PubMed

Chaudhari, Namrata; Talwar, Priti; Parimisetty, Avinash; Lefebvre d'Hellencourt, Christian; Ravanan, Palaniyandi

2014-01-01

Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse but, inflammation and/or ER stress may be basic mechanisms increasing the severity or complicating the condition of the disease. Chronic ER stress and activation of the unfolded-protein response (UPR) through endogenous or exogenous insults may result in impaired calcium and redox homeostasis, oxidative stress via protein overload thereby also influencing vital mitochondrial functions. Calcium released from the ER augments the production of mitochondrial Reactive Oxygen Species (ROS). Toxic accumulation of ROS within ER and mitochondria disturbs fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways have been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease, and others. In this review, we have discussed the UPR signaling pathways, and networking between ER stress-induced inflammatory pathways, oxidative stress, and mitochondrial signaling events, which further induce or exacerbate ER stress.

Modulation of stimulus-induced 20-Hz activity for the tongue and hard palate during tongue movement in humans.

PubMed

Maezawa, Hitoshi; Onishi, Kaori; Yagyu, Kazuyori; Shiraishi, Hideaki; Hirai, Yoshiyuki; Funahashi, Makoto

2016-01-01

Modulation of 20-Hz activity in the primary sensorimotor cortex (SM1) may be important for oral functions. Here, we show that 20-Hz event-related desynchronization/synchronization (20-Hz ERD/ERS) is modulated by sensory input and motor output in the oral region. Magnetic 20-Hz activity was recorded following right-sided tongue stimulation during rest (Rest) and self-paced repetitive tongue movement (Move). To exclude proprioception effects, 20-Hz activity induced by right-sided hard palate stimulation was also recorded. The 20-Hz activity in the two conditions was compared via temporal spectral evolution analyses. 20-Hz ERD/ERS was detected over bilateral temporoparietal areas in the Rest condition for both regions. Moreover, 20-Hz ERS was significantly suppressed in the Move condition for both regions. Detection of 20-Hz ERD/ERS during the Rest condition for both regions suggests that the SM1 functional state may be modulated by oral stimulation, with or without proprioceptive effects. Moreover, the suppression of 20-Hz ERS for the hard palate during the Move condition suggests that the stimulation-induced functional state of SM1 may have been modulated by the movement, even though the movement and stimulation areas were different. Sensorimotor function of the general oral region may be finely coordinated through 20-Hz cortical oscillation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

ER-2 Doppler Radar (EDOP) Investigations of the Eyewall of Hurricane Bonnie CAMEX-3

NASA Technical Reports Server (NTRS)

Heymsfield, G. M.; Halverson, J.; Simpson, J.; Tian, L.; Bui, P.; Einaudi, Franco (Technical Monitor)

2000-01-01

A persistent, mesoscale region of intense eyewall convection contained within Hurricane Bonnie on 23 August 1998 is examined from multiple observations synthesized from the NASA ER-2 and DC-8 aircraft. The intense convection occurred late in the day as Bonnie was attaining its minimum central pressure and during a stage when the inner core featured a markedly asymmetric structure. The main purpose of this paper is to describe the internal structure of a convective burst and its relationship to the warm core using a synthesis of high-resolution satellite, aircraft radar, and in situ data. An exceptionally vigorous eyewall tower penetrating to nearly 18 km is described. A second intense eyewall tower, adjacent to the eye, is shown to be associated with a mesoscale subsiding current of air that extends horizontally nearly 20 km into the eye interior. The subsidence occupies a substantial depth within the eye and appears to be a much larger scale feature than the convectively-induced, symmetric overturning which commonly occurs on the upper-level flanks of convective towers in other tropical environments.

TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation.

PubMed

Graham, Daniel B; Lefkovith, Ariel; Deelen, Patrick; de Klein, Niek; Varma, Mukund; Boroughs, Angela; Desch, A Nicole; Ng, Aylwin C Y; Guzman, Gaelen; Schenone, Monica; Petersen, Christine P; Bhan, Atul K; Rivas, Manuel A; Daly, Mark J; Carr, Steven A; Wijmenga, Cisca; Xavier, Ramnik J

2016-12-13

Significant insights into disease pathogenesis have been gleaned from population-level genetic studies; however, many loci associated with complex genetic disease contain numerous genes, and phenotypic associations cannot be assigned unequivocally. In particular, a gene-dense locus on chromosome 11 (61.5-61.65 Mb) has been associated with inflammatory bowel disease, rheumatoid arthritis, and coronary artery disease. Here, we identify TMEM258 within this locus as a central regulator of intestinal inflammation. Strikingly, Tmem258 haploinsufficient mice exhibit severe intestinal inflammation in a model of colitis. At the mechanistic level, we demonstrate that TMEM258 is a required component of the oligosaccharyltransferase complex and is essential for N-linked protein glycosylation. Consequently, homozygous deficiency of Tmem258 in colonic organoids results in unresolved endoplasmic reticulum (ER) stress culminating in apoptosis. Collectively, our results demonstrate that TMEM258 is a central mediator of ER quality control and intestinal homeostasis. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

75 FR 17703 - Combined Notice of Filings # 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-07

...: Southwest Power Pool, Inc submits Substitute Sixth Revised Sheet 14 et al to its FERC Electric Tariff, Fifth...: Central Maine Power Company. Description: Central Maine Power Company submits Engineering and Procurement.... Docket Numbers: ER10-911-001. Applicants: Wisconsin Electric Power Company. Description: Wisconsin...

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.

Validation of a Case Definition for Pediatric Brain Injury Using Administrative Data.

PubMed

McChesney-Corbeil, Jane; Barlow, Karen; Quan, Hude; Chen, Guanmin; Wiebe, Samuel; Jette, Nathalie

2017-03-01

Health administrative data are a common population-based data source for traumatic brain injury (TBI) surveillance and research; however, before using these data for surveillance, it is important to develop a validated case definition. The objective of this study was to identify the optimal International Classification of Disease , edition 10 (ICD-10), case definition to ascertain children with TBI in emergency room (ER) or hospital administrative data. We tested multiple case definitions. Children who visited the ER were identified from the Regional Emergency Department Information System at Alberta Children's Hospital. Secondary data were collected for children with trauma, musculoskeletal, or central nervous system complaints who visited the ER between October 5, 2005, and June 6, 2007. TBI status was determined based on chart review. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each case definition. Of 6639 patients, 1343 had a TBI. The best case definition was, "1 hospital or 1 ER encounter coded with an ICD-10 code for TBI in 1 year" (sensitivity 69.8% [95% confidence interval (CI), 67.3-72.2], specificity 96.7% [95% CI, 96.2-97.2], PPV 84.2% [95% CI 82.0-86.3], NPV 92.7% [95% CI, 92.0-93.3]). The nonspecific code S09.9 identified >80% of TBI cases in our study. The optimal ICD-10-based case definition for pediatric TBI in this study is valid and should be considered for future pediatric TBI surveillance studies. However, external validation is recommended before use in other jurisdictions, particularly because it is plausible that a larger proportion of patients in our cohort had milder injuries.

The SANT domain of human MI-ER1 interacts with Sp1 to interfere with GC box recognition and repress transcription from its own promoter.

PubMed

Ding, Zhihu; Gillespie, Laura L; Mercer, F Corinne; Paterno, Gary D

2004-07-02

To gain insight into the regulation of hmi-er1 expression, we cloned a human genomic DNA fragment containing one of the two hmi-er1 promoters and consisting of 1460 bp upstream of the translation initiation codon of hMI-ER1. Computer-assisted sequence analysis revealed that the hmi-er1 promoter region contains a CpG island but lacks an identifiable TATA element, initiator sequence and downstream promoter element. This genomic DNA was able to direct transcription of a luciferase reporter gene in a variety of human cell lines, and the minimal promoter was shown to be located within-68/+144 bp. Several putative Sp1 binding sites were identified, and we show that Sp1 can bind to the hmi-er1 minimal promoter and increase transcription, suggesting that the level of hmi-er1 expression may depend on the availability of Sp1 protein. Functional analysis revealed that hMI-ER1 represses Sp1-activated transcription from the minimal promoter by a histone deacetylase-independent mechanism. Chromatin immunoprecipitation analysis demonstrated that both Sp1 and hMI-ER1 are associated with the chromatin of the hmi-er1 promoter and that overexpression of hMI-ER1 in cell lines that allow Tet-On-inducible expression resulted in loss of detectable Sp1 from the endogenous hmi-er1 promoter. The mechanism by which this occurs does not involve binding of hMI-ER1 to cis-acting elements. Instead, we show that hMI-ER1 physically associates with Sp1 and that endogenous complexes containing the two proteins could be detected in vivo. Furthermore, hMI-ER1 specifically interferes with binding of Sp1 to the hmi-er1 minimal promoter as well as to an Sp1 consensus oligonucleotide. Deletion analysis revealed that this interaction occurs through a region containing the SANT domain of hMI-ER1. Together, these data reveal a functional role for the SANT domain in the action of co-repressor regulatory factors and suggest that the association of hMI-ER1 with Sp1 represents a novel mechanism for the negative regulation of Sp1 target promoters.

The Fossil Fauna of the Islands Region of Western Lake Erie.

ERIC Educational Resources Information Center

Bowe, Lulu M., Comp.

The islands of western Lake Erie are rock-bound isles that abound in rocky outcrops and quarries. The rocks of these islands are of two distinct types, Silurian dolomites and Devonian limestones. The dolomites, exposed in the Bass Islands and Sister Islands are virtually devoid of fossils. Conversely, the limestones of Johnson Island, Marblehead,…

Central Administration of 1-Deoxynojirimycin Attenuates Hypothalamic Endoplasmic Reticulum Stress and Regulates Food Intake and Body Weight in Mice with High-Fat Diet-Induced Obesity.

PubMed

Kim, Jongwan; Yun, Eun-Young; Quan, Fu-Shi; Park, Seung-Won; Goo, Tae-Won

2017-01-01

The α -glucosidase inhibitor, 1-deoxynojirimycin (DNJ), is widely used for its antiobesity and antidiabetic effects. Researchers have demonstrated that DNJ regulates body weight by increasing adiponectin levels, which affects energy intake and prevents diet-induced obesity. However, the mechanism by which centrally administered DNJ exerts anorexigenic effects has not been studied until now. We investigated the effect of DNJ in the hypothalamus of mice with high-fat diet-induced obesity. Results showed that intracerebroventricular (ICV) administration of DNJ reduced hypothalamic ER stress, which activated the leptin-induced Janus-activated kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway to cause appetite suppression. We conclude that DNJ may reduce obesity by moderating feeding behavior and ER stress in the hypothalamic portion of the central nervous system (CNS).

Cyclopentadienyl Rhenium (Technetium) Tricarbonyl Complexes Integrated in Estrogen Receptor Ligands for ER+ Tumor Imaging

DTIC Science & Technology

2006-10-01

determined by imaging correlate well with those determined by immunoassay methods on surgical biopsies. Because of the short half-life of fluorine -18, this...immunoassay methods on surgical biopsies. Currently, the most effective ER imaging agent is a fluorine -18 labeled estrogen. However, because of the short...substituent to the central pentacycle, including nucleophilic addition of organometallic reagents, addition of electrophiles to the cyclopentadiene

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.

Energy conversion of X-ray, ultraviolet and infrared radiation in Gd2O3 crystals doped with Er3+ ions

NASA Astrophysics Data System (ADS)

Trofimova, E. S.; Pustovarov, V. A.; Kuznetsova, Yu. A.; Zatsepin, A. F.

2017-09-01

Spectra of photoluminescence (PL) and X-ray excited luminescence (XRL) in region of 1.5-5.0 eV, PL excitation spectra (2.8-5.8 eV), PL decay kinetics were measured in Gd2O3 crystals doped both with Er3+ and Zn2+ ions. Synchrotron radiation (VEPP-3 storage ring, Novosibirsk, Russia) were used for XRL measurements. PL spectra were studied at room temperature and T= 88 K under excitation with energy Eexc: a) in fundamental absorption region (Eexc≥Eg); b) in intracenter excitation region (Eexc

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%.

Glioblastoma Multiforme and Lipid Nanocapsules: A Review.

PubMed

Aparicio-Blanco, Juan; Torres-Suárez, Ana-Isabel

2015-08-01

Epidemiological data on central nervous system disorders call for a focus on the major hindrance to brain drug delivery, blood-central nervous system barriers. Otherwise, there is little chance of improving the short-term survival of patients with diseases such as glioblastoma multiforme, which is one of the brain disorders associated with many years of life lost. Targetable nanocarriers for treating malignant gliomas are a unique way to overcome low chemotherapeutic levels at target sites devoid of systemic toxicity. This review describes the currently available targetable nanocarriers, focusing particularly on one of the newest nanocarriers, lipid nanocapsules. All of the strategies that are likely to be exploited by lipid nanocapsules to bypass blood-central nervous system barriers, including the most recent targeting approaches (mesenchymal cells), and novel administration routes (convection enhanced delivery) are discussed, together with their most remarkable achievements in glioma-implanted animal models. Although these systems are promising, much research remains to be done in this field.

Ryegrass cv. Lema and guava cv. Paluma biomonitoring suitability for estimating nutritional contamination risks under seasonal climate in Southeastern Brazil.

PubMed

Bulbovas, Patricia; Camargo, Carla Z S; Domingos, Marisa

2015-08-01

The risks posed by nutrient deposition due to air pollution on ecosystems and their respective services to human beings can be appropriately estimated by bioindicator plants when they are well acclimated to the study region environmental conditions. This assumption encouraged us to comparatively evaluate the accumulation potential of ryegrass cv. Lema and guava cv. Paluma macro and micronutrients. We also indicated the most appropriate species for biomonitoring nutrient contamination risks in tropical areas of Southeastern Brazil, which are characterized by marked dry and wet seasons and complex mixtures of air pollutants from different sources (industries, vehicle traffic and agriculture). The study was conducted in 14 sites with different neighboring land uses, within the Metropolitan Region of Campinas, central-eastern region of São Paulo State. The exposure experiments with ryegrass and guava were consecutively repeated 40 (28 days each) and 12 (84 days each) times, respectively, from Oct/2010 to Sept/2013. Macro and micronutrients were analyzed and background concentrations and enrichment ratios (ER) were estimated to classify the contamination risk within the study region. Significantly higher ER suggested that ryegrass were the most appropriate accumulator species for N, S, Mg, Fe, Mn, Cu and Zn deposition and guava for K, Ca, P and B deposition. Based on these biomonitoring adjustments, we concluded that the nutrient deposition was spatially homogeneous in the study area, but clear seasonality in the contamination risk by nutritional inputs was evidenced. Significantly higher contamination risk by S, Fe, K and B occurred during the dry season and enhanced contamination risk by Mn, Cu and Zn were highlighted during the wet season. Distinctly high contamination risk was estimated for S, Fe and Mn in several exposure experiments. Copyright © 2015 Elsevier Inc. All rights reserved.

Initial activation of STIM1, the regulator of store-operated calcium entry

PubMed Central

Zhou, Yubin; Srinivasan, Prasanna; Razavi, Shiva; Seymour, Sam; Meraner, Paul; Gudlur, Aparna; Stathopulos, Peter B; Ikura, Mitsuhiko; Rao, Anjana; Hogan, Patrick G

2013-01-01

Physiological Ca2+ signalling in T lymphocytes and other cells depends on the STIM-ORAI pathway of store-operated Ca2+ entry. STIM1 and STIM2 are Ca2+ sensors located in the endoplasmic reticulum (ER) membrane, with ER-luminal domains that monitor cellular Ca2+ stores and cytoplasmic domains that gate ORAI channels in the plasma membrane. The STIM ER-luminal domain dimerizes or oligomerizes upon dissociation of Ca2+, but the mechanism transmitting activation to the STIM cytoplasmic domain has not been defined. Here we demonstrate, using Tb3+–acceptor energy transfer, that dimerization of STIM1 ER-luminal domains can initiate an extensive conformational change in murine STIM1 cytoplasmic domains. The conformational change, triggered by apposition of the predicted coiled-coil 1 (CC1) regions, releases the ORAI-activating domains from their interaction with the CC1 regions and allows physical extension of the STIM1 cytoplasmic domain across the gap between ER and plasma membrane to communicate with ORAI channels. PMID:23851458

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.

Endoplasmic reticulum stress in the pathogenesis of hypertension.

PubMed

Young, Colin N

2017-08-01

What is the topic of this review? This review highlights the emerging role of disruptions in endoplasmic reticulum (ER) function, namely ER stress, as a contributor to hypertension. What advances does it highlight? This review presents an integrative view of ER stress in cardiovascular control systems, including systems within the brain, kidney and peripheral vasculature, as related to development of hypertension. The endoplasmic reticulum (ER) is a cellular organelle specialized in the synthesis, folding, assembly and modification of proteins. In situations of increased protein demand, complex signalling pathways, termed the unfolded protein response, influence a series of cellular feedback loops to control ER function strictly. Although this is initially a compensatory attempt to maintain cellular homeostasis, chronic activation of the unfolded protein response, known as ER stress, leads to sustained changes in cellular function. A growing body of literature points to ER stress in diverse cardioregulatory systems, including the brain, kidney and vasculature, as central to the development of hypertension. Here, these recent findings from essential and obesity-related forms of hypertension are highlighted in an integrative manner, with discussion of the potential upstream causes and downstream consequences of ER stress. Given that hypertension is a leading medical and socio-economic global challenge, emerging findings suggest that targeting ER stress might represent a viable strategy for the treatment of hypertensive disease. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

25 years of elevation changes of the Greenland Ice Sheet from ERS, Envisat, and CryoSat-2 radar altimetry

NASA Astrophysics Data System (ADS)

Sandberg Sørensen, Louise; Simonsen, Sebastian B.; Forsberg, René; Khvorostovsky, Kirill; Meister, Rakia; Engdahl, Marcus E.

2018-08-01

The shape of the large ice sheets responds rapidly to climate change, making the elevation changes of these ice-covered regions an essential climate variable. Consistent, long time series of these elevation changes are of great scientific value. Here, we present a newly-developed data product of 25 years of elevation changes of the Greenland Ice Sheet, derived from satellite radar altimetry. The data product is made publicly available within the Greenland Ice Sheets project as part of the ESA Climate Change Initiative programme. Analyzing repeated elevation measurements from radar altimetry is widely used for monitoring changes of ice-covered regions. The Greenland Ice Sheet has been mapped by conventional radar altimetry since the launch of ERS-1 in 1991, which was followed by ERS-2, Envisat and currently CryoSat-2. The recently launched Sentinel-3A will provide a continuation of the radar altimetry time series. Since 2010, CryoSat-2 has for the first time measured the changes in the coastal regions of the ice sheet with radar altimetry, with its novel SAR Interferometric (SARIn) mode, which provides improved measurement over regions with steep slopes. Here, we apply a mission-specific combination of cross-over, along-track and plane-fit elevation change algorithms to radar data from the ERS-1, ERS-2, Envisat and CryoSat-2 radar missions, resulting in 25 years of nearly continuous elevation change estimates (1992-2016) of the Greenland Ice Sheet. This analysis has been made possible through the recent reprocessing in the REAPER project, of data from the ERS-1 and ERS-2 radar missions, making them consistent with Envisat data. The 25 years of elevation changes are evaluated as 5-year running means, shifted almost continuously by one year. A clear acceleration in thinning is evident in the 5-year maps of elevation following 2003, while only small elevation changes observed in the maps from the 1990s.

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.

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.

78 FR 65636 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

...-001 Applicants: AEP Texas Central Company Description: TCC-TNC-South Texas Electric Cooperative Amd... p.m. ET 11/15/13 Docket Numbers: ER13-2289-001 Applicants: AEP Texas North Company Description: TCC...: AEP Texas Central Company Description: TCC-TNC-Texas New Mexico Power Company ERCOT TSA to be...

77 FR 65872 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-31

...-000. Applicants: AEP Texas Central Company. Description: TCC-Sendero Wind Energy PDA to be effective...: AEP Texas Central Company. Description: TCC-Midway Farms Wind IA to be effective 9/24/2012. Filed Date.... Docket Numbers: ER13-177-000. Applicants: AEP Texas North Company. Description: TNC-Higher Power Energy...

A Molecular Web: Endoplasmic Reticulum Stress, Inflammation, and Oxidative Stress

PubMed Central

Chaudhari, Namrata; Talwar, Priti; Parimisetty, Avinash; Lefebvre d’Hellencourt, Christian; Ravanan, Palaniyandi

2014-01-01

Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse but, inflammation and/or ER stress may be basic mechanisms increasing the severity or complicating the condition of the disease. Chronic ER stress and activation of the unfolded-protein response (UPR) through endogenous or exogenous insults may result in impaired calcium and redox homeostasis, oxidative stress via protein overload thereby also influencing vital mitochondrial functions. Calcium released from the ER augments the production of mitochondrial Reactive Oxygen Species (ROS). Toxic accumulation of ROS within ER and mitochondria disturbs fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways have been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease, and others. In this review, we have discussed the UPR signaling pathways, and networking between ER stress-induced inflammatory pathways, oxidative stress, and mitochondrial signaling events, which further induce or exacerbate ER stress. PMID:25120434

Software aspects of the Geant4 validation repository

NASA Astrophysics Data System (ADS)

Dotti, Andrea; Wenzel, Hans; Elvira, Daniel; Genser, Krzysztof; Yarba, Julia; Carminati, Federico; Folger, Gunter; Konstantinov, Dmitri; Pokorski, Witold; Ribon, Alberto

2017-10-01

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 is easily accessible 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 article, we describe the functionality and the current status of various components of DoSSiER as well as the technology choices we made.

Software Aspects of the Geant4 Validation Repository

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

Dotti, Andrea; Wenzel, Hans; Elvira, Daniel

2016-01-01

The Geant4, GeantV and GENIE collaborations regularly perform validation and regression tests for simulation results. DoSSiER (Database of Scientic 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 is easily accessible 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 article, we describe the functionality and the current status of various components of DoSSiER as well as the technology choices we made.

Bivalent ligands that target μ opioid (MOP) and cannabinoid1 (CB1) receptors are potent analgesics devoid of tolerance.

PubMed

Le Naour, Morgan; Akgün, Eyup; Yekkirala, Ajay; Lunzer, Mary M; Powers, Mike D; Kalyuzhny, Alexander E; Portoghese, Philip S

2013-07-11

Given that μ opioid (MOP) and canabinoid (CB1) receptors are colocalized in various regions of the central nervous system and have been reported to associate as heteromer (MOP-CB1) in cultured cells, the possibility of functional, endogenous MOP-CB1 in nociception and other pharmacologic effects has been raised. As a first step in investigating this possibility, we have synthesized a series of bivalent ligands 1-5 that contain both μ agonist and CB1 antagonist pharmacophores for use as tools to study the functional interaction between MOP and CB1 receptors in vivo. Immunofluorescent studies on HEK293 cells coexpressing both receptors suggested 5 (20-atom spacer) to be the only member of the series that bridges the protomers of the heteromer. Antinociceptive testing in mice revealed 5 to be the most potent member of the series. As neither a mixture of monovalent ligands 9 + 10 nor bivalents 2-5 produced tolerance in mice, MOR-CB1 apparently is not an important target for reducing tolerance.

Geology of the Stegall Mountain 7.5-minute quadrangle, Shannon and Carter Counties, south-central Missouri

USGS Publications Warehouse

Harrison, Richard W.; Orndorff, Randall C.; Weary, David J.

2002-01-01

The bedrock exposed in the Stegall Mountain Quadrangle, Missouri, comprises Mesoproterozoic aged volcanic rocks overlain by Late Cambrian and Early Ordovician aged dolomite, sandstone, and chert. The sedimentary rocks are nearly flat-lying except where they drape around knobs of the volcanic rocks or where they are adjacent to faults. The carbonates are karstified and the area contains numerous sinkholes, springs, caves, and losing-streams. This map is one of several being produced under the U.S. Geological Survey National Cooperative Geologic Mapping Program to provide geologic data applicable to land-use problems in the Ozarks of south-central Missouri. Ongoing and potential industrial and agricultural development in the Ozarks region has presented issues of ground-water quality in karst areas. A National Park in this region (Ozark National Scenic Riverways, Missouri ) is concerned about the effects of activities in areas outside of their stewardship on the water resources that define the heart of this Park. This task applies geologic mapping and karst investigations to address issues surrounding competing land use in south-central Missouri. This task keeps geologists from the USGS associated with the park and allows the Parks to utilize USGS expertise and aid the NPS on how to effectively use geologic maps for Park management. For more information see: http://geology.er.usgs.gov/eespteam/Karst/index.html

Geologic Map of the Wilderness and Handy Quadrangles, Oregon, Carter, and Ripley Counties, Missouri

USGS Publications Warehouse

Harrison, Richard W.; McDowell, Robert C.

2003-01-01

The bedrock exposed in the Wilderness and Handy Quadrangles, Missouri, comprises Early Ordovician aged dolomite, sandstone, and chert. The sedimentary rocks are nearly flat-lying except where they are adjacent to faults. The carbonate rocks are karstified and the area contains numerous sinkholes, springs, caves, and losing-streams. This map is one of several being produced under the U.S. Geological Survey National Cooperative Geologic Mapping Program to provide geologic data applicable to land-use problems in the Ozarks of south-central Missouri. Ongoing and potential industrial and agricultural development in the Ozarks region has presented issues of ground-water quality in karst areas. These quadrangles contain significant areas of the Mark Twain National Forest, including part of the Eleven Point National Scenic Riverway and the Irish Wilderness Roadless Area. A National Park in this region (Ozark National Scenic Riverways, Missouri ) is concerned about the effects of activities in areas outside of their stewardship on the water resources that define the heart of this Park. This task applies geologic mapping and karst investigations to address issues surrounding competing land use in south-central Missouri. For more information see: http://geology.er.usgs.gov/eespteam/Karst/index.html

Geologic map of the Fremont quadrangle, Shannon, Carter, and Oregon Counties, Missouri

USGS Publications Warehouse

Orndorff, Randall C.

2003-01-01

The bedrock exposed in the Fremont Quadrangle, Missouri, comprises Early Ordovician aged dolomite, sandstone, and chert. The sedimentary rocks are nearly flat-lying except where they are adjacent to faults. The carbonate rocks are karstified and the area contains numerous sinkholes, springs, caves, and losing-streams. This map is one of several being produced under the U.S. Geological Survey National Cooperative Geologic Mapping Program to provide geologic data applicable to land-use problems in the Ozarks of south-central Missouri. Ongoing and potential industrial and agricultural development in the Ozarks region has presented issues of ground-water quality in karst areas. National Park in this region (Ozark National Scenic Riverways, Missouri) is concerned about the effects of activities in areas outside of their stewardship on the water resources that define the heart of this Park. This task applies geologic mapping and karst investigations to address issues surrounding competing land use in south-central Missouri. This task keeps geologists from the USGS associated with the park and allows the Parks to utilize USGS expertise and aid the NPS on how to effectively use geologic maps for Park management. For more information see: http://geology.er.usgs.gov/eespteam/Karst/index.html

Brainstem Regions Involved in the Expiration Reflex. A c-fos Study in Anesthetized Cats

PubMed Central

Poliacek, Ivan; Halasova, Erika; Jakus, Jan; Murin, Peter; Barani, Helena; Stransky, Albert; Bolser, Donald C

2009-01-01

Expression of the immediate-early gene c-fos, a marker of neuronal activation, was employed to localize brainstem neuronal populations functionally related to the expiration reflex (ER). Twelve spontaneously breathing, non-decerebrate, pentobarbital anesthetized cats were used. The level of Fos-like immunoreactivity (FLI) in 6 animals with repetitive ERs mechanically induced from the glottis (296±9 ERs) was compared to FLI in 6 control non-stimulated cats. Respiratory rate, arterial blood pressure, and end tidal CO2 concentration remained stable during the experiment. In the medulla, increased FLI was found in the region of nucleus tractus solitarii (p<0.001), in the ventrolateral medulla along with the lateral tegmental field (p<0.01), and in the vestibular nuclei (p<0.01). In the pons, increased FLI was detected in the caudal extensions of the lateral parabrachial and Kölliker-Fuse nuclei (p<0.05). Within the rostral mesencephalon FLI was enhanced in the midline area (p<0.05). A lower level of ER-related FLI compared to control animals was detected in the pontine raphe region (p<0.05) and the lateral division of mesencephalic periaqueductal gray (p<0.05). The results suggest that the ER is coordinated by a complex long loop of medullary-pontine-mesencephalic neuronal circuits, some of which may differ from those of other respiratory reflexes. The FLI related to the expulsive behavior ER differs from that induced by laryngeal stimulation and laryngeal adductor responses, particularly in ventrolateral medulla and mesencephalon. PMID:17964550

Late-onset of spinal neurodegeneration in knock-in mice expressing a mutant BiP.

PubMed

Jin, Hisayo; Mimura, Naoya; Kashio, Makiko; Koseki, Haruhiko; Aoe, Tomohiko

2014-01-01

Most human neurodegenerative diseases are sporadic, and appear later in life. While the underlying mechanisms of the progression of those diseases are still unclear, investigations into the familial forms of comparable diseases suggest that endoplasmic reticulum (ER) stress is involved in the pathogenesis. Binding immunoglobulin protein (BiP) is an ER chaperone that is central to ER function. We produced knock-in mice expressing a mutant BiP that lacked the retrieval sequence in order to evaluate the effect of a functional defect in an ER chaperone in multi-cellular organisms. Here we report that heterozygous mutant BiP mice revealed motor disabilities in aging. We found a degeneration of some motoneurons in the spinal cord accompanied by accumulations of ubiquitinated proteins. The defect in retrieval of BiP by the KDEL receptor leads to impaired activities in quality control and autophagy, suggesting that functional defects in the ER chaperones may contribute to the late onset of neurodegenerative diseases.

Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue.

PubMed

Kawasaki, Noritaka; Asada, Rie; Saito, Atsushi; Kanemoto, Soshi; Imaizumi, Kazunori

2012-01-01

Adipose tissue plays a central role in maintaining metabolic homeostasis under normal conditions. Metabolic diseases such as obesity and type 2 diabetes are often accompanied by chronic inflammation and adipose tissue dysfunction. In this study, we observed that endoplasmic reticulum (ER) stress and the inflammatory response occurred in adipose tissue of mice fed a high-fat diet for a period of 16 weeks. After 16 weeks of feeding, ER stress markers increased and chronic inflammation occurred in adipose tissue. We found that ER stress is induced by free fatty acid (FFA)-mediated reactive oxygen species (ROS) generation and up-regulated gene expression of inflammatory cytokines in 3T3-L1 adipocytes. Oral administration to obese mice of chemical chaperons, which alleviate ER stress, improved chronic inflammation in adipose tissue, followed by the suppression of increased body weight and improved insulin signaling. These results indicate that ER stress plays important pathophysiological roles in obesity-induced adipose tissue dysfunction.

β-Cell Dysfunction Due to Increased ER Stress in a Stem Cell Model of Wolfram Syndrome

PubMed Central

Shang, Linshan; Hua, Haiqing; Foo, Kylie; Martinez, Hector; Watanabe, Kazuhisa; Zimmer, Matthew; Kahler, David J.; Freeby, Matthew; Chung, Wendy; LeDuc, Charles; Goland, Robin; Leibel, Rudolph L.; Egli, Dieter

2014-01-01

Wolfram syndrome is an autosomal recessive disorder caused by mutations in WFS1 and is characterized by insulin-dependent diabetes mellitus, optic atrophy, and deafness. To investigate the cause of β-cell failure, we used induced pluripotent stem cells to create insulin-producing cells from individuals with Wolfram syndrome. WFS1-deficient β-cells showed increased levels of endoplasmic reticulum (ER) stress molecules and decreased insulin content. Upon exposure to experimental ER stress, Wolfram β-cells showed impaired insulin processing and failed to increase insulin secretion in response to glucose and other secretagogues. Importantly, 4-phenyl butyric acid, a chemical protein folding and trafficking chaperone, restored normal insulin synthesis and the ability to upregulate insulin secretion. These studies show that ER stress plays a central role in β-cell failure in Wolfram syndrome and indicate that chemical chaperones might have therapeutic relevance under conditions of ER stress in Wolfram syndrome and other forms of diabetes. PMID:24227685

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.

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

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)

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.

Description of the physical environment an coal-mining history of West-Central Indiana, with emphasis on six small watersheds

USGS Publications Warehouse

Martin, Jeffrey D.; Crawford, Charles G.; Duwelius, Richard F.; Renn, Danny E.

1990-01-01

Pond Creek and the unnamed tributary to Big Branch are streams that drain mined and unreclaimed watersheds. Approximately one-half of the Pond Creek watershed is unmined, agricultural land. Soils are very well-drained shaly silty loams that have formed or' steeply sloping spoil banks. Both watersheds contain numerous impoundments of water and have enclosed areas that do not contribute surface runoff to streamflow. The ridges of mine spoil are covered with pine trees, but much of the soil surface is devoid of vegetation.

The megageomorphology of the radar rivers of the eastern Sahara

NASA Technical Reports Server (NTRS)

Mccauley, John F.; Breed, Carol S.; Schaber, Gerald G.

1986-01-01

The Eastern Sahara is devoid of surface drainage; this unusual characteristic distinguishes its morphology from that of most other desert regions where running water dominates landscape development. A map derived from SIR-A/B and LANDSAT images and the literature, shows the major presently known paleodrainages in the Eastern Sahara. This compilation permits consideration of the key questions: Where did the radar rivers come from and where did they go? Analysis of SIR-A data led McCauley et al. to suggest that the radar rivers, because of their southwestward trends, once flowed into the Chad basin. This key North African feature is a regional structural low formed in the Early Cretaceous in response to initial opening of the South Atlantic. The problem of the origin of headwaters for the radar rivers was less tractable. The idea that the source areas of the radar rivers might originally have been the same as those later captured by the Nile was proposed tentatively. A more extensive review of the Cenozoic tectonic history of North Africa reveals no reason now to suppose that the Central African tributaries of the present Nile were ever connected to the large alluvial valleys in southwestern Egypt and northwestern Sudan. formed in the Early Cretaceous in response to initial opening of the South Atlantic. The problem of the origin of headwaters for the radar rivers was less tractable. The idea that the source areas of the radar rivers might originally have been the same as those (The Ethiopian Highlands) later captured by the Nile was proposed tentatively. A more extensive review of the Cenozoic tectonic history of North Africa reveals no reason now to support that the Central African tributaries of the present Nile were ever connected to the large alluvial valleys in southwestern Egypt and northwestern Sudan.

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.

Characteristics of breast cancer in Central China, literature review and comparison with USA.

PubMed

Chen, Chuang; Sun, Si; Yuan, Jing-Ping; Wang, Yao-Huai; Cao, Tian-Ze; Zheng, Hong-Mei; Jiang, Xue-Qing; Gong, Yi-Ping; Tu, Yi; Yao, Feng; Hu, Ming-Bai; Li, Juan-Juan; Sun, Sheng-Rong; Wei, Wen

2016-12-01

This work was to analyze characteristics of breast cancer (BC) in Central China, summarize main characteristics in China and compare with USA. BC main characteristics from four hospitals in Central China from 2002 to 2012 were collected and analyzed. All the single and large-scale clinical reports covering at least ten years were selected and summarized to calculate the BC characteristics of China. BC Characteristics in USA were selected based on the database from Surveillance, Epidemiology, and End Results (SEER) Program. Age distribution in Central China was normal with one age peak at 45-49 years, displaying differences from USA and Chinese American with two age peaks. BC characteristics in Central China displayed distinct features from USA and Chinese American, including significant younger onset age, lower proportion of patients with stage I, lymph node negative, small tumor size and ER positive. A total ten long-term and large-scale clinical reports were selected for BC characteristics of Mainland China analysis. A total of 53,571 BC patients were enrolled from 1995 to 2012. The main characteristics of BC in Mainland China were similar as that in Central China, but were significant different from developed regions of China (Hong Kong and Taiwan), USA and Chinese American. BC characteristics in Central China displayed representative patterns of Mainland China, while showed distinct patterns from Chinese patients in other developed areas and USA. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Heat flow and thermal processes in the Jornada delMuerto, New Mexico

NASA Technical Reports Server (NTRS)

Reiter, M.

1985-01-01

Most heat flow data in rifts are uncertain largely because of hydrologic disturbances in regions of extensive fracturing. Estimates of heat flow in deep petroleum tests within a large basin of the Rio Grande rift, which has suffered little syn-rift fracturing, may begin to provide clearer insight into the relationships between high heat flow and crustal thinning processes. The Jornada del Muerto is a large basin located in the Rio Grande rift of south central New Mexico. The region of interest within the Jornada del Muerto is centered about 30 km east of the town of Truth or Consequences, and is approximately 60 km north-south by 30 km east-west. High heat flows are estimated for the region. Values increase from about 90 mWm(-2) in the northern part of the study area to about 125 mWm(-2) in the southern part. These high heat flows are rather enigmatic because in the immediate vicinities of the sites there is little evidence of Cenozoic volcanism or syn-rift extensional tectonics. It is suggested that the geothermal anomaly in the southern Jornada del Muerto (approx. 125 to approx. 95 mWm(-2) results from some type of mass movement-heat transfer mechanism operating in the crust just below the elastic layer. This conclusion is consistent with the geologic and geophysical data which describe a thin crust, apparently devoid of features indicative of extensional-tectonics in the upper part of the lastic crust.

Eta Carinae and the Homunculus: An Astrophysical Laboratory

NASA Technical Reports Server (NTRS)

Gull, Theodore R.

2006-01-01

High spatial resolution spectroscopy with HST/STIS between 1998.0 and 2004.2 has provided much exciting information about the central binary system and the physics of its N-rich, C,O-poor ejecta. Stellar He I profiles, noticeably blue-shifted relative to P Cygni H and Fe II line profiles, originate from the ionized wind region between two massive companions. Changes in profiles of He I singlet and triplet lines provide clues to the excitation mechanisms involved as the hot, UV companion moves in its highly eccentric orbit. For 90% of the 5.54-year period, the spectra of nearby Weigelt blobs and the Little Homunculus include highly excited emission lines of Ar, Ne, and Fe. During the few month-long spectroscopic minimum, these systems are deprived of Lyman continuum. Recombination, plus cooling, occurs. In the skirt region between the bipolar Homunculus, a neutral emission region, devoid of hydrogen emission, glows in Ti II, Fe I, Sr II, Sc II, etc. We find the ejecta to have Ti/Ni abundances nearly 100 times solar, not due to nuclear processing, but due to lack of oxygen. Many metals normally tied up in interstellar dust remain in gaseous phase. Much information is being obtained on the physical processes in these warm N-rich gases, whose excitation varies with time in a predictable pattern. Indeed recent GRB high dispersion spectra include signatures of circumGRB warm gases. This indicates that the early, primordial massive stars have warm massive ejecta reminiscent to that around Eta Carinae.

COMPACT DUST CONCENTRATION IN THE MWC 758 PROTOPLANETARY DISK

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

Marino, S.; Casassus, S.; Perez, S.

2015-11-01

The formation of planetesimals requires that primordial dust grains grow from micron- to kilometer-sized bodies. Dust traps caused by gas pressure maxima have been proposed as regions where grains can concentrate and grow fast enough to form planetesimals, before radially migrating onto the star. We report new VLA Ka and Ku observations of the protoplanetary disk around the Herbig Ae/Be star MWC 758. The Ka image shows a compact emission region in the outer disk, indicating a strong concentration of big dust grains. Tracing smaller grains, archival ALMA data in band 7 continuum shows extended disk emission with an intensitymore » maximum to the northwest of the central star, which matches the VLA clump position. The compactness of the Ka emission is expected in the context of dust trapping, as big grains are trapped more easily than smaller grains in gas pressure maxima. We develop a nonaxisymmetric parametric model inspired by a steady-state vortex solution with parameters adequately selected to reproduce the observations, including the spectral energy distribution. Finally, we compare the radio continuum with SPHERE scattered light data. The ALMA continuum spatially coincides with a spiral-like feature seen in scattered light, while the VLA clump is offset from the scattered light maximum. Moreover, the ALMA map shows a decrement that matches a region devoid of scattered polarized emission. Continuum observations at a different wavelength are necessary to conclude whether the VLA-ALMA difference is an opacity or a real dust segregation.« less

Plant Virus Infection and the Ubiquitin Proteasome Machinery: Arms Race along the Endoplasmic Reticulum.

PubMed

Verchot, Jeanmarie

2016-11-19

The endoplasmic reticulum (ER) is central to plant virus replication, translation, maturation, and egress. Ubiquitin modification of ER associated cellular and viral proteins, alongside the actions of the 26S proteasome, are vital for the regulation of infection. Viruses can arrogate ER associated ubiquitination as well as cytosolic ubiquitin ligases with the purpose of directing the ubiquitin proteasome system (UPS) to new targets. Such targets include necessary modification of viral proteins which may stabilize certain complexes, or modification of Argonaute to suppress gene silencing. The UPS machinery also contributes to the regulation of effector triggered immunity pattern recognition receptor immunity. Combining the results of unrelated studies, many positive strand RNA plant viruses appear to interact with cytosolic Ub-ligases to provide novel avenues for controlling the deleterious consequences of disease. Viral interactions with the UPS serve to regulate virus infection in a manner that promotes replication and movement, but also modulates the levels of RNA accumulation to ensure successful biotrophic interactions. In other instances, the UPS plays a central role in cellular immunity. These opposing roles are made evident by contrasting studies where knockout mutations in the UPS can either hamper viruses or lead to more aggressive diseases. Understanding how viruses manipulate ER associated post-translational machineries to better manage virus-host interactions will provide new targets for crop improvement.

Simulation study on the trembling shear behavior of eletrorheological fluid.

PubMed

Yang, F; Gong, X L; Xuan, S H; Jiang, W Q; Jiang, C X; Zhang, Z

2011-07-01

The trembling shear behavior of electrorheological (ER) fluids has been investigated by using a computer simulation method, and a shear-slide boundary model is proposed to understand this phenomenon. A thiourea-doped Ba-Ti-O ER fluid which shows a trembling shear behavior was first prepared and then systematically studied by both theoretical and experimental methods. The shear curves of ER fluids in the dynamic state were simulated with shear rates from 0.1 to 1000 s(-1) under different electric fields. The simulation results of the flow curves match the experimental results very well. The trembling shear curves are divided into four regions and each region can be explained by the proposed model.

Intrahospital teleradiology from the emergency room

NASA Astrophysics Data System (ADS)

Fuhrman, Carl R.; Slasky, B. S.; Gur, David; Lattner, Stefanie; Herron, John M.; Plunkett, Michael B.; Towers, Jeffrey D.; Thaete, F. Leland

1993-09-01

Off-hour operations of the modern emergency room presents a challenge to conventional image management systems. To assess the utility of intrahospital teleradiology systems from the emergency room (ER), we installed a high-resolution film digitizer which was interfaced to a central archive and to a workstation at the main reading room. The system was designed to allow for digitization of images as soon as the films were processed. Digitized images were autorouted to both destinations, and digitized images could be laser printed (if desired). Almost real time interpretations of nonselected cases were performed at both locations (conventional film in the ER and a workstation in the main reading room), and an analysis of disagreements was performed. Our results demonstrate that in spite of a `significant' difference in reporting, `clinically significant differences' were found in less than 5% of cases. Folder management issues, preprocessing, image orientation, and setting reasonable lookup tables for display were identified as the main limitations to the systems' routine use in a busy environment. The main limitation of the conventional film was the identification of subtle abnormalities in the bright regions of the film. Once identified on either system (conventional film or soft display), all abnormalities were visible and detectable on both display modalities.

For Debate: Personalized Health Care: As Exemplified by Home Sodium Measurements in a Child with Central Diabetes Insipidus and Impaired Thirst Perception.

PubMed

van der Linde, A A A; van Herwaarden, A E; Oosting, J D; Claahsen-van der Grinten, H L; de Grouw, E P L M

2018-04-01

We describe a 6-year old boy with central diabetes insipidus (CDI) caused by destruction of the pituitary gland due to treatment of an optical pathway glioma. He has been treated with chemotherapy and has had several debulking operations over the past years and consequently developed central hypocortisolism, hypothyroidism and CDI. The treatment of CDI was gravely complicated by an impaired thirst perception and compulsive drinking behavior. He was frequently seen at the ER or admitted due to dysregulation of fluid balance. In order to provide better self-reliance, home point of care testing (POCT) sodium measurement was introduced. Realizing POCT sodium measurement resulted in a significant decrease of ER visits and clinical admissions due to dysregulation of fluid balance. This case is an example of personalized health care and has led to better self-reliance and quality of life. Copyright© of YS Medical Media ltd.

Improved Outcomes of Breast-Conserving Therapy for Patients With Ductal Carcinoma in Situ

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

Halasz, Lia M.; Sreedhara, Meera; Chen, Yu-Hui

2012-03-15

Purpose: Patients treated for ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) and radiation therapy (RT) at our center from 1976 to 1990 had a 15% actuarial 10-year local recurrence (LR) rate. Since then, improved mammographic and pathologic evaluation and greater attention to achieving negative margins may have resulted in a lower risk of LR. In addition, clinical implications of hormone receptor and HER-2 status in DCIS remain unclear. We sought to determine the following: LR rates with this more modern approach; the relation between LR and HER-2 status; and clinical and pathologic factors associated with HER-2{sup +} DCIS.more » Methods and Materials: We studied 246 consecutive patients who underwent BCS and RT for DCIS from 2001 to 2007. Of the patients, 96 (39%) were Grade III and the median number of involved tissue blocks was 3. Half underwent re-excision and 222 (90%) had negative margins (>2 mm). All received whole-breast RT (40-52 Gy) and 99% (244) received a tumor bed boost (8-18 Gy). Routine estrogen receptor (ER), progesterone receptor (PR), and HER-2 immunohistochemistry was instituted in 2003. Results: With median follow-up of 58 months, there were no LRs. Seven patients (3%) developed contralateral breast cancer (4 invasive and 3 in situ). Among 163 patients with immunohistochemistry, 124 were ER/PR{sup +}HER-2{sup -}, 27 were ER/PR{sup +}HER-2{sup +}, 6 were ER{sup -}/PR{sup -}HER-2{sup +}, and 6 were ER{sup -}/PR{sup -}HER-2{sup -}. On univariable analysis, HER-2{sup +}was significantly associated with Grade III, ER{sup -}/PR{sup -}, central necrosis, comedo subtype, more extensive DCIS, and postmenopausal status. On multivariable analysis, Grade III and postmenopausal status remained significantly associated with HER-2{sup +}. Conclusions: In an era of mammographically identified DCIS, larger excisions, widely negative margins and the use of a tumor bed boost, we observed no LR regardless of ER/PR/HER-2 status. Factors associated with HER-2{sup +}DCIS included more extensive DCIS, Grade III, ER{sup -}/PR{sup -}, central necrosis, comedo subtype, and postmenopausal status. Further follow-up and additional studies are required to confirm these results.« less

Estrogen Receptor α L543A,L544A Mutation Changes Antagonists to Agonists, Correlating with the Ligand Binding Domain Dimerization Associated with DNA Binding Activity*

PubMed Central

Arao, Yukitomo; Hamilton, Katherine J.; Coons, Laurel A.; Korach, Kenneth S.

2013-01-01

A ligand-dependent nuclear transcription factor, ERα has two transactivating functional domains (AF), AF-1 and AF-2. AF-1 is localized in the N-terminal region, and AF-2 is distributed in the C-terminal ligand-binding domain (LBD) of the ERα protein. Helix 12 (H12) in the LBD is a component of the AF-2, and the configuration of H12 is ligand-inducible to an active or inactive form. We demonstrated previously that the ERα mutant (AF2ER) possessing L543A,L544A mutations in H12 disrupts AF-2 function and reverses antagonists such as fulvestrant/ICI182780 (ICI) or 4-hydoxytamoxifen (OHT) into agonists in the AF2ER knock-in mouse. Our previous in vitro studies suggested that the mode of AF2ER activation is similar to the partial agonist activity of OHT for WT-ERα. However, it is still unclear how antagonists activate ERα. To understand the molecular mechanism of antagonist reversal activity, we analyzed the correlation between the ICI-dependent estrogen-responsive element-mediated transcription activity of AF2ER and AF2ER-LBD dimerization activity. We report here that ICI-dependent AF2ER activation correlated with the activity of AF2ER-LBD homodimerization. Prevention of dimerization impaired the ICI-dependent ERE binding and transcription activity of AF2ER. The dislocation of H12 caused ICI-dependent LBD homodimerization involving the F-domain, the adjoining region of H12. Furthermore, F-domain truncation also strongly depressed the dimerization of WT-ERα-LBD with antagonists but not with E2. AF2ER activation levels with ICI, OHT, and raloxifene were parallel with the degree of AF2ER-LBD homodimerization, supporting a mechanism that antagonist-dependent LBD homodimerization involving the F-domain results in antagonist reversal activity of H12-mutated ERα. PMID:23733188

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-site feedback about volounteers and citizens needs within pilot groups activities. The app modules will be later re-designed according to the methodological and technical feedback gained during pilot study. Training curricula for citizens are planned to increase awareness, skills on smart phone utilities and efficient jargon for hazard contest. The expected results are: a) an easy-to-use interface for "human-data" in crisis support, b) a maximised utility of peer-produced data gathering, c) the development of human resources as technical tools d) a self-based awareness improvement.

Kinematics of the Ethiopian Rift and Absolute motion of Africa and Somalia Plates

NASA Astrophysics Data System (ADS)

Muluneh, A. A.; Cuffaro, M.; Doglioni, C.

2013-12-01

The Ethiopian Rift (ER), in the northern part of East African Rift System (EARS), forms a boundary zone accommodating differential motion between Africa and Somalia Plates. Its orientation was influenced by the inherited Pan-African collisional system and related lithospheric fabric. We present the kinematics of ER derived from compilation of geodetic velocities, focal mechanism inversions, structural data analysis, and construction of geological profiles. GPS velocity field shows a systematic eastward magnitude increase in NE direction in the central ER. In the same region, incremental extensional strain axes recorded by earthquake focal mechanism and fault slip inversion show ≈N1000E orientation. This deviation between GPS velocity trajectories and orientation of incremental extensional strain is developed due to left lateral transtensional deformation. This interpretation is consistent with the en-échelon pattern of tensional and transtensional faults, the distribution of the volcanic centers, and the asymmetry of the rift itself. Small amount of vertical axis blocks rotation, sinistral strike slip faults and dyke intrusions in the rift accommodate the transtensional deformation. We analyzed the kinematics of ER relative to Deep and Shallow Hot Spot Reference Frames (HSRF). Comparison between the two reference frames shows different kinematics in ER and also Africa and Somalia plate motion both in magnitude and direction. Plate spreading direction in shallow HSRF (i.e. the source of the plumes locates in the asthenosphere) and the trend of ER deviate by about 27°. Shearing and extension across the plate boundary zone contribute both to the style of deformation and overall kinematics in the rift. We conclude that the observed long wavelength kinematics and tectonics are consequences of faster SW ward motion of Africa than Somalia in the shallow HSRF. This reference frame seems more consistent with the geophysical and geological constraints in the Rift. The faster SW motion of Africa with respect to Somalia plate is due to a possibly lower viscosity in the top asthenosphere (Low-Velocity Zone) beneath Africa. These findings have significant implications for the evolution of continental rifting in transtensional settings and provide evidence for the kinematics and tectonics of the Ethiopian rift in the context of the Africa-Somalia plate interaction in the mantle reference frame.

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

Gerald Heymsfield

Data was taken with the NASA ER-2 aircraft with the Cloud Radar System and other instruments in conjunction with the DOE ARM CLASIC field campaign. The flights were near the SGP site in north Central Oklahoma and targeted small developing convection. The CRS is a 94 GHz nadir pointing Doppler radar. Also on board the ER-2 was the Cloud Physics Lidar (CPL). Seven science flights were conducted but the weather conditions did not cooperate in that there was neither developing convection, or there was heavy rain.

Effects of Warming on CO2 Fluxes in an Alpine Meadow Ecosystem on the Central Qinghai-Tibetan Plateau.

PubMed

Ganjurjav, Hasbagan; Gao, Qingzhu; Zhang, Weina; Liang, Yan; Li, Yawei; Cao, Xujuan; Wan, Yunfan; Li, Yue; Danjiu, Luobu

2015-01-01

To analyze CO2 fluxes under conditions of climate change in an alpine meadow on the central Qinghai-Tibetan Plateau, we simulated the effect of warming using open top chambers (OTCs) from 2012 to 2014. The OTCs increased soil temperature by 1.62°C (P < 0.05), but decreased soil moisture (1.38%, P < 0.05) during the experiments. The response of ecosystem CO2 fluxes to warming was variable, and dependent on the year. Under conditions of warming, mean gross ecosystem productivity (GEP) during the growing season increased significantly in 2012 and 2014 (P < 0.05); however, ecosystem respiration (ER) increased substantially only in 2012 (P < 0.05). The net ecosystem CO2 exchange (NEE) increased marginally in 2012 (P = 0.056), did not change in 2013(P > 0.05), and increased significantly in 2014 (P = 0.034) under conditions of warming. The GEP was more sensitive to climate variations than was the ER, resulting in a large increase in net carbon uptake under warming in the alpine meadow. Under warming, the 3-year averages of GEP, ER, and NEE increased by 19.6%, 15.1%, and 21.1%, respectively. The seasonal dynamic patterns of GEP and NEE, but not ER, were significantly impacted by warming. Aboveground biomass, particularly the graminoid biomass increased significantly under conditions of warming. Soil moisture, soil temperature, and aboveground biomass were the main factors that affected the variation of the ecosystem CO2 fluxes. The effect of warming on inter- and intra-annual patterns of ecosystem CO2 fluxes and the mechanism of different sensitivities in GEP and ER to warming, require further researched.

Effects of Warming on CO2 Fluxes in an Alpine Meadow Ecosystem on the Central Qinghai–Tibetan Plateau

PubMed Central

Ganjurjav, Hasbagan; Gao, Qingzhu; Zhang, Weina; Liang, Yan; Li, Yawei; Cao, Xujuan; Wan, Yunfan; Li, Yue; Danjiu, Luobu

2015-01-01

To analyze CO2 fluxes under conditions of climate change in an alpine meadow on the central Qinghai–Tibetan Plateau, we simulated the effect of warming using open top chambers (OTCs) from 2012 to 2014. The OTCs increased soil temperature by 1.62°C (P < 0.05), but decreased soil moisture (1.38%, P < 0.05) during the experiments. The response of ecosystem CO2 fluxes to warming was variable, and dependent on the year. Under conditions of warming, mean gross ecosystem productivity (GEP) during the growing season increased significantly in 2012 and 2014 (P < 0.05); however, ecosystem respiration (ER) increased substantially only in 2012 (P < 0.05). The net ecosystem CO2 exchange (NEE) increased marginally in 2012 (P = 0.056), did not change in 2013(P > 0.05), and increased significantly in 2014 (P = 0.034) under conditions of warming. The GEP was more sensitive to climate variations than was the ER, resulting in a large increase in net carbon uptake under warming in the alpine meadow. Under warming, the 3-year averages of GEP, ER, and NEE increased by 19.6%, 15.1%, and 21.1%, respectively. The seasonal dynamic patterns of GEP and NEE, but not ER, were significantly impacted by warming. Aboveground biomass, particularly the graminoid biomass increased significantly under conditions of warming. Soil moisture, soil temperature, and aboveground biomass were the main factors that affected the variation of the ecosystem CO2 fluxes. The effect of warming on inter- and intra-annual patterns of ecosystem CO2 fluxes and the mechanism of different sensitivities in GEP and ER to warming, require further researched. PMID:26147223

Visualization of Endoplasmic Reticulum and Mitochondria in Aurantiochytrium limacinum by the Expression of EGFP with Cell Organelle-Specific Targeting/Retaining Signals.

PubMed

Okino, Nozomu; Wakisaka, Hiroyoshi; Ishibashi, Yohei; Ito, Makoto

2018-04-01

Thraustochytrids are single cell marine eukaryotes that produce large amounts of polyunsaturated fatty acids such as docosahexaenoic acid. In the present study, we report the visualization of endoplasmic reticulum (ER) and mitochondria in a type strain of the thraustochytrid, Aurantiochytrium limacinum ATCC MYA-1381, using the enhanced green fluorescent protein (EGFP) with specific targeting/retaining signals. We expressed the egfp gene with ER targeting/retaining signals from A. limacinum calreticulin or BiP/GRP78 in the thraustochytrid, resulting in the distribution of EGFP signals at the perinuclear region and near lipid droplets. ER-Tracker™ Red, an authentic fluorescent probe for the visualization of ER in mammalian cells, also stained the same region. We observed small lipid droplets generated from the visualized ER in the early growth phase of cell culture. Expression of the egfp gene with the mitochondria targeting signal from A. limacinum cytochrome c oxidase resulted in the localization of EGFP near the plasma membrane. The distribution of EGFP signals coincided with that of MitoTracker® Red CMXRos, which is used to visualize mitochondria in eukaryotes. The ER and mitochondria of A. limacinum were visualized for the first time by EGFP with thraustochytrid cell organelle-specific targeting/retaining signals. These results will contribute to classification of the intracellular localization of proteins expressed in ER and mitochondria as well as analyses of these cell organelles in thraustochytrids.

Fluorescence Dynamics in the Endoplasmic Reticulum of a Live Cell: Time-Resolved Confocal Microscopy.

PubMed

Ghosh, Shirsendu; Nandi, Somen; Ghosh, Catherine; Bhattacharyya, Kankan

2016-09-19

Fluorescence dynamics in the endoplasmic reticulum (ER) of a live non-cancer lung cell (WI38) and a lung cancer cell (A549) are studied by using time-resolved confocal microscopy. To selectively study the organelle, ER, we have used an ER-Tracker dye. From the emission maximum (λmaxem) of the ER-Tracker dye, polarity (i.e. dielectric constant, ϵ) in the ER region of the cells (≈500 nm in WI38 and ≈510 nm in A549) is estimated to be similar to that of chloroform (λmaxem =506 nm, ϵ≈5). The red shift by 10 nm in λmaxem in the cancer cell (A549) suggests a slightly higher polarity compared to the non-cancer cell (WI38). The fluorescence intensity of the ER-Tracker dye exhibits prolonged intermittent oscillations on a timescale of 2-6 seconds for the cancer cell (A549). For the non-cancer cell (WI38), such fluorescence oscillations are much less prominent. The marked fluorescence intensity oscillations in the cancer cell are attributed to enhanced calcium oscillations. The average solvent relaxation time (<τs >) of the ER region in the lung cancer cell (A549, 250±50 ps) is about four times faster than that in the non-cancer cell (WI38, 1000±50 ps). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

1.6 μm microchip laser

NASA Astrophysics Data System (ADS)

Šulc, J.; Jelínková, H.; Ryba-Romanowski, W.; Lukasiewicz, T.

2009-03-01

Properties of new pulsed-diode-pumped Er:YVO4 and Er:YVO4+CaO microchip lasers working in an ``eye-safe'' spectral region were investigated. As a pumping source, a fiber coupled (core diameter-200 μm) laser diode emitting radiation at wavelength 976 nm was used. The laser diode was operating in pulsed regime with 3 ms pulse width, and 20 Hz repetition rate. The result obtained was 175 mW and 152 mW output peak power for the Er:YVO4 and Er:YVO4+CaO lasers, respectively. The maximal efficiency with respect to the absorbed power was ~ 5%. The laser emission for Er:YVO4 microchip was observed in detail in the range 1593 nm to 1604 nm with respect to pumping. However, for Er:YVO4+CaO crystal only 1604 nm was generated.

EBS7 is a plant-specific component of a highly conserved endoplasmic reticulum-associated degradation system in Arabidopsis

PubMed Central

Liu, Yidan; Zhang, Congcong; Wang, Dinghe; Su, Wei; Liu, Linchuan; Wang, Muyang; Li, Jianming

2015-01-01

Endoplasmic reticulum (ER)-associated degradation (ERAD) is an essential part of an ER-localized protein quality-control system for eliminating terminally misfolded proteins. Recent studies have demonstrated that the ERAD machinery is conserved among yeast, animals, and plants; however, it remains unknown if the plant ERAD system involves plant-specific components. Here we report that the Arabidopsis ethyl methanesulfonate-mutagenized brassinosteroid-insensitive 1 suppressor 7 (EBS7) gene encodes an ER membrane-localized ERAD component that is highly conserved in land plants. Loss-of-function ebs7 mutations prevent ERAD of brassinosteroid insensitive 1-9 (bri1-9) and bri1-5, two ER-retained mutant variants of the cell-surface receptor for brassinosteroids (BRs). As a result, the two mutant receptors accumulate in the ER and consequently leak to the plasma membrane, resulting in the restoration of BR sensitivity and phenotypic suppression of the bri1-9 and bri1-5 mutants. EBS7 accumulates under ER stress, and its mutations lead to hypersensitivity to ER and salt stresses. EBS7 interacts with the ER membrane-anchored ubiquitin ligase Arabidopsis thaliana HMG-CoA reductase degradation 1a (AtHrd1a), one of the central components of the Arabidopsis ERAD machinery, and an ebs7 mutation destabilizes AtHrd1a to reduce polyubiquitination of bri1-9. Taken together, our results uncover a plant-specific component of a plant ERAD pathway and also suggest its likely biochemical function. PMID:26371323

Divergent oestrogen receptor-specific breast cancer trends in Ireland (2004-2013): Amassing data from independent Western populations provide etiologic clues.

PubMed

Mullooly, Maeve; Murphy, Jeanne; Gierach, Gretchen L; Walsh, Paul M; Deady, Sandra; Barron, Thomas I; Sherman, Mark E; Rosenberg, Philip S; Anderson, William F

2017-11-01

The aetiology and clinical behaviour of breast cancers vary by oestrogen receptor (ER) expression, HER2 expression and over time. Data from the United States and Denmark show rising incidence rates for ER+ and falling incidence rates for ER- breast cancers. Given that Ireland is a somewhat similar Western population but with distinctive risk exposures (especially for lactation), we analysed breast cancer trends by ER status; and for the first time, by the joint expression of ER±/HER2±. We assessed invasive breast cancers (n = 24,845; 2004-2013) within the population-based National Cancer Registry of Ireland. The population at risk was obtained from the Irish Central Statistics Office (n = 10,401,986). After accounting for missing ER and HER2 data, we assessed receptor-specific secular trends in age-standardised incidence rates (ASRs) with the estimated annual percentage change (EAPC) and corresponding 95% confidence intervals (95% CI). Age-period-cohort models were also fitted to further characterise trends accounting for age, calendar-period and birth-cohort interactions. ASRs increased for ER+ (EAPC: 2.2% per year [95% CI: 0.97, 3.45%/year]) and decreased for ER- cancers (EAPC: -3.43% per year [95% CI: -5.05, -1.78%/year]), as well as for specific age groups at diagnosis (<30-49, 50-64 and ≥65 years). ER+/HER2- cancers rose, ER+/HER2+ cancers were statistically flat and ER-/HER± cancers declined. Secular trends for ER± cancers in Ireland were like those previously observed. Stratification by HER2± expression did not substantively alter ER± trends. The divergence of ER± incidence rates among independent Western populations likely reflects calendar-period and/or risk factor changes with differential effects for ER+ and ER- breast cancers. Published by Elsevier Ltd.

Mixing Layer Formation near the Tropopause Due to Gravity Wave Critical Level Interactions in a Cloud-Resolving Model.

NASA Astrophysics Data System (ADS)

Moustaoui, Mohamed; Joseph, Binson; Teitelbaum, Hector

2004-12-01

A plausible mechanism for the formation of mixing layers in the lower stratosphere above regions of tropical convection is demonstrated numerically using high-resolution, two-dimensional (2D), anelastic, nonlinear, cloud-resolving simulations. One noteworthy point is that the mixing layer simulated in this study is free of anvil clouds and well above the cloud anvil top located in the upper troposphere. Hence, the present mechanism is complementary to the well-known process by which overshooting cloud turrets causes mixing within stratospheric anvil clouds. The paper is organized as a case study verifying the proposed mechanism using atmospheric soundings obtained during the Central Equatorial Pacific Experiment (CEPEX), when several such mixing layers, devoid of anvil clouds, had been observed. The basic dynamical ingredient of the present mechanism is (quasi stationary) gravity wave critical level interactions, occurring in association with a reversal of stratospheric westerlies to easterlies below the tropopause region. The robustness of the results is shown through simulations at different resolutions. The insensitivity of the qualitative results to the details of the subgrid scheme is also evinced through further simulations with and without subgrid mixing terms. From Lagrangian reconstruction of (passive) ozone fields, it is shown that the mixing layer is formed kinematically through advection by the resolved-scale (nonlinear) velocity field.

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

Experimental optimum design and luminescence properties of NaY(Gd)(MoO4)2:Er3+ phosphors

NASA Astrophysics Data System (ADS)

Jia-Shi, Sun; Sai, Xu; Shu-Wei, Li; Lin-Lin, Shi; Zi-Hui, Zhai; Bao-Jiu, Chen

2016-06-01

Three-factor orthogonal design (OD) of Er3+/Gd3+/T (calcination temperature) is used to optimize the luminescent intensity of NaY(Gd)(MoO4)2:Er3+ phosphor. Firstly, the uniform design (UD) is introduced to explore the doping concentration range of Er3+/Gd3+. Then OD and range analysis are performed based on the results of UD to obtain the primary and secondary sequence and the best combination of Er3+, Gd3+, and T within the experimental range. The optimum sample is prepared by the high temperature solid state method. Photoluminescence excitation and emission spectra of the optimum sample are detected. The intense green emissions (530 nm and 550 nm) are observed which originate from Er3+ 2H11/2→ 4I15/2 and 4S3/2→4I15/2, respectively. Thermal effect is investigated in the optimum NaY(Gd3+)(MoO4)2:Er3+ phosphors, and the green emission intensity decreases as temperature increases. Project supported by Education Reform Fund of Dalian Maritime University, China (Grant No. 2015Y37), the Natural Science Foundation of Liaoning Province, China (Grant Nos. 2015020190 and 2014025010), the Open Fund of the State Key Laboratory on Integrated Optoelectronics, China (Grant No. IOSKL2015KF27), and the Fundamental Research Funds for the Central Universities, China (Grant No. 3132016121).

Disruption of the mitochondria-associated ER membrane (MAM) plays a central role in palmitic acid-induced insulin resistance.

PubMed

Shinjo, Satoko; Jiang, Shuying; Nameta, Masaaki; Suzuki, Tomohiro; Kanai, Mai; Nomura, Yuta; Goda, Nobuhito

2017-10-01

The mitochondria-associated ER membrane (MAM) is a specialized subdomain of ER that physically connects with mitochondria. Although disruption of inter-organellar crosstalk via the MAM impairs cellular homeostasis, its pathological significance in insulin resistance in type 2 diabetes mellitus remains unclear. Here, we reveal the importance of reduced MAM formation in the induction of fatty acid-evoked insulin resistance in hepatocytes. Palmitic acid (PA) repressed insulin-stimulated Akt phosphorylation in HepG2 cells within 12h. Treatment with an inhibitor of the ER stress response failed to restore PA-mediated suppression of Akt activation. Mitochondrial reactive oxygen species (ROS) production did not increase in PA-treated cells. Even short-term exposure (3h) to PA reduced the calcium flux from ER to mitochondria, followed by a significant decrease in MAM contact area, suggesting that PA suppressed the functional interaction between ER and mitochondria. Forced expression of mitofusin-2, a critical component of the MAM, partially restored MAM contact area and ameliorated the PA-elicited suppression of insulin sensitivity with Ser473 phosphorylation of Akt selectively improved. These results suggest that loss of proximity between ER and mitochondria, but not perturbation of homeostasis in the two organelles individually, plays crucial roles in PA-evoked Akt inactivation in hepatic insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

SAN PEDRO PARKS WILDERNESS, NEW MEXICO.

USGS Publications Warehouse

Santos, Elmer S.; Weisner, Robert C.

1984-01-01

The San Pedro Parks Wilderness occupies 62. 7 sq mi of the Santa Fe National Forest in north-central New Mexico. Several copper mines, many copper prospects, and a few uranium prospects occur in sedimentary units in the vicinity of the wilderness. These units, where they extend into the wilderness, constitute only a small volume of rock and, judging from analyses of samples and from field observations, are devoid of copper and uranium concentration. Prospects on several of about 65 mining claims within the wilderness revealed concentrations of manganese or barite but only in volumes too small to be considered a demonstrated resource.

NSAI activity study of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives.

PubMed

Darias, V; Abdallah, S S; Tello, M L; Delgado, L D; Vega, S

1994-12-01

A series of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives endowed with anti-inflammatory and related pharmacological properties were submitted to a more extensive study to know their exact pharmacological profile and their possible side effects. The studied compounds possess a remarkable analgesic activity, devoid of central effects. They also show an interesting anti-inflammatory profile evidenced by their effectiveness in different experimental models of inflammation. In addition, these compounds exhibit none or very little activity on CNS, scarce toxicity and low gastrointestinal aggressivity.

Energy transfer and optical gain properties of P{sub 2}O{sub 5}-ZnO-LiF: (Yb{sup 3+}, Er{sup 3+}) glasses

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

Reddy, C. Parthasaradhi, E-mail: cgparthasaradhi@gmail.com, E-mail: ktrkreddy@gmail.com; Naresh, V.; Reddy, K. T. Ramakrishna, E-mail: cgparthasaradhi@gmail.com, E-mail: ktrkreddy@gmail.com

2015-06-24

The present paper reports on the results pertaining to the emission properties of 0.5 mol% Er{sup 3+} and together (0.5 Yb{sup 3+} /0.5 Er{sup 3+}) doped PZL (P{sub 2}O{sub 5}-ZnO-LiF) glasses prepared by a melt quenching method. From the optical absorption data, absorption and stimulated emission cross-sections have been evaluated using McCumber’s theory and further cross-sectional gain has also been computed for Yb{sup 3+}/Er{sup 3+} doped glass. On exciting the single (Er{sup 3+}) and dual rare earth ions (Yb{sup 3+}/Er{sup 3+}) doped glass sample at λ{sub exci} = 379 nm, three emission bands in the visible region {sup 2}H{sub 11/2}→{sup 4}I{sub 15/2}more » (526 nm), {sup 4}S{sub 3/2}→{sup 4}I{sub 15/2} (549 nm) and {sup 4}F{sub 9/2}→{sup 4}I{sub 15/2} (664 nm) are observed and while at λ{sub exci} = 980 nm (Laser Diode) excitation a broad emission at 1530 nm attributed to {sup 4}H{sub 13/2}→{sup 4}I{sub 15/2} is observed in the NIR region. The enhancement in visible and NIR emission intensities with the addition of Yb{sup 3+} to Er{sup 3+} due to an energy transfer process from Yb{sup 3+} to Er{sup 3+} has been explained in terms of an energy level diagram.« less

Properties of solar ephemeral regions at the emergence stage

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

Yang, Shuhong; Zhang, Jun, E-mail: shuhongyang@nao.cas.cn, E-mail: zjun@nao.cas.cn

2014-01-20

For the first time, we statistically study the properties of ephemeral regions (ERs) and quantitatively determine their parameters at the emergence stage based on a sample of 2988 ERs observed by the Solar Dynamics Observatory. During the emergence process, there are three kinds of kinematic performances, i.e., separation of dipolar patches, shift of the ER's magnetic centroid, and rotation of the ER's axis. The average emergence duration, flux emergence rate, separation velocity, shift velocity, and angular speed are 49.3 minutes, 2.6 × 10{sup 15} Mx s{sup –1}, 1.1 km s{sup –1}, 0.9 km s{sup –1}, and 0.°6 minute{sup –1}, respectively.more » At the end of emergence, the mean magnetic flux, separation distance, shift distance, and rotation angle are 9.3 × 10{sup 18} Mx, 4.7 Mm, 1.1 Mm, and 12.°9, respectively. We also find that the higher the ER magnetic flux is, (1) the longer the emergence lasts, (2) the higher the flux emergence rate is, (3) the further the two polarities separate, (4) the lower the separation velocity is, (5) the larger the shift distance is, (6) the slower the ER shifts, and (7) the lower the rotation speed is. However, the rotation angle seems not to depend on the magnetic flux. Not only at the start time, but also at the end time, the ERs are randomly oriented in both the northern and the southern hemispheres. Finally, neither the anti-clockwise-rotated ERs nor the clockwise rotated ones dominate the northern or the southern hemisphere.« less

Inhibition of endoplasmic reticulum stress improves coronary artery function in type 2 diabetic mice.

PubMed

Choi, Soo-Kyoung; Lim, Mihwa; Yeon, Soo-In; Lee, Young-Ho

2016-06-01

What is the central question of this study? Endoplasmic reticulum (ER) stress has been reported to be involved in type 2 diabetes; however, the role of exacerbated ER stress in vascular dysfunction in type 2 diabetes remains unknown. What is the main finding and its importance? The main findings of this study are that ER stress is increased in the coronary arteries in type 2 diabetes, and inhibition of ER stress using taurine-conjugated ursodeoxycholic acid improves vascular function, which is associated with normalization of the myogenic response and endothelium-dependent relaxation. Vascular dysfunction is a major complication in type 2 diabetes. Although endoplasmic reticulum (ER) stress has been suggested to be a contributory factor in cardiovascular diseases, the relationship between ER stress and vascular dysfunction in type 2 diabetes remains unclear. Thus, in the present study, we examined whether ER stress contributes to coronary artery dysfunction and whether inhibition of ER stress ameliorates vascular function in type 2 diabetes. Type 2 diabetic mice and their control counterparts were treated with an ER stress inhibitor (taurine-conjugated ursodeoxycholic acid, 150 mg kg(-1)  day(-1) , by i.p. injection) for 2 weeks or not treated. The myogenic response and endothelium-dependent relaxation were measured in pressurized coronary arteries. In type 2 diabetic mice, blood glucose and body weight were elevated compared with control mice. The myogenic response was potentiated and endothelium-dependent relaxation impaired in coronary arteries from the type 2 diabetic mice. Interestingly, treatment with the ER stress inhibitor normalized the myogenic responses and endothelium-dependent relaxation. These data were associated with an increase in ER stress marker expression or phosphorylation (IRE1-XBP-1 and PERK-eIF2α) in type 2 diabetic mice, which were reduced by treatment with the ER stress inhibitor. Inhibition of ER stress normalizes the myogenic response and improves vascular function in type 2 diabetes. Therefore, ER stress could be a potential target for cardiovascular diseases in diabetes mellitus. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Energy dissipation channels affecting photoluminescence from resonantly excited Er{sup 3+} ions doped in epitaxial ZnO host films

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

Akazawa, Housei, E-mail: akazawa.housei@lab.ntt.co.jp; Shinojima, Hiroyuki

2015-04-21

We identified prerequisite conditions to obtain intense photoluminescence at 1.54 μm from Er{sup 3+} ions doped in ZnO host crystals. The epitaxial ZnO:Er films were grown on sapphire C-plane substrates by sputtering, and Er{sup 3+} ions were resonantly excited at a wavelength of 532 nm between energy levels of {sup 4}I{sub 15/2} and {sup 2}H{sub 11/2}. There is a threshold deposition temperature between 500 and 550 °C, above which epitaxial ZnO films become free of miss-oriented domains. In this case, Er{sup 3+} ions are outside ZnO crystallites, having the same c-axis lattice parameters as those of undoped ZnO crystals. The improved crystallinity wasmore » correlated with enhanced emissions peaking at 1538 nm. Further elevating the deposition temperature up to 650 °C generated cracks in ZnO crystals to relax the lattice mismatch strains, and the emission intensities from cracked regions were three times as large as those from smooth regions. These results can be consistently explained if we assume that emission-active Er{sup 3+} ions are those existing at grain boundaries and bonded to single-crystalline ZnO crystallites. In contrast, ZnO:Er films deposited on a ZnO buffer layer exhibited very weak emissions because of their degraded crystallinity when most Er{sup 3+} ions were accommodated into ZnO crystals. Optimizing the degree of oxidization of ZnO crystals is another important factor because reduced films suffer from non-radiative decay of excited states. The optimum Er content to obtain intense emissions was between 2 and 4 at. %. When 4 at. % was exceeded, the emission intensity was severely attenuated because of concentration quenching as well as the degradation in crystallinity. Precipitation of Er{sub 2}O{sub 3} crystals was clearly observed at 22 at. % for films deposited above 650 °C. Minimizing the number of defects and impurities in ZnO crystals prevents energy dissipation, thus exclusively utilizing the excitation energy to emissions from Er{sup 3+} ions.« less

78 FR 21927 - Notice of Commission Staff Attendance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-12

... activities of the Southern Company Services, Inc.: Southeastern Regional Transmission Planning (SERTP... above-referenced meeting will be held at: Georgia Transmission Corporation (GTC) Headquarters--Tucker... proceedings: Docket No. ER13-908, Alabama Power Company et al. Docket No. ER13-913, Ohio Valley Electric...

Geologic Map of the Big Spring Quadrangle, Carter County, Missouri

USGS Publications Warehouse

Weary, David J.; McDowell, Robert C.

2006-01-01

The bedrock exposed in the Big Spring quadrangle of Missouri comprises Late Cambrian and Early Ordovician aged dolomite, sandstone, and chert. The sedimentary rocks are nearly flat lying except where they are adjacent to faults. The carbonate rocks are karstified, and the area contains numerous sinkholes, springs, caves, and losing streams. This map is one of several being produced under the U.S. Geological Survey (USGS) National Cooperative Geologic Mapping Program to provide geologic data applicable to land-use problems in the Ozarks of south-central Missouri. Ongoing and potential industrial and agricultural development in the Ozarks region has presented issues of ground-water quality in karst areas. A national park in this region (Ozark National Scenic Riverways, Missouri) is concerned about the effects of activities in areas outside of their stewardship on the water resources that define the heart of this park. This task applies geologic mapping and karst investigations to address issues surrounding competing land use in south-central Missouri. This task keeps geologists from the USGS associated with the park and allows the park to utilize USGS expertise and aid the NPS on how to effectively use geologic maps for park management. For more information, see: http://geology.er.usgs.gov/eespteam/Karst/index.html

Geologic map of the Van Buren South quadrangle, Carter County, Missouri

USGS Publications Warehouse

Weary, D.J.; Schindler, J.S.

2004-01-01

The bedrock exposed in the Van Buren South quadrangle, Missouri, comprises Late Cambrian and Early Ordovician aged dolomite, sandstone, and chert. The sedimentary rocks are nearly flat-lying except where they are adjacent to faults. The carbonate rocks are karstified and the area contains numerous sinkholes, springs, caves, and losing-streams. This map is one of several being produced under the U.S. Geological Survey National Cooperative Geologic Mapping Program to provide geologic data applicable to land-use problems in the Ozarks of south-central Missouri. Ongoing and potential industrial and agricultural development in the Ozarks region has presented issues of ground-water quality in karst areas. A National Park in this region (Ozark National Scenic Riverways, Missouri ) is concerned about the effects of activities in areas outside of their stewardship on the water resources that define the heart of this Park. This task applies geologic mapping and karst investigations to address issues surrounding competing land use in south-central Missouri. This task keeps geologists from the USGS associated with the park and allows the Parks to utilize USGS expertise and aid the NPS on how to effectively use geologic maps for Park management. For more information see: http://geology.er.usgs.gov/eespteam/Karst/index.html

Geologic map of the Low Wassie Quadrangle, Oregon and Shannon counties, Missouri

USGS Publications Warehouse

Weems, Robert E.

2002-01-01

The bedrock exposed in the Low Wassie Quadrangle, Missouri, comprises Late Cambrian and Early Ordovician aged dolomite, sandstone, and chert. The sedimentary rocks are nearly flat-lying except where they are adjacent to faults. The carbonates are karstified and the area contains numerous sinkholes, springs, caves, and losing-streams. This map is one of several being produced under the U.S. Geological Survey National Cooperative Geologic Mapping Program to provide geologic data applicable to land-use problems in the Ozarks of south-central Missouri. Ongoing and potential industrial and agricultural development in the Ozarks region has presented issues of ground-water quality in karst areas. A National Park in this region (Ozark National Scenic Riverways, Missouri ) is concerned about the effects of activities in areas outside of their stewardship on the water resources that define the heart of this Park. This task applies geologic mapping and karst investigations to address issues surrounding competing land use in south-central Missouri. This task keeps geologists from the USGS associated with the park and allows the Parks to utilize USGS expertise and aid the NPS on how to effectively use geologic maps for Park management. For more information see: http://geology.er.usgs.gov/eespteam/Karst/index.html.

Geologic map of the Winona Quadrangle, Shannon County, Missouri

USGS Publications Warehouse

Orndorff, R.C.; Harrison, R.W.

2001-01-01

The bedrock exposed in the Winona Quadrangle, Missouri, comprises Mesoproterozoic aged volcanic rocks overlain by Late Cambrian and Early Ordovician aged dolomite, sandstone, and chert. The sedimentary rocks are nearly flat-lying except where they drape around knobs of the volcanic rocks or where they are adjacent to faults. The carbonates are karstified and the area contains numerous sinkholes, springs, caves, and losing-streams. This map is one of several being produced under the U.S. Geological Survey National Cooperative Geologic Mapping Program to provide geologic data applicable to land-use problems in the Ozarks of south-central Missouri. Ongoing and potential industrial and agricultural development in the Ozarks region has presented issues of ground-water quality in karst areas. A National Park in this region (Ozark National Scenic Riverways, Missouri ) is concerned about the effects of activities in areas outside of their stewardship on the water resources that define the heart of this Park. This task applies geologic mapping and karst investigations to address issues surrounding competing land use in south-central Missouri. This task keeps geologists from the USGS associated with the park and allows the Parks to utilize USGS expertise and aid the NPS on how to effectively use geologic maps for Park management. For more information see: http://geology.er.usgs.gov/eespteam/Karst/index.html

Application of probabilistic event attribution in the summer heat extremes in the western US to emissions traced to major industrial carbon producers

NASA Astrophysics Data System (ADS)

Mera, R. J.; Allen, M. R.; Mote, P.; Ekwurzel, B.; Frumhoff, P. C.; Rupp, D. E.

2015-12-01

Heat waves in the western US have become progressively more severe due to increasing relative humidity and nighttime temperatures, increasing the health risks of vulnerable portions of the population, including Latino farmworkers in California's Central Valley and other socioeconomically disadvantaged communities. Recent research has shown greenhouse gas emissions doubled the risk of the hottest summer days during the 2000's in the Central Valley, increasing public health risks and costs, and raising the question of which parties are responsible for paying these costs. It has been argued that these costs should not be taken up solely by the general public through taxation, but that additional parties can be considered, including multinational corporations who have extracted and marketed a large proportion of carbon-based fuels. Here, we apply probabilistic event attribution (PEA) to assess the contribution of emissions traced to the world's 90 largest major industrial carbon producers to the severity and frequency of these extreme heat events. Our research uses very large ensembles of regional climate model simulations to calculate fractional attribution of policy-relevant extreme heat variables. We compare a full forcings world with observed greenhouse gases, sea surface temperatures and sea ice extent to a counter-factual world devoid of carbon pollution from major industrial carbon producers. The results show a discernable fraction of record-setting summer temperatures in the western US during the 2000's can be attributed to emissions sourced from major carbon producers.

InSAR coherence study of unusual rain events in the Atacama Desert

NASA Astrophysics Data System (ADS)

Jordan, T. E.; Scott, C. P.; Lohman, R.

2017-12-01

The Atacama Desert (AD) occupies much of Chile at latitudes 18-27°S. The surficial materials vary, dependent on proximity to the ocean, slope, position within a surface water drainage system, mean annual rainfall, human land disturbance, and the local history of climate changes. Three major divisions of soil composition include: near coastal zone of silicate mineral soils, mostly devoid of plants; central hyperarid zone dominated by gypsum, devoid of plants; eastern zone of silicate-based soils, very sparse plants. The AD in March 2015 experienced the largest rain event of modern history, and again in June 2017 almost as much rain fell within the study area (24.2-25.7°S, coast to Andes Mountains). Those natural experiments set the stage for InSAR remote sensing of surface changes in a 24,000 square kilometer area. We used interferometric coherence of radar to measure the similarity in the reflective ground properties at the time of two SAR acquisitions, and a time series of European Space Agency's Sentinel-1A data sets acquired between January 2015 and August 2017. Date pairs lacking an intervening rain event reveal extensive regions of high coherence, and in those areas we focus on the temporal evolution of coherence across dates of, and following dates of, the major rains. Permanent change of the surface is most extensive in the eastern and western sectors, yet the degree of permanent change was small except in valley bottoms. In the sector with gypsum soil small degrees of permanent change occurred over 30% of the surface including in narrow (1-3 km) elongate (10-60 km) stripes that cross-cut topography, likely revealing rain bands. The spatial pattern of transient change in coherence differs. Over half the gypsum-dominated zone displays a transient change signal, whose spatial pattern corresponds to geomorphological forms; older landforms display greater transient coherence changes. In the silicate-dominated eastern region the transient signals are smaller. In both zones the transient change in coherence recovered to the pre-rain conditions over several months. Analysis to date indicates that the transient signal in the driest AD reflects an interaction of water with the CaSO4 mineral structure, whereas in the eastern zone it more likely reflects liquid water retention.

Subcellular Localization of Arabidopsis 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase1

PubMed Central

Leivar, Pablo; González, Víctor M.; Castel, Susanna; Trelease, Richard N.; López-Iglesias, Carmen; Arró, Montserrat; Boronat, Albert; Campos, Narciso; Ferrer, Albert; Fernàndez-Busquets, Xavier

2005-01-01

Plants produce diverse isoprenoids, which are synthesized in plastids, mitochondria, endoplasmic reticulum (ER), and the nonorganellar cytoplasm. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) catalyzes the synthesis of mevalonate, a rate-limiting step in the cytoplasmic pathway. Several branches of the pathway lead to the synthesis of structurally and functionally varied, yet essential, isoprenoids. Several HMGR isoforms have been identified in all plants examined. Studies based on gene expression and on fractionation of enzyme activity suggested that subcellular compartmentalization of HMGR is an important intracellular channeling mechanism for the production of the specific classes of isoprenoids. Plant HMGR has been shown previously to insert in vitro into the membrane of microsomal vesicles, but the final in vivo subcellular localization(s) remains controversial. To address the latter in Arabidopsis (Arabidopsis thaliana) cells, we conducted a multipronged microscopy and cell fractionation approach that included imaging of chimeric HMGR green fluorescent protein localizations in transiently transformed cell leaves, immunofluorescence confocal microscopy in wild-type and stably transformed seedlings, immunogold electron microscopy examinations of endogenous HMGR in seedling cotyledons, and sucrose density gradient analyses of HMGR-containing organelles. Taken together, the results reveal that endogenous Arabidopsis HMGR is localized at steady state within ER as expected, but surprisingly also predominantly within spherical, vesicular structures that range from 0.2- to 0.6-μm diameter, located in the cytoplasm and within the central vacuole in differentiated cotyledon cells. The N-terminal region, including the transmembrane domain of HMGR, was found to be necessary and sufficient for directing HMGR to ER and the spherical structures. It is believed, although not directly demonstrated, that these vesicle-like structures are derived from segments of HMGR-ER. Nevertheless, they represent a previously undescribed subcellular compartment likely capable of synthesizing mevalonate, which provides new evidence for multiorganelle compartmentalization of the isoprenoid biosynthetic pathways in plants. PMID:15618432

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.

I'm not a doctor but I play one on TV: E.R. and the place of contemporary health care in fixing crisis.

PubMed

Lepofsky, Jonathan; Nash, Sally; Kaserman, Bonnie; Gesler, Wil

2006-06-01

This paper is an examination of the popular TV drama E.R. What is notable for health geographers about E.R. is how the show offers a representation of health care and the role of place in creating ways to provide care. Indeed, the place of health care-the emergency room-is the point of reference for the show's weekly dramas and centers the activity on the screen. We posit that the show's success stems from how crisis has become a central component of discourses about health care and that E.R. offers one highly seductive interpretation of how to deal with crisis in health care and care delivery. E.R. provides a representation of crisis by constructing three scales of intervention as the best sites to respond to and fix crisis: bodies, medical networks, and the urban social relations of the city. Order is designed around these scales which serve to map out where medical interventions can be made within the discursive regime of crisis. What E.R. provides is a powerful, if limited, "realistic" portrayal about the role of health care today-a role that is increasingly considered to be shaped by the need to intervene in crisis.

UDP-glucose:glycoprotein glucosyltransferase (UGGT1) promotes substrate solubility in the endoplasmic reticulum

PubMed Central

Ferris, Sean P.; Jaber, Nikita S.; Molinari, Maurizio; Arvan, Peter; Kaufman, Randal J.

2013-01-01

Protein folding in the endoplasmic reticulum (ER) is error prone, and ER quality control (ERQC) processes ensure that only correctly folded proteins are exported from the ER. Glycoproteins can be retained in the ER by ERQC, and this retention contributes to multiple human diseases, termed ER storage diseases. UDP-glucose:glycoprotein glucosyltransferase (UGGT1) acts as a central component of glycoprotein ERQC, monoglucosylating deglucosylated N-glycans of incompletely folded glycoproteins and promoting subsequent reassociation with the lectin-like chaperones calreticulin and calnexin. The extent to which UGGT1 influences glycoprotein folding, however, has only been investigated for a few selected substrates. Using mouse embryonic fibroblasts lacking UGGT1 or those with UGGT1 complementation, we investigated the effect of monoglucosylation on the soluble/insoluble distribution of two misfolded α1-antitrypsin (AAT) variants responsible for AAT deficiency disease: null Hong Kong (NHK) and Z allele. Whereas substrate solubility increases directly with the number of N-linked glycosylation sites, our results indicate that additional solubility is conferred by UGGT1 enzymatic activity. Monoglucosylation-dependent solubility decreases both BiP association with NHK and unfolded protein response activation, and the solubility increase is blocked in cells deficient for calreticulin. These results suggest that UGGT1-dependent monoglucosylation of N-linked glycoproteins promotes substrate solubility in the ER. PMID:23864712

A natural compound jaceosidin ameliorates endoplasmic reticulum stress and insulin resistance via upregulation of SERCA2b.

PubMed

Ouyang, Zijun; Li, Wanshuai; Meng, Qianqian; Zhang, Qi; Wang, Xingqi; Elgehama, Ahmed; Wu, Xudong; Shen, Yan; Sun, Yang; Wu, Xuefeng; Xu, Qiang

2017-05-01

Increased endoplasmic reticulum (ER) stress has emerged as a vital contributor to dysregulated glucose homeostasis, and impaired function of sarco-endoplasmic reticulum Ca 2+ -ATPase 2b (SERCA2b) is one of the central mechanisms underlying ER stress. In this study, we reported that SERCA2b upregulation contributed to the amelioration of ER stress and insulin resistance by a small natural compound jaceosidin. In a model of differentiated C2C12 myotubes, jaceosidin-triggered SERCA2b upregulation enhanced insulin sensitivity and decreased ER stress. Moreover, the activity of Ca 2+ -ATPase in thapsigargin-treated myotubes was also augmented by jaceosidin. Furthermore, jaceosidin significantly suppressed blood glucose levels, improved glucose tolerance and lowered body weight, but did not alter food intake in insulin-resistant obese mice. In addition, this compound markedly reduced lipid accumulation, suppressed the expression of lipogenic genes in liver and ameliorated liver injury. The ameliorative effects of jaceosidin were due to its ability to reduce ER stress via increasing the expression of SERCA2b in the muscles of obese mice. Taken together, jaceosidin could improve ER stress and attenuate insulin resistance via SERCA2b upregulation in mice skeletal muscles. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

78 FR 2383 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-11

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 2 Take notice.../13. Docket Numbers: ER10-3079-004; ER12-126-006. Applicants: Tyr Energy, LLC, Trademark Merchant Energy, LLC. Description: Updated Market Power Analysis for the Southwest Power Pool Region of Tyr Energy...

Hydrophobic-domain-dependent protein-protein interactions mediate the localization of GPAT enzymes to ER subdomains

USDA-ARS?s Scientific Manuscript database

The endoplasmic reticulum (ER) is a dynamic network that consists of numerous regions or subdomains with discrete morphological features and functional properties, including those involved in protein and oil-body formation, anterograde transport of secretory proteins, the exchange of macromolecules ...

The Endoplasmic Reticulum: A Central Player in Cell Signalling and Protein Synthesis

NASA Astrophysics Data System (ADS)

Llewelyn Roderick, H.; Berridge, Michael J.; Bootman, Martin D.

In addition to being the principle intracellular Ca 2+ store, the endoplasmic reticulum (ER) is the initial site of synthesis and folding of membrane and secretory proteins. These two roles of the ER are intimately linked. First, the function of many proteins involved in Ca 2+ handling are modulated by Ca 2+ and second, ER lumenal Ca 2+ modulates protein synthesis and folding. Within the ER, Ca 2+ is stored by low affinity high capacity Ca 2+ binding proteins and is maintained at a free concentration between 0.1 and 1 μM relative to 0.1 μM cytosolic Ca 2+. This concentration gradient is maintained by the action of the Sarco-Endoplasmic Reticulum ATPases (SERCa) which hydrolyse ATP to pump Ca 2+ into the ER. Following stimulation Ca 2+ is released from the ER through several classes of ligand gated channels. The most well characterized of these being the inositol 1,4,5-trisphosphate receptor ( IP 3 R) and the Ryanodine receptor (RyR) families of proteins. This release of Ca 2+ results in a drop of ER free Ca 2+ to levels as low as 10 μM. This decrease in lumenal Ca 2+ inhibits further release through the channels and increases the rate of re-sequestration of Ca 2+ into the ER by the SERCa pumps. Under these conditions, in addition to effects on Ca 2+ handling proteins, protein synthesis is inhibited, chaperones dissociate from their substrates, secondary modifications of proteins are inhibited and the retention of many proteins within the ER is lost. Furthermore, a signalling cascade resulting in the up-regulation of many proteins involved in protein folding and Ca 2+ homeostasis is initiated. This review will focus on the proteins involved in the regulation ER lumenal Ca 2+ and the role of ER lumenal Ca 2+ in cell signalling and protein synthesis.

DISTRIBUTION OF MAGNETIC BIPOLES ON THE SUN OVER THREE SOLAR CYCLES

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

Tlatov, Andrey G.; Vasil'eva, Valerya V.; Pevtsov, Alexei A., E-mail: tlatov@mail.r, E-mail: apevtsov@nso.ed

We employ synoptic full disk longitudinal magnetograms to study latitudinal distribution and orientation (tilt) of magnetic bipoles in the course of sunspot activity during cycles 21, 22, and 23. The data set includes daily observations from the National Solar Observatory at Kitt Peak (1975-2002) and Michelson Doppler Imager on board the Solar and Heliospheric Observatory (MDI/SOHO, 1996-2009). Bipole pairs were selected on the basis of proximity and flux balance of two neighboring flux elements of opposite polarity. Using the area of the bipoles, we have separated them into small quiet-Sun bipoles (QSBs), ephemeral regions (ERs), and active regions (ARs). Wemore » find that in their orientation, ERs and ARs follow Hale-Nicholson polarity rule. As expected, AR tilts follow Joy's law. ERs, however, show significantly larger tilts of opposite sign for a given hemisphere. QSBs are randomly oriented. Unlike ARs, ERs also show a preference in their orientation depending on the polarity of the large-scale magnetic field. These orientation properties may indicate that some ERs may form at or near the photosphere via the random encounter of opposite polarity elements, while others may originate in the convection zone at about the same location as ARs. The combined latitudinal distribution of ERs and ARs exhibits a clear presence of Spoerer's butterfly diagram (equatorward drift in the course of a solar cycle). ERs extend the ARs' 'wing' of the butterfly diagram to higher latitudes. This high latitude extension of ERs suggests an extended solar cycle with the first magnetic elements of the next cycle developing shortly after the maximum of the previous cycle. The polarity orientation and tilt of ERs may suggest the presence of poloidal fields of two configurations (new cycle and old cycle) in the convection zone at the declining phase of the sunspot cycle.« less

Loss-of-function PCSK9 mutants evade the unfolded protein response sensor GRP78 and fail to induce endoplasmic reticulum stress when retained.

PubMed

Lebeau, Paul; Platko, Khrystyna; Al-Hashimi, Ali A; Byun, Jae Hyun; Lhoták, Šárka; Holzapfel, Nicholas; Gyulay, Gabriel; Igdoura, Suleiman A; Cool, David R; Trigatti, Bernardo; Seidah, Nabil G; Austin, Richard C

2018-05-11

The proprotein convertase subtilisin/kexin type-9 (PCSK9) plays a central role in cardiovascular disease (CVD) by degrading hepatic low-density lipoprotein receptor (LDLR). As such, loss-of-function (LOF) PCSK9 variants that fail to exit the endoplasmic reticulum (ER) increase hepatic LDLR levels and lower the risk of developing CVD. The retention of misfolded protein in the ER can cause ER stress and activate the unfolded protein response (UPR). In this study, we investigated whether a variety of LOF PCSK9 variants that are retained in the ER can cause ER stress and hepatic cytotoxicity. Although overexpression of these PCSK9 variants caused an accumulation in the ER of hepatocytes, UPR activation or apoptosis was not observed. Furthermore, ER retention of endogenous PCSK9 via splice switching also failed to induce the UPR. Consistent with these in vitro studies, overexpression of PCSK9 in the livers of mice had no impact on UPR activation. To elucidate the cellular mechanism to explain these surprising findings, we observed that the 94-kDa glucose-regulated protein (GRP94) sequesters PCSK9 away from the 78-kDa glucose-regulated protein (GRP78), the major activator of the UPR. As a result, GRP94 knockdown increased the stability of GRP78-PCSK9 complex and resulted in UPR activation following overexpression of ER-retained PCSK9 variants relative to WT secreted controls. Given that overexpression of these LOF PCSK9 variants does not cause UPR activation under normal homeostatic conditions, therapeutic strategies aimed at blocking the autocatalytic cleavage of PCSK9 in the ER represent a viable strategy for reducing circulating PCSK9. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Expression and localization of aromatase P450AROM, estrogen receptor-α, and estrogen receptor-β in the developing fetal bovine frontal cortex.

PubMed

Peruffo, A; Giacomello, M; Montelli, S; Corain, L; Cozzi, B

2011-06-01

The enzyme aromatase (P450(AROM)) converts testosterone (T) into 17-β estradiol (E(2)) and is crucial for the control of development of the central nervous system during ontogenesis. The effects of E(2) in various brain areas are mediated by the estrogen receptor alpha (ER-α) and the estrogen receptor beta (ER-β). During fetal development, steroids are responsible for the sexual differentiation of the hypothalamus. Estrogens are also able to exert effects in other brain areas of the fetus including the frontal cortex, where they act through estrogen receptors (ERs) modulating cognitive function and affective behaviors. In this study we have determined the expression profiles of P450(AROM) and ERs in the fetal bovine frontal cortex by quantitative Real-Time PCR (qRT-PCR) throughout the prenatal development. The data show that the patterns of expression of both ERs are strongly correlated during pregnancy and increase in the last stage of gestation. On the contrary, the expression of P450(AROM) has no correlation with ERs expression and is not developmentally regulated. Moreover, we performed immunochemical studies showing that fetal neurons express P450(AROM) and the ERs. P450(AROM) is localized in the cytoplasm and only seldom present in the fine extensions of the cells; ER-α is detected predominantly in the soma whereas ER-β is only present in the nucleus of a few cells. This study provides new data on the development of the frontal cortex in a long gestation mammal with a large convoluted brain. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Simultaneous observation of up/down conversion photoluminescence and colossal permittivity properties in (Er+Nb) co-doped TiO2 materials

NASA Astrophysics Data System (ADS)

Tse, Mei-Yan; Tsang, Ming-Kiu; Wong, Yuen-Ting; Chan, Yi-Lok; Hao, Jianhua

2016-07-01

We have investigated the optical and dielectric properties of rutile TiO2 doped with Nb and Er, i.e., (Er0.5Nb0.5)xTi1-xO2. The up/downconversion photoluminescence was observed in the visible and near-infrared region from the materials under 980 nm laser diode excitation. The upconversion emissions are attributed to the energy transfer between Er ions in the excited states. Moreover, the dielectric measurements indicate that the fabricated materials simultaneously present colossal permittivity properties with relatively low dielectric loss. Our work demonstrates the coexistence of both interesting luminescence and attractive dielectric characteristics in (Er+Nb) co-doped TiO2, showing the potential for multifunctional applications.

Intrapulpal Temperature Increase During Er:YAG Laser-Aided Debonding of Ceramic Brackets.

PubMed

Yilanci, Hilal; Yildirim, Zeynep Beyza; Ramoglu, Sabri Ilhan

2017-04-01

The purpose of this study was to evaluate the temperature changes in the pulp chamber while using a newly introduced application of Er:YAG laser to debond ceramic brackets in a study model with a pulpal circulation with and without thermocycled samples. An esthetic alternative to stainless steel brackets, ceramic brackets have been proposed. However, because of their low fracture resistance and high bond strengths, ceramic brackets can cause a problem when they are being removed using conventional techniques. Experimental Groups A and B were established for samples with or without thermocycling. The same 20 maxillary central incisor and 20 premolar teeth were used in both groups. Pulpal blood microcirculation was simulated using an apparatus described in a previous study. Monocrystalline brackets were bonded by using Transbond XT. In Group A, brackets were debonded using the Er:YAG laser (600 mJ, 2 Hz, long pulse, and no air or water spray) after being stored in distilled water for 24 h. In Group B, brackets were debonded using the same laser system as that used in Group A after being stored in distilled water for 24 h and then thermocycled for a total of 5000 cycles between 5°C and 55°C. The laser irradiation duration and intrapulpal temperature changes were measured. In Group B, the intrapulpal temperature increase of the central incisors was significantly higher than that of the premolar teeth. In the central incisor and premolar teeth groups, there were no statistically significant difference between Groups A and B (p > 0.05). A positive correlation was found between laser irradiation duration and temperature increase (p < 0.01). The use of Er:YAG laser is an effective method for debonding the monocrystalline ceramic brackets. This method can be used safely under the consideration of intrapulpal temperature changes.

Comparative evaluation of ERTS imagery for resource inventory in land use planning

NASA Technical Reports Server (NTRS)

Simonson, G. H. (Principal Investigator)

1973-01-01

The author has identified the following significant results. Numerous previously unmapped faults in central Oregon have been distinguished on ERTS-1 imagery. Tectonic mapping of fault-controlled linears demonstrates the utility of ERTS-1 imagery as a mean of illustrating and studying the regional tectonics of the state. Soil colors observed on ERTS-1 frame 1075-18150-5 at the eastern end of the Columbia basin correlate very well with those from descriptions of soils from that area. Digital output from frame 1021-18151 has shown the enhanced ability to interpret such features as joint patterns, shadowed landslide blocks, bottomlands, and drainage patterns. Widespread use of wheat-fallow rotation in northern Umatilla County, Oregon, insures that nearly one-half of the cultivated soil is devoid of vegetation much of the time. On ERTS-1 imagery, fallow fields are only slightly darker than fields of wheat stubble at the western end of the transect. Similar climate-related contrasts in soil color are visible on ERTS-1 Imagery from several other portions of the Columbia Basin. Absence of steep topography in the area mentioned, however, minimizes the disturbing effect caused by shadows.

Settlement patterns reflected in assemblages from the Pleistocene/Holocene transition of North Central China

USGS Publications Warehouse

Madsen, D.B.; Elston, R.G.; Bettinger, R.L.; Xu, C.; Zhong, K.

1996-01-01

Survey along the margins of the Helan Mountains in the Ningxia Hui and Nei Mongol Autonomous Regions discloses variability in the distribution and assemblage composition among 47 archaeological localities, and suggests a reduction in hunter-gatherer residential mobility through time. Late Palaeolithic tool assemblages are less frequent, smaller, and relatively uniform from site to site. They tend to be found near canyon mouths on the mountain front, or around springs in the middle to upper reaches of fans, suggesting limited variation in both length of stay and subsistence strategies. In contrast, early Neolithic sites, more abundant and variable in size and complexity, are located near fan toes or lower fan springs where water could be more easily diverted. Larger more diverse assemblages suggest long-term residential bases, while smaller specialized assemblages, devoid of microliths, indicate short-term camps and resource processing locations. This helps confirm a similar pattern identified in materials collected by the Sino-Swedish expedition, in the northern Alashan. Together they suggest that the trend towards decreased residential mobility is associated with increasingly intensive and specialized use of seed resources that may be related to the early development of plant husbandry. ?? 1996 Academic Press Limited.

Imaging a non-singular rotating black hole at the center of the Galaxy

NASA Astrophysics Data System (ADS)

Lamy, F.; Gourgoulhon, E.; Paumard, T.; Vincent, F. H.

2018-06-01

We show that the rotating generalization of Hayward’s non-singular black hole previously studied in the literature is geodesically incomplete, and that its straightforward extension leads to a singular spacetime. We present another extension, which is devoid of any curvature singularity. The obtained metric depends on three parameters and, depending on their values, yields an event horizon or not. These two regimes, named respectively regular rotating Hayward black hole and naked rotating wormhole, are studied both numerically and analytically. In preparation for the upcoming results of the Event Horizon Telescope, the images of an accretion torus around Sgr A*, the supermassive object at the center of the Galaxy, are computed. These images contain, even in the absence of a horizon, a central faint region which bears a resemblance to the shadow of Kerr black holes and emphasizes the difficulty of claiming the existence of an event horizon from the analysis of strong-field images. The frequencies of the co- and contra-rotating orbits at the innermost stable circular orbit (ISCO) in this geometry are also computed, in the hope that quasi-periodic oscillations may permit to compare this model with Kerr’s black hole on observational grounds.

Quantitative Spectroscopy of Supergiants in the Local Group Dwarf Galaxy IC 1613: Metallicity and Distance

NASA Astrophysics Data System (ADS)

Berger, Travis A.; Kudritzki, Rolf-Peter; Urbaneja, Miguel A.; Bresolin, Fabio; Gieren, Wolfgang; Pietrzyński, Grzegorz; Przybilla, Norbert

2018-06-01

We present a spectral analysis of 21 blue supergiant stars of spectral types late B to early A within the Local Group dwarf galaxy IC 1613, based on VLT Focal Reducer and Low Dispersion Spectrograph 2 low-resolution spectra. Combining our results with studies of early B-type blue supergiants, we report a wide bimodal distribution of metallicities with two peaks around [Z] ∼ ‑0.50 dex and [Z] ∼ ‑0.85 dex. The bimodal distribution correlates with spatial location, when compared with column densities of neutral hydrogen in IC 1613. While the low [Z] objects appear in regions of relatively high ISM H I column densities or close to them, the high [Z] supergiants are found in the central H I hole that is almost devoid of hydrogen. This suggests there are varied chemical evolution histories for the young stellar populations in IC 1613. Utilizing the flux-weighted gravity–luminosity relation, we determine IC 1613's distance modulus as m ‑ M = 24.39 ± 0.11 mag. This value is in agreement within previous distance measurements using the near-infrared period–luminosity relationship of Cepheids and the tip of the red giant branch.

RINT1 functions as a multitasking protein at the crossroads between genomic stability, ER homeostasis, and autophagy.

PubMed

Grigaravicius, Paulius; von Deimling, Andreas; Frappart, Pierre-Olivier

2016-08-02

RINT1 was first identified as an RAD50-interacting protein and its function was therefore linked to the maintenance of genomic stability. It was also shown that RINT1 was a key player in ER-Golgi trafficking as a member of an ER tethering complex interacting with STX18. However, due to early embryonic lethality of rint1-null mice, the in vivo functions of RINT1 remained for the most part elusive. We recently described the consequences of Rint1 inactivation in various neuronal cells of the central nervous system. We observed that lack of RINT1 in vivo triggers genomic instability and ER stress leading to depletion of the neural progenitor pool and neurodegeneration. Surprisingly, we also observed inhibition of autophagy in RINT1-deficient neurons, indicating an involvement of RINT1 in the regulation of neuronal autophagy. Here, we summarize our main RINT1 findings and discuss its putative roles in autophagy.

Density Enhancements and Voids Following Patchy Reconnection

NASA Astrophysics Data System (ADS)

Guidoni, S. E.; Longcope, D. W.

2011-04-01

We show, through a simple patchy reconnection model, that retracting reconnected flux tubes may present elongated regions relatively devoid of plasma, as well as long lasting, dense central hot regions. Reconnection is assumed to happen in a small patch across a Syrovatskiiˇ (non-uniform) current sheet (CS) with skewed magnetic fields. The background magnetic pressure has its maximum at the center of the CS plane and decreases toward its edges. The reconnection patch creates two V-shaped reconnected tubes that shorten as they retract in opposite directions, due to magnetic tension. One of them moves upward toward the top edge of the CS, and the other one moves downward toward the top of the underlying arcade. Rotational discontinuities (RDs) propagate along the legs of the tubes and generate parallel supersonic flows that collide at the center of the tube. There, gas-dynamic shocks that compress and heat the plasma are launched outwardly. The descending tube moves through the bottom part of the CS where it expands laterally in response to the decreasing background magnetic pressure. This effect may decrease plasma density by 30%-50% of background levels. This tube will arrive at the top of the arcade that will slow it to a stop. Here, the perpendicular dynamics is halted, but the parallel dynamics continues along its legs; the RDs are shut down, and the gas is rarified to even lower densities. The hot post-shock regions continue evolving, determining a long lasting hot region on top of the arcade. We provide an observational method based on total emission measure and mean temperature that indicates where in the CS the tube has been reconnected.

Regional differences in the blood-brain-barrier of the subfornical organs of rats and ducks (Anas platyrhynchos).

PubMed

Schmid, H A

1995-01-01

Recently published electrophysiological data investigated the effect of blood borne and brain intrinsic substances on the activity of neurons in the duck subfornical organ (SFO). This study defines histologically the region in the duck SFO, where blood borne substances can possibly influence neuronal activity. Intravenous injection of Evans blue, a dye which labels brain structures devoid of a blood brain barrier (BBB), resulted in diffuse labelling of the duck SFO from the anterior commissure to the end of the organ in rostrocaudal extension. In addition, specifically labelled neurons could be observed just rostral to the diffuse Evans blue labelling and in an area dorsomedial to the large central blood vessel. The majority of the somata of these heavily stained neurons were located inside the BBB, whereas in the areas with diffuse Evans blue labelling, thus being outside the BBB, labelled cells were rarely observed. Intravenous injection of Evans blue in rats resulted similarly in diffuse labelling of the parenchyma of the medial and caudal part of the SFO, with only a few, but heavily stained cells with fusiform somata. The rostral region of the rat SFO, which is known to have a functional BBB, shows hardly any diffuse labelling, but there the majority of neurons show strong Evans blue fluorescence. It is concluded that the heavily labelled somata inside the BBB have axonal or dendritic projections to BBB-free areas, where they can take up the dye. This study gives a functional description of the extension of the SFO areas without a BBB of rats and ducks. It is concluded that blood borne agents can affect those SFO neurons which have their somata located outside the BBB as well as those located inside the BBB which have terminals projecting to BBB free regions.

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

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

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

Oh, Yohan; Chung, Kwang Chul, E-mail: kchung@yonsei.ac.kr

Highlights: Black-Right-Pointing-Pointer ZNF131 directly interacts with ER{alpha}. Black-Right-Pointing-Pointer The binding affinity of ZNF131 to ER{alpha} increases upon E2 stimulation. Black-Right-Pointing-Pointer ZNF131 inhibits ER{alpha}-mediated trans-activation by suppressing its homo-dimerization. Black-Right-Pointing-Pointer ZNF131 inhibits ER{alpha}-dimerization and E2-induced breast cancer cell proliferation. Black-Right-Pointing-Pointer ZNF131 inhibits estrogen signaling by acting as an ER{alpha}-co-repressor. -- Abstract: Steroid hormone estrogen elicits various physiological functions, many of which are mediated through two structurally and functionally distinct estrogen receptors, ER{alpha} and ER{beta}. The functional role of zinc finger protein 131 (ZNF131) is poorly understood, but it is assumed to possess transcriptional regulation activity due to the presence of amore » DNA binding motif. A few recent reports, including ours, revealed that ZNF131 acts as a negative regulator of ER{alpha} and that SUMO modification potentiates the negative effect of ZNF131 on estrogen signaling. However, its molecular mechanism for ER{alpha} inhibition has not been elucidated in detail. Here, we demonstrate that ZNF131 directly interacts with ER{alpha}, which consequently inhibits ER{alpha}-mediated trans-activation by suppressing its homo-dimerization. Moreover, we show that the C-terminal region of ZNF131 containing the SUMOylation site is necessary for its inhibition of estrogen signaling. Taken together, these data suggest that ZNF131 inhibits estrogen signaling by acting as an ER{alpha}-co-repressor.« less

The Sigma-1 Receptor as a Pluripotent Modulator in Living Systems.

PubMed

Su, Tsung-Ping; Su, Tzu-Chieh; Nakamura, Yoki; Tsai, Shang-Yi

2016-04-01

The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum (ER) protein that resides specifically in the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), an interface between ER and mitochondria. In addition to being able to translocate to the plasma membrane (PM) to interact with ion channels and other receptors, Sig-1R also occurs at the nuclear envelope, where it recruits chromatin-remodeling factors to affect the transcription of genes. Sig-1Rs have also been reported to interact with other membranous or soluble proteins at other loci, including the cytosol, and to be involved in several central nervous system (CNS) diseases. Here, we propose that Sig-1R is a pluripotent modulator with resultant multiple functional manifestations in living systems. Published by Elsevier Ltd.

Transmembrane domain-dependent protein-protein interactions participate in the localization of GPAT enzymes to ER subdomains

USDA-ARS?s Scientific Manuscript database

The endoplasmic reticulum (ER) is a dynamic network that consists of numerous regions or subdomains with discrete morphological features and functional properties, including those involved in protein and oil-body formation, anterograde transport of secretory proteins, the exchange of macromolecules ...

North polar region of Mars: imaging results from viking 2.

PubMed

Cutts, J A; Blasius, K R; Briggs, G A; Carr, M H; Greeley, R; Masursky, H

1976-12-11

During October 1976, the Viking 2 orbiter acquired approximately 700 high-resolution images of the north polar region of Mars. These images confirm the existence at the north pole of extensive layered deposits largely covered over with deposits of perennial ice. An unconformity within the layered deposits suggests a complex history of climate change during their time of deposition. A pole-girdling accumulation of dunes composed of very dark materials is revealed for the first time by the Viking cameras. The entire region is devoid of fresh impact craters. Rapid rates of erosion or deposition are implied. A scenario for polar geological evolution, involving two types of climate change, is proposed.

Microwave sol–gel synthesis and upconversion photoluminescence properties of CaGd{sub 2}(WO{sub 4}){sub 4}:Er{sup 3+}/Yb{sup 3+} phosphors with incommensurately modulated structure

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

Lim, Chang Sung; Aleksandrovsky, Aleksandr; Department of Photonics and Laser Technologies, Siberian Federal University, Krasnoyarsk 660079

2015-08-15

CaGd{sub 2−x}(WO{sub 4}){sub 4}:Er{sup 3+}/Yb{sup 3+} phosphors with the doping concentrations of Er{sup 3+} and Yb{sup 3+} (x=Er{sup 3+}+Yb{sup 3+}, Er{sup 3+}=0.05, 0.1, 0.2 and Yb{sup 3+}=0.2, 0.45) have been successfully synthesized by the microwave sol–gel method. The crystal structure of CaGd{sub 2−x}(WO{sub 4}){sub 4}:Er{sup 3+}/Yb{sup 3+} tungstates have been refined, and upconversion photoluminescence properties have been investigated. The synthesized particles, being formed after the heat-treatment at 900 °C for 16 h, showed a well crystallized morphology. Under the excitation at 980 nm, CaGd{sub 2}(WO{sub 4}){sub 4}:Er{sup 3+}/Yb{sup 3+} particles exhibited a strong 525-nm and a weak 550-nm emission bandsmore » in the green region and a very weak 655-nm emission band in the red region. The Raman spectrum of undoped CaGd{sub 2}(WO{sub 4}){sub 4} revealed about 12 narrow lines. The strongest band observed at 903 cm{sup −1} was assigned to the ν{sub 1} symmetric stretching vibration of WO{sub 4} tetrahedrons. The spectra of the samples doped with Er and Yb obtained under the 514.5 nm excitation were dominated by Er{sup 3+} luminescence preventing the recording of these samples Raman spectra. Concentration quenching of the erbium luminescence at {sup 2}H{sub 11/2}→{sup 4}I{sub 15/2} transition is weak in the range of erbium doping level x{sub Er}=0.05–0.2, while, for transition {sup 4}S{sub 3/2}→{sup 4}I{sub 15/2}, the signs of concentration quenching become pronounced at x{sub Er}=0.2. - Graphical abstract: CaGd{sub 2−x}(WO{sub 4}){sub 4}:Er{sup 3+}/Yb{sup 3+} phosphors with the doping concentrations of Er{sup 3+} and Yb{sup 3+} (x=Er{sup 3+}+Yb{sup 3+}, Er{sup 3+}=0.05, 0.1, 0.2 and Yb{sup 3+}=0.2, 0.45) have been successfully synthesized by the microwave sol–gel method and the crystal structure refinement, and upconversion photoluminescence properties have been investigated. - Highlights: • CaGd{sub 2−x}(WO{sub 4}){sub 4}:Er{sup 3+}/Yb{sup 3+} phosphors have been synthesized by the microwave sol–gel method. • The crystal structure of CaGd{sub 2−x}(WO{sub 4}){sub 4}:Er{sup 3+}/Yb{sup 3+} tungstates have been refined. • The upconversion photoluminescence properties have been investigated.« less

Endoplasmic reticulum proteins SDF2 and SDF2L1 act as components of the BiP chaperone cycle to prevent protein aggregation.

PubMed

Fujimori, Tsutomu; Suno, Ryoji; Iemura, Shun-Ichiro; Natsume, Tohru; Wada, Ikuo; Hosokawa, Nobuko

2017-08-01

The folding of newly synthesized proteins in the endoplasmic reticulum (ER) is assisted by ER-resident chaperone proteins. BiP (immunoglobulin heavy-chain-binding protein), a member of the HSP70 family, plays a central role in protein quality control. The chaperone function of BiP is regulated by its intrinsic ATPase activity, which is stimulated by ER-resident proteins of the HSP40/DnaJ family, including ERdj3. Here, we report that two closely related proteins, SDF2 and SDF2L1, regulate the BiP chaperone cycle. Both are ER-resident, but SDF2 is constitutively expressed, whereas SDF2L1 expression is induced by ER stress. Both luminal proteins formed a stable complex with ERdj3 and potently inhibited the aggregation of different types of misfolded ER cargo. These proteins associated with non-native proteins, thus promoting the BiP-substrate interaction cycle. A dominant-negative ERdj3 mutant that inhibits the interaction between ERdj3 and BiP prevented the dissociation of misfolded cargo from the ERdj3-SDF2L1 complex. Our findings indicate that SDF2 and SDF2L1 associate with ERdj3 and act as components in the BiP chaperone cycle to prevent the aggregation of misfolded proteins, partly explaining the broad folding capabilities of the ER under various physiological conditions. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Pre-ischemia melatonin treatment alleviated acute neuronal injury after ischemic stroke by inhibiting endoplasmic reticulum stress-dependent autophagy via PERK and IRE1 signalings.

PubMed

Feng, Dayun; Wang, Bao; Wang, Lei; Abraham, Neeta; Tao, Kai; Huang, Lu; Shi, Wei; Dong, Yushu; Qu, Yan

2017-04-01

Melatonin has demonstrated a potential protective effect in central nervous system. Thus, it is interesting to determine whether pre-ischemia melatonin administration could protect against cerebral ischemia/reperfusion (IR)-related injury and the underlying molecular mechanisms. In this study, we revealed that IR injury significantly activated endoplasmic reticulum (ER) stress and autophagy in a middle cerebral artery occlusion mouse model. Pre-ischemia melatonin treatment was able to attenuate IR-induced ER stress and autophagy. In addition, with tandem RFP-GFP-LC3 adeno-associated virus, we demonstrated pre-ischemic melatonin significantly alleviated IR-induced autophagic flux. Furthermore, we showed that IR induced neuronal apoptosis through ER stress related signalings. Moreover, IR-induced autophagy was significantly blocked by ER stress inhibitor (4-PBA), as well as ER-related signaling inhibitors (PERK inhibitor, GSK; IRE1 inhibitor, 3,5-dibromosalicylaldehyde). Finally, we revealed that melatonin significantly alleviated cerebral infarction, brain edema, neuronal apoptosis, and neurological deficiency, which were remarkably abolished by tunicamycin (ER stress activator) and rapamycin (autophagy activator), respectively. In summary, our study provides strong evidence that pre-ischemia melatonin administration significantly protects against cerebral IR injury through inhibiting ER stress-dependent autophagy. Our findings shed light on the novel preventive and therapeutic strategy of daily administration of melatonin, especially among the population with high risk of cerebral ischemic stroke. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparative study of upper lip frenectomy with the CO2 laser versus the Er, Cr: YSGG laser

PubMed Central

Pié-Sánchez, Jordi; España-Tost, Antonio J.; Arnabat-Domínguez, Josep

2012-01-01

Objectives: To compare upper lip frenulum reinsertion, bleeding, surgical time and surgical wound healing in frenectomies performed with the CO2 laser versus the Er, Cr:YSGG laser. Study design: A prospective study was carried out on 50 randomized pediatric patients who underwent rhomboidal resection of the upper lip frenulum with either the CO2 laser or the Er,Cr:YSGG laser. Twenty-five patients were assigned to each laser system. All patients were examined at 7, 14, 21 days and 4 months after the operation in order to assess the surgical wound healing. Results: Insertion of the frenulum, which was preoperatively located between the upper central incisors, migrated to the mucogingival junction as a result of using both laser systems in all patients. Only two patients required a single dose of 650 mg of paracetamol, one of either study group. CO2 laser registered improved intraoperative bleeding control results and shorter surgical times. On the other hand, the Er,Cr:YSGG laser achieved faster healing. Conclusions: Upper lip laser frenectomy is a simple technique that results in minimum or no postoperative swelling or pain, and which involves upper lip frenulum reinsertion at the mucogingival junction. The CO2 laser offers a bloodless field and shorter surgical times compared with the Er,Cr:YSGG laser. On the other hand, the Er,Cr:YSGG laser achieved faster wound healing. Key words:Frenectomy, upper lip frenulum, CO2 laser, Er,Cr:YSGG laser, laser. PMID:22143683

Inter-regional comparison of land-use effects on stream metabolism

USGS Publications Warehouse

Bernot, M.J.; Sobota, D.J.; Hall, R.O.; Mulholland, P.J.; Dodds, W.K.; Webster, J.R.; Tank, J.L.; Ashkenas, L.R.; Cooper, L.W.; Dahm, Clifford N.; Gregory, S.V.; Grimm, N. B.; Hamilton, S.K.; Johnson, S.L.; McDowell, W.H.; Meyer, J.L.; Peterson, B.; Poole, G.C.; Maurice, Valett H.M.; Arango, C.; Beaulieu, J.J.; Burgin, A.J.; Crenshaw, C.; Helton, A.M.; Johnson, L.; Merriam, J.; Niederlehner, B.R.; O'Brien, J. M.; Potter, J.D.; Sheibley, R.W.; Thomas, S.M.; Wilson, K.

2010-01-01

1. Rates of whole-system metabolism (production and respiration) are fundamental indicators of ecosystem structure and function. Although first-order, proximal controls are well understood, assessments of the interactions between proximal controls and distal controls, such as land use and geographic region, are lacking. Thus, the influence of land use on stream metabolism across geographic regions is unknown. Further, there is limited understanding of how land use may alter variability in ecosystem metabolism across regions.2. Stream metabolism was measured in nine streams in each of eight regions (n = 72) across the United States and Puerto Rico. In each region, three streams were selected from a range of three land uses: agriculturally influenced, urban-influenced, and reference streams. Stream metabolism was estimated from diel changes in dissolved oxygen concentrations in each stream reach with correction for reaeration and groundwater input.3. Gross primary production (GPP) was highest in regions with little riparian vegetation (sagebrush steppe in Wyoming, desert shrub in Arizona/New Mexico) and lowest in forested regions (North Carolina, Oregon). In contrast, ecosystem respiration (ER) varied both within and among regions. Reference streams had significantly lower rates of GPP than urban or agriculturally influenced streams.4. GPP was positively correlated with photosynthetically active radiation and autotrophic biomass. Multiple regression models compared using Akaike's information criterion (AIC) indicated GPP increased with water column ammonium and the fraction of the catchment in urban and reference land-use categories. Multiple regression models also identified velocity, temperature, nitrate, ammonium, dissolved organic carbon, GPP, coarse benthic organic matter, fine benthic organic matter and the fraction of all land-use categories in the catchment as regulators of ER.5. Structural equation modelling indicated significant distal as well as proximal control pathways including a direct effect of land-use on GPP as well as SRP, DIN, and PAR effects on GPP; GPP effects on autotrophic biomass, organic matter, and ER; and organic matter effects on ER.6. Overall, consideration of the data separated by land-use categories showed reduced inter-regional variability in rates of metabolism, indicating that the influence of agricultural and urban land use can obscure regional differences in stream metabolism. ?? 2010 Blackwell Publishing Ltd.

A petrologic study of the Teanaway Basalt: Eocene slab window volcanism in central WA

NASA Astrophysics Data System (ADS)

Roepke, E.; Tepper, J. H.; Ivener, D.

2013-12-01

The Teanaway Basalt (TB) includes subaerial basalt to andesite flows, mafic to felsic tuffs, and rhyolite domes in the Central Cascades of Washington State. These volcanics overlie the extensive ~47 Ma Teanaway Dike Swarm (TDS) that cuts the underlying Swauk Formation. This study focuses on the tectonic setting of eruption and geochemical variations relating to geography and stratigraphy within the TB. The western-most area of the TB, Easton Ridge (ER), is compared with the eastern-most area of the TB, Liberty Ridge (LR) - 40 km to the east of ER. The bimodal TB consists predominantly of basaltic andesite and andesite (45.3-63.1 wt% SiO2) with subordinate rhyolite (75.9-79.4 wt% SiO2). The mafic rocks classify as primarily medium-K tholeiites (0.1-3.0 wt% K2O), but a few samples classify as alkaline. Enrichment in LILE and depletion in HFSE on spidergrams are indicative of an arc setting. However, compared with the modern Cascade Arc, the TB is distinctly higher in Fe2O3T (8.8-17.1 wt%) and TiO2 (1.1-2.7 wt%), and distinctly lower in Al2O3 (11.2-14.6) and K2O, with a similar range of Mg #s (0.15-0.48). Most tectonic discrimination plots characterize the TB as MORB, but some indicate an arc or within-plate setting. Preliminary Pb isotopic data (206Pb/204Pb = 19.13-19.19, 207Pb/204Pb = 15.62-15.64, and 208Pb/204Pb = 38.78-38.90) indicate the TB and TDS are more enriched than Cascade Arc rocks in 206Pb/204Pb and 208Pb/204Pb. Overall, these geochemical data are consistent with a model in which asthenospheric mantle ascending through a slab window interacts with mantle wedge that has previously acquired arc chemical traits. The existence of a slab window in this region during the mid-Eocene is compatible with plate reconstructions and evidence of extension that have been attributed to subduction of the Resurrection-Kula ridge (Haeussler et al., 2003). Harker plots show lavas at LR are generally more enriched than those at ER in Fe2O3T (11.9-17.1 wt% vs 8.8-15.7 wt%) MnO (0.16-0.28 wt% vs 0.11-0.24 wt%), and TiO2 (1.2-2.4 wt% vs 0.8-2.7 wt%), and have a narrower range of CaO (1.5-9.4 wt%) and Na2O (1.5-3.3 wt%) concentrations. Both LR and ER samples display modest LREE enrichment (La/Yb = 2.1-3.7) and similar incompatible element ratios, suggesting similar sources. ER samples show a broader range of REE contents but extend to lower levels, and have smaller negative Eu anomalies (Eu/Eu* = 0.55-0.96). Pearce element ratio plots suggest much of the variation reflects different degrees of plag+cpx fractionation. Alkaline lavas are restricted to ER and the central area of the TB. Differences in concentration at similar Mg# (most notably in Fe2O3T, TiO2, MnO, and Na2O) suggest multiple parent magmas, probably from similar mantle sources. With increasing stratigraphic height in the ~1.6 km thick LR section, there are general decreases in SiO2 (60 to 54 wt%), and general increases in CaO (4 to 8 wt%), MnO (0.1-0.15 wt%), and P2O5 (0.2-0.65 wt%). Mg# displays several cycles of decrease followed by increase, each extending over 400-1000m. These trends are suggestive of an evolving system that experienced multiple replenishment events.

Selective export of autotaxin from the endoplasmic reticulum.

PubMed

Lyu, Lin; Wang, Baolu; Xiong, Chaoyang; Zhang, Xiaotian; Zhang, Xiaoyan; Zhang, Junjie

2017-04-28

Autotaxin (ATX) or ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) is a secretory glycoprotein and functions as the key enzyme for lysophosphatidic acid generation. The mechanism of ATX protein trafficking is largely unknown. Here, we demonstrated that p23, a member of the p24 protein family, was the protein-sorting receptor required for endoplasmic reticulum (ER) export of ATX. A di-phenylalanine (Phe-838/Phe-839) motif in the human ATX C-terminal region was identified as a transport signal essential for the ATX-p23 interaction. Knockdown of individual Sec24 isoforms by siRNA revealed that ER export of ATX was impaired only if Sec24C was down-regulated. These results suggest that ATX is selectively exported from the ER through a p23, Sec24C-dependent pathway. In addition, it was found that AKT signaling played a role in ATX secretion regulation to facilitate ATX ER export by enhancing the nuclear factor of activated T cell-mediated p23 expression. Furthermore, the di-hydrophobic amino acid motifs (FY) also existed in the C-terminal regions of human ENPP1 and ENPP3. Such a p23, Sec24C-dependent selective ER export mechanism is conserved among these ENPP family members. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

Gupta, Tushar; Robles, Maria Teresa Sáenz; Schowalter, Rachel M.

Polyomaviruses induce cell proliferation and transformation through different oncoproteins encoded within the early region (ER): large T antigen (LT), small T antigen (sT) and, in some cases, additional components. Each virus utilizes different mechanisms to achieve transformation. For instance, the LTs of Simian virus 40 (SV40), BK and/or JC virus can induce transformation; but Merkel Cell Polyomavirus (MCPyV) requires expression of sT. Lymphotropic Papovavirus (LPV) is closely related to Human Polyomavirus 9 (HuPyV9) and, under similar conditions, mice expressing LPV.ER exhibit higher rates of tumor formation than mice expressing SV40.ER. We have investigated the contributions of individual LPV.ER components tomore » cell transformation. In contrast to SV40, LPV.ER transforms mouse embryonic fibroblasts (MEFs), but expression of LPV LT is insufficient to transform MEFs. Furthermore, LPV sT induces immortalization and transformation of MEFs. Thus, in the case of LPV, sT is the main mediator of oncogenesis. - Highlights: • Characterization of early region products from the Lymphotropic Polyomavirus (LPV). • On its own, sT immortalizes and transforms mouse primary cells, and is able to block p53 activation. • Combined LT and sT expression induces a greater rate of proliferation than either LT or sT alone.« less

Choline kinase inhibition induces exacerbated endoplasmic reticulum stress and triggers apoptosis via CHOP in cancer cells

PubMed Central

Sanchez-Lopez, E; Zimmerman, T; Gomez del Pulgar, T; Moyer, M P; Lacal Sanjuan, J C; Cebrian, A

2013-01-01

Endoplasmic reticulum (ER) is a central organelle in eukaryotic cells that regulates protein synthesis and maturation. Perturbation of ER functions leads to ER stress, which has been previously associated with a broad variety of diseases. ER stress is generally regarded as compensatory, but prolonged ER stress has been involved in apoptosis induced by several cytotoxic agents. Choline kinase α (ChoKα), the first enzyme in the Kennedy pathway, is responsible for the generation of phosphorylcholine (PCho) that ultimately renders phosphatidylcholine. ChoKα overexpression and high PCho levels have been detected in several cancer types. Inhibition of ChoKα has demonstrated antiproliferative and antitumor properties; however, the mechanisms underlying these activities remain poorly understood. Here, we demonstrate that ChoKα inhibitors (ChoKIs), MN58b and RSM932A, induce cell death in cancer cells (T47D, MCF7, MDA-MB231, SW620 and H460), through the prolonged activation of ER stress response. Evidence of ChoKIs-induced ER stress includes enhanced production of glucose-regulated protein, 78 kDa (GRP78), protein disulfide isomerase, IRE1α, CHOP, CCAAT/enhancer-binding protein beta (C/EBPβ) and TRB3. Although partial reduction of ChoKα levels by small interfering RNA was not sufficient to increase the production of ER stress proteins, silencing of ChoKα levels also show a decrease in CHOP overproduction induced by ChoKIs, which suggests that ER stress induction is due to a change in ChoKα protein folding after binding to ChoKIs. Silencing of CHOP expression leads to a reduction in C/EBPβ, ATF3 and GRP78 protein levels and abrogates apoptosis in tumor cells after treatment with ChoKIs, suggesting that CHOP maintains ER stress responses and triggers the pro-apoptotic signal. Consistent with the differential effect of ChoKIs in cancer and primary cells previously described, ChoKIs only promoted a transient and moderated ER stress response in the non-tumorogenic cells MCF10A. In conclusion, pharmacological inhibition of ChoKα induces cancer cell death through a mechanism that involves the activation of exaggerated and persistent ER stress supported by CHOP overproduction. PMID:24287694

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.

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.

ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43

NASA Astrophysics Data System (ADS)

Stoica, Radu; de Vos, Kurt J.; Paillusson, Sébastien; Mueller, Sarah; Sancho, Rosa M.; Lau, Kwok-Fai; Vizcay-Barrena, Gema; Lin, Wen-Lang; Xu, Ya-Fei; Lewis, Jada; Dickson, Dennis W.; Petrucelli, Leonard; Mitchell, Jacqueline C.; Shaw, Christopher E.; Miller, Christopher C. J.

2014-06-01

Mitochondria and the endoplasmic reticulum (ER) form tight structural associations and these facilitate a number of cellular functions. However, the mechanisms by which regions of the ER become tethered to mitochondria are not properly known. Understanding these mechanisms is not just important for comprehending fundamental physiological processes but also for understanding pathogenic processes in some disease states. In particular, disruption to ER-mitochondria associations is linked to some neurodegenerative diseases. Here we show that the ER-resident protein VAPB interacts with the mitochondrial protein tyrosine phosphatase-interacting protein-51 (PTPIP51) to regulate ER-mitochondria associations. Moreover, we demonstrate that TDP-43, a protein pathologically linked to amyotrophic lateral sclerosis and fronto-temporal dementia perturbs ER-mitochondria interactions and that this is associated with disruption to the VAPB-PTPIP51 interaction and cellular Ca2+ homeostasis. Finally, we show that overexpression of TDP-43 leads to activation of glycogen synthase kinase-3β (GSK-3β) and that GSK-3β regulates the VAPB-PTPIP51 interaction. Our results describe a new pathogenic mechanism for TDP-43.

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.

Influence of semi-quantitative oestrogen receptor expression on adjuvant endocrine therapy efficacy in ductal and lobular breast cancer - a TEAM study analysis.

PubMed

van de Water, Willemien; Fontein, Duveken B Y; van Nes, Johanna G H; Bartlett, John M S; Hille, Elysée T M; Putter, Hein; Robson, Tammy; Liefers, Gerrit-Jan; Roumen, Rudi M H; Seynaeve, Caroline; Dirix, Luc Y; Paridaens, Robert; Kranenbarg, Elma Meershoek-Klein; Nortier, Johan W R; van de Velde, Cornelis J H

2013-01-01

Multiple studies suggest better efficacy of chemotherapy in invasive ductal breast carcinomas (IDC) than invasive lobular breast carcinomas (ILC). However, data on efficacy of adjuvant endocrine therapy regimens and histological subtypes are sparse. This study assessed endocrine therapy efficacy in IDC and ILC. The influence of semi-quantitative oestrogen receptor (ER) expression by Allred score was also investigated. Dutch and Belgian patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were randomized to exemestane (25mg daily) alone or following tamoxifen (20mg daily) for 5 years. Inclusion was restricted to IDC and ILC patients. Histological subtype was assessed locally; ER expression was centrally reviewed according to Allred score (ER-poor (<7; n=235); ER-rich (7; n=1789)). Primary end-point was relapse-free survival (RFS), which was the time from randomization to disease relapse. Overall, 2140 (82%) IDC and 463 (18%) ILC patients were included. RFS was similar for both endocrine treatment regimens in IDC (hazard ratio (HR) for exemestane was 0.83 (95%confidence interval (CI) 0.67-1.03)), and ILC (HR 0.69 (95%CI 0.45-1.06)). Irrespective of histological subtype, patients with ER-rich Allred scores allocated to exemestane alone had an improved RFS (multivariable HR 0.71 (95%CI 0.56-0.89)). In contrast, patients with ER-poor Allred scores allocated to exemestane had a worse RFS (multivariable HR 2.33 (95%CI 1.32-4.11)). Significant effect modification by ER-Allred score was confirmed (multivariable p=0.003). Efficacy of endocrine therapy regimens was similar for IDC and ILC. However, ER-rich patients showed superior efficacy to upfront exemestane, while ER-poor patients had better outcomes with sequential therapy, irrespective of histological subtype, emphasising the relevance of quantification of ER expression. Copyright © 2012 Elsevier Ltd. All rights reserved.

Polyglycerol-opioid conjugate produces analgesia devoid of side effects.

PubMed

González-Rodríguez, Sara; Quadir, Mohiuddin A; Gupta, Shilpi; Walker, Karolina A; Zhang, Xuejiao; Spahn, Viola; Labuz, Dominika; Rodriguez-Gaztelumendi, Antonio; Schmelz, Martin; Joseph, Jan; Parr, Maria K; Machelska, Halina; Haag, Rainer; Stein, Christoph

2017-07-04

Novel painkillers are urgently needed. The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy and report the synthesis and analgesic efficacy of the standard opioid morphine covalently attached to hyperbranched polyglycerol (PG-M) by a cleavable linker. With its high-molecular weight and hydrophilicity, this conjugate is designed to selectively release morphine in injured tissue and to prevent blood-brain barrier permeation. In contrast to conventional morphine, intravenous PG-M exclusively activated peripheral opioid receptors to produce analgesia in inflamed rat paws without major side effects such as sedation or constipation. Concentrations of morphine in the brain, blood, paw tissue, and in vitro confirmed the selective release of morphine in the inflamed milieu. Thus, PG-M may serve as prototype of a peripherally restricted opioid formulation designed to forego central and intestinal side effects.

Breast cancer and exposure to aircraft, road, and railway-noise: a case-control study based on health insurance records.

PubMed

Hegewald, Janice; Schubert, Melanie; Wagner, Mandy; Dröge, Patrik; Prote, Ursel; Swart, Enno; Möhler, Ulrich; Zeeb, Hajo; Seidler, Andreas

2017-11-01

Objectives Aircraft, road, and rail traffic noise can cause sleep disturbances. Since night work and shorter sleep durations have been linked to increased risks of breast cancer, we examined if 24-hour, or day- or night-time traffic noise exposure may also increase the risk of breast cancer. Methods To investigate the noise-related risks of breast cancer, the pseudonymized insurance records of three large statutory health companies (2005-2010) for women aged ≥40 years living in the region surrounding the Frankfurt international airport were analyzed with address-specific acoustic data representing aircraft, road, and rail-traffic noise. Noise exposure among women with incident breast cancer (N=6643) were compared with that of control subjects (N=471 596) using logistic regression and adjusting for age, hormone replacement therapy, education and occupation (only available for 27.9%), and a regional proportion of persons receiving long-term unemployment benefits as an ecological indicator of socioeconomic level. Analyses were also stratified according to estrogen receptor (ER) status. Results An increased odds ratio (OR) was observed for ER negative (ER-) tumors at 24-hour aircraft noise levels 55-59 dB [OR 55-59 dB 1.41, 95% confidence interval (CI) 1.04-1.90] but not for ER positive (ER+) breast cancers (OR 55-59 dB 0.95, 95% CI 0.75-1.20). Clear associations between road and rail traffic noise were not observed. Conclusions The results indicate increased aircraft noise may be an etiologic factor for ER- breast cancers. However, information regarding potential confounding factors was largely unattainable. Further research is required to understand how environmental noise may be involved in the pathogenesis of ER- breast cancers.

Relationship between CYP1A2 Localization and Lipid Microdomain Formation as a Function of Lipid Composition

PubMed Central

Brignac-Huber, Lauren M.; Reed, James R.; Eyer, Marilyn K.

2013-01-01

Cytochrome P450 (P450) function requires the interaction of P450 and NADPH-cytochrome P450 reductase (CPR) in membranes, and is frequently studied using reconstituted systems composed solely of phosphatidylcholine. There is increasing evidence that other endoplasmic reticulum (ER) lipids can affect P450 structure, activity, and interactions with CPR. Some of these lipid effects have been attributed to the formation of organized liquid-ordered (lo) domains. The goal of this study was to determine if lo domains were formed in P450 reconstituted systems mimicking the ER membrane. CYP1A2, when incorporated in “ER-like” lipid vesicles, displayed detergent insolubility after treatment with Brij 98 and centrifugation in a sucrose gradient. Lipid probes were employed to identify domain formation in both ER-like vesicles and model membranes known to form lo domains. Changes in fluorescence resonance energy transfer (FRET) using an established donor/acceptor FRET pair in both ER-like and model lo-forming systems demonstrated the coexistence of lo- and liquid-disordered domains as a function of cholesterol and sphingomyelin content. Similarly, 6-dodecanoyl-2-dimethylaminonaphthalene (laurdan), a probe that reports on membrane organization, showed that cholesterol and sphingomyelin increased membrane order. Finally, brominated-phosphatidylcholine allowed for monitoring of the location of both CPR and CYP1A2 within the lo regions of ER-like systems. Taken together, the results demonstrate that ER-like vesicles generate microdomains, and both CYP1A2 and CPR predominantly localize into lo membrane regions. Probe fluorescent responses suggest that lipid microdomains form in these vesicles whether or not enzymes are included in the reconstituted systems. Thus, it does not appear that the proteins are critical for stabilizing lo domains. PMID:23963955

Brain ACE2 overexpression reduces DOCA-salt hypertension independently of endoplasmic reticulum stress

PubMed Central

de Queiroz, Thyago Moreira; Sriramula, Srinivas; Feng, Yumei; Johnson, Tanya; Mungrue, Imran N.; Lazartigues, Eric

2014-01-01

Endoplasmic reticulum (ER) stress was previously reported to contribute to neurogenic hypertension while neuronal angiotensin-converting enzyme type 2 (ACE2) overexpression blunts the disease. To assess which brain regions are important for ACE2 beneficial effects and the contribution of ER stress to neurogenic hypertension, we first used transgenic mice harboring a floxed neuronal hACE2 transgene (SL) and tested the impact of hACE2 knockdown in the subfornical organ (SFO) and paraventricular nucleus (PVN) on deoxycorticosterone acetate (DOCA)-salt hypertension. SL and nontransgenic (NT) mice underwent DOCA-salt or sham treatment while infected with an adenoassociated virus (AAV) encoding Cre recombinase (AAV-Cre) or a control virus (AAV-green fluorescent protein) to the SFO or PVN. DOCA-salt-induced hypertension was reduced in SL mice, with hACE2 overexpression in the brain. This reduction was only partially blunted by knockdown of hACE2 in the SFO or PVN, suggesting that both regions are involved but not essential for ACE2 regulation of blood pressure (BP). DOCA-salt treatment did not increase the protein levels of ER stress and autophagy markers in NT mice, despite a significant increase in BP. In addition, these markers were not affected by hACE2 overexpression in the brain, despite a significant reduction of hypertension in SL mice. To further assess the role of ER stress in neurogenic hypertension, NT mice were infused intracerebroventricularlly with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, during DOCA-salt treatment. However, TUDCA infusion failed to blunt the development of hypertension in NT mice. Our data suggest that brain ER stress does not contribute to DOCA-salt hypertension and that ACE2 blunts neurogenic hypertension independently of ER stress. PMID:25519733

Toward Rechargeable Persistent Luminescence for the First and Third Biological Windows via Persistent Energy Transfer and Electron Trap Redistribution.

PubMed

Xu, Jian; Murata, Daisuke; Ueda, Jumpei; Viana, Bruno; Tanabe, Setsuhisa

2018-05-07

Persistent luminescence (PersL) imaging without real-time external excitation has been regarded as the next generation of autofluorescence-free optical imaging technology. However, to achieve improved imaging resolution and deep tissue penetration, developing new near-infrared (NIR) persistent phosphors with intense and long duration PersL over 1000 nm is still a challenging but urgent task in this field. Herein, making use of the persistent energy transfer process from Cr 3+ to Er 3+ , we report a novel garnet persistent phosphor of Y 3 Al 2 Ga 3 O 12 codoped with Er 3+ and Cr 3+ (YAG G:Er-Cr), which shows intense Cr 3+ PersL (∼690 nm) in the deep red region matching well with the first biological window (NIR-I, 650-950 nm) and Er 3+ PersL (∼1532 nm) in the NIR region matching well with the third biological window (NIR-III, 1500-1800 nm). The optical imaging through raw-pork tissues (thickness of 1 cm) suggests that the emission band of Er 3+ can achieve higher spatial resolution and more accurate signal location than that of Cr 3+ due to the reduced light scattering at longer wavelengths. Furthermore, by utilizing two independent electron traps with two different trap depths in YAG G:Er-Cr, the Cr 3+ /Er 3+ PersL can even be recharged in situ by photostimulation with 660 nm LED thanks to the redistribution of trapped electrons from the deep trap to the shallow one. Our results serve as a guide in developing promising NIR (>1000 nm) persistent phosphors for long-term optical imaging.

Females and males are highly similar in language performance and cortical activation patterns during verb generation.

PubMed

Allendorfer, Jane B; Lindsell, Christopher J; Siegel, Miriam; Banks, Christi L; Vannest, Jennifer; Holland, Scott K; Szaflarski, Jerzy P

2012-10-01

To test the existence of sex differences in cortical activation during verb generation when performance is controlled for. Twenty male and 20 female healthy adults underwent functional magnetic resonance imaging (fMRI) using a covert block-design verb generation task (BD-VGT) and its event-related version (ER-VGT) that allowed for intra-scanner recordings of overt responses. Task-specific activations were determined using the following contrasts: BD-VGT covert generation>finger-tapping; ER-VGT overt generation>repetition; ER-VGT overt>covert generation. Lateral cortical regions activated during each contrast were used for calculating language lateralization index scores. Voxelwise regressions were used to determine sex differences in activation, with and without controlling for performance. Each brain region showing male/female activation differences for ER-VGT overt generation>repetition (isolating noun-verb association) was defined as a region of interest (ROI). For each subject, the signal change in each ROI was extracted, and the association between ER-VGT activation related to noun-verb association and performance was assessed separately for each sex. Males and females performed similarly on language assessments, had similar patterns of language lateralization, and exhibited similar activation patterns for each fMRI task contrast. Regression analysis controlling for overt intra-scanner performance either abolished (BD-VGT) or reduced (ER-VGT) the observed differences in activation between sexes. The main difference between sexes occurred during ER-VGT processing of noun-verb associations, where males showed greater activation than females in the right middle/superior frontal gyrus (MFG/SFG) and the right caudate/anterior cingulate gyrus (aCG) after controlling for performance. Better verb generation performance was associated with increased right caudate/aCG activation in males and with increased right MFG/SFG activation in females. Males and females exhibit similar activation patterns during verb generation fMRI, and controlling for intra-scanner performance reduces or even abolishes sex differences in language-related activation. These results suggest that previous findings of sex differences in neuroimaging studies that did not control for task performance may reflect false positives. Copyright © 2011 Elsevier Srl. All rights reserved.

78 FR 2389 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-11

...; ER10-2814-002; ER10-3026-002. Applicants: Copper Mountain Solar 1, LLC, Copper Mountain Solar 2, LLC, Energia Sierra Juarez U.S., LLC, Mesquite Power, LLC, Mesquite Solar 1, LLC, San Diego Gas & Electric... Power Analysis for the Southwest Power Pool, Inc. Region of Copper Mountain Solar 1, LLC, et. al. Filed...

(abstract) Monitoring Seasonal Change in Taiga Forests Using ERS-1 SAR Data

NASA Technical Reports Server (NTRS)

Way, JoBea; Rignot, Eric; McDonald, Kyle; Viereck, Leslie; Williams, Cynthia; Adams, Phyllis; Payne, Cheryl; Wood, William

1993-01-01

Sensitivity of radar backscatter to the dielectric and geometric character of forested regions suggests significant changes in backscatter are expected with season due to freezing temperatures, snow, wind, leaf fall, and drought. The first European Remote Sensing Satellite, ERS-1, offers a unique opportunity to monitor a complete seasonal cycle for the Alaskan taiga forest ecosystem with synthetic aperture radar. During the 3-day repeat Commissioning Phase of ERS-1, from August 1991to December 1991, ERS-1 SAR data were collected in the region of Manley Hot Springs, Alaska, along the Tanana River, west of Fairbanks. In parallel with the SAR data collection, meteorological data from three weather stations positioned in three forest stands were collected continuously along with in situ measurements of the dielectric and moisture properties of the canopy and of ground cover which were collected during each overflight. The in situ data were collected in floodplain forest stands dominated by balsam poplar, white spruce, and black spruce. These results from the Commissioning Phase as well as preliminary results from the 35-day Repeat Phase will be presented.

Diet-induced obesity induces endoplasmic reticulum stress and insulin resistance in the amygdala of rats☆

PubMed Central

Castro, Gisele; C. Areias, Maria Fernanda; Weissmann, Lais; Quaresma, Paula G.F.; Katashima, Carlos K.; Saad, Mario J.A.; Prada, Patricia O.

2013-01-01

Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala. PMID:24251109

Influence of Landmarks on Wayfinding and Brain Connectivity in Immersive Virtual Reality Environment

PubMed Central

Sharma, Greeshma; Kaushal, Yash; Chandra, Sushil; Singh, Vijander; Mittal, Alok P.; Dutt, Varun

2017-01-01

Spatial navigation is influenced by landmarks, which are prominent visual features in the environment. Although previous research has focused on finding advantages of landmarks on wayfinding via experimentation; however, less attention has been given to identifying the key attributes of landmarks that facilitate wayfinding, including the study of neural correlates (involving electroencephalogram, EEG analyses). In this paper, we combine behavioral measures, virtual environment, and EEG signal-processing to provide a holistic investigation about the influence of landmarks on performance during navigation in a maze-like environment. In an experiment, participants were randomly divided into two conditions, Landmark-enriched (LM+; N = 17) and Landmark-devoid (LM-; N = 18), and asked to navigate from an initial location to a goal location in a maze. In the LM+ condition, there were landmarks placed at certain locations, which participants could use for wayfinding in the maze. However, in the LM- condition, such landmarks were not present. Beyond behavioral analyses of data, analyses were carried out of the EEG data collected using a 64-channel device. Results revealed that participants took less time and committed fewer errors in navigating the maze in the LM+ condition compared to the LM- condition. EEG analyses of the data revealed that the left-hemispheric activation was more prominent in the LM+ condition compared to the LM- condition. The event-related desynchronization/synchronization (ERD/ERS) of the theta frequency band, revealed activation in the left posterior inferior and superior regions in the LM+ condition compared to the LM- condition, suggesting an occurrence of an object-location binding in the LM+ condition along with spatial transformation between representations. Moreover, directed transfer function method, which measures information flow between two regions, showed a higher number of active channels in the LM- condition compared to the LM+ condition, exhibiting additional wiring cost associated with the cognitive demands when no landmark was available. These findings reveal pivotal role of the left-hemispheric region (especially, parietal cortex), which indicates the integration of available sensory cues and current memory requirements to encode contextual information of landmarks. Overall, this research helps to understand the role of brain regions and processes that are utilized when people use landmarks in navigating maze-like environments. PMID:28775698

Modulation of estrogenic action in clear cell carcinoma of the ovary (Review)

PubMed Central

TANASE, YASUHITO; YAMADA, YOSHIHIKO; SHIGETOMI, HIROSHI; KAJIHARA, HIROTAKA; OONOGI, AKIRA; YOSHIZAWA, YORIKO; FURUKAWA, NAOTO; HARUTA, SHOJI; YOSHIDA, SHOZO; SADO, TOSHIYUKI; OI, HIDEKAZU; KOBAYASHI, HIROSHI

2012-01-01

Two histologic types, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC), are the common histology in ovarian cancer patients who have associated endometriosis. However, both tumor types have distinct clinicopathological characteristics and molecular phenotypes. EAC is predominantly positive for estrogen receptor (ER), but CCC specifically exhibits lower ER expression. This study reviews the current understanding of the role of the ER information in the pathogenesis of CCC, as well as the English language literature for biochemical studies on ER expression and estrogenic action in CCC. The iron-mediated oxidative stress occurs due to repeated hemorrhage in endometriosis, then this compound oxidatively modifies genomic DNA and, subsequently, ER depletion may be observed. There are a number of factors that interfere with ER expression and estrogen activity, which include DNA methylation of the promoter region, histone deacetylation, heme and iron binding, chromatin remodeling and ubiquitin ligase activity. Loss of estrogen function may be a turning point in CCC progression and aggressiveness. PMID:22969838

[Changes in vitamin A intake following the social marketing of red palm oil among children and women in Burkina Faso].

PubMed

Zagré, No l-Marie; Delisle, Hélène; Tarini, Ann; Delpeuch, Francis

2002-01-01

This paper focuses on changes in vitamin A (VA) intakes as part of the evaluation of a pilot project on social marketing of red palm oil (RPO) as a VA supplement for mothers and children in central-north Burkina Faso. The objectives of the 30-month project are to demonstrate the feasibility and effectiveness of introducing RPO in non-consuming areas. RPO is collected from women in the South-West region and it is sold in project sites by village volunteers. RPO is promoted by community workers trained in persuasive communication and social marketing. The target population is free to buy and consume RPO. Evaluation design includes data collected at onset, then 12 and 24 months later, from the same sample of 210 mothers and their children randomly selected in seven project sites. Children were 1 to 3 years old at onset. Blood samples were collected at baseline from mothers and children for serum retinol determination by HPLC. VA intakes are estimated by a semi-quantitative food frequency questionnaire, using the conventional beta-carotene to retinol conversion factors and the newly revised lower factors. VA deficiency is a major public health problem in the area: 64% of mothers and 85% of children had serum retinol concentrations < 0,70 mumol/l at baseline. VA came mainly from plant foods, particularly fruits and dark green vegetables which provided more than 90% of the dietary VA at onset of the project. Mean vitamin A intakes are low. We found 138 106 mug ER for the children and 302 +/- 235 microg ER for the mothers with conventional factors and 64 +/- 58 microg ER and 133 +/- 162 microg ER, respectively, with the revised factors. One year later, one third of respondents had consumed RPO in the previous week, and it supplied around 56% of the VA intake of children and 67% of mothers (36% and 46% respectively for the whole group). VA intakes were significantly increased at 510 +/- 493 microg ER and 801 +/- 913 microg ER for the children and their mothers respectively (347 +/- 443 microg ER and 568 +/- 803 microg ER respectively, with the revised factors). Analyzing serum retinol and dietary data collected at baseline, it was found that VA intakes < 62,5% of safe level of intake were highly sensitive to low serum retinol (< 0,70 micromol/l) and using revised conversion factors to assess total VA intake slightly enhanced sensitivity. The proportion of mothers and children at risk of inadequate VA intake changed from nearly 100% at baseline to 60% one year later. The results show that promoting RPO (and other VA rich foods) was effective in improving VA intakes. This improvement will hopefully be sustained and even further enhanced during the remaining 12 months of the project, after which repeated measurement of serum retinol and VA intakes will allow the actual impact of the project to be truly assessed.

Demodicosis in black bears (Ursus americanus) from Florida.

PubMed

Forrester, D J; Spalding, M G; Wooding, J B

1993-01-01

Demodicosis was diagnosed in five black bears (Ursus americanus) from north-central Florida. The first bear examined, a 5-yr-old male, had severe alopecia except for the dorsal neck, paws, and ears. The skin was characterized by moderate orthokeratotic hyperkeratosis, and mild to moderate follicular hyperkeratosis. Superficial dermatitis, follicular pustules, and epidermal pustules were present, but rare. Specimens of Demodex sp. were seen most commonly within hair follicles devoid of hair and at the infundibulum of sebaceous glands. Four additional bears from the same area also had some degree of alopecia and skin scrapings were positive for Demodex sp. This mite may be common, although its prevalence is not known.

Diversion and Illicit Sale of Extended Release Tapentadol in the United States

PubMed Central

Surratt, Hilary L.; Le Lait, Marie-Claire; Stivers, Yami; Bebarta, Vikhyat S.; Freifeld, Clark C.; Brownstein, John S.; Burke, John J.; Kurtz, Steven P.; Dasgupta, Nabarun

2016-01-01

Objective.  Prescription opioid analgesics are commonly prescribed for moderate to severe pain. An unintended consequence of prescribing opioid analgesics is the abuse and diversion of these medications. Tapentadol ER is a recently approved centrally acting analgesic with synergistic mechanisms of action: μ-opioid receptor agonism and inhibition of norepinephrine reuptake. We assessed the amount of diversion and related cost of obtaining tapentadol IR (Nucynta®) and tapentadol ER (Nucynta ER®) as well as other Schedule II opioid medications in street transactions in the United States using the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System. Methods.  The Drug Diversion Program measures the number of cases opened by 260 drug diversion investigators in 49 states. StreetRxTM uses a crowd-sourcing Website to collect the prices paid for licit or illicit drugs. Results.  The population-based rates of diversion were 0.003 (tapentadol IR), 0.001 (tapentadol ER), and 1.495 (other Schedule II opioid tablets) reports per 100,000 population. The tapentadol ER rate was lower than the other Schedule II opioid tablets (P < 0.001) and tapentadol IR (P= 0.004). Diversion rates based on drug availability were 0.03 (tapentadol IR), 0.016 (tapentadol ER), and 0.172 (other Schedule II opioid tablets) per 1,000 prescriptions dispensed. The median street price per milligram was $0.18 (tapentadol IR), $0.10 (tapentadol ER), and $1.00 (other Schedule II opioid tablets). Discussion.  Our results indicate that tapentadol ER is rarely sold illicitly in the United States. When sold illicitly, tapentadol ER costs less than other Schedule II opioid products. PMID:26814267

Characterization of protein--DNA interactions using surface plasmon resonance spectroscopy with various assay schemes.

PubMed

Teh, Huey Fang; Peh, Wendy Y X; Su, Xiaodi; Thomsen, Jane S

2007-02-27

Specific protein-DNA interactions play a central role in transcription and other biological processes. A comprehensive characterization of protein-DNA interactions should include information about binding affinity, kinetics, sequence specificity, and binding stoichiometry. In this study, we have used surface plasmon resonance spectroscopy (SPR) to study the interactions between human estrogen receptors (ER, alpha and beta subtypes) and estrogen response elements (ERE), with four assay schemes. First, we determined the sequence-dependent receptors' binding capacity by monitoring the binding of ER to various ERE sequences immobilized on a sensor surface (assay format denoted as the direct assay). Second, we screened the relative affinity of ER for various ERE sequences using a competition assay, in which the receptors bind to an ERE-immobilized surface in the presence of competitor ERE sequences. Third, we monitored the assembly of ER-ERE complexes on a SPR surface and thereafter the removal and/or dissociation of the ER (assay scheme denoted as the dissociation assay) to determine the binding stoichiometry. Last, a sandwich assay (ER binding to ERE followed by anti-ER recognition of a specific ER subtype) was performed in an effort to understand how ERalpha and ERbeta may associate and compete when binding to the DNA. With these assay schemes, we reaffirmed that (1) ERalpha is more sensitive than ERbeta to base pair change(s) in the consensus ERE, (2) ERalpha and ERbeta form a heterodimer when they bind to the consensus ERE, and (3) the binding stoichiometry of both ERalpha- and ERbeta-ERE complexes is dependent on salt concentration. With this study, we demonstrate the versatility of the SPR analysis. With the involvement of various assay arrangements, the SPR analysis can be further extended to more than kinetics and affinity study.

Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection.

PubMed

Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida T G; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

2015-08-01

Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s--the active form of the UPR mediator XBP1--and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection. © 2015 The Authors.

Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection

PubMed Central

Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida TG; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

2015-01-01

Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s—the active form of the UPR mediator XBP1—and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection. PMID:26113366

Molecular evidence that rough endoplasmic reticulum is the site of calreticulin translation in Petunia pollen tubes growing in vitro.

PubMed

Suwińska, Anna; Lenartowski, Robert; Smoliński, Dariusz Jan; Lenartowska, Marta

2015-07-01

In germinating pollen grains and growing pollen tubes, CRT is translated on ER membrane-bound ribosomes in the regions where its activity is required for stabilization of tip-focused Ca (2+) gradient. Pollen tube growth requires coordination of signaling, exocytosis, and actin cytoskeletal organization. Many of these processes are thought to be controlled by finely tuned regulation of cytoplasmic Ca(2+) in discrete regions of the tube cytoplasm. Most notably, a mechanism must function to maintain a steep gradient of Ca(2+) that exists at the tip of growing pollen tube. Several pieces of evidence point to calreticulin (CRT) as a key Ca(2+)-binding/-buffering protein involved in pollen germination and pollen tube growth. We previously hypothesized that in germinating pollen and growing tubes, CRT is translated on the ribosomes associated with endoplasmic reticulum (ER) in the regions where its activity might be required. In this report, we have addressed this idea by identifying the sites where CRT mRNA, CRT protein, 18S rRNA, and rough ER are localized in Petunia pollen tubes. We observed all four components in the germinal aperture of pollen grains and in subapical regions of elongating tubes. These results seem to support our idea that CRT is translated on ER membrane-bound ribosomes during pollen germination and pollen tube growth. In elongated pollen tubes, we found CRT mainly localized in the subapical zone, where ER and Golgi stacks are abundant. In eukaryotic cells, these organelles serve as mobile intracellular stores of easily releasable Ca(2+), which can be buffered by proteins such as CRT. Therefore, we postulate that subapical-localized CRT is involved in pollen tube growth by maintaining the stable tip-focused Ca(2+) gradient and thus modulating local Ca(2+) concentration within the tube cytoplasm.

Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer's disease.

PubMed

Sharoar, M G; Shi, Q; Ge, Y; He, W; Hu, X; Perry, G; Zhu, X; Yan, R

2016-09-01

Pathological features in Alzheimer's brains include mitochondrial dysfunction and dystrophic neurites (DNs) in areas surrounding amyloid plaques. Using a mouse model that overexpresses reticulon 3 (RTN3) and spontaneously develops age-dependent hippocampal DNs, here we report that DNs contain both RTN3 and REEPs, topologically similar proteins that can shape tubular endoplasmic reticulum (ER). Importantly, ultrastructural examinations of such DNs revealed gradual accumulation of tubular ER in axonal termini, and such abnormal tubular ER inclusion is found in areas surrounding amyloid plaques in biopsy samples from Alzheimer's disease (AD) brains. Functionally, abnormally clustered tubular ER induces enhanced mitochondrial fission in the early stages of DN formation and eventual mitochondrial degeneration at later stages. Furthermore, such DNs are abrogated when RTN3 is ablated in aging and AD mouse models. Hence, abnormally clustered tubular ER can be pathogenic in brain regions: disrupting mitochondrial integrity, inducing DNs formation and impairing cognitive function in AD and aging brains.

Biological Control Agents of Hydrilla Verticillata; Final Report on Surveys in East Africa, 1981-1984.

DTIC Science & Technology

1986-07-01

terminal buds, attributable to insect feeding, but no causative agent was found. Some stems had obviously been grazed by fish, probably Tilapia ziulii...dispersal of the phytophagous Tilapia zillii through much of the region may also have played a part in stressing the plant. However, it seems...in nutrients. Most have high populations of depauperate Tilapia and, possibly as a result, are seemingly devoid of sub- 4merged vegetation. Pistia was

Cholinergic and nitrergic neuronal networks in the goldfish telencephalon.

PubMed

Giraldez-Perez, Rosa M; Gaytan, Susana P; Pasaro, Rosario

2013-01-01

The general organization of cholinergic and nitrergic elements in the central nervous system seems to be highly conserved among vertebrates, with the involvement of these neurotransmitter systems now well established in sensory, motor and cognitive processing. The goldfish is a widely used animal model in neuroanatomical, neurophysiological, and behavioral research. The purpose of this study was to examine pallial and subpallial cholinoceptive, cholinergic and nitrergic populations in the goldfish telencephalon by means of histochemical and immunohistochemical techniques in order to identify neurons containing acetylcholinesterase (AChE), choline acetyltransferase (ChAT), NADPH-diaphorase (NADPHd), and neuronal nitric oxide synthase (nNOS), and to relate their distribution to their putative functional significance. Regions containing AChE-labeled neurons represented terminal fields of cholinergic inputs as well as a widespread distribution of AChE-related enzymes; these regions also usually contained NADPHd-labeled neurons and often contained small numbers of nNOS-positive cells. However, the ventral subdivisions of the medial and lateral parts of the dorsal telencephalic area, and the ventral and lateral parts of the ventral telencephalic area, were devoid of nNOS-labeled cells. ChAT-positive neurons were found only in the lateral part of the ventral telencephalic area. ChAT- and nNOS-positive fibers exhibited a radial orientation, and were seen as thin axons with en-passant boutons. The distribution of these elements could help to elucidate the role of cholinergic and nitrergic neuronal networks in the goldfish telencephalon.

Canine Retina Has a Primate Fovea-Like Bouquet of Cone Photoreceptors Which Is Affected by Inherited Macular Degenerations

PubMed Central

Guziewicz, Karina E.; Iwabe, Simone; Swider, Malgorzata; Scott, Erin M.; Savina, Svetlana V.; Ruthel, Gordon; Stefano, Frank; Zhang, Lingli; Zorger, Richard; Sumaroka, Alexander; Jacobson, Samuel G.; Aguirre, Gustavo D.

2014-01-01

Retinal areas of specialization confer vertebrates with the ability to scrutinize corresponding regions of their visual field with greater resolution. A highly specialized area found in haplorhine primates (including humans) is the fovea centralis which is defined by a high density of cone photoreceptors connected individually to interneurons, and retinal ganglion cells (RGCs) that are offset to form a pit lacking retinal capillaries and inner retinal neurons at its center. In dogs, a local increase in RGC density is found in a topographically comparable retinal area defined as the area centralis. While the canine retina is devoid of a foveal pit, no detailed examination of the photoreceptors within the area centralis has been reported. Using both in vivo and ex vivo imaging, we identified a retinal region with a primate fovea-like cone photoreceptor density but without the excavation of the inner retina. Similar anatomical structure observed in rare human subjects has been named fovea-plana. In addition, dogs with mutations in two different genes, that cause macular degeneration in humans, developed earliest disease at the newly-identified canine fovea-like area. Our results challenge the dogma that within the phylogenetic tree of mammals, haplorhine primates with a fovea are the sole lineage in which the retina has a central bouquet of cones. Furthermore, a predilection for naturally-occurring retinal degenerations to alter this cone-enriched area fills the void for a clinically-relevant animal model of human macular degenerations. PMID:24599007

High-mobility group (HMG) protein HMG-1 and TATA-binding protein-associated factor TAF(II)30 affect estrogen receptor-mediated transcriptional activation.

PubMed

Verrier, C S; Roodi, N; Yee, C J; Bailey, L R; Jensen, R A; Bustin, M; Parl, F F

1997-07-01

The estrogen receptor (ER) belongs to a family of ligand-inducible nuclear receptors that exert their effects by binding to cis-acting DNA elements in the regulatory region of target genes. The detailed mechanisms by which ER interacts with the estrogen response element (ERE) and affects transcription still remain to be elucidated. To study the ER-ERE interaction and transcription initiation, we employed purified recombinant ER expressed in both the baculovirus-Sf9 and his-tagged bacterial systems. The effect of high-mobility group (HMG) protein HMG-1 and purified recombinant TATA-binding protein-associated factor TAF(II)30 on ER-ERE binding and transcription initiation were assessed by electrophoretic mobility shift assay and in vitro transcription from an ERE-containing template (pERE2LovTATA), respectively. We find that purified, recombinant ER fails to bind to ERE in spite of high ligand-binding activity and electrophoretic and immunological properties identical to ER in MCF-7 breast cancer cells. HMG-1 interacts with ER and promotes ER-ERE binding in a concentration- and time-dependent manner. The effectiveness of HMG-1 to stimulate ER-ERE binding in the electrophoretic mobility shift assay depends on the sequence flanking the ERE consensus as well as the position of the latter in the oligonucleotide. We find that TAF(II)30 has no effect on ER-ERE binding either alone or in combination with ER and HMG-1. Although HMG-1 promotes ER-ERE binding, it fails to stimulate transcription initiation either in the presence or absence of hormone. In contrast, TAF(II)30, while not affecting ER-ERE binding, stimulates transcription initiation 20-fold in the presence of HMG-1. These results indicate that HMG-1 and TAF(II)30 act in sequence, the former acting to promote ER-ERE binding followed by the latter to stimulate transcription initiation.

ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1.

PubMed

Pasten, Consuelo; Cerda, Joaquín; Jausoro, Ignacio; Court, Felipe A; Cáceres, Alfredo; Marzolo, Maria-Paz

2015-11-01

ApoER2 and its ligand Reelin participate in neuronal migration during development. Upon receptor binding, Reelin induces the proteolytic processing of ApoER2 as well as the activation of signaling pathway, including small Rho GTPases. Besides its presence in the central nervous system (CNS), Reelin is also secreted by Schwann cells (SCs), the glial cells of the peripheral nervous system (PNS). Reelin deficient mice (reeler) show decreased axonal regeneration in the PNS; however neither the presence of ApoER2 nor the role of the Reelin signaling pathway in the PNS have been evaluated. Interestingly SC migration occurs during PNS development and during injury-induced regeneration and involves activation of small Rho GTPases. Thus, Reelin-ApoER2 might regulate SC migration during axon regeneration in the PNS. Here we demonstrate the presence of ApoER2 in PNS. After sciatic nerve injury Reelin was induced and its receptor ApoER2 was proteolytically processed. In vitro, SCs express both Reelin and ApoER2 and Reelin induces SC migration. To elucidate the molecular mechanism underlying Reelin-dependent SC migration, we examined the involvement of Rac1, a conspicuous small GTPase family member. FRET experiments revealed that Reelin activates Rac1 at the leading edge of SCs. In addition, Tiam1, a major Rac1-specific GEF was required for Reelin-induced SC migration. Moreover, Reelin-induced SC migration was decreased after suppression of the polarity protein PAR3, consistent with its association to Tiam1. Even more interesting, we demonstrated that PAR3 binds preferentially to the full-length cytoplasmic tail of ApoER2 corresponding to the splice-variant containing the exon 19 that encodes a proline-rich insert and that ApoER2 was required for SC migration. Our study reveals a novel function for Reelin/ApoER2 in PNS, inducing cell migration of SCs, a process relevant for PNS development and regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

Caspase-12 ablation preserves muscle function in the mdx mouse

PubMed Central

Moorwood, Catherine; Barton, Elisabeth R.

2014-01-01

Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin. Several downstream consequences of dystrophin deficiency are triggers of endoplasmic reticulum (ER) stress, including loss of calcium homeostasis, hypoxia and oxidative stress. During ER stress, misfolded proteins accumulate in the ER lumen and the unfolded protein response (UPR) is triggered, leading to adaptation or apoptosis. We hypothesized that ER stress is heightened in dystrophic muscles and contributes to the pathology of DMD. We observed increases in the ER stress markers BiP and cleaved caspase-4 in DMD patient biopsies, compared with controls, and an increase in multiple UPR pathways in muscles of the dystrophin-deficient mdx mouse. We then crossed mdx mice with mice null for caspase-12, the murine equivalent of human caspase-4, which are resistant to ER stress. We found that deleting caspase-12 preserved mdx muscle function, resulting in a 75% recovery of both specific force generation and resistance to eccentric contractions. The compensatory hypertrophy normally found in mdx muscles was normalized in the absence of caspase-12; this was found to be due to decreased fibre sizes, and not to a fibre type shift or a decrease in fibrosis. Fibre central nucleation was not significantly altered in the absence of caspase-12, but muscle fibre degeneration found in the mdx mouse was reduced almost to wild-type levels. In conclusion, we have identified heightened ER stress and abnormal UPR signalling as novel contributors to the dystrophic phenotype. Caspase-4 is therefore a potential therapeutic target for DMD. PMID:24879640

A Bowl of Hematite-Rich 'Berries'

NASA Technical Reports Server (NTRS)

2004-01-01

This graph shows two spectra of outcrop regions near the Mars Exploration Rover Opportunity's landing site. The blue line shows data for a region dubbed 'Berry Bowl,' which contains a handful of the sphere-like grains dubbed 'blueberries.' The yellow line represents an area called 'Empty' next to Berry Bowl that is devoid of berries. Berry Bowl's spectrum still shows typical outcrop characteristics, but also exhibits an intense hematite signature, seen as a 'magnetic sextet.' Hematite is an iron-bearing mineral often formed in water. These spectra were taken by the rover's Moessbauer spectrometer on the 46th (Empty) and 48th (Berry Bowl) martian days, or sols, of its mission.

The application of the airship to regions lacking in transport infrastructure

NASA Technical Reports Server (NTRS)

Coughlin, S.

1975-01-01

The requirements for two areas of airship application are considered. The first of these are those countries where there is a need to move consignments that are too large for the existing transport systems; the second are those regions where ground characteristics have resulted in an area totally devoid of transport. The needs of the second group are considered in detail since they also require transport to provide social as well as economic growth. With this problem in mind, a philosophy is put forward for using airships in conjunction with LASH vessels. A specimen design is outlined and the initial costs estimated.

Photonic band edge assisted spontaneous emission enhancement from all Er3+ 1-D photonic band gap structure

NASA Astrophysics Data System (ADS)

Chiasera, A.; Meroni, C.; Varas, S.; Valligatla, S.; Scotognella, F.; Boucher, Y. G.; Lukowiak, A.; Zur, L.; Righini, G. C.; Ferrari, M.

2018-06-01

All Er3+ doped dielectric 1-D Photonic Band Gap Structure was fabricated by rf-sputtering technique. The structure was constituted by of twenty pairs of SiO2/TiO2 alternated layers doped with Er3+ ions. The scanning electron microscopy was used to check the morphology of the structure. Transmission measurements put in evidence the stop band in the range 1500 nm-1950 nm. The photoluminescence measurements were obtained by optically exciting the sample and detecting the emitted light in the 1.5 μm region at different detection angles. Luminescence spectra and luminescence decay curves put in evidence that the presence of the stop band modify the emission features of the Er3+ ions.

Estrogen Receptor Folding Modulates cSrc Kinase SH2 Interaction via a Helical Binding Mode.

PubMed

Nieto, Lidia; Tharun, Inga M; Balk, Mark; Wienk, Hans; Boelens, Rolf; Ottmann, Christian; Milroy, Lech-Gustav; Brunsveld, Luc

2015-11-20

The estrogen receptors (ERs) feature, next to their transcriptional role, important nongenomic signaling actions, with emerging clinical relevance. The Src Homology 2 (SH2) domain mediated interaction between cSrc kinase and ER plays a key role in this; however the molecular determinants of this interaction have not been elucidated. Here, we used phosphorylated ER peptide and semisynthetic protein constructs in a combined biochemical and structural study to, for the first time, provide a quantitative and structural characterization of the cSrc SH2-ER interaction. Fluorescence polarization experiments delineated the SH2 binding motif in the ER sequence. Chemical shift perturbation analysis by nuclear magnetic resonance (NMR) together with molecular dynamics (MD) simulations allowed us to put forward a 3D model of the ER-SH2 interaction. The structural basis of this protein-protein interaction has been compared with that of the high affinity SH2 binding sequence GpYEEI. The ER features a different binding mode from that of the "two-pronged plug two-hole socket" model in the so-called specificity determining region. This alternative binding mode is modulated via the folding of ER helix 12, a structural element directly C-terminal of the key phosphorylated tyrosine. The present findings provide novel molecular entries for understanding nongenomic ER signaling and targeting the corresponding disease states.

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.

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.

Dancing with the Stars: Using Image Analysis to Study the Choreography of the Endoplasmic Reticulum and Its Partners and of Movement Within Its Tubules.

PubMed

Griffing, Lawrence R

2018-01-01

In this chapter, approaches to the image analysis of the choreography of the plant endoplasmic reticulum (ER) labeled with fluorescent fusion proteins ("stars," if you wish) are presented. The approaches include the analyses of those parts of the ER that are attached through membrane contact sites to moving or nonmoving partners (other "stars"). Image analysis is also used to understand the nature of the tubular polygonal network, the hallmark of this organelle, and how the polygons change over time due to tubule sliding or motion. Furthermore, the remodeling polygons of the ER interact with regions of fundamentally different topology, the ER cisternae, and image analysis can be used to separate the tubules from the cisternae. ER cisternae, like polygons and tubules, can be motile or stationary. To study which parts are attached to nonmoving partners, such as domains of the ER that form membrane contact sites with the plasma membrane/cell wall, an image analysis approach called persistency mapping has been used. To study the domains of the ER that are moving rapidly and streaming through the cell, the image analysis of optic flow has been used. However, optic flow approaches confuse the movement of the ER itself with the movement of proteins within the ER. As an overall measure of ER dynamics, optic flow approaches are of value, but their limitation as to what exactly is "flowing" needs to be specified. Finally, there are important imaging approaches that directly address the movement of fluorescent proteins within the ER lumen or in the membrane of the ER. Of these, fluorescence recovery after photobleaching (FRAP), inverse FRAP (iFRAP), and single particle tracking approaches are described.

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

Endoplasmic reticulum proteostasis impairment in aging.

PubMed

Martínez, Gabriela; Duran-Aniotz, Claudia; Cabral-Miranda, Felipe; Vivar, Juan P; Hetz, Claudio

2017-08-01

Perturbed neuronal proteostasis is a salient feature shared by both aging and protein misfolding disorders. The proteostasis network controls the health of the proteome by integrating pathways involved in protein synthesis, folding, trafficking, secretion, and their degradation. A reduction in the buffering capacity of the proteostasis network during aging may increase the risk to undergo neurodegeneration by enhancing the accumulation of misfolded proteins. As almost one-third of the proteome is synthetized at the endoplasmic reticulum (ER), maintenance of its proper function is fundamental to sustain neuronal function. In fact, ER stress is a common feature of most neurodegenerative diseases. The unfolded protein response (UPR) operates as central player to maintain ER homeostasis or the induction of cell death of chronically damaged cells. Here, we discuss recent evidence placing ER stress as a driver of brain aging, and the emerging impact of neuronal UPR in controlling global proteostasis at the whole organismal level. Finally, we discuss possible therapeutic interventions to improve proteostasis and prevent pathological brain aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Roles for Ca2+ mobilization and its regulation in mast cell functions: recent progress.

PubMed

Holowka, David; Wilkes, Marcus; Stefan, Christopher; Baird, Barbara

2016-04-15

Ca(2+)mobilization in response to cross-linking of IgE bound to its high affinity receptor, FcεRI, on mast cells is central to immune allergic responses. Stimulated tyrosine phosphorylation caused by this cross-linking activates store-operated Ca(2+)entry that results in sustained Ca(2+)oscillations dependent on Rho family GTPases and phosphoinositide synthesis. Coupling of the endoplasmic reticulum (ER) Ca(2+)sensor, stromal interaction molecule 1 (STIM1), to the Ca(2+)-selective channel, Orai1, is regulated by these elements and depends on membrane organization, both at the plasma membrane and at the ER. Mitochondria also contribute to the regulation of Ca(2+)mobilization, and we describe recent evidence that the ER membrane protein vesicle-associated membrane protein-associated protein (VAP) plays a significant role in the coupling between ER and mitochondria in this process. In addition to granule exocytosis, Ca(2+)mobilization in these cells also contributes to stimulated outward trafficking of recycling endosomes and to antigen-stimulated chemotaxis, and it is pathologically regulated by protozoan parasitic invasion. © 2016 Authors; published by Portland Press Limited.

Bifunctional NaYF4:Er3+/Yb3+ submicron rods, implemented in quantum dot sensitized solar cell(Conference Presentation)

NASA Astrophysics Data System (ADS)

Guerrero, J. Pablo; Cerdán Pasarán, Andrea; López-Luke, Tzarara; Ramachari, D.; Esparza, Diego; De la Rosa Cruz, Elder; Romero Arellano, Victor Hugo

2016-09-01

In this work are presented the results obtained with solar cells sensitized with quantum dots of cadmium sulphide (CdS) incorporating luminescent materials (NaYF4:Yb/Er). The study revealed that through using a bifunctional layer of NaYF4:Yb/Er submicron rods, the infrared radiation is absorbed in 980nm to generate luminescence in the visible region to 530nm, under the UP-conversion process, in the same way simultaneously, NaYF4:Yb/Er layer causes scattering toward the quantum dots, the emission and scattering generated by this material is reabsorbed by the QD-CdS, and these in turn are absorbing in its range of solar radiation absorption, Thus generates an increase in the electron injection into the semiconductor of TiO2. The results of a cell incorporating NaYF4: Yb/Er at 0.07M shown photoconversion efficiencies of 3.39% improving efficiency with respect to the reference solar cell without using NaYF4: Yb/Er of 1.99%. The obtained values of current and voltage showed a strong dependence of the percentage of NaYF4 Yb/Er, and the mechanism of incorporation of this material.

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.

TSA protects H9c2 cells against thapsigargin-induced apoptosis related to endoplasmic reticulum stress-mediated mitochondrial injury.

PubMed

Li, Zhiping; Liu, Yan; Dai, Xinlun; Zhou, Qiangqiang; Liu, Xueli; Li, Zeyu; Chen, Xia

2017-05-01

Endoplasmic reticulum stress (ERS) 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. Recently, TSA has shown protective effects on ERS and its mechanisms related to ER pathway has been previously characterized. However, whether TSA exerts its protective role via metabolic events remain largely undefined. Objectives : To explore the possible involvement of the metabolic changes during ERS and to better understand how TSA influence mitochondrial function to facilitate cellular adaptation. Results : TSA is an inhibitor of histone deacetylase which could significantly inhibit H9c2 cell apoptosis induced by Thapsigargin (TG). It also intervene the decrease of mitochondrial membrane potential. By immunofluorescence staining, we have shown that GRP78 was concentrated in the perinuclear region and co-localized with ER. However, treatments with TG and TSA could let it overlap with the mitochondrial marker MitoTracker. Cellular fractionation also confirmed the location of GRP78 in mitochondrion. TSA decreases ERS-induced cell apoptosis and mitochondrial injury may related to enhance the location of GRP78 in mitochondrion.

Quantifying and Mapping the Digital Divide from an Internet Point of View

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

Cottrell, R.Les; /SLAC; Khan, Shahryar

2008-09-18

Quantitative knowledge of the magnitude, extent and trends of the Digital Divide are critical to understand and identify the regions most in need of help, to make rational decisions on how to address the problems and to make cases for executives, funding agencies and politicians. We report on a project (PingER) to measure the Digital Divide from the point of view of Internet performance. The PingER project has been measuring Internet performance since 1995 and with the increased emphasis on measuring and tracking the Digital Divide, it now covers over 700 hosts in over 150 countries that between them containmore » over 99% of the world's Internet connected population. In this paper we will describe the how PingER works, it deployment, the data analysis, and presentation. We also introduce a new PingER visualization tool (ViPER) that provides a more appealing interactive visualization of the PingER data and also works on mobile PDAs. We will also show results from PingER that illustrate the magnitude, extent and trends for the Digital Divide, and also compare PingER results with some human development and technology indices.« less

Compound heterozygous mutations (p.Leu13Pro and p.Tyr294*) associated with factor VII deficiency cause impaired secretion through ineffective translocation and extensive intracellular degradation of factor VII.

PubMed

Suzuki, Keijiro; Sugawara, Takeshi; Ishida, Yoji; Suwabe, Akira

2013-02-01

Congenital coagulation factor VII (FVII) deficiency is a rare coagulation disease. We investigated the molecular mechanisms of this FVII deficiency in a patient with compound heterozygous mutations. A 22-year-old Japanese female was diagnosed with asymptomatic FVII deficiency. The FVII activity and antigen were greatly reduced (activity, 13.0%; antigen, 10.8%). We analyzed the F7 gene of this patient and characterized mutant FVII proteins using in vitro expression studies. Sequence analysis revealed that the patient was compound heterozygous with a point mutation (p.Leu13Pro) in the central hydrophobic core of the signal peptides and a novel non-sense mutation (p.Tyr294*) in the catalytic domain. Expression studies revealed that mutant FVII with p.Leu13Pro (FVII13P) showed less accumulation in the cells (17.5%) and less secretion into the medium (64.8%) than wild type showed. Truncated FVII resulting from p.Tyr294* (FVII294X) was also decreased in the cells (32.0%), but was not secreted into the medium. Pulse-chase experiments revealed that both mutants were extensively degraded intracellularly compared to wild type. The majority of FVII13P cannot translocate into endoplasmic reticulum (ER). However, a small amount of FVII13P was processed normally with post-translational modifications and was secreted into the medium. The fact that FVII294X was observed only in ER suggests that it is retained in ER. Proteasome apparently plays a central role in these degradations. These findings demonstrate that both mutant FVIIs impaired secretion through ineffective translocation to and retention in ER with extensive intracellular degradation, resulting in an insufficient phenotype. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mobilization of Ca2+ by Cyclic ADP-Ribose from the Endoplasmic Reticulum of Cauliflower Florets1

PubMed Central

Navazio, Lorella; Mariani, Paola; Sanders, Dale

2001-01-01

The NAD+ metabolite cADP-Rib (cADPR) elevates cytosolic free Ca2+ in plants and thereby plays a central role in signal transduction pathways evoked by the drought and stress hormone abscisic acid. cADPR is known to mobilize Ca2+ from the large vacuole of mature cells. To determine whether additional sites for cADPR-gated Ca2+ release reside in plant cells, microsomes from cauliflower (Brassica oleracea) inflorescences were subfractionated on sucrose density gradients, and the distribution of cADPR-elicited Ca2+ release was monitored. cADPR-gated Ca2+ release was detected in the heavy-density fractions associated with rough endoplasmic reticulum (ER). cADPR-dependent Ca2+ release co-migrated with two ER markers, calnexin and antimycin A-insensitive NADH-cytochrome c reductase activity. To investigate the possibility that contaminating plasma membrane in the ER-rich fractions was responsible for the observed release, plasma membrane vesicles were purified by aqueous two-phase partitioning, everted with Brij-58, and loaded with Ca2+: These vesicles failed to respond to cADPR. Ca2+ release evoked by cADPR at the ER was fully inhibited by ruthenium red and 8-NH2-cADPR, a specific antagonist of cADPR-gated Ca2+ release in animal cells. The presence of a Ca2+ release pathway activated by cADPR at higher plant ER reinforces the notion that, alongside the vacuole, the ER participates in Ca2+ signaling. PMID:11299392

Conceptualizing gambling disorder with the process model of emotion regulation.

PubMed

Rogier, Guyonne; Velotti, Patrizia

2018-06-25

Introduction Nowadays, gambling disorder (GD) is a worldwide health issue and there is a growing need to both improve our understanding of this disorder and to tailor specific interventions for its treatment. Moreover, theoretical models and preliminary empirical results suggest that difficulty in regulating emotional states might be involved in GD. However, literature describing clinical and theoretical aspects of emotional dysregulation among pathological gamblers (PGs) shows a lack of systematic description. Objectives We aimed to provide, within an exhaustive theoretical framework of emotion regulation (ER) processing, empirical evidence supporting a conceptual model of GD as an ER affliction. Methods We commented on empirical evidence on the relationship between ER and GD in the light of two main conceptual models of emotion (dys)regulation. Results The results suggest there are actual deficits of ER processing among PGs, manifesting themselves through different ways and in different steps of the ER timeline. In addition, dysregulation of positive emotions may play a central role in GD. From a clinical point of view, we pointed out that deficits in ER might be multiple in nature and an assessment for GD should be accurate to identify the specific components accounting for the development and maintenance of the disorder. It should also orientate the clinician in selecting therapeutic objectives. Conclusions The nature of emotional states that are difficult to regulate might account for the GD severity and indicate the subtype of PGs the patient belongs to. Treatment programs should be tailored on the specificity of PGs.

Regulation of G-protein coupled receptor traffic by an evolutionary conserved hydrophobic signal.

PubMed

Angelotti, Tim; Daunt, David; Shcherbakova, Olga G; Kobilka, Brian; Hurt, Carl M

2010-04-01

Plasma membrane (PM) expression of G-protein coupled receptors (GPCRs) is required for activation by extracellular ligands; however, mechanisms that regulate PM expression of GPCRs are poorly understood. For some GPCRs, such as alpha2c-adrenergic receptors (alpha(2c)-ARs), heterologous expression in non-native cells results in limited PM expression and extensive endoplasmic reticulum (ER) retention. Recently, ER export/retentions signals have been proposed to regulate cellular trafficking of several GPCRs. By utilizing a chimeric alpha(2a)/alpha(2c)-AR strategy, we identified an evolutionary conserved hydrophobic sequence (ALAAALAAAAA) in the extracellular amino terminal region that is responsible in part for alpha(2c)-AR subtype-specific trafficking. To our knowledge, this is the first luminal ER retention signal reported for a GPCR. Removal or disruption of the ER retention signal dramatically increased PM expression and decreased ER retention. Conversely, transplantation of this hydrophobic sequence into alpha(2a)-ARs reduced their PM expression and increased ER retention. This evolutionary conserved hydrophobic trafficking signal within alpha(2c)-ARs serves as a regulator of GPCR trafficking.

Lagrangian photochemical modeling studies of the 1987 Antarctic spring vortex. I - Comparison with AAOE observations

NASA Technical Reports Server (NTRS)

Jones, R. L.; Austin, J.; Mckenna, D. S.; Anderson, J. G.; Fahey, D. W.; Farmer, C. B.; Vedder, J. F.

1989-01-01

Results from the Lagrangian photochemical model integrated along computed air parcel trajectories intersected by the ER-2 aircraft are presented and compared with AAOE observations. According to the model, the BrO observations made from the ER-2 within the dehydrated denitrified region are consistent with there being approximately 5 parts per trillion by volume of BrO(y) at 428 K in spring. Within the high ClO region, ozone destruction rates are expected to exceed 2 percent/d with approximately 80 percent due to the ClO dimer mechanism.

Long-Term Variability of UV Irradiance in the Moscow Region according to Measurement and Modeling Data

NASA Astrophysics Data System (ADS)

Chubarova, N. E.; Pastukhova, A. S.; Galin, V. Ya.; Smyshlyaev, S. P.

2018-03-01

We have found distinct long-period changes in erythemal UV radiation ( Q er) characterized by a pronounced decrease at the end of the 1970s and a statistically significant positive trend of more than 5%/10 years since 1979 over the territory of the Moscow region according to the measurements and reconstruction model. The positive Q er trend is shown to be associated mainly with a decrease in the effective cloud amount and total ozone content (TOC). Due to these variations, UV resources have significantly changed in spring for the population with the most vulnerable skin type I, which means a transition from the UV optimum to UV moderate excess conditions. The simulation experiments using the INM-RSHU chemistry climate model (CCM) for several scenarios with and without anthropogenic factors have revealed that the variations in the anthropogenic emissions of halogens have the most significant impact on the variability of TOC and Q er. Among natural factors, noticeable effects are observed due to volcanic aerosol. The calculations of the cloud transmittance of Q er are generally consistent with the measurements; however, they do not reproduce the observed value of the positive trend.

Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells.

PubMed

Jeong, Kwon; Kim, Kiyoon; Kim, Hunsung; Oh, Yoojung; Kim, Seong-Jin; Jo, Yunhee; Choe, Wonchae

2015-06-01

Hypoxia is an important form of physiological stress that induces cell death, due to the resulting endoplasmic reticulum (ER) stress, particularly in solid tumors. Although previous studies have indicated that cyclophilin B (CypB) plays a role in ER stress, there is currently no direct information supporting the mechanism of CypB involvement under hypoxic conditions. However, it has previously been demonstrated that ER stress positively regulates the expression of CypB. In the present study, it was demonstrated that CypB is transcriptionally regulated by hypoxia-mediated activation of transcription factor 6 (ATF6), an ER stress transcription factor. Subsequently, the effects of ATF6 on CypB promoter activity were investigated and an ATF6-responsive region in the promoter was identified. Hypoxia and ATF6 expression each increased CypB promoter activity. Collectively, these results demonstrate that ATF6 positively regulates the expression of CypB by binding to an ATF6-responsive region in the promoter, which may play an important role in the attenuation of apoptosis in the adaption to hypoxia. These results suggest that CypB may be a key molecule in the adaptation of cells to hypoxic conditions.

Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells

PubMed Central

JEONG, KWON; KIM, KIYOON; KIM, HUNSUNG; OH, YOOJUNG; KIM, SEONG-JIN; JO, YUNHEE; CHOE, WONCHAE

2015-01-01

Hypoxia is an important form of physiological stress that induces cell death, due to the resulting endoplasmic reticulum (ER) stress, particularly in solid tumors. Although previous studies have indicated that cyclophilin B (CypB) plays a role in ER stress, there is currently no direct information supporting the mechanism of CypB involvement under hypoxic conditions. However, it has previously been demonstrated that ER stress positively regulates the expression of CypB. In the present study, it was demonstrated that CypB is transcriptionally regulated by hypoxia-mediated activation of transcription factor 6 (ATF6), an ER stress transcription factor. Subsequently, the effects of ATF6 on CypB promoter activity were investigated and an ATF6-responsive region in the promoter was identified. Hypoxia and ATF6 expression each increased CypB promoter activity. Collectively, these results demonstrate that ATF6 positively regulates the expression of CypB by binding to an ATF6-responsive region in the promoter, which may play an important role in the attenuation of apoptosis in the adaption to hypoxia. These results suggest that CypB may be a key molecule in the adaptation of cells to hypoxic conditions. PMID:26137159

Enhanced frequency upconversion study in Er3+/Yb3+ doped/codoped TWTi glasses

NASA Astrophysics Data System (ADS)

Azam, Mohd; Rai, Vineet Kumar

2018-04-01

Er3+/Yb3+ doped/codoped TeO2-WO3-TiO2 (TWTi) glasses have been prepared by using the melt-quenching technique. The upconversion (UC) emission spectra of the developed glasses have been recorded upon 980 nm laser excitation. Three intense UC emission bands have been observed within the green and red region centered at ˜532 nm, ˜553 nm and ˜669 nm corresponding to the 2H11/2→4I15/2, 4S3/2→4I15/2 and 4F9/2→4I15/2 transitions respectively in the singly Er3+ doped glass. On introducing Yb3+ ions in the singly Er3+ doped glass, an enhancement of about ˜ 12 times and ˜50 times in the green and red bands respectively have been observed even at low pump power ˜ 364 mW followed by two photon absorption process. Colour tunability from yellowish green to pure green colour region has been observed on varying the pump power. The prepared glass can be used to produce NIR to green upconverter and colour tunable display devices.

Measurements and Calculations of Microwave Radiance and Reflectivity for Storm-Associated Frozen Hydrometeors

NASA Technical Reports Server (NTRS)

Wang, James R.; Skofronick-Jackson, Gail; Meneghini, Robert; Heymsfield, Gerald; Manning, Will; Busalacchi, Antonio J. (Technical Monitor)

2000-01-01

During the TEFLUN-B (Texas-Florida under-flights for the Tropical Rainfall Measuring Mission (TRMM)) field experiment of August-September, 1998, a number of ER-2 aircraft flights with a host of microwave instruments were conducted over many convective storms, including some hurricanes, in the coastal region of Florida and Texas. These instruments include MIR (Millimeter-wave Imaging Radiometer), AMPR (Advanced Microwave Precipitation Radiometer), and EDOP (ER-2 Doppler Radar). EDOP is operated at the frequency of 9.7 GHz, while the AMPR and the MIR together give eleven channels of radiometric measurements in the frequency range of 10-340 GHz. The concurrent measurements from these instruments provide unique data sets for studying the details of the microphysics of hydrometeors. Preliminary examination of these data sets shows features that are generally well understood; i.e., radiometric measurements at frequencies <= 37 GHz mainly respond to rain, while those at frequencies >= 150 GHz, to snow and ice clouds above the freezing level. In this paper we present results of comparisons between these measurements and model calculations of brightness temperature and radar reflectivity. For simplicity the analysis is limited to the anvil region of the storms where only frozen hydrometeors are present. Various models of particle size distribution (e.g., Gunn-Marshall, Sekhon-Srivastava, and the Central Equatorial Pacific Experiment (CEPEX)) are examined in the calculations of brightness temperatures at the MIR frequencies and radar reflectivity at the EDOP frequency. Estimation of ice water path is made based on the best agreement between the measurements and calculations of brightness temperature and reflectivity. Problems associated with these analyses and measurement accuracy will be discussed.

Concentration effect of Er{sup 3+} ions on structural and spectroscopic properties of CdNb{sub 2}O{sub 6} phosphors

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

Ghafouri, Sanaz Aian; Erdem, Murat, E-mail: merdem@marmara.edu.tr; Ekmekçi, M. Kaan

2014-12-15

Excitation and emission spectra of a visible room-temperature Er{sup 3+} ions luminescence from powders. - Highlights: • This is the first report on spectroscopic properties of CdNb{sub 2}O{sub 6}:Er{sup 3+}. • The crystalline sizes are affected as the concentration of Er{sup 3+} ions increased. • Quenching of the luminescence was observed to be above 1.0 mol% Er{sup 3+}. - Abstract: This study is focused on the synthesis and characterization of CdNb{sub 2}O{sub 6} compounds doped with of Er{sup 3+} ions. Powders were synthesized by using the molten salt method and annealed at 900 °C for 4 h. The synthesized particlesmore » were structurally characterized by using X-ray diffraction, scanning electron microscopy. A single phase of the CdNb{sub 2}O{sub 6} was determined and the size of the particles was found to be affected by the presence and the concentration of Er{sup 3+} ions. Luminescence properties of each sample were investigated by measuring accurately the emission and excitation spectra at room temperature in the wavelength range of 200–1700 nm by exciting the Er{sup 3+} ions at 379 nm and 805 nm. Quenching of the luminescence in both visible and near infrared spectral regions was observed to be above 1.0 mol% Er{sup 3+} concentration.« less

An early ethylene up-regulated gene encoding a calmodulin-binding protein involved in plant senescence and death

NASA Technical Reports Server (NTRS)

Yang, T.; Poovaiah, B. W.

2000-01-01

35S-Labeled calmodulin (CaM) was used to screen a tobacco anther cDNA library. A positive clone (NtER1) with high homology to an early ethylene-up-regulated gene (ER66) in tomato, and an Arabidopsis homolog was isolated and characterized. Based on the helical wheel projection, a 25-mer peptide corresponding to the predicted CaM-binding region of NtER1 (amino acids 796-820) was synthesized. The gel-mobility shift assay showed that the peptide formed a stable complex with CaM only in the presence of Ca(2+). CaM binds to NtER1 with high affinity (K(d) approximately 12 nm) in a calcium-dependent manner. Tobacco flowers at different stages of development were treated with ethylene or with 1-methylcyclopropene for 2 h before treating with ethylene. Northern analysis showed that the NtER1 was rapidly induced after 15 min of exposure to ethylene. However, the 2-h 1-methylcyclopropene treatment totally blocked NtER1 expression in flowers at all stages of development, suggesting that NtER1 is an early ethylene-up-regulated gene. The senescing leaves and petals had significantly increased NtER1 induction as compared with young leaves and petals, implying that NtER1 is developmentally regulated and acts as a trigger for senescence and death. This is the first documented evidence for the involvement of Ca(2+)/CaM-mediated signaling in ethylene action.

Fault and anthropogenic processes in central California constrained by satellite and airborne InSAR and in-situ observations

NASA Astrophysics Data System (ADS)

Liu, Zhen; Lundgren, Paul

2016-07-01

The San Andreas Fault (SAF) system is the primary plate boundary in California, with the central SAF (CSAF) lying adjacent to the San Joaquin Valley (SJV), a vast structural trough that accounts for about one-sixth of the United Sates' irrigated land and one-fifth of its extracted groundwater. The CSAF displays a range of fault slip behavior with creeping in its central segment that decreases towards its northwest and southeast ends, where the fault transitions to being fully locked. At least six Mw ~6.0 events since 1857 have occurred near the Parkfield transition, most recently in 2004. Large earthquakes also occurred on secondary faults parallel to the SAF, the result of distributed deformation across the plate boundary zone. Recent studies have revealed the complex interaction between anthropogenic related groundwater depletion and the seismic activity on adjacent faults through stress interaction. Despite recent progress, many questions regarding fault and anthropogenic processes in the region still remain. For example, how is the relative plate motion accommodated between the CSAF and off-fault deformation? What is the distribution of fault creep and slip deficit at shallow depths? What are the spatiotemporal variations of fault slip? What are the spatiotemporal characteristics of anthropogenic and lithospheric processes and how do they interact with each other? To address these, we combine satellite InSAR and NASA airborne UAVSAR data to image on and off-fault deformation. The UAVSAR data cover fault perpendicular swaths imaged from opposing look directions and fault parallel swaths since 2009. The much finer spatial resolution and optimized viewing geometry provide important constraints on near fault deformation and fault slip at very shallow depth. We performed a synoptic InSAR time series analysis using ERS-1/2, Envisat, ALOS and UAVSAR interferograms. The combined C-band ERS-1/2 and Envisat data provide a long time interval of SAR data over the region, but are subject to severe decorrelation. The L-band ALOS and UAVSAR SAR sensors provide improved coherence compared to the shorter wavelength radar data. Joint analysis of UAVSAR and ALOS interferometry measurements show clear variability in deformation along the fault strike, suggesting variable fault creep and locking at depth and along strike. Modeling selected fault transects reveals a distinct change in surface creep and shallow slip deficit from the central creeping section towards the Parkfield transition. In addition to fault creep, the L-band ALOS, and especially ALOS-2 ScanSAR interferometry, show large-scale ground subsidence in the SJV due to over-exploitation of groundwater. Groundwater related deformation is spatially and temporally variable and is composed of both recoverable elastic and non-recoverable inelastic components. InSAR time series are compared to GPS and well-water hydraulic head in-situ time series to understand water storage processes and mass loading changes. We are currently developing poroelastic finite element method models to assess the influence of anthropogenic processes on surface deformation and fault mechanics. Ongoing work is to better constrain both tectonic and non-tectonic processes and understand their interaction and implication for regional earthquake hazard.

Regulation of AKT Phosphorylation at Ser473 and Thr308 by Endoplasmic Reticulum Stress Modulates Substrate Specificity in a Severity Dependent Manner

PubMed Central

Yung, Hong Wa

2011-01-01

Endoplasmic reticulum (ER) stress is a common factor in the pathophysiology of diverse human diseases that are characterised by contrasting cellular behaviours, from proliferation in cancer to apoptosis in neurodegenerative disorders. Coincidently, dysregulation of AKT/PKB activity, which is the central regulator of cell growth, proliferation and survival, is often associated with the same diseases. Here, we demonstrate that ER stress modulates AKT substrate specificity in a severity-dependent manner, as shown by phospho-specific antibodies against known AKT targets. ER stress also reduces both total and phosphorylated AKT in a severity-dependent manner, without affecting activity of the upstream kinase PDK1. Normalisation to total AKT revealed that under ER stress phosphorylation of Thr308 is suppressed while that of Ser473 is increased. ER stress induces GRP78, and siRNA-mediated knock-down of GRP78 enhances phosphorylation at Ser473 by 3.6 fold, but not at Thr308. Substrate specificity is again altered. An in-situ proximity ligation assay revealed a physical interaction between GRP78 and AKT at the plasma membrane of cells following induction of ER stress. Staining was weak in cells with normal nuclear morphology but stronger in those displaying rounded, condensed nuclei. Co-immunoprecipitation of GRP78 and P-AKT(Ser473) confirmed the immuno-complex consists of non-phosphorylated AKT (Ser473 and Thr308). The interaction is likely specific as AKT did not bind to all molecular chaperones, and GRP78 did not bind to p70 S6 kinase. These findings provide one mechanistic explanation for how ER stress contributes to human pathologies demonstrating contrasting cell fates via modulation of AKT signalling. PMID:21445305

Modeling Endoplasmic Reticulum Network Maintenance in a Plant Cell.

PubMed

Lin, Congping; White, Rhiannon R; Sparkes, Imogen; Ashwin, Peter

2017-07-11

The endoplasmic reticulum (ER) in plant cells forms a highly dynamic network of complex geometry. ER network morphology and dynamics are influenced by a number of biophysical processes, including filament/tubule tension, viscous forces, Brownian diffusion, and interactions with many other organelles and cytoskeletal elements. Previous studies have indicated that ER networks can be thought of as constrained minimal-length networks acted on by a variety of forces that perturb and/or remodel the network. Here, we study two specific biophysical processes involved in remodeling. One is the dynamic relaxation process involving a combination of tubule tension and viscous forces. The other is the rapid creation of cross-connection tubules by direct or indirect interactions with cytoskeletal elements. These processes are able to remodel the ER network: the first reduces network length and complexity whereas the second increases both. Using live cell imaging of ER network dynamics in tobacco leaf epidermal cells, we examine these processes on ER network dynamics. Away from regions of cytoplasmic streaming, we suggest that the dynamic network structure is a balance between the two processes, and we build an integrative model of the two processes for network remodeling. This model produces quantitatively similar ER networks to those observed in experiments. We use the model to explore the effect of parameter variation on statistical properties of the ER network. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Psychosocial Work Stressors, Work Fatigue, and Musculoskeletal Disorders: Comparison between Emergency and Critical Care Nurses in Brunei Public Hospitals.

PubMed

Abdul Rahman, Hanif; Abdul-Mumin, Khadizah; Naing, Lin

2017-03-01

Little evidence estimated the exposure of psychosocial work stressors, work-related fatigue, and musculoskeletal disorders for nurses working in South-East Asian region, and research on this subject is almost nonexistent in Brunei. The main aim of our study was to provide a comprehensive exploration and estimate exposure of the study variables amongst emergency (ER) and critical care (CC) nurses in Brunei. The study also aims to compare whether experiences of ER nurses differ from those of CC nurses. This cross-sectional study was implemented in the ER and CC departments across Brunei public hospitals from February to April 2016 by using Copenhagen Psychosocial Questionnaire II, Occupational Fatigue Exhaustion Recovery scale, and Cornell Musculoskeletal Discomfort Questionnaire. In total, 201 ER and CC nurses (82.0% response rate) participated in the study. Quantitative demands of CC nurses were significantly higher than ER nurses. Even so, ER nurses were 4.0 times more likely [95% confidence interval (2.21, 7.35)] to experience threats of violence, and 2.8 times more likely [95% confidence interval: (1.50, 5.29)] to experience chronic fatigue. The results revealed that nurses experienced high quantitative demands, work pace, stress, and burnout. High prevalence of chronic and persistent fatigue, threats of violence and bullying, and musculoskeletal pain at the neck, shoulder, upper and lower back, and foot region, was also reported. This study has provided good estimates for the exposure rate of psychosocial work stressors, work-related fatigue, and musculoskeletal disorders among nurses in Brunei. It provided important initial insight for nursing management and policymakers to make informed decisions on current and future planning to provide nurses with a conducive work environment. Copyright © 2017. Published by Elsevier B.V.

Tung Tree DGAT1 and DGAT2 Have Nonredundant Functions in Triacylglycerol Biosynthesis and Are Localized to Different Subdomains of the Endoplasmic Reticulum[W

PubMed Central

Shockey, Jay M.; Gidda, Satinder K.; Chapital, Dorselyn C.; Kuan, Jui-Chang; Dhanoa, Preetinder K.; Bland, John M.; Rothstein, Steven J.; Mullen, Robert T.; Dyer, John M.

2006-01-01

Seeds of the tung tree (Vernicia fordii) produce large quantities of triacylglycerols (TAGs) containing ∼80% eleostearic acid, an unusual conjugated fatty acid. We present a comparative analysis of the genetic, functional, and cellular properties of tung type 1 and type 2 diacylglycerol acyltransferases (DGAT1 and DGAT2), two unrelated enzymes that catalyze the committed step in TAG biosynthesis. We show that both enzymes are encoded by single genes and that DGAT1 is expressed at similar levels in various organs, whereas DGAT2 is strongly induced in developing seeds at the onset of oil biosynthesis. Expression of DGAT1 and DGAT2 in yeast produced different types and proportions of TAGs containing eleostearic acid, with DGAT2 possessing an enhanced propensity for the synthesis of trieleostearin, the main component of tung oil. Both DGAT1 and DGAT2 are located in distinct, dynamic regions of the endoplasmic reticulum (ER), and surprisingly, these regions do not overlap. Furthermore, although both DGAT1 and DGAT2 contain a similar C-terminal pentapeptide ER retrieval motif, this motif alone is not sufficient for their localization to specific regions of the ER. These data suggest that DGAT1 and DGAT2 have nonredundant functions in plants and that the production of storage oils, including those containing unusual fatty acids, occurs in distinct ER subdomains. PMID:16920778

Role of N-terminal 28-amino-acid region of Rhizopus oryzae lipase in directing proteins to secretory pathway of Aspergillus oryzae.

PubMed

Hama, Shinji; Tamalampudi, Sriappareddy; Shindo, Naoki; Numata, Takao; Yamaji, Hideki; Fukuda, Hideki; Kondo, Akihiko

2008-07-01

To develop a new approach for improving heterologous protein production in Aspergillus oryzae, we focused on the functional role of the N-terminal region of Rhizopus oryzae lipase (ROL). Several N-terminal deletion variants of ROL were expressed in A. oryzae. Interestingly, a segment of 28 amino acids from the C-terminal region of the propeptide (N28) was found to be critical for secretion of ROL into the culture medium. To further investigate the role of N28, the ROL secretory process was visualized in vivo using ROL-green fluorescent protein (GFP) fusion proteins. In cells producing ROL with N28, fluorescence observations showed that the fusion proteins are transported through endoplasmic reticulum (ER), Golgi, and cell wall, which is one of the typical secretory processes in a eukaryotic cell. Because the expression of the mature ROL-GFP fusion protein induced fluorescence accumulation without its translocation into the ER, N28 is considered to play a crucial role in protein transport. When N28 was inserted between the secretion signal and GFP, fluorescence observations showed that GFP, which is originally a cytoplasmic protein, was efficiently translocated into the ER of A. oryzae, resulting in an enhanced secretion of mature GFP after proteolytic cleavage of N28. These findings suggest that N28 facilitates protein translocation into ER and can be a promising candidate for improving heterologous protein production in A. oryzae.

Monitoring Delamination of Plasma-Sprayed Thermal Barrier Coatings by Reflectance-Enhanced Luminescence

NASA Technical Reports Server (NTRS)

Eldridge, Jeffrey I.; Bencic, Timothy J.

2006-01-01

Highly scattering plasma-sprayed thermal barrier coatings (TBCs) present a challenge for optical diagnostic methods to monitor TBC delamination because scattering attenuates light transmitted through the TBC and usually degrades contrast between attached and delaminated regions of the TBC. This paper presents a new approach where reflectance-enhanced luminescence from a luminescent sublayer incorporated along the bottom of the TBC is used to identify regions of TBC delamination. Because of the higher survival rate of luminescence reflecting off the back surface of a delaminated TBC, the strong scattering exhibited by plasma-sprayed TBCs actually accentuates contrast between attached and delaminated regions by making it more likely that multiple reflections of luminescence off the back surface occur before exiting the top surface of the TBC. A freestanding coating containing sections designed to model an attached or delaminated TBC was prepared by depositing a luminescent Eu-doped or Er-doped yttria-stabilized zirconia (YSZ) luminescent layer below a plasma-sprayed undoped YSZ layer and utilizing a NiCr backing layer to represent an attached substrate. For specimens with a Eu-doped YSZ luminescent sublayer, luminescence intensity maps showed excellent contrast between unbacked and NiCr-backed sections even at a plasma-sprayed overlayer thickness of 300 m. Discernable contrast between unbacked and NiCr-backed sections was not observed for specimens with a Er-doped YSZ luminescent sublayer because luminescence from Er impurities in the undoped YSZ layer overwhelmed luminescence originating form the Er-doped YSZ sublayer.

Mechanosensitive ion channel Piezo1 is expressed in antral G cells of murine stomach.

PubMed

Lang, Kerstin; Breer, Heinz; Frick, Claudia

2018-02-01

G cells in the antrum region of the murine stomach produce gastrin, the central hormone for controlling gastric activities. Secretion of gastrin is induced mainly by protein breakdown products but also by distensions of the stomach wall. Although G cells respond to protein fragments via distinct chemosensory receptor types, the mechanism underlying G cell activation upon distention is entirely ambiguous. Mechanosensitive ion channels are considered as potential candidates for such a task. Therefore, we explore the possibility of whether Piezo1, a polymodal sensor for diverse mechanical forces, is expressed in antral G cells. The experimental analyses revealed that the vast majority of G cells indeed expressed Piezo1. Within flask-like G cells at the base of the antral invaginations, the Piezo1 protein was primarily located at the basolateral portion, which is thought to be the release site for the exocytic secretion of gastrin. In the spindle-like G cells, which are oriented parallel to the invaginations, Piezo1 protein was restricted to the cell body where the hormone was also located, whereas the long processes appeared to be devoid of Piezo1 protein. Our results suggest that mechanosensitive channels such as Piezo1, located in close proximity to hormone-release sites, enable G cells to respond directly to antrum distensions with gastrin secretion.

Denticle-embedded ampullary organs in a Cretaceous shark provide unique insight into the evolution of elasmobranch electroreceptors

NASA Astrophysics Data System (ADS)

Vullo, Romain; Guinot, Guillaume

2015-10-01

Here, we report a novel type of dermal denticle (or placoid scale), unknown among both living and fossil chondrichthyan fishes, in a Cretaceous lamniform shark. By their morphology and location, these dermal denticles, grouped into clusters in the cephalic region, appear to have been directly associated with the electrosensory ampullary system. These denticles have a relatively enlarged (˜350 μm in diameter), ornamented crown with a small (˜100 μm) asterisk- or cross-shaped central perforation connected to a multi-alveolate internal cavity. The formation of such a complex structure can be explained by the annular coalescence and fusion, around an ampullary vesicle, of several developmental units still at papillary stage (i.e. before mineralization), leading to a single denticle embedding an alveolar ampulla devoid of canal. This differs from larger typical ampullae of Lorenzini with a well-developed canal opening in a pore of the skin and may represent another adaptive response to low skin resistance. Since it has been recently demonstrated that ampullary organs arise from lateral line placodes in chondrichthyans, this highly specialized type of dermal denticle (most likely non-deciduous) may be derived from the modified placoid scales covering the superficial neuromasts (pit organs) of the mechanosensory lateral line system of many modern sharks.

Evaluation of Six Mosquito Traps for Collection of Aedes albopictus and Associated Mosquito Species in a Suburban Setting in North Central Florida

DTIC Science & Technology

2009-03-01

fever and dengue virus vectors in most of the world. Although Ae. aegypti prefer- entially...crucians s.l., An . quadrima-T a b le 3 . M ea n co ll ec ti o n (6 S E M ) o f m o sq u it o es p er tr a p p in g p er io d b y sp ec ie s in 6 tr a p...review. Bull Entomol Res 70:525–532. Gubler DJ. 1997. Dengue and dengue hemorrhagic fever : its history and resurgence as a global public

Extraction of ozone and chlorophyll-A distribution from AVIRIS data

NASA Technical Reports Server (NTRS)

Schaepman, M.; Itten, K. I.; Schlaepfer, D.; Kurer, U.; Veraguth, S.; Keller, J.

1995-01-01

The potential of airborne imaging spectrometry for assessing and monitoring natural resources is studied. Therefore, an AVIRIS scene of the NASA's MacEurope 1991 campaign - acquired in Central Switzerland - is used. The test site consists of an urban area, the Lake Zug with its surrounding fields, the Rigi mountain in the center of the test site, and the Lake of Four Cantons. The region is covered by the AVIRIS flight #910705, run 6 and 7 of the NASA ER-2 aircraft resulting in an average nominal pixel size of about 18 m. Simultaneous to the ER-2 overflight spectroradiometric measurements have been taken in various locations. Preselected reference targets were measured in the field with a GER Mark V spectroradiometer, and radiance measurements were taken to the lake using a Li-Cor LI 1800UW specroradiometer below and above the water surface. A comprehensive meteorological data set was obtained by joining the POLLUMET experiment which carried out measurements to investigate the summer smog in Switzerland on the same day. The quality assessment for the actual data set can be found in detail in Meyer et al. A parametric approach calculating the location of the airplane was used to simulate the observation geometry. This parametric preprocessing procedure, which takes care of effects of flight line and attitude variations as well as the pixel-by-pixel topographic corrections is described in Meyer.

Hawaii Regional Sediment Management (RSM): Regional Sediment Budget for the West Maui Region

DTIC Science & Technology

2016-06-01

Increased sedimentation associated with loss of forest land, historical agriculture practices, stream channelization , and rapid development has...ER D C/ CH L TR -1 6- 5 Regional Sediment Management (RSM) Program Hawaii Regional Sediment Management (RSM): Regional Sediment Budget...acwc.sdp.sirsi.net/client/default. Regional Sediment Management (RSM) Program ERDC/CHL TR-16-5 June 2016 Hawaii Regional Sediment Management

Spaceborne radar interferometry for coastal DEM construction

USGS Publications Warehouse

Hong, S.-H.; Lee, C.-W.; Won, J.-S.; Kwoun, Oh-Ig; Lu, Z.

2005-01-01

Topographic features in coastal regions including tidal flats change more significantly than landmass, and are characterized by extremely low slopes. High precision DEMs are required to monitor dynamic changes in coastal topography. It is difficult to obtain coherent interferometric SAR pairs especially over tidal flats mainly because of variation of tidal conditions. Here we focus on i) coherence of multi-pass ERS SAR interferometric pairs and ii) DEM construction from ERS-ENVISAT pairs. Coherences of multi-pass ERS interferograms were good enough to construct DEM under favorable tidal conditions. Coherence in sand dominant area was generally higher than that in muddy surface. The coarse grained coastal areas are favorable for multi-pass interferometry. Utilization of ERS-ENVISAT interferometric pairs is taken a growing interest. We carried out investigation using a cross-interferometric pair with a normal baseline of about 1.3 km, a 30 minutes temporal separation and the height sensitivity of about 6 meters. Preliminary results of ERS-ENVISAT interferometry were not successful due to baseline and unfavorable scattering conditions. ?? 2005 IEEE.

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.

Imaging the secretory compartments involved in the intracellular traffic of CHS-4, a class IV chitin synthase, in Neurospora crassa.

PubMed

Rico-Ramírez, Adriana M; Roberson, Robert W; Riquelme, Meritxell

2018-03-27

In Neurospora crassa hyphae the localization of all seven chitin synthases (CHSs) at the Spitzenkörper (Spk) and at developing septa has been well analyzed. Hitherto, the mechanisms of CHSs traffic and sorting from synthesis to delivery sites remain largely unexplored. In Saccharomyces cerevisiae exit of Chs3p from the endoplasmic reticulum (ER) requires chaperone Chs7p. Here, we analyzed the role of CSE-7, N. crassa Chs7p orthologue in the biogenesis of CHS-4 (orthologue of Chs3p). In a N. crassa Δcse-7 mutant, CHS-4-GFP no longer accumulated at the Spk and septa. Instead, fluorescence was retained in hyphal subapical regions in an extensive network of elongated cisternae (NEC) referred to previously as tubular vacuoles. In a complemented strain expressing a copy of cse-7 the localization of CHS-4-GFP at the Spk and septa was restored, providing evidence that CSE-7 is necessary for the localization of CHS-4 at hyphal tips and septa. CSE-7 was revealed at delimited regions of the ER at the immediacies of nuclei, at the NEC, and remarkably also at septa and the Spk. The organization of the NEC was dependent on the cytoskeleton. SEC-63, an extensively used ER marker, and NCA-1, a SERCA-type ATPase previously localized at the nuclear envelope, were used as markers to discern the nature of the membranes containing CSE-7. Both SEC-63 and NCA-1 were found at the nuclear envelope, but also at regions of the NEC. However, at the NEC only NCA-1 co-localized extensively with CSE-7. Observations by transmission electron microscopy revealed abundant rough ER sheets and distinct electron translucent smooth flattened cisternae, which could correspond collectively to the NEC, thorough the subapical cytoplasm. This study identifies CSE-7 as the putative ER receptor for its cognate cargo, the polytopic membrane protein CHS-4, and elucidates the complexity of the ER system in filamentous fungi. Copyright © 2018. Published by Elsevier Inc.

ESR1 Is Co-Expressed with Closely Adjacent Uncharacterised Genes Spanning a Breast Cancer Susceptibility Locus at 6q25.1

PubMed Central

Dunbier, Anita K.; Anderson, Helen; Ghazoui, Zara; Lopez-Knowles, Elena; Pancholi, Sunil; Ribas, Ricardo; Drury, Suzanne; Sidhu, Kally; Leary, Alexandra; Martin, Lesley-Ann; Dowsett, Mitch

2011-01-01

Approximately 80% of human breast carcinomas present as oestrogen receptor α-positive (ER+ve) disease, and ER status is a critical factor in treatment decision-making. Recently, single nucleotide polymorphisms (SNPs) in the region immediately upstream of the ER gene (ESR1) on 6q25.1 have been associated with breast cancer risk. Our investigation of factors associated with the level of expression of ESR1 in ER+ve tumours has revealed unexpected associations between genes in this region and ESR1 expression that are important to consider in studies of the genetic causes of breast cancer risk. RNA from tumour biopsies taken from 104 postmenopausal women before and after 2 weeks treatment with an aromatase (oestrogen synthase) inhibitor was analyzed on Illumina 48K microarrays. Multiple-testing corrected Spearman correlation revealed that three previously uncharacterized open reading frames (ORFs) located immediately upstream of ESR1, C6ORF96, C6ORF97, and C6ORF211 were highly correlated with ESR1 (Rs = 0.67, 0.64, and 0.55 respectively, FDR<1×10−7). Publicly available datasets confirmed this relationship in other groups of ER+ve tumours. DNA copy number changes did not account for the correlations. The correlations were maintained in cultured cells. An ERα antagonist did not affect the ORFs' expression or their correlation with ESR1, suggesting their transcriptional co-activation is not directly mediated by ERα. siRNA inhibition of C6ORF211 suppressed proliferation in MCF7 cells, and C6ORF211 positively correlated with a proliferation metagene in tumours. In contrast, C6ORF97 expression correlated negatively with the metagene and predicted for improved disease-free survival in a tamoxifen-treated published dataset, independently of ESR1. Our observations suggest that some of the biological effects previously attributed to ER could be mediated and/or modified by these co-expressed genes. The co-expression and function of these genes may be important influences on the recently identified relationship between SNPs in this region and breast cancer risk. PMID:21552322

Role for Human Mediator Subunit MED25 in Recruitment of Mediator to Promoters by Endoplasmic Reticulum Stress-responsive Transcription Factor ATF6α*

PubMed Central

Sela, Dotan; Conkright, Juliana J.; Chen, Lu; Gilmore, Joshua; Washburn, Michael P.; Florens, Laurence; Conaway, Ronald C.; Conaway, Joan Weliky

2013-01-01

Transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. In response to ER stress, ATF6α translocates from its site of latency in the ER membrane to the nucleus, where it activates RNA polymerase II transcription of ER stress response genes upon binding sequence-specifically to ER stress response enhancer elements (ERSEs) in their promoter-regulatory regions. In a recent study, we demonstrated that ATF6α activates transcription of ER stress response genes by a mechanism involving recruitment to ERSEs of the multisubunit Mediator and several histone acetyltransferase (HAT) complexes, including Spt-Ada-Gcn5 (SAGA) and Ada-Two-A-containing (ATAC) (Sela, D., Chen, L., Martin-Brown, S., Washburn, M.P., Florens, L., Conaway, J.W., and Conaway, R.C. (2012) J. Biol. Chem. 287, 23035–23045). In this study, we extend our investigation of the mechanism by which ATF6α supports recruitment of Mediator to ER stress response genes. We present findings arguing that Mediator subunit MED25 plays a critical role in this process and identify a MED25 domain that serves as a docking site on Mediator for the ATF6α transcription activation domain. PMID:23864652

Fine Mapping of a Gene (ER4.1) that Causes Epidermal Reticulation of Tomato Fruit and Characterization of the Associated Transcriptome

PubMed Central

Cui, Lipeng; Qiu, Zhengkun; Wang, Zhirong; Gao, Jianchang; Guo, Yanmei; Huang, Zejun; Du, Yongchen; Wang, Xiaoxuan

2017-01-01

The hydrophobic cuticle that covers the surface of tomato (Solanum lycopersicum) fruit plays key roles in development and protection against biotic and abiotic stresses, including water loss, mechanical damage, UV radiation, pathogens, and pests. However, many details of the genes and regulatory mechanisms involved in cuticle biosynthesis in fleshy fruits are not well understood. In this study, we describe a novel tomato fruit phenotype, characterized by epidermal reticulation (ER) of green fruit and a higher water loss rate than wild type (WT) fruit. The ER phenotype is controlled by a single gene, ER4.1, derived from an introgressed chromosomal segment from the wild tomato species S. pennellii (LA0716). We performed fine mapping of the single dominant gene to an ~300 kb region and identified Solyc04g082540, Solyc04g082950, Solyc04g082630, and Solyc04g082910as potential candidate genes for the ER4.1 locus, based on comparative RNA-seq analysis of ER and WT fruit peels. In addition, the transcriptome analysis revealed that the expression levels of genes involved in cutin, wax and flavonoid biosynthesis were altered in the ER fruit compared with WT. This study provides new insights into the regulatory mechanisms and metabolism of the fruit cuticle. PMID:28798753

Estrogen receptor and progesterone receptor as predictive biomarkers of response to endocrine therapy: a prospectively powered pathology study in the Tamoxifen and Exemestane Adjuvant Multinational trial.

PubMed

Bartlett, John M S; Brookes, Cassandra L; Robson, Tammy; van de Velde, Cornelis J H; Billingham, Lucinda J; Campbell, Fiona M; Grant, Margaret; Hasenburg, Annette; Hille, Elysée T M; Kay, Charlene; Kieback, Dirk G; Putter, Hein; Markopoulos, Christos; Kranenbarg, Elma Meershoek-Klein; Mallon, Elizabeth A; Dirix, Luc; Seynaeve, Caroline; Rea, Daniel

2011-04-20

The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included a prospectively planned pathology substudy testing the predictive value of progesterone receptor (PgR) expression for outcome of estrogen receptor-positive (ER-positive) early breast cancer treated with exemestane versus tamoxifen. Pathology blocks from 4,781 TEAM patients randomly assigned to exemestane versus tamoxifen followed by exemestane for 5 years of total therapy were collected centrally, and tissue microarrays were constructed from samples from 4,598 patients. Quantitative analysis of hormone receptors (ER and PgR) was performed by using image analysis and immunohistochemistry, and the results were linked to outcome data from the main TEAM trial and analyzed relative to disease-free survival and treatment. Of 4,325 eligible ER-positive patients, 23% were PgR-poor (Allred < 4) and 77% were PgR- rich (Allred ≥ 5). No treatment-by-marker effect for PgR was observed for exemestane versus tamoxifen (PgR-rich hazard ratio [HR], 0.83; 95% CI, 0.65 to 1.05; PgR-poor HR, 0.85; 95% CI, 0.61 to 1.19; P = .88 for interaction). Both PgR and ER expression were associated with patient prognosis in univariate (PgR HR, 0.53; 95% CI, 0.43 to 0.65; P < .001; ER HR, 0.66; 95% CI, 0.51 to 0.86; P = .002), and multivariate analyses (P < .001 and P = .001, respectively). A trend toward a treatment-by-marker effect for ER-rich patients was observed. Preferential exemestane versus tamoxifen treatment benefit was not predicted by PgR expression; conversely, patients with ER-rich tumors may derive additional benefit from exemestane. Quantitative analysis of ER and PgR expression provides highly significant information on risk of early relapse (within 1 to 3 years) during treatment.

Estrogen Receptor and Progesterone Receptor As Predictive Biomarkers of Response to Endocrine Therapy: A Prospectively Powered Pathology Study in the Tamoxifen and Exemestane Adjuvant Multinational Trial

PubMed Central

Bartlett, John M.S.; Brookes, Cassandra L.; Robson, Tammy; van de Velde, Cornelis J.H.; Billingham, Lucinda J.; Campbell, Fiona M.; Grant, Margaret; Hasenburg, Annette; Hille, Elysée T.M.; Kay, Charlene; Kieback, Dirk G.; Putter, Hein; Markopoulos, Christos; Kranenbarg, Elma Meershoek-Klein; Mallon, Elizabeth A.; Dirix, Luc; Seynaeve, Caroline; Rea, Daniel

2011-01-01

Purpose The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included a prospectively planned pathology substudy testing the predictive value of progesterone receptor (PgR) expression for outcome of estrogen receptor–positive (ER-positive) early breast cancer treated with exemestane versus tamoxifen. Patients and Methods Pathology blocks from 4,781 TEAM patients randomly assigned to exemestane versus tamoxifen followed by exemestane for 5 years of total therapy were collected centrally, and tissue microarrays were constructed from samples from 4,598 patients. Quantitative analysis of hormone receptors (ER and PgR) was performed by using image analysis and immunohistochemistry, and the results were linked to outcome data from the main TEAM trial and analyzed relative to disease-free survival and treatment. Results Of 4,325 eligible ER-positive patients, 23% were PgR-poor (Allred < 4) and 77% were PgR- rich (Allred ≥ 5). No treatment-by-marker effect for PgR was observed for exemestane versus tamoxifen (PgR-rich hazard ratio [HR], 0.83; 95% CI, 0.65 to 1.05; PgR-poor HR, 0.85; 95% CI, 0.61 to 1.19; P = .88 for interaction). Both PgR and ER expression were associated with patient prognosis in univariate (PgR HR, 0.53; 95% CI, 0.43 to 0.65; P < .001; ER HR, 0.66; 95% CI, 0.51 to 0.86; P = .002), and multivariate analyses (P < .001 and P = .001, respectively). A trend toward a treatment-by-marker effect for ER-rich patients was observed. Conclusion Preferential exemestane versus tamoxifen treatment benefit was not predicted by PgR expression; conversely, patients with ER-rich tumors may derive additional benefit from exemestane. Quantitative analysis of ER and PgR expression provides highly significant information on risk of early relapse (within 1 to 3 years) during treatment. PMID:21422407

File Assignment in a Central Server Computer Network.

DTIC Science & Technology

1979-01-01

somewhat artificial for many applications. Sometimes important variables must be known in advance when they are more appropriately decision variables... intellegently , we must have some notion of the errors that may be introduced. We must account for two types of er:ors. The first is the error

Roles of N-glycans in the polymerization-dependent aggregation of mutant Ig-μ chains in the early secretory pathway.

PubMed

Giannone, Chiara; Fagioli, Claudio; Valetti, Caterina; Sitia, Roberto; Anelli, Tiziana

2017-02-03

The polymeric structure of secretory IgM allows efficient antigen binding and complement fixation. The available structural models place the N-glycans bound to asparagines 402 and 563 of Ig-μ chains within a densely packed core of native IgM. These glycans are found in the high mannose state also in secreted IgM, suggesting that polymerization hinders them to Golgi processing enzymes. Their absence alters polymerization. Here we investigate their role following the fate of aggregation-prone mutant μ chains lacking the Cμ1 domain (μ∆). Our data reveal that μ∆ lacking 563 glycans (μ∆5) form larger intracellular aggregates than μ∆ and are not secreted. Like μ∆, they sequester ERGIC-53, a lectin previously shown to promote polymerization. In contrast, μ∆ lacking 402 glycans (μ∆4) remain detergent soluble and accumulate in the ER, as does a double mutant devoid of both (μ∆4-5). These results suggest that the two C-terminal Ig-μ glycans shape the polymerization-dependent aggregation by engaging lectins and acting as spacers in the alignment of individual IgM subunits in native polymers.

Roles of N-glycans in the polymerization-dependent aggregation of mutant Ig-μ chains in the early secretory pathway

PubMed Central

Giannone, Chiara; Fagioli, Claudio; Valetti, Caterina; Sitia, Roberto; Anelli, Tiziana

2017-01-01

The polymeric structure of secretory IgM allows efficient antigen binding and complement fixation. The available structural models place the N-glycans bound to asparagines 402 and 563 of Ig-μ chains within a densely packed core of native IgM. These glycans are found in the high mannose state also in secreted IgM, suggesting that polymerization hinders them to Golgi processing enzymes. Their absence alters polymerization. Here we investigate their role following the fate of aggregation-prone mutant μ chains lacking the Cμ1 domain (μ∆). Our data reveal that μ∆ lacking 563 glycans (μ∆5) form larger intracellular aggregates than μ∆ and are not secreted. Like μ∆, they sequester ERGIC-53, a lectin previously shown to promote polymerization. In contrast, μ∆ lacking 402 glycans (μ∆4) remain detergent soluble and accumulate in the ER, as does a double mutant devoid of both (μ∆4–5). These results suggest that the two C-terminal Ig-μ glycans shape the polymerization-dependent aggregation by engaging lectins and acting as spacers in the alignment of individual IgM subunits in native polymers. PMID:28157181

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.

ERS-1 SAR monitoring of ice growth on shallow lakes to determine water depth and availability in north west Alaska

NASA Technical Reports Server (NTRS)

Jeffries, Martin; Morris, Kim; Liston, Glen

1996-01-01

Images taken by the ERS-1 synthetic aperture radar (SAR) were used to identify and to differentiate between the lakes that freeze completely to the bottom and those that do not, on the North Slope, in northwestern Alaska. The ice thickness at the time each lake froze completely is determined with numerical ice growth model that gives a maximum simulated thickness of 2.2 m. A method combining the ERS-1 SAR images and numerical ice growth model was used to determine the ice growth and the water availability in these regions.

Composition of gaseous organic carbon during ECOCEM in Beirut, Lebanon: new observational constraints for VOC anthropogenic emission evaluation in the Middle East

NASA Astrophysics Data System (ADS)

Salameh, Thérèse; Borbon, Agnès; Afif, Charbel; Sauvage, Stéphane; Leonardis, Thierry; Gaimoz, Cécile; Locoge, Nadine

2017-01-01

The relative importance of eastern Mediterranean emissions is suspected to be largely underestimated compared to other regions worldwide. Here we use detailed speciated measurements of volatile organic compounds (VOCs) to evaluate the spatial heterogeneity of VOC urban emission composition and the consistency of regional and global emission inventories downscaled to Lebanon (European Monitoring and Evaluation Programme, EMEP; Atmospheric Chemistry and Climate Model Intercomparison Project, ACCMIP; and MACCity, Monitoring Atmospheric Composition and Climate and megaCITY Zoom for the Environment). The assessment was conducted through the comparison of the emission ratios (ERs) extracted from the emission inventories to the ones obtained from the hourly observations collected at a suburban site in Beirut, Lebanon, during summer and winter ECOCEM (Emissions and Chemistry of Organic Carbon in the Eastern Mediterranean) campaigns. The observed ERs were calculated using two independent methods. ER values from both methods agree very well and are comparable to the ones of the road transport sector from near-field measurements for more than 80 % of the species. There is no significant seasonality in ER for more than 90 % of the species, unlike the seasonality usually observed in other cities worldwide. Regardless of the season, ERs agree within a factor of 2 between Beirut and other representative cities worldwide, except for the unburned fuel fraction and ethane. ERs of aromatics (except benzene) are higher in Beirut compared to northern post-industrialized countries and even the Middle Eastern city Mecca. The comparison of the observed ER to the ones extracted from the ACCMIP and MACCity global emission inventories suggests that the overall speciation of anthropogenic sources for major hydrocarbons that act as ozone and secondary organic aerosol (SOA) precursors in ACCMIP is better represented than other species. The comparison of the specific road transport ERs, relative to acetylene derived from near-field measurements, to ERs from ACCMIP and EMEP emission inventories for the road transport sector showed that ERs of more reactive species are usually consistent within a factor of 2 with EMEP, while xylenes and toluene are underestimated by over a factor of 2 by ACCMIP. The observed heterogeneity of anthropogenic VOC emission composition between Middle Eastern cities can be significant for reactive VOCs but is not depicted by global emission inventories. This suggests that systematic and detailed measurements are needed in the eastern Mediterranean Basin in order to better constrain emission inventory.

Internet Performance Analysis of South Asian Countries Using End-to-End Internet Performance Measurements

DOE PAGES

Ali, Saqib; Wang, Guojun; Cottrell, Roger Leslie; ...

2018-05-28

Internet performance is highly correlated with key economic development metrics of a region. According to World Bank, the economic growth of a country increases 1.3% with a 10% increase in the speed of the Internet. Therefore, it is necessary to monitor and understand the performance of the Internet links in the region. It helps to figure out the infrastructural inefficiencies, poor resource allocation, and routing issues in the region. Moreover, it provides healthy suggestions for future upgrades. Therefore, the objective of this paper is to understand the Internet performance and routing infrastructure of South Asian countries in comparison to themore » developed world and neighboring countries using end-to-end Internet performance measurements. The South Asian countries comprise nearly 32% of the Internet users in Asia and nearly 16% of the world. The Internet performance metrics in the region are collected through the PingER framework. The framework is developed by the SLAC National Accelerator Laboratory, USA and is running for the last 20 years. PingER has 16 monitoring nodes in the region, and in the last year PingER monitors about 40 sites in South Asia using the ubiquitous ping facility. The collected data is used to estimate the key Internet performance metrics of South Asian countries. The performance metrics are compared with the neighboring countries and the developed world. Particularly, the TCP throughput of the countries is also correlated with different development indices. Further, worldwide Internet connectivity and routing patterns of the countries are investigated to figure out the inconsistencies in the region. Furthermore, the performance analysis revealed that the South Asia region is 7-10 years behind the developed regions of North America (USA and Canada), Europe, and East Asia.« less

Internet Performance Analysis of South Asian Countries Using End-to-End Internet Performance Measurements

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

Ali, Saqib; Wang, Guojun; Cottrell, Roger Leslie

Internet performance is highly correlated with key economic development metrics of a region. According to World Bank, the economic growth of a country increases 1.3% with a 10% increase in the speed of the Internet. Therefore, it is necessary to monitor and understand the performance of the Internet links in the region. It helps to figure out the infrastructural inefficiencies, poor resource allocation, and routing issues in the region. Moreover, it provides healthy suggestions for future upgrades. Therefore, the objective of this paper is to understand the Internet performance and routing infrastructure of South Asian countries in comparison to themore » developed world and neighboring countries using end-to-end Internet performance measurements. The South Asian countries comprise nearly 32% of the Internet users in Asia and nearly 16% of the world. The Internet performance metrics in the region are collected through the PingER framework. The framework is developed by the SLAC National Accelerator Laboratory, USA and is running for the last 20 years. PingER has 16 monitoring nodes in the region, and in the last year PingER monitors about 40 sites in South Asia using the ubiquitous ping facility. The collected data is used to estimate the key Internet performance metrics of South Asian countries. The performance metrics are compared with the neighboring countries and the developed world. Particularly, the TCP throughput of the countries is also correlated with different development indices. Further, worldwide Internet connectivity and routing patterns of the countries are investigated to figure out the inconsistencies in the region. Furthermore, the performance analysis revealed that the South Asia region is 7-10 years behind the developed regions of North America (USA and Canada), Europe, and East Asia.« less

China’s Rise and Reconfiguration of Central Asia’s Geopolitics: A Case for U.S. Pivot to Eurasia

DTIC Science & Technology

2015-07-01

comprehensive security” organization that is a China alternative to U.S.-pro- moted “collective security” alliance structures.57 This is not to dismiss...diversifica- tion of its gas and cotton exports-dependent economy. Kyrgyzstan is by far the least authoritarian state in Central Asia and, in the long run, may...Authorities have also failed to resuscitate its relatively isolated economy overly dependent on aluminum and cotton exports and ev- er-expanding drug flows

7 CFR 201.51 - Inert matter.

Code of Federal Regulations, 2012 CFR

2012-01-01

... (other than grasses) with over one-half of the embryo missing. (2) Grass florets and caryopses classed as... caryopses devoid of embryo and/or endosperm; (iv) Immature florets of quackgrass (Agropyron repens) in which..., devoid of both embryo and endosperm, such as occur in but not limited to the following plant families...

7 CFR 201.51 - Inert matter.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (other than grasses) with over one-half of the embryo missing. (2) Grass florets and caryopses classed as... caryopses devoid of embryo and/or endosperm; (iv) Immature florets of quackgrass (Agropyron repens) in which..., devoid of both embryo and endosperm, such as occur in but not limited to the following plant families...

7 CFR 201.51 - Inert matter.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (other than grasses) with over one-half of the embryo missing. (2) Grass florets and caryopses classed as... caryopses devoid of embryo and/or endosperm; (iv) Immature florets of quackgrass (Agropyron repens) in which..., devoid of both embryo and endosperm, such as occur in but not limited to the following plant families...

Description of two new Bathyaethiops species (Teleostei: Alestidae) from the Congo basin.

PubMed

Moritz, Timo; Schliewen, Ulrich K

2016-06-02

Two new species of Bathyaethiops (Teleostei: Characiformes: Alestidae) are described. Bathyaethiops baka n. sp. is a dwarf species with the largest known specimen being only 24.4 mm SL. The species is characterized by an incomplete squamation and a large humeral spot. Bathyaethiops baka n. sp. is known so far only from the Ngoko River of Southeastern Cameroon, a tributary of the Sangha River in the northern Congo basin. The second species, Bathyaethiops flammeus n. sp., shows a diagnostic spot in front of the dorsal-fin base, which is devoid of melanophores and bright red in life. The species is described from the Bakéré River at Yambula-Bakéré, a locality north-west of Kisangani in the Central Congo basin. Other records of Bathyaethiops flammeus n. sp. from the Tshuapa respectively Ruki River at Boende and Eala, Central Congo basin, suggests a wider geographic distribution. A key to all species of Bathyaethiops is provided.

Multi-Sensor Remote Sensing of Forest Dynamics in Central Siberia

NASA Technical Reports Server (NTRS)

Ransom, K. J.; Sun, G.; Kharuk, V. I.; Howl, J.

2011-01-01

The forested regions of Siberia, Russia are vast and contain about a quarter of the world's forests that have not experienced harvesting. However, many Siberian forests are facing twin pressures of rapidly changing climate and increasing timber harvest activity. Monitoring the dynamics and mapping the structural parameters of the forest is important for understanding the causes and consequences of changes observed in these areas. Because of the inaccessibility and large extent of this forest, remote sensing data can play an important role for observing forest state and change. In Central Siberia, multi-sensor remote sensing data have been used to monitor forest disturbances and to map above-ground biomass from the Sayan Mountains in the south to the taiga-tundra boundaries in the north. Radar images from the Shuttle Imaging Radar-C (SIR-C)/XSAR mission were used for forest biomass estimation in the Sayan Mountains. Radar images from the Japanese Earth Resources Satellite-1 (JERS-1), European Remote Sensing Satellite-1 (ERS-1) and Canada's RADARSAT-1, and data from ETM+ on-board Landsat-7 were used to characterize forest disturbances from logging, fire, and insect damage in Boguchany and Priangare areas.

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.

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

Fabrication and Luminescence Characterization of a Silica Nanomatrix Embedded with NaYF4:Yb:Er:Tm@NaGdF4/Fe3O4 Nanoparticles

NASA Astrophysics Data System (ADS)

Thangaraju, Dheivasigamani; Santhana, Vedi; Matsuda, Satoshi; Hayakawa, Yasuhiro

2018-05-01

Hexagonal NaYF4:Yb:Er:Tm@NaGdF4 core-shell nanocrystals were synthesized using a seed mediated hot injection method, and monodispersed Fe3O4 (4 nm) nanoparticles were prepared from iron(II) actylacetonate by a precursor thermal decomposition method. Structural and morphology verified NaYF4:Yb:Er:Tm@NaGdF4 and Fe3O4 nanoparticles were utilized for the preparation of NaYF4:Yb:Er:Tm@NaGdF4/Fe3O4@SiO2 nanocomposite using a micro-emulsion method. Existence of Fe3O4 in NaYF4:Yb:Er:Tm@NaGdF4 in SiO2 nano-spheres were confirmed with transmission electron microscopy. Luminescence measurement revealed that NaYF4:Yb:Er:Tm@NaGdF4 exhibited strong emissions at green and red regions, in addition to a weak blue emission also observed under 980 nm excitation. Up-conversion emission of the nanoparticle-embedded silica nanocomposite showed that the up-conversion emission was not affected by Fe3O4 nanoparticles.

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.

Characterization of an estrogen-responsive element implicated in regulation of the rainbow trout estrogen receptor gene.

PubMed

Le Dréan, Y; Lazennec, G; Kern, L; Saligaut, D; Pakdel, F; Valotaire, Y

1995-08-01

We previously reported that the expression of the rainbow trout estrogen receptor (rtER) gene is markedly increased by estradiol (E2). In this paper, we have used transient transfection assays with reporter plasmids expressing chloramphenicol acetyl transferase (CAT), linked to 5' flanking regions of the rtER gene promoter, to identify cis-elements responsible for E2 inducibility. Deletion analysis localized an estrogen-responsive element (ERE), at position +242, with one mutation on the first base compared with the consensus sequence. This element confers estrogen responsiveness to CAT reporter linked to both the herpes simplex virus thymidine kinase promoter and the homologous rtER promoter. Moreover, using a 0.2 kb fragment of the rtER promoter encompassing the ERE and the rtER DNA binding domain obtained from a bacterial expression system, DNase I footprinting experiments demonstrated a specific protection covering 20 bp (+240/+260) containing the ERE sequence. Based on these studies, we believe that this ERE sequence, identified in the rtER gene promoter, may be a major cis-acting element involved in the regulation of the gene by estrogen.

Trends and sources of ozone and sub-micron aerosols at the Mt. Bachelor Observatory (MBO) during 2004-2015

NASA Astrophysics Data System (ADS)

Zhang, Lei; Jaffe, Daniel A.

2017-09-01

In this paper, we report the climatology of tropospheric ozone (O3) and sub-micron aerosol scattering at the Mt. Bachelor Observatory (MBO, 2.8 km asl) in central Oregon, USA, during 2004-2015. The seasonal cycle for O3 showed a bimodal pattern with peaks in April and July, while aerosol scattering (σsp) was lognormally distributed with a very high peak in August and a smaller peak in May. The mean O3 concentrations showed positive and significant trends in all seasons except winter, with a slope of 0.6-0.8 ppbv yr-1. Monthly criteria for isolating free tropospheric (FT) and boundary layer influenced (BLI) air masses at MBO were obtained based on comparison of MBO water vapor (WV) distributions to those of Salem (SLE) and Medford (MFR), Oregon, at equivalent pressure level. In all seasons, FT O3 was, on average, higher than BLI O3, but the seasonal patterns were rather similar. For σsp the FT mean in spring was higher, but the BLI mean in summer was significantly higher, indicating the importance of regional wildfire smoke. To better understand the causes for the seasonal and interannual trends at MBO, we identified four major categories of air masses that impact O3, carbon monoxide (CO) and aerosols: upper troposphere and lower stratosphere (UTLS) O3 intrusion, Asian long-range transport (ALRT), Arctic air pollution (AAP) and plumes from the Pacific Northwest region (PNW). ALRT and PNW plumes can be further divided into wildfires (WF), industrial pollution (IP) and mineral dust (MD). Over the 12 years of observations, 177 individual plume events have been identified. Enhancement ratios (ERs) and Ångström exponents (AEs) of aerosols were calculated for all events. The lowest slope of Δσsp/ΔO3 is a unique feature of UTLS events. PNW-WF events have the highest averages for Δσsp/ΔCO, Δσsp/ΔO3 and Δσsp/ΔNOy compared to other events. These ERs decrease during long-range transport due to the shorter residence time of aerosols compared to the other pollutants. ALRT-WF events have lower absorption AEs (Åap) than PNW-WF, implying that brown carbon (BrC) is generated from biomass burning but its fraction decreases during long-range transport. Signatures of ERs and AEs are useful tools to identify different plume categories. These results demonstrate the increasing impact of baseline O3 on US air quality due to both global sources and regional wildfire events.

Involvement of the Nrf2-proteasome pathway in the endoplasmic reticulum stress response in pancreatic β-cells

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

Lee, Sanghwan; Hur, Eu-gene; Ryoo, In-geun

2012-11-01

The ubiquitin-proteasome system plays a central role in protein quality control through endoplasmic reticulum (ER)-associated degradation (ERAD) of unfolded and misfolded proteins. NF-E2‐related factor 2 (Nrf2) is a transcription factor that controls the expression of an array of phase II detoxification and antioxidant genes. Nrf2 signaling has additionally been shown to upregulate the expression of the proteasome catalytic subunits in several cell types. Here, we investigated the role of Nrf2 in tunicamycin-induced ER stress using a murine insulinoma β-cell line, βTC-6. shRNA-mediated silencing of Nrf2 expression in βTC-6 cells significantly increased tunicamycin-induced cytotoxicity, elevated the expression of the pro-apoptotic ERmore » stress marker Chop10, and inhibited tunicamycin-inducible expression of the proteasomal catalytic subunits Psmb5 and Psmb6. The effects of 3H-1,2-dithiole-3-thione (D3T), a small molecule Nrf2 activator, on ER stress were also examined in βTC-6 cells. D3T pretreatment reduced tunicamycin cytotoxicity and attenuated the tunicamycin-inducible Chop10 and protein kinase RNA-activated‐like ER kinase (Perk). The protective effect of D3T was shown to be associated with increased ERAD. D3T increased the expression of Psmb5 and Psmb6 and elevated chymotrypsin-like peptidase activity; proteasome inhibitor treatment blocked D3T effects on tunicamycin cytotoxicity and ER stress marker changes. Similarly, silencing of Nrf2 abolished the protective effect of D3T against ER stress. These results indicate that the Nrf2 pathway contributes to the ER stress response in pancreatic β-cells by enhancing proteasome-mediated ERAD. -- Highlights: ► Nrf2 silencing in pancreatic β-cells enhanced tunicamycin-mediated ER stress. ► Expression of the proteasome was inducible by Nrf2 signaling. ► Nrf2 activator D3T protected β-cells from tunicamycin-mediated ER stress. ► Protective effect of D3T was associated with Nrf2-dependent proteasome induction.« less

77 FR 68759 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... LLC, BE Rayle LLC, Cedar Brakes I, L.L.C., Cedar Brakes II, L.L.C., Central Power & Lime LLC, Triton Power Michigan LLC, Utility Contract Funding, L.L.C. Description: JPMorgan Sellers' Notice of Non... that the Commission received the following electric rate filings: Docket Numbers: ER10-1821-003...

75 FR 6197 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... Contract Funding, L.L.C., Vineland Energy LLC, Central Power & Lime LLC, Cedar Brakes II, L.L.C., J.P..., 2010. Take notice that the Commission received the following electric rate filings: Docket Numbers: ER97-870-016. Applicants: Sunoco Power Marketing LLC. Description: Sunoco Power Marketing, LLC submits...

The recent changes and topics in CONTRAIL project

NASA Astrophysics Data System (ADS)

Machida, Toshinobu; Umezawa, Taku; Sawa, Yousuke; Niwa, Yosuke; Matsueda, Hidekazu

2016-04-01

CONTRAIL (Comprehensive Observation Network for TRace gases by AIrLiner) project has been conducted since 2005 with Continuous CO2 Measuring Equipment (CME) and Automatic air Sampling Equipment (ASE) onboard commercial airliners for observations of atmospheric greenhouse gases. Japan Airlines (JAL) offers eight Boeing 777-200ER airplanes modified for CONTRAIL; CME and ASE can be installed on all and five of them, respectively. ASE measurements have provided the long records of greenhouse gases in the upper troposphere along the flight route between Japan and Australia. In addition, we started a new sampling program between Japan and Europe in 2012 to obtain data at higher latitudes and the UT/LS region. When the 777-200ER airplane was not operated for the observation route, we used Manual air Sampling Equipment (MSE) for taking air onboard as substitute for ASE. Since flight routes with 777-200ER have been restricted only to Asian countries and Hawaii in the last few years, additional two Boeing 777-300ERs were modified to install CME and expand area coverage of CO2 observations to Europe, Australia and the east coast of US in 2015-2016. We also present our recent data analysis for intensive CME observations over Delhi, India, which indicates a significant impact of Indian wintertime agriculture on the regional carbon budget.

Medications influencing central cholinergic pathways affect fixation stability, saccadic response time and associated eye movement dynamics during a temporally-cued visual reaction time task.

PubMed

Naicker, Preshanta; Anoopkumar-Dukie, Shailendra; Grant, Gary D; Modenese, Luca; Kavanagh, Justin J

2017-02-01

Anticholinergic medications largely exert their effects due to actions on the muscarinic receptor, which mediates the functions of acetylcholine in the peripheral and central nervous systems. In the central nervous system, acetylcholine plays an important role in the modulation of movement. This study investigated the effects of over-the-counter medications with varying degrees of central anticholinergic properties on fixation stability, saccadic response time and the dynamics associated with this eye movement during a temporally-cued visual reaction time task, in order to establish the significance of central cholinergic pathways in influencing eye movements during reaction time tasks. Twenty-two participants were recruited into the placebo-controlled, human double-blind, four-way crossover investigation. Eye tracking technology recorded eye movements while participants reacted to visual stimuli following temporally informative and uninformative cues. The task was performed pre-ingestion as well as 0.5 and 2 h post-ingestion of promethazine hydrochloride (strong centrally acting anticholinergic), hyoscine hydrobromide (moderate centrally acting anticholinergic), hyoscine butylbromide (anticholinergic devoid of central properties) and a placebo. Promethazine decreased fixation stability during the reaction time task. In addition, promethazine was the only drug to increase saccadic response time during temporally informative and uninformative cued trials, whereby effects on response time were more pronounced following temporally informative cues. Promethazine also decreased saccadic amplitude and increased saccadic duration during the temporally-cued reaction time task. Collectively, the results of the study highlight the significant role that central cholinergic pathways play in the control of eye movements during tasks that involve stimulus identification and motor responses following temporal cues.

Endoplasmic reticulum stress-mediated upregulation of miR-29a enhances sensitivity to neuronal apoptosis.

PubMed

Nolan, Katie; Walter, Franziska; Tuffy, Liam P; Poeschel, Simone; Gallagher, Ross; Haunsberger, Stefan; Bray, Isabella; Stallings, Raymond L; Concannon, Caoimhín G; Prehn, Jochen H M

2016-03-01

Disturbance of homeostasis within the endoplasmic reticulum (ER) lumen leads to the accumulation of unfolded and misfolded proteins. This results in the activation of an evolutionary conserved stress response termed ER stress that, if unresolved, induces apoptosis. Previously the Bcl-2 homology domain 3-Only Protein Puma was identified as a mediator of ER stress-induced apoptosis in neurons. In the search of alternative contributors to ER stress-induced apoptosis, a downregulation of the anti-apoptotic Bcl-2 family protein Mcl-1 was noted during ER stress in both mouse cortical neurons and human SH-SY5Y neuroblastoma cells. Downregulation of Mcl-1 was associated with an upregulation of microRNA-29a (miR-29a) expression, and subsequent experiments showed that miR-29a targeted the 3'-untranslated region of the anti-apoptotic Bcl-2 family protein, Mcl-1. Inhibition of miR-29a expression using sequence-specific antagomirs or the overexpression of Mcl-1 decreased cell death following tunicamycin treatment, while gene silencing of Mcl-1 increased cell death. miR-29a did not alter the signalling branches of the ER stress response, rather its expression was controlled by the ER stress-induced transcription factor activating-transcription-factor-4 (ATF4). The current data demonstrate that the ATF4-mediated upregulation of miR-29a enhances the sensitivity of neurons to ER stress-induced apoptosis. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Effect of bracket bonding with Er: YAG laser on nanomechanical properties of enamel.

PubMed

Alavi, Shiva; Birang, Reza; Hajizadeh, Fatemeh; Banimostafaee, Hamed

2014-01-01

The aim of this study was to compare the effects of conventional acid etching and laser etching on the nano-mechanical properties of the dental enamel using nano-indentation test. In this experimental in vitro study, buccal surfaces of 10 premolars were divided into three regions. One of the regions was etched with 37% phosphoric acid and another etched with Er:YAG laser, the third region was not etched. The brackets were bonded to both of etched regions. After thermocycling for 500 cycles, the brackets were removed and the teeth were decoronated from the bracket bonding area. Seven nano-indentations were applied at 1-31 μm depth from the enamel surface in each region. Mean values of the hardness and elastic modulus were analyzed with repeated measures analysis of variance and Tukey HSD tests, using the SPSS software (SPSS Inc., version16.0, Chicago, Il, USA). P < 0.05 was considered as significant. The hardness up to 21 μm in depth and elastic modulus up to 6 μm in depth from the enamel surface for laser-etched enamel had significantly higher values than control enamel and the hardness up to 11 μm in depth and elastic modulus up to 6 μm in depth for acid-etched enamel had significantly lower values than the control enamel. The mechanical properties of the enamel were decreased after bracket bonding with conventional acid etching and increased after bonding with Er:YAG laser.

Quantifying cortical development in typically developing toddlers and young children, 1-6 years of age.

PubMed

Remer, Justin; Croteau-Chonka, Elise; Dean, Douglas C; D'Arpino, Sara; Dirks, Holly; Whiley, Dannielle; Deoni, Sean C L

2017-06-01

Cortical maturation, including age-related changes in thickness, volume, surface area, and folding (gyrification), play a central role in developing brain function and plasticity. Further, abnormal cortical maturation is a suspected substrate in various behavioral, intellectual, and psychiatric disorders. However, in order to characterize the altered development associated with these disorders, appreciation of the normative patterns of cortical development in neurotypical children between 1 and 6 years of age, a period of peak brain development during which many behavioral and developmental disorders emerge, is necessary. To this end, we examined measures of cortical thickness, surface area, mean curvature, and gray matter volume across 34 bilateral regions in a cohort of 140 healthy children devoid of major risk factors for abnormal development. From these data, we observed linear, logarithmic, and quadratic patterns of change with age depending on brain region. Cortical thinning, ranging from 10% to 20%, was observed throughout most of the brain, with the exception of posterior brain structures, which showed initial cortical thinning from 1 to 5 years, followed by thickening. Cortical surface area expansion ranged from 20% to 108%, and cortical curvature varied by 1-20% across the investigated age range. Right-left hemisphere asymmetry was observed across development for each of the 4 cortical measures. Our results present new insight into the normative patterns of cortical development across an important but under studied developmental window, and provide a valuable reference to which trajectories observed in neurodevelopmental disorders may be compared. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Clusterin expression in elastofibroma dorsi.

PubMed

Aigelsreiter, Ariane; Pichler, Martin; Pixner, Thomas; Janig, Elke; Schuller, Monika; Lackner, Carolin; Scheipl, Susanne; Beham, Alfred; Regauer, Sigrid

2013-05-01

Elastofibroma dorsi is a benign soft tissue lesion composed of abnormal elastic fibers. Degenerated elastic fibers in skin and liver are associated with clusterin, an apoprotein that shares functional properties with small heat shock proteins. We evaluated the staining pattern and possible role of clusterin in elastofibroma dorsi. Twenty-one subcutaneous elastofibromas from the scapular region were evaluated with Elastica van Gieson and Orcein stains, immunohistochemically with antibodies to clusterin, smooth muscle actin, S-100, vimentin and CD34 and correlated with clinical data with respect to physical trauma. Clusterin correlated with the staining pattern of Elastica van Gieson and labelled abnormal broad coarse fibrillar and globular elastic fibers in all elastofibromas. Orcein stains additionally identified fine oxytalan fibers which were not stained by clusterin. Clusterin staining was observed only on the outside of the elastin fibers, while the cores of fibers and globules were unstained. 4/21 elastofibromas showed cellular nodules with a myxoid/collagenous stroma. The round to oval cells showed cytoplasmic staining with vimentin and clusterin; CD34 labelled mostly cell membranes. The cells lacked SMA and S-100 expression. The central areas of the nodules were devoid of elastic fibers, but the periphery contained coarse fibers and globules. 9/ 11 patients, for whom clinical data were available, reported trauma to the scapular region. Many investigated ED were associated with trauma, which supports a reactive/degenerative etiology of ED. The abnormal large elastic fibers in all ED were enveloped by clusterin. Clusterin deposition may protect elastic fibers from degradation and thus contribute indirectly to the tumor-like presentation of ED.

The cnm locus, a canine homologue of human autosomal forms of centronuclear myopathy, maps to chromosome 2.

PubMed

Tiret, Laurent; Blot, Stéphane; Kessler, Jean-Louis; Gaillot, Hugues; Breen, Matthew; Panthier, Jean-Jacques

2003-09-01

Myotubular/centronuclear myopathies are a nosological group of hereditary disorders characterised by severe architectural and metabolic remodelling of skeletal muscle fibres. In most myofibres, nuclei are found at an abnormal central position within a halo devoid of myofibrillar proteins. The X-linked form (myotubular myopathy) is the most prevalent and severe form in human, leading to death during early postnatal life. Maturation of fibres is not completed and fibres resemble myotubes. Linkage analysis in human has helped to identify MTM1 as the morbid gene. MTM1 encodes myotubularin, a dual protein phosphatase. In families in which myotubular myopathy segregates, detected mutations in MTM1 abolish the specific phosphatase activity targeting the second messenger phosphatidylinositol 3-phosphate. Autosomal forms (centronuclear) have a later onset and are often compatible with life. At birth, fibres are normally constituted but progressively follow remodelling with a secondary centralisation of nuclei. Their prevalence is low; hence, no linkage data can be performed and no molecular aetiology is known. In the Labrador Retriever, a spontaneous disorder strikingly mimics the clinical evolution of the human centronuclear myopathy. We have established a canine pedigree and show that the disorder segregates as an autosomal recessive trait in that pedigree. We have further mapped the dog locus to a region on chromosome 2 that is orthologous to human chromosome 10p. To date, no human MTM1 gene member has been mapped to this genetic region. This report thus describes the first spontaneous mammalian model of centronuclear myopathy and defines a new locus for this group of diseases.

Spirometry in primary care: An analysis of spirometry test quality in a regional primary care asthma program

PubMed Central

Licskai, Christopher J; Sands, Todd W; Paolatto, Lisa; Nicoletti, Ivan; Ferrone, Madonna

2012-01-01

BACKGROUND: Primary care office spirometry can improve access to testing and concordance between clinical practice and asthma guidelines. Compliance with test quality standards is essential to implementation. OBJECTIVE: To evaluate the quality of spirometry performed onsite in a regional primary care asthma program (RAP) by health care professionals with limited training. METHODS: Asthma educators were trained to perform spirometry during two 2 h workshops and supervised during up to six patient encounters. Quality was analyzed using American Thoracic Society (ATS) 1994 and ATS/European Respiratory Society (ERS) 2003 (ATS/ERS) standards. These results were compared with two regional reference sites: a primary care group practice (Family Medical Centre [FMC], Windsor, Ontario) and a teaching hospital pulmonary function laboratory (London Health Sciences Centre [LHSC], London, Ontario). RESULTS: A total of 12,815 flow-volume loops (FVL) were evaluated: RAP – 1606 FVL in 472 patient sessions; reference sites – FMC 4013 FVL in 573 sessions; and LHSC – 7196 in 1151 sessions. RAP: There were three acceptable FVL in 392 of 472 (83%) sessions, two reproducible FVL according to ATS criteria in 428 of 469 (91%) sessions, and 395 of 469 (84%) according to ATS/ERS criteria. All quality criteria – minimum of three acceptable and two reproducible FVL according to ATS criteria in 361 of 472 (77%) sessions and according to ATS/ERS criteria in 337 of 472 (71%) sessions. RAP met ATS criteria more often than the FMC (388 of 573 [68%]); however, less often than LHSC (1050 of 1151 [91%]; P<0.001). CONCLUSIONS: Health care providers with limited training and experience operating within a simple quality program achieved ATS/ERS quality spirometry in the majority of sessions in a primary care setting. The quality performance approached pulmonary function laboratory standards. PMID:22891184

Extreme Precipitation and Emergency Room Visits for Gastrointestinal Illness in Areas with and without Combined Sewer Systems: An Analysis of Massachusetts Data, 2003-2007.

PubMed

Jagai, Jyotsna S; Li, Quanlin; Wang, Shiliang; Messier, Kyle P; Wade, Timothy J; Hilborn, Elizabeth D

2015-09-01

Combined sewer overflows (CSOs) occur in combined sewer systems when sewage and stormwater runoff are released into water bodies, potentially contaminating water sources. CSOs are often caused by heavy precipitation and are expected to increase with increasing extreme precipitation associated with climate change. The aim of this study was to assess whether the association between heavy rainfall and rate of emergency room (ER) visits for gastrointestinal (GI) illness differed in the presence of CSOs. For the study period 2003-2007, time series of daily rate of ER visits for GI illness and meteorological data were organized for three exposure regions: a) CSOs impacting drinking water sources, b) CSOs impacting recreational waters, c) no CSOs. A distributed lag Poisson regression assessed cumulative effects for an 8-day lag period following heavy (≥ 90th and ≥ 95th percentile) and extreme (≥ 99th percentile) precipitation events, controlling for temperature and long-term time trends. The association between extreme rainfall and rate of ER visits for GI illness differed among regions. Only the region with drinking water exposed to CSOs demonstrated a significant increased cumulative risk for rate (CRR) of ER visits for GI for all ages in the 8-day period following extreme rainfall: CRR: 1.13 (95% CI: 1.00, 1.28) compared with no rainfall. The rate of ER visits for GI illness was associated with extreme precipitation in the area with CSO discharges to a drinking water source. Our findings suggest an increased risk for GI illness among consumers whose drinking water source may be impacted by CSOs after extreme precipitation. Jagai JS, Li Q, Wang S, Messier KP, Wade TJ, Hilborn ED. 2015. Extreme precipitation and emergency room visits for gastrointestinal illness in areas with and without combined sewer systems: an analysis of Massachusetts data, 2003-2007. Environ Health Perspect 123:873-879; http://dx.doi.org/10.1289/ehp.1408971.

Disease Transmission by Misfolded Prion-Protein Isoforms, Prion-Like Amyloids, Functional Amyloids and the Central Dogma

PubMed Central

Daus, Martin L.

2016-01-01

In 1982, the term “prions” (proteinaceous infectious particles) was coined to specify a new principle of infection. A misfolded isoform of a cellular protein has been described as the causative agent of a fatal neurodegenerative disease. At the beginning of prion research scientists assumed that the infectious agent causing transmissible spongiform encephalopathy (TSE) was a virus, but some unconventional properties of these pathogens were difficult to bring in line with the prevailing viral model. The discovery that prions (obviously devoid of any coding nucleic acid) can store and transmit information similarly to DNA was initially even denoted as being “heretical” but is nowadays mainly accepted by the scientific community. This review describes, from a historical point of view, how the “protein-only hypothesis” expands the Central Dogma. Definition of both, the prion principle and the Central Dogma, have been essential steps to understand information storage and transfer within and among cells and organisms. Furthermore, the current understanding of the infectivity of prion-proteins after misfolding is summarized succinctly. Finally, prion-like amyloids and functional amyloids, as found in yeast and bacteria, will be discussed. PMID:26742083

Disease Transmission by Misfolded Prion-Protein Isoforms, Prion-Like Amyloids, Functional Amyloids and the Central Dogma.

PubMed

Daus, Martin L

2016-01-04

In 1982, the term "prions" (proteinaceous infectious particles) was coined to specify a new principle of infection. A misfolded isoform of a cellular protein has been described as the causative agent of a fatal neurodegenerative disease. At the beginning of prion research scientists assumed that the infectious agent causing transmissible spongiform encephalopathy (TSE) was a virus, but some unconventional properties of these pathogens were difficult to bring in line with the prevailing viral model. The discovery that prions (obviously devoid of any coding nucleic acid) can store and transmit information similarly to DNA was initially even denoted as being "heretical" but is nowadays mainly accepted by the scientific community. This review describes, from a historical point of view, how the "protein-only hypothesis" expands the Central Dogma. Definition of both, the prion principle and the Central Dogma, have been essential steps to understand information storage and transfer within and among cells and organisms. Furthermore, the current understanding of the infectivity of prion-proteins after misfolding is summarized succinctly. Finally, prion-like amyloids and functional amyloids, as found in yeast and bacteria, will be discussed.

Trib3 Is Developmentally and Nutritionally Regulated in the Brain but Is Dispensable for Spatial Memory, Fear Conditioning and Sensing of Amino Acid-Imbalanced Diet

PubMed Central

Örd, Tiit; Innos, Jürgen; Lilleväli, Kersti; Tekko, Triin; Sütt, Silva; Örd, Daima; Kõks, Sulev; Vasar, Eero; Örd, Tõnis

2014-01-01

Tribbles homolog 3 (TRIB3) is a mammalian pseudokinase that is induced in neuronal cell cultures in response to cell death-inducing stresses, including neurotrophic factor deprivation. TRIB3 is an inhibitor of activating transcription factor 4 (ATF4), the central transcriptional regulator in the eukaryotic translation initiation factor 2α (eIF2α) phosphorylation pathway that is involved in the cellular stress response and behavioral processes. In this article, we study the expression of Trib3 in the mouse brain, characterize the brain morphology of mice with a genetic ablation of Trib3 and investigate whether Trib3 deficiency alters eIF2α-dependent cognitive abilities. Our data show that the consumption of a leucine-deficient diet induces Trib3 expression in the anterior piriform cortex, the brain region responsible for detecting essential amino acid intake imbalance. However, the aversive response to leucine-devoid diet does not differ in Trib3 knockout and wild type mice. Trib3 deletion also does not affect long-term spatial memory and reversal learning in the Morris water maze and auditory or contextual fear conditioning. During embryonic development, Trib3 expression increases in the brain and persists in the early postnatal stadium. Neuroanatomical characterization of mice lacking Trib3 revealed enlarged lateral ventricles. Thus, although the absence of Trib3 does not alter the eIF2α pathway-dependent cognitive functions of several areas of the brain, including the hippocampus, amygdala and anterior piriform cortex, Trib3 may serve a role in other central nervous system processes and molecular pathways. PMID:24732777

Inactivation of pecS restores the virulence of mutants devoid of osmoregulated periplasmic glucans in the phytopathogenic bacterium Dickeya dadantii.

PubMed

Bontemps-Gallo, Sébastien; Madec, Edwige; Lacroix, Jean-Marie

2014-04-01

Dickeya dadantii is a phytopathogenic enterobacterium that causes soft rot disease in a wide range of plant species. Maceration, an apparent symptom of the disease, is the result of the synthesis and secretion of a set of plant cell wall-degrading enzymes (PCWDEs), but many additional factors are required for full virulence. Among these, osmoregulated periplasmic glucans (OPGs) and the PecS transcriptional regulator are essential virulence factors. Several cellular functions are controlled by both OPGs and PecS. Strains devoid of OPGs display a pleiotropic phenotype including total loss of virulence, loss of motility and severe reduction in the synthesis of PCWDEs. PecS is one of the major regulators of virulence in D. dadantii, acting mainly as a repressor of various cellular functions including virulence, motility and synthesis of PCWDEs. The present study shows that inactivation of the pecS gene restored virulence in a D. dadantii strain devoid of OPGs, indicating that PecS cannot be de-repressed in strains devoid of OPGs.

Scintillation properties of Nd 3+, Tm 3+, and Er 3+ doped LuF 3 scintillators in the vacuum ultra violet region

NASA Astrophysics Data System (ADS)

Yanagida, Takayuki; Kawaguchi, Noriaki; Fukuda, Kentaro; Kurosawa, Shunsuke; Fujimoto, Yutaka; Futami, Yoshisuke; Yokota, Yuui; Taniue, Kojiro; Sekiya, Hiroyuki; Kubo, Hidetoshi; Yoshikawa, Akira; Tanimori, Toru

2011-12-01

In order to develop novel vacuum ultra violet (VUV) emitting scintillators, we grew Nd 0.5%, Tm 0.5%, and Er 0.5% doped LuF3 scintillators by the μ-pulling down method, because LuF3 has a very wide band gap and Nd3+, Tm3+, and Er3+ luminescence centers show fast and intense 5d-4f emission in VUV region. Transmittance and X-ray induced radioluminescence were studied in these three samples using our original spectrometer made by Bunkou-Keiki company. In the VUV region, transmittance of 20-60% was achieved for all the samples. The emission peaks appeared at approximately 180, 165, and 164 nm for Nd3+, Tm3+, and Er3+ doped LuF3, respectively. Using PMT R8778 (Hamamatsu), we measured their light yields under 241Am α-ray excitation. Compared with Nd:LaF3 scintillator, which has 33 photoelectrons/5.5 MeV α, Nd:LuF3 and Tm:LuF3 showed 900±90 and 170±20 ph/5.5 MeV-α, respectively. Only for the Nd doped one, we can detect 137Cs 662 keV γ-ray photoabsorption peak and the light yield of 1200±120 ph/MeV was measured. We also investigated their decay time profiles by picosecond pulse X-ray equipped streak camera, and the main decay component of Nd:LuF3 turned out to be 7.63 ns.

Up-conversion routines of Er{sup 3+}–Yb{sup 3+} doped Y{sub 6}O{sub 5}F{sub 8} and YOF phosphors

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

Park, Sangmoon, E-mail: spark@silla.ac.kr; Yang, Wonseok; Park, Chu-Young

2015-11-15

Highlights: • Single-phase optical materials of Y{sub 6}O{sub 5}F{sub 8}:Er and YOF:Er were prepared. • Effective spectral converting properties were observed in Y{sub 6}O{sub 5}F{sub 8}:Er,Yb. • 980 nm diode laser was irradiated for up-converting analysis. • A multi-photon process in the phosphors was investigated. - Abstract: Optical materials composed of a Y{sub 6(1−p−q)}Er{sub 6p}Yb{sub 6q}O{sub 5}F{sub 8} (p = 0.001–0.1, q = 0.005–0.1) solid solution with Y{sub 0.99}Er{sub 0.01}OF were prepared via a solid-state reaction using excess NH{sub 4}F flux at 950 °C for 30 min. X-ray diffraction patterns of Y{sub 6(1−p−q)}Er{sub 6p}Yb{sub 6q}O{sub 5}F{sub 8} and Y{sub 0.99}Er{submore » 0.01}OF were compared upon altering the synthesis temperature and the molar ratio of the NH{sub 4}F flux to the Y{sup 3+} (Er{sup 3+}, Yb{sup 3+}) ions. The effective spectral-conversion properties of Er{sup 3+} and Er{sup 3+}–Yb{sup 3+} ions in Y{sub 6}O{sub 5}F{sub 8} phosphors were monitored during excitation with a 980 nm wavelength diode-laser. Selection of appropriate Er{sup 3+} and/or Yb{sup 3+} concentrations in the Y{sub 6}O{sub 5}F{sub 8} structure led to achievement of the desired up-conversion emission, from the green to the red regions of the spectra. Furthermore, the mechanism of up-conversion in the phosphors was described by an energy-level schematic. Up-conversion emission spectra and the dependence of the emission intensity on pump power (between 193 and 310 mW) in the Y{sub 6(0.995−q)}Er{sub 0.03}Yb{sub 6q}O{sub 5}F{sub 8} phosphors were also investigated.« less

SDSS-IV MaNGA: the impact of diffuse ionized gas on emission-line ratios, interpretation of diagnostic diagrams and gas metallicity measurements

NASA Astrophysics Data System (ADS)

Zhang, Kai; Yan, Renbin; Bundy, Kevin; Bershady, Matthew; Haffner, L. Matthew; Walterbos, René; Maiolino, Roberto; Tremonti, Christy; Thomas, Daniel; Drory, Niv; Jones, Amy; Belfiore, Francesco; Sánchez, Sebastian F.; Diamond-Stanic, Aleksandar M.; Bizyaev, Dmitry; Nitschelm, Christian; Andrews, Brett; Brinkmann, Jon; Brownstein, Joel R.; Cheung, Edmond; Li, Cheng; Law, David R.; Roman Lopes, Alexandre; Oravetz, Daniel; Pan, Kaike; Storchi Bergmann, Thaisa; Simmons, Audrey

2017-04-01

Diffuse ionized gas (DIG) is prevalent in star-forming galaxies. Using a sample of 365 nearly face-on star-forming galaxies observed by Mapping Nearby Galaxies at APO, we demonstrate how DIG in star-forming galaxies impacts the measurements of emission-line ratios, hence the interpretation of diagnostic diagrams and gas-phase metallicity measurements. At fixed metallicity, DIG-dominated low ΣHα regions display enhanced [S II]/Hα, [N II]/Hα, [O II]/Hβ and [O I]/Hα. The gradients in these line ratios are determined by metallicity gradients and ΣHα. In line ratio diagnostic diagrams, contamination by DIG moves H II regions towards composite or low-ionization nuclear emission-line region (LI(N)ER)-like regions. A harder ionizing spectrum is needed to explain DIG line ratios. Leaky H II region models can only shift line ratios slightly relative to H II region models, and thus fail to explain the composite/LI(N)ER line ratios displayed by DIG. Our result favours ionization by evolved stars as a major ionization source for DIG with LI(N)ER-like emission. DIG can significantly bias the measurement of gas metallicity and metallicity gradients derived using strong-line methods. Metallicities derived using N2O2 are optimal because they exhibit the smallest bias and error. Using O3N2, R23, N2 = [N II]/Hα and N2S2Hα to derive metallicities introduces bias in the derived metallicity gradients as large as the gradient itself. The strong-line method of Blanc et al. (IZI hereafter) cannot be applied to DIG to get an accurate metallicity because it currently contains only H II region models that fail to describe the DIG.

Observations and modelling of inflation in the Lazufre volcanic region, South America

NASA Astrophysics Data System (ADS)

Pearse, J.; Lundgren, P.

2010-12-01

The Central Volcanic Zone (CVZ) is an active volcanic arc in the central Andes, extending through Peru, southwestern Bolivia, Chile, and northwestern Argentina [De Silva, 1989; De Silva and Francis, 1991]. The CVZ includes a number of collapsed calderas, remnants of catastrophic eruptions, which are now thought to be inactive. However, recent Interferometric Synthetic Aperture Radar (InSAR) observations [Pritchard and Simons, 2004] show surface deformation occurring at some of these large ancient volcanic regions, indicating that magma chambers are slowly inflating beneath the surface. The mechanisms responsible for the initiation and growth of large midcrustal magma chambers remains poorly understood, and InSAR provides an opportunity for us to observe volcanic systems in remote regions that are otherwise difficult to monitor and observe. The Lastarria-Cordon del Azufre ("Lazufre" [Pritchard and Simons, 2002]) volcanic area is one such complex showing recent deformation, with average surface uplift rates of approximately 2.5 cm/year [Froger et al., 2007; Ruch et al, 2008]. We have processed InSAR data from ERS-1/2 and Envisat in the Lazufre volcanic area, including both ascending and descending satellite tracks. Time series analysis of the data shows steady uplift beginning in about 2000, continuing into 2010. We use boundary-element elastic models to invert for the depth and shape of the magmatic source responsible for the surface deformation. Given data from both ascending and descending tracks, we are able to resolve the ambiguity between the source depth and size, and constrain the geometry of the inflating magma source. Finite element modelling allows us to understand the effect of viscoelasticity on the development of the magma chamber.

Statistical organelle dissection of Arabidopsis guard cells using image database LIPS.

PubMed

Higaki, Takumi; Kutsuna, Natsumaro; Hosokawa, Yoichiroh; Akita, Kae; Ebine, Kazuo; Ueda, Takashi; Kondo, Noriaki; Hasezawa, Seiichiro

2012-01-01

To comprehensively grasp cell biological events in plant stomatal movement, we have captured microscopic images of guard cells with various organelles markers. The 28,530 serial optical sections of 930 pairs of Arabidopsis guard cells have been released as a new image database, named Live Images of Plant Stomata (LIPS). We visualized the average organellar distributions in guard cells using probabilistic mapping and image clustering techniques. The results indicated that actin microfilaments and endoplasmic reticulum (ER) are mainly localized to the dorsal side and connection regions of guard cells. Subtractive images of open and closed stomata showed distribution changes in intracellular structures, including the ER, during stomatal movement. Time-lapse imaging showed that similar ER distribution changes occurred during stomatal opening induced by light irradiation or femtosecond laser shots on neighboring epidermal cells, indicating that our image analysis approach has identified a novel ER relocation in stomatal opening.

Spectroscopy and visible frequency upconversion in Er3+-Yb3+: TeO2-ZnO glass.

PubMed

Mohanty, Deepak Kumar; Rai, Vineet Kumar

2014-01-01

The UV-Vis-NIR absorption studies of the Er(3+)/Er(3+)-Yb(3+) doped/codoped TeO2-ZnO (TZO) glasses fabricated by the melting and quenching method has been performed. The spectroscopic radiative parameters viz. radiative transition probabilities, branching ratios and lifetimes have been determined from the absorption spectrum by using Judd-Ofelt theory. The near infrared (NIR) to visible frequency upconversion (UC) have been monitored by using an excitation of 976 nm wavelength radiation from a CW diode laser. The effect of codoping with Yb(3+) ions on the intensity of the UC emission bands from the Er(3+) ions throughout visible region has been studied. The mechanism responsible for the observed upconversion emissions in the prepared samples have been explained on the basis of excited state absorption and efficient energy transfer processes. Copyright © 2013 Elsevier B.V. All rights reserved.

Inter- and intraconfigurational luminescence of Er3+ ions in BaY2F8 under VUV excitation

NASA Astrophysics Data System (ADS)

Kirm, M.; Lichtenberg, H.; Makhov, V. N.; Negodin, E.; Ouvarova, T. V.; Suljoti, E.; True, M.; Zimmerer, G.

Using energy- and time-resolved spectroscopy the luminescence properties of Er3+ doped BaY2F8 crystals were investigated at 10 K under VUV synchrotron radiation excitation. Radiative intraconfigurational f - f and interconfigurational d - f transitions in Er3+ ions were observed under f - d excitation. Whereas the onset of S-4(3/2) population via f - d excitation starts at 59 900 cm(-1) , efficient excitation of emissions arising from the P-2(3/2) state begins only above 67 000 cm(-1) in VUV region. Such behaviour can be explained by a cross-relaxation process of the type (F-2(2)(5/2) , I-4(15/2))-->(P-2(3/2) , P-2(3/2)) taking place within f -states of Er3+ ions finally populating the emitting P-2(3/2) state.

Expression of a truncated form of the endoplasmic reticulum chaperone protein, σ1 receptor, promotes mitochondrial energy depletion and apoptosis.

PubMed

Shioda, Norifumi; Ishikawa, Kiyoshi; Tagashira, Hideaki; Ishizuka, Toru; Yawo, Hiromu; Fukunaga, Kohji

2012-07-06

The σ1 receptor (σ(1)R) regulates endoplasmic reticulum (ER)/mitochondrial interorganellar Ca(2+) mobilization through the inositol 1,4,5-trisphosphate receptor (IP(3)R). Here, we observed that expression of a novel splice variant of σ(1)R, termed short form σ(1)R (σ(1)SR), has a detrimental effect on mitochondrial energy production and cell survival. σ(1)SR mRNA lacks 47 ribonucleotides encoding exon 2, resulting in a frameshift and formation of a truncated receptor. σ(1)SR localizes primarily in the ER at perinuclear regions and forms a complex with σ(1)R but not with IP(3)R in the mitochondrion-associated ER membrane. Overexpression of both σ(1)R and the truncated isoform promotes mitochondrial elongation with increased ER mitochondrial contact surface. σ(1)R overexpression increases the efficiency of mitochondrial Ca(2+) uptake in response to IP(3)R-driven stimuli, whereas σ(1)SR overexpression reduces it. Most importantly, σ(1)R promotes ATP production via increased mitochondrial Ca(2+) uptake, promoting cell survival in the presence of ER stress. By contrast, σ(1)SR suppresses ATP production following ER stress, enhancing cell death. Taken together, the newly identified σ(1)SR isoform interferes with σ(1)R function relevant to mitochondrial energy production under ER stress conditions, promoting cellular apoptosis.

Identifying high-risk areas of bacillary dysentery and associated meteorological factors in Wuhan, China.

PubMed

Li, Zhenjun; Wang, Ligui; Sun, Weige; Hou, Xuexin; Yang, Haiyan; Sun, Lina; Xu, Shuai; Sun, Qiangzheng; Zhang, Jingshan; Song, Hongbin; Lin, Hualiang

2013-11-21

Spatial distribution of bacillary dysentery incidence was mapped at the district level in Wuhan, China. And a generalized additive time series model was used to examine the effect of daily weather factors on bacillary dysentery in the high-risk areas, after controlling for potential confounding factors. Central districts were found to be the high-risk areas. The time series analysis found an acute effect of meteorological factors on bacillary dysentery occurrence. A positive association was found for mean temperature (excess risk (ER) for 1°C increase being 0.94% (95% confidence interval (CI): 0.46% to 1.43% on the lag day 2), while a negative effect was observed for relative humidity and rainfall, the ER for 1% increase in relative humidity was -0.21% (95% CI: -0.34% to -0.08%), and the ER for 1 mm increase in rainfall was -0.23% (95% CI: -0.37% to -0.09%). This study suggests that bacillary dysentery prevention and control strategy should consider local weather variations.

Roles of silkworm endoplasmic reticulum chaperones in the secretion of recombinant proteins expressed by baculovirus system.

PubMed

Imai, Saki; Kusakabe, Takahiro; Xu, Jian; Li, Zhiqing; Shirai, Shintaro; Mon, Hiroaki; Morokuma, Daisuke; Lee, Jae Man

2015-11-01

Baculovirus expression vector system (BEVS) is widely used for production of recombinant eukaryotic proteins in insect larvae or cultured cells. BEVS has advantages over bacterial expression system in producing post-translationally modified secreted proteins. However, for some unknown reason, it is very difficult for insects to secrete sufficiently for certain proteins of interest. To understand the reasons why insect cells fail to secrete some kinds of recombinant proteins, we here employed three mammalian proteins as targets, EPO, HGF, and Wnt3A, with different secretion levels in BEVS and investigated their mRNA transcriptions from the viral genome, subcellular localizations, and interactions with silkworm ER chaperones. Moreover, we observed that no significantly influence on the secretion amounts of all three proteins when depleting or overexpressing most endogenous ER chaperone genes in cultured silkworm cells. However, among all detected ER chaperones, the depletion of BiP severely decreased the recombinant protein secretion in BEVS, indicating the possible central role of Bip in silkworm secretion pathway.

Use of the Er:YAG laser for improved plating in maxillofacial surgery: comparison of bone healing in laser and drill osteotomies.

PubMed

Lewandrowski, K U; Lorente, C; Schomacker, K T; Flotte, T J; Wilkes, J W; Deutsch, T F

1996-01-01

Surgical reconstruction of bony defects in the maxillofacial region involves fixation of bony fragments with mini and micro plates. Bone stabilization during hole drilling is often challenging due to the need to apply pressure when using a conventional mechanical Hall drill. In addition, fragmentation of the fragile bones may occur and complicate the reconstruction. The pulsed Er:YAG laser offers an attractive alternative drilling modality because it does not require physical contact with the bone in order to drill holes, cuts bone with minimal thermal damage, and allows precise control of bone cutting. The objective of this study was to investigate the pulsed Er:YAG laser as an alternative to the mechanical bur by comparing bone healing using both modalities. Bone healing in an inferior border defect of the rat mandible was examined using either an Er:YAG laser or a mechanical bur for drilling. The healing of osteotomies in facial bones and of screw holes for plate stabilization of free bone fragments was studied. All defects healed by 4 weeks postoperatively. Histologic evaluation demonstrated no difference in the amount of newly formed woven bone at the osteotomy site or screw holes made by either the laser or the drill. The extent of thermal damage at the osteotomy sites was comparable in laser and mechanically cut bone fragments. On the basis of this study we suggest that the Er: YAG laser can be used clinically in thin, fragile bones in the maxillofacial region.

The signaling mechanisms of hippocampal endoplasmic reticulum stress affecting neuronal plasticity-related protein levels in high fat diet-induced obese rats and the regulation of aerobic exercise.

PubMed

Cai, Ming; Wang, Hong; Li, Jing-Jing; Zhang, Yun-Li; Xin, Lei; Li, Feng; Lou, Shu-Jie

2016-10-01

High fat diet (HFD)-induced obesity has been shown to reduce the levels of neuronal plasticity-related proteins, specifically brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN), in the hippocampus. However, the underlying mechanisms are not fully clear. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating gene expression and protein production by affecting stress signaling pathways and ER functions of protein folding and post-translational modification in peripheral tissues of obese rodent models. Additionally, HFD that is associated with hyperglycemia could induce hippocampal ERS, thus impairing insulin signaling and cognitive health in HFD mice. One goal of this study was to determine whether hyperglycemia and hyperlipidemia could cause hippocampal ERS in HFD-induced obese SD rats, and explore the potential mechanisms of ERS regulating hippocampal BDNF and SYN proteins production. Additionally, although regular aerobic exercise could reduce central inflammation and elevate hippocampal BDNF and SYN levels in obese rats, the regulated mechanisms are poorly understood. Nrf2-HO-1 pathways play roles in anti-ERS, anti-inflammation and anti-apoptosis in peripheral tissues. Therefore, the other goal of this study was to determine whether aerobic exercise could activate Nrf2-HO-1 in hippocampus to alleviate obesity-induced hippocampal ERS, which would lead to increased BDNF and SYN levels. Male SD rats were fed on HFD for 8weeks to establish the obese model. Then, 8weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that HFD-induced obesity caused hyperglycemia and hyperlipidemia, and significantly promoted hippocampal glucose transporter 3 (GLUT3) and fatty acid transport protein 1 (FATP1) protein expression. These results were associated with the activation of hippocampal ERS and ERS-mediated apoptosis. At the same time, we found that excessive hippocampal ERS not only significantly decreased proBDNF-the precursor of mature BDNF, but also attenuated p38/ERK-CREB signaling pathways and activated NLRP3-IL-1β pathways in obese rats. These results were associated with reduced BDNF and SYN protein production. However, these adverse changes were obviously reversed by aerobic exercise intervention through activating the Nrf2-HO-1 pathways. These results suggest that dietary obesity could induce hippocampal ERS in male SD rats, and excessive hippocampal ERS plays a critical role in decreasing the levels of BDNF and SYN. Moreover, aerobic exercise could activate hippocampal Nrf2 and HO-1 to relieve ERS and heighten BDNF and SYN production in obese rats. Copyright © 2016 Elsevier Inc. All rights reserved.

pyres: a Python wrapper for electrical resistivity modeling with R2

NASA Astrophysics Data System (ADS)

Befus, Kevin M.

2018-04-01

A Python package, pyres, was written to handle common as well as specialized input and output tasks for the R2 electrical resistivity (ER) modeling program. Input steps including handling field data, creating quadrilateral or triangular meshes, and data filtering allow repeatable and flexible ER modeling within a programming environment. pyres includes non-trivial routines and functions for locating and constraining specific known or separately-parameterized regions in both quadrilateral and triangular meshes. Three basic examples of how to run forward and inverse models with pyres are provided. The importance of testing mesh convergence and model sensitivity are also addressed with higher-level examples that show how pyres can facilitate future research-grade ER analyses.

Responsibility modulates pain-matrix activation elicited by the expressions of others in pain

PubMed Central

Cui, Fang; Abdelgabar, Abdel-Rahman; Keysers, Christian; Gazzola, Valeria

2015-01-01

Here we examine whether brain responses to dynamic facial expressions of pain are influenced by our responsibility for the observed pain. Participants played a flanker task with a confederate. Whenever either erred, the confederate was seen to receive a noxious shock. Using functional magnetic resonance imaging, we found that regions of the functionally localized pain-matrix of the participants (the anterior insula in particular) were activated most strongly when seeing the confederate receive a noxious shock when only the participant had erred (and hence had full responsibility). When both or only the confederate had erred (i.e. participant's shared or no responsibility), significantly weaker vicarious pain-matrix activations were measured. PMID:25800210

Structural and waveguiding characteristics of Er3+:Yb3Al5-yGayO12 films grown by the liquid phase epitaxy

NASA Astrophysics Data System (ADS)

Hlásek, T.; Rubešová, K.; Jakeš, V.; Nekvindová, P.; Kučera, M.; Daniš, S.; Veis, M.; Havránek, V.

2015-11-01

Erbium (Er3+) doped ytterbium garnet (Er:Yb3Al5-yGayO12; y = 0, 0.55 and 1.1) single crystalline thick films have been grown by the low-temperature liquid phase epitaxy method (LPE). The composition of the films was determined using the high resolution XRD, the particle-induced X-ray emission spectroscopy (PIXE) and the particle-induced gamma-ray emission spectroscopy (PIGE). The lattice mismatch between films and substrates was investigated by the high-resolution X-ray diffraction. The surface analysis was carried out by the atomic force microscopy (AFM). Pure infrared emission of Er3+ ions was observed in all films containing gallium. The characteristics such as refractive index, thickness and light propagation were studied by the m-line spectroscopy (MLS) using several wavelengths (633, 964, 1311 and 1552 nm). All samples, where y = 1.1, were multimode waveguides. For these reasons, the Er:Yb3Al3.9Ga1.1O12 seems to be a promising material for light amplifiers in the IR region.

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

Bamunusinghe, Devinka, E-mail: dbamu001@ucr.ed; Hemenway, Cynthia L., E-mail: cindy_hemenway@ncsu.ed; Nelson, Richard S., E-mail: rsnelson@noble.or

Potato virus X (PVX) infection leads to certain cytopathological modifications of the host endomembrane system. The subcellular location of the PVX replicase was previously unknown while the PVX TGBp3 protein was previously reported to reside in the ER. Using PVX infectious clones expressing the green fluorescent protein reporter, and antisera detecting the PVX replicase and host membrane markers, we examined the subcellular distribution of the PVX replicase in relation to the TGBp3. Confocal and electron microscopic observations revealed that the replicase localizes in membrane bound structures that derive from the ER. A subset of TGBp3 resides in the ER atmore » the same location as the replicase. Sucrose gradient fractionation showed that the PVX replicase and TGBp3 proteins co-fractionate with ER marker proteins. This localization represents a region where both proteins may be synthesized and/or function. There is no evidence to indicate that either PVX protein moves into the Golgi apparatus. Cerulenin, a drug that inhibits de novo membrane synthesis, also inhibited PVX replication. These combined data indicate that PVX replication relies on ER-derived membrane recruitment and membrane proliferation.« less

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

Assessment of transmitral flow after mitral valve edge-to-edge repair using High-speed particle image velocimetry

NASA Astrophysics Data System (ADS)

Jeyhani, Morteza; Shahriari, Shahrokh; Labrosse, Michel; Kadem, Lyes

2013-11-01

Approximately 500,000 people in North America suffer from mitral valve regurgitation (MR). MR is a disorder of the heart in which the mitral valve (MV) leaflets do not close securely during systole. Edge-to-edge repair (EtER) technique can be used to surgically treat MR. This technique produces a double-orifice configuration for the MV. Under these un-physiological conditions, flow downstream of the MV forms a double jet structure that may disturb the intraventricular hemodynamics. Abnormal flow patterns following EtER are mainly characterized by high-shear stress and stagnation zones in the left ventricle (LV), which increase the potential of blood component damage. In this study, a custom-made prosthetic bicuspid MV was used to analyze the LV flow patterns after EtER by means of digital particle image velocimetry (PIV). Although the repair of a MV using EtER technique is an effective approach, this study confirms that EtER leads to changes in the LV flow field, including the generation of a double mitral jet flow and high shear stress regions.

Proteocephalid tapeworms (Cestoda: Onchoproteocephalidea) of loaches (Cobitoidea): Evidence for monophyly and high endemism of parasites in the Far East.

PubMed

Scholz, Tomáš; de Chambrier, Alain; Shimazu, Takeshi; Ermolenko, Alexey; Waeschenbach, Andrea

2017-02-01

The parasite fauna of loaches (Cypriniformes: Cobitoidea), a group of small bottom-dwelling freshwater fishes with a mostly Eurasian distribution, remains a largely unknown quantity. Here we revise the taxonomy of tapeworms of the genus Proteocephalus Weinland, 1858 (Cestoda: Proteocephalidae) that had been found in loaches from the Palaearctic Region (Central Europe, Japan and Russia [Primorsky Region]). Molecular phylogenetic analysis based on two nuclear (ssr- and lsrDNA) and two mitochondrial genes (cox1 and rrnL) revealed a monophyletic group consisting of four valid species nesting within the Proteocephalus-aggregate: (i) Proteocephalus sagittus (Grimm, 1872) from Barbatula barbatula (Europe, Russia and Tajikistan), (ii) Proteocephalus demshini n. sp. from Barbatula toni (Russian Far East - Primorsky Region), (iii) Proteocephalus midoriensis Shimazu, 1990 from Lefua echigonia (Japan) and L. costata (Russia) (new host and geographical record), and (iv) Proteocephalus misgurni n. sp. from Misgurnus anguillicaudatus (Russia; Primorsky Region). Proteocephalus sagittus and P. demshini, and P. midoriensis and P. misgurni were recovered as sister taxa, respectively. Proteocephalus sagittus and P. demshini are characterized by having proglottids that are wider than long, an elongate to pyriform cirrus-sac and the vitelline follicles that form wide lateral bands. Proteocephalus midoriensis and P. misgurni are characterized by having proglottids that are more elongate and an ovoid to almost spherical cirrus-sac and the vitelline follicles forming narrow lateral bands. Proteocephalus demshini differs from P. sagittus in the posterolateral extent of the vitelline follicles, whereas P. misgurni can be distinguished from P. midoriensis mainly by the relative size of the ovary, posterior extent of the vitelline follicles and width of the scolex. Unlike most species of the Proteocephalus-aggregate that possess an apical sucker, all species from loaches are devoid of any apical organ. The existence of two new species in loaches from the Primorsky Region of Russia indicates high endemism of fish parasites in this region. A key to the identification of recognized species from loaches is provided. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The suprachiasmatic nucleus in the sheep: retinal projections and cytoarchitectural organization.

PubMed

Tessonneaud, A; Cooper, H M; Caldani, M; Locatelli, A; Viguier-Martinez, M C

1994-10-01

The retinal innervation, cytoarchitectural, and immunohistochemical organization of the suprachiasmatic nucleus (SCN) was studied in the domestic sheep. The SCN is a large elongated nucleus extending rostrocaudally for roughly 3 mm in the hypothalamus. The morphology is unusual in that the rostral part of the nucleus extends out of the main mass of the hypothalamus onto the dorsal aspect of the optic chiasm. Following intraocular injection of wheat-germ agglutinin-horseradish peroxidase or tritiated amino acids, anterograde label is distributed throughout the SCN. Retinal innervation of the SCN is bilaterally symmetric or predominantly ipsilateral. Quantitative image analysis demonstrates that, although the amount of autoradiographic label is greatest in the ventral and central parts of the nucleus, density varies progressively between different regions. In addition to the SCN, retinal fibers are also seen in the medial preoptic area, the anterior and lateral hypothalamic area, the dorsomedial hypothalamus, the retrochiasmatic area, and the basal telencephalon. Whereas the SCN can be identified using several techniques, complete delineation of the nucleus requires combined tract tracing, cytoarchitectural, and histochemical criteria. Compared with the surrounding hypothalamic regions, the SCN contains smaller, more densely packed neurons, and is largely devoid of myelinated fibers. Cell soma sizes are smaller in the ventral SCN than in the dorsal or lateral parts, but an obvious regional transition is lacking. Using Nissl, myelin, acetylcholinesterase, and cytochrome oxidase staining, the SCN can be clearly distinguished in the rostral and medial regions, but is less differentiated toward the caudal pole. Immunohistochemical demonstration of several neuropeptides shows that the neurochemical organization of the sheep SCN is heterogeneous, but that it lacks a distinct compartmental organization. Populations of different neuropeptide-containing cells are found throughout the nucleus, although perikarya positive for vasoactive intestinal polypeptide and fibers labeled for methionine-enkephalin are predominant ventrally; neurophysin-immunoreactive cells are more prominent in the dorsal region and toward the caudal pole. The results suggest that the intrinsic organization of the sheep SCN is characterized by gradual regional transitions between different zones.

Crevice corrosion - NaCl concentration map for grade-2 titanium at elevated temperature

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

Tsujikawa, Shigeo; Kojima, Yoichi

1993-12-31

The repassivation potential, ER, for metal/metal-crevice of Commercially Pure Titanium, C.P.Ti, was determined in NaCl solutions at temperatures up to 250C. The ER has its least noble value near 100C and becomes more noble as the temperature increases. As shown in previous research, the shrinkage of the repassivation region should continue with increasing temperatures. However, in conducting this same experiment at temperatures higher than 100C, an examination of the NaCl concentration - temperature - crevice corrosion map verifies that the repassivation region began to expand again when the temperature exceeded 140C. This expansion continued as the temperature continued to increase.

The endoplasmic reticulum stress response in aging and age-related diseases

PubMed Central

Brown, Marishka K.; Naidoo, Nirinjini

2012-01-01

The endoplasmic reticulum(ER) is a multifunctional organelle within which protein folding, lipid biosynthesis, and calcium storage occurs. Perturbations such as energy or nutrient depletion, disturbances in calcium or redox status that disrupt ER homeostasis lead to the misfolding of proteins, ER stress and up-regulation of several signaling pathways coordinately called the unfolded protein response (UPR). The UPR is characterized by the induction of chaperones, degradation of misfolded proteins and attenuation of protein translation. The UPR plays a fundamental role in the maintenance of cellular homeostasis and thus is central to normal physiology. However, sustained unresolved ER stress leads to apoptosis. Aging linked declines in expression and activity of key ER molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the UPR. One mechanism to explain age associated declines in cellular functions and age-related diseases is a progressive failure of chaperoning systems. In many of these diseases, proteins or fragments of proteins convert from their normally soluble forms to insoluble fibrils or plaques that accumulate in a variety of organs including the liver, brain or spleen. This group of diseases, which typically occur late in life includes Alzheimer's, Parkinson's, type II diabetes and a host of less well known but often equally serious conditions such as fatal familial insomnia. The UPR is implicated in many of these neurodegenerative and familial protein folding diseases as well as several cancers and a host of inflammatory diseases including diabetes, atherosclerosis, inflammatory bowel disease and arthritis. This review will discuss age-related changes in the ER stress response and the role of the UPR in age-related diseases. PMID:22934019

Preconditioning with Endoplasmic Reticulum Stress Ameliorates Endothelial Cell Inflammation

PubMed Central

Leonard, Antony; Paton, Adrienne W.; El-Quadi, Monaliza; Paton, James C.; Fazal, Fabeha

2014-01-01

Endoplasmic Reticulum (ER) stress, caused by disturbance in ER homeostasis, has been implicated in several pathological conditions such as ischemic injury, neurodegenerative disorders, metabolic diseases and more recently in inflammatory conditions. Our present study aims at understanding the role of ER stress in endothelial cell (EC) inflammation, a critical event in the pathogenesis of acute lung injury (ALI). We found that preconditioning human pulmonary artery endothelial cells (HPAEC) to ER stress either by depleting ER chaperone and signaling regulator BiP using siRNA, or specifically cleaving (inactivating) BiP using subtilase cytotoxin (SubAB), alleviates EC inflammation. The two approaches adopted to abrogate BiP function induced ATF4 protein expression and the phosphorylation of eIF2α, both markers of ER stress, which in turn resulted in blunting the activation of NF-κB, and restoring endothelial barrier integrity. Pretreatment of HPAEC with BiP siRNA inhibited thrombin-induced IκBα degradation and its resulting downstream signaling pathway involving NF-κB nuclear translocation, DNA binding, phosphorylation at serine536, transcriptional activation and subsequent expression of adhesion molecules. However, TNFα-mediated NF-κB signaling was unaffected upon BiP knockdown. In an alternative approach, SubAB-mediated inactivation of NF-κB was independent of IκBα degradation. Mechanistic analysis revealed that pretreatment of EC with SubAB interfered with the binding of the liberated NF-κB to the DNA, thereby resulting in reduced expression of adhesion molecules, cytokines and chemokines. In addition, both knockdown and inactivation of BiP stimulated actin cytoskeletal reorganization resulting in restoration of endothelial permeability. Together our studies indicate that BiP plays a central role in EC inflammation and injury via its action on NF-κB activation and regulation of vascular permeability. PMID:25356743

Preconditioning with endoplasmic reticulum stress ameliorates endothelial cell inflammation.

PubMed

Leonard, Antony; Paton, Adrienne W; El-Quadi, Monaliza; Paton, James C; Fazal, Fabeha

2014-01-01

Endoplasmic Reticulum (ER) stress, caused by disturbance in ER homeostasis, has been implicated in several pathological conditions such as ischemic injury, neurodegenerative disorders, metabolic diseases and more recently in inflammatory conditions. Our present study aims at understanding the role of ER stress in endothelial cell (EC) inflammation, a critical event in the pathogenesis of acute lung injury (ALI). We found that preconditioning human pulmonary artery endothelial cells (HPAEC) to ER stress either by depleting ER chaperone and signaling regulator BiP using siRNA, or specifically cleaving (inactivating) BiP using subtilase cytotoxin (SubAB), alleviates EC inflammation. The two approaches adopted to abrogate BiP function induced ATF4 protein expression and the phosphorylation of eIF2α, both markers of ER stress, which in turn resulted in blunting the activation of NF-κB, and restoring endothelial barrier integrity. Pretreatment of HPAEC with BiP siRNA inhibited thrombin-induced IκBα degradation and its resulting downstream signaling pathway involving NF-κB nuclear translocation, DNA binding, phosphorylation at serine536, transcriptional activation and subsequent expression of adhesion molecules. However, TNFα-mediated NF-κB signaling was unaffected upon BiP knockdown. In an alternative approach, SubAB-mediated inactivation of NF-κB was independent of IκBα degradation. Mechanistic analysis revealed that pretreatment of EC with SubAB interfered with the binding of the liberated NF-κB to the DNA, thereby resulting in reduced expression of adhesion molecules, cytokines and chemokines. In addition, both knockdown and inactivation of BiP stimulated actin cytoskeletal reorganization resulting in restoration of endothelial permeability. Together our studies indicate that BiP plays a central role in EC inflammation and injury via its action on NF-κB activation and regulation of vascular permeability.

Chemical Chaperone TUDCA Preserves Cone Photoreceptors in a Mouse Model of Leber Congenital Amaurosis

PubMed Central

Zhang, Tao; Baehr, Wolfgang; Fu, Yingbin

2012-01-01

Purpose. Mutations in either retinoid isomerase (RPE65) or lecithin-retinol acyltransferase (LRAT) lead to Leber congenital amaurosis (LCA). By using the Lrat–/– mouse model, previous studies have shown that the rapid cone degeneration in LCA was caused by endoplasmic reticulum (ER) stress induced by S-opsin aggregation. The purpose of this study is to examine the efficacy of an ER chemical chaperone, tauroursodeoxycholic acid (TUDCA), in preserving cones in the Lrat–/– model. Methods. Lrat–/– mice were systemically administered with TUDCA and vehicle (0.15 M NaHCO3) every 3 days from P9 to P28. Cone cell survival was determined by counting cone cells on flat-mounted retinas. The expression and subcellular localization of cone-specific proteins were analyzed by western blotting and immunohistochemistry, respectively. Results. TUDCA treatment reduced ER stress and apoptosis in Lrat–/– retina. It significantly slowed down cone degeneration in Lrat–/– mice, resulting in a ∼3-fold increase in cone density in the ventral and central retina as compared with the vehicle-treated mice at P28. Furthermore, TUDCA promoted the degradation of cone membrane–associated proteins by enhancing the ER-associated protein degradation pathway. Conclusions. Systemic injection of TUDCA is effective in reducing ER stress, preventing apoptosis, and preserving cones in Lrat–/– mice. TUDCA has the potential to lead to the development of a new class of therapeutic drugs for treating LCA. PMID:22531707

Central and peripheral effects of chronic food restriction and weight restoration in the rat.

PubMed

Kinzig, Kimberly P; Hargrave, Sara L; Tao, Erin E

2009-02-01

Previous studies have demonstrated that some endocrine consequences of long-term caloric restriction persist after weight restoration in human subjects. Here we evaluate effects of chronic food restriction in rats that were restricted to 70% of control kcal for 4 wk and subsequently weight restored. Measures were taken from rats at 80% (chronically restricted; CR), 90% (partially weight restored; PR), 100% (fully weight restored; FR), and after 4 wk at 100% body weight of controls (extended weight restored; ER). Plasma insulin and leptin were decreased, and ghrelin was increased in CR compared with controls. Leptin and ghrelin normalized with weight restoration at PR, FR, and ER; however, baseline insulin was not normalized until the ER state. Hypothalamic mRNA expression levels for proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY) revealed significantly less POMC mRNA expression in CR and PR rats, and significantly less arcuate NPY mRNA in PR and FR. In the dorsomedial hypothalamus, CR, PR, and FR rats had significantly increased NPY expression that was not normalized until the ER state. In response to a test meal, insulin and ghrelin release patterns were altered through the FR stage, and ghrelin remained affected at ER. Collectively, these data demonstrate that mere weight restoration is not sufficient to normalize hypothalamic gene expression levels and endocrine responses to a meal, and that meal-related ghrelin responses persist despite weight restoration for up to 4 wk.

Regular and platform switching: bone stress analysis varying implant type.

PubMed

Gurgel-Juarez, Nália Cecília; de Almeida, Erika Oliveira; Rocha, Eduardo Passos; Freitas, Amílcar Chagas; Anchieta, Rodolfo Bruniera; de Vargas, Luis Carlos Merçon; Kina, Sidney; França, Fabiana Mantovani Gomes

2012-04-01

This study aimed to evaluate stress distribution on peri-implant bone simulating the influence of platform switching in external and internal hexagon implants using three-dimensional finite element analysis. Four mathematical models of a central incisor supported by an implant were created: External Regular model (ER) with 5.0 mm × 11.5 mm external hexagon implant and 5.0 mm abutment (0% abutment shifting), Internal Regular model (IR) with 4.5 mm × 11.5 mm internal hexagon implant and 4.5 mm abutment (0% abutment shifting), External Switching model (ES) with 5.0 mm × 11.5 mm external hexagon implant and 4.1 mm abutment (18% abutment shifting), and Internal Switching model (IS) with 4.5 mm × 11.5 mm internal hexagon implant and 3.8 mm abutment (15% abutment shifting). The models were created by SolidWorks software. The numerical analysis was performed using ANSYS Workbench. Oblique forces (100 N) were applied to the palatal surface of the central incisor. The maximum (σ(max)) and minimum (σ(min)) principal stress, equivalent von Mises stress (σ(vM)), and maximum principal elastic strain (ε(max)) values were evaluated for the cortical and trabecular bone. For cortical bone, the highest stress values (σ(max) and σ(vm) ) (MPa) were observed in IR (87.4 and 82.3), followed by IS (83.3 and 72.4), ER (82 and 65.1), and ES (56.7 and 51.6). For ε(max), IR showed the highest stress (5.46e-003), followed by IS (5.23e-003), ER (5.22e-003), and ES (3.67e-003). For the trabecular bone, the highest stress values (σ(max)) (MPa) were observed in ER (12.5), followed by IS (12), ES (11.9), and IR (4.95). For σ(vM), the highest stress values (MPa) were observed in IS (9.65), followed by ER (9.3), ES (8.61), and IR (5.62). For ε(max) , ER showed the highest stress (5.5e-003), followed by ES (5.43e-003), IS (3.75e-003), and IR (3.15e-003). The influence of platform switching was more evident for cortical bone than for trabecular bone, mainly for the external hexagon implants. In addition, the external hexagon implants showed less stress concentration in the regular and switching platforms in comparison to the internal hexagon implants. © 2012 by the American College of Prosthodontists.

77 FR 41398 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... Energy Partners, Inc., CSW Energy Services, Inc., AEP Texas Central Company, AEP Retail Energy Partners...: 5 p.m. ET 7/24/12. Docket Numbers: ER12-2200-000. Applicants: Mehoopany Wind Energy LLC. Description: MBR Application of Mehoopany Wind Energy LLC to be effective 8/31/2012. Filed Date: 7/3/12 Accession...

Sleep apnoea.

PubMed

Jun, Jonathan C; Chopra, Swati; Schwartz, Alan R

2016-03-01

Sleep apnoea is a disorder characterised by repetitive pauses in breathing during sleep caused by airway occlusion (obstructive sleep apnoea) or altered control of breathing (central sleep apnoea). In this Clinical Year in Review, we summarise high-impact research from the past year pertaining to management, diagnosis and cardio-metabolic consequences of sleep apnoea. Copyright ©ERS 2016.

77 FR 48135 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-13

...: J.P. Morgan Ventures Energy Corporation, Triton Power Michigan LLC, BE Allegheny LLC, BE CA LLC, BE... Contract Funding, L.L.C., Central Power & Lime LLC, Cedar Brakes II, L.L.C., J.P. Morgan Commodities Canada...; ER10-2898-008. Applicants: J.P. Morgan Ventures Energy Corporation, Triton Power Michigan LLC, BE...

The IRE1/bZIP60 pathway are activated by potexvirus and potyvirus small membrane binding proteins

USDA-ARS?s Scientific Manuscript database

The endoplasmic reticulum provides an environment for protein synthesis, folding and distribution to all corners of the cell. With respect to protein synthesis and folding, quality production is central to maintaining homeostasis. When conditions occur that disrupt the folding capacity of the ER cau...

NRL Fact Book 1992-1993

DTIC Science & Technology

1993-06-01

administering contractual support for lab-wide or multiple buys of ADP systems, software, and services. Computer systems located in the Central Computing Facility...Code Dr. D.L. Bradley Vacant Mrs. N.J. Beauchamp Dr. W.A. Kuperman Dr. E.R. Franchi Dr. M.H. Orr Dr. J.A. Bucaro Mr. L.B. Palmer Dr. D.J. Ramsdale Mr

Bilismen er skadelig for miljoeet, men spiller jeg noen rolle : en studie av holdninger til og bruk av transportmidler blant ungdom i Oslo : summary

DOT National Transportation Integrated Search

1999-04-01

The report throws light on attitudes toward environmental consequences of transport means among young people in Oslo. A central question is whether young people's use of transport modes is related to their attitudes toward the environmental consequen...

The central repeat domain 1 of Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) prevents cis MHC class I peptide presentation

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

Kwun, Hyun Jin; Ramos da Silva, Suzane; Department of Pathology, Botucatu School of Medicine at Sao Paulo State University, Sao Paulo

KSHV LANA1, a latent protein expressed during chronic infection to maintain a viral genome, inhibits major histocompatibility complex class I (MHC I) peptide presentation in cis as a means of immune evasion. Through deletional cloning, we localized this function to the LANA1 central repeat 1 (CR1) subregion. Other CR subregions retard LANA1 translation and proteasomal processing but do not markedly inhibit LANA1 peptide processing by MHC I. Inhibition of proteasomal processing ablates LANA1 peptide presentation. Direct expression of LANA1 within the endoplasmic reticulum (ER) overcomes CR1 inhibition suggesting that CR1 acts prior to translocation of cytoplasmic peptides into the ER.more » By physically separating CR1 from other subdomains, we show that LANA1 evades MHC I peptide processing by a mechanism distinct from other herpesviruses including Epstein-Barr virus (EBV). Although LANA1 and EBV EBNA1 are functionally similar, they appear to use different mechanisms to evade host cytotoxic T lymphocyte surveillance.« less

Applied Meteorology Unit (AMU) Quarterly Report Third Quarter FY · 13

NASA Technical Reports Server (NTRS)

Bauman, William; Crawford, Winifred; Watson, Leela; Shafer, Jaclyn; Huddleston, Lisa

2013-01-01

The AMU team worked on seven tasks for their customers: (1) Ms. Crawford completed the objective lightning forecast tool for east -central Florida airports and delivered the tool and the final report to the customers. (2) Ms. Shafer continued work for Vandenberg Air Force Base on an automated tool to relate pressure gradients to peak winds. (3) Dr. Huddleston updated and delivered the tool that shows statistics on the timing of the first lightning strike of the day in the Kennedy Space Center (KSC)/Cape Canaveral Air Force Station (CCAFS) area. (4) Dr. Bauman continued work on a severe weather forecast tool focused on the Eastern Range (ER). (5) Ms. Crawford acquired the software and radar data needed to create a dual-Doppler analysis over the east-central Florida and KSC/CCAFS areas. (6) Mr. Decker continued developing a wind pairs database for the Launch Services Program to use when evaluating upper-level winds for launch vehicles. (7) Dr. Watson continued work to assimilate observational data into the high-resolution model configurations she created for Wallops Flight Facility and the ER.

Dynamics of Sensorimotor Oscillations in a Motor Task

NASA Astrophysics Data System (ADS)

Pfurtscheller, Gert; Neuper, Christa

Many BCI systems rely on imagined movement. The brain activity associated with real or imagined movement produces reliable changes in the EEG. Therefore, many people can use BCI systems by imagining movements to convey information. The EEG has many regular rhythms. The most famous are the occipital alpha rhythm and the central mu and beta rhythms. People can desynchronize the alpha rhythm (that is, produce weaker alpha activity) by being alert, and can increase alpha activity by closing their eyes and relaxing. Sensory processing or motor behavior leads to EEG desynchronization or blocking of central beta and mu rhythms, as originally reported by Berger [1], Jasper and Andrew [2] and Jasper and Penfield [3]. This desynchronization reflects a decrease of oscillatory activity related to an internally or externally-paced event and is known as Event-Related Desynchronization (ERD, [4]). The opposite, namely the increase of rhythmic activity, was termed Event-Related Synchronization (ERS, [5]). ERD and ERS are characterized by fairly localized topography and frequency specificity [6]. Both phenomena can be studied through topographiuthc maps, time courses, and time-frequency representations (ERD maps, [7]).

Peroxisomal membrane ascorbate peroxidase is sorted to a membranous network that resembles a subdomain of the endoplasmic reticulum.

PubMed Central

Mullen, R T; Lisenbee, C S; Miernyk, J A; Trelease, R N

1999-01-01

The peroxisomal isoform of ascorbate peroxidase (APX) is a novel membrane isoform that functions in the regeneration of NAD(+) and protection against toxic reactive oxygen species. The intracellular localization and sorting of peroxisomal APX were examined both in vivo and in vitro. Epitope-tagged peroxisomal APX, which was expressed transiently in tobacco BY-2 cells, localized to a reticular/circular network that resembled endoplasmic reticulum (ER; 3,3'-dihexyloxacarbocyanine iodide-stained membranes) and to peroxisomes. The reticular network did not colocalize with other organelle marker proteins, including three ER reticuloplasmins. However, in vitro, peroxisomal APX inserted post-translationally into the ER but not into other purified organelle membranes (including peroxisomal membranes). Insertion into the ER depended on the presence of molecular chaperones and ATP. These results suggest that regions of the ER serve as a possible intermediate in the sorting pathway of peroxisomal APX. Insight into this hypothesis was obtained from in vivo experiments with brefeldin A (BFA), a toxin that blocks vesicle-mediated protein export from ER. A transiently expressed chloramphenicol acetyltransferase-peroxisomal APX (CAT-pAPX) fusion protein accumulated only in the reticular/circular network in BFA-treated cells; after subsequent removal of BFA from these cells, the CAT-pAPX was distributed to preexisting peroxisomes. Thus, plant peroxisomal APX, a representative enzymatic peroxisomal membrane protein, is sorted to peroxisomes through an indirect pathway involving a preperoxisomal compartment with characteristics of a distinct subdomain of the ER, possibly a peroxisomal ER subdomain. PMID:10559442

Ubiquitin-dependent Protein Degradation at the Yeast Endoplasmic Reticulum and Nuclear Envelope

PubMed Central

Zattas, Dimitrios; Hochstrasser, Mark

2014-01-01

The endoplasmic reticulum (ER) is the primary organelle in eukaryotic cells where membrane and secreted proteins are inserted into or across cell membranes. Its membrane bilayer and luminal compartments provide a favorable environment for the folding and assembly of thousands of newly synthesized proteins. However, protein folding is intrinsically error-prone, and various stress conditions can further increase levels of protein misfolding and damage, particularly in the ER, which can lead to cellular dysfunction and disease. The ubiquitin-proteasome system (UPS) is responsible for the selective destruction of a vast array of protein substrates, either for protein quality control or to allow rapid changes in the levels of specific regulatory proteins. In this review, we will focus on the components and mechanisms of ER-associated protein degradation (ERAD), an important branch of the UPS. ER membranes extend from subcortical regions of the cell to the nuclear envelope, with its continuous outer and inner membranes; the nuclear envelope is a specialized subdomain of the ER. ERAD presents additional challenges to the UPS beyond those faced with soluble substrates of the cytoplasm and nucleus. These include recognition of sugar modifications that occur in the ER, retrotranslocation of proteins across the membrane bilayer, and transfer of substrates from the ER extraction machinery to the proteasome. Here we review characteristics of ERAD substrate degradation signals (degrons), mechanisms underlying substrate recognition and processing by the ERAD machinery, and ideas on the still unresolved problem of how substrate proteins are moved across and extracted from the ER membrane. PMID:25231236

Frequency upconversion and fluorescence intensity ratio method in Yb3+-ion-sensitized Gd2O3:Er3+-Eu3+ phosphors for display and temperature sensing

NASA Astrophysics Data System (ADS)

Ranjan, Sushil Kumar; Soni, Abhishek Kumar; Rai, Vineet Kumar

2017-09-01

Near infrared (NIR) to visible frequency upconversion emission studies in Er3+-Eu3+/Er3+-Eu3+-Yb3+ co-doped/tri-doped Gd2O3 phosphors prepared by the co-precipitation technique have been explored under 980 nm laser diode radiation. The developed phosphors were characterized with the help of XRD, FE-SEM and FTIR analysis. No upconversion (UC) emission was found in the Eu3+-doped Gd2O3 phosphor. UC emission from Eu3+ ions along with Er3+ ions was observed in Er3+-Eu3+ and Er3+-Eu3+-Yb3+ co-doped/tri-doped phosphors. The UC emission arising from the Er3+ and Eu3+ ions was enhanced several times due to the incorporation of Yb3+ ions. The processes involved in the UC emission were obtained on the basis of the effect of energy transfer/sensitization through the Yb3+ → Er3+ → Eu3+ process. The red/green intensity ratio was improved from 0.16 to 1.50 and 1.01 to 1.50 for Er3+-Eu3+-Yb3+ tri-doped phosphors as compared to the Er3+-doped and Er3+-Yb3+ co-doped phosphors, respectively, at a fixed pump power density. A UC fluorescence intensity ratio (FIR)-based temperature sensing study was performed in the prepared Er3+-Eu3+-Yb3+ tri-doped Gd2O3 phosphors for green upconversion emission bands in the 300 K-443 K temperature range. A maximum sensor sensitivity of about ˜0.0043 K-1 at 300 K was achieved for the synthesized tri-doped phosphors upon excitation with a 980 nm laser diode. The colour coordinates lying in the green-yellow region are invariant, with variation in pump power density and temperature. The observed results support the utility of the prepared tri-doped phosphors in optical temperature sensing, display devices and NIR to visible upconverters.

From alarm systems to smart houses.

PubMed

Vlaskamp, F J

1992-01-01

The percentage of senior citizens in the Netherlands will rise in coming years. The expected percentage for the year 2010 of persons over age 65 in the total population is 15%. More persons over age 65 than ever before will continue to live in their own environment. Emergency response systems (ERS) can support independent living. The most common type of organization distributing ERS is a small, partly subsidized local alarm organization run by a social welfare office for the elderly. Government subsidy has been reduced in recent years which has motivated small organizations to join together into larger regional organizations in order to get a more solid financial base. On the other hand new semi-commercial and commercial organizations have come into being. These developments are part of the growing importance of home care, leading to more medical applications of ERS. User satisfaction with ERS is high. Portable triggers can enhance the effectiveness of the system. However, many users do not wear the portable trigger when feeling well. Future technical developments will result in multifunctionality of ERS-devices. In the long term the hardware of today will be integrated in a multimedia home terminal replacing the telephone. The portable trigger will remain the only specific hardware at home for ERS.

Sex-specific neural circuits of emotion regulation in the centromedial amygdala.

PubMed

Wu, Yan; Li, Huandong; Zhou, Yuan; Yu, Jian; Zhang, Yuanchao; Song, Ming; Qin, Wen; Yu, Chunshui; Jiang, Tianzi

2016-03-23

Sex-related differences in emotion regulation (ER) in the frequency power distribution within the human amygdala, a brain region involved in emotion processing, have been reported. However, how sex differences in ER are manifested in the brain networks which are seeded on the amygdala subregions is unclear. The goal of this study was to investigate this issue from a brain network perspective. Utilizing resting-state functional connectivity (RSFC) analysis, we found that the sex-specific functional connectivity patterns associated with ER trait level were only seeded in the centromedial amygdala (CM). Women with a higher trait-level ER had a stronger negative RSFC between the right CM and the medial superior frontal gyrus (mSFG), and stronger positive RSFC between the right CM and the anterior insula (AI) and the superior temporal gyrus (STG). But men with a higher trait-level ER was associated with weaker negative RSFC of the right CM-mSFG and positive RSFCs of the right CM-left AI, right CM-right AI/STG, and right CM-left STG. These results provide evidence for the sex-related effects in ER based on CM and indicate that men and women may differ in the neural circuits associated with emotion representation and integration.

Integrating in Silico and in Vitro Approaches To Predict Drug Accessibility to the Central Nervous System.

PubMed

Zhang, Yan-Yan; Liu, Houfu; Summerfield, Scott G; Luscombe, Christopher N; Sahi, Jasminder

2016-05-02

Estimation of uptake across the blood-brain barrier (BBB) is key to designing central nervous system (CNS) therapeutics. In silico approaches ranging from physicochemical rules to quantitative structure-activity relationship (QSAR) models are utilized to predict potential for CNS penetration of new chemical entities. However, there are still gaps in our knowledge of (1) the relationship between marketed human drug derived CNS-accessible chemical space and preclinical neuropharmacokinetic (neuroPK) data, (2) interpretability of the selected physicochemical descriptors, and (3) correlation of the in vitro human P-glycoprotein (P-gp) efflux ratio (ER) and in vivo rodent unbound brain-to-blood ratio (Kp,uu), as these are assays routinely used to predict clinical CNS exposure, during drug discovery. To close these gaps, we explored the CNS druglike property boundaries of 920 market oral drugs (315 CNS and 605 non-CNS) and 846 compounds (54 CNS drugs and 792 proprietary GlaxoSmithKline compounds) with available rat Kp,uu data. The exact permeability coefficient (Pexact) and P-gp ER were determined for 176 compounds from the rat Kp,uu data set. Receiver operating characteristic curves were performed to evaluate the predictive power of human P-gp ER for rat Kp,uu. Our data demonstrates that simple physicochemical rules (most acidic pKa ≥ 9.5 and TPSA < 100) in combination with P-gp ER < 1.5 provide mechanistic insights for filtering BBB permeable compounds. For comparison, six classification modeling methods were investigated using multiple sets of in silico molecular descriptors. We present a random forest model with excellent predictive power (∼0.75 overall accuracy) using the rat neuroPK data set. We also observed good concordance between the structural interpretation results and physicochemical descriptor importance from the Kp,uu classification QSAR model. In summary, we propose a novel, hybrid in silico/in vitro approach and an in silico screening model for the effective development of chemical series with the potential to achieve optimal CNS exposure.

Spirometry quality-control strategies in a multinational study of the prevalence of chronic obstructive pulmonary disease.

PubMed

Pérez-Padilla, Rogelio; Vázquez-García, Juan Carlos; Márquez, María Nelly; Menezes, Ana Maria B

2008-08-01

We report the characteristics of a centralized spirometry quality-control program developed for a population-based survey of the prevalence of chronic obstructive pulmonary disease in 5 cities: São Paulo, Brazil; México City, México; Montevideo, Uruguay; Santiago, Chile; and Caracas, Venezuela (the Latin American Project for the Investigation of Obstructive Lung Diseases [PLATINO]). We developed and used a 3-level quality-control system. Level 1: The spirometer used in the survey (EasyOne), gives quality-control messages to the user/clinician. All the spirometry technicians were trained by the same team, with the aim of meeting what became the 2005 spirometry quality criteria of the American Thoracic Society/European Respiratory Society (ATS/ERS). Level 2: In each of the 5 cities a local supervisor identified poor-quality spirometries that needed to be repeated. Level 3: Once a week during the survey, all spirometry results were sent via e-mail to the study's quality-control center in México City for review and feedback. In the overall totals at the end of the study, 94% of the 5,315 subjects had spirometries that met the 1994 ATS quality criteria, and 89% met the 2005 ATS/ERS criteria. In their overall totals at the end of the study, 90% of the 64 spirometry technicians were successful in getting 86% of their subjects to meet the 1994 ATS criteria, and got 75% of their subjects to meet the 2005 ATS/ERS criteria. In the first 10 subjects they tested, 90% of the 64 spirometry technicians were successful in getting 70% of their subjects to meet the 1994 ATS criteria, and got 60% of their subjects to meet the 2005 ATS/ERS criteria. Standardization of equipment, training, and supervision of spirometry is essential in a multinational spirometry survey. Centralized quality control can be done via e-mail with good reliability and low cost.

Can spatial patterns along climatic gradients predict ecosystem responses to climate change? Experimenting with reaction-diffusion simulations.

PubMed

Roitberg, Elena; Shoshany, Maxim

2017-01-01

Following a predicted decline in water resources in the Mediterranean Basin, we used reaction-diffusion equations to gain a better understanding of expected changes in properties of vegetation patterns that evolve along the rainfall transition between semi-arid and arid rainfall regions. Two types of scenarios were investigated: the first, a discrete scenario, where the potential consequences of climate change are represented by patterns evolving at discrete rainfall levels along a rainfall gradient. This scenario concerns space-for-time substitutions characteristic of the rainfall gradient hypothesis. The second, a continuous scenario, represents explicitly the effect of rainfall decline on patterns which evolved at different rainfall levels along the rainfall gradient prior to the climate change. The eccentricity of patterns that emerge through these two scenarios was found to decrease with decreasing rainfall, while their solidity increased. Due to their inverse modes of change, their ratio was found to be a highly sensitive indicator for pattern response to rainfall decline. An eccentricity ratio versus rainfall (ER:R) line was generalized from the results of the discrete experiment, where ERs above this line represent developed (recovered) patterns and ERs below this line represent degraded patterns. For the rainfall range of 1.2 to 0.8 mm/day, the continuous rainfall decline experiment with ERs that lie above the ER:R line, yielded patterns less affected by rainfall decline than would be expected according to the discrete representation of ecosystems' response. Thus, for this range, space-for-time substitution represents an overestimation of the consequences of the expected rainfall decline. For rainfall levels below 0.8 mm/day, eccentricity ratios from the discrete and continuous experiments practically converge to the same trend of pattern change along the ER:R line. Thus, the rainfall gradient hypothesis may be valid for regions characterized by this important rainfall range, which typically include desert fringe ecosystems.

Application of the GREAT-ER model for environmental risk assessment of nonylphenol and nonylphenol ethoxylates in China.

PubMed

Zhang, Lai; Cao, Yan; Hao, Xuewen; Zhang, Yongyong; Liu, Jianguo

2015-12-01

The environmental risk presented by "down-the-drain" chemicals to receiving rivers in large urban areas has received increasing attention in recent years. Geo-referenced Regional Environmental Assessment Tool for European Rivers (GREAT-ER) is a typical river catchment model that has been specifically developed for the risk assessment of these chemicals and applied in many European rivers. By utilizing the new version of the model, GREAT-ER 3.0, which is the first completely open source software for worldwide application, this study represents the first attempt to conduct an application of GREAT-ER in the Wenyu River of China. Aquatic exposure simulation and an environmental risk assessment of nonylphenol (NP) and its environmental precursor nonylphenol ethoxylates (NPEOs) were conducted effectively by GREAT-ER model, since NP is one of typical endocrine disrupting chemicals (EDCs) and its environmental precursor NPEOs as a "down-the-drain" chemical are extensively used in China. In the result, the predicted environmental concentrations (PECs) of NP and NPEOs in the water of Wenyu River were 538 and 4320 ng/L, respectively, at the regional scale, and 1210 and 8990 ng/L, respectively, at the local scale. From the results profile of the RCR, the combination of high emissions from large STPs with insufficient dilution of the river caused the high RCR. The PECs of NP in the sediment were in the range of 216.8-8218.3 ng/g (dry weight), which was consistent with the available monitoring data. The study showed the worldwide applicability and reliability of GREAT-ER as a river catchment model for the risk assessment of these chemicals and also revealed the general environmental risks presented by NP and NPEOs in the Wenyu River catchment in Beijing due to the extensive use of these chemicals. The results suggest that specific control or treatment measures are probably warranted for these chemicals to reduce their discharge in major cities.

Endoplasmic Reticulum Stress and Obesity.

PubMed

Yilmaz, Erkan

2017-01-01

In recent years, the world has seen an alarming increase in obesity and closely associated with insulin resistance which is a state of low-grade inflammation, the latter characterized by elevated levels of proinflammatory cytokines in blood and tissues. A shift in energy balance alters systemic metabolic regulation and the important role that chronic inflammation, endoplasmic reticulum (ER) dysfunction, and activation of the unfolded protein response (UPR) play in this process.Why obesity is so closely associated with insulin resistance and inflammation is not understood well. This suggests that there are probably other causes for obesity-related insulin resistance and inflammation. One of these appears to be endoplasmic reticulum (ER) stress.The ER is a vast membranous network responsible for the trafficking of a wide range of proteins and plays a central role in integrating multiple metabolic signals critical in cellular homeostasis. Conditions that may trigger unfolded protein response activation include increased protein synthesis, the presence of mutant or misfolded proteins, inhibition of protein glycosylation, imbalance of ER calcium levels, glucose and energy deprivation, hypoxia, pathogens or pathogen-associated components and toxins. Thus, characterizing the mechanisms contributing to obesity and identifying potential targets for its prevention and treatment will have a great impact on the control of associated conditions, particularly T2D.

Effect of bracket bonding with Er: YAG laser on nanomechanical properties of enamel

PubMed Central

Alavi, Shiva; Birang, Reza; Hajizadeh, Fatemeh; Banimostafaee, Hamed

2014-01-01

Background: The aim of this study was to compare the effects of conventional acid etching and laser etching on the nano-mechanical properties of the dental enamel using nano-indentation test. Materials and Methods: In this experimental in vitro study, buccal surfaces of 10 premolars were divided into three regions. One of the regions was etched with 37% phosphoric acid and another etched with Er:YAG laser, the third region was not etched. The brackets were bonded to both of etched regions. After thermocycling for 500 cycles, the brackets were removed and the teeth were decoronated from the bracket bonding area. Seven nano-indentations were applied at 1-31 μm depth from the enamel surface in each region. Mean values of the hardness and elastic modulus were analyzed with repeated measures analysis of variance and Tukey HSD tests, using the SPSS software (SPSS Inc., version16.0, Chicago, Il, USA). P < 0.05 was considered as significant. Results: The hardness up to 21 μm in depth and elastic modulus up to 6 μm in depth from the enamel surface for laser-etched enamel had significantly higher values than control enamel and the hardness up to 11 μm in depth and elastic modulus up to 6 μm in depth for acid-etched enamel had significantly lower values than the control enamel. Conclusion: The mechanical properties of the enamel were decreased after bracket bonding with conventional acid etching and increased after bonding with Er:YAG laser. PMID:24688560

Peroxisomal Ascorbate Peroxidase Resides within a Subdomain of Rough Endoplasmic Reticulum in Wild-Type Arabidopsis Cells1

PubMed Central

Lisenbee, Cayle S.; Heinze, Michael; Trelease, Richard N.

2003-01-01

Previously we reported (R.T. Mullen, C.S. Lisenbee, J.A. Miernyk, R.N. Trelease [1999] Plant Cell 11: 2167–2185) that overexpressed ascorbate peroxidase (APX), a peroxisomal membrane protein, sorted indirectly to Bright Yellow-2 cell peroxisomes via a subdomain of the endoplasmic reticulum (ER; peroxisomal endoplasmic reticulum [pER]). More recently, a pER-like compartment also was identified in pumpkin (Cucurbita pepo) and transformed Arabidopsis cells (K. Nito, K. Yamaguchi, M. Kondo, M. Hayashi, M. Nishimura [2001] Plant Cell Physiol 42: 20–27). Here, we characterize more extensively the localization of endogenous Arabidopsis peroxisomal APX (AtAPX) in cultured wild-type Arabidopsis cells (Arabidopsis var. Landsberg erecta). AtAPX was detected in peroxisomes, but not in an ER subcompartment, using immunofluorescence microscopy. However, AtAPX was detected readily with immunoblots in both peroxisomal and ER fractions recovered from sucrose (Suc) density gradients. Most AtAPX in microsomes (200,000g, 1 h pellet) applied to gradients exhibited a Mg2+-induced shift from a distribution throughout gradients (approximately 18%–40% [w/w] Suc) to ≥42% (w/w) Suc regions of gradients, including pellets, indicative of localization in rough ER vesicles. Immunogold electron microscopy of the latter fractions verified these findings. Further analyses of peroxisomal and rough ER vesicle fractions revealed that AtAPX in both fractions was similarly associated with and located mostly on the cytosolic face of the membranes. Thus, at the steady state, endogenous peroxisomal AtAPX resides at different levels in rough ER and peroxisomes. Collectively, these findings show that rather than being a transiently induced sorting compartment formed in response to overexpressed peroxisomal APX, portions of rough ER (pER) in wild-type cells serve as a constitutive sorting compartment likely involved in posttranslational routing of constitutively synthesized peroxisomal APX. PMID:12805617

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

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.

Neural correlates of spatial and nonspatial attention determined using intracranial electroencephalographic signals in humans

PubMed Central

Park, Ga Young; Kim, Taekyung; Park, Jinsick; Lee, Eun Mi; Ryu, Han Uk; Kim, Sun I.; Kim, In Young; Husain, Masud

2016-01-01

Abstract Few studies have directly compared the neural correlates of spatial attention (i.e., attention to a particular location) and nonspatial attention (i.e., attention to a feature in the visual scene) using well‐controlled tasks. Here, we investigated the neural correlates of spatial and nonspatial attention in humans using intracranial electroencephalography. The topography and number of electrodes showing significant event‐related desynchronization (ERD) or event‐related synchronization (ERS) in different frequency bands were studied in 13 epileptic patients. Performance was not significantly different between the two conditions. In both conditions, ERD in the low‐frequency bands and ERS in the high‐frequency bands were present bilaterally in the parietal cortex (prominently on the right hemisphere) and frontal regions. In addition to these common changes, spatial attention involved right‐lateralized activity that was maximal in the right superior parietal lobule (SPL), whereas nonspatial attention involved wider brain networks including the bilateral parietal, frontal, and temporal regions, but still had maximal activity in the right parietal lobe. Within the parietal lobe, spatial attention involved ERD or ERS in the right SPL, whereas nonspatial attention involved ERD or ERS in the right inferior parietal lobule. These findings reveal that common as well as different brain networks are engaged in spatial and nonspatial attention. Hum Brain Mapp 37:3041–3054, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27125904

Localization to Mature Melanosomes by Virtue of Cytoplasmic Dileucine Motifs Is Required for Human OCA2 Function

PubMed Central

Sitaram, Anand; Piccirillo, Rosanna; Palmisano, Ilaria; Harper, Dawn C.; Dell'Angelica, Esteban C.; Schiaffino, M. Vittoria

2009-01-01

Oculocutaneous albinism type 2 is caused by defects in the gene OCA2, encoding a pigment cell-specific, 12-transmembrane domain protein with homology to ion permeases. The function of the OCA2 protein remains unknown, and its subcellular localization is under debate. Here, we show that endogenous OCA2 in melanocytic cells rapidly exits the endoplasmic reticulum (ER) and thus does not behave as a resident ER protein. Consistently, exogenously expressed OCA2 localizes within melanocytes to melanosomes, and, like other melanosomal proteins, localizes to lysosomes when expressed in nonpigment cells. Mutagenized OCA2 transgenes stimulate melanin synthesis in OCA2-deficient cells when localized to melanosomes but not when specifically retained in the ER, contradicting a proposed primary function for OCA2 in the ER. Steady-state melanosomal localization requires a conserved consensus acidic dileucine-based sorting motif within the cytoplasmic N-terminal region of OCA2. A second dileucine signal within this region confers steady-state lysosomal localization in melanocytes, suggesting that OCA2 might traverse multiple sequential or parallel trafficking routes. The two dileucine signals physically interact in a differential manner with cytoplasmic adaptors known to function in trafficking other proteins to melanosomes. We conclude that OCA2 is targeted to and functions within melanosomes but that residence within melanosomes may be regulated by secondary or alternative targeting to lysosomes. PMID:19116314

Contribution of Topology Determinants of a Viral Movement Protein to Its Membrane Association, Intracellular Traffic, and Viral Cell-to-Cell Movement▿†

PubMed Central

Genovés, A.; Pallás, V.; Navarro, J. A.

2011-01-01

The p7B movement protein (MP) of Melon necrotic spot virus (MNSV) is a single-pass membrane protein associated with the endoplasmic reticulum (ER), the Golgi apparatus (GA), and plasmodesmata (Pd). Experimental data presented here revealed that the p7B transmembrane domain (TMD) was sufficient to target the green fluorescent protein (GFP) to ER membranes. In addition, the short extramembrane regions of p7B were essential for subsequent ER export and transport to the GA and Pd. Microsomal partitioning and bimolecular fluorescence assays supported a type II topology of p7B in planta. Mutations affecting conventional determinants of p7B membrane topology, such as the TMD secondary structure, the overall hydrophobicity profile, the so-called “aromatic belt,” and the net charge distribution on either side of the TMD, were engineered into infectious RNAs to investigate the relationship between the MP structure and MNSV cell-to-cell movement. The results revealed that (i) the overall hydrophobic profile and the α-helix integrity of the TMD were relevant for virus movement, (ii) modification of the net charge balance of the regions flanking both TMD sides drastically reduced cell-to-cell movement, (iii) localization of p7B to the GA was necessary but not sufficient for virus movement, and (iv) membrane insertion was essential for p7B function in virus movement. Our results therefore indicate that MNSV cell-to-cell movement requires sequential transport of p7B from the ER via the GA to Pd, which is modulated by a combination of several signals with different strengths in the extramembrane regions and TMD of the MP. PMID:21593169

SDSS-IV MaNGA: Spatially Resolved Star Formation Main Sequence and LI(N)ER Sequence

NASA Astrophysics Data System (ADS)

Hsieh, B. C.; Lin, Lihwai; Lin, J. H.; Pan, H. A.; Hsu, C. H.; Sánchez, S. F.; Cano-Díaz, M.; Zhang, K.; Yan, R.; Barrera-Ballesteros, J. K.; Boquien, M.; Riffel, R.; Brownstein, J.; Cruz-González, I.; Hagen, A.; Ibarra, H.; Pan, K.; Bizyaev, D.; Oravetz, D.; Simmons, A.

2017-12-01

We present our study on the spatially resolved Hα and M * relation for 536 star-forming and 424 quiescent galaxies taken from the MaNGA survey. We show that the star formation rate surface density ({{{Σ }}}{SFR}), derived based on the Hα emissions, is strongly correlated with the M * surface density ({{{Σ }}}* ) on kiloparsec scales for star-forming galaxies and can be directly connected to the global star-forming sequence. This suggests that the global main sequence may be a consequence of a more fundamental relation on small scales. On the other hand, our result suggests that ∼20% of quiescent galaxies in our sample still have star formation activities in the outer region with lower specific star formation rate (SSFR) than typical star-forming galaxies. Meanwhile, we also find a tight correlation between {{{Σ }}}{{H}α } and {{{Σ }}}* for LI(N)ER regions, named the resolved “LI(N)ER” sequence, in quiescent galaxies, which is consistent with the scenario that LI(N)ER emissions are primarily powered by the hot, evolved stars as suggested in the literature.

A cataract-causing connexin 50 mutant is mislocalized to the ER due to loss of the fourth transmembrane domain and cytoplasmic domain.

PubMed

Somaraju Chalasani, Madhavi Latha; Muppirala, Madhavi; G Ponnam, Surya Prakash; Kannabiran, Chitra; Swarup, Ghanshyam

2013-01-01

Mutations in the eye lens gap junction protein connexin 50 cause cataract. Earlier we identified a frameshift mutant of connexin 50 (c.670insA; p.Thr203AsnfsX47) in a family with autosomal recessive cataract. The mutant protein is smaller and contains 46 aberrant amino acids at the C-terminus after amino acid 202. Here, we have analysed this frameshift mutant and observed that it localized to the endoplasmic reticulum (ER) but not in the plasma membrane. Moreover, overexpression of the mutant resulted in disintegration of the ER-Golgi intermediate compartment (ERGIC), reduction in the level of ERGIC-53 protein and breakdown of the Golgi in many cells. Overexpression of the frameshift mutant partially inhibited the transport of wild type connexin 50 to the plasma membrane. A deletion mutant lacking the aberrant sequence showed predominant localization in the ER and inhibited anterograde protein transport suggesting, therefore, that the aberrant sequence is not responsible for improper localization of the frameshift mutant. Further deletion analysis showed that the fourth transmembrane domain and a membrane proximal region (231-294 amino acids) of the cytoplasmic domain are needed for transport from the ER and localization to the plasma membrane. Our results show that a frameshift mutant of connexin 50 mislocalizes to the ER and causes disintegration of the ERGIC and Golgi. We have also identified a sequence of connexin 50 crucial for transport from the ER and localization to the plasma membrane.

Connections of Precipitable Water Vapor and Total Ozone Anomalies over European Russia with the North Atlantic Oscillation: Specific Features of Summer 2010

NASA Astrophysics Data System (ADS)

Sitnov, S. A.; Mokhov, I. I.; Bezverkhny, V. A.

2017-12-01

Based on the measurements of precipitable water vapor (PWV) and total column ozone (TCO) from the MODIS satellite instruments (Aqua/Terra platforms), the connections between the North Atlantic Oscillation (NAO) and the anomalies in PWV and TCO over European Russia (ER) in summer 2010 are analyzed. It is found that the PWV (TCO) anomalies over the northern ER in summer 2010 positively (negatively) correlated with the NAO, and the local correlations reached 0.68 (-0.55). The physical mechanisms of the correlations are discussed. A comparative analysis of the relationships between the NAO and the regional PWV and TCO anomalies over ER during the summer seasons of 2000-2015 is carried out.

Visualization of removal of trapped air from the apical region in simulated root canals by laser-activated irrigation using an Er,Cr:YSGG laser.

PubMed

Peeters, Harry Huiz; De Moor, Roeland J G; Suharto, Djoko

2015-08-01

The aim of this visualization study was to obtain a better understanding of the mechanism by which trapped air is removed from the apical region of simulated root canals by activation of an irrigant using an erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser during endodontic procedures. A high-speed imaging system with high temporal and spatial resolution was used to visualize laser-induced shock waves in a resin block model with a curved root canal (inner diameter at the apex 0.08 mm, taper 4 %, crown height 10 mm, overall length 40 mm) and a glass cylinder model with a straight root canal (inner diameter 1 mm, crown height 10 mm, overall length 40 mm). The study utilized MZ3 and RFT3 tips in each model, without water or air spray, and with an average power of 1 W at 35 Hz. Laser-activated irrigation overcame the airlock effect by releasing air trapped in the air column. The mechanism underlying the removal of trapped air from the apical region using an Er,Cr:YSGG laser in a dry root canal is via the disruption of the surface tension at the solution-air interface. This disruption, caused by bubble implosion (cavitation), displaces air in the form of bubbles from the apical region toward the solution, which allows the solution to travel apically.

Modulatory role of androgenic and estrogenic neurosteroids in determining the direction of synaptic plasticity in the CA1 hippocampal region of male rats

PubMed Central

Pettorossi, Vito Enrico; Di Mauro, Michela; Scarduzio, Mariangela; Panichi, Roberto; Tozzi, Alessandro; Calabresi, Paolo; Grassi, Silvarosa

2013-01-01

Abstract Estrogenic and androgenic neurosteroids can rapidly modulate synaptic plasticity in the brain through interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used electrophysiological recordings in slices of young and adolescent male rats to explore the influence of sex neurosteroids on synaptic plasticity in the CA1 hippocampal region, by blocking ARs or ERs during induction of long‐term depression (LTD) and depotentiation (DP) by low‐frequency stimulation (LFS) and long‐term potentiation (LTP) by high‐frequency stimulation (HFS). We found that LTD and DP depend on ARs, while LTP on ERs in both age groups. Accordingly, the AR blocker flutamide affected induction of LTD reverting it into LTP, and prevented DP, while having no effect on HFS‐dependent LTP. Conversely, ER blockade with ICI 182,780 (ICI) markedly reduced LTP, but did not influence LTD and DP. However, the receptor blockade did not affect the maintenance of either LTD or LTP. Moreover, we found that similar to LTP and LTD induced in control condition, the LTP unveiled by flutamide during LFS and residual LTP induced by HFS under ICI depended on N‐methyl‐d aspartate receptor (NMDAR) activation. Furthermore, as the synaptic paired‐pulse facilitation (PPF) was not affected by either AR or ER blockade, we suggest that sex neurosteroids act primarily at a postsynaptic level. This study demonstrates for the first time the crucial role of estrogenic and androgenic neurosteroids in determining the sign of hippocampal synaptic plasticity in male rat and the activity‐dependent recruitment of androgenic and estrogenic pathways leading to LTD and LTP, respectively. PMID:24744863

Modulatory role of androgenic and estrogenic neurosteroids in determining the direction of synaptic plasticity in the CA1 hippocampal region of male rats.

PubMed

Pettorossi, Vito Enrico; Di Mauro, Michela; Scarduzio, Mariangela; Panichi, Roberto; Tozzi, Alessandro; Calabresi, Paolo; Grassi, Silvarosa

2013-12-01

Estrogenic and androgenic neurosteroids can rapidly modulate synaptic plasticity in the brain through interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used electrophysiological recordings in slices of young and adolescent male rats to explore the influence of sex neurosteroids on synaptic plasticity in the CA1 hippocampal region, by blocking ARs or ERs during induction of long-term depression (LTD) and depotentiation (DP) by low-frequency stimulation (LFS) and long-term potentiation (LTP) by high-frequency stimulation (HFS). We found that LTD and DP depend on ARs, while LTP on ERs in both age groups. Accordingly, the AR blocker flutamide affected induction of LTD reverting it into LTP, and prevented DP, while having no effect on HFS-dependent LTP. Conversely, ER blockade with ICI 182,780 (ICI) markedly reduced LTP, but did not influence LTD and DP. However, the receptor blockade did not affect the maintenance of either LTD or LTP. Moreover, we found that similar to LTP and LTD induced in control condition, the LTP unveiled by flutamide during LFS and residual LTP induced by HFS under ICI depended on N-methyl-d aspartate receptor (NMDAR) activation. Furthermore, as the synaptic paired-pulse facilitation (PPF) was not affected by either AR or ER blockade, we suggest that sex neurosteroids act primarily at a postsynaptic level. This study demonstrates for the first time the crucial role of estrogenic and androgenic neurosteroids in determining the sign of hippocampal synaptic plasticity in male rat and the activity-dependent recruitment of androgenic and estrogenic pathways leading to LTD and LTP, respectively.

Nuclear receptor coactivators function in estrogen receptor- and progestin receptor-dependent aspects of sexual behavior in female rats

PubMed Central

Molenda-Figueira, Heather A.; Williams, Casey A.; Griffin, Andreana L.; Rutledge, Eric M.; Blaustein, Jeffrey D.; Tetel, Marc J.

2008-01-01

The ovarian hormones, estradiol (E) and progesterone (P) facilitate the expression of sexual behavior in female rats. E and P mediate many of these behavioral effects by binding to their respective intracellular receptors in specific brain regions. Nuclear receptor coactivators, including Steroid Receptor Coactivator-1 (SRC-1) and CREB Binding Protein (CBP), dramatically enhance ligand-dependent steroid receptor transcriptional activity in vitro. Previously, our lab has shown that SRC-1 and CBP modulate estrogen receptor (ER)-mediated induction of progestin receptor (PR) gene expression in the ventromedial nucleus of the hypothalamus (VMN) and hormone-dependent sexual receptivity in female rats. Female sexual behaviors can be activated by high doses of E alone in ovariectomized rats, and thus are believed to be ER-dependent. However, the full repertoire of female sexual behavior, in particular, proceptive behaviors such as hopping, darting and ear wiggling, are considered to be PR-dependent. In the present experiments, the function of SRC-1 and CBP in distinct ER- (Exp. 1) and PR- (Exp. 2) dependent aspects of female sexual behavior was investigated. In Exp. 1, infusion of antisense oligodeoxynucleotides to SRC-1 and CBP mRNA into the VMN decreased lordosis intensity in rats treated with E alone, suggesting that these coactivators modulate ER-mediated female sexual behavior. In Exp. 2, antisense to SRC-1 and CBP mRNA around the time of P administration reduced PR-dependent ear wiggling and hopping and darting. Taken together, these data suggest that SRC-1 and CBP modulate ER and PR action in brain and influence distinct aspects of hormone-dependent sexual behaviors. These findings support our previous studies and provide further evidence that SRC-1 and CBP function together to regulate ovarian hormone action in behaviorally-relevant brain regions. PMID:16769066

Emotions induced by intracerebral electrical stimulation of the temporal lobe.

PubMed

Meletti, Stefano; Tassi, Laura; Mai, Roberto; Fini, Nicola; Tassinari, Carlo Alberto; Russo, Giorgio Lo

2006-01-01

To assess the quality and frequency of emotions induced by intracerebral electrical stimulation of the temporal lobe. Behavioral responses were obtained by electrical stimulation in 74 patients undergoing presurgical video-stereo-EEG monitoring for drug-resistant epilepsy. Intracerebral electrical stimulation was performed by delivering trains of electrical stimuli of alternating polarity; the intensity could vary from 0.2 to 3 mA. Stimulation frequency was 1 Hz or 50 Hz. Nine hundred thirty-eight stimulation procedures were performed. Seventy-nine emotional responses (ERs) were obtained (8.4%). Of these, 67 were "fear responses." Sad feelings were evoked 3 times, happy-pleasant feelings 9 times. Anger and disgust were never observed. The following variables affected the incidence of ER: (a) Anatomical site of stimulation. ERs (always fear) were maximal at the amygdala (12%) and minimal for lateral neocortical stimulation (3%, p < 0.01). (b) Pathology. Stimulation of a temporal lobe with hippocampal sclerosis was associated with a lower frequency of ERs compared with stimulation of a temporal lobe with no evidence of atrophy in the medial temporal structures. (c) Stimulation frequency. ERs were 12% at 50 Hz versus 6.0% at 1 Hz (p < 0.01). (d) Gender. In women fear responses were 16% compared with 3% in men (p < 0.01). There were no gender differences when analyzing nonemotional responses. These data confirm the role of the medial temporal lobe region in the expression of emotions, especially fear-related behaviors. Fear was observed more frequently in the absence of medial temporal sclerosis, supporting the hypothesis that emotional behaviors induced by stimulation are positive phenomena, strictly related to the physiological function of these regions. Further investigations should address why women express fear behaviors more frequently than men.

Chinese life cycle impact assessment factors.

PubMed

Yang, J X; Nielsen, P H

2001-04-01

The methodological basis and procedures for determination of Chinese normalization references and weighting factors according to the EDIP-method is described. According to Chinese industrial development intensity and population density, China was divided into three regions and the normalization references for each region were calculated on the basis of an inventory of all of the region's environmental emissions in 1990. The normalization reference was determined as the total environmental impact potential for the area in question in 1990 (EP(j)90) divided by the population. The weighting factor was determined as the normalization reference (ER(j)90) divided by society's target contribution in the year 2000 based on Chinese political reduction plans, ER(j)T2000. This paper presents and discuss results obtained for eight different environmental impact categories relevant for China: global warming, stratospheric ozone depletion, acidification, nutrient enrichment, photochemical ozone formation and generation of bulk waste, hazardous waste and slag and ashes.

A newly discovered impact crater in Titan's Senkyo: Cassini VIMS observations and comparison with other impact features

USGS Publications Warehouse

Buratti, B.J.; Sotin, Christophe; Lawrence, K.; Brown, R.H.; Le, Mouelic S.; Soderblom, J.M.; Barnes, J.; Clark, R.N.; Baines, K.H.; Nicholson, P.D.

2012-01-01

Senkyo is an equatorial plain on Titan filled with dunes and surrounded by hummocky plateaus. During the Titan targeted flyby T61 on August 25, 2009, the Cassini Visual and Infrared Mapping Spectrometer (VIMS) onboard the Cassini spacecraft observed a circular feature, centered at 5.4?? N and 341??W, that superimposes the dune fields and a bright plateau. This circular feature, which has been named Paxsi by the International Astronomical Union, is 120??10 km in diameter (measured from the outer edge of the crater rim) and exhibits a central bright area that can be interpreted as the central peak or pit of an impact crater. Although there are only a handful of certain impact craters on Titan, there are two other craters that are of similar size to this newly discovered feature and that have been studied by VIMS: Sinlap (Le Mou??lic et al, 2008) and Selk (Soderblom et al, 2010). Sinlap is associated with a large downwind, fan-like feature that may have been formed from an impact plume that rapidly expanded and deposited icy particles onto the surface. Although much of the surrounding region is covered with dunes, the plume region is devoid of dunes. The formation process of Selk also appears to have removed (or covered up) dunes from parts of the adjacent dune-filled terrain. The circular feature on Senkyo is quite different: there is no evidence of an ejecta blanket and the crater itself appears to be infilled with dune material. The rim of the crater appears to be eroded by fluvial processes; at one point the rim is breached. The rim is unusually narrow, which may be due to mass wasting on its inside and subsequent infill by dunes. Based on these observations, we interpret this newly discovered feature to be a more eroded crater than both Sinlap and Selk. Paxsi may have formed during a period when Titan was warmer and more ductile than it is currently. ?? 2011 Elsevier Ltd. All rights reserved.

The Central Molecular Zone of the Milky Way: Lessons about Star Formation from an extreme Environment

NASA Astrophysics Data System (ADS)

Kauffmann, Jens; Thushara Pillai, G. S.; Zhang, Qizhou; Lu, Xing; Immer, Katharina

2015-08-01

The Central Molecular Zone of the Milky Way (CMZ; innermost ~100pc) hosts a number of remarkably dense and massive clouds. These are subject to extreme environmental conditions, including very high cosmic ray fluxes and strong magnetic fields. Exploring star formation under such exceptional circumstances is essential for several of reasons. First, the CMZ permits to probe an extreme point in the star formation parameter space, which helps to test theoretical models. Second, CMZ clouds might help to understand the star formation under extreme conditions in more distant environments, such as in starbursts and the early universe.One particularly striking aspect is that — compared to the solar neighborhood — CMZ star formation in dense gas is suppressed by more than an order of magnitude (Longmore et al. 2012, Kauffmann et al. 2013). This questions current explanations for relations between the dense gas and the star formation rate (e.g., Gao & Solomon 2004, Lada et al. 2012). In other words, the unusually dense and massive CMZ molecular clouds form only very few stars, if any at all. Why is this so?Based on data from ALMA, CARMA, and SMA interferometers, we present results from the Galactic Center Molecular Cloud Survey (GCMS), the first study of a comprehensive sample of molecular clouds in the CMZ. This research yields a curious result: most of the major CMZ clouds are essentially devoid of significant substructure of the sort usually found in regions of high-mass star formation (Kauffmann et al. 2013). Preliminary analysis indicates that some clouds rather resemble homogeneous balls of gas. This suggests a highly dynamic picture of cloud evolution in the CMZ where clouds form, disperse, and re-assemble constantly. This concept is benchmarked against a new ALMA survey and first results from a legacy survey on the SMA.It is plausible that dense clouds in other galaxies have a similar internal structure. Instruments like ALMA and the JWST will soon permit to resolve such regions in nearby galaxies.

Transport properties of two-dimensional metal-phthalocyanine junctions: An ab initio study

NASA Astrophysics Data System (ADS)

Liu, Shuang-Long; Wang, Yun-Peng; Li, Xiang-Guo; Cheng, Hai-Ping

We study two dimensional (2D) electronic/spintronic junctions made of metal-organic frameworks via first-principles simulation. The system consists of two Mn-phthalocyanine leads and a Ni-phthalocyanine center. A 2D Mn phthalocyanine sheet is ferromagnetic half metal and a 2D Ni phthalocyanine sheet is nonmagnetic semiconductor. Our results show that this system has a large tunnel magnetic resistance. The transmission coefficient at Fermi energy decays exponentially with the length of the central region which is not surprising. However, the transmission of the junction can be tuned using gate voltage by up to two orders of magnitude. The origin of the change lies in the mode matching between the lead and the center electronic states. Moreover, the threshold gate voltage varies with the length of the center region which provides a way of engineering the transport properties. Finally, we combine non-equilibrium Green's function and Boltzmann transport equation to compute conductance of the junction. This work was supported by the US Department of Energy (DOE), Office of Basic Energy Sciences (BES), under Contract No. DE-FG02-02ER45995. Computations were done using the utilities of NERSC and University of Florida Research Computing.

GBNV encoded movement protein (NSm) remodels ER network via C-terminal coiled coil domain

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

Singh, Pratibha; Savithri, H.S., E-mail: bchss@biochem.iisc.ernet.in

Plant viruses exploit the host machinery for targeting the viral genome–movement protein complex to plasmodesmata (PD). The mechanism by which the non-structural protein m (NSm) of Groundnut bud necrosis virus (GBNV) is targeted to PD was investigated using Agrobacterium mediated transient expression of NSm and its fusion proteins in Nicotiana benthamiana. GFP:NSm formed punctuate structures that colocalized with mCherry:plasmodesmata localized protein 1a (PDLP 1a) confirming that GBNV NSm localizes to PD. Unlike in other movement proteins, the C-terminal coiled coil domain of GBNV NSm was shown to be involved in the localization of NSm to PD, as deletion of thismore » domain resulted in the cytoplasmic localization of NSm. Treatment with Brefeldin A demonstrated the role of ER in targeting GFP NSm to PD. Furthermore, mCherry:NSm co-localized with ER–GFP (endoplasmic reticulum targeting peptide (HDEL peptide fused with GFP). Co-expression of NSm with ER–GFP showed that the ER-network was transformed into vesicles indicating that NSm interacts with ER and remodels it. Mutations in the conserved hydrophobic region of NSm (residues 130–138) did not abolish the formation of vesicles. Additionally, the conserved prolines at positions 140 and 142 were found to be essential for targeting the vesicles to the cell membrane. Further, systematic deletion of amino acid residues from N- and C-terminus demonstrated that N-terminal 203 amino acids are dispensable for the vesicle formation. On the other hand, the C-terminal coiled coil domain when expressed alone could also form vesicles. These results suggest that GBNV NSm remodels the ER network by forming vesicles via its interaction through the C-terminal coiled coil domain. Interestingly, NSm interacts with NP in vitro and coexpression of these two proteins in planta resulted in the relocalization of NP to PD and this relocalization was abolished when the N-terminal unfolded region of NSm was deleted. Thus, the NSm interacts with NP via its N-terminal unfolded region and the NSm–NP complex could in turn interact with the ER membrane via the C-terminal coiled coil domain of NSm to form vesicles that are targeted to PD and there by assist the cell to cell movement of the viral genome complex. - Highlights: • GBNV NSm localizes to plasmodesmata via the C-terminal coiled coil domain. • GBNV NSm interacts with endoplasmic reticulum network and remodels it to vesicles. • The C-terminal coiled domain alone is responsible for vesicle formation. • The N-terminal unfolded region of NSm is involved in the re-localization of NP to PD.« less

Palmitate-induced ER stress and subsequent C 1 HOP activation attenuates leptin and IGF1expression in the brain

USDA-ARS?s Scientific Manuscript database

Background: The peptide hormones insulin-like growth factor-1 (IGF1) and leptin mediate a myriad of biological effects both in the peripheral and central nervous systems. The transcription of these two hormones is regulated by the transcription factor C/EBPa, which in turn is negatively regulated by...

Roles of ER, SRC-1, and CBP Phosphorylation in Estrogen Receptor-Regulated Gene Expression

DTIC Science & Technology

1999-06-01

J. S. Sutcliff, P. Fang, R. J. Galjaard, Y. H. Jiang, C. S. localization of three repair genes: the xeroderma pigmentosum group C gene Benton, J. M...receptor-mediated scription efficiency, a central DNA-binding domain, which me- transcription; SRC-1, p300/CBP, and RAC3/ACTR/AIB1 pos - diates receptor

Using model analyses and surface-atmosphere exchange measurements from the Howland AmeriFlux Site in Maine, USA, to improve understanding of forest ecosystem C cycling

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

Hollinger, David Y.; Davidson, Eric A.; Richardson, Andrew D.

2013-03-25

Summary of research carried out under Interagency Agreement DE-AI02-07ER64355 with the USDA Forest Service at the Howland Forest AmeriFlux site in central Maine. Includes a list of publications resulting in part or whole from this support.

Simulated MERTIS observation of the Rudaki-Kuiper craters area on Mercury

NASA Astrophysics Data System (ADS)

D'Amore, M.; Helbert, J.; Maturilli, A.; Ferrari, S.; Bauch, K.; D'Incecco, P.; Hiesinger, H.; Head, J. W.; Holsclaw, G. M.; Lorin, D. D.; Denevi, B. W.; Stockstill-Cahill, K. R.

2013-12-01

The MErcury Radiometer and Thermal infrared Imaging Spectrometer (MERTIS) is part of the payload of the BepiColombo mission. The mission is scheduled for launch in 2015 with arrival at Mercury in 2021. To achieve MERTIS's scientific goals the instrument maps the surface of Mercury with a spatial resolution of 500m for the spectrometer channel and 2km for the radiometer channel. MERTIS spans wavelength ranges of 7-14 and 7-40 μm with its two channels. Among it scientific goals, MERTIS will infer rock-forming minerals, map surface composition, and study surface temperature variations on Mercury with an uncooled microbolometer detector. To exploit the full potential of the unique MERTIS dataset, an extensive calibration campaign has been performed. This includes radiometric, spectral, and geometric calibration. In addition we have performed measurement of analog materials at temperatures of up to 500°C - similar to the peak temperatures expected at Mercury - with the MERTIS qualification model in the Planetary Emissivity Laboratory. These measurements allow for the evaluation of the MERTIS performance in direct comparison with the laboratory spectrometer. They also enable the creation of synthetic MERTIS datasets. For this purpose we use data from the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft as baseline. MESSENGER can provide geological information as well as spectral information in the UV, visible and near-infrared wavelengths range. For a first test we have selected the Kuiper-Rudaki region. The region has been extensively covered by measurements from the MESSENGER spacecraft. Recent analysis of observations by the Mercury Atmospheric and Surface Composition Spectrometer (MASCS) instrument on the MESSENGER spacecraft with an unsupervised hierarchical clustering method shows at global scales two major units: a Polar region (PR) spectrally flat and redder than the equatorial region (ER). The study area is primarily classified as a homogeneous expanse of the equatorial region (ER) cluster. Further clustering shows that the study area belongs to the 'core' ER, in opposition to some smaller patches of a transitional sub-unit, that are transitional region between global ER and the polar region (PR) cluster. Assuming a set of several potential mineralogies for the study area and modeled surface temperature at different local times we can obtain at PEL the spectra in the mid-infrared spectral range. Combining these with our knowledge of the MERTIS performance we can produce simulated MERTIS datasets of the study region at different point of the mission.

SNX14 mutations affect endoplasmic reticulum-associated neutral lipid metabolism in autosomal recessive spinocerebellar ataxia 20.

PubMed

Bryant, Dale; Liu, Yang; Datta, Sanchari; Hariri, Hanaa; Seda, Marian; Anderson, Glenn; Peskett, Emma; Demetriou, Charalambos; Sousa, Sergio; Jenkins, Dagan; Clayton, Peter; Bitner-Glindzicz, Maria; Moore, Gudrun E; Henne, W Mike; Stanier, Philip

2018-06-01

Mutations in SNX14 cause the autosomal recessive cerebellar ataxia 20 (SCAR20). Mutations generally result in loss of protein although several coding region deletions have also been reported. Patient-derived fibroblasts show disrupted autophagy, but the precise function of SNX14 is unknown. The yeast homolog, Mdm1, functions in endoplasmic reticulum (ER)-lysosome/vacuole inter-organelle tethering, but functional conservation in mammals is still required. Here, we show that loss of SNX14 alters but does not block autophagic flux. In addition, we find that SNX14 is an ER-associated protein that functions in neutral lipid homeostasis and inter-organelle crosstalk. SNX14 requires its N-terminal transmembrane helices for ER localization, while the Phox homology (PX) domain is dispensable for subcellular localization. Both SNX14-mutant fibroblasts and SNX14KO HEK293 cells accumulate aberrant cytoplasmic vacuoles, suggesting defects in endolysosomal homeostasis. However, ER-late endosome/lysosome contact sites are maintained in SNX14KO cells, indicating that it is not a prerequisite for ER-endolysosomal tethering. Further investigation of SNX14- deficiency indicates general defects in neutral lipid metabolism. SNX14KO cells display distinct perinuclear accumulation of filipin in LAMP1-positive lysosomal structures indicating cholesterol accumulation. Consistent with this, SNX14KO cells display a slight but detectable decrease in cholesterol ester levels, which is exacerbated with U18666A. Finally, SNX14 associates with ER-derived lipid droplets (LD) following oleate treatment, indicating a role in ER-LD crosstalk. We therefore identify an important role for SNX14 in neutral lipid homeostasis between the ER, lysosomes and LDs that may provide an early intervention target to alleviate the clinical symptoms of SCAR20.

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.

National Wetland Plant List Indicator Rating Definitions

DTIC Science & Technology

2012-07-01

ER D C/ CR RE L TN -1 2- 1 National Wetland Plant List Indicator Rating Definitions Co ld R eg io ns R es ea rc h an d En gi ne er in... Rating Definitions Robert W. Lichvar Cold Regions Research and Engineering Laboratory U.S. Army Engineer Research and Development Center 72 Lyme...status ratings in the United States. In 2012 the list, now called the National Wetland Plant List, was updated and approved for use for various

PRK by Er:YAG laser: in-vitro studies and first in-vivo experiences

NASA Astrophysics Data System (ADS)

Steiner, Rudolf W.; Leiacker, Richard; Russ, Detlef; Seiler, Theo

1996-01-01

Photorefractive keratectomy (PRK) is usually performed by an excimer laser at 193 nm wavelength. Ablatio of corneal tissue is, however, not only possible in the UV region of the optical spectrum but also in the IR where water is an excellent absorber. Therefore, an Er:YAG laser was used at 2.94 micrometer wavelength as an alternative laser light source to perform in vitro studies of corneal ablation and also first clinical experiments to correct myopia of patients with blind eyes.

Final Technical Report on DOE Awards DE-FG03 94ER61918, DE-FG06 94ER61918 to Oregon Health Sciences University, September 15, 1994 - September 29, 1999

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

Krages, Kathryn Pyle

1999-11-23

This report describes the activities conducted with DOE funds at Oregon Health Sciences University between 9/15/94 and 9/29/99. The activities fall into four major categories: Information Technology, Information Services and Support, Medical Informatics and Outcomes Research, and collaboration with other institutions. The focus of these activities was to implement and maintain a regional healthcare information network.

Luminescence studies on Er3+ -doped zincfluorophosphate glasses for 1.53 μm laser applications

NASA Astrophysics Data System (ADS)

Sreedhar, V. B.; Vijaya, N.; Ramachari, D.; Jayasankar, C. K.

2017-02-01

The Er3+-doped zincfluorophosphate glasses have been prepared by conventional melt-quenching technique and characterized through X-ray diffraction, differential thermal analysis, Raman, visible and near-infrared (NIR) emission spectra and decay time measurements. Judd-Ofelt intensity parameters (Ωλ, λ = 2, 4 and 6) have been derived from the absorption spectrum and inturn used to calculate the radiative properties for the fluorescent levels of Er3+ ions. The studied glasses exhibit intense green and weak red emissions under 378 nm excitation and an intense NIR emission at 1.53 μm under 980 nm laser diode excitation. The wavelength dependence of gain cross-section for different values of population inversion (γ) has been derived from the McCumber theory. Lifetime for the 4I13/2 level of Er3+ ion is found to decrease from 7.17 to 1.42 ms whereas the gain bandwidth increases from 143.5 to 263.9 × 10-28 cm3 with increase of Er3+ concentration from 0.001 to 2.0 mol %. The results indicate that the glasses may be suitable for the development of optical amplifier in the 1.53 μm optical region.

Observations of highly sheared turbulence in the H-mode pedestal using Phase Contrast Imaging on DIII-D

NASA Astrophysics Data System (ADS)

Rost, J. C.; Marinoni, A.; Davis, E. M.; Porkolab, M.; Burrell, K. H.

2017-10-01

Highly sheared turbulence with short radial correlation lengths has been measured near the top of the H-mode pedestal, in addition to the previously measured highly-sheared turbulence measured in the Er well. Turbulence in regions of large velocity shear is characterized by radial correlation lengths shorter than the poloidal wavelength (L < λ 2 cm) and large Doppler-shifted frequencies (f > 200 kHz). The phase contrast imaging (PCI) diagnostic on DIII-D is ideally suited to measuring this density turbulence due to the measurement geometry and high frequency bandwidth. Radial localization is achieved by optical filtering, varying the ExB profile, and shifting the plasma position. Reconfiguration of the Er well, such as at the L-H transition or the transition to wide pedestal QH-mode, shows a near-instantaneous change (t < 1 ms) to the sheared turbulence in the Er well ( 1 cm inside the separatrix). In contrast, the sheared turbulence near the top of the pedestal ( 2 cm inside the separatrix) varies over times scales of tens of ms, consistent with pedestal evolution. Work supported by the US Department of Energy under DE-FG02-94ER54235 and DE-FC02-04ER54698.

Recommendations of the DNA Commission of the International Society for Forensic Genetics (ISFG) on quality control of autosomal Short Tandem Repeat allele frequency databasing (STRidER).

PubMed

Bodner, Martin; Bastisch, Ingo; Butler, John M; Fimmers, Rolf; Gill, Peter; Gusmão, Leonor; Morling, Niels; Phillips, Christopher; Prinz, Mechthild; Schneider, Peter M; Parson, Walther

2016-09-01

The statistical evaluation of autosomal Short Tandem Repeat (STR) genotypes is based on allele frequencies. These are empirically determined from sets of randomly selected human samples, compiled into STR databases that have been established in the course of population genetic studies. There is currently no agreed procedure of performing quality control of STR allele frequency databases, and the reliability and accuracy of the data are largely based on the responsibility of the individual contributing research groups. It has been demonstrated with databases of haploid markers (EMPOP for mitochondrial mtDNA, and YHRD for Y-chromosomal loci) that centralized quality control and data curation is essential to minimize error. The concepts employed for quality control involve software-aided likelihood-of-genotype, phylogenetic, and population genetic checks that allow the researchers to compare novel data to established datasets and, thus, maintain the high quality required in forensic genetics. Here, we present STRidER (http://strider.online), a publicly available, centrally curated online allele frequency database and quality control platform for autosomal STRs. STRidER expands on the previously established ENFSI DNA WG STRbASE and applies standard concepts established for haploid and autosomal markers as well as novel tools to reduce error and increase the quality of autosomal STR data. The platform constitutes a significant improvement and innovation for the scientific community, offering autosomal STR data quality control and reliable STR genotype estimates. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Bid Participates in Genotoxic Drug-Induced Apoptosis of HeLa Cells and Is Essential for Death Receptor Ligands' Apoptotic and Synergistic Effects

PubMed Central

Concannon, Caoimhin G.; Rehm, Markus; Kögel, Donat; Prehn, Jochen H. M.

2008-01-01

Background The BH3-only protein Bid is an important component of death receptor-mediated caspase activation. Bid is cleaved by caspase-8 or -10 into t-Bid, which translocates to mitochondria and triggers the release of caspase-activating factors. Bid has also been reported to be cleaved by other proteases. Methodology/Principal Findings To test the hypothesis that Bid is a central mediator of stress-induced apoptosis, we investigated the effects of a small molecule Bid inhibitor on stress-induced apoptosis, and generated HeLa cells deficient for Bid. Stable knockdown of bid lead to a pronounced resistance to Fas/CD95- and TRAIL-induced caspase activation and apoptosis, and significantly increased clonogenic survival. While Bid-deficient cells were equally sensitive to ER stress-induced apoptosis, they showed moderate, but significantly reduced levels of apoptosis, as well as increased clonogenic survival in response to the genotoxic drugs Etoposide, Oxaliplatin, and Doxorubicin. Similar effects were observed using the Bid inhibitor BI6C9. Interestingly, Bid-deficient cells were dramatically protected from apoptosis when subtoxic concentrations of ER stressors, Etoposide or Oxaliplatin were combined with subtoxic TRAIL concentrations. Conclusions/Significance Our data demonstrate that Bid is central for death receptor-induced cell death and participates in anti-cancer drug-induced apoptosis in human cervical cancer HeLa cells. They also show that the synergistic effects of TRAIL in combination with either ER stressors or genotoxic anti-cancer drugs are nearly exclusively mediated via an increased activation of Bid-induced apoptosis signalling. PMID:18665234

Neutron diffraction study of antiferromagnetic ErNi3Ga9 in magnetic fields

NASA Astrophysics Data System (ADS)

Ninomiya, Hiroki; Sato, Takaaki; Matsumoto, Yuji; Moyoshi, Taketo; Nakao, Akiko; Ohishi, Kazuki; Kousaka, Yusuke; Akimitsu, Jun; Inoue, Katsuya; Ohara, Shigeo

2018-05-01

We report specific heat, magnetization, magnetoresistance, and neutron diffraction measurements of single crystals of ErNi3Ga9. This compound crystalizes in a chiral structure with space group R 32 . The erbium ions form a two-dimensional honeycomb structure. ErNi3Ga9 displays antiferromagnetic order below 6.4 K. We determined that the magnetic structure is slightly amplitude-modulated as well as antiferromagnetic with q = (0 , 0 , 0.5) . The magnetic properties are described by an Ising-like model in which the magnetic moment is always along the c-axis owing to the large uniaxial anisotropy caused by the crystalline electric field effect in the low temperature region. When the magnetic field is applied along the c-axis, a metamagnetic transition is observed around 12 kOe at 2 K. ErNi3Ga9 possesses crystal chirality, but the antisymmetric magnetic interaction, the so-called Dzyaloshinskii-Moriya (DM) interaction, does not contribute to the magnetic structure, because the magnetic moments are parallel to the DM-vector.

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.

BaY2F8 doped with Er3+: An upconverter material for photovoltaic application

NASA Astrophysics Data System (ADS)

Boccolini, A.; Faoro, R.; Favilla, E.; Veronesi, S.; Tonelli, M.

2013-08-01

Fluoride crystals (BaY2F8) doped with Er3+ ions with different doping level have been grown with a home-made Czochralski furnace. A spectroscopic characterization consisting in both absorption and fluorescence measurements were performed in order to investigate the upconversion mechanism occurring when the material is excited with a radiation at 1557 nm. The measured emission spectrum shows a photoluminescence mainly distributed in the Near Infrared (NIR) region at ≃1 μm. The spectral conversion due to the upconversion makes this material suitable for photovoltaic applications, especially if we combine it with a crystalline silicon solar cell. A device made of single face solar cell+upconverter material (PV-UC) was designed and his external quantum efficiency (EQE) at 1557 nm was measured. EQE values of 6.5% and 4.1% were reached under 8.5 W cm-2 power density illumination for the 30%Er3+ and 20%Er3+ samples, respectively.

A regional high-resolution carbon flux inversion of North America for 2004

NASA Astrophysics Data System (ADS)

Schuh, A. E.; Denning, A. S.; Corbin, K. D.; Baker, I. T.; Uliasz, M.; Parazoo, N.; Andrews, A. E.; Worthy, D. E. J.

2010-05-01

Resolving the discrepancies between NEE estimates based upon (1) ground studies and (2) atmospheric inversion results, demands increasingly sophisticated techniques. In this paper we present a high-resolution inversion based upon a regional meteorology model (RAMS) and an underlying biosphere (SiB3) model, both running on an identical 40 km grid over most of North America. Current operational systems like CarbonTracker as well as many previous global inversions including the Transcom suite of inversions have utilized inversion regions formed by collapsing biome-similar grid cells into larger aggregated regions. An extreme example of this might be where corrections to NEE imposed on forested regions on the east coast of the United States might be the same as that imposed on forests on the west coast of the United States while, in reality, there likely exist subtle differences in the two areas, both natural and anthropogenic. Our current inversion framework utilizes a combination of previously employed inversion techniques while allowing carbon flux corrections to be biome independent. Temporally and spatially high-resolution results utilizing biome-independent corrections provide insight into carbon dynamics in North America. In particular, we analyze hourly CO2 mixing ratio data from a sparse network of eight towers in North America for 2004. A prior estimate of carbon fluxes due to Gross Primary Productivity (GPP) and Ecosystem Respiration (ER) is constructed from the SiB3 biosphere model on a 40 km grid. A combination of transport from the RAMS and the Parameterized Chemical Transport Model (PCTM) models is used to forge a connection between upwind biosphere fluxes and downwind observed CO2 mixing ratio data. A Kalman filter procedure is used to estimate weekly corrections to biosphere fluxes based upon observed CO2. RMSE-weighted annual NEE estimates, over an ensemble of potential inversion parameter sets, show a mean estimate 0.57 Pg/yr sink in North America. We perform the inversion with two independently derived boundary inflow conditions and calculate jackknife-based statistics to test the robustness of the model results. We then compare final results to estimates obtained from the CarbonTracker inversion system and at the Southern Great Plains flux site. Results are promising, showing the ability to correct carbon fluxes from the biosphere models over annual and seasonal time scales, as well as over the different GPP and ER components. Additionally, the correlation of an estimated sink of carbon in the South Central United States with regional anomalously high precipitation in an area of managed agricultural and forest lands provides interesting hypotheses for future work.

Internal control regions for transcription of eukaryotic tRNA genes.

PubMed Central

Sharp, S; DeFranco, D; Dingermann, T; Farrell, P; Söll, D

1981-01-01

We have identified the region within a eukaryotic tRNA gene required for initiation of transcription. These results were obtained by systematically constructing deletions extending from the 5' or the 3' flanking regions into a cloned Drosophila tRNAArg gene by using nuclease BAL 31. The ability of the newly generated deletion clones to direct the in vitro synthesis of tRNA precursors was measured in transcription systems from Xenopus laevis oocytes, Drosophila Kc cells, and HeLa cells. Two control regions within the coding sequence were identified. The first was essential for transcription and was contained between nucleotides 8 and 25 of the mature tRNA sequence. Genes devoid of the second control region, which was contained between nucleotides 50 and 58 of the mature tRNA sequence, could be transcribed but with reduced efficiency. Thus, the promoter regions within a tRNA gene encode the tRNA sequences of the D stem and D loop, the invariant uridine at position 8, and the semi-invariant G-T-psi-C sequence. Images PMID:6947245

Localization and Divergent Profiles of Estrogen Receptors and Aromatase in the Vocal and Auditory Networks of a Fish with Alternative Mating Tactics

PubMed Central

Fergus, Daniel J.; Bass, Andrew H.

2013-01-01

Estrogens play a salient role in the development and maintenance of both male and female nervous systems and behaviors. The plainfin midshipman (Porichthys notatus), a teleost fish, has two male reproductive morphs that follow alternative mating tactics and diverge in multiple somatic, hormonal and neural traits, including the central control of morph-specific vocal behaviors. After we identified duplicate estrogen receptors (ERβ1 and ERβ2) in midshipman, we developed antibodies to localize protein expression in the central vocal-acoustic networks and saccule, the auditory division of the inner ear. As in other teleost species, ERβ1 and ERβ2 were robustly expressed in the telencephalon and hypothalamus in vocal-acoustic and other brain regions shown previously to exhibit strong expression of ERα and aromatase (estrogen synthetase, CYP19) in midshipman. Like aromatase, ERβ1 label co-localized with glial fibrillary acidic protein (GFAP) in telencephalic radial glial cells. Quantitative PCR revealed similar patterns of transcript abundance across reproductive morphs for ERβ1, ERβ2, ERα and aromatase in the forebrain and saccule. In contrast, transcript abundance for ERs and aromatase varied significantly between morphs in and around the sexually polymorphic vocal motor nucleus (VMN). Together, the results suggest that VMN is the major estrogen target within the estrogen-sensitive hindbrain vocal network that directly determines the duration, frequency and amplitude of morph-specific vocalizations. Comparable regional differences in steroid receptor abundances likely regulate morph-specific behaviors in males and females of other species exhibiting alternative reproductive tactics. PMID:23460422

Extreme Precipitation and Emergency Room Visits for Gastrointestinal Illness in Areas with and without Combined Sewer Systems: An Analysis of Massachusetts Data, 2003–2007

PubMed Central

Li, Quanlin; Wang, Shiliang; Messier, Kyle P.; Wade, Timothy J.; Hilborn, Elizabeth D.

2015-01-01

Background Combined sewer overflows (CSOs) occur in combined sewer systems when sewage and stormwater runoff are released into water bodies, potentially contaminating water sources. CSOs are often caused by heavy precipitation and are expected to increase with increasing extreme precipitation associated with climate change. Objectives The aim of this study was to assess whether the association between heavy rainfall and rate of emergency room (ER) visits for gastrointestinal (GI) illness differed in the presence of CSOs. Methods For the study period 2003–2007, time series of daily rate of ER visits for GI illness and meteorological data were organized for three exposure regions: a) CSOs impacting drinking water sources, b) CSOs impacting recreational waters, c) no CSOs. A distributed lag Poisson regression assessed cumulative effects for an 8-day lag period following heavy (≥ 90th and ≥ 95th percentile) and extreme (≥ 99th percentile) precipitation events, controlling for temperature and long-term time trends. Results The association between extreme rainfall and rate of ER visits for GI illness differed among regions. Only the region with drinking water exposed to CSOs demonstrated a significant increased cumulative risk for rate (CRR) of ER visits for GI for all ages in the 8-day period following extreme rainfall: CRR: 1.13 (95% CI: 1.00, 1.28) compared with no rainfall. Conclusions The rate of ER visits for GI illness was associated with extreme precipitation in the area with CSO discharges to a drinking water source. Our findings suggest an increased risk for GI illness among consumers whose drinking water source may be impacted by CSOs after extreme precipitation. Citation Jagai JS, Li Q, Wang S, Messier KP, Wade TJ, Hilborn ED. 2015. Extreme precipitation and emergency room visits for gastrointestinal illness in areas with and without combined sewer systems: an analysis of Massachusetts data, 2003–2007. Environ Health Perspect 123:873–879; http://dx.doi.org/10.1289/ehp.1408971 PMID:25855939

[Retention cysts of the vocal cords (author's transl)].

PubMed

Grundmann, E W

1979-05-01

Present day knowledge in laryngology maintains that the free edge of the true cord mucosa is devoid of glands so that retention cysts should not occur in this tissue. When such cysts do occur, it is difficult to define their pathogenesis. Reference is made to the author's earlier study which found a regular occurrence of mucous glands in the squamous epithelial region of the vocal cords. A retention cyst in the true cord is described histologically in the present report. The glands responsible for these cysts are believed to function by moistening the mucous membrane of the vocal cords.

Simple bone cyst of mandible mimicking periapical cyst.

PubMed

Hs, Charan Babu; Rai, Bhagawan Das; Nair, Manju A; Astekar, Madhusudan S

2012-05-29

Simple bone cysts (SBC) are pseudocysts occurring less commonly in the maxillofacial region. The uncertain and unclear etiopathogenesis led to numerous synonyms to refer this particular cyst. These cysts are devoid of an epithelial lining and are usually empty or contain blood or straw-colored fluid. In jaws initially it mimics a periapical cyst and later can lead to cortical bone expansion warranting for radical approach, which is seldom required. SBC is predominantly diagnosed in first two decades of life. Here we report a case of solitary bone cyst mimicking a periapical cyst of a mandibular molar in a 37-year-old patient.

Cytolethal distending toxins require components of the ER-associated degradation pathway for host cell entry.

PubMed

Eshraghi, Aria; Dixon, Shandee D; Tamilselvam, Batcha; Kim, Emily Jin-Kyung; Gargi, Amandeep; Kulik, Julia C; Damoiseaux, Robert; Blanke, Steven R; Bradley, Kenneth A

2014-07-01

Intracellular acting protein exotoxins produced by bacteria and plants are important molecular determinants that drive numerous human diseases. A subset of these toxins, the cytolethal distending toxins (CDTs), are encoded by several Gram-negative pathogens and have been proposed to enhance virulence by allowing evasion of the immune system. CDTs are trafficked in a retrograde manner from the cell surface through the Golgi apparatus and into the endoplasmic reticulum (ER) before ultimately reaching the host cell nucleus. However, the mechanism by which CDTs exit the ER is not known. Here we show that three central components of the host ER associated degradation (ERAD) machinery, Derlin-2 (Derl2), the E3 ubiquitin-protein ligase Hrd1, and the AAA ATPase p97, are required for intoxication by some CDTs. Complementation of Derl2-deficient cells with Derl2:Derl1 chimeras identified two previously uncharacterized functional domains in Derl2, the N-terminal 88 amino acids and the second ER-luminal loop, as required for intoxication by the CDT encoded by Haemophilus ducreyi (Hd-CDT). In contrast, two motifs required for Derlin-dependent retrotranslocation of ERAD substrates, a conserved WR motif and an SHP box that mediates interaction with the AAA ATPase p97, were found to be dispensable for Hd-CDT intoxication. Interestingly, this previously undescribed mechanism is shared with the plant toxin ricin. These data reveal a requirement for multiple components of the ERAD pathway for CDT intoxication and provide insight into a Derl2-dependent pathway exploited by retrograde trafficking toxins.

Cytolethal Distending Toxins Require Components of the ER-Associated Degradation Pathway for Host Cell Entry

PubMed Central

Eshraghi, Aria; Dixon, Shandee D.; Tamilselvam, Batcha; Kim, Emily Jin-Kyung; Gargi, Amandeep; Kulik, Julia C.; Damoiseaux, Robert; Blanke, Steven R.; Bradley, Kenneth A.

2014-01-01

Intracellular acting protein exotoxins produced by bacteria and plants are important molecular determinants that drive numerous human diseases. A subset of these toxins, the cytolethal distending toxins (CDTs), are encoded by several Gram-negative pathogens and have been proposed to enhance virulence by allowing evasion of the immune system. CDTs are trafficked in a retrograde manner from the cell surface through the Golgi apparatus and into the endoplasmic reticulum (ER) before ultimately reaching the host cell nucleus. However, the mechanism by which CDTs exit the ER is not known. Here we show that three central components of the host ER associated degradation (ERAD) machinery, Derlin-2 (Derl2), the E3 ubiquitin-protein ligase Hrd1, and the AAA ATPase p97, are required for intoxication by some CDTs. Complementation of Derl2-deficient cells with Derl2:Derl1 chimeras identified two previously uncharacterized functional domains in Derl2, the N-terminal 88 amino acids and the second ER-luminal loop, as required for intoxication by the CDT encoded by Haemophilus ducreyi (Hd-CDT). In contrast, two motifs required for Derlin-dependent retrotranslocation of ERAD substrates, a conserved WR motif and an SHP box that mediates interaction with the AAA ATPase p97, were found to be dispensable for Hd-CDT intoxication. Interestingly, this previously undescribed mechanism is shared with the plant toxin ricin. These data reveal a requirement for multiple components of the ERAD pathway for CDT intoxication and provide insight into a Derl2-dependent pathway exploited by retrograde trafficking toxins. PMID:25078082

Water masers and ammonia (1, 1) and (2, 2) towards six regions in the Carina Nebula

NASA Astrophysics Data System (ADS)

Breen, S. L.; Green, C.-E.; Cunningham, M. R.; Voronkov, M. A.; Horiuchi, S.; Green, J. A.

2018-01-01

We present water maser and ammonia (1, 1) and (2, 2) observations, towards six regions in the Carina Nebula, conducted with the Australia Telescope Compact Array. In total five water masers were detected within two of the target fields, and we provide their accurate positions and characteristics. These five water masers constitute all of the known masers detected towards star formation regions in the Carina Nebula and we argue, that given the evidence for active star formation, and the presence of many high-mass stars, the Carina Nebula is uncharacteristically devoid of masers. Our results are consistent with the Carina Nebula having a lack of young high-mass stars, despite the presence of older high-mass stars. Ammonia (1, 1) and (2, 2) emission was detected towards all but one of the target fields and we find that their linewidths and derived temperatures are consistent with the presence of young star formation regions.

Brazing of Carbon Carbon Composites to Cu-clad Molybdenum for Thermal Management Applications

NASA Technical Reports Server (NTRS)

Singh, M.; Asthana, R.; Shpargel, T> P.

2007-01-01

Advanced carbon carbon composites were joined to copper-clad molybdenum (Cu/Mo) using four active metal brazes containing Ti (Cu ABA, Cusin-1 ABA, Ticuni, and Ticusil) for potential use in thermal management applications. The brazed joints were characterized using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and Knoop microhardness measurements across the joint region. Metallurgically sound C-C/Cu/Mo joints, devoid of interfacial cracks formed in all cases. The joint interfaces were preferentially enriched in Ti, with Cu ABA joints exhibiting the largest interfacial Ti concentrations. The microhardness measurements revealed hardness gradients across the joint region, with a peak hardness of 300-350 KHN in Cusin-1 ABA and Ticusil joints and 200-250 KHN in Cu ABA and Ticuni joints, respectively.

Multi-nucleate retinal pigment epithelium cells of the human macula exhibit a characteristic and highly specific distribution.

PubMed

Starnes, Austin C; Huisingh, Carrie; McGwin, Gerald; Sloan, Kenneth R; Ablonczy, Zsolt; Smith, R Theodore; Curcio, Christine A; Ach, Thomas

2016-01-01

The human retinal pigment epithelium (RPE) is reportedly 3% bi-nucleated. The importance to human vision of multi-nucleated (MN)-RPE cells could be clarified with more data about their distribution in central retina. Nineteen human RPE-flatmounts (9 ≤ 51 years, 10 > 80 years) were imaged at 12 locations: 3 eccentricities (fovea, perifovea, near periphery) in 4 quadrants (superior, inferior, temporal, nasal). Image stacks of lipofuscin-attributable autofluorescence and phalloidin labeled F-actin cytoskeleton were obtained using a confocal fluorescence microscope. Nuclei were devoid of autofluorescence and were marked using morphometric software. Cell areas were approximated by Voronoi regions. Mean number of nuclei per cell among eccentricity/quadrant groups and by age were compared using Poisson and binominal regression models. A total of 11,403 RPE cells at 200 locations were analyzed: 94.66% mono-, 5.31% bi-, 0.02% tri-nucleate, and 0.01% with 5 nuclei. Age had no effect on number of nuclei. There were significant regional differences: highest frequencies of MN-cells were found at the perifovea (9.9%) and near periphery (6.8%). The fovea lacked MN-cells almost entirely. The nasal quadrant had significantly more MN-cells compared to other quadrants, at all eccentricities. This study demonstrates MN-RPE cells in human macula. MN-cells may arise due to endoreplication, cell fusion, or incomplete cell division. The topography of MN-RPE cells follows the topography of photoreceptors; with near-absence at the fovea (cones only) and high frequency at perifovea (highest rod density). This distribution might reflect specific requirements of retinal metabolism or other mechanisms addressable in further studies.

Central and peripheral haemodynamic effects of non-steroidal anti-inflammatory drugs in man.

PubMed

Wennmalm, A; Carlsson, I; Edlund, A; Eriksson, S; Kaijser, L; Nowak, J

1984-01-01

The haemodynamic effects of non-steroidal anti-inflammatory (NSAI) drugs can be attributed either to their common property of inhibiting the formation of prostaglandins (PG) in the cardiovascular system, or to direct actions on the tone and sensitivity of the resistance vessels in various regions. Indomethacin (IND) is the most frequently studied NSAI drug, in animals and in man. Its cardiovascular effects differ somewhat from those of other NSAI, due to the fact that, besides inhibiting PG formation, IND acts as a direct vasoconstrictor. The stimulatory effect of IND in vascular smooth muscle results in an increased systemic vascular resistance which, although partially compensated by a decreased cardiac output, gives rise to a moderate increase in systemic blood pressure. The vasoconstrictor effect of IND is of particular interest in patients with ischemic heart disease, since it lowers their already decreased coronary flow, and may thereby accentuate the risk of myocardial infarction. Administration of IND also leads to a decreased blood flow in the splanchnic region, the kidneys, and the brain. The cerebral blood flow is lowered by 25-35%; in addition, IND almost entirely erases the hyperemic flow response to hypercapnia. Of other NSAI drugs, at least aspirin and naproxen are completely devoid of such actions on the cerebral circulation. A common vascular effect of all NSAI drugs is a diminution of reactive hyperemia, the local hyperemia that develops in a tissue subjected to a short period of arterial occlusion. Part of this hyperemic response is dependent on an intact vascular PG formation and consequently it is inhibited when PG formation is blocked. In contrast, NSAI drugs do not affect the functional increase in the blood flow in working skeletal muscle.

Hurricane Wind Field Measurements with Scanning Airborne Doppler Lidar During CAMEX-3

NASA Technical Reports Server (NTRS)

Rothermel, Jeffry; Cutten, D. R.; Howell, J. N.; Darby, L. S.; Hardesty, R. M.; Traff, D. M.; Menzies, R. T.

2000-01-01

During the 1998 Convection and Moisture Experiment (CAMEX-3), the first hurricane wind field measurements with Doppler lidar were achieved. Wind fields were mapped within the eye, along the eyewall, in the central dense overcast, and in the marine boundary layer encompassing the inflow region. Spatial coverage was determined primarily by cloud distribution and opacity. Within optically-thin cirrus slant range of 20- 25 km was achieved, whereas no propagation was obtained during penetration of dense cloud. Measurements were obtained with the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS) on the NASA DC-8 research aircraft. MACAWS was developed and operated cooperatively by the atmospheric lidar remote sensing groups of NOAA Environmental Technology Laboratory, NASA Marshall Space Flight Center, and Jet Propulsion Laboratory. A pseudo-dual Doppler technique ("co-planar scanning") is used to map the horizontal component of the wind at several vertical levels. Pulses from the laser are directed out the left side of the aircraft in the desired directions using computer-controlled rotating prisms. Upon exiting the aircraft, the beam is completely eyesafe. Aircraft attitude and speed are taken into account during real-time signal processing, resulting in determination of the ground-relative wind to an accuracy of about 1 m/s magnitude and about 10 deg direction. Beam pointing angle errors are about 0.1 deg, equivalent to about 17 m at 10 km. Horizontal resolution is about 1 km (along-track) for typical signal processor and scanner settings; vertical resolution varies with range. Results from CAMEX-3 suggest that scanning Doppler wind lidar can complement airborne Doppler radar by providing wind field measurements in regions that are devoid of hydrometeors. At present MACAWS observations are being assimilated into experimental forecast models and satellite Doppler wind lidar simulations to evaluate the relative impact.

Regional Characteristics of U.S. Farms and Farmers in the 1980's. ERS Staff Report No. AGES880128.

ERIC Educational Resources Information Center

Smith, Matthew G.; Hines, Fred

Farms and the people who live on them differ dramatically from one part of the United States to another. These differences are prominent both from one region to the next as well as between farms and people in the same region. The varying characteristics of agriculture and the farm population have helped shape regional experiences in the 1980s. In…

Modelling and stability analysis of switching impulsive power systems with multiple equilibria

NASA Astrophysics Data System (ADS)

Zhu, Liying; Qiu, Jianbin; Chadli, Mohammed

2017-12-01

This paper tries to model power systems accompanied with a series of faults in the form of switched impulsive Hamiltonian systems (SIHSs) with multiple equilibria (ME) and unstable subsystems (US), and then analyze long-term stability issues of the power systems from the viewpoint of mathematics. According to the complex phenomena of switching actions of stages and generators, impulses of state, and existence of multiple equilibria, this paper first introduces an SIHS with ME and US to formulate a switching impulsive power system composed of an active generator, a standby generator, and an infinite load. Then, based on special system structures, a unique compact region containing all ME is determined, and novel stability concepts of region stability (RS), asymptotic region stability (ARS), and exponential region stability (ERS) are defined for such SIHS with respect to the region. Third, based on the introduced stability concepts, this paper proposes a necessary and sufficient condition of RS and ARS and a sufficient condition of ERS for the power system with respect to the region via the maximum energy function method. Finally, numerical simulations are carried out for a power system to show the effectiveness and practicality of the obained novel results.

Identifying high-risk areas of bacillary dysentery and associated meteorological factors in Wuhan, China

PubMed Central

Li, Zhenjun; Wang, Ligui; Sun, Weige; Hou, Xuexin; Yang, Haiyan; Sun, Lina; Xu, Shuai; Sun, Qiangzheng; Zhang, Jingshan; Song, Hongbin; Lin, Hualiang

2013-01-01

Spatial distribution of bacillary dysentery incidence was mapped at the district level in Wuhan, China. And a generalized additive time series model was used to examine the effect of daily weather factors on bacillary dysentery in the high-risk areas, after controlling for potential confounding factors. Central districts were found to be the high-risk areas. The time series analysis found an acute effect of meteorological factors on bacillary dysentery occurrence. A positive association was found for mean temperature (excess risk (ER) for 1°C increase being 0.94% (95% confidence interval (CI): 0.46% to 1.43% on the lag day 2), while a negative effect was observed for relative humidity and rainfall, the ER for 1% increase in relative humidity was −0.21% (95% CI: −0.34% to −0.08%), and the ER for 1 mm increase in rainfall was −0.23% (95% CI: −0.37% to −0.09%). This study suggests that bacillary dysentery prevention and control strategy should consider local weather variations. PMID:24257434

Statolith action by the numbers: Physics and feasbility

NASA Astrophysics Data System (ADS)

Todd, Paul; Yoder, Thomas; Staehelin, L. Andrew

2016-07-01

All modern (and ancient) studies make it clear that statolith motion is required for gravisensing, and some evidence indicates a role for statolith-microfilament interaction. In this study two components of statolith action are considered quantitatively: (1) the movement of statoliths through the columella cell cytoplasm and (2) forces at the site of action of the statolith. (1) Statoliths move through the cytoplasm in the presence of viscous and elastic forces that may be considered separately. The viscous component may be characterized as a solution with a viscosity of approximately 40 centiPoise. Statoliths are deflected from perfectly vertical trajectories by various obstacles, including actin filaments, and their velocities are influenced by interactions between statoliths. Channeling flow is commonly observed, but this cannot be due to the breaking of actin filaments by the force of the sedimenting statolith, as about 600 pN force is required to break a filament, and the force due to gravity on the amyloplast is about 0.07 pN. Under least viscous conditions the randomly-directed Brownian diffusion velocity of the amyloplast is about 10% the sedimentation velocity. (2) Intimate association of statoliths with the cortical ER region requiring gravitational force is postulated. Thin-section micrographs clearly show an interface between the cortex and the central cytoplasm of the columella cell in vascular plant species that have been studied. Whether or not an exchange of chemical components is required, experiments, including observations in low gravity, have demonstrated that the statolith is shallowly embedded in this cortical region to the extent that deformation occurs consistent with Newton's third law. Relieving the gravitational force results in instantaneous motion of the amyloplast away from the cortex. The following inquiry was made concerning the physics at the interface between the statolith and the material of the cortical ER region. How much force does the statolith exert on the interface between the ER cortex and inner cytoplasm? What is the origin of the elastic force that opposes the penetration of the statolith and that causes it to rebound when the gravitational force is relieved? Candidates considered included actin filaments, endoplasmic membrane, an immiscible-phase interface, and a miscible-phase interface. Forces estimated to produce a 300nm indentation in such interfaces were 100, 30, 0.3, and <1 pN, respectively. The gravitational force on a single statolith is typically 0.1 pN or less. These numbers suggest that the statolith is interacting with an aqueous-aqueous interface with low interfacial tension (<1 μN/m). Further quantitative testing of these notions should be performed on forthcoming low-gravity sub-orbital crewed flights on which dynamic microscopy can be performed during several seconds of increased g-loading followed by some ten minutes of reduced gravity.

Mapping mesoscale variability of the Azores Current using TOPEX/POSEIDON and ERS 1 altimetry, together with hydrographic and Lagrangian measurements

NASA Astrophysics Data System (ADS)

Hernandez, Fabrice; Le Traon, Pierre-Yves; Morrow, Rosemary

1995-12-01

The SEMAPHORE mesoscale air/sea experiment was conducted in the Azores-Madeira region from July to November 1993. TOPEX/POSEIDON (T/P) and ERS 1 were flying simultaneously at that time. The main purposes of this paper are to evaluate the estimation of the oceanic mesoscale circulation from the two different sets of altimetric data (T/P and ERS 1) and to compare the results with in situ measurements provided by the SEMAPHORE hydrographic surveys and surface drifters (three expendable bathytermograph conductivity-temperature-depth surveys in a 500-km2 box and a set of 47 Lagrangian surface drifters drogued at 150 m). Comparisons are carried out through the maps obtained by objective analysis from the four data sets. The mapping accuracy of T/P, ERS 1, T/P and ERS 1 combined, and in situ data is investigated, as well as the sensitivity of the mapping to the correlation functions used. There is a good qualitative agreement between altimetric maps and corresponding drifter and hydrographic maps for the three hydrographic surveys. Correlations are about 0.8, and the regression fit is about 0.6-0.7; the lower values are due to the smooth climatology used to reference the altimetric maps. The correlation for time differences is better, with regression lines not significantly different from 1, especially when ERS 1 and T/P are combined. T/P mapping is almost as good as ERS 1 mapping, which was rather unexpected since the ERS 1 space-time sampling is better suited for the mesoscale. This may reflect the fact that the signal mapped by the hydrography and drifters does not contain the high frequency/wavenumber components. T/P and ERS 1 combined provide better results, although the improvement is not as large as expected, probably for the same reason.

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.

Production of Internal Transport Barriers via self-generated flows in Alcator C-Mod

NASA Astrophysics Data System (ADS)

Fiore, Catherine L.

2011-10-01

New results suggest that changes observed in the intrinsic toroidal rotation influence ITB formation in Alcator C-Mod that arise when the resonance for ICRF minority heating is positioned off-axis at or outside of the plasma half-radius. These ITBs form in a reactor relevant regime, without particle or momentum injection, with Ti ~Te, and with monotonic q profiles (qmin < 1). C-Mod H-mode plasmas exhibit strong intrinsic co-current rotation that increases with increasing stored energy without external drive. With the resonance position off-axis, the rotation decreases in the center of the plasma resulting in a radial rotation profile with a central well which deepens and moves farther off-axis when the ICRF resonance is at the plasma half-radius. This profile results in strong ExB shear (>1.5x105 Rad/sec) in the region where the ITB foot is observed. The self generated ExB shearing increases rapidly after the H-mode transition in off-axis ICRF heated discharges, before other profile changes are observed. Gyrokinetic analyses indicate that this spontaneous shearing rate is comparable to the linear ITG growth rate at the ITB location and may be responsible for stabilizing the underlying turbulence. Detailed measurement of the ion temperature demonstrates that the radial profile also flattens as the ICRF resonance position moves off axis. This decreases R/LTi in the barrier region, lessening the drive for the ITG turbulence and the resulting particle transport. The reduction in particle transport resulting from increase in core stability allows the neoclassical pinch to peak the density and pressure on axis. This suggests that spontaneous rotation is a potential tool for plasma profile control in reactor plasmas. The experimental results and corresponding gyrokinetic study will be presented. US-DoE DE-FC02-99ER54512 and DE-FG03-96ER54373.

Tunable upconversion luminescence of monodisperse Y2O3: Er3+/Yb3+/Tm3+ nanoparticles

NASA Astrophysics Data System (ADS)

Wu, Qibai; Lin, Shaoteng; Xie, Zhongxiang; Zhang, Liqing; Qian, Yannan; Wang, Yaodong; Zhang, Haiyan

2017-12-01

Monodisperse Y2O3: Er3+/Yb3+/Tm3+ nanoparticles with various dopant concentrations have been synthesized successfully by a homogeneous precipitation method. Their phase structures and surface morphologies have been characterized using X-ray diffraction (XRD) and scanning electron microscopy (SEM). The diversities of upconversion luminescence spectra and CIE coordinates of prepared samples are investigated in detail at room temperature under 980 nm excitation. Through adjusting the concentrations of Yb3+, Tm3+ and Er3+ ions, three upconversion emission bands in red, green and blue region could be tunable to achieve the color of interest and near white light emission can be obtained in the tri-doped Y2O3 nanoparticles for a variety of application.

Mid-infrared emission and Raman spectra analysis of Er(3+)-doped oxyfluorotellurite glasses.

PubMed

Chen, Fangze; Xu, Shaoqiong; Wei, Tao; Wang, Fengchao; Cai, Muzhi; Tian, Ying; Xu, Shiqing

2015-04-10

This paper reports on the spectroscopic and structural properties in Er(3+)-doped oxyfluorotellurite glasses. The compositional variation accounts for the evolutions of Raman spectra, Judd-Ofelt parameters, radiative properties, and fluorescent emission. It is found that, when maximum phonon energy changes slightly, phonon density plays a crucial role in quenching the 2.7 μm emission generated by the Er(3+):(4)I11/2→(4)I13/2 transition. The comparative low phonon density contributes strong 2.7 μm emission intensity. The high branching ratio (18.63%) and large emission cross section (0.95×10(-20)  cm(2)) demonstrate that oxyfluorotellurite glass contained with 50 mol.% TeO2 has potential application in the mid-infrared region laser.

Structural insight into the antagonistic action of diarylheptanoid on human estrogen receptor alpha.

PubMed

Geetha Rani, Yuvaraj; Lakshmi, Baddireddi Subhadra

2018-03-30

Estrogen receptor α (ER α) is an important therapeutic target in the regulation of ligand dependent signaling in breast cancer. The current study investigates the anti-estrogenic potential of the Diarylheptanoid, 5-hydroxy-7-(4-hydroxy-3 methoxyphenyl)-1-phenyl-3-heptanone (DAH) in silico. Rigid Docking analysis of DAH at the ligand binding domain (LBD) of ER α showed hydrogen bond interactions with Arg394 and Glu353 at the active site, similar to the positive controls 4-Hydroxy Tamoxifen (4-OHT) and Fulvestrant (FUL). The protein and the protein-DAH complexes were further analyzed using molecular dynamics simulations for a time scale of 50 ns using GROMACS. Root mean square fluctuation (RMSF) analysis showed large fluctuations at the N-terminal region of Helices (H) 3, 9 and at the C-terminal region of H11, which could be involved in the antagonistic conformational change. Interestingly, H12 appeared to move away from the ligand binding pocket and occupy the co-activator binding groove at the LBD of ER α. Secondary structure analysis of the protein upon binding of DAH and CUR showed structural change from α-helix to Turn conformation at H4. We hypothesize that this structural change at H4, similar to the positive control, could hinder the activity of AF-2 by blocking the binding of co-activator. These conformational changes in ER α indicate an anti-estrogenic and therapeutic potential of the DAH.

A synthesis of mineralization styles and geodynamic settings of the Paleozoic and Mesozoic metallic ore deposits in the Altay Mountains, NW China

NASA Astrophysics Data System (ADS)

Yang, Fuquan; Geng, Xinxia; Wang, Rui; Zhang, Zhixin; Guo, Xuji

2018-06-01

The Altay Mountains within the Xinjiang region of northwestern China hosts major metallic ore deposits. Here we review the geological characteristics, metallogenic features and tectonic settings of these deposits. The metallic ore deposits in the Altay Mountains occur mainly within four regions: North Altay, Central Altay, South Altay and Erqis. We recognize seven types of metallic ore deposits in the Altay Mountains: VMS, submarine volcanogenic iron, magmatic, skarn, pegmatite, hydrothermal vein (Cu-Zn, Fe) and orogenic gold. Among these types, the VMS, pegmatite, orogenic gold and skarn deposits are the most common. Most of the rare metal pegmatite deposits are distributed in Central Altay, with only a few in South Altay. The VMS, submarine volcanogenic type iron and skarn-type deposits are distributed in South Altay, whereas the orogenic-type gold deposits are distributed in the Erqis Fault belt. The hydrothermal vein-type deposits occur in the Erqis Fault belt and Chonghu'er Basin in South Altay. Magmatic-type deposits are mostly in the Erqis Fault belt and Central Altay. Based on isotopic age data, the VMS, submarine volcanogenic-type Fe and skarn-type Cu, Pb, Zn, Fe mineralization occurred during Early-Middle Devonian (∼410-377 Ma), orogenic-type Au, magmatic-type Cu-Ni, and a small number of skarn-type Fe, hydrothermal vein-type Cu-Zn, pegmatite-type rare-metal deposits in Early-Middle Permian (293-261 Ma), pegmatite-type rare-metal deposits, few skarn-type Fe deposit in Early-Middle Triassic (248-232 Ma), and dominantly represented by pegmatite-type rare-metal deposits in Late Triassic-Early Jurassic (223-180 Ma). The metallic ore deposits in the Altay Mountains formed in various tectonic settings, such as the Early-Middle Devonian continental arc and oceanic island arc, Early-Middle Permian post-collisional extensional setting, and Triassic-Early Jurassic intracontinental setting.

Effects of multi-pulsed coaxial helicity injection on dynamics of spherical torus

NASA Astrophysics Data System (ADS)

Kanki, T.; Nagata, M.; Kagei, Y.

2012-10-01

The mechanism to rebuild the magnetic fields and to amplify the currents in the high-q spherical torus (ST) by the multi-pulsed coaxial helicity injection is investigated using the resistive nonlinear 3D-MHD simulations. During the driven phase, the dynamics is almost axisymmetric because the magnetic fluctuation level of n=0 mode compared with other higher modes is much larger. The toroidal current It is effectively amplified due to the merging of plasmoid ejected from the gun region with the pre-existing ST in the confinement region. The poloidal flux is not significantly amplified because the current sheet generated by the merging process does not rapidly decay. The negative toroidal flow vt is then induced in the direction of It around the central open flux column (OFC) region by inductive toroidal electric field Et (=-vzBr) because of the plasmoid ejection. The strong poloidal flow vz (=ErBt) is also driven from the gun to confinement region due to the Lorentz force. As the result of vz, the flow vortices associated with the dynamo effect are caused around the upper confinement region. During the decay phase, the closed field lines are regenerated due to the dissipation of magnetic fluctuations. The helical distortion of the OFC becomes small, and then ordered magnetic field structures without flows are built. Just after turning off the external electric field, the poloidal flow from the confinement to gun region is caused by the pressure gradients. The parallel current density λ concentrated in the OFC diffuses to the core region, but does not relax in the direction of the Taylor state due to the pressure gradients.

Grp94 Protein Delivers γ-Aminobutyric Acid Type A (GABAA) Receptors to Hrd1 Protein-mediated Endoplasmic Reticulum-associated Degradation.

PubMed

Di, Xiao-Jing; Wang, Ya-Juan; Han, Dong-Yun; Fu, Yan-Lin; Duerfeldt, Adam S; Blagg, Brian S J; Mu, Ting-Wei

2016-04-29

Proteostasis maintenance of γ-aminobutyric acid type A (GABAA) receptors dictates their function in controlling neuronal inhibition in mammalian central nervous systems. However, as a multisubunit, multispan, integral membrane protein, even wild type subunits of GABAA receptors fold and assemble inefficiently in the endoplasmic reticulum (ER). Unassembled and misfolded subunits undergo ER-associated degradation (ERAD), but this degradation process remains poorly understood for GABAA receptors. Here, using the α1 subunits of GABAA receptors as a model substrate, we demonstrated that Grp94, a metazoan-specific Hsp90 in the ER lumen, uses its middle domain to interact with the α1 subunits and positively regulates their ERAD. OS-9, an ER-resident lectin, acts downstream of Grp94 to further recognize misfolded α1 subunits in a glycan-dependent manner. This delivers misfolded α1 subunits to the Hrd1-mediated ubiquitination and the valosin-containing protein-mediated extraction pathway. Repressing the initial ERAD recognition step by inhibiting Grp94 enhances the functional surface expression of misfolding-prone α1(A322D) subunits, which causes autosomal dominant juvenile myoclonic epilepsy. This study clarifies a Grp94-mediated ERAD pathway for GABAA receptors, which provides a novel way to finely tune their function in physiological and pathophysiological conditions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Black phosphorus saturable absorber for a diode-pumped passively Q-switched Er:CaF2 mid-infrared laser

NASA Astrophysics Data System (ADS)

Li, Chun; Liu, Jie; Guo, Zhinan; Zhang, Han; Ma, Weiwei; Wang, Jingya; Xu, Xiaodong; Su, Liangbi

2018-01-01

A multilayer black phosphorus, as a novel two dimensional saturable absorber, has superb saturable absorption properties for a Er:CaF2 solid-state pulse laser. The pulse laser is realized at mid-infrared region with the passively Q-switched technology by a diode-pumping. The high-quality black phosphorus saturable absorber is fabricated by liquid phase exfoliation method. The pulse laser generates the pulses operation with the pulse duration of 954.8 ns, the repetition rate of 41.93 kHz, the pulse energy of 4.25 μJ and the peak power of 4.45 W. Our work demonstrates that black phosphorus could be used as a kind of efficient mid-infrared region optical absorber for ultrafast photonics.

CTR1 phosphorylates the central regulator EIN2 to control ethylene hormone signaling from the ER membrane to the nucleus in Arabidopsis

USDA-ARS?s Scientific Manuscript database

The gaseous phytohormone ethylene (C2H4) mediates numerous aspects of growth and development. Genetic analysis has identified a number of critical elements in the ethylene signaling (1), but how these elements interact biochemically to transduce the signal from the ethylene receptor complex at the e...

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

Central and peripheral hemodynamic responses to passive limb movement: the role of arousal

PubMed Central

Venturelli, Massimo; Amann, M.; McDaniel, J.; Trinity, J. D.; Fjeldstad, A. S.

2012-01-01

The exact role of arousal in central and peripheral hemodynamic responses to passive limb movement in humans is unclear but has been proposed as a potential contributor. Thus, we used a human model with no lower limb afferent feedback to determine the role of arousal on the hemodynamic response to passive leg movement. In nine people with a spinal cord injury, we compared central and peripheral hemodynamic and ventilatory responses to one-leg passive knee extension with and without visual feedback (M+VF and M-VF, respectively) as well as in a third trial with no movement or visual feedback but the perception of movement (F). Ventilation (V̇e), heart rate, stroke volume, cardiac output, mean arterial pressure, and leg blood flow (LBF) were evaluated during the three protocols. V̇e increased rapidly from baseline in M+VF (55 ± 11%), M-VF (63 ± 13%), and F (48 ± 12%) trials. Central hemodynamics (heart rate, stroke volume, cardiac output, and mean arterial pressure) were unchanged in all trials. LBF increased from baseline by 126 ± 18 ml/min in the M+VF protocol and 109 ± 23 ml/min in the M-VF protocol but was unchanged in the F protocol. Therefore, with the use of model that is devoid of afferent feedback from the legs, the results of this study reveal that, although arousal is invoked by passive movement or the thought of passive movement, as evidenced by the increase in V̇e, there is no central or peripheral hemodynamic impact of this increased neural activity. Additionally, this study revealed that a central hemodynamic response is not an obligatory component of movement-induced LBF. PMID:22003056

Nearshore Placement Techniques in Southern Lake Michigan

DTIC Science & Technology

2018-03-01

ER D C /C HL T R- 18 -3 Regional Sediment Management (RSM) Program Nearshore Placement Techniques in Southern Lake Michigan Co as ta...online library at http://acwc.sdp.sirsi.net/client/default. Regional Sediment Management (RSM) Program ERDC/CHL TR-18-3 March 2018 Nearshore...This study was conducted for Headquarters, U.S. Army Corps of Engineers (HQUSACE), Washington, DC, under the USACE Regional Sediment Management

Description of the physical environment and coal-mining history of west-central Indiana, with emphasis on six small watersheds

USGS Publications Warehouse

Martin, Jeffrey D.; Crawford, Charles G.; Duwelius, R.F.; Renn, D.E.

1987-01-01

Information on the geology, geomorphology, soils, climate, hydrology, water use, land use, population, and coal mining history of Clay, Owen, Sullivan, and Vigo Counties in Indiana is summarized. Site-specific information is given on the morphology , geology, soils, land use, coal mining history, and hydrologic instrumentation of the six watersheds which are each less than 3 sq mi in area. The Wabash, White, and Eel Rivers are the major drainages in west-central Indiana. Average annual precipitation is about 39.5 in/yr and average annual runoff is about 13 in/yr. The most productive aquifers are confined or unconfined outwash aquifers located along the major rivers. Bedrock aquifers are regionally insignificant but are the sole source of groundwater for areas that lack outwash, alluvium, or sand and gravel lenses in till. Indiana has more than 17 billion short tons of recoverable coal reserves; about 11% can be mined by surface methods. Almost half of Indiana 's surface reserves are in Clay, Owen, Sullivan, and Vigo Counties. More than 50,000 acres in west-central Indiana have been disturbed by surface coal mining from 1941 through 1980. Big Slough and Hooker Creek are streams that drain unmined, agricultural watersheds. Row-crop corn and soybeans are the principal crops. Soils are moderately well drained silt loams, and the watersheds well developed dendritic drainage systems. Unnamed tributaries drain mined and reclaimed watersheds. Ridges of mine spoil have been graded to a gently rolling topography. Soils are well drained and consist of 6 to 12 inches of silt-loam topsoil that was stockpiled and then replaced over shale and sandstone fragments of the graded mine spoil. Grasses and legumes form the vegetative cover in each watershed. Pond Creek and an unnamed tributary to Big Branch are streams that drain mined and unreclaimed watersheds. Soils are very well drained shaly silty loams that have formed on steeply sloping banks. Both watersheds contain numerous impoundments of water and have enclosed areas that do not contribute surface runoff to streamflow. The ridges of mine spoil are covered with pine trees, but much of the soil surface is devoid of vegetation. (Lantz-PTT)

Endoplasmic Reticulum Stress in Mice Increases Hepatic Expression of Genes Carrying a Premature Termination Codon via a Nutritional Status-Independent GRP78-Dependent Mechanism.

PubMed

Harada, Nagakatsu; Okuyama, Maiko; Yoshikatsu, Aya; Yamamoto, Hironori; Ishiwata, Saori; Hamada, Chikako; Hirose, Tomoyo; Shono, Masayuki; Kuroda, Masashi; Tsutsumi, Rie; Takeo, Jiro; Taketani, Yutaka; Nakaya, Yutaka; Sakaue, Hiroshi

2017-11-01

Nonsense-mediated mRNA decay (NMD) degrades mRNAs carrying a premature termination codon (PTC) in eukaryotes. Cellular stresses, including endoplasmic reticulum (ER) stress, inhibit NMD, and up-regulate PTC-containing mRNA (PTC-mRNA) levels in several cell lines. However, whether similar effects exist under in vivo conditions that involve systemic nutritional status is unclear. Here, we compared the effects of pharmacological induction of ER stress with those of nutritional interventions on hepatic PTC-mRNA levels in mice. In mouse livers, the ER stress inducer tunicamycin increased PTC-mRNA levels of endogenous marker genes. Tunicamycin decreased body weight and perturbed nutrient metabolism in mice. Food restriction or deprivation mimicked the effect of tunicamycin on weight loss and metabolism, but did not increase PTC-mRNA levels. Hyperphagia-induced obesity also had little effect on hepatic PTC-mRNA levels. Meanwhile, in mouse liver phosphorylation of eIF2α, a factor that regulates NMD, was increased by both tunicamycin and nutritional interventions. Hepatic expression of GRP78, a central chaperone in ER stress responses, was increased by tunicamycin but not by the nutritional interventions. In cultured liver cells (Hepa), exogenous overexpression of a phosphomimetic eIF2α failed to increase PTC-mRNA levels. However, GRP78 overexpression in Hepa cells increased PTC-mRNA and PTC-mRNA-derived protein levels. ER stress promoted localization of GRP78 to mitochondria, and exogenous expression of a GRP78 fusion protein targeted to mitochondria mimicked the effect of wild type GRP78. These results indicate that GRP78, but not nutritional status, is a potent up-regulator of hepatic PTC-mRNA levels during induction of ER stress in vivo. J. Cell. Biochem. 118: 3810-3824, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Low Power Radiation Hard GaAs RAM

DTIC Science & Technology

1984-03-01

the collector space-charge region. Therefore, the current can be ex- pressed by qD D qDP qVa Jra (-k + 4 1n) (e" IF- - 1 ) .(27) 7n p In case Va >> 26...unlimited. 4. PERFORMING ORGANIZATION REPORT NUMBER(S) SMONITORING ORGANIZATION REPORT NUM11ER(S) MRDC41 131 .68A a. %#M6rOP IG 1 RA IZATION Ib...ICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ZATIN( 1 4.be W=seAdvanced Research Projects Contract No. MDA9O3-83-C-M07 Agec 1DoD

Estimating the Occupational Morbidity for Migrant and Seasonal Farmworkers in New York State: a Comparison of Two Methods

PubMed Central

Earle-Richardson, Giulia B.; Brower, Melissa A.; Jones, Amanda M.; May, John J.; Jenkins, Paul L.

2008-01-01

Purpose To compare occupational morbidity estimates for migrant and seasonal farmworkers obtained from survey methods versus chart review methods, and to estimate the proportion of morbidity treated at federally recognized migrant health centers (MHCs) in a highly agricultural region of New York. Methods Researchers simultaneously conducted: a) an occupational injury and illness survey among agricultural workers; b) MHC chart review; and c) hospital emergency room (ER) chart reviews. Results Of the 24 injuries reported by 550 survey subjects, 54.2% received treatment MHCs 16.7% at ERs, 16.7% at some other facility, and 12.5% were untreated. For injuries treated at MHCs or ERs, the incidence density based on survey methods was 29.3 injuries per 10,000 worker-weeks versus 27.4 by chart review. The standardized morbidity ratio (SMR) for this comparison was 1.07 (95% CI = 0.65 – 1.77). Conclusion Survey data indicate that 71% of agricultural injury and illness can be captured with MHC and ER chart review. MHC and ER incidence density estimates show strong correspondence between the two methods. A chart review-based surveillance system, in conjunction with a correction factor based on periodic worker surveys, would provide a cost-effective estimate of the occupational illness and injury rate in this population. PMID:18063238

Geological investigations and hydrogeologic model development in support of DoD and DOE environmental programs on Kirtland Air Force Base, New Mexico, U.S.A.

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

Gibson, J.D.; Pratt, G.; Davidson, H.

This paper presents results of preliminary geologic site characterization and hydrogeologic conceptual model development for the 250-km{sup 2} Kirtland Air Force Base (KAFB) and associated lands in central New Mexico. The research, development, and other operational activities of the Department of Defense (DoD) and Department of Energy (DOE) on KAFB over the last 50 years have resulted in diverse hazardous, radioactive, and mixed-waste environmental concerns. Because multiple federal, state, and local agencies are responsible for administrating the involved lands and because of the nature of many U.S. environmental regulations, individual contaminated and potentially contaminated DoD and DOE environmental restoration (ER)more » sites on KAFB are commonly handled as distinct entities with little consideration for the cumulative environmental and health risk from all sites. A site-wide characterization program has been undertaken at Sandia National Laboratories/New Mexico (SNL/NM), under the auspices of the DOE, to construct a conceptual hydrogeologic model for the base. This conceptual model serves as the basis for placing each ER site into a broader context for evaluating background (i.e., non-contaminated) conditions and for modeling of possible contaminant pathways and travel-times. Regional and local hydrogeologic investigations from KAFB can be used as models for characterizing and evaluating other sites around the world where combined civilian and military environmental programs must work together to resolve environmental problems that may present health risks to workers and the general public.« less

High energy Er-doped Q-switched fiber laser with WS2 saturable absorber

NASA Astrophysics Data System (ADS)

Li, Lu; Wang, Yonggang; Wang, Zhen Fu; Wang, Xi; Yang, Guowen

2018-01-01

The report presents a stable Q-switched Er-doped fiber (EDF) laser with WS2-based saturable absorber (SA). The SA is obtained by mixing WS2 dispersion with polyvinyl alcohol (PVA) into polystyrene cells, and then evaporating them to form WS2/PVA film. The modulation depth (MD) of WS2/PVA is 2% and the saturable intensity (Isat) is 27.2 MW/cm2. Employing the WS2/PVA film into EDF laser cavity, stable Q-switched operation is achieved with central wavelength of 1560 nm. The repetition rate can be tuned from 16.15 to 60.88 kHz with increasing pump power from 30 to 320 mW. The single pulse energy increases from 82 to 195 nJ and then decreases down to 156 nJ with increasing pump power from 30 to 320 mW. The pulse width shows the same variation trend. The shortest pulse duration of 2.396 μs and the maximum single pulse energy of 195 nJ are obtained at the pump power of 220 mW. To the best of our knowledge, 195 nJ is the largest single pulse energy at 1.55 μm region with TMDs as Q-switcher. The signal-to-noise ratio (SNR) is measured to be 60 dB at the pump power of 130 mW. The long term stability of working is good too. The experimental results evidently show that the WS2/PVA SA can work as a promising Q-switcher for high power fiber lasers.

Cloned Erwinia chrysanthemi out genes enable Escherichia coli to selectively secrete a diverse family of heterologous proteins to its milieu.

PubMed

He, S Y; Lindeberg, M; Chatterjee, A K; Collmer, A

1991-02-01

The out genes of the enterobacterial plant pathogen Erwinia chrysanthemi are responsible for the efficient extracellular secretion of multiple plant cell wall-degrading enzymes, including four isozymes of pectate lyase, exo-poly-alpha-D-galacturonosidase, pectin methylesterase, and cellulase. Out- mutants of Er. chrysanthemi are unable to export any of these proteins beyond the periplasm and are severely reduced in virulence. We have cloned out genes from Er. chrysanthemi in the stable, low-copy-number cosmid pCPP19 by complementing several transposon-induced mutations. The cloned out genes were clustered in a 12-kilobase chromosomal DNA region, complemented all existing out mutations in Er. chrysanthemi EC16, and enabled Escherichia coli strains to efficiently secrete the extracellular pectic enzymes produced from cloned Er. chrysanthemi genes, while retaining the periplasmic marker protein beta-lactamase. DNA sequencing of a 2.4-kilobase EcoRI fragment within the out cluster revealed four genes arranged colinearly and sharing substantial similarity with the Klebsiella pneumoniae genes pulH, pulI, pulJ, and pulK, which are necessary for pullulanase secretion. However, K. pneumoniae cells harboring the cloned Er. chrysanthemi pelE gene were unable to secrete the Erwinia pectate lyase. Furthermore, the Er. chrysanthemi Out system was unable to secrete an extracellular pectate lyase encoded by a gene from a closely related plant pathogen. Erwinia carotovora ssp. carotovora. The results suggest that these enterobacteria secrete polysaccharidases by a conserved mechanism whose protein-recognition capacities have diverged.

A novel CISD2 mutation associated with a classical Wolfram syndrome phenotype alters Ca2+ homeostasis and ER-mitochondria interactions

PubMed Central

Rouzier, Cécile; Moore, David; Delorme, Cécile; Lacas-Gervais, Sandra; Ait-El-Mkadem, Samira; Fragaki, Konstantina; Burté, Florence; Serre, Valérie; Bannwarth, Sylvie; Chaussenot, Annabelle; Catala, Martin

2017-01-01

Abstract Wolfram syndrome (WS) is a progressive neurodegenerative disease characterized by early-onset optic atrophy and diabetes mellitus, which can be associated with more extensive central nervous system and endocrine complications. The majority of patients harbour pathogenic WFS1 mutations, but recessive mutations in a second gene, CISD2, have been described in a small number of families with Wolfram syndrome type 2 (WFS2). The defining diagnostic criteria for WFS2 also consist of optic atrophy and diabetes mellitus, but unlike WFS1, this phenotypic subgroup has been associated with peptic ulcer disease and an increased bleeding tendency. Here, we report on a novel homozygous CISD2 mutation (c.215A > G; p.Asn72Ser) in a Moroccan patient with an overlapping phenotype suggesting that Wolfram syndrome type 1 and type 2 form a continuous clinical spectrum with genetic heterogeneity. The present study provides strong evidence that this particular CISD2 mutation disturbs cellular Ca2+ homeostasis with enhanced Ca2+ flux from the ER to mitochondria and cytosolic Ca2+ abnormalities in patient-derived fibroblasts. This Ca2+ dysregulation was associated with increased ER-mitochondria contact, a swollen ER lumen and a hyperfused mitochondrial network in the absence of overt ER stress. Although there was no marked alteration in mitochondrial bioenergetics under basal conditions, culture of patient-derived fibroblasts in glucose-free galactose medium revealed a respiratory chain defect in complexes I and II, and a trend towards decreased ATP levels. Our results provide important novel insight into the potential disease mechanisms underlying the neurodegenerative consequences of CISD2 mutations and the subsequent development of multisystemic disease. PMID:28335035

Decadal modulation of the relationship between intraseasonal tropical variability and ENSO

NASA Astrophysics Data System (ADS)

Gushchina, Daria; Dewitte, Boris

2018-05-01

The El Niño Southern Oscillation (ENSO) amplitude is modulated at decadal timescales, which, over the last decades, has been related to the low-frequency changes in the frequency of occurrence of the two types of El Niño events, that is the Eastern Pacific (EP) and Central Pacific (CP) El Niños. Meanwhile ENSO is tightly linked to the intraseasonal tropical variability (ITV) that is generally enhanced prior to El Niño development and can act as a trigger of the event. Here we revisit the ITV/ENSO relationship taking into account changes in ENSO properties over the last six decades. The focus is on two main components of ITV, the Madden-Julian Oscillation (MJO) and convectively coupled equatorial Rossby waves (ER). We show that the ITV/ENSO relationship exhibits a decadal modulation that is not related in a straight-forward manner to the change in occurrence of El Niño types and Pacific decadal modes. While enhanced MJO activity associated to EP El Niño development mostly took place over the period 1985-2000, the ER activity is enhanced prior to El Niño development over the whole period with a tendency to relate more to CP El Niño than to EP El Niño. In particular the relationship between ER activity and ENSO was particularly strong for the period 2000-2015, which results in a significant positive long-term trend of the predictive value of ER activity. The statistics of the MJO and ER activity is consistent with the hypothesis that they can be considered a state-dependent noise for ENSO linked to distinct lower frequency climate modes.

Diosgenin promotes oligodendrocyte progenitor cell differentiation through estrogen receptor-mediated ERK1/2 activation to accelerate remyelination.

PubMed

Xiao, Lin; Guo, Dazhi; Hu, Chun; Shen, Weiran; Shan, Lei; Li, Cui; Liu, Xiuyun; Yang, Wenjing; Zhang, Weidong; He, Cheng

2012-07-01

Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is a prerequisite for remyelination after demyelination, and impairment of this process is suggested to be a major reason for remyelination failure. Diosgenin, a plant-derived steroid, has been implicated for therapeutic use in many diseases, but little is known about its effect on the central nervous system. In this study, using a purified rat OPC culture model, we show that diosgenin significantly and specifically promotes OPC differentiation without affecting the viability, proliferation, or migration of OPC. Interestingly, the effect of diosgenin can be blocked by estrogen receptor (ER) antagonist ICI 182780 but not by glucocorticoid and progesterone receptor antagonist RU38486, nor by mineralocorticoid receptor antagonist spirolactone. Moreover, it is revealed that both ER-alpha and ER-beta are expressed in OPC, and diosgenin can activate the extracellular signal-regulated kinase 1/2 (ERK1/2) in OPC via ER. The pro-differentiation effect of diosgenin can also be obstructed by the ERK inhibitor PD98059. Furthermore, in the cuprizone-induced demyelination model, it is demonstrated that diosgenin administration significantly accelerates/enhances remyelination as detected by Luxol fast blue stain, MBP immunohistochemistry and real time RT-PCR. Diosgenin also increases the number of mature oligodendrocytes in the corpus callosum while it does not affect the number of OPCs. Taking together, our results suggest that diosgenin promotes the differentiation of OPC into mature oligodendrocyte through an ER-mediated ERK1/2 activation pathway to accelerate remyelination, which implicates a novel therapeutic usage of this steroidal natural product in demyelinating diseases such as multiple sclerosis (MS). Copyright © 2012 Wiley Periodicals, Inc.

Mitochondrial metabolic regulation by GRP78

PubMed Central

Prasad, Manoj; Pawlak, Kevin J.; Burak, William E.; Perry, Elizabeth E.; Marshall, Brendan; Whittal, Randy M.; Bose, Himangshu S.

2017-01-01

Steroids, essential for mammalian survival, are initiated by cholesterol transport by steroidogenic acute regulatory protein (StAR). Appropriate protein folding is an essential requirement of activity. Endoplasmic reticulum (ER) chaperones assist in folding of cytoplasmic proteins, whereas mitochondrial chaperones fold only mitochondrial proteins. We show that glucose regulatory protein 78 (GRP78), a master ER chaperone, is also present at the mitochondria-associated ER membrane (MAM), where it folds StAR for delivery to the outer mitochondrial membrane. StAR expression and activity are drastically reduced following GRP78 knockdown. StAR folding starts at the MAM region; thus, its cholesterol fostering capacity is regulated by GRP78 long before StAR reaches the mitochondria. In summary, GRP78 is an acute regulator of steroidogenesis at the MAM, regulating the intermediate folding of StAR that is crucial for its activity. PMID:28275724

The Need for High-Resolution Crustal Magnetic Field Data on Mars

NASA Technical Reports Server (NTRS)

Raymond, C. A.; Russell, C. T.; Purucker, M. E.; Smrekar, S. E.

2000-01-01

Magnetometer observations from the Mars Global Surveyor spacecraft (MAG/ER on MGS) have confirmed that Mars does not presently have an internally-generated dipole magnetic field, and have also revealed intense remanent magnetism in the Martian crust. The remanent magnetic anomalies, most prevalent in the southern highlands region, are a record of the past history of the internal Mars dipole field. The MAG/ER data constitute a valuable data set for constraining the early thermal evolution of Mars and the history of the planetary magnetic field. However, the data lack the resolution needed to draw definite conclusions regarding the time history of the field. High-resolution magnetometer observations, obtained at low-altitude, are needed to complement and extend the MGS/ER data set and allow a definitive time history of the internal Mars dynamo to be constructed.

Emotion dysregulation and functional connectivity in children with and without a history of major depressive disorder.

PubMed

Lopez, Katherine C; Luby, Joan L; Belden, Andy C; Barch, Deanna M

2018-04-01

Recent interest has emerged in understanding the neural mechanisms by which deficits in emotion regulation (ER) early in development may relate to later depression. Corticolimbic alterations reported in emotion dysregulation and depression may be one possible link. We examined the relationships between emotion dysregulation in school age, corticolimbic resting-state functional connectivity (rs-FC) in preadolescence, and depressive symptoms in adolescence. Participants were 143 children from a longitudinal preschool onset depression study who completed the Children Sadness Management Scale (CSMS; measuring ER), Child Depression Inventory (CDI-C; measuring depressive symptoms), and two resting-state MRI scans. Rs-FC between four primary regions of interest (ROIs; bilateral dorsolateral prefrontal cortex [dlPFC] and amygdala) and six target ROIs thought to contribute to ER were examined. Findings showed that ER in school age did not predict depressive symptoms in adolescence, but did predict preadolescent increases in dlPFC-insula and dlPFC-ventromedial PFC rs-FC across diagnosis, as well as increased dlPFC-dorsal anterior cingulate cortex (dACC) rs-FC in children with a history of depression. Of these profiles, only dlPFC-dACC rs-FC in preadolescence predicted depressive symptoms in adolescence. However, dlPFC-dACC connectivity did not mediate the relationship between ER in school age and depressive symptoms in adolescence. Despite the absence of a direct relationship between ER and depressive symptoms and no significant rs-FC mediation, the rs-FC profiles predicted by ER are consistent with the hypothesis that emotion dysregulation is associated with abnormalities in top-down control functions. The extent to which these relationships might confer greater risk for later depression, however, remains unclear.

Mouse fat storage-inducing transmembrane protein 2 (FIT2) promotes lipid droplet accumulation in plants.

PubMed

Cai, Yingqi; McClinchie, Elizabeth; Price, Ann; Nguyen, Thuy N; Gidda, Satinder K; Watt, Samantha C; Yurchenko, Olga; Park, Sunjung; Sturtevant, Drew; Mullen, Robert T; Dyer, John M; Chapman, Kent D

2017-07-01

Fat storage-inducing transmembrane protein 2 (FIT2) is an endoplasmic reticulum (ER)-localized protein that plays an important role in lipid droplet (LD) formation in animal cells. However, no obvious homologue of FIT2 is found in plants. Here, we tested the function of FIT2 in plant cells by ectopically expressing mouse (Mus musculus) FIT2 in Nicotiana tabacum suspension-cultured cells, Nicotiana benthamiana leaves and Arabidopsis thaliana plants. Confocal microscopy indicated that the expression of FIT2 dramatically increased the number and size of LDs in leaves of N. benthamiana and Arabidopsis, and lipidomics analysis and mass spectrometry imaging confirmed the accumulation of neutral lipids in leaves. FIT2 also increased seed oil content by ~13% in some stable, overexpressing lines of Arabidopsis. When expressed transiently in leaves of N. benthamiana or suspension cells of N. tabacum, FIT2 localized specifically to the ER and was often concentrated at certain regions of the ER that resembled ER-LD junction sites. FIT2 also colocalized at the ER with other proteins known to be involved in triacylglycerol biosynthesis or LD formation in plants, but not with ER resident proteins involved in electron transfer or ER-vesicle exit sites. Collectively, these results demonstrate that mouse FIT2 promotes LD accumulation in plants, a surprising functional conservation in the context of a plant cell given the apparent lack of FIT2 homologues in higher plants. These results suggest also that FIT2 expression represents an effective synthetic biology strategy for elaborating neutral lipid compartments in plant tissues for potential biofuel or bioproduct purposes. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Activation of ER stress and mTORC1 suppresses hepatic sortilin-1 levels in obese mice

PubMed Central

Ai, Ding; Baez, Juan M.; Jiang, Hongfeng; Conlon, Donna M.; Hernandez-Ono, Antonio; Frank-Kamenetsky, Maria; Milstein, Stuart; Fitzgerald, Kevin; Murphy, Andrew J.; Woo, Connie W.; Strong, Alanna; Ginsberg, Henry N.; Tabas, Ira; Rader, Daniel J.; Tall, Alan R.

2012-01-01

Recent GWAS have identified SNPs at a human chromosom1 locus associated with coronary artery disease risk and LDL cholesterol levels. The SNPs are also associated with altered expression of hepatic sortilin-1 (SORT1), which encodes a protein thought to be involved in apoB trafficking and degradation. Here, we investigated the regulation of Sort1 expression in mouse models of obesity. Sort1 expression was markedly repressed in both genetic (ob/ob) and high-fat diet models of obesity; restoration of hepatic sortilin-1 levels resulted in reduced triglyceride and apoB secretion. Mouse models of obesity also exhibit increased hepatic activity of mammalian target of rapamycin complex 1 (mTORC1) and ER stress, and we found that administration of the mTOR inhibitor rapamycin to ob/ob mice reduced ER stress and increased hepatic sortilin-1 levels. Conversely, genetically increased hepatic mTORC1 activity was associated with repressed Sort1 and increased apoB secretion. Treating WT mice with the ER stressor tunicamycin led to marked repression of hepatic sortilin-1 expression, while administration of the chemical chaperone PBA to ob/ob mice led to amelioration of ER stress, increased sortilin-1 expression, and reduced apoB and triglyceride secretion. Moreover, the ER stress target Atf3 acted at the SORT1 promoter region as a transcriptional repressor, whereas knockdown of Atf3 mRNA in ob/ob mice led to increased hepatic sortilin-1 levels and decreased apoB and triglyceride secretion. Thus, in mouse models of obesity, induction of mTORC1 and ER stress led to repression of hepatic Sort1 and increased VLDL secretion via Atf3. This pathway may contribute to dyslipidemia in metabolic disease. PMID:22466652

Maturation of hepatic lipase. Formation of functional enzyme in the endoplasmic reticulum is the rate-limiting step in its secretion.

PubMed

Ben-Zeev, Osnat; Doolittle, Mark H

2004-02-13

Among three lipases in the lipase gene family, hepatic lipase (HL), lipoprotein lipase, and pancreatic lipase, HL exhibits the lowest intracellular specific activity (i.e. minimal amounts of catalytic activity accompanied by massive amounts of inactive lipase mass in the endoplasmic reticulum (ER)). In addition, HL has a distinctive sedimentation profile, where the inactive mass overlaps the region containing active dimeric HL and trails into progressively larger molecular forms. Eventually, at least half of the HL inactive mass in the ER reaches an active, dimeric conformation (t(1/2) = 2 h) and is rapidly secreted. The remaining inactive mass is degraded. HL maturation occurs in the ER and is strongly dependent on binding to calnexin in the early co-/post-translational stages. Later stages of HL maturation occur without calnexin assistance, although inactive HL at all stages appears to be associated in distinct complexes with other ER proteins. Thus, unlike other lipases in the gene family, HL maturation is the rate-limiting step in its secretion as a functional enzyme.

Identification of novel indole based heterocycles as selective estrogen receptor modulator.

PubMed

Singla, Ramit; Prakash, Kunal; Bihari Gupta, Kunj; Upadhyay, Shishir; Dhiman, Monisha; Jaitak, Vikas

2018-04-24

In the present study, we have designed and synthesized indole derivatives by coalescing the indole nucleus with chromene carbonitrile and dihydropyridine nucleus. Two compounds 5c and 6d were selected from series I and II after sequential combinatorial library generation, docking, absorption, distribution, metabolism and excretion (ADME) filtering, anti-proliferative activity, cytotoxicity, and ER-α competitor assay kit by utilizing estrogen receptor-α (ER-α) dominant T47D BC cells line and PBMCs (Peripheral Blood Mononuclear Cells). Cell imaging experiment suggested that both the compounds successfully cross cellular biomembrane and accumulate in nuclear, cytoplasmic and plasma membrane region. Semiquantitative RT-PCR and Western blotting experiments further supported that both compounds reduced the expression of mRNA and receptor protein of ER-α, thereby preventing downstream transactivation and signaling pathway in T47D cells line. Current findings imply that 5c and 6d represent novel ER-α antagonists and may be used in the development of chemotherapy for the management of BC. Copyright © 2018 Elsevier Inc. All rights reserved.

Peroxisomes, lipid droplets, and endoplasmic reticulum “hitchhike” on motile early endosomes

PubMed Central

Guimaraes, Sofia C.; Schuster, Martin; Bielska, Ewa; Dagdas, Gulay; Kilaru, Sreedhar; Meadows, Ben R.A.; Schrader, Michael

2015-01-01

Intracellular transport is mediated by molecular motors that bind cargo to be transported along the cytoskeleton. Here, we report, for the first time, that peroxisomes (POs), lipid droplets (LDs), and the endoplasmic reticulum (ER) rely on early endosomes (EEs) for intracellular movement in a fungal model system. We show that POs undergo kinesin-3– and dynein-dependent transport along microtubules. Surprisingly, kinesin-3 does not colocalize with POs. Instead, the motor moves EEs that drag the POs through the cell. PO motility is abolished when EE motility is blocked in various mutants. Most LD and ER motility also depends on EE motility, whereas mitochondria move independently of EEs. Covisualization studies show that EE-mediated ER motility is not required for PO or LD movement, suggesting that the organelles interact with EEs independently. In the absence of EE motility, POs and LDs cluster at the growing tip, whereas ER is partially retracted to subapical regions. Collectively, our results show that moving EEs interact transiently with other organelles, thereby mediating their directed transport and distribution in the cell. PMID:26620910

Binding to membrane proteins within the endoplasmic reticulum cannot explain the retention of the glucose-regulated protein GRP78 in Xenopus oocytes.

PubMed

Ceriotti, A; Colman, A

1988-03-01

We have studied the compartmentation and movement of the rat 78-kd glucose-regulated protein (GRP78) and other secretory and membrane proteins in Xenopus oocytes. Full length GRP78, normally found in the lumen of rat endoplasmic reticulum (ER), is localized to a membraneous compartment in oocytes and is not secreted. A truncated GRP78 lacking the C-terminal (KDEL) ER retention signal is secreted, although at a slow rate. When the synthesis of radioactive GRP78 is confined to a polar (animal or vegetal) region of the oocyte and the subsequent movement across the oocyte monitored, we find that both full-length and truncated GRP78 move at similar rates and only slightly slower than a secretory protein, chick ovalbumin. In contrast, a plasma membrane protein (influenza haemagglutinin) and two ER membrane proteins (rotavirus VP10 and a mutant haemagglutinin) remained confined to their site of synthesis. We conclude that the retention of GRP78 in the ER is not due to its tight binding to a membrane-bound receptor.

78 FR 40469 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-05

.... Docket Numbers: ER10-3300-004. Applicants: La Paloma Generating Company, LLC. Description: Triennial Updated Market Power Analysis for the Southwest Region of La Paloma Generating Company, LLC. Filed Date: 6...